Document 2Nq7DXN7JkarwRXENwxMGpEQr

Comments and Studies on the Use of Polychlorinated Biphenyls in Response to an Order of the United States Court of Appeals for the District of Columbia Circuit EntrauiraUl hHdk Af-- Mtwaiy IS. IMS VMmO HMM H--Hk Bfacf flw H---- DRILL. FRIESS, HAYS, LOOMIS ft SHAFFER. INC CMWklMI tm Toxicoioty iVOl N. Fon Myer Driv -- Suit* 204 -- Arlington, va 2220V HOMS 2Z1920 ncniCTp unmii wnw uieuiei eemxai litxcutic* I ' i i m. ggPIPKDff U8T, cent(3. Closed Tanka, contd. X31 - 26 Equipment LI at CT-0767-0770 5T-0767 cor.td. Steam traced vent te drum outdoors. Manlld. Dippln* hole with cap. Fixed overflew* at 4 level* back t diphenyl atore tank 07-07*8 by ateaa traced line with eight glaaa and right angle croaa place* with blank flange*. Lover part of veaiel Jacketed for ateas from the 70 lb. main. Angle thermometer >0" long through aide of veaeel. Bottom outlet to header leading to the * ehlonnatora. S. 0. at each jchlorlnater. CT-076S f 3 Aroclor I960 flnlehed product atorage tank. Made by Orever. D*g. C-609. Horn, ateel 10* die. x 96* long on atraight aide, dlehed haeda, ah*11 4", heada 9/16". Teat tank 60# and coll JOO# Hydro. Freaa. Cell 2" xHy pip* with 1" xHy naera. Veiled cenatruetlon throughout. All inaide and fig. aurfaeea* coila, aupporta, etc., to be apreyed flrat .006" *lnc and then .006" tin. Same aa CT-0769. Order B7711 on */17/>6, Req. 69251. Chg. out 61566.00. CaCla vent trap. CT-0769 # * Aroclor 126* Flnlehed product Storage Tank. Same aa CT-0766. CT-0770 Tubular heat exchanger eada by Hooter. Jfeg. B651, Plant A, Site 12" Ala. x 5'0" Ig. having 19 * 2* 00 11 ga. Monel Tub#*, Monel tube ahaeta. Monel reducer and carbon ataal Jacket and back-up ring# on flangte. Order B5M8 on 5/1/76* Jleq. 69605. Frie* *660.00 Above Mo. 1 atlll 50*3, aupported by 5rd floor ateel. Plant "9* (Xjunwleh Plant) cortlnut to reeeawnd monel for the cond#naera on the vacuum atlll*. Sea alao item PI-01378. Only monel in contact with the good* on the deaeendlng* aide of the condensing system. 0X39220 X o o tn 03 CD LH Uj CD t noTTCTZB UTnuii vcaaxjrro latnxaCE cevtuot tiTicatioa i m. EQCIPMEHT U3T, eentd XII - 27 Iqulpnent Uat CT-C770 - 0771 Cloaed Tanka, eentd. _ CT-0770, eentd. Hr. Thrift, December 5. 19*9, releed the quaatlen ef the neceaalty ef ualng aoncl fer tha vaeuw atlll condanaera and aubaequent veaaela. Hr. Bllanburg of Annlaton replied, 15th Decanter, 19*9, atatlng that iron omtounaaon of tha Areclore would have a bad affect on tha reaiatlvity and tha power factor ef tha producta. Steal alao ha a tana tha darkening ef Aroclora at tenperaturea ef 80*0. or higher. Neaara. Hodge a and Barbra ef tha KTVMtrlch plant replied that aonel waa aatl a factory fer the eondeneera and racalvera but that there were no reaaone to believe ataal would not be eetlafectery. Although Oaneral'Electric Ccaqany report that ateel la aatlafactery for ateraga and treatoent veaiala, EruHirlch plant do not ear* to rlak tha uoe of ataal bacauaa of tha high atandarda required by 0. X. fer Aroclora. CT-0771 Hemal varnna receiver Bade by Nootar. Ih*g. C-793. (Plant l). Site 3'6" die. x 5'6" atr. aide, 3/B" ahall, bottoa and removable head, A auppert brackata on outalde of tank ef ateel. 8" IP alia xHy Monel coll with 2" inlet and 1" outlat with Honel bare and U belta. 3 tuna 5' dla. along alda and 3 tuna aplral on bottom. 60/ Hyd. teat en tank and 300# en coll. Order B7JT9 en A/1A/36, Beq. 69118. Price $32*0.00. On eeeond floor level, 12* level. Bldg. CX. Ho. 1 atlll. Betum line, for apollt oaterlal, to tha atilL ef tha vacua atlll receiver* Tha coven/carry tha following oenneetlcne: Inlet froo condanaera CT-0770, 01378 via eight glaaaea. Tha cylindrical aurfaee of the eight glaar fitting la ataaa jacketed and eo la tha pipe froa the condanaer te the tight glaaa. Hanlld with hand hole and dipping opening. 0139221 I C H- j U) j nap* c 3^ ss5 ? = 5Ci ^sn 5" H`ra r HC rM(mA n pi o5 c 3 *>t- -a>9 X o o cn co un Llj J gl. gPI2HPff UST. eontd m - :e Equipment Lift Cl-0771-0779 Cleeed Tanka, eontd. CT-0771 eontd. Inal vaeuun gauge and aercuxy O-gauge. Thane recorder wall. Vent cock. Steen coll in and out, Thla cell goea well down into the botton dlah ot the receiver, Vecuun line to the top of coke scrubber CT-0753 and -01396, Bottom outlet to punp 7-098* for delivery to the Sparkler prate and to Blackner puapa, 7-0565/ -01037/ for delivery to the blending tank. CT-0779, Electric atrip haatera to drawing 0-8*7, fenerly uaed on i theta veaaele have been abandoned/ ao no copy of the drawing hat been repeated for MCL. Material 1268 requirea H. 7. ateas In the coll to keep it aoltan. There la only ana receiver far each vaeuun etlll In the crude room,no fractionation being attempted, There la no gauge glaee or level indicator/ only a gauging hole.*'a receiver will hold a full batch fron the etlll. CT-0779 #1 blending tank aadt by Graver, ftfg. *-862. balded eteel tank 7* dla. z 7' high dlahed heada 4*. ahell 3/8".- All lnalC. aurfacea and noatlea apiayed .005 tine then .003 tin. 2" xJty pipe coll and aupportt. Take and drive eupporte. Ceet brenxe turbine etirrer and bronze theft. Teat tank 60# and coll 300#, hydrostatic Freaeure. Order BT707 on A/17/36, had. 69227, etig. out $599.00. On 2nd floor level, 12' level. Bldg. CE. Sane aa CT-0780 But aee page 21, aectlon VZ 0139222 .1 X oo 03 03 ir | .* I| W --_ ' l^f \ T%vrtcrxs> nmiui loinorto ximuci comux litioxtich XII. EgPirKPflr LIST. eontd. XII - 29 Equips nt U't CT-D779-C760 Closed Tanks, eontd. i 3 CT-0779 eontd. See alee CT-01599, #2 Blender end CT-C780, filtrate i Jteeelver. " Drawings 2-662 end *-6658 ere essentially the eeae. ii! Drawings A-*59 and A-6855 of the hearing have been requested Drawings D-2076, 2077* show the agitator rotor and stator. Anniston, Deesober 1$, 19*9,state that their blenders are ! of steel, sprayed with sine then with tin and that the ' agitator In one case is of Tobin bronse (stated to be 60* Cu. 59.i$f 2n, 0.75 Sr>), and in the ether ease la of steel, sprayed with sine then with tin. 1 The sprayed agitator Is said to be satisfactory. Plant *B", s January 5, 1$50, state 0.005" Zn then 0.005" Sn for the i tanka, and their agitators are of bronse of unknown ecego- i sltlon, probably "ordinary coaAerclal bronse". Anniston and Plant "B" agree In distrusting plain steal for these I weasels. Anniston suggest Aluaimua. \ i CT-C780 #1 filtrate reeelver tank. Dog. 1-662, Beds by Oraear. Velded steel tank 7' die. z 7* high, dished heads j", shell 5/6". Baae as CT-0779. i Materials 1260 and 1254 tan be run froa the reeeleera CT-0760 and 01400 to bulk store tanks. Other Materials are filled off into dnau. i i To save tine. Most of the control tests are done on sasgles i 1 taken before filtration. i Material 1266 needs B.P. steaa to keep It fluid. The filtrate receivers are like the blenders CT-0779 and 01599 except that the filtrate receivers heve no agitators. f 0139223 i a I o -* *- 3 3V s * n*5 8 5S-2s n55 > - x 5 #-8B B u:*-X* O fVVl)I oIf5 balea*> D O 0ca3 !CD Ii un i LU LU t i ^ X* - woricTP nmmi ucsexrro tunuci eovtuas utiutxov f III. ECUT fwyr Uff, eantd Closed Tanks, contd. HI * 50 Bqulpaent list CT-0785 O806 CT-07B5 Middle acid tank south of CR on foundstion. Mads by Goodrich, I>*f. C-825. "Vulcalok" llnss - stssl tk. 7'O' If x 6*6", shell 5/16", dished head 5/16", bottoa 7/16", *" outlet for safety plw on bettm. 18" feanhole and cover, 5-5" flgd. outlets in head, 5/16" Trlflex llnlns, rubber covered float and eerd for aeaeudng device. Head with 6 - lj" couplints for railings. I Order B9?3 on 5/19/5, Req, 69966. Chg. out 69*5.65. South of CR on foundation. Saae as 078* and 0786. CT-0766 Vest add tank, aaae as CT-O78* and 0785. CT-0606 storage tank and chlerinator with atlrrer and fas burner. (Oas fired ohlorlnator). Made by Kilpatrick and Sons Pdy. Co. D*g. >a56*. Cast Iron, 6* If x 4* 11" deep lnalde, wall 2" thick, bottoa 3" thick and dished in 3". 3" outlet at lower na. Marked g-*59, weight 12,675#. Machining outside of top flange but without holes and aachlnlng outlet in rla Including drilling and tapping holes. Cost of aachlne work 636.00. Ordsr B6162 on 4/26/36, Raq. 69596, 1 Cost *517.65. On 12* level 3k comer Bldg. CR. Brewing C&30 gas heater on exit-line. ` Subsidiary drewings i Fr. relief door on 6'0" Cl atoratank Cla^> for alaetdc atrip heater Tent for Cl tank Shear pin unit -- for drive on agitator Brick setting Drive for atlrrer 6*3" x 10*11* eteel shell for tank Tent stack for still heater Still heater B-613 B-684 B-686 C--66065? -888 1-881 >-689 1-886 This gas-hasted chlodnater la also sailed 8-0*59. The chlorine entere the gas-fired chlodnater through a per forated pipe ring, and there la a separate Inlet plpr I 0139124 o -t VI xn 5 5 SS ic- *-i I> s5? h: 5 0*xH C4(An nn s5 5s X o o (J1 Lj LH U_j L y rnnn.na uruui Moasurro mnum cornua _ ' | I hi - 51 Squlpaant Ult CT-0808 Cloud Tank*, contd. CT-0808, contd. with a ample open end for uae when the perforated pipe bectett choked. The cover carries a wide neck through whioh Material recovered fro the aonel catch veaael CT-01P58 can be returned by Meant of a wide ateel funnel. There la another neck, wide enough to adalt a sailing bottle alao uaed aa a gauging hole. Inlet fro #1 chlorineter CT-01265 by'a gas-heated gravity line or via pump P-0907 through llnea with B. f. ataaa tracing. 9* Monel duct, with cleaning flangea, ritea at *5* fro the chlorlnator cover, then deacenda at *5* to the noncl gaa chakber CT-OI256. fro the Monel cheaper onwarda the ducting to the acrubber la of ateel with cleaning flangea. Ceaapreaaed air connection into the chlorine Inlet for clearing (net very eucceaaful). Agitator with water cooled etufflng box. Thar recorder wall. Botto outlet with gaa flanc heating, to the retort veeeela 11-026 and 11-027 In an adjoining lean-*.: building. Bee Drawing S-667 for the farnaee setting, 1-681 for the ateel casing of the setting 1-666 for the drive C-605 for shear plr for drive B-613 for pressure relief door on furnace 1-686 for vent stack, 1 F-J2A which shows a shallower veaael; the chlorlnator pot la alnllar but la *'11" deep. The final chlorination to high chlorine content la acre easily done in this separate chlorlnator because higher tenperatures are needed to keep the charge aolten. 0119215 c*1 j5 - j Ul H s 5 S * = K3S * *1 11*hn* hOnmrn H r> r;sto rto 3s o o 0CO3 Lli i U~i LU LTi rurscTOB nmiui ncsaurro issrtxsci eorxuot litiutioz Cl. BCPIPMPff IIST. eontd. Closed Tanka, eontd. m- 32 Bqulpaent List CT-0608 - 0852 CT-0808 eontd. Drawings B-664 strip haster S-666 elaap for atrip heatar B-689 vent ataek for furnace have net been requested as they ere net of Interest, Strip heetere ere net new used. CT-0631 Veter condenser Bade by Heine Seller oapany. b>l. B483 (Plant a), used es teaperature control for Arocler condenser CT-0770. 12 tubes. 1 ' OD 10 OA seaaless steel tubing 10'-0i" lens. 10'0" overs 11 length of 6" std. pipe shell single pees. Order BST73 on 5/11/56, Red. 69576. Trice 196.00, Used on #1 vacuum still. Safety valve on shell, CT-0633 Chlorine ter puchased froa leader Iron Works. Site 3* die, z 16' made up eocplete Including colls. Inner shell, and grating, lb's, S-880 and B-659- Order B-2B13 on 2/5/37. Red- 76475 on 1/26/37. chg. out *790.00 on 3/31/37- . Bast chloftastor. #3 chlorlnator, gee CT-C7*4. CT-0648 TCB stg. tank. Made by Oraver. tank dug. S 4413 Coll C*412 for steaa Oensral 1066 tank 6' IB t 25'6' long welded. 3/8" shell. 7/16* dished heads. 13-26* and 2-24* die. aa&hele openings on top. 2-1* xHy. W. S. pipe coll. 71* approx. Order 13634 on 2/17/37. Red. 76931 on 2/12. Price *920.00 West of CR underground. Pyrunol Plant, CT-O852 Rayaond 2 stage cyclone dust collector sent to B by Anniston Plant. lech cyclone approx. 20" dla. - 21" str, section 32" depth of cone, steel construction, used with B-0105. In lesn-to of building CR. Ro drawing. 0139226 I i V fr- Cn rH -^ <3 v* 3 mgn 512 SPSS * >(p^h 5R w - n X o o U7 lX un uu Cn 1 j 1 1 HI. RCwIPKEW UST, contd. Clod Tanks* eontd. Cl - 33 Bqulpacnt tut CT-0968 n-01164 CT-0966 Sc rubber liquor puap tank purchased fren Mooter. Deg. C-*6l6. Steel vertical jacketed* elte 4*6" IS z 5'6* long with jacket. Order B15673 on 8/2/57. Req. 81*58 on 8/2/37. 2rice 1575.00. CT-01C13 #1A scrubber liquor punp tank aade by leader. (tog. C-*6l6. Size *'6" IS z 5'6" vertical* ateel, flange quality, all welded. Jacketed. Order B *16* on */29/3B, Req. 87029 on 3/9/38. Brice 15&2.00 On 36* level 8E corner CR. * CT-0101* Scrubber tank aade by Belntx. Ihg. C-*8*5. Steel 12" dla. std. wrought steel pip# 10'10" high, dished end and other end fitted with 3/** faced and drilled fig. with 5/8" oover plate. Steel plate* and distributer. Use 5 eu. ft. 1* Cl Raachlg rings pkg.. Order B3933 on 3/V36, Req. 86921 on 3/V38. Brice 1139.00. on top of CT-01013* fix scrubber. CT-01162 Scrubber tank aade by Beintz. Owg. C57*3. Velded steel scrubber* size 12* IS z J1. Order B19519 on 9/27/39, Req 1977 on 9/19 Brice 1102.00. Tent line to CT-0848. () CT-OII63 Catch Tank 55 gal. steel drum. Bor CT-0762. Rate to CT-0U6*. Chg. out Ill.bO, 11/27/39. (*) (*J Both CT-01162 and CT-01163 are on vents of CT-01321 and 02621, Byranal Blant. ' CT-0116* Catch Tank. Sue ss CT-01163 Bor CT-01162, Byranol Blant 0139227 . * k- o -t j o *5 -<i KS 5 * 3i *&z*sn sO3m5*m:irnn H ft RS ?5 - > 3* un ^I ntneTD urmui MOXSXXTO mtlUCI COTBJLAX bXTXOXTXOX PI. ECPIPHP1T LIST, contd Closed Tenk*, oeetd. m - j* Squlpaent List CT-01258 . 01279 CT-01258 Monel |M ebubar aade by Mooter. Dwg. C-5825. ' *> dla. x *' high con* true tad of Non*I. Ordir S7835 on */3/*0, Req. 6061 on 3/27, *0, R*q. fio6l on 3/27/*0. . Chg. out $867.00. On pi exit frea fir* hooted chlorlnxtor me oonel ve**el l* t the lowest point of the go* exit line froo the gas-heated chlorlnotor. Solid Aroelor which collect* in It 1* removed by head end returned to the chlorlnxtor with x *ub*equ*nt bxteh. CT-01259 Cyclone Tank oxde by Helntx. Bwg. *5821. 2*6" dlx. x 6'7" high constructed of 3/16* atoel plate. Order *73*5 on */27/*0. Req. 6062 on 3/27/*0. Trice $92.00. Bong frea roof of Bldg, on 38' lovel. CT-01259>01279 , 01280 , 01281, 01282, cyclone* on chlorln xtor off-gas, follow the scrubbing tower* CT-0759 etc. Drain through S. O'* to the return seal pipe* between towers and circulation tanks. Off-gas to the aaln leading to the BC1 absorption systems. See drawing B-5821 (This drawing not yet found April 5, 19*7). tee drawing *-660. CT-01263 Monel condenser aade by Mooter. Dwg. C-6l**. *2* die. x 63" high cone bottom condenser constructed of 3/16 Monel aetal welded construction throughout. ' Order *-836* on */9/*0. Req. 8198 on */l/*0. Price $928.00 This vessel is obsolete. CT-OI279 Cyclone separator aade by Mooter Dug. 5821. 2* dlx. x 6'7* high cyclons separator made of steel and welded throughout. Order *13177 on 6/12/40. Req. 10232 on 6/5/*0. Chg. out $66.25. Per use at CT-0968. ' ( 0119221 \ X o o CD un lu Co j nencTB tanatuu,i mure uicuici eenuii mxutxoa Ilia ECOXrKgHT LIST, ccntd Clod T*nfc$ contd. XII . 35 Equipment List CT-012S0 - 01321 CT-01280 Cyclone separator Md by Hooter. IHg. -5821. 2' die. * 6'7" high cyclone separator made of steel " and welded throughout. Order 13177 6/12/to. Req. 10232 on 6/5/AO. Price 166.25/ At CT-0762 eaat scrubber CT-01281 Cyclone separator. Same as CT-01279 and 1262. At CT-0759 . 2nd fro* Z scrubber. CT-012B2 Cyclone separator. Sene as CT-01279 1200 - 1261. Used st CT-0?60. 3rd from I scrubber. CT-01283 Chlorlnator made by Leader Iron Works, Inc. Xfeg. 16209. 3a x 16' steel vertical chi or. welded const. Older -1*119 on 6/21/AO, Req. 10*00 on C/ll/*0. frlce $780.00 )tI Bast of CT-0833. #* chlorlnator. Bee CT-07**. CT-01310 #5 Aroclor 1260 Storage Tank made by Leader Iren Works. Dwg. C-609. Herlsontal 10' 00 x 261 long on str. shell, lncld. colls, etc. Ositted 2-3" nestles changed 18" nos. to 2*" and added covers for 2*" nos. Tanks, colls, coll supports. Inside of nos. and manholes and manholes and nos. and Inside covers must be sprayed with sine ' 0.005" thick followed by a sprayed cost of 0.003" tin. I i Order B132*0 on 6/ll/*0, Req. 10*32 on 6/11/AO Price $2200.00. Underground S of CT-06A8. Pump P-0929. i I CT-01321 Pyranol Mixing Tank made by Hooter. I Drawing 06*55. t 1*' 00 x 10' high steel tank with 3/8" shell, f 1/2" std. leuiekle radius heads, entire Interior % sprayed with sdn. thickness of .015" Ain. 4 ' *2" Quadruples turbo sdxer complete Including ! 4 Turbo adaptor assembly -- off set from centre. (1) Order B20976 on 9/27/*0. Chg. out $2930.00 (2) Order 21762 on 10/6/*l, Req. 1366*. Cost $7*0.00 0139229 CD 1 LH i LU UD table of contents Cxtcutivt Summary ...................................................................................... Page X I. introduction ................................................................................................. X7 IX. luiho Episode ............................................................................................ III. Body Burdens, Metabolism, andKinetics........................... 29 XV. Cenersl Toxicity ........................................................................... SI V. skin and Other Cutaneous Tissues ................................... 59 VI. Effect of PCtS on Liver ........................................................ 6X VXX. Gastric Lesions .............................................................................. SS VIII. Carcinogenesis*. Experimentaland Clinical ............... as XX. Reproductive Effects .................................................................. 103 X. Mutagenesis ...................................................................................... 117 XI. Other Health Effscts ................................................................ 123 XII. epidemiology................................................................................... 145 XIII. References ........................................................................................ 1S5 XIV. Glossary of Terms ....................................................................... 205 Curricula vitae - Category X Team Curricula vitae - Category II Team hons 221921 nortcm nmuii icumc ninuict ccnuai imutiev XIX. BCUIfBCTT LIST, contd. Closed Tanks, contd. ni - 56 Bquipaent List CT-01521 01597 CT-01321 contd. .. Driven by NSC-01288, Motor M01718. 1$" stsus coll* *5 turn*, 18* dlaaeter,through the cover. 9600 lap. m!lone. Outdoors. Bverdur or fUnnlttd piping. Bronte vslves. ' Bettoo outlet to Taber pusp f015*0 delivering to filter press f-0159. Copped Inlet on cover for Attapulgus Berth. Msnlld. Steen coll. Dlsl them. Vent to sod-U vent box. Best lnsulstion (gone). CT-01577 Still receiver tank node by Nooter. ft*g. C-795, B-708g# like CT-0771. fA #1*5. 5'8* * 5'8" Monel oetxl receiver, conplete with cover, coll. etc. Olsss wool lnsulstion 2" end i' finished cost. Order B*157 on 6/27/*!, Beq. 18515 * 2/17/*l. fries $5295.00. IS corner of 12' level plmtfors In Bldg. CB. 1 used on #2 still S-062. CT-01578 Condenser tank Bade*by Mooter, fteg. B651. 12* ZD x 5' long Jlonel natal. Order B*137 on 10/20/A1. Beq. 18515 on 2/17/*l. fries $650.00 V of CT-1*13 en 20'6* level platfom. Bldg. CB. Like CT-0770. Deed on #2 still. CT-01596 Vacoun scrubber purchased fro* Conbustlon Engineering Co. Brewing C-807. 51 ID x 10' high, steel construction including gretlng end screen. Order B8560 on */*/*!. Beq. 19909 on */V*l fries $260.00. N one on 29' platfom. Like CT-0753. On #2 still, coke scrubber. CT-01397 Veter host exchenger nade by Leader Iron Works. Dwg. B-*85. 6* die. x 10' long. 12 tube. Order B832* on Beq. 19993, fries $119.00 North of CT-0851. On #2 still. Spore. . C119130 J C H W- v. r wi H V) H O O cn CP LTt jr II nOTterte nmiiLi yenure :iidiuci conxut imextiei m. tcrcyjgyT us?. contd. Closed Tanks, contd. HI - 37 equipment List CT-0139S 02*91 CT-01398 CT-01399 Cooler tank udi by Leader. Dwg. B6**. 2'6" 10 x 3' Wgh steel cooler tank cookiete with cell. Order B832* or VV'l. R*Q. 19993. >rlce $152.00 South one on 29' platform Died on #2 etlll. Vented. S-6239 and #2 blending tank made by Hooter. Dwg./D-10290, general arrangement. 7' ID x 7' high, complete with coll, agitator, and drive aupport, sine and tin lined, earns to be chipped and ground smooth. Order Bfi325 on */*/*2, Neq. 19990 on */*/*2 Chg. out $950-00. Driven by H-02170. Middle one of 3, north end of 121 level platform. Vertical bearing for agitator shaft, A-6853. Compare CT-0779 Newport experience shows the need for adequate heetlng and agitation in blending higher Arcelor*. ' CT-01*00 #2 filtrate receiver, made by Mooter. 7' ID x 7* high incl. coll and supporting legs. Inside of tank zinc sprayed, all seams chipped and ground. 1" glass wool insulations 2$" fin, coat. Order B&323 on */*/*l, 8*9* 19992, Brice $925.00 Heatons of 3 north end of 12* level platform, CR. Dwg. C-6863. See CT-0780. CT-01*13 Separator tank made by Helnts Steel. Deed on #2 still. Dwg. C6957. 3' ID x 6' high tangential separator with Integral vapor pipe coexists. Order B10722 on 5/9/*l Req. 20*29 on 5/l/*l. Chg. out $3B2.50. North one on 29' level platform Bldg. GX. CT-01*32 5th chlorlnator. See CT-07**. Mooter. Drawing 16209. CT-01*91 Heat exchanger tank made by Leader Iron. g. B*83, CABI #217. 6" dla. x 20' long, all steel, 12 tubes Order B21*79 on 9/19/*l. *eq. 2*89* on 9/19/*l. Chg. out $1*0.00. Used on #2 vacuum still system. 0139231 cj =j;"i HUJ R g fi 82 2 BP- 5 > -* rH 5" r> n r ISho Sin 3? nn c> is 5s O o ou>i 1 i UTi JC. I nortcTU nmuii toiiun xxaruxci eonuoi litioatio* 331. EgJIPWTST LIST, contd. Closed Tanks, contd. 331 - 38 Zqulpbent LI at CT-02086 -02621 CT-02086 Air blowing tank. Like CT-0750. 01-02*04 This store tank haa been aat up outdoor* to hold tha tri -tetrs-chloro benzene mixture, which la bought in rail cara and unloaded by pop F-Oil11. Tha tank la a vortical cylindrical vaaaal 1J`0" X, 20'0* high on straight aide with done top and bettos. Total capacity 20,000 U.S. gallena. It haa a bottom outlet, with a atrainer box, to pump F-02077 delivering to either of tha Fyranol blending tanka. The tank haa a Varec depth Indicator with atainleaa ateel exposed parte, a vent pipe, a dip pipe for air blowing, an Internal a teas coll, and external heat insulation. " - r . * ` I .-* verrx: Kr. Bartre, 19*7, aald that a hatch tank to hold filtered Fyranola, pending final approval, would be a convenience, CT-02621 An additional blender, CT-02621 baa been Installed out dcore for asking Fyranola. It la a vertical cyclmdncal ateel tank 10'6" IB 2J'0" high with flat top and bottea. Total capacity 14,600 U.S. gallons. The bottoe alopea 2* to the bottoe outlet, which laada through a strainer box to a Taber puap F-02179, dellvsrtng to the filter Frees, F-0172. The tank baa a 7l B.F. Llghtnln alxer Installed hori zontally lew dowr. through the straight aide, the exposed parte of tha alxer being aetalllxed with 0.015" of alu&inlun. The veeacl alao haa a Varec depth gauge with stainless ateel float etc, a vent pipe to a aoda line vent box, an internal steaai cell with T.I.C.rlten I-Ol69*.set at 50*C. (tin-sprayed themo well), and external heat insu lation. There la alao a dip pipe through which dry air free the Lectrodryer FC-046 can bs blomby a heat con nection with Corty coupling to agitate and dry the contents 1 of the tank. Attapulgus earth la Introduced through a I funnel fitted to an opening (with screw cap) in the top of j the tank. 0119332 I V OHHJ rzn Si: 5ni *" -- ?=g 8=: SI" nnr **4 HC inInfi ft 5 S! 55 X o o cn CP 1 un j nntenB nnuui seaixFro i>cuin csnuti UTiunei i. ;. - ' x::. Ecmpgxr list. cent*. *ii * ' qjlpn*.-.t List 1 Kt:! In MCC manual* the CT am. OT itiu of equipment ore t listed under "T'\ e. C CJed Timka tnd Open Tnki, hn sr nn O o ocn> 0139133 u~ i -C LU noTKTD nmuti acwtxrro iiisuki eonun utiutios xii. EqpiywDn1 list, conta zzi - *o SquipMbt List D-012 Drysrs P-012 Maker, Devine, 48" die. a 30" long, druM 3/8" thick, relied eteel, Machined end pollshod. Housing to be of #16 go, Monel, Order 8 7378 on 4/14/36, Iteq. 65124 on 4/14/>6. Price 41668,00 quot. 3/17/76, In lean*tc on floor on found, of concrete. Driven by h-0827 - 3 Hf Wegner Motor thru HSC-OOS. Jonee Speed Seducer. The pen le heated by gee flanes. Sketch hewing drw slde-knlfe, dip pen end eeeentlel dlnenelone on 48" dlen. x 30" long steel drun. Monel hood flaker -- drg. B-67J, chutes for finished product. Drg. D-518. See drawing S-374. Oeneral arrangenent, end C-627, weighing truck. Dryer for Attepulgue garth. In 1046 e vertical steel tank with internal steea colls was Installed at the Kmanrlch plant. It wee still the only equlpMent for drying earth at the KruBTlsh plant In 1955, but reliance was placed Mainly on supplies drawn fro* Anniston. Vlth the Krmrlch plant dryer, the earth was fed In through a hand-bole In the rever, and withdrawn, as required, by Means of a twin diaper arrange went on the wide bottesi outlet. See hand sketch sent to MCI April 1947. At Anniston the earth is arrtentd, 20 Mean, thar. dried In tray* about 3" deep, place In an electrically heated cupboard. Each tray contains a weighed aawunt. as that the correct charge of earth can be put into the traatMe.it tank directly frcM the dryer. 0139234 C*! H5 wsn S 3: a nQ 5 J5S 8$ sg:" HH O <A ?n rn ?s ft as un i I I f III. KVJTmrr LIST, contd. Dryer*, contd. Z3X >41 Squlpoant Uat Cry Pry*r for Attaplugui Earth contd. In 19*7 at the Lnatarieh plant the Attapulgut earth ** being dried In vertical cylindrical atael **ee*l with cone bottQB, and an internal ataaa sail. The earth wee rad in through a hand hole in the eever and withdrawn aa wanted through twin daaper* In the bottoa. See the aketch J aent to NCL with the drawinga collected in 19*7. The cover of tble dryer had a vapour vent, but there waa so poaltlv* aoveaent of air through the veaael, and the electrically heated ahelf dryer uaed at annlaton (aec page 5 of the report 'hot* a on the Annie ton Arcelor plant" Savercroft and Mather, September 19*7), would appear sore likely to glee thorough drying. The eteaa heated dryer waa atlll in uac at the Xrtanrlch plant March 31, 193*. Tba reference of Schwartlng and othere, Movasber 12, 1933. page 10, to an alectrloally heated dryer refare to a atlll earlier unit which had been abandoned. 0119235 t O-ln* n *sf!i = Onk *2H h: H9 "f fIflf * O in 3P nn ? r3 5* X oo cn 05 ( i LTi LTi i .* m. SQUingNT list, conta. XJ1 - *2 Equlpnent Uat F-0106 - 0172 Flltcra P-0106 ' Steal filter purchased fro* Hooter. Swg. C-3775* Site 12" die. x 3'10-3/** high. leg aupporta, glees wool packing. Order B35U on 2/19/36. Beq. 67729 on 2/l*/36. 2rt.ee 156.00 quot. 2/5/36. " Femerly need on chlorine gaa, bat need in 19*6 to filter out iron ate. Inpurl tie* froa the SCI sea eating froa other departments through a long steel line. P-0113 Sperry 2*" brente filter preaa. Cover for electric oven heater fer preaa -- Srg. *-685 Replaced by Sparkler prose P-0172. Steel support and pan for Sperry filter S-7121, 3/*" pipe coll for filter catch pan -- A-7136. P-0159 Oenoral Electric Filter Preaa. Serial #6166966. Type PT30. Accessories Included. 3 BP notor and * eeapartneat drying oven. Port 0, Cap. 25/30 gal. per am. Else 12", 20 chancers. Seated and lnsuleted teel cover* with pulllea, eabla. counter weight and atrip boater*. Pyianol plant. P-0172 Order *18935 an 9/21/39.- Itoq. 1991 an 2/20/39. Chg. out $98*.00 00 11/30/39. Sparkler filter. Serial *6*. Model l6-dl2 all bronse oonatruetlen with laproved Scavenger plate, plates to be arranged ao entire set can be reaoved. Sterna tracing lnalda the lagging, then a natal shield over all. Steal lag* and floor flanges for belting to floor. Served by punp 7-098*. Order B103O2 on */2/*l, Heq. 20*30 on */30/*i. Price $630.00 par quot. 3/19/*l. On ground floor center of Bldg. C*. Installed for Atoclora, but later transferred to uee on Pyranole. Chain hoist, KSC-01*95, provided fer lifting cut the neat of plates. KSC-0210B 011923d nontrn nmmi imrc ninuei eoriuti lxtxcatxos m. SCTIPHDff LIST, eontd. Z3I >43 Squlpnent Liat F-0172 - 0239 niter*, eontd. F-0172, eontd. Staple* of filter paper for the Sparkler preae F-0172, which waa then bein* uaed ai Aroclora, bought under the reference "#21-18 niter paper", $2,735 P*r 100 ahaeta. Sparkler Kfg. Co. Mundelein, were aent to London, April 9. 1947, P-0236 P-0172 waa aoved to the fyranol departaent and replaced by a 33" Sparkler. See Operating Instruction* 6/10/54, and Hr. Karden'a notea of August 1950. Sparklar niter, 330-12 eell type,304 Stalnleaa Heel, with jacket for 30 pal*. 33* Sparklar preaa for Areelora installed In plaee of P-0172, P-0172 beln* used for Pyranela. P-0239 Sweetland. Site 10 XH, 54 leave*. 523 aq.ft, C-I. body, lined with thick nickel. Nickel valve* and outlet Una, with puwp 7-01757 Out of use In 1955. (Pyranol plant). Hj Safi gS2 s si r H *s o -- n? R~ So *n*$ n 4O wfrV)) HO xn nr ss f3 55 X o 0 01 05 Lj LH -C _____ I 0139237 ; '4 ! runem omiut mnute ntruKi eernui liticitio* i' I' XII. ICPirnKT LIST, contd. XII - 44 Xqulpmwnt Llat PC-045 KnacH 7C-045 Oca heater for No. I atlll. Steal aha11 5/16" x 3'9" " dla. x 4'lOj" long, lined with Inaulatlng fire brick, etc. 1 coll 2" xUy pipe, 12 tuma formed into 2* die coll with apare blocka end lega. Drawing B-866. Req. 69659 on 5/14/56, Order B9&65 on 5/29/56. Deed to heat material in 8-043, punped thru coll by 2-0593. Tent atack drawing 9-689 (could not be found In 1946.} Piping detail*, drawing C-815, waa aent to London April 24, 1947. At plant B In 19*6, there war* two natural gae burner* aimed tangentially Into the bottem of each furnace, and there waa aoaw evidence of damage due to overheating of the loweat part of the coll, The central "diamy" Inalde the coll waa wade aa a aolld cylinder of firebrick and plaetlc refractory aaterlal built 19 on a circular plate auapended on a central ateel lifting bar. Bead rooa and a auapenalen hook are required over each furnace, for maintenance work. The aaterlal froa the atlll la puaped downwarde through the 0011 m the furnace of the new atlll, but upward* in the old atlll. The main reaeon for thl* la thet thl* arrangeaent enable* the coll of the deep atlll to be on the um level aa that of the ahallow one. At Annlaton the aaterlal la pumped upward* beoauae thl* put* the coldeat Arocler in at the bottom where the coll la aoat In danger of overheating. Thl* car. have little advantage, except toward* the end of the run, when the taaperature apread between the inlet and the outlet la greater. There la a therao-recorder pocket In the inlet of each coll, and another in the outlet. There are valvea or. the circulation line*, by which the cell can be aucked empty. See Section V3, page 16, Theae alao help in locating any blockage in the circulation eyatea. 0139231 X o o con) 1I i U~i jr vsoTBCTXs nmuii nuuro mnwei eenuoi iitiwio* . .' III. BOttlPHEKT LIST, eontd. - *5 Bqulpment List PC-0*5 066 -- fjmcti, centd. FJ-0A5 eontd. Hr. Puree? reported, December 5, 1951, that the eolle last about 12 month!, but uy require cleaning every 3 or * montha to remove pluga. At Newport the atlll coll la Interchangeable with that of the diphenyl department atlll. A temperature difference recorder controller waa Inatalled on the heater coll at Newport, and a COa connection made to the furnace for emergency uae. At Annlaten there la a 12-polnt Micromax temperature recorder on the chlorination ayatem, and one for each of the two vacuuai etllla. PC-0A6 Electric, Air Drying furnace purchaaed from Lectrodryer <1i Corp. Serial 270, Site BWC-2J0, dual-ebaorber type. AO# preaaure. **0 volta, tingle phaae, 60 cy. A-6 hour* operation. 300 amp. heater on each aide thermoatatl- t cally controlled, at 270*P. See T-01*. Order B7*03 on A/1 A/36, JteQ. 69119 on A/lA/36. Price $1,350.00 on 6/30/36. Baa blower with Motor M-01A86 for acavenglng. Serve! the alr-blowlng tanka CT-0750 and CT-02066, and the melter CT-0763, In the latter caae at preaaure enough to blow the charge to the chlorlnator. Brlnga the dew point of the air to between 10*P. and 10*P. lylea, Soffrenko and Miller (Pyranol report March gt, 19A7, page 60) atate that the dry air ahould be checked twice a month for lta moiature content, and that the alumina needa renewal about once a year. PC-066 Steel Beater furnace for No. 2 atlll. Drawing 0*3*79. Brick lining, cell, bumera and atack. S. V. corner of the 20*6" level platform, Bldg. OR. Generally like PC-0*5. Drawing 0-3*79 (elating April 19*6)' 0139239 o-1 Ha HX M HX n*n S22 o 3s X o o <J1 05 ln i LO 1 EXECUTIVE SUMMARY Tne present study on the potential health effects in human populations from exposure to commercial polychlorinated biphenyl (PCB) mixtures under occupational or other environmental conditions was conducted by a teats of specialists in the medical, toxicological, and epidamiologicsl sciences designated as the Category I teats. Draft material for the study report ws reviewed by a second group of specialists designated as the Category i: team, and other scientists, leading to comments and suggestions for improvement which were incorporated into the draft report. The available body of scientific literature on health effects of PCM in humane and in test animal systems was reviewed and analysed with emphasis on the relationships linking exposure, dosage to the biological target, end occurrence of specific health effects In the aniaal or human. Both the tosicological end epidemiological date from acute end chronic animal end human exposures wars considered In generating assessments of the prob ability of occurrence of any specific health effect In humans. Ths results of these assessments ere summarised below, separately Itemised under each sajor health effect. It should be noted that each assessment applies to ths potential for development of that effect under the type end level of human exposures actually encountered In the u.S. during the pest decades, with the moat intensive Integrated exposures having occurred In manufacturing operations that were terminated in this country in 1977. MOMS 221922 nntCTD nmuii leiime xssmaset cornuos lxyxutxo* l .' I xii. ecpipkes? urr, eontd. XII - *6 Iqulpment List 1-016 - o**i Instruments t 1-016 Taylor Temperature Controller. Drawing D**17, Size 1, #36JR323. Direet acting, self acting, with " std. double tested valve lnd. stsaa strainer. Range t1 110*P. to 170*P., get 122*, 25* tubing 3/** union hub connection placed 7' frea bulb end. Order B3**3 on 3/10/37. Rs*. 76979 on 2/15/37- Chg. out 3/31/31, 176.57. Cn CT-08*8, Pyranol blender. 3-0106 Rotaaeter Instrument purchased frea Eeoneay Equipment Co. Serial #10166. for scrubber TV-0162. No. 6, Pig. 25 bronze with stainless steel float calibrated for aax. cap. of 300 gph water. Order S19959 on 11/10/37, Req. 83079- Pries 666.70 I-020* Pexbero. DP cell. Stainless Steel body. Ml diaphragm. 1-02*1 TIC, UX. 2 point Mlcroaax. Range changed to 0-600*C. Used to replsce K5C-0666. \ 1-C361 falaer Supertar Dial Thenacaettr, 6" cone Mercury actuated. Range 0-150*C., 25' stainless steel connecting tubing with adj. claap, fig. to be located 9' free end of bulb. Order BI8365 on 8/23/*0, Req. 12533 on 6/23/*0. On 1269 stg. tk. CT-01310. fries <56.50 I-C398 pulton Sulphon Taaperatur* regulator #931 with 6A bulb and 20* of capillary - Bronze body stainless steel trla, to be used on steaa si 65# pressure. Range No. 76K-190P. to 250*P. Size 1, press N. C. on CT-07*8 diphenyl stg. tk. Order B23310 on 10/28/*0, Req. 1*583 cn 10/26/*. Price <69.05 I-0**1 L*k6 point tenpersture recorder. Serial #389329, #*0352M, Model S, mlcroaax strip chart teaperature recorder. Type DC potentiometer - aultl point curve printing, record numbered and color dot for each 0139240 1 i Clj * LTt LTi CZt 1 nsncTD urtmii imum zaanujtcz eemui imunn xii. zcgimprr ust, contd. xn - *7 Equipment Id at 1-0**1-01128 Instrument!, contd. 10**1 contd. thermocouple. Hate cycle - 30 aec. normal Ter each point. Order B13260 on 6/l8/*l, Req. 81078 on 6/17/*l. Price $595.00. In aeeend floor control room, Bldg. Clt. 1-<S*3 Vatt hour meter Instrument purchaaed from General Electric. Serial 21-220-7*5. #85 x 905. Type V5A, 220 to 5 CT uae. Order 8 9118 on */15/*l. Req. 20515 on */l*/*l- Chg. out $52.*0 on 6/30/*l. In cabinet outalde Z wall BldC. CR. 1-0577 Palmer Dial Thenometer. CAB1 #217* Range 0-150`C. In Pyranol Mixing Tank CT-01521. 15 ft. stainless ateel apeclal amor flexible tub In* plain bulb. Order 820*58 on 12/1/41, Beq. 8**85 on 9/9/*l. Chg. out $*9.59 on 1^27/*!. 1-0855 Bailey Integrating and Recording Plow Steam flowmeter. Serial #1399611. Order B115&9 on 9/*5/*5, Req. 67905 or. 5/ll/*5. Price $5*8.00 In control room E wall. For atetm from the 800 lb. main. Suppllea the ejectors, the high preaaure colla In the alr-blowlng tanka, and melter. See RSC-0682 for the low pressure steam netsr. Taylor Pullscope recording controller on the Mo. 1 still vacuum syatam. Chlorine flew recorder controller on Do. 5 chlorlnator. Bee also R3C-0663, page 6l. 0668, page 61. 0675* page 61. 0662* page '5. 0705* page 63. 1-01118 Pcxboro steam flow controller, 0 - 8000 lba. per he\r. 01392*1 CHM "*" nSE > -I r ts: llr .*-3m e4 * SS El ao 03 IK LTi LH \ J m. sgoiynprr ust, eontd Pi - ho Zoulpaent Ust 1-015*7 - 080*5 Instruments, eontd. 1-015*7 Taylor n, 2 pen, with alars and shut off waive. Chlorine lines. 0 - 100 pslg. 1-0189* 1-019*1 1-02019 1-020*5 Teylor pulsecpe TI C. 0-150*0. wortong st 50*C. Tin-sprayed thenso well. On blender CT-02621. Controls Pieher diaphraga wslwe on stean to coll In CT-02621. Pyranol blender. Poxboro. D.?. cell for chlorine liquid in store tank. Taylor pulscope UtC. Worthington heter, gallons, well water. See also M3C - 0663 0668 0675 0682 0705 0770 01393 0139242 !' 1 UTi LH 1 1 * nortsTB Dmuii Boturo Dinuet eoniut lxtxcatxo* . . ' PI. BOCIPKPrr LIST, contd. HI - *9 Squlpaent Hat L-0J1 Elcvatora L-0J1 Bucket elevator fro* General Conveyor *Kf(. Co. ! Drawing 1*670. I4. to be 22'*-ll/l6" OA c to c take up ahafte and 20`6" casing and bead auction 3/16" and . boot 1/*", 6" belting, * ply It covered pinched 10-7/32" for bucketa of *$ x 3* chrome ateal. Order BIW55 on 5/15/36, Mq. 701*0 on 5/25/36, i Price 91.20. Driven by M-083*. Drive drawing B-661. Solid Aroclora (dianantled 1952). See alao V**, *5, *6 eonveyora fro* flaker D-012 to elevator 1>-031, and chain holat MSC-01*93 over the 1 Sparkler filter S-0172, and electric holat KSC-0655 for , aolld Aroclora, A chain holat la uaed alao to lift baga of Use to the atlll operetlng platform. on MSC -! 4 (A j n*n g 2 r P. 5 2 v> r>a> e rm (A o o z* 1 i U*i lh LU 0139243 wwiciii* nmuii mo**xto ninun nmut lxtxsitxo* XII. ECJIPKEMT UST, contd. XII - 50 Equipment Uat B-0790 - 065* Hotere note t The sotora are changed to other dutlea froa time to time , but the following detalla will earve to indicate the type* of aotora uaad. 00790 Waatlnghouae Motor 3 HP-1750 REM. Serial 7*35. Type CS, eq, cage Induction actor, horlt., frame V225, 220/440 V. 3 ph., 60 cy., 6/* asp., 55*C. teap., rise, atyle 80106&Y, claae 1, total encloeed, ball baanng. lUc'd. 6/20/35* (#6056.5077) $76.96. On pusp P-0346. ' M-0B27 Motor 3 HP 1200 HPM fro* Vagner Electric Co. Serial #1716199, horizontal Induction aotor, totally encloeed, fan oooled, ball bearing, 3 ph, 60 cy, 220/4*0 volte, 8.2/4.1 asp., type CPI, fraae 25*, nodel V425198. Order Sl6* or */23/36, lUq. 69376 on 4/23/36. Chg. out $9*. 16 Also drive* V-046 thru aecond chain on link belt; drive* D-012 fleleer thru MSC>039 apeed reducer and ehaln. M-0630 Motor 2 HP 1600 purchaaed froa Oeneral Electric. Serial KX>1*07, Eorlaontal Induction, totally encloeed, fan cooled ball bearing, fraae 225, 2HP 17*0 HPM, 220/**0 volte, 5.61/2.81 anp., type X, 3 ph., 60 cy., nodel SX-225-A715. Order S8169 on 4/23/36, Heq. 69377 on */23/36. ` Chg. out $73.6* on 6/30/36. Drive* P-0565. M-0832 Motor 3 HP 1200 HPM purchaaed froa Vagner Electric. Serial 171*95*. Honaontal induction, totally encloaed, fan cooled, bell bearing, 220/**0 volta, fraae 25*, 3 ph., 60 cy., type CPI, aodel V*2J198, 8.2/4.1 aap. Order *8178 on 4/23/36, Heq. 69378 on */23/36. Chg. out 49*.l6 on 6/30/36. On blower B-09*. M-083* Oaared head aotor 2 HP 1200 HPM purchaaed froa Heeter Electric Co. Serial KE-975, air Jacketed, totally encloaed, fen cooled, 11*0 to 220 HPM single reduction parallel geared heed, 220/440 volta, 3 ph., fraae 25*. type PA, style *7*76, 55* cont. rating, 6.2/3.1 w. Drives 1-031. Order S6156 on 4/24/J6. Req. 69373. Chg. out 4109.14. 0139244 C H -T H ti H r5n g32 Cl R X ^5l Sg1" pi pj r 3n `4 ^0 w1/1 5 r> R os f3 5S o 0 01 03 LZl 1 1 LH nnuui vovujrre minuet eonuti liticatxow ! ( j . I XII, ECUIPMEirr UST, contd. ni - 51 Equipment tist M-0835 - 0648 Motors, contd. H-0635 Reeves vertlcsl motod rive 1$ H? l800 lint purchased from Bates Co. Motor serial 191*691, motodrive unit serial MD-1136. Site 4253-E-18, model V 34J223, 3ph, 60 cy., 1.9 amp., frame 2*, * to 1 speed variation and 50 to 1 gear reduction, hand chain control and chain in place of standard hand wheel. Order B 7376 on */l*/36, Req, 69123. Charged out >300.96. Drives V-O**. M-0836 Reeves vertical motodrive, same aa.M-0835 Drives V-0*5. M-0641 Oeared head vertical mounted motor 5 HP purchased from Master Electric Co. Serial HE-968. 220,4*0 volts, 3 ph., 60 cy., totally enclosed, fan cooled, ball bearing, type PA, frame 11230 # 25* DP - 1725 to 60.2 RPM Style *7*76 - cent. 55*C. Order B 6155 on 4/24/36, Req. 69375 on 4/23/36. Chg. out >211.84 on 6/30. Drives stirrer In blending tank CT-0779* H-o*6 Vertical mounted induction motor. 1 BP lBOO purchased from General Electric. Serial EF-2773. Totally enclosed fan cooled, ball bearing, thrust type with ring base and drip cover, 3 ph., 60 ey., 220/**0 volts, 1720 RPM. Model 5K204A1550. Praam 20*Y. Order B 8175 on 4/23/36, Req. 69371. C>. out >55.44. Drives P-0573. M-0847 Vertical mounted induction motor 1 Hp lBOO purchased from Oeneral Electric Co. Serial EP-2779* Totally enclosed, fan cooled, ball bearing, etc. same as M-08*6. Drives P-0909. M-06*8 Vertical mounted induction motor 1 HP lBOO purchased from General Electric Co. Serial EP-2777. Totally enclosed, fan cooled, ball bearing, thrust type with ring base and drip cover, 3 ph., 60 cy. 220/4*0 volts, 1720 RPM, model 5K204A1550, frame 20*Y. Order B8175 on 4/23/36, Req. 69371. Chg. out >55.44 Drives P-067*. 0139245 eHVH ?i*5 a= ?> S 5 -X e H ps 8w- c nz rnn a5 rs 55 C3 1 un un un norvns nnmii ioiiut muiuci eomui imoxtioi XII, tWIFMENT UST, eontd X3I - 52 Equipment Lit M-06*9 - 0671 Wet on, eontd. H-08*9 Wagner horlz. induction motor 9 HF l800 Serial #171*562, totally enclosed, fan cooled, ball bearing, type CFI, frame 25*, model W-50J195, 5 ph., 60 cy., 220/**0 volte 1750 RFM, 12.6/6.5 amp. Order B-8177, Rq. 69572, chg. ojt 197.06 6/50/56 Drives F-0578. On pump F-0578, on Mo. 2 chlorinetor. W-0650 Horizontal induction Wagner motor 5 HF 1800 Serial 1716576. Same ea M-06*9 and 0651. Drives F-0579. C*i pump F-0579 i on #5 ehlorlnator. W-O651 Motor same as M-o8*9 and O650. Serial 1716577. M-0855 Vertical mounted induction motor 5 HF lfiOO C. I. Makers. Serial FF-110*. Totally enclosed, fan cooled, bell bearing, thruat type with ring bsae and drip cover, 5 ph., 60 cy., 220/**0 volte, 1750 RFK, model 5X225*2*50, 8.5*/*.27 amp.,frame 2257, type K. Order B 617* on */25/56, Req. 69567. Chg. out >95.92. Drivea F-O565 M-065* Motor Serial FT-5696 aame aa M-0852 and 5, on CT-0766. M-O856 Vertical mounted Induction motor 5 HF 1800. Made by 0. I. Serial P?-2*57. Thruat type and drip cover, ring base, class 1, group d, underwriters #5*7*727- Explosion proof, ball besMng, 1720 RFM, 5 ph., 60 cy., model 5X225X2**6, 220/**0 volts, 6.*2/*.21 amp., frame 225Y, type K Order Bfil72 on 6/26/56, Req. 69566 on 4/25/56. Chg. out >115.56 on 7/15/56. Drlvea F-0585. M-0871 Vertical induction motor 5 HF - 1750 RFM from 0. E. Serial PF-3177. Totally encloaed, fan cooled, ball bearing, thruat type with ring baae and drip cover. 220/**0 volte, 13.9/6.95 sap., frame 25* Y, type K, t 60 cy., 3 ph., model 5K25*S1930. Order Bfil73 on */23/36, Req. 69569. Chg. out >12*.21 on 7/51/56. Still pump drive, drives F-0593. 0139246 1 C"1 M" *-1 HMM nxn O3 *aS-B On-- ri r o--n 8 " - 8 3 wwto *4 r> rr. mr cc> *4 rx -> 1 U~i un U i i i i m. tgnywprr ust. contd. Z3I - 53 Bqulparnt Uit M-0873 - 091* Motor*, contd. ` M-0&73 Vertical mounted Induction motor 5 * 1730 RPM. Purchased fro 0. I. Serial 77-3107. 220/440 volt, i i 60 ey., 3 ph., totally enclosed, fan cooled, ball bearin*, thrust type with rin* bate and drip cover. ! Model 5K254B1930, 13.9/6.93 ap., frame 25*Y, type X. Order B6176 on 4/23/36, Req. 69370. Ch*. out 1124.21 on 7/31/36. Drive* 7-0592 In tank outside. ! M-0&75 Boriaontal induction motor 1 B? 1200 Bade by 0. X. Serial DT-5227, Totally endoaed, fan cooled, 60 ey., 1130 RTM, Model 5X204*1036, 220/440 v., 3.'*5/1.73 amp., from* 204, type Z, 3 Phase. Order 813188 on 7/2/36, Req. 71152, ch*. out 7/21. Drive* 7-0595. M-0663 Vertical Mounted Induction motor 1 H7 l800 purchased free Continental Zqulpnent Co. Serial 50496. Totally enclosed, fan eooled, ball bearlnc, thruat type with rin* base and drip cover. 2.9 asp, 3 ph., 60 ey., 220/440 v., 1750 RTM, type KCT20. Ordered for spare. Drive* 7-0604. Trice 648.00. Order 8-13196, Req. 711*7 on 7/1/36. M-0904 Motor 3 H? - 1200 purchased from Continental Electric Co. Serial 51704. Totally enclosed, fan cooled, nomal starting current, squirrel cage induction motor, 3 ph., 60 ey., 220/440 volt*, 1150 R7M, 55* ecnt. rlo, type K7 254, 6.4/4.2 a^>. Order 817*31 on 9/1/36. R*Q 72637, Ch*. out 690.40 on 10/24. Drives 8-0105 In Bid*. CR. M-0914 Blsdaoer motor 7i H7 l800 made by Louis Allis. Serial 2175*3. Totally enclosed, fan cooled, type JZ, 3 ph, 60 ey., 220/440 volts, 1750 R7K, frame 28*, class 53d, fens B, lfi.4/9.2 arep. Order B21241 on 10/22/36, Req. 7*03*, Ch*. out 6133.12 Drives Naphthalene pump 7-0617 for CT-0347. I 0139247 Lj LTt LH ^1 runten Tii nnuui idhutc xaamjutex comui litxaaTxo* J i m. tcuirMQT ijgr, contc. m * 5* SqUlpOent Hat M-0955 - 01t29 Motor* eontd. M-0955 fortable "Ughtnln-Miser" 1/4 R? 1725 purchaaed fron Mixing Iquipaent Co. Kiser Serial 37106, Motor Serial KE-4536. CABX 106/1936. Model C-4, 3' folding acntl Mtal propeller aonel abaft, 4/2 anp., 110/220 volta, tingle phaae, 60 cy., claaa 1, grpup d, exploiton proof, underwriter* P-519372, extension oord and attachment plug. ) Order B13*0 on 1/19/37, Meq. 76212 on 1/18. ! Chg. out $109.42 on 2/27/371 Deed for drux shipments. M-0975 Motor 5 HP l'SOO purchaaed froa Wagner Electric Co. Serial 1725336. Totally encloaed, fan cooled, ball bearing. Induction awtor, type CPI, frame 25$, Model V30J2*7, 3 ph, 60 cy. 220/440 volta, 12.6/6,3 aap. cent, rating 55 *C. - Order *2834 on 2/9/37, Meq. 76765 on 2/5/37. Coat $95.61. (Vi P-0629. On No. 1 chlorinetor pump P-0629. . M-O965 Vagner Vertical Motor 7$ HP - lBOO RPM. Serial #1726961. Totally encloaed, fan cooled, ball bearing, type CP-2, fraae 234Y, 440V, 60 cy., 3 ph., 18.4/9.2 amp. 1750 RPM, Model V40V143. Order B3323 on 2/12/ 37 and Meq. 76927. Chg. out $133.98. Inat. to drive submerged pump in TCB atg. tank 0-08*8. cn P-0346. M-01229 ` Vertical Mounted Induction Motor 1 HP lBOO purehaeed fron Louie Allis. Serial 269797. Totally end. fan cooled, ball bearing, thruat type with ring baae and drip cover, weatherproof conduit connect.un box, type IS, fraae 20*V, claaa L, fore B. 220/440 volta, 3 ph, 60 cy., 3/1.5 aap. eont. 55*C., 1730 RPM, Order B3853 on 3/4/36, Maq. 66689 on 3/3/38. Chg. out $55.20 on 4/29/58. (ki puap P-0731. 0139248 6* o-1 hs --I Hin 3 l" 822 S S5 * 55 8: S" rs*j rm -4 aO mia - n rpi rw* c la 3s CD i un un rtoncnx nnuui mnwiaaro ninun comui imunei PI. ECTIPHEKT UST, eontd. PI - 55 Equipment Hat M-01377 - 01573 Wotora, eontd. H-01377 0. X. Motor JBN lBOO MM. Sena! MR-6969. Totally enclosed, fan cooled, aq. cafe, induction motor, type X, ball bearing, 220/Mi T, 60 cy., 3 ph., frame 25*, 1760 MM, model 5X25*691. 5.**/2-72 amp. Order B15955 on 9/26/36* Raq. 91711, Chg. out 675.00. On P-01111. K~01*56 Veatinghouse horizontal motor 3/* M 1200 Serial *139. Totally encl. fan cooled, low starting current, *40 volts, 5 Ph., 60 cy., 1160 MM. Type CS, frame 20*, 2.6/1.3 amp., style 1707136., 55*C. rlae, Chg. out maeh. 6*1.03 on 12/29/39 Order B17367 on 12/18/39. Req, 1357 on 8/31/39 on Blower B-01*8. M~01*69 0. X. Motor 3 M-1200. Serial #KT-10671. Totally encl. fan cooled, modal 5*25**102*, frame 25*. type K, 220/**07, 3 ph., 60 ey., ' 1165 MM, 9-06/*.53 amp., eent. 55*C. nee. Order B18935 on 9/21/39, Req. 1991 on 9/20/39. Chg. out 672.*7 on 11/30/39. On gear pump to P-0159. M-01*86 M-01501 M-01573 Oeneral Pectrlc Motor 1/* HP 1800, totally encl., model 5 XH*7AB96*. type EH, 110 volts, single phase, 3>* amp., 55* Cent. Order B17923 on 10/17/39, Req. 1531 on 9/8/39. Coat 62*.25. On Xmctrodyer PC-0*6. Replaced by M-01706. Motorised car apotter 5 HP 16*0 MM purchaaed from Link Belt Ce. motor aerial 307939, apotter aerial 5252. 220/**0 volts, 60 ey., 3 ph, type IX, frame 225 W, claaa 3, form B, 17.2/6.6 amp. 55*0. Order B267*l on 12/29/39, Req. 5126 on 12/29/39. Chg. out 6373.66. On track 11 at load doek. 0139242 OH- nx gH, rSE t>* pH- 3> 8co=w! xH H n cn H ft ss > f* 3" oo ui co :ud i UTi i un lo 2 Yusho Disease Separate consideration was devoted to the Yusho episode recoqmsing the special character of the human exposures to nigh concentrations of mixtures of PCBs and their thermal degradation products, polychlorinated dibenxofurans (PCDFs) and polychlori nated quaterphenyls (PCQ*). Several conclusions reached by the Category I team are of importancet (a) it is impossible to stipulate whether any of the health effects observed is causally related to PCS exposure, since the other nalogenated compounds are also biologically active; (b) the dosage patterns experienced by Yusho patients and U.S, industrial workers (FCB-expoaed) are not at all comparable; the letter group experienced low level, long time period exposures primarily vie inhalation end sum contact, with only minimal oral ingestion; <c) the similar health effects seen in Yusho patients from the Japanese and Taiwanese episodes of exposure to contaminated cooking oils point to the same type of toxic mixtures resulting from thermal heat ex changer action in the two events; (d) because of points <a>-(o above, and the fact that at least the PCDTs in the Yusho oils are potentially more toxic than the PCta on the basis of animal data, it is not possible to extrapolate the Yusho experience to prediction of acute and sub-chronic effects of commercial pet mixtures in the human; (e) finally, with respect to predic tions of human carcinogenesis from the Yusho type of exposure the date are so incomplete that conclusions regarding any types and amounts of excess cancers attrlbuttable to those exposures nave to await further definitive study. MOMS 221923 J i Il JDI ggri?KEVT LIST* contd XII - 56 Squipnent Hat M-01622 - 01660 Hotora, contd. M-01622 Ocneral Sleetrle netor 7i HP, 3600 RTM, Serial SU7108. Totally enclosed fan coded, type D, nodal 5*H25*C25, franc 25*, 220/**0 v., 3 ph., 60 ey., 3*35 HP*, Drives HL-0*5 Order B*ll8 on 2/20/*0, Heq. 6737 on 2/10. Chg. out $11*.96. I *-01629 Vertical notor 7$ HP purchased frees Turbo. Made by Vestlnghouse. Serial 26*0. Totally enclosed, fan cooled, franc 28*, class 1, HP* at full load 1735. cont. rating at full load 55*C. rise, 220/**O volts, 3 ph, 60 cy., 18.8/9.* a*p., style 1071192. Order *83,37 on 5/20/*0, Heq. 8**1 on */9/*0, chg. out $112.66. (hi NSC-01205. Driving agitator in CT-O808, final ehlorlnator. M-C1650 Inula Allis notor % HP, serial 25833*. 1750 HTM, type JS, franc 25*, class *3N, form B, 220/**0 v., 3 ph, 60 ey., 13/6.5 anp., full load 55*C. cont. Order B26263, Heq. 85*32 on 12/2*/37. (hi Sparkler press puap. N-01656 *-01660 Vagner Eeetrle Motor 5 HP 1800 RPH Serial 1758959. Horizontal totally encloaed, fan cooled, ball bearing, laaa base and pulley, type CPI, franc 25*, 220/**0 v,, 3 ph., 60 ey., 1750 HP*, eont. rating 5*CP, sodel 1B8J247B, 13.2/6.6 anp. Order B12802 00 7/8/*0, Heq. 10231 on 6/5/*0, chg. out $87.92. Drives p-01056 Taber Horisontal puiep. * Oeneral lleetrle Motor 1 HP 1800 HP* purchased fron Tsber Serial 0C1902. Totally encloaed. fan cooled, vertical nountad, ball bearing, thrust type, with ring base and drip bover, 3 ph, 60 ey., 220/**0 vnlta, 1720 HP*, nodel 5K20*A1550, franc 20*Y, type X, 3.11/1.56 anp., eont. 55*C. riae Order B13111 on 6/10/*0, Heq. on 6/10/*0, chg. out $50.19. Drives new Taber aub. puap P-0909. 0139250 i OH- z -n jEH n?n g22 nMXn* On CI p *5P jcw pi n r Cw Hn Rn e h 35 D O WCJJ CO i LTi Cn eri I XII, tetnyKENT LIST* conid Wotor,, contd. X3I - 57 Equipment List W-0116697- 01T?5 *O: rH - H= W at HXn *caB. ^5mnm P--z*) c--n 51" HPzi n3 rnW - O v> M-01697 Motor made by Vaener 1/3 HP, CAB2 169. 30" dia. type S-6CVS, style l2*9-b622 portable circulating fan, I single ph., 60 cy., 116 volt,, complete with (uarda, 'poor column, and cord, B16528 on 7/26/*0. Req. 11797 on 7/26/b0. Che. out $60.58. Qsed on operatlne platform near chlorlnator. ' 3? Oi 5- rz > 3* W-01706 Vertical mounted induction motor 3 HP 1800 made by \I 0. E. serial JU3*98. Totally enclosed, fan cooled, ball bearing, thrust type with rtn* base and drip cover, model 5K225a*26*, frame 225W, type X, 220/**0 v., D O 3 Ph., 60 ey., 1730 RPH, 8.5*/*.27 amp., cont. 55*C, rise. v Order Bl8**3 on 8/23/*0, Rsq. 12560 on 8/23/*0. tn 09 Che. out 192.2b on 10/31/b0. (hi P-0929 Taber. M-01718 Replaced by M-01501. Louis Allis Wotor 7i HP-1800 RPK, Serial 333985. Totally enclosed, fan cooled, vsathensroof conduit connection box. Type JX, frame 28b, 220/bbOV. 3 ph., 60 cy., 1750 RPH, Class 0, form R, 19.6-9.8 amp., full load temp, rise 55*C. trine hours cent. Order B21C?1 onyjO/bO, Req. 1367*. - 1 ~i t Che. out $113-00 on 10/31/b0. Drives (Pslk Reducer MSC-01288) on Turbo Mixer for U~i CT-01381. W-01752 ' Motor 1 HP-1800. Serial 776*0. Totally enclosed, ball bearine, squirrel cac*, weather proof threaded type connection box, type CS, frame V-20*, 220/bb0 v., 3 Ph., 60 ey., 1750 RPM. ` Order B26350 on 12/*/*0 and Req. 15836. Che. OMt $36.98. Cbi B-03*. M-01772 Levis Motor 1/2 HP 3600 made by 0, X. Serial J33, CABI 169, totally encl,, model 5X*9BC756a, type X. rite 55`C., **0 v., 3 ph., 3*50 RPM, amp. 7. Che. out $25.00, Raq. 1666J on 12/30/b0. Use with P-0378 on 0T-o6*0. 0139251 ; i tiotKTD nnuut lonum mnuct cornuo* inmnoi XII. BCTIPPBfT US?. contd. XII - 5C Cqulpttent Us t K-01811 - 01995 Motors, contd. K-01811 Louis Allis Kotor 2 HP lSoo HPK Serial 365375. *' Totally enclosed, fan cooled, norms1 starting current. Cl conduit connection boa, less bsse end pulley. 20/4*0 i volts, 3 ph., 60 cy., 1750 RPM, type JS, frame 225, clsss K, form K, code H, 5.6/2.6 sap. Order B*136 on 3/7/41, Req. 18313 on 2/17/41 Ch*. out 165.36 on 6/30/41. Ch ground floor N. E. of P-0172 on P-01037. K-0ie50 Louis Allis Kotor 1 HP 1600 RPM Serial 395205 Totally enclosed, fan cooled, ball bearing 220/4*0 v., 3 ph. 60 cy., 1740 JtPK, type IS, frame 204, class L, form B, 3.1/1.55 tap. Order B7*ll on 3/26/41, Rsq. 1963* on 3/26/41. Ch*. out 136.98. On (round floor. M-01656 Louis Allis motor 5 HP 1800 RPM Serial 391009. Totally enclosed, fan cooled, vertical fl(d. mounted (CZ conduit connection box) normal startlns current, 3 ph, 60 cy., 220/440 v., 1750 RPM, type JS, frame 25* VB, class N, form B, code H, 1.3/6.5 amp. full load temp, rise 55*C. Order B6380 on 3/13/41, Rsq. 19213 on 3/13/41. Ctg. out $109.7* on 6/30/41. On P-0997 top of S-062. M-C1839 Unit heater from Am. Blower Corp. Serial 1939. Order B8936 on 4/11/41 and Bsq. 202*0. Chg. out $48.73. In iec-01393. K-01995 Motor 1/3 HP 1800 RPM mads by 0. X. Explosion Proof, class 1, (roup d, underwriters No. PA352-094. Totally enclosed, fan cooled, ball bearing, i type X, frame *54, model 5K454C102*A, tesp. rise 55*0. trine rating cent., 4*0 v., 3 ph, 60 cy, 1725 RPM. 55 amp. Order B*625 on 2/21/41, Req. 18520 on 7/21/41. Chg. out $29.75 on 9/30/41. On P-01054. f 0139252 OH- H V> H nIn g22 r. R5 H >O e C ift Mz HC n Ifl Hz r nn *s ^> a* O o 07 03 un )u i LJ narrcm Karmui imun mnun ccrxrut liticatio* XII. SCCIPMENT LIST. cent a. XII - 59 equipment List M-02170 - 051* Motors, contd. M-02170 Oeared head actor 5 HP l800 KPM. Made toy Master Klee. Serial PD*9. Parallel, air jacketed, fan cooled, * totally enclosed, frame / 25*, 60 KPM on mixer shaft, barrel amounting for vertical openetion, style 1035*3, 220/M0 v., 3 ph., 60 cy., 1725 KPM, type PA, aap. 13/6.5, 3 ph, trine hours cont. PI/TX 55 *C. Order B3560 on 4/B/42, Heq. 30060 on 2/10/42. Chs. out $259.25. Ch CT-01399# #2 blender. M-02175 Office Pan. M-02877 Drives P-01111 at loading dock - 5 HP. M-03133 Drives F-015*0. M-0*592 Drives Side entering agitator in #2 six tank CT-02621. H.0*691 Drives P-02077 at TOCS storage. M-04617 Exhaust fan - located In pyranol press room. M-04025 Drives P-02077. M-051* Drives F-02251. O**! HZ --P 3H n * r> 22 ES5 a* 3>P p H -- -->aXp 8 w- Si1" pzH* n 3 pntvn> Hzr Prr s* c? a* D 0 01 CD 1 lh Cn lu 0139253 3* I nencnt nmuii aoMxrro mnuci eenust litiutioi i CI. ECPIfKE?*! IIST. eontd X3I - 60 Squlpment Hat HL-0*5 mu KL-0*5 "Helix-Seal" Impact mill purchased from Vllllama T. C. A pul. Co. Serial #939*. Slxe #1. laaa drlva pulley-Driven at 5300 WM thru V bait drive fumlahed by Monaante. Order B2J71 on 2/1/37. Maq. 76576. Price 1*20.00. Meat lean-to. Hand fed. for aolid Aroclora. Di amentled 1952. $i; HWH * S" s "5H *tn x>am ee v* pai rnwtfi H SK > - rx 35 X oo a 4 cn 01392S4 4 i ' I '* ` XII. ggPI7HENT UST, contd. I Mlacellaneous Equipment XII - 61 equipment Llt MSC-O639 - 0675 t KSC-0639 Speed reducer made by V. A. Jonea Foundry, Serial 85967* #105DW, sasemfcly #1, style A, 36 to 1 ratio, low speed baft to be 7i" Instead of A" extension. Order BC2*2 on */2*/36, Req. 69*09 on */S*/36, Fries $156.00 Driven by M-0&27, drives D-012. CR, lean-to,'. M5C-0655 Shepard Electric Uftabout Holet. Serial 36306, AAO volta, AC, 3 ph, 60 cy., single speed control i with motor drive trolley. Holst speed 18' per min., lift 19'. Moist motor 3 HF. Travel motor 3/A BF. Order B7A05 on A/lA/36, Req. 691*0. Chs. out $906.70. HSC-0663 Multiple temperature recorder *0112-291 Micromax Model S strip chart, 2 prints, surface panel $300.00, Made by Leeds and Northrup, Serial 276758. Order *9975 on 5/19/36, Req. 69970. In lean-to. Bids. CR. MSC-0668 KSC-0675 Ltd Temp. Recorder atade by Leeds and Northrup. Peg. *.666, Serial 276607. (1) #A035*-291 Mlcramax model S strip chart, multiple teaq>. recorder, * point. (Multiple colored dote lnetead $* . .of mabere on print wheel). Surface panel mounting 65 00 (2) Ertrm for high contact for operating alarm $20.00 Order *9976 on 5/19/36, Req. 69969, Chg. out $*91.82. South wall, weet Instrument, Bldg. CR.(See note on next pg.) Replaced by I-02AA. Temperature Recorder purchaeed from Leeds and Northrup. Serial 27678*. #*0353-291 Mlcromax, model S, strip chart multiple point tetperature recorder for 3 prints. (Multi-colored dote instead of numbers on print wheel.) Surface panel mounting $*00.00. extra for high contact for operating alarm, $20.00. 3 thermocouples to fit wheels. Our >rg. B-666. Order B9977 on 5/19/36, Req. 69968, Chg. out $32*.05. South wall, eaet instrument, Bldg. CR. (See note on top of next page.) 0139255 HH s O oH_ F S Si > - x rh> p s 5?n 1"* Hz i nw O v> H SK ?5 f~a> a* X o o uo>i L3 s LH i Cn un ( I Cl. -* ' ECUIP.T list, eontd. S2 - 62 Equipment list WSC-0668 - 0676 Miscellaneous Equipment, eontd. MSC-0668 -0675 Note; Record the following tesg>ersturee; " Botch temperatures in chlorlnators: CT-07** 07*5 0833 0126? I 0606 I Ooode temperature in diphenyl store tank CT-C7*8 Coil inlet temperature on the ttlllt 8-0*3 and 062. outlet ' ....................................................... vapour temperature entering the condenser. Ooode temperature In receiver. Ooode temperature In blending tank, CT-0779. RCS-O676 Brewing 8-666 shove thermo-couple veils. Brewing B-6868 shows monel thermo-couple veils ss used In distilled Aroclors, Ou electric Vster Cooler for drinking vster. Mode by 0. X. Compressor 63*1356, cabinet 6600607. Model RM-51, pressure type, 110 v., single phase, 60 cy. Order Bl*0*5 on 7/l*/36, Req. 71*32. Chg. out 7/31/31, $176.00. On 121 level, Bldg. CR. 0139256 O^ H5 --*! H Vi H 0 n5 H- Oz> 8o n:_ Smr 3 VVIi i ss ?3 a5 *> X o o J raortcra onuui unturro iwsnuet cumxai tmoaTiox -* ' XII. ECPiyKPTT LIST, centd. X2I - 63 Equlpaent List sc-068l * -75* Miscellaneous Equipment, contd. C-066l Rail truck purchased from Nutting Truck Caopany. Dug. C-827. Welded construction, wheel# equipped with Hyatt Roller Bearings. Uaed as weigh truck for still pots on SC-093. Includes track. Order 81113* on 6/3/36, Req. 870395. In lean-to Bldg. CR, nsc-0662 Brown aech. flowmeter. Serial 115969. Recording and Integrating steaa at 65# ga< press. Dry sat, orifice Bonel In *" std, hont, line, (used on 80 lb, sain). Max. flow *000#/hr. Model 2221-x*0. 2 lga, 25* of J* copper tubing and connectors - Mononeter valves. Elec, clock for 110 v 60 cy. Order 81*60* on 7/22/36, Req. 715*8 on 7/20, ehg. out $280.00 KSC-C705 Falaer Industrial Therewneter CABI #89. #2*9 - *5* reclining Industrial there, 12" scale, steel separable socket - 30" long with 1" std. pipe thread. Range 0-200*C. No nickel plating, case painted reg, lacquer. Order BI826I, ehg. out $28.05 on 10/31/36. On Buffer tank CT-0750. use-0718 Lab and Office of Dept. CABI #89 - 1936. 20* x 10* x 10' high Includes partition and elec, lights on W corner of CR, MSC-0725 Laboratory testing equipment. See reports on 0. S, testing, wc-073* Electric drying oven, CABI 89-1936, Cat. 776*, 3 heat oven with one shelf anJ 9525 thereoneter fork 110 v., AC current. Belongs to the fyranol Dept, Order B23080 on 11/16/36, Req, 7*628. Chg. out $26.60, O H +* H in H 7X Sn hxo n 2 5- O r onz *5 P s=: i rxH. 1 r! H "rn(A O v> h--m nrn s a*W- > O o C<PJi IUD i un un _____ 1 013S257 norrmr lamuai itonxiro niruict eenuot urmrios , .' i iii Cl. ICPlTHBff LIST, contd. Miscellaneous Equipment, contd. m * 64 SqulpBent Uot WC-C760 - 0903 KSC-0760 Vacuus jst swde by Vorthin*ton. Hi 3Tt>~S atd. 3 stage at can jat ejector with 2nd stage condensing and fitted with Jat type intercooler. Jet to be Cl bronze nozzlaa, heads, acnal nozzlea. Order B7*0* on 4/1H/36, Beq. 692U on 4/1*. Chg. out $796.00 on 6/30/36, * X of MSC-01392 Bid*. CB. Bjectora MSC-0760, 01392. and 01686 are In a row running north and eouth In the building, and they are Inter* connected eo 'that the centre one can aerve as a spare for either of the other two, to serve the vacuus stills 8-0*3 and 062. Cast iron bodies with aonsl Jets, larbate ejectors were to be tried. (Anniston were using ejector* with two stages of Barbate Jets, then a wet condenser, and then two sore Karbste stages.) Peulty behaviour, due to erosion or corrosion, or to wet or dirty steas, is very objectionable as allowing \ ] water to get back into the goods. Karbste units have to be very carefully supported to prevent strains fro* the pipe lines. i More recently procelaln units have been Installed st the Kruaarleh plant. i MSC-0770 Super Tank Qauge Bade by Varez. Pig. 68, Oastight. Use on tank according to i B/T S-*366, Monsanto Brewing. i All BBterlal to bo standard, alUBlnua float, stainless 4 steel tape and float guide wires. 1 Order B3569 on 2/16/37, Beq. 77035. Chg. out $t $17*.80. On CT-0648. TCB store tank. i t MSC-0903 Steel cabinet Bade by Hedart. CABI #139. 1 unit 48" wide and 2*" deep x 6'3" high 9" ledge,bln fronts, dividers and 2 doors on lower part with lock. Order BJ013 on 2/18/38, Beq. 86579 on 2/17/38. Chg, out $50.31. I \ 0119258 4 k e -t - nSac1 nn FS5 r H X> Cl 5 2 n10 a> O o cn <P un j 1 ` ' ]I XJJ. ECUIPKPT1 LIST, eontd. I Miscellaneous Zqulpnent, centd. rri - 65 Squlpaent Llt KSC-0971 - 01392 MSC-0971 10 tteel box locker* a*de by Medart. CAB1 139* Olive" green tteel trrtnged 2 vide x 5 high. Coop let* with 'I lock*, 2 key* Tor etch lock x 3 setter key* eoonon to *11. Lockert 12 x 12 x 15" deep. Order B15781 on 9/23/56, Req. 91603 on 9/21/38* Cott $25.75. M5C-01061 Two loading rasp* sad* by Monsanto. For one ton chlorine cylinders, utlng I-bet* support end concrete footings { with 2-beas nils. Sett tide, outside Bldg. OR. 1 MSC-0109* Drying Oven purchased fron 0. Z. Used with P-0159 In the Fyrsnol plant, t eonpartment electric drying oven with 115-230 volt heating elesent*. 3 HP aotor. Order Bl8?35 on 9/21/39, Beg. 1991 on 9/20/39. KSC-01191 Metal Desk and Stool. Desk 36-5/32" wide, *2* high front, 5*" high back, 31" deep. Stool 30" high. Order B5169 on 3/*/*0, Req. 71*8 on 2/29/*0. MSC-01205 speed reducer ude by Falk. Serial N0127-928. Site 28EEX, RPM 1750 to 160, ntlo 9.7. Order B8337 on 5/20/*0, Req. 89*1 on */9/*0. Chg. out $169.9*. Driven by M-01629 on CT-OBOfi. tOC-01288 Falk Motor Reducer 7* HP. Serial M0131-8*2. #**EU, output speed 1750 to *1.9 RPM, service factor It, ntlo *1.9. Order B21071 on 9/30/*0, Req. 1367* on 9/30/*0. Chg. out $3*1.9* on 10/31/*0. On CT-01321, Pyranol blender. MSC-01392 #2t Worthington vacuus jet 3 stage. Type 9-10-11. Worth of nsC-0760. Sase aa RSC-01686. 0139259 I| I i u* Cn lo Lj -3- Bardens, metabolism, and Kinetics Sosa general observations dsnvs Cron consider ation of the data on the storage, distribution, metabolism, and excretion of commercial PCB mixtures (with associated impurities such as the PCDfs) in mammalian systems. The dynamics of the pathways by which these processes occur in tost animal models have been explored intensively and have been fairly well worked out. The variability of PCI effects with species of test animal model has been investigated for a number of important effects, and some general structure versus activity rules have emerged from these studies. There thus exists a conceptual frimework, but not experimental data, for describing such phenomena in humans, further. Important data on the biochemical interactions of PCVs`, PCDFe, and metabolites with tissues have been obtained that bear directly on interpretation of toxic effects in these tissues. General Toxicity from acute, subchronic, and chronic studies of PCI effects in test animal models, a general summary of health effects encountered Includes) (a) a low order of acute toxicityr (b) skin lesionst <e) effects on liver tissue"that are generally reversible at lower doses but thee trend toward irreversibility with increased doming j <d) effects on the gastric mucosai (e) effects on the menstrual cycls and on reproduction) HONS 221924 TBottcro nnuui xossjutto tiinuei eemui x-xtxutxo* * ' m. ECPirmyr list, contd. Miscellaneous Equipment, contd. Cl - 66 ' Kqulpmint List nsc-oi393 - oeioe NSC-01393 Control Room. Dr*win* C-9646. Structurml itwl, floor plot*. Bid*, til* 12 x 12 x 3. fyrobar roof, door and Instrument panel for 1-0441. HSC-01495 i ton feerless hoist and trolley. Nodal C, 11* lift. Modal J trolley. Order B1750B on B/6/41, Req. 23095 on 6/6/41. Ch*. out 172.74 on 11/27/41. Used to reaove platea of filter f-0172 for cleanln*. KSC-016B6 #2$ Vorthlnfton 3 ata*e vacuum Jet. Type 9-10-11. North of MSC-01392. Same aa NSC-01392- NSC-01699 Lockers (4) made by Medart. CASI 152.1939 2 only 15 * 16 * 60 dark *reen. #14 and #15. 2 only 15 * 15 * 36 double tier. #12 and #13. Order B3439 on 3/6/39. HSC-OI877 Canvma tent for tank car. Approx. 7' dla. x 7* high with awln* boom, to ralae and lower tent Into a wooden box alone west wall of CS. To be located at load dock at track #11, SV comer CS. Alao elec. ll*ht In tant. order B20696 on 9/7/43, Req. 46441 on 9/4/43. HSC-OI679 South dock, wood, muriatic loadIn*. Alao awln* plank and wood dedOn*. On track 11 weat of CS. 5* * 5`6". 1943. , NSC-01916 North load dock made of ateel with awln* plank. 5' x 7' Ion*, 9`6" high. 5x5 angle column* with 6" channel* to rupport i" steel d*ctan*. li" pipe railing*. North of H5C-01679. SV of CS on track 11. 1936. HSC-02071 Stoneware oink. NSC-02108 Steel Hood and IX;et, 2' x *' counter balanced with 6" dla. steel duct to outside of Bid*. Hood located over f-0159 C. E. filter frees. 0139260 o*. -=1 H in h FgS C -* : C>" --H XC>l o--n fi i?*1 H* nh Rwtrt HO S f pj n oc x X D O ttno Llj l U~i _____ 1 Lj i L nofKTts *iTTJLXkii acsaxjrro innuti cenouot lxtxutxok i m. tCUlPWDfr UST, centd. XII - 67 Kquipaent list MSC-02*26 - 0***2 Klseellaneous Equipment, contd. MSC-02*26 Ducts, hoods, dampers. HSC-03*17 Air cond. unit. KSC-03523 Vsc. ejector. Worthington, Porcelain, Barbate. 10" porcelain condenser. 10 lb. hr. sir st 2 cbs. i 130 pslg stein. 63*2. well witer. MSC-03611 Duct snd hood. HSC-03689 Haveg sink. *' B" * 19" x lB MSC-03706 MSC-C37*1 KSC-C3E35 HSC-0*016 Water cooler. Drinking wHna*tVe4r e 1/2 T ehsln hoist shove 2-0172/1 1/2 T ehsln hoist - #2 nlixx tankj Work bench Pyrsnol plant MSC-0*109 Xdghtnin sixer (only - not netor) 7i K? side entering natalllsed with 0.015* Al. See CT-02621. HSC-0*132 Water cooler. MSC-0***2 Bend hoist. Bester* for plant cfflce snd for Instrument end control Oss supply snd altering. room. Wster hose with steas nixing Jet for cleaning the floor. Desks. Clothes locker*. Teat bench. 2hone. Clock. 2rsaed Instructions for special pieces of equipment. Drinking water supply. 2irst aid cabinet. 21 re tin* g extinguishers.Sorlnklers Installed In ell_; - Hose connections for casual gas hasting. roona. Waste cans. Used wster collection. 0119261 lighting. i t. X o o I un _____ 1 1 i L m . 66 Equipment Ust 01-06*0 - 0751 Open Tanka OT-06*0 Drum, 110 gsl. ICC5, C1BI #217-19*1. With float valve on city water line. Connect 3 QPM pump P-0376. To pump from drum through rot one ter to add absorption system. Black Iron $16.30 as trails from Dept. 360. Seal cant for barometric legs or the ejectors. HSC-O76C, >01292, -01665. On the ground floor. OT-0751 Steel vessel *'0* I.D. x 6'0* high, for city water, to conform to state law. OSH HH K x fi C -5 T r n5 >x r> 5 ^n 8 wc X8 ^3 1 <> Sn Pm 8> Hs x D O 0139 262 \jTt 1u J TlCTtCTTS KXTZXUkLl UIIUTC ZVCtnLUCB COTEU9I LI7IU7I0* m . EOinyKHTT LIST. eentd. JQI - 69 Equipment List F-0346-0575 Pumpe Vote: The pump* ere changed around from one duty to another. In the course of ordinary maintenance work, but the details given below will serve to show what type of pump Is used for ar.y given duty. Overtlaed popi may be used In aoae cases to diminish the number of types re quired in the department. . F-03*6 Swaby Submerged rump made up 11/18/29. Size #l|, Cast Iron. On CT-08*B, In TCB store tank, CT-06*B. T-C37B Chat. Lewis pump Serial *597, Type BA-*Bl, cast iron vertically split shell cent, pump. Cl bed plate connected with' flex, coupling, direct to 1/* H7 3600 WM motor. OZ M-0*66, 3 gal. TM - 35' head, 3*50 JtPM. Order B693 on 1/15/31. Trice 166,00 Inc1.motor, M-01772. Boosts city water to HC1 absorber. T-0*27 Borltontal cast Iron pump 1) HP Monsanto Design. Direct connected, cold rolled steel shaft. Includes base, coupling and c guard. F-0565 Blackmer pump. Serial 197033, type PA-50L bronxe rotary pump, bronze lining, bronze steam jacketed heads, monel shaft. Cl base, 1.65 sp, gr., tesg>. 350 to 500T. - 50 gal. Order B-B170 on */23/36. Chg. out 155.*5 on 6/30/36. Pistillate transfer pump. T-0571 T-0573 Oberdorfer gear pump for filter preee. Motor M-01650. Vertical submerged centrirugel pap purchased from Die Engineering Equipment Co. Serial 33007, Size L~0S with li" inlet and 1" outlet. Compare F-060*, whleh le a Taber piu& on #* scrubber CT-0759- T-057* Ditto. T-0575 Taber submerged pump, Serial 33009. Order B7517 on */16/36. Req. 9161. Chg. out *177.60 on 6/30. Direct to vertical H-06*6 In CT-0756 on #1 scrubber. Same as T-0573 and 057*. 01392C3 -oI sh^H 5H axn X^fot nnr5n* rm5i** - H'ns 1HOft *Wrn(A *n*1 fart c fa 5s D O u$ 1 *JTt _____ l UU i L  -i nuiwiK dtuui aosaurro iiitimci cotbusi litioztiow X3i, gqnrwewr list, ccntd m - 70 Equipment Uit P-0576 - 0580 Pumps, contd. P-057B Tiber horizontal centrifugal pump. Serial 33040. Type L-2, Zi" inlet 2" outlet connections. Semi-steel with monel shift and Miter Jacketed stuffing boxes. Bed piste reedy to receive motor. 20' etstle heed, rite 80 f.p.m. 1.5 tp. gr. st 500*P. Dees M-0849, On #2 chlorine tor, CT-0744. Order B8237 on 4/J4/36, lleq. 69401. Chg. out $152.92 on 6/30. There er* four pumps P-0576, 0579, O629 end 0907, one for esch main chlorlnstor. Uquor in from chlorlnstor bottom outlet end out beck to the chlorlnstor. The charge esn be pumped. If necesssry, from one ehlcrlnstor to another, or to the sir-blowing vessels CT-0750 end CT-20S6. Bo. 1 chlorlnstor esn be emptied by gravity to the gss-fired chlorlnstor CT-o6o8, end there Is also s pump line fer the seme service (disused). The charge from Bo. 1 chlorlnstor can be pumped directly to Mo. 1 vacuum still S-043, There is a line by which partly chlorinated diphenyl can be pumped from s chlorlnstor to any scrubbing tank, CT-0759, -0760, -0761 or 01014. There is sampling cock on esch pump delivery, with a small box to hold the used sample material, and to deliver it back to the pump intake. P-0579 Taber horizontal centrifugal pump. Serial 33041, Same as 0576-80. Per middle chlorlnstor CT-0744, uses M-0&50. On #3 chlorlnstor CT-OS33. P-0580 Taber horizontal centrifugal pump. Serial 33042. Same sa 0576-79. Pros blow tank CT-0750. Uses M-OB51. 0139264 3n JH1 r -`5 > *- 3 oo --ift n C VI Sr : 3nvt (ft HO nR s * > D O tn 03 L1 un _____ 1 1 j nnw utbliu.1 num uimici ccrrgaaei utioxtiob (i t 1 j i i m SCPI2HPTT LIST, contd. m - ?i Equipment Lilt 7-0582 - 0595 fungi, contd, 7-0582 Tiber vert, submerged centrlft^Ai puap,' 'Serl . 350*8, , Pig, 19*0, use C-3, 2*" inlet, 2" outlet connections, bronze except shift which is onel metal. il'6" length of column pipe. Span puap for underground tanks, Order *751* on 4/16/36, Saq. 69158. Chg. out (409.20, Direct to M-O652. Sane as 2-0583 and 0364. Used in Arcelor 1260 store tank. Submerged pump in CT-C76B TCB store. 2-0583 Taber vert. sub*. cent. pump. Serial 33049. Ir. CT-0769, direct to M-0853. Sane as 2-0582-0584, Aroclor storage. 1tt 2-0584 Taber vert. sub. cent. pump. Serial 33030. In CT-0768, 1254 store tank, direct to M-0654. Same as 2-0362 and 0563. 2-0565 Taber vert. sub. cent. pump. Serial 33069, Dvg. A3&7, Type C-3, fig, 1940, 2' inlet and outlet. Cl body, renewable bronze bearings, bronze lapellor Mounted on nickel steel shaft. Length 11'6", sump cover plate, cap. 30 gal. p.B., 60* static head, sp. gr. 1.18 at temp, 165*-170*7. Driven by H-O656 in CT-0748, Blphenl store tank. Order 27518 on 4/16/36, Jleq. 69162. Chg. out (257.62. i 2-0592 Taber vert. sub. cent, pump. Serial 33113, type C-3, Pig. 1940, 2" inlet and outlet. All iron construction i on nickel steel shaft length 11 *6". Cap. 50 g.p.m., 60' static head, p. gr. 1.366 at 70* to 90*P. In j CT-07*St driven by M-0&73- Order 27516 on 4/16/36. j Seq. 69160, chg. out (255.41. 4 general service and diphenyl tank. t t 7-0593 Taber vert. sub. cent. puap. Serial 33111. Typa L-2, I fig. 19*0, 2j" inlet and 2" outlet, casing, yoke, 1 l^ellor nade of steel shaft nickel steel, coluvt l supporting intermediate bearing, wrought iron. Length 7*9*. i 0139245 1i ' LH __ 1 \jTt j fuTterxs id.muii naaaarro mnuci ceroui utiaxrxo* i xii. gqnwcNT ust. contd. 4umpa. contd. m - 72 lqulpment Llt 4-0595 - 0629 . 4-0593 contd. Cap. 75 0PM, static head 15', p. gr. 1.6 at tanp. 700*4. Driven by M-0871. On Humber 1 atill. Order F7515 on */l6/36, Req, 69159- Chg. out 4562.91. In atill 5-0*3. Sane aa 4-057*. Suap plate. Drawing A-*93. 4-059* Spare motor aamt aa 4-0593. Serial 33112. Driven by M-0&72. 4-0595 Obardorfar gear pump. Serial 2635. #7A3B unicedar pump, all bronta (ear type. 10-15 04* at 20# preaaure. Vied to circulate Aroclor on No. 1 atill cooling ayate, Order B13168 on 7/6/36, Req. 71152. Coat 476.60. 4-060* Vert, aub. cent. pump. Tabor. Serial 33207, Site L-CB, 1*" inlet and 1* outlet. All Iron conat., open impeller on nickel ateel a haft. Sane aa 4-0573-* and 5. In CT-075*. Order B13195 on 7/2/36, Req. 711*8 on 7/3/36. On #3 acrubber, CT-0761. 4-0615 Blackner Punp Serial #2017*7. Size 502, 50 fallen per aln. right hand rotary gear pump. Bronze with bronze liner and nonel ahaft. Steam jacketed heada. Order B208l8 en 10/16/36. Req. 73912 on 10/16/36 CDs. out 41*6.27 on 11/30 Direct to 3 U 1600 M-01**9. On filter preaa 4-0159. ,l 4-0617 Blactoer pump. Serial 201902. Size 100L, all iron. i Jacketed right hand pump, bate plate for motor, and flex, J t coupling, direct connected (M-091*). Order 8212*1 en i 10/22/36, Req. 7*03*. Chg. out 41*5-20. i Spare pump. i f 4-0629 Taber horlx. cent. pump. Serial 33708. Type L-2, 2$" i Inlet and 2" outlet. Size 103. Order B2633 on 2/9/37. < Req. 76766 on 2/5/37. Chg. out 4152.52. Direct to M-0975i On No. 1 chlorlnator. 4 0139266 1 om - -mt 4 01 * ci nn Ir X o o ccno un _____ 1 cn j V nertcm aamixn inim rnnuci ecmMt imutiov m- 73 Bqulpoent Llt XII. tcn?ttKT LIST. contd. #* Tunps, contd. i 7-067* - 098* 7-067* On #1A scrubber, CT-01013, driven by otor H-08*8 on No. 1 chlcrlnator. 7-07H Taber sub. cent, pump. Serial 8*722, 81 so L-GB, 1*" Inlet and 1" outlet. Order B365* on 3/A/38, Req. 86691 on 3/3/30. Chg. out 817*.25. In CT-01013. 1 l 7-0907 Taber hons. cent, pump. Serial 36622. Site 103, typo L-2, 2$" lnlot and 2" outlet connections, seal-steel through out with aonol shaft and water Jackotsd stuffing boxes, with bod plate ready to receive actor, 20' static i1 head, rate 60 07M, 1.5 ap. gr. at 500*F. Order B120O1 on 6/5/*0, Req. 10230 on 6/5/*0. Chg. out 8155.28, driven by M-OI656 to circulate liquor for ehlonnator CT-01263, #* chlorlnstor. 7-0909 Taber sub. pump. Serial 36676. Site t-CB with l" Inlet and 1* outlet, all Iron const., open Impeller on nickel steel shaft. Order B13110 on 6/10/*0. Keq. 10366 on 6/10/so. Chg. out 8193.75- On CT-O968 scrubber llq. tank. Also on CT-0760. 7-0529 Taber sub. punp. Serial 36853. Site C-3, fig. 19*0, vertical 21" Inlet and 2" outlet. Bronxe except shaft to be aonel aatal, lg. of col. pipe 11'6*. Order Bl8**2 on 8/23/*0. Keq. 12559 on 8/23/*0. Chg. out 8*0*.59. On stg. tank CT-01310. Driven by M-01706. 7-0932 Kpper cast iron punp. JOB1 #169. Site 1" rotary, geared, complete with base, gears, pinion, big stand and adapter plate for notor aountlng. 7-098* Roper punp. All iron series "0" rotary puaq> for $7K. 1.6 sp. gr. 50' head punp, spiral gears pkgd. stuffing box with non-graphltlc white asbestos pkg. built In by-pass and cosplete with base, drive gears. Order B*ll8 on 2/17/*l. Keq. 16322 on 2/17/*l. ?or filter in CR. to Sparkler filter R-C172. Replaced by 7-0571. A j 0119287 i o o on CD t U~i I _____ I _____ I I ncrrwcTts> nromi waixm mnutt cotbui i ! HI. EOPIRMPiT UST. eontd. ZZZ - 7* Iquipment 11 at 2-0997 - 01*56 Fumpa, eontd. .. 2-0957 Taber vert. *ub. puap. Serial 57662. Type CL*, 2|" Inlet and 2" die charge for 75 02K agalnat 25* head, 2up of dynamo atael with wrought iron pip* oolumn and nickel ateel abaft, water cooled, etufflng box. Order B6379 on 3/13/*l. Raq. 19*1* on 3/13/*l. Chg. out |**6,53. Xn S-062. Driven by M-OIB56. Shaft haa two Intermediate C.Z. bearing*. 41I i 2-01037 Blaclo&er puap.. Serial 2*6056. 5V032O2 bronze, alzc 5H- with baa* and relief valve. Still receiver to blender. Order B160S7 on 7/21/*l. R*q. 22**9 on 7/*l/*l. Chg. out *177.56. On gr. fl. NX of 2-0172. 2-C105* Fuwp nade by Veil. Serial 13132. Type DSI, alxe 1". Uaaa city water. Order B*625 on 2/21/*l. Req. 18520 on 2/2l/*l. Coat *65.00. Cn TW-0221. Driven by N-01995. 2-01056 Taber herla. cent. puap. Serial 36316, Type L-2, alxe 103, 2i* inlet 2" outlet caeplet* with baac. Order B19730 on 9/3/*l. req. 2*125 on 9/*/*l. Chg. out *157.** on */31/**. On #* chlorinetor CT-01263, ' I 2-01111 Blacteer 2p Serial 2*9113. #5 01 all iron ateaa Jacketed puap with Cl baae plate and gear drive ready to 1 receive our 3 E2 l800 R2N motor else 511. Order Bl63*9 on 7/23/*1, Req. 22597. Chg.out *105-05. Driven by M-02677. For dlacharging rail tanka. I } 1 ] t 2-01256 Bladcaer puap. Serial 269500, Size 1202-50. Fig. 3203 complete with relief valve. No baae. #2 atlll receiver to blending tanka. Order B2S303 on l/26/*3. Req. *0312 on l?/>0/*2. Chg. out *13*.63. Bronx*e ' 0139261 j WH W_ *o S S22 * n r p (*1 I a 8b: Si"nXH n ^ rPWI C Vi mn xn rw* ?s -( rx a >* X o o cn co t un _____ 1 nonsro nnrnii ioiiuto xsamucg esnuti UTiomov HI. . * ' ECfinrHEKT LIST, contd. ni - 75 Bqulpment list 7-01177 - 02?51 Tump*, contd. 7-01277 Taber vert, rub. cent. pump. Serial *0890. Type Cl-*, li" inlet, 1" outlet, else 38*. to be dynteo teel with wrought iron pipe, column erp. of pump 75 07M at 15' bead for liquid 1.8 *p. gr. Order *8875 on 7/12/*3, Keq. *5713 on */16/*3. Chg. out **3*.00 on 12/17/*3. At 5-061 Spare. Sane aa 7-0997. #2 atlll pump (apare). 7-01509 2* Taber pump. 60 DTK. 130 ft. TDK. Steel with monel ahaft, flexible coupling. M-0301*. S. 0. 1.5 500*7. 7-015*0 0. X. filter pump - N. V. comer of lean-to. Taber pump 30* atalnleaa ateel, 2* auction, 1$" diecharge, located lndoora. Tumpe from old Tyranol blender CT-01321 to filter preaaoa. 7-01757 Cki Sweetland filter 7-0239. Mow ured on 7-0238. >0* atainleaa ateel 2*, 100 gpm. Motor M-03718. 7-02052 2* Taber. Sami-ateel, monel abaft, water jacketed tufflng box. 1.5 S. 0.,500*7. 7-02077 7-02078 Slackmer pvap, from TTCB store to blenders. Bronx* lined, with monel abaft. M.V. of Bldg. Cft. Taber 3* x 2$* 150 gpm. 60 ft. bead. Borlxontal Impeller. 7-02179 Teber Tump from new blender CT-02621 to filters. Motor M-0*025. 7-02251 Viking pump on Aroclor mixers. M-051*. Tyranol plant. \ 0119169 i o o ccon Cli 1 LH 1 _____ 1 LQ j 4 it) porphyria; {9} affects on eh* ladnay; and (h) miieailiniaui changes including hematologic alterations, thymic atrophy, and lymphatic changes. There is a considerable range of apeciea ausceptibillty to biological activity of the PCte, with one representative comparison of order of decroaeing activity being mint, monkey, rat. It is concluded that there is no basis for determining which apeciea most accurately serves as a model for prediction of general subchronic/chronic tosicity in man; rather, the judg ment of the most suitable surrogate for man ouat be made indepen dently for eech major health effect. Finally, it la notad that although ehara is some similarity between acute health effect phenomena produced by PCI exposure in the monkey end human Yusho disease, it would be Incorrect to equate Yusho disease with PCI intoxication because of the much more complex mixture of compounds encountarsd In Yusho oil than in a commercial PC* mixture. Skin end Other Cutaneous Tlseuee Commercial PCls ers capable of producing skin lesions in the monkey model and in exposed humans. Chronic administra tion of PC*s to the monkey produces chloracne. In humanm occu pationally exposed to PCie akin disorders including chloracne have occasionally been observed. these skin dlsordsrs have been shown to be rseenible in soma of the animal and human studies. MONS 221925 nonent laTXxuxi aosixrro ivsnuo curnut litiutioi XII. gtlWgST UST. contd. m - 76 Equipment List Pumps, contd. WotC ! London Engineering Dept. Pinal Report n the start -up of the Newport Arcelor plant elite* that Hawvorthy pumpi were not found satisfactory in use. Oood jacketing le needed. There wae trouble fro eorroelon of eore pluga in acme pumps, leading to leakage of steam into the goods. Steel end covers were used later. The sane reports discuss the difficulties encountered with the still pump, which was located in a small secondary vessel, below the vacuum still. ' 0139270 j i CH- 2 SS t- o >nn 8 Smx i*ii "rn -* H tr. C (A n an ri**i o ~a >* Oo tn C<0 un * CD CD * i U nenens nnuui uiiun intuiei ccmui imutioi l )i Cl. EgglfMEHT LIST, centd. Retorts HI > 77 Bqulpaent List *-026 - 027 *-C26 Aroelor 1269 Retort assembled and traded by Monsanto, rota from Rooter. 1516.00 for Jaclctt from Gravtr. Req. *69906. Burners free Surface Combustion. Beq. 6977*. Burners - gas fired. ' Jacket, steal, firebrick lined, bolding J'O1 QD x 3'fi" lg. over dished bottom still pot with cover. Equipped with 2 gas burners and stack. Still pot 1/2" fire box stetl,reteovable so residue can be du^ed. *027 Aroelor 1269 Retort - Sane as R-026. Drawings: B-6*6 Retort. 1-665 Betting. : B-37* Oeneral arrangement of solid Aredor plant. C-C70 Oas heater for discharge line. C-621 Platform for retorts. i Nr. Soffranko In 19*7 cenentad that the retorts would be better with thicker bottoms than shown In drawing B-6*6, and that spare retorts should bs held. 0 1 ^HWH i5 * n w 122 ^a f<t1 rk > *- 1 r- > 8 si ?B X o o ccon ) i co 0139271 j/ f wcimbi nmmi uiiurre xasmAxeg cermet ljtiutioi hi. EcrrrmT ust, contd. hi - re Equipment Uat 8-0*5 Stills 5-0*5 He. 1 Vacuus mil purchased fix* Onvr. Plant A Drawing C-B09. size 6' Cl#, x 5'6" long on straight 14#, 1/2" shell, dished heed 5/8" supporting brockets 60# Hydro press test. Order B-7705 on */17/56, Jteq. 69225. Chg. out $556.00 on 2nd floor, 12' level. i 8-0*5, No. 1 still, st the Enra-lch plant, is of the shallower type, like the Anniston stills, and like then i It has s vertical vapour pipe (with Hagan separator Inside the still), leading to the top of a vertical condenser, CT-0770, whenss No. 2 still Is of the deeper type, and has a cyclone, CT-01*15 In place of the vertical vapour i pipe and the sepaatcr. The cyclone returns a considerable amount of darkish liquid,through a sight glass,to a return line going nearly to the bottoa of the still body. Hr. Purzey, December 11, 1951 reported that the cyclone gave better coloured distillate than did the Hagan separator. Anniston, January 1950, reported satisfactory perfomance of their Hagan separators. Newport have the internal Hagan separator. In s report dated Ifcrch 51, 1952, Hr. Dalton of the Krunnrlch plant Mentions s modification to the Hagan separator at the Xrunrlch plant. The Aroclor colour was better after the change, but It waa not eartaln that the alteration really eausad the laprovement. There la no attest at fractionation, and the condensing systems were planned to give the lowest proesure drop attainable, conaueve with removal of coloured entrolrasent \ particles, the deeper pattern of still 8-062 waa chosen i to give acre disengagement space for vapour, but It does i not appaar to have given any battsr coloured distillate, and It has the disadvantage of requiring a longer shaft etc. for the submerged pump. The condenser oo No. 1 still delivers to receiver CT-0771 0119212 H WJ ^ c* s a*-- sn^-- --z O m* sn r.1 Snr -O4 itnfi *4 O zr pi pi ?! ** > a* X oo <J1 TI LTt LO rU rmorscro nmiui intun ninwei nrsui lxtxutxos hi. tauzrysxr xjst. contd. XII - 79 Equipment List S-OAJ Stills, contd. S-0*3 contd. Ho. 2 still has hast exchanger CT-01*91, head tank CT-01398 with gravity flew (ef cooling water only) to oendtnstr CT-01376. CT-01396 has an internal soil (not used) and there is no teapereture control Inatruaant . The distillate goes te receiver pT-01377 The temperature ef the distillate is roughly controlled by hand adjustaent ef the flew of water fron CT-01398 te the condenser CT-01376. The Newport vacuum still was provided with s subsidiary veeeal, located st s lowwr level than the wain veeeel, and containing the submerged puap. VIth this arrangeaent. It was hoped to diminish the liability of cavitation of the puap, and to permit the use of a such shorter shaft for the pu^ lope11 or. The arrangement, however, was unsatisfactory, largely because the pvmp gland wae exposed to hot liquid Aroclor (See the lendon Rnglneerlng Dept. final Report on the start-up of the Newport plant). Racrcus different gland packings were tried, the gland was given e lantern ring, fed with liquid Aroclor etc. etc., but finally a long vertical sterna Jacketed pipe was fitted on tep of the secondary vecccl, to carry the . stuffing box above the level of the charge In the aeln still. This location also put the driving aotor Into cooler surroundings, and tha new arrangeaent has been Bade to werk satisfactorily, though It brought back the. troubles of the long ehaft. In the puap eseeably, the pump le hung froa s aanlld on the still cover, on A wide pipe down the centre of which the r~--~~T shaft runs. The delivery pipe fron the pump runs independently up through the sane aanlld on the cover of the still (welded through). Differential expansion aay distort the sllgnacnt of the parts, and aay 0119273 c 5* -"H Pi X S K5 >-z r O 1 - oP>I I 3pi rnvs V) -i n SK 8s > -* rs *! > a* X oo $ CP Cli i LTi i CO uu nenens nmiui uaiurrc mrauct etmu0i utiutisi j I { | ' ` ) . .' hi, touiywjrr us?. conte. 302 - 60 Equl paent Llet Stills, contd. #-0*3 contd. " displace the lapeller axially within lta Main#. Another trouble which appeared wee that air leaking In through the #land could travel down the central pipe around the abaft and cause cavitation In the puep. the rowdy for this la to have holes In the pipe, c-i--ml cat In# with the aaln vapour apace In the vessel. Die stuffing box la water cooled; the bearings inside the still say give trouble, this clearance wuat be Just right. Carbon bushings have shewn seas pretties. It has to be reawttbered that the charge contains a fair aneunt of solid (lias) etc. which sight ledge to sobs extent In the still Instead of flowing to the secondary vessel. The Internal bearings are lubricated by Arodor bled off the pusp delivery line, but thsy Bay beeowe choked by the solid Batter in the charge. Bee also the description of the Anniston etlll and punp ' on pagee 20-, Section VI,.above, and coMtents on the distillation process, pages Section VII. Prow the bottott of the condenser at the Krunsrlch plant, the dlstlllste passes through a Jacketed line to a Jacketed sight glass with saspling fitting, and so to one of the receivers CT-C771 or CT-01377. There is a ring of gas burners around each condenser exit, to deal with the hesvler Aroclors, but the burners are not such used. Condenser CT-077C can be cooled by Aroelor circulated by pusp f-0595 through the condenser shell space then through heat exchanger, CT-0631 (cooled with well water) and through a sight glass to head tank CT-0766, and so back to the pusp. This systea is alternative to the cooling by distilled water used on this condenser, but It has gone out of use since the Krunsrlch plant gave up the production of the higher Aroclors. 0139274 O"1 =H ---1 H V) H ri X fi g = nr n nz >r --* z> fi " W n*-4 n 4 nVr) * O V) nn wc>t" M ->S)E X oo cn CP i i LH r ) j ' -J*. r*vrwcrtB Dfiuu i noiiurti tnnuct ccrnuas lxtxoatxox XII. BOTPHgNT LIST, eontd. Hi . 6l Equlpnent List Stills, eontd. B-0*5 eontd. There is s stein snd water cell in the hesd tank to keep the Arcelor st around 110-120"C. There Is s Taylor Pull scope tsapersturs controller 1-0510 controlling s valve on the stem inlet to the ooll. This Aroelor cooling is more convenient for higher Aroclors, but the water systaa is preferred for the lower Aroclors. The systea normally works st sbout atmospheric pressure though the vent (on the top of hest exchanger CT-0EJ1 is usually kept closed, snd there is s pop valve st the sane point). The sketch on page XII - 62 will serve to show the arrangewent snd to Indicate certain alnor features not described stove. gseh still has s bottom outlet which will cce^letely onpty the still, also an outlet st about the sane level of the top of tha botton dish, which will leave about 60 U.S. gallons of bottens in the still. Both deliver to open topped cans on snail wheeled "dollies'' under a hood ventilated by suction fan B-01*8. Rising stea gats valves are used on these outlets snd gas flanea are freely used to hut then for sene tine before the still is to be tapped. Botton outlet also to ensrgsncy tank CT-07*9. but this vsassl Is new used as sxtrs storage for diphenyl. The deeper still has s therno well obliquely through the tide wall, about 7*6" below the cover, but this well was not in use May 1955. Bach still body has s B5 A B relief disc of A17b, 6" diameter, vacuum supported, calibrated to rupture st 25 pslg. The receivers do net have relief discs. 013927S 1 I chn*n eh ssi own 8"- n P! Oc S ** > a* X oo cn OP LH LQ U*I J nsrtcTD nrrnui hovuxto iiibwci eenuat litiutiov COOLING ' Xi: - Ei SYSTEM AROCLOR CONDENSERS. *B' JUl> IQi %r at> kpwM* tH tMf, V *V 2 r c* na" *n -- r -i -- pi R"- C1 Sr 3ntmrt n rf*s nr oi *arE- ha*> X oo cn CP i LH LQ Cn 0U9276 norms nriuui wnuro ninua eoevuat iitiostio* XII. ECUIrtg?C LIST, contd. XII - 82a Equipment Ut 5-0*3 -0*3, contd. Drawings fi *63 A *93 vater-coeled condenser on No. 1 still Sump plate for submerged pump /CT-0831 -01397 -01*91 5-0*3 B 6** B 31 B 662 Head tank for cooling medium Tubular condenser -----------------Vapour exit pipe ---------------------- CT-C1398 ct- C770 01376 S-0*2 C 795 Re cel ver ---------------- CT-C771 C-807 C 809 Coke tower ------- --------------No. 1 still -.............. ............... CT-C753 5-0*2 C eis Piping of vacuum a till - PC-0*5,CT-0770,-01377 C 86* like B *63, on No, 2 still ---------------------5-062 C 69*2 Flplng diagram, No, 2 atill -------------- $-062 C 69*3 Flplng diagram. No. 2 atill------ ----------- S-062 D 69** No. 2 atill ------------------------ -....................... S-062 E 6952 General layout No, 2 atill--------------------- S-062 D 6956 General layout. No. 2 atill with cyclone, receiver, and coke scrubbers. D 6957 Cyclone on No, 2 atill ------------- - S-062 B 70E2 Monel condenser on No. 2 still CT-0137S 0139277 1. OIH1H w -f fi gfi 22 cnS X> '- *ze *"* B D PI 8 *" 5l" PI B f " 3PltrotI *4 fr'i pi pi ?5 p3 a! O o 5 j un Co _____ 1 nortcTXB nmiui naiun mnun eornaas utiutidi XII. EgPIfHPff LIST, eontd. XII Iquipmert Hat 5-062 -0*59 .. Stills, contd. -062 #2 Vacuum atlll purchased from Mootar. Serial #52. Dug. D-69**. 6' IS x ll'lO" atr. shell, internal pip**, etc. Std. dlh*d head*. Claa* wool Insulation 5* with 1/2" flnlah coat. Order B10750 on 5/12/*l, Req. 20*21 on *A6/*1. Ch*. out 2950.00. Suspended between 20'6" and 12' platform in CR. 5-0*59 Is another number for C-O808, gas fired ehlorlnator. OHs H wh ni |12n --n rnj rk e K *"v>* n - Sr 3$! i s?3 O o CO un i CO CO 013S27* J j  -J> nortcTXB nmrni measure xssraues eemus Lxrxcarxoa l 4< \ { i 1 m. BCOTBKPff LIST, contd, \ Scales n: - 6'. Zqulp*nt List aC-054 . CJ6 5C-09* . Howe Portable Scale 1B22, Serial 1363205, all Iron platform 30}" x 30}". Cap. 1500 lb. Order B9986 on 5/20/36, Req. 69955, ***"1 H"*- SC-09B Howe scale. Serial 1361566. #1*20 Sksleton type, tall I i besrint, dormant scale, cap, 2500# with double beams. Mat fora 16 x 36. All sietal Inel. steel shaft. Order Bl*351 on 7/20/36. Req. 71536 on 7/17/36. Brice *213.85- SC-Cl00 Scale purchased from Hie facet Weight Scale Company, Serial 39992, Style 1226, cap. 200# on retie or 10 to 1. dal with indicator travel 12}" under wgt, and 2}" ever wgt. Bitted with bag holder for 100 to 200# bags. All on swinging rack. Order B17906 on 9/19/36. Req. 728*3. Chg. out *289.*!. In lean-to near V0*A and V-*5- 80-02*6 1000 lbs. capacity, Pyranol Mant X o o (4 I LH uo LO 11 0139279 * - 5- Effects PCI Mixtures are capable of 9iniritin9 iaportant facta on liver tissue in aniaal models. Thaaa affacta include: (a) increase in livar weights; (b) histopathologic changes in livar including enlarged hepatocytes, deposition of fat droplet* in tissue, and tiasua nacroais 2nd call death; (e) enlargement of the liver; Id) the occurrence of adenofibroaia, a benign lesion; and (e> an increase in proliferative lesions of the liver, including increases in hyperplastic foci and nodular hyperplasia. These increases in proliferative lesions appear to increase in severity with increasing degree of chlorination of the PCI Mixture, as seen in the greater potency of Aroclor 1200 over Aroclor 1254. The effects on liver tissue are gen erally reversible et lower doses but trend toward irreversibility with increased dosing. however, in contrast with the positive findings of PCI effects on liver tissue in aniaal Models, no significant effects on liver function tests have been observed frea clinical data on huaan populations exposed to PCIs in the occupational setting. Purtber, there has been no epideaiological finding of liver disease in O.S. occupationally-exposed personnel. Also, as noted in the Tusbo discussion about persons exposed to eontaai- nated cooking oil with a PCS content of 1000 ppa, there was no finding of liver disease in the categories of either jaundice or hepatocellular injury. MOMS 221926 nmem nrtuui bmsuto mewutcs eemut liticatios * ' m XCOIWgNT LIST, eontd. 3QI* 6* Equipment list r-oi* Transformer T-01* Transformer made by Vestlnghouse. Serial 530335* 200 KVA, type SK, now used kkO volt primary 110/220 volt secondary. On the heater of the Lectrodryer PC-M6. Cost 110.00, Outside SV corner Bldf. CX. Also used formerly for strip heaters In tha still receivers, etc. H9 H *I ^ LTi i LO cr* ii 01392S0 i i *b nwicTD nmuti ioiiun :nuei eormti lxtxutxoi 301. gcmmc list. contd 301 - 65 IgulpBtnt Ust TV-0166 - 0318 Towers TV-0366 Pused Silica Tower purchased fra Amereel Co. Inc. 1 *T3" bend trap. IS absorbers sections 1/P 0111 6" ID x 6`6" C to center. Order Bl6l, Req. 69399* Sane as TV-OI63. Recorded as obsolete design. .. TV-01&2 Scrubbing XC1 tower aode by Haveg. Drawing C-4705. "41" std. 2*6" dla. 10'2B deep, 5/8" thick walla x 3/*" . thick bottom, machined dished head, and connecting material, 2" thick Haveg drilled plate with necessary supports 4.3", 1-6" and 1-10" std. Haveg nipple type outlets with rigs. Order 20264 on 10/5/37, Req. 6323* on 10/5/37. Chg. out $666.56 on 12/31/37. (ki 36' level steel struct, aouth side of OR. Tv-0206 Scrubbing Tower purchased free Mooter. Drawing R-5615 support, drawing 0-561* tower. 17*16" ZD * 6* wllded steel eonat..tower, welded steel scrubber support for tower. Order B73*6 on 3/27/40. Req, 8063 on 3/27/40. Chg. out 1277.00 on 4/30/40. Above CT-0756, scrubber by pusp tank. TV-0221 HC1 absorption tower purchased free Pan Steel Metallurgical Corp. Serial 955-19*1. Drawing D-4300 foreign, PA #1*7. Type AU-400. The tower, fittings and piping Bade of Barbate. Oas line of Haveg. Cap. to produce 205" Saume HC1 at 4620# per hour. Order M625 on 2/81/41. Req. 185? on 2/21/41. Chg. out $5321.13 on 6/21/41. Cki steel struct. S of CR. Schwartlng and ethers "Process Description -- Per Arodora", Novenber 12, 1953, state that the Pansteel off-gas ab sorbers are constructed of Haveg 60, and have Tantalus hast exchange surfaces. TV-0312 Absorption tower. Paneteel AL-300. Haveg 60 parts, Tantalua tubes, (sene tantalum parts salvaged fra an older unit. ) 0119281 &^ n * nS |j2 on 8=: o o (3 CD t LTi UD Lj nortcTD nnuui Hoanurro :nuct eonuoi ixtxutxok XIX. CRAVING LIST NCte ; Some of the earlier drawing* were made at the JPQ plant, and the later one* at the XruiBsrteh plant. A* the two plant* have lnde> *' pendent numbering *y*tema it is necessary to specify which plant * 1* concerned. The drawing* marked "A" In celuan 2 on the following , page* are from the J2C plant, wherea* the*e marked *B* are from the ' KruBBrich plant, r* In column 3, on the following page*, the letter *L" Indicate* that print* of drawing* were sent to Mr, Cooper, London, by air mall, April 24, 1947. . "5" Indicate* that print* of drawing* were *ent to Mr. Cooper, London, by surface mall, April 24, 1947. *N" Indicate* that the drawing* in question do net appear to be of Interact to MCI. "K" Indicate* that the drawing* were not available April 23, 1947. "2" Indicate* that the drawing* were found July 26, 1930, and that print* were sent to Mr, Buis, London. 0119282 o^ S 1- HSrs W x -Xnf 853 2 cRS >r ~h nX> 8ns 5g"n*- S"R H r> 8s . *a* * O O w 1j lh US ru 1 nonero dtiuui wiuto innun esmui litiutiox *i m. wnyrorr list, conta Conveyor* V-044 Screw conveyer ute by I*Mueller MPToX. Drawing C-816, Site 6", 6'Si" trough length with outlet at each end. Cover of galvanised iron. Cl trough end* with sine and tin sprayed. lteq. 6S909 (hi botten CT-0764 - North Conveyer. From etg. bln to bagging seale and back to boot of elevator, driven by N-0EJ5. layout - 1-877. Flew Sheet - B-640 V-0*$ Screw conveyer wade by Sssmueller KF Ce. Drwg. C-8l6. - Site 6", 6'6-i" trough length with outlet at each end - cover of galv. Iron. CZ trough enda with sine and tin i eprayed. Ileq. 69909. on bottom of CT-0765 south conveyor. Frcn storage bln to bagging scale and back to boot of elevator, driven by H-06}6. 1 -0*6 Screw conveyor wade by leeeueller KF Co. Drawing C-l6, Sane aa V-044 and 0*5. Frcn flaker discharge to elevator boot. Driven by chain on M-0627. All these were part of the equipment for Solid Arodors: dismantled in ' 195 C He- an5 ft r Cl 14 Jl t>- o H *- I>Cnl 8 S1*h**1 jHo?np"1A hn nR 85 3 hS Oo U1 05 t I U~i Uj 0119283 , runcTO lumui boutc d>9uki cotiuii ixtioatzo* Cl. DKAWIWO LIST Drawing Kunbar Tit la Xquipaant Husher i A-32* A 1 S Oaa-heated chlorination pot{aaa **-888) CT-O808 i i *0*6 N Muriatic treatment aaeaal ' CT-0S61 l 1 F-352 N Fractionating colian(not Aroclor plant) F-370 A L 8 Oonaral layout layout F-373 A 1 6 Bucta Tor procaaa fuaea.eolld Aroclora D-012 ate. F-37* A 1 S layout, aolld Aroclora layout F-375 N Structural ataal F-376 N Staal and foundation F*38o N Electrical layout F-381 K Electrical conduita F-382 * Lighting F-383 If Berrloe llnaa F-38* * Foundation datalla 9065 N Structural ataal, Miriatlc tsaar F-386 A I 8 Flplng layout Piping F-389 N Electrical datalla F-39* N Oan. arrt. BC1 abaorptlon *"*59 A 1 8 Soaring for blender ahaft CT-0779 Saa not# on pmga 86 in thlo auction, i i 0139194 1 C^ >S4 ^ H Wj S 1 ft S3O* *** " r> c O pi 3 * 5P 8*: ii:SH KO V4eff)tt * r> nK * > 3* X oo UZi tI un I uO jr y XII. DTUVTMC LIST, contd. Drawing Humber B-483 A-4g3 A-501 C-502B Iv* 512 lv-518 C-605 0-609 0-615 0-640 0-643 0-644 0-645 0-646 O-651 A LS A LS N M A LS A IS A LS 0M A LS A L8 8 A LS A IS A. 1 s A LS Title Iqulpnent Number Veter-cooled condenaer Tor vac.atlll Stsp plat* for aubnerged puap In vac. till ^ lead-lined tray for 8C1 abaorber CT-O83I CT-01307 CT-01491 S-04J Sand flltar for wrlatlc add Storage hopper for aolld Aroclor Chut* for Aroclor flake ,CT-C764\ ^T-076y 0-012 Shear pin on drive of pea-heated ehlonnator Store tanka CT-0808 CT-0748 CT-O749 CT-0768 CT-0769 CT-01310 Sallef door gae-flred chlorlnator furnace CT-0808 Plow aheet Separator, not lnatalled Plow aheet Cooler on vac. atlll ayatea CT-0766 CT-OI598 Cyclone on aolld Aroclor plant CT-0751 Still pota for aolld Aroclor Beat exchanger on vacuus atlll ` K-026 8-027 CT-0770. CT-OUTS'-. * not* on p*f* 86 in thl* tcctlon. 01392B5 ^o h -^ ^ (ft H fi r n Si2 rfiS M 5-5 rP -* 5fS 8w- gg; * * nw rxt rn 8s ?3 55 X 0 0 0tn) -_ j :CD un uo un rtwwp nnuui ioiiun mnun eoraui utiutioi . . ' XII. DRAWING LIST, contd. . c: - 89 Drawing Lilt * Drawing - Kunber Title Iqulpsont Husber B-655 A I S Stack for solid Aroelor plant CT-0751 B-65* A 1 S Support for stack CT-0751 B-6&8 N Floor gratings B-6J9 B-660 A L S Chlorine Inlet A L S Cyclone - not Identified CT-C7*5 ' CT-OE55 B-661 A L S Klsvator drive, solid Arodors L-0J1 B-662 A L S Vacuus still vapour pip* 8-042 B-663 A N Supports for vent line scrubber CT-0762 B-66* A M Vac, still furnace vent pip* 5-042 B-666 A I S Tbarsocoupl* wells B-875 A L S Hood, etc, of flaker 0*102 B-66* B-685 B-686 B-689 C-795 A obsol Strip heater clmay ror chlerlnator ete A obsol- Heater for Sperry press tt A H Vent stack A Vent stack A L 8 Vacuus still receiver CT-0808 F-0172 FC-0*5 FC-045 CT-0771 CT-01377 C-798 A I 8 Cade breather CT-0762 C-799 A L 8 Diphenyl head tank CT-0767 C-800 A L 8 Scrubber liquor tank -------- ---- ---------- ------------- u--------------------* See not* on pagc/ln this section. CT-0754 CT-C755 CT-0756 0139286 1 i 1t OT W= ^- -4 Irt * SS "i 82 = 585 r ^* sX 8w5n *5 ns s X oo cn o) i LTt j - nenens nnuui iiuto xaacuk*et eomui litioatioit HI. PIUVIWO LIST, contd. XII - 90 Sr*wins List Drawing Hunter Title Xqulpnent Hunter c-8o* A M Hot water collection tank CT-C752 C-607 C-809 A 1 S Coke acrubber A 1 5 #1 vacuus atlll CT-C753 CT-01396 S-0*3 c-fiio A L S Halt tank Tor high boiler* etc. CT-0763 C-815 C-8l6 A L S Piping of vaeuus atlll A 1 S Arcelor conveyor FC-W5 CT-0770 CT-01378 v-o** C-818 A L S Chlorine vapourlzer CT-07*3 C-621 H flatfors for atlll pota 8-026, 8-027 C-822 A I S Chlorlnator relief connection CT-C7** C-B25 A 1 S Kinetic add atore tanka CT-C78* CT-0785 CT-0766 CT-0795 C-827 A L S Weighing truck, aolid Aroclor plant MSC-0681 C-829 X Llat of sotora C-830 F-eje A I s Gaa-heater for die charge of gaa-haated cT-oeoe chlorlnator N 18* fractionating colusn, not in ' Aroclor plant C-8*7 H Beider for atrip heater cT-0771 See not* on page In thl aectlon. 0139287 cmS " 3 ?TS i^2 585 f 55 > 8 1 in lsr n nr 4 HO v\ni -ns nfn oC ! f3 a8 X O O 9c1p --- .. 1 LJ * un iwi _____1 < * j - -t noTtcns nrniui vomutto tviiuici eormot utiutioi XII. DBAVINC LIST. contd. xri - 91 Drawing List Drawing Mutter C-8*8 1-876 E-B62 E-663 C-66* I-86J E-867 E-870 1-877 E-880 E-881 E-886 E-888 E-689 E-896 D-978 Title Equipment Number N Holder for strip heater CT-0771 N Floor grstlng I S #1 Blending tank and #1 Flltrste receiver CT-0779 CT-0760 I S Buffer tank (air Slowing tank) * A M Heat exchanger for #2 vaeuun still (see drawing B-*83) CT-0750 S-062 A 1 8 Setting for stills for solid Aroclor R-C26, R-027 A L 8 Setting for rireheated chlorlnator CT-0808 H Conveyor for Aroclor flake L-031 1 8 Conveyor for Aroclor flake (layout) V-OA* A I 8 Chlorlnator CT-07** CT-07*5 cr-oejj A 1 8 Shell for gas-fired chlorlnator furnace ct-o8o8 I 8 Shell for stove and trick setting S-OAJ F-0A5 1 8 Drive for gas-fired chlorlnator CT-0808 N HC1 absorption tower N Floor grating, HC1 tower B L 8 Diphenyl store tank CT-037 * See the note on peg* 86 In thli section. 0139288 c sIfl -I n zS 2 S 85 Z - * 5S S "2 C C 4 rr S p zH H cVn> * O V) zfs* tnn" Oc ?3 3* X D O cn i LH j LO CO -J -. nsTtcTB nmaii miufo ninuci cenuii LiTiaariow i t I1 1 -- * i ' ` 301. DRAWING UST, eontd. XZ2 - 92 Prewlng List Drawing Number Title C-1117 B N foundation of P-978 P-2C76 B L S Turbo agitator for blending tank P-2077 B 1 S Stator for above C-3*79 B M Beating furnace for coll of #2 vacuus still C-3775 B 1 S filter for MCI gas P-*252, B L 8 Hurlstic tank P-*300 N Phnsteel drawing BC1 absorber *-*>66 B t H Varec. Oauge on Pyranol sixer *-**15 B L S T.C.B. Store tanks P-**59 B 1 S Rubber-lined treatment tank with agitator C-*16 B 1 S Scrubber liquor ptnp tank ' *-*679 V Obsolete, Layout for BC1 absorber *-*689 N Obsolete, Piping of HC1 absorber C-*705 B 1 8 Baveg tower (obsolete) for BC1 abs. C-*8*5 B 1 8 Scrubber liquor tank -C5711 M Ooodrlch rubber-lined tanka C-57*3 B L S Scrubber In Pyranol plant C-5S1* B 1 8 Obsolete, HC1 tower Bqulpnent Number CT-0779 CT-0779 PC-066 P-0106 CT-01260 CT-01321 CT-0861 CT-0968 CT-01013 IV-0182 . CT-010* CT-01575 CT-01162 TV-0206 * * See the note on page 66 In this section. 0139219 c*! HS H V> H gig -cj 2 n 2 5 r> C"n R" - oo cn to i i LO LQ -6- Gastric Lesions When tasted in monkeys and rodents, KBs show species specificity with respect to a toxic effect on tha gastric epithelium, or stomach lining. In tha monkey, with Aroclor 1242, thara is a mucous conversion of tha gastric epithelium that can bast be described as a dysplastic growth pattern. This growth pattern does not constitute a neoplastic transformation. In rodents, PCls do not evoke this affect on the gastric mucosa. In humans occupationally exposed to PCBe there are no clinical findings to date of gastric lesions, and no evidence of atomach cancer due to this exposure. Carcinogenesisi experimental and Clinical A sixeable volume of animal experimental work has been directed toward chronic studies In several species * the mouse, the rat, and the dog. There are some areas of Interpretation that are still under debate by the investigators concerned, but in the opinion of the Category I tesm the following represents conclusions that can be drawn from presently available datat (a) the evidence on carcinogenicity is negative for gastrointes tinal carcinoma and bladder carcinoma in rats'and hepatocellular carcinoma in the dogt (b) some studies have reported an increase in hepatocellular carcinoma in mice and rats exposed to commer cial KVa chronically, whereas other studies have afforded nega tive results. MOMS 221927 - \ nonero omtui aossxrro tiinuct cctbuii lxtxo*txo J. * ` Cl. DRAWING ust. eontd. m - 9> Bravine List Drawlnc Number B-5615 B N B-5621 t Title Obsolete, KC1 tower support Cyclone C-5625 B 1 S Monel pss chamber on flrebested chlorination system C-61** B M f Monel condenser 1-6209 B 1 S Chlorinetor 8-6*55 B L 8 Fyranol miner 1-6636 B 1 S Assembly of blendinc tank A-6653 V Acltator in blendinc tank B-6868 Thermocouple wells C-6663 B L 8 Filtrate receiver 1-69*1 V Flstfox* of still C-69*2 B L 8 fiplnc diacram for #2 vac. still C-69*3 B L 8 Monel piplnc diacram for #2 vac.still B-69** B 1 8 #2 Vac. Still 8-69*5 8-69*6 Exhaust System .mentioned on p.Cl-6. N t Control room 1-6952 B 1 8 General layout #2 mill Equipment Number CT-01259 CT-01279 CT-01280 CT-012B2 CT-01256 CT-01263 CT-07** CT-01263 CT-01521 CT-0779 CT-01599 CT-01399 CT-01A00 8-062 8-062 8-062 8-062 8-062 St* the note en pa|t 66 in this section. 0133290 ^ h ss g3 = P*eo>- efi H*- 5 mX> PI o"n Rc c"w h dC wv* HO rr nn 8* S3 X D O ui ) ! |CD i D^i i CD CD rwrtrm> nmmi icauro nmun eemui lztiutioh HI. DRAWING US?, contd. Drawing Lift Title D-6956 B L 3 Oeneral layout #2 atlll C-6957 B L S Cyclone on #2 vac. still B-7062 B L S Honel condenser #2 vac. still B-7121 N Support for Sperry press A-7156 N ftps coll under Sperry press A-6863 H Bearing for blending tank (See drg. A-*59) D-10292 B L S flplng of air blowing tank Hand B L S Dryer for Attapulgus Barth sketch (Sec corresp. file Mar, 25/A7) XII - 9* Drawing list Bqulpocnt Hunter S-062 S-062 S-062 F-0113 F-0113 layout of ehlorlnators) #2 Arcelor atlll J to HCL, Juno 7, 19^ Detail of chlorinator") . ,_k_ {Swan Chemical Co.) ) t6 "CL *h 15' * See the note on put 66 of this section. 0139291 c -i ^ V) -4 ?Is g22 rSS -z rc ""Rn xw 4Srx 4ncV"nn) a 0W =n4 rnns la 55 oo S /CD 4 Cn i CD k L - nermie nmuii inimo mnuei eerzuoi imutiw ' j . ; * i | ; ; ' ;* ! 1 XIV. HISTORY OF THE PROCESS IN MONSANTO. xiv - 1 History of the hVNii In the years 1927 - 1926, the 5wann Chemical Coopany developed e process for asking diphenyl, but et the expected demand for it * did not continue, other outlets were sought for the diphenyl. Aroclors were produced In the laboratory in 1929, *nd a they showed good electrical properties, fire resistance, and general Inertness, the Oeneral Electric Company became interested, and developed the use of Aroclors in transformers and eapadtators. A plant was Installed to produce 3000 lbs ./day at Anniston. In 1935 Monsanto acquired the Swann Coopany, so gaining access to their Aroelor patents. As the deaand for Aroclors Increased, additional production equipment was installed, located at the Monsanto Illinois factory {then plant "B" and now called the XruanAch plant). This equipment came on streaa in September 1936. The Xruanrlch plant site was chose partly because of the avails kl 11 ty of chlorine there, but when chlorine consumption overtook the production, and chlorine had to be purchased, proximity to the diphenyl production at Anniston had acre weight, and additional capacity, largely designed on the plsnt 1" model, was installed at Anniston in 1941. By 19*6 both plants had doubled their capacity, to give a t'dtal production capacity approaching 2 million pounds s month. About 1954 chlorine calls were installed at Annietcn. The Newport plant wma designed, aalnly cn Imuieb plant lnfoimstion, but to a less extent on Anniston Information, under Newport Project No. 12 of the London Central bigineering Department. Chlorination started at Newport in June 1951, Mr. Clegorn from Anniston spsndlng some time st Newport to aaalat in starting the diphenyl and Aroelor plants there, The first production of pyranol by MCC was in 1956, when Pyranol i486 was bade for tht Oeneral Electric Company, the blending being done at first in rail tanks. Pyranol 1495 was made In July 1938. The use of tln-tetrsphenyl started in 19*4, since when the main production has been of 1467 (TCB - 1260 mixture plue tln-tetraphenyl). 0139292 o- --. S nan sis am >* r H5 g*: Sm ln "r ii rt X o o 03 co CD 1 Cn ^w L, I|| . j 1 --" --------* I rwrtervB nmuii sosexjrro usnjjrts corzaaox lxticstios , . '* XV. OPPUTIKO INSTRUCTIONS. XV - 1 Operating Instructions Op*r*tin* lnttructlon* were *lv*n in the report of Lyles, Soffranko end Becker, November 19*7 ps**s 8* * end e reviced verclon wee put out by the Knnwnrlch Plant Stenderd* Deportment, August 10, 195*, " (copy cent to Newport, Hey 23, 1955) feint* csllln* for apeclel mention ere: -- 1. Cere in meltln* diphenyl received In ear*. The flrct move 1* to melt e hole, from the surface, down to the bottom of the tank to prevent development of pressure from the heat of the tank coil or jacket, 2. Usual rail track routine In handlln* cars. 3. Exclusion of rain etc. *. Proper use of tracln* on pipe lines', lines to be blown clear after use where necessary. 5- Tank vests and overflow lines to be maintained above the meltln* point of diphenyl 6, Charge* in the diphenyl measurln* tank to be kept hot. 7. Pi re precautions In handlln* diphenyl, toluene, and butyl acetate and mixtures eontalnln* them, ' 6. ChleMnator charge* kept as cool as possible, and not circu lated In the early sta*e of chlorination. 9. Watch Inlet preasure on chlorine line to chlorlnator. 10. Care In emptyin* chlorlnator* not to suck back the scrubber charge. 11. Keep chlorlnator charge out of the chlorine feed line. 12. Watch gravity and te^>erature of scrubber for Indication of poor absorption of chlorine In the chlorlnator*. 01392S3 v X oo cr i Cn CD I|| ncrttrra nmuii acaaaaro isstmasci eonuoi tin caries i i rv, operating instructions, canto. .. XV - s n Operating Instruction* 1>. Control air-fc lowing temperature to suit th* Aroclor being handled. 1*. Cheek dryness of sir from Lectrodryer t proper Interval*, 15. Ouard agalntt burning or coking th* still colls. 16. The ususl care In lighting ga* furnace*. 17- Care In dealing with hot material tapped froa th* still*. IS. Cleanliness In handling finished Aroclor*. 19- Vlth higher Aroclors take special care against blockage of lines. 20. Safety precautions as discussed under "Bassrds", Section S, above. Pyrenela Operating Instructions rslstlng specifically to th* Kra&rlch plant are given on pages 33* of the report "Dept. A-2*6 Pyranol Process", Lyles, Soffranko and Killer, March 2*, 19*7, Oepy #8 sent to MCL October 15, 19*7). Points Mentioned are: 1. Cheeking the Moisture content of incoming cars of trlchlorobenaene. Air blowing at about 50*C. to remove excess moisture. 2. Sampling of Materials at various stages for submission to General Electric Company. 3. Exclusion of Moisture, HC1 fume and dirt. *. As a woridng rule, in adjusting blends of TCB with Aroclor 1260, I 1 part of 1260 added to 80 parts of the blend will raise th* Sp. Or. about 0.001 and the refractive Index about 0.0001.* 013$ 294 I V- C ^- r, * n 22 E ri 5 H ?O *M* n x o o cn 03 i L1 I - npncrxB nrmui nevium iiipuki eenuot lxtxutxov i . .' XV, OPERATING INSTHPCTIOKS, centd. XV - 3 0pr*tin* Instruction* Pyranola. eontd. 5. Blends cent*Inin* tln-tetrephenyl sre to be wre (stout 80*C.) when filtered, otherwise sea* TTP may cone out of solution. 6. Vsterproof cloth oecr the doses of the filtered roll tanks to exclude aoisture and dirt while trsvellin*. 7. Aveldance of delay in dealln* with sables because of the nunerous testln* stages required. 1 ) X oo cn O* Cn i CD un 0119295 "- - riorsms urxuui nenxno manuuci comut ut:bh:w Cm H= m-- Sw5 n * fi 832 J C. P E 1 Adetowl edgment 5I I c 8 *--in* e n Sr n ACKKCVLEDGWPiT 3r nn ?! *?-3 a* To Mr. J. Soffranco who was in charge of the Krumrlch plant A rodor Dept, in 19*7, and to the forenan, Mr. Errol Smith. The report "Dept. 2*6, Aroclor froceaa" by Lylea, Soffranke and Becker, November 6, 19*6 m of very great help in taaeabllng information for the Newport project, alao the companion report 'Dept. A-2*6, Pyranol froceaa" Lylea, Soffranko and Killer, March 2*, 19*7. The reporta by Schwartlng and other*, 196? and 195*, have been uaed In the preaent revlalon of the proceaa detail!. Acknowledgment la due alao to other Kruamrich plant people who helped then and later. Dr. E. E- Hardy waa of great help at Annlaton In 19*7 In explaining the proceaa and locating information. To Meaara. Ellenburi and Wood for guidance around the Annlaton plant, and to Meaara. Baker and Dunlop for analytical information. Hr. Clegom waa very helpful during a vialt in March 1955. X oo cn 05 Cn !0 Cn *i , i L I i 0139296 i I riortcro ummi mossjjtto iiiciun cotkuos tmoiries Index r*t 1 INDEX ACETONE, SOLUBILITY TEST OH AR0C1OR5 DISCUSSED---------------- VII-11 Acid number, conversion of KOH figure Into NsCH figure -- IX-63 KOH v. NsOH values------------------------------------------IX-40 Acid number, test method*-------------------------------------IX-62-, IX-12? Acknowledgment--------------------- ----------- ------------- ---------- Section XVI Agricultural uses of Aroclora ------- ------ ------------- ------------ V3I-21 Alr-blcwlng of chlorination' product------------------ ....... VI-13- ceementa on -------- VII-A Air bloving tanks, ate.--------------- ------ --------------- ni-17a Air, dry air needed In unloading VI-35 Air dryer -............... -......... ------------- ------------------------------------- HI-45 Analytical Methods, see "Specifications k Test Methods" and -- ---------------- "Control Tests" Anthraqulnone derivatives, as stabilizers In Aroclora -- VII-9 report mentioned VII-34 determination of ------------ VII-9 AFHA--------------------------------------------------------------------------------------------- eee"Colour" Appearance eee"Colour" Applications of Products ---------------- VII-1B-, VII-30, H-5 literature survey Mentioned -- VII-32 Aroclora, advantages of ----------------------------------------------------- VII-19 aa animal repellents S-5 are coeplex mixtures ------------------ jj-2 blending of to give intermediate Aroelor ----VII-11 butyl acetate blends ---------- see "Butyl Acetate" causes of high chloride content------------ VII-15- changing production from one grade to another - VI-13 ----------------------- VI-25 colour troubles ---------------------- VII-10- crystalIllation troubles ----VII-11-, VII-2 damaged by heating In iron -------------------- VII-7 effect of aetals on--------- VI-34, VII-1, VII-7, XII-l iij isomer ratios v. chlorination conditions --------- VII-3 need for tin etc. lining in store vessels--------VI-35 1I physical and chemical properties ---------------- III-7 I (solid) crystallization point Method ---------------- U-&7 solid, distillation------------------ VI-24- aelld, manufacture discontinued ---------V-2 solid, process details------------------------------------ VI-7- selld, specifications------------------------------1X-16, II-30 pacifications for -------------- I2-11-, 11-26- 1 i j 0139297 I X o o cn 03 l un _. 1 L nweip nmxu.t ntiurre wnuei nmui imeiriei Index h|i 2 Aroclor, toluene blende ------------------------------------------- ---- VII-7 test nethod ---------------- IX-68- uneteble lapurltles in ------------------------------ II-l, VII-16 viscosity index le high ----------------VII-19 see aleo finished product# Askareli --------------------------------- I-A bulletin---- ------------------------------------------------------------VII*JO Attapulgue earth, alternative nateriala unsatisfactory -- VII-7 dosage of ------------------ VI-27 dryer ------------------------- El -*0drylng of ----------- ---------- ----------- VI-27, VII-7 renotes T.T.F. ------------- ---------------------- VII-7 aaaple aent to MCI. ............................ ------ XX-9 opacification ------------------------------------- II-3 BATCH RECORDS------------------------------------------aee "Operatin* Record#" Benxone, eaaple aant to HCL -------------------------- ...........................a-9 Biphenyl------------------------- ------------------------------- ---- aee "Biphenyl" Elending1 of Aroclora alth butyl acetate II-*0 of Aroclora with toluene VI-29- of different Aroclora, product not neceaaarlly equivalent to product of direct chlorination U-2,VI1-11 for Pyranols------------------------------------------------------- VI-32- Blendln* Tanka ------------- ---------------------------------------- SI-28-, etc. Blowers-------------------------------------- --..................---- SI-6 Bollln* point raa*e---------- aee "Olatlllln* rang#" Bulldln*a -------------------------- aee "Plant layout" Bulletin# on application of product#------- -- aee "Application#" Butyl acetate - Aroclor bland#, teat aethoda ---------- S-175- Butyl acetate blenda, aentlcned-------------- --------------- II-AO precaution# in handling------ IX-AO colour of blends with Aroclora(test aethod )U-178 quality of ---------------- 11-10 specification for -------------- 11*29 capacity of run-------------------------------------------------- ---------------- x-iCarbon, no specification ----------*-- II-3 Catalyst------------------------------------------- *------------see "Iron turnings" Ce reelora ------------------.............. ---- 11-163 Changing froa one Aroclor to another------------------VI-13, VI-2JCheaieal reaction# with Aroclora -------------- VII-21 0139298 HUj Fan c*g n2fi 2cI >a * *zrHs 5 n Ri BH H* SWm nn _> o o cn l1 i O cc O nerscrs* nmuo-i nasurro mnuei esmwi litiutki Index r*c 3 Chemistry of the Process ..................................................... Section II see eleo "Concents on the Process" Chemistry of action of chloride scavengers --------------------- 11-182 Chloride scevengert ------------------ "Scavenger*" Chlorides In tlntetraphenyl, teat method ----------------------- IX-133- Chlorlde test in boiler water ----------------XX-107* Oeneral Electric ------------- aee "Oeneral llectrlc" Chlorination, batch data------------------------------------------------------- 71-5 chart of % Cl, v. lb. Cla to finish----------- 71-*9 cheaiatry of ---------------- 11-2, 711-3 continuous, discussed --------------------- 7II-2 no circulation of charge at firat ---------- 71-6 procesa in detail ----------------------- vi-A- ' purging of gaa Inlet line------------------ 7I-6a rate of ---------- see "Chlorine flow rates" record charts---------------- 71-37- unstable byeproducts mentioned -- U-l, 711-16 Chlorlnator for solid Aroclors ------------------ 3Q1-30- Chlorinatcra XII-7- etc. Inlet fitting -------- -------------- VII-2 Chlorine consumption figures ------- see "Production atandards" determination, total chlorine ------------ IX-52-, ix-6S - Oeneral glectrlc method, sae - "Oeneral Electric" distributors ---------------- ......--------XII-9, 7II-2 flow ratal ------------------- --------------------------- VII-1 handling of ------------------- --------- ----------........ VI-2 o mts on -------- ..-------- --....... 711-2 altering etc. --------------- --------- ... 71-3-, 7I-6a- no apeclfleatlon -------------- -- ...------------------ --- II-3 quality, canments ------- ----------- ........-------- ... ix-8 use of snlfl gas etc. ---- ---------------- VI-2, 7II-2 Chlorphenola in Aroclors ----------- ------- ----------------- 711-10 mentioned -....................................IX-8 Cliff-Char sae "Carbon" Cloaad Tanka -------------------- HI-7- Cocks, choice of ------------------------ HI-5 Coke ecrubbera see "Scrubbers" Colour, eee also "Slectrophotometer" test methods, Aroclor 1271 (solid) ------------- 1X-101 Aroclors 1270 snd 1271 in toluens solution IX-100,-lC3a Aroclors --........... ......... ............. ------------------- IX-57- 0139299 O H~ H Vi H ww n c e> n * > r w- H 3 > Ci V) tVftI * sm n rn > 5 *4 X oo tn CO With respect to the possibility of caneer Unkid to exposure of human* to PCS*, epidemiological studios show to date essentially neqative results for hepatocellular carcinoma, gastro intestinal carcinoma and all other forms of cancer. There is a ingle preliminary study that purports to show an increase in melanoma (skin cancer I in occupationally exposed people, but the full data display and analysis have not been made for this study. In contrast, in two larger and more detailed studies, this finding has not been confirmedr no excess incidence of melanoma in exposed personnel has been observed. Retrospective mortality studios of PCB-expoaed human populations hsve not demonstrated a consistent relationship between extent of exposure and the development of any par ticular typo of cancer. The human studies In hepatocellular carcinoma are not comprehensive, but to the extent that they have been developed the results do not confirm the projection of a risk for liver cancer based on the animal studios. Some findings of increases In lymphatic and hematopoietic malignancies were below the level of statistical significance, and were refuted by observations of changes in the opposite direction in other epidemiological studies. Even findings of statistically signif icant differences between exposed and control populatlona with respect to the incidence of rectal cancer in woman at one plant have not been confirmed by observations in other studies. The variance In these findings points up ths Important principle that the Standard Mortality Ratio <SHR) may vary widely in different HONS 221928 nuiKUi imuui RCKUjrre nceuici nmui litioitiom Index rage * Colour, diphenyl----------------- ---------------------..............---- ix-93 general (aPHa)~lX-^7- (Haxen)---------------------------- -------------------- .... IX-153 Pyranols --------------------------------- ...------------- ------------ 11-57- Coroents on the Froceee ----------.----Section VII Compatibility dote (Aroelor)---------------------- .....--...... m-16 Competitive product*-------------------------------------...----------.... XX-183 Consumption figure* ........................... see 'Cost dots" ............................. -flow Sheets" --................................. ................"TieId figures" Control tests, in blending Pyranols --------------------- ---- V3-32- Control tests .................section VIII Conversion factors ..................................... H-12b Conveyors d-86 s Corrosion test ........................ see "Oaneral Electric" Cost data ....................................... see Section X Cost sheets --------------------------------------- -----------....------ -------- X-27- Crystalllxatlon in Aroclort, see "Aroclort, crystallisation trouble" Crystalllxlnc point test Method, Aroelor ................ IX-&7 control test Method--- VIII-1- dlphenyl XX-9^ glycldyl phenyl ether-.-IX-I6I trl-tetra chlorobenzene 11-167 Crystal structure, test Method for Aroelor 1271-------IX-103a Cyclones, on chlorlnators ------------------------------- VI-9- on stills -------- ---------------------------------- El-78 DENSITY-------------------- ------ ---- see `Specific gravity" Design Reports ---------------- ------------------------------------ - VU-31 Dlbutyl diphenyl tin, as a scavenger ------------VII-8, VII-22 Dielectric cenatand and power factor, test Method -- XX-1AS- Dlelectrtc strength, teat Method ---------- 11-135- D: phenyl, ccMnts on quality -------------------- IX-8 Diphenyl handling VI-1- Dlphanyl Measuring tank SI-25 Diphenyl, phys. and them, properties ------------------- III-l- saaple tent to MCI -------------- IX-9 specification -------------------- II-1 test Method (colour) -------------- 11-93 Dlttlllttlen-------------------------------------------------------------------------- TI-1*- cewnti on VII-A- 0139300 b H H%R H_ H n "" *? nn ZZ o o cn cn 11 L - nettCTO nmuii umno msuin comui iitioatios Index rm 5 i Dlstlllstlon, of solid Aroelors ------- -------------- ---- S-24- record charts ------------ .------------------- --- S-40- seMi-continuous--------------------- ---...........-- S-21- I uss of Moderate vscuub ---- VI-23 Distilled high boilers ----------------- see High boilers, distilled Distilling Jlenge, Test Method, Aroelors etc. ----.-- IX-74- dlphenyl --------------------- IX-95 general------------------------------S-41- I glyeldyl phenyl ether --- XX-162 tAchlorobensene etc.-----IX-70 trt-tetrm chlorobenzene XX-168- Dietrtbutlon list --- --------------------- ----------------- see title page Drawing list--------------------------------------------- ------------- si-86- see also the drawings listed under Many of the Itehs in the equlpaent list In Section SI Dryer -- ----------------------------------------- ,--.--.... see "Air dryer* Dryer for Attapulgus earth -------------------- see Attapulgus sarth Du font wiseoslty Method (farlln)IX-179 BAItTH----------- -------- -------- ------------ --------------- see Attapulgua earth Barth treatment of Aroelors ---------- see "TreatMent* Bffeet of Metals on Aroelors---------- see `Aroelors" Xjeetors-------- ------------------------------------------------------ VI-23, SI-64 Blectrleal grades of Materials ------------ SI-7 SectA eel properties of Aroelors III-6, SI-16, VS-32, SI-17 SectA eel stabiUty, test Method -------------- S-6l lieCtrleel test apparatus, cleaning of---------- S-154 IleetAeel teat Methods----------------------------------- SI-32-.S-155 - eoMcnts on ---------------- S-163 SectA cal uses for Aroelors ---------- SI-20, SI-21 SeetrophotOMeter, operation of -------------- S-106bBlevatora ------------------ SI-49 toergur,ey Measures ------------------------ S-57Squlpaent Set ------------------ Section SI general note ---------------- SI-1 Svaporatlon loss data (Aroelors) ---------- III-6 RNCHLOX---- ------------------------------------------------ ------------------------S-183 filter*---------------------------------------- -------- ------------- --------- --- SI-42- A Itration of Aroelon, after earth tmtsent---- S-27-, S-33 F i 1039301 X j I/I H K gS O H ) cSi at > x r >e> s=: > r X o o cn Cn '- noTtrrtt nmtui nuno tusuiei ccnust imuftei Index hi* 6 Finished Products, causes of defects ---- chlorine contanta -- ---------------- TIH* ...-------------- n-i comanta on quality-- 11atad --------- ------------- ....--------- 711-9 ...-- I-*, i-a phya. and cha*. prop, --------- ... m-7- apac. and taat nethods aaa .................. ---- (action 12 ----------- Aroclors ---- Hontara Fire Hazards Fire point, taat method -- FIalter ------------ Flaklnc of solid Aroclors *----- Fpranols XX -6 -- 12-82 ------ -------------- SI-AO .................... 71.24 Flash point, tast aathod ...... Flow actar for ohlorlne, sea-- ---.-.Chlorine flow rstas" "Chlorine Betaring' Flow Shasta ........ ----------------- ..... Paction IV Pubs exhaust ayataa ....--.--... *aa "Blowers" GASKETS------------------------- -------------- -212-2 attacked bp TCB blonds 711-17 for druBa -------------- - 71-54 to resist Aroclors .........--...... 711-19 General Electric Test Methods, ocments on - ... 711-12- 12-40 12-180 corToslen tast -------- - 12-85 Inorganic chlorides tast < -12-77 - aanpllng -- ---- 71-52 . 12-40 Glycldyl phenyl ether, chaaieal nature of --------- ---*1-4 chloride content of - 711-8 dataminatlon of In Inertaens 12-165 hazards In handling of ------ 12-161 spaelflcationa ---------------------- -- 12-5 taat Bathods ----------------------------- 12-161- RA2AM5S------------------------------------ --- Section S see alio -------------- ----"teergancy Measures" Kazan colour determination net hod -- ------------------ 12-155 BC1, -----------------............................... sea "taydrogan chloride" Hast of draperstlen ------------ eeB#OMeeeB*k#omOO JJ*2 of metlon ..................................... -...............^.a------. X2*-2 0119302 O ;J ^s H in h Sg" 822 Cn > -X "-S pn S w- g" nnr 'zh hO n i/t H fl nx rn S5 a a* oo En co cn ru L - Index fag* 7 High boilers, distilled, phys. and chex. prop. ----. 111-5- handling of------------------------------ ---............. TZ-1- no speelflestion -------------------- ix-1 staples sent to MCL ---------------- IX-9 see also ---------------------- "gantowax" History of the process -------------- Section XIV1 Hold point -------------------- see "CrystalUsing point" Mydrsulle fluids ------------------ VII-20 see also under "Research reports" VII-33 etc. Hydrogen chloride, absorbers d-85 absorption, Anniston ------ VII-11- cooling k scrubbing VI-9-.VI-11- equipment is outdoors,etc. V-2 process in detail ---- vi-11- see also -------------------- ---- "Muriatic acid" INEItlSSNS ---------- -------------------------------------------------------- ----------1-4 Inorganic chloride test ------------see "General electric" Instruments ---------------------- HI-46- Introductory Hots see front of book Inventory, dally -----------------------VI-46a awithly-----------------------n-47-, Vl-50- Iron, determination of in Aroclers etc, -----------IX-84 general method -------------- IX-91- Zron turnings, preparation of ---------------- VH-1 wastage of In use ---------- VII-1 Isomeric ratio, Aroclors VII-3 trl-tetra chlorobenaene ---------- XX-I69- JOIHTINO AMS PACKINGS see "Oaaksts" usouit ngnRDDiTS-------- ----------------------------- x-a, x-16 lay-out of plant -------------------- v-1- Le c trodrye r ------------ aes Air dryer Lime (hydrated), addition of------------------------------- VI-16, VI-22 apedflcatlon ..... ................. .. XX-3 loss on hasting st 100*C., test method ---------- IX-73 0U9303 4I * o -CI -'I H- n t x ns* J an5 p> *^* cpX> x ?3 X O o en i cn iJL'.O '- ^ 4 *. nancrm nmmi mum ninuct comui utjoitici index f|t 6 MAJOXT RESEARCH REPORT (MCL) (reference) ------------------- - VU-31 Melting point test method, Arcelor 1271 ---- 12-103 general --........--------- n-50- also ------- "Crystallising point" Melt tank for Santowmx----------------..................... .. VI-2, XII-24 Hill for solid Aroclore -------------- ----------------- HZ-60 Miscellaneous Equipment------- --------XII-61- Molsture --------------- ----------------------- ---------- ------- see "Water" Hontsrs, mentioned ----.....................-- ---------------->-- J,3 i phye. properties ----------------- -- HI-17 eoftenlng point test method ------------ 12-59 epeclfleatlen -------- -----11-17 i test methods--------------------------------------- 11-59. 12-111 s use in chlorine cells suggested ------- VII-21 r n uses, electrical ---- --------------- VII-20, -21 Monthly reports ------------------ ------------------------------------ 2-7- see also ------------- ----- "Inventory, monthly" Motors---- ------- -- ----- -------------------------- XII-50- Muriatlc acid, carbon treatment of ----------- ------VI-11- bateh records ---- VI-45 Muriatic add, speclAeatlen ---------------- ---- n-39 see also --------------- ------- "Hydrogen chloride" VOKDfCIATUJB -- -------------------------- ------- ------ ----------- ------------ 1-2- OOOOJl, TOT KRBQD, AROCLOR 1270 ------ ----------- ------ ------- ------ II-99 general -------12-56 Off-gas ---------------- --------- ------ see "Hydrogen chloride" Open Tanks ------ ------------ ------ ----------------------- -- -------- XU-68 Operating Sets -- -------------------------- --- --------------- Section 2 Operating Instructions, abstract of -------- ------------ -- XV-1 - report mentioned------------ VII-31 Operating Records -------------- ---- ------------ ------------ - VI-36Outline of Process --------- ------ ----------- --------- -- see "Synopsis" PACXZNO ---------- ------------ ------------------------ ------ ------ ----- -- VI-34- see also "Effects of metals" Pacttngs for pump glands ------- ------- ----------------- XII-2 to 4 Parlin viscosity method ---------- ----------------------- - 12-179 Parr bomb ----------........-----------.....----- see "Chlorine" i 4 0119304 4 o - S ^ R* R gn 2 ZS5 5? Cl VI n i 1" - fi VI VI r> n i > o o oi I L.n t%dttct*x> nrrnui oiuto ninukici eonutt ixtxoitxoi i t Index i fl 9 Fitint fodtlon ..--.......------------ ----------------------- VII-8, VII-22 Phenoxy prepen* oxide ----------- ....... sea 'Olyddyl phenyl ether" Physical and Chemical Oats----......................section HI eee also------- -----"Specification*" Pipe line*, not* on -- ------ *------- --................... xn-l Plant lay-out ................------ ...----------............... V-l- riant Kacorl* -------------- ------------ .......... "Proc*** record* " rieeticlaere------------.... ---------------- -------------------- -------- - IX-18} Plsstlclsars, uae of Areel or* ......--------------------- .... VII .21 P.r.O. (phenoxy propone oxide) ----- eee "Olyddyl phenyl ether" i Power factor, teat Method ......--.-11-1*4. Practice figure* ......................................... X*37 t rrevlou* report* on the proce** --------...... VI1-2J. Previous reports, see also "Introductory Notes* at front of book Process, for the different Aroclors ---- ------------ -------.--1-2 In detail --....--Section VI record* --------------------------- vx-36- reports -----------..--........... IH "Previous reports" see also Section X Production standards --........................................ -- X-4, X-38, X-ll. ------------- aee also "Practics figures* Production eunaarles --.......................... ............... ............. ....... .. X-17- Publl cations ------ ...------------------ --.viI-29 ---------- ------------ see also "Bulletins* and 'Reports" Paps --------------------.......--XII-69- Pyrelen* ...------ ---------- ............----------- ............-----IX.183 Pyronols, batch record eheet-----------------.--........... VI-16 consent* on blending of------- --....----- ---------- VII-7 listed---------------..............--------------- ------ ----------------I-* spedflostlona ----........... XX-18-, IX-31, 11-36- *p. tr.-tesp. data------ --------- ...-----------........ HI-12 test Mthod for T.C.B. content -----------...------ - IX-106^y^OClOn 00 0 1*3*ee**e *aofc****e****e**eme* *****a**eae QUEHCH2N0 OP STX1X BOTTOMS VX-18 IUV MTEUALS, testing of bulks before blending for pjranole --------------- ----------------- VI-32 Receivers for vacuua stills------------ ...----VI-15-,VI-21, XII-27 Record Sheet* --------.------see "Operating Record*" 013930S c h * s^ HWH nn = 5 R5 he * 9> N- --3 rp -* Srj fCi Q"IA- % fir 9n r* 3 K H r> ms rn g* *f 3> a* O o ;C3 1 cn * nonerv nmrni oixjtto nivuia rnnui imuTiei Index face 20 Refractive Index Teat Method, Aroclors etc. --................... XX-64a general ...-------.--- U-157- glycidyl phenyl ether -- U-163 Reports (previous) process *--------------.......... ................VII-23re search ....----------------------- VII-25- Research reports ........... --*--..................................................-- --VII-25- Reslatent paints and drum lacquers (Aroclor) ------- ------ VI-55 Resistivity, Aroc lore---- ------------------- ------------ --- 121-16 test aethod ------ -------------- ----------........... II-141- Retorts for solid Aroclors ------------------------ ---------------------d-77 Ring and ball test asthod ------......... sm 'Softening point' .. t SAFETY------------------ ----------- --------------- --------------------- see "Hazards" Samples sent to MCL, raw Materials IX-9 finished products -------------- 21-183 Sailing procedure, Aroclors etc. -- VI-28, VIZ-14, XX-IOB- Santouax, Belt tank for ------------------------- VI-2, HI-24 saaple sent to MCI ---------------------------- IX-9 ) Santovax R, phys. and chemical properties------ ------ - HI-5Scale of Working -----.......................... --- sea "dapscity of Riant* Scavengers for chlorides, addition of ------------------- VI-33 alternatives ---------- VII-8, VII-22 chemistry of -------------- H-182 ecaunts on -------------- VII-8 effect of on chloride test ------ VI-33 patent position ------ VII-8, VII-22 removed by earth treatment VI-33,VU-7 Seevsngers,. see also ------------ ---'Dlbutyl diphenyl tin* ---------------"oiycldyl phenyl ether* ------"tin tetrephenyl* Scrubber liquor, changes in density of -------- VI-7, VI-10 Inventory factors ------------ VI-53 Scrubbers on off-gas --------------------- -- XII-22- etc. handling of ----------- ------- VI-6, VI-10- Serubbers on vaeuin stllla ---- ------ ------- Cl-19 etc. consents on VII--4-- lapregnatlon of ----------- --- VII-4- Scrubbing of off-gas, cements on --------------- VII-3 Services, requirements of --- ---------- ------ ------------- X-12e, 1-39 *iift gas --....... ............................. --...------ see "Chlorine" Softening point, method of determination, control test-- VIII-2- Arodors and t Montars ------ IV-59 r i* j CL39306 J1 b- c** -ri -n ran= "r rri rx > * x r -*s 5 I1" r nr aH 4 nV) O (A r> sr nn s zl O o tn 03 i cn cn j * i * i i i i t j i f ce 11iJ i1 1 1 I i ji fc-- Index Fat* II Softening pointa, of Aroelora (charts) ----- -------- - III-10of Montare (table)------------- --........... - III-17 Solid Aroelora------------------------- ----------- see 'Aroelora* solid" Solubility data (Aroelor*)--------- --------- ---- ....----------- 313-16 Solubility of gases in Aroelore --------- --- ------ --------- 331-16 Speelfl c* ti on*-------------- ------ .........------- ------Section IX Specific gravity, teat Method, Aroelora -------- --------------- 33-71- general Method ---------------- 13-96glyeldyl phenyl etbar------ 33-16* trlchlorobaasene------------ 33-69 Specific gravity vs. chlorine content (Aroclon#hart --- 311-15 vs. lbs. chlorine and f chlorine content (Aroelore) chart------ -- n-*8 vs. teaperature (Aroelora) ---------- 333-12Stability test -------------- ----------------- set "General Electric" Stability teat Method (TCB) teat Method -------------33-120Stablllietlon f TCB ----------- --------------------- --....... .............. 33-10 Stabilizers for Aroelora------ ------------------- Til-9 Still*------ ------ -------- -------- -- ----------- eee "Vacuus tills" Sulphates, teat Method in Fyranols etc. ---------- 33-17* Synopsis of Brocas* ----------------- i-l- TAKC OF CONTOffS ------ ------- ---------- see front of book Tanks, closed --------------------- -------- ------. 31j-7- open ZII--68 Terphenyle, phys. and chan. prop. ---------------......... 333-6 see alao --------- "High boilers" and "Santee**" Test Methods, MCL report Mentioned---- ------ ------...--VII-31 ---------------------------- -Section 33 eee also -- ------ ------- -----------"Control tests" Thsnal data ---------------------- ------- -- -- U-2 Tin tetraphsnyl, ehemletry of action--------------- VJI-1* erystalllzos out fron Aroelora --------VH-8 - determination of in Pyranols ---------------33-129 effect of on chloride test---- 33-lSl, -162 Mentioned ------ ---------.............................. I-* petent position-------------------- T1I-6, VII-22 removed by Attapulgus earth ------ VII-7, V33-15 aanple eent to net ----------------------------- --- 33.9 specification 13-*- ts*t Methods 33-132- u*e of................... ............................... -------- VI-33 013930? i *o1 -- w -r PI g H*o n 2 O- nn ?5 o "S fi rsi nSp" 4x4 H O nW Ifi hn fi n ?! ~>r hs* a* o c un _1 nmeis nrmu.i rime ninwei eenuti utiutici Index h(t 12 Toluene blends, epedfl cations for -----.............. ---- U-27- epeclfi cation------ ------------ ------- ----------.................... JX-S Towers ------ - - --------------si-8} Toxicity --------------- -------------------------------------- -------- vn-19, rr-i- lUtntun reslew Mentioned-------- -- -------------- VII-29 references ----------- -------------- --III-2 wnunt on Inhale ------------------------------------------------VI-5* "TreetMent" of aistllled Aroelcr# -- .....................--- VI-27- HMiU no ------------- 7II-- see nine 'Attapulfus oarth" Trlchlorcbeniene, quality of, cements on ----- IX-8- dlscusslon of----------------- ---jj-8- phys. and cbea, properties -- m-6 aa^le sent to MCL ----------------- ix-9 solvent offset ---------- VII-17 specification for row nets riel---------------IX-8 finished product --- IX-55 teat Methods ------------------------------------------ IX-68- Trl-tetrochlorobenssna, cheaper then trlchloro ix~*0 looser!c ratio ------------ 11-168- opeelflcatlon of ----------H-7 test Methods --------- U-167- use of --------------------------------- VII-8 Turbidity, tost Method ------------- ------ -----------11-159- see also under --------- "colour" OXSTABLE BTl-PftamCTS OF CELORUUTIOW....... ..............--H-l, VH-16 boss for products -------------- sea applications of products Utilities ---------------- ----------- --......... ........................ see "Sereloee* VACUUM STILL HXA.TIKO COILS.....................-------------------- XU-**- ete. sketch ---------------- VI-2Os Vacuus stills -------- ------ ... --- m-78- ddseusslon of ------------------ -- V3I-5* opentlen of ------------------ VI-1*- Vslvee, choice of ---------------- XII-5 Vapoteiter 1 1 ' -- XI-6- Vnpcurlaer for chlorine----- V3-2- Vapour pres sura a of Aroelors -------------- Hi-8. curves --........ ----HI-9a- at low tenperaturae (report Mentioned)--------- VII-29 0139301 * i* *1 "i -= '-I ^ WH n*r g j? ^ S 85 ! * a. tj n *Wf S" r, r n H* HO VW* px* nr* r: n oc S JS x o 0 01 to <1____ I )( cn co iTvrxu.1 nurrc uirum nmui inmnei Index hit 1) Vegetitlpn, effect cf Arcelor* on ------ ------- -----. H-5 Vlseoeltie* of Arocler* ....................... .-- ............. ........ *--- 131-6- chart* -------------- 331-10- viacolty, coneerin graph --------------------*-U-6lb general teit Method -------- ---3X-112- parlin Method (Pu font) ------------------ IX-179 teIt Method--- ---- -----IX-6la- water, test ktthod, DJ AR0CL0RS ETC. --IX-65-, IX-1, XX-10A- for trace* ....... ....... ............--IX-65- Welghlng aoelei ----------- ---------- ---------- ---------- HI-83 Welfare ------------------------------------ Section S ytvtvt -------------------------- **e "Biphenyl" TXXI2> FUTURES ------------------------------------------------------------ x-15 computation of X-3- tandard ------------------------------ X-ll- 01X9309 -8- studies, and that undue emphasis should not bs placed on the SMR found in one study unless it has been confirmed uy similar findings in repest or psrsllel studies. Reproductive Effects Experimental work with commercial PCD mixtures end smmal models hes been directed to the reproductive process itself, to teratogenesis in the offspring, and to possible fetotoxiclty. in moet test species PCle produce deleterious effects on reproduction at high dosages, in the female monkey at relatively high dosages, difficulties are encountered m con ception, in implantation of the fertilised ovum, and in carrying the fetus to term. Similarly dosed, the male monkey does not transmit these difficulties to the reproductive process, in the human, exposed occupationally or otherwise to PCIe, there is in general no evidence for adverse effects on the reproductive process, although there are little data from which to draw con clusions. In the very special case of Yusho exposure to high levels of PCSe and other polychlorinated hydrocarbons, the new born in significant proportion were pigmented, small, and shewed a retarded rate of growth. However, this pigmentation disap peared and the infants caught up with control population infants in total growth. The potential for PCb-indueed teratoganeeis, or produc tion of defects in the embryo or fetua, has been investigated in several species of test animals. Host animal tests have yielded negative results when PCHe were administered to pregnant females during the critical periods for organogenesis. MOMS 221929 9 possible exceptions eo this statement might be noted, in mice, a single congener, 3,4,3',4'-tetrachlorobiphenyl, in duced* a behavioral defect {"waltzing syndrome*) that may be related to an anatomical defect in the inner ear. PCBs in mice ay produce some delay in implantation. In rata, no gross teratological changes were observed, but sosie alterations in thyroid structure or function produced by PCS administration slight Call under the definition of terata. In dogs and in swine, no teratologlcal effects were noted at lower PCS dosesj however at the highest doses of PCB in the feed, at which the dasi suffers marked reduction in food consusiption and is therefore nutritionally deficient, there ars dose-related teratological effects in the offspring. In monkaya dosed with pels, there are no dose-related abnormalities in the offspring, but they are mailer In alia. Based on those observations, it Is the Cate gory l team's conclusion that coamarcial pels prassnt no appreciabla risk of taratoganlcity In offspring of human famalas exposad undar occupational conditions In tost animals, .e. rata, dogs, and rabbits, PCBs are fetotoxlc when administered at relatively high doses to the pregnant female. In the human, tho only reported epidemiological evidence for fetotoxlclty in expoeed populations items from the unique Yusho event, in which causation may not be linked to PCBs. MOMS 221930 10 - Mutaoeneaia Investigations of poasibla rautaganasis from acuta or chronic expoauraa to comnarcial PCls hava shown nagstiva raaulta in a aanaa of i_n vitro and i_n vivo teat ayatama. I to la tad bactanal taat ayatama (Amaa t*.;> and human lymphocytaa in cul* tura ahowad no avidanca for pCB-inducad mutation or tranaformat ion. With wi vivo ayatama in intact aniaalat (a) cytoganttic taata for altarationa of coll atructuraa or for induction of chromoaomo abnonualitiaa yialdad nagativa raaulta> and (b) both tha mouaa micronucloua taat and tha dominant lathal taat damonatratad negative raaulta. incubation of human lymphocytaa in cultura with pcia cauaad an altaration in glucose tranaport through tha call meabranea. Thara la no significant avidanca that PCBa ara mutagenic in taat ayatama, and no raporta of auch activity in human populationa. It ia quite unlikely that commercial Kl mixturaa would exert mutagenic activity in humana. Thia concluaion ia eonaiatant with tha lack of axcaaa cancer incidence obaerved in pet-expoaed human populationa. other wealth Effects Thia grouping lncludaa anayme induction, iamuno* competence, and porphyria. PCta induce nixed function oxidaaaa (NPO) in tha liver of taat aninala. Tha important issue ia whether or not thia procaaa includes tha specific induction of cytochrome P-448 aa a general property of tha PC8a, with tha added implication that same oxidase system ia baing induced that MOMS 221931 u CQUH be involved in chemical carcinogenaais. Several conclu sions vsrs reached with respect to this issuet (a) the pre dominant effect of commercial pCSs is cytochrome P-450 induction, not P-441; < b) commercial PCBs in the U.S. can contain up to about 2 pp* of PCors( and <c> the PCDrs can induce cytochrone p-441. Prom these observations in animal eodel systems and our judgment, it is concluded that under conditions of u.s. occu pational exposure to PCta, none of the HTO-inducing actions of the eosuxercial mixtures will be of toxicological significance over the lifetime of a pcs-expased person. with respect to potential PCS effects on iaaunocompetence in test animal aystees, some observations are pertinent to tbs assessment of probable haserd in the human. It has been ob served in chicks that if the PCI dosages are high enough, atrophy of the splenic pulp and necrosis of the lymphoid system can be demonstrated. similar indicators of change in ismunocompetenee can also be produced in ducklings, mice, and monkeys as a conse quence of severe change in nutritional status. High doses of PCBs leading to marked reduction of food intake and utilization can lead to such changes in nutritional status. These considera tions lead to two general conclusions relative to the PCS-exposed humsnsi (a) as projected from animal studies, if the PCS dosage is high enough to leed to genorel toxicity in the human (e.j., decreased food inteks, fell in body weight, fell in weight gein). mons zzmz 12 - immunosuppression may be demonstrable secondary to malnutntion; and (b) at lower dost levels, there is no likelihood of signifi cant immunoauppraaaion. ' Porphyria, or deposition of porphyrin-derived pigments in liver and urine, has been observed in experimental animals such as the rat and rabbit dosed with PCSs. The effect has a delayed onset, and, especially in the rat, seams to take place by mechanisms different from those employed by known chemical porphyria-producers in the human. It is concluded that, aside from the unique case of Yusho disease, no evidence has accrued for the occurrence of porphyria in populations exposed to PCSs even under high level occupational exposure conditions. epidemiology This section (XII) of the study presents a separate, independent assessment of the recorded epidemiological literature and data bases on human exposures to commercial PCSs, and on the significance of the health effects attributed to these exposures. Summary points in this assessment include the following: (a) mortality data, based on very small numbers of deaths, do not confirm a carcinogenic effect of PCSS in mam (b> data on human skin lesions in relation to PCS exposures have shown variability in incidence of this effect with geographical locus and with In creasing blood level indicators of exposure) (c) data from studies of liver ensymee snd liver function suggest changes in one or more ensymee related to PCS exposure that are not associated MONS 221933 - 13 with liver disease end that occur it levels below those it which chloraene occurs; <d> there 11 frequently i positive cor- relition between PCS levels ind triglyceride levels in blood; rnd <e) epiden iolog ical diti on reproductive effects, hem to Logy ind immunology in humans exposed to PCBs do not suggest abnorslities in these eysteiss or processes. guman Occupitionsl Exposure Levels Of the virious effects noted in animal test systems, only densetological effects, including toes ehlorecne, hive been clearly demonstrated in human populations at the dosage levels associated with occupational exposures, table 1 summarises the nature and intensity of some exposures that have occurred to per sonnel involved occupationally with pchs and the biological indices that have accompanied these exposures, measured as PC8 content in blood and adipose tissue. Sines the risk to human health from even high level occu pational exposures hie been shown by the studies available to be low, it may be concluded that much lower human exposure levels do not present significant risks. MOMS 221934 till tltMl a CIS7JI Matt * mm C1W1I uuwr* 0M* ua I1WM CltMl u*m mtt *-- MU (1H1I U Mil I1MUI a OMatrata la Mr | *01 (Ml la UM PUM * Nn nr Maun** a. SUtteE? lb* *OI IMI in Mtm timm Tint ptf wll|an*^ A (KB UN*) 9 0 B P M- JM m- w M*-1M n < 1M. u 1BN M M la a*a. n- cm IM mt. * im- tm 11 u * tm-um IJ MM-- 14* JU IM-IM* 11 13 H IM 4- Ul US-ISM UQ IM-IIW ___ *M tr.-lMO L- TJ It* 41 L-in t- IS L-IU a- ii b- U 1*1111 N- 19 1-M 1 IM 1M-4IS ,, L-24 2-271 0-4 .2-10 UU2 2io-im It* 44 20- 190 b-m 34-2409 0- 9| 10- 290 tc`tf :'?S HONS 221935 it- Hi Nrta par miia* MB. ' ----------- 14 L- ii It* 14 kH v~ u T- 14 BMipoaa Tita4 Mltl fU Hill" tto. ifcw'iBim U utility ' L- 14 It* J 1- SI 4- I* 4 L- 14 ii*- 1* 1- 17 n L- at 12- n It* 4 i- ii v u M IS la u L- 11 It* 4 La-- 11 11 1* 4- I* 1T1-1'f4l4---- L- 22 a- n 1T2--1*M L- 1] 4- 1 1v1*- ials L- I4t 12- 42 i- u MMOBi HMD 055------TTW1 44-ITS " 1* u TOT 1 Kii 1 2inM M41--4uT4ii 114U.2 W14--11M'l ItS i1..4l T1-T4- -1j.r4n " ' mrliMIra rrrti-- si- ttxai 49 pUaH BMlyaBa ara iifnMiil m part* par MlUna (IjKltMiau tom myall. il< aiipoaa tiaaaa r--lpaai u urnuad ia partapar allm. riria al lapi pa*uhii--inprulr ibumw Mil Uua Lha tor uubihu p.pTlpuaal -00C. *L* P9a ucliiP 1-Kk Ihm^l 4-P94. plia taa HOa *IT Kk urlik S-POa nl hipai, plua ub 4-P9a. HONS 221936 17 I. INTRODUCTION A. Origin* Methodology of the Study In August 1981. the-firm of consultants in toxicology. Drill, friers, Hays, Loomis and Shaffar, Inc., Arlington, Virginia, (DPHLS) antarad into a contract with tha Edison Clactric Institute (BtX) and tha National Elaetrical Nanufaeturars7 Association (HIMAt wharaby DFHLS agraad to examine tha toxicological and epidemiological litsratura on polychlorinated biphenyls (PCBs) and provide EBI and NEMA with DFHLS1 independent, professional opinion on thm human health affects of pets at varying dosages or mxpoaurt levels. To this end, thb principal scientific stadias and data compilations available on toxicological and spldtmlologleal affects of PCSs, as commercial mixtures and as purif lad single congeners, have been reviewed by a team of scientists designated as the category I teem. Members of the category I team are ors. v.A. Drill, s.L. rriess, K.n. Hays, T.A. Loomis, and C.8. Shaffer from DFHU, Additionally, Or. c. Matanoeki of the Johns Hopkins University has acted as an independent member of the Category I team charged with study of the pertinent epidemiological literature on pels and their human health affects, leeding to sn independent aasessaent and evalu ation of the prebebiiity, causality, and reality of these effects. Category I team review of the animal snd human data rammltad in draft material on the relationships bstwean PCS tpMon and specific health effects in tast animals and In HONS 221937 13 exposed human populations, further, where humeri dste were Lick. ing or incomplete, the Category I teem members developed specific projections or opinions as to the probebility of occurrence of certain health effects in exposed humans, based on the existing animal/human data bases. Health effect areas scrutinized in cluded: general toxicity; effects on skin and other cutaneous tissues; effects on liver; effects on gastric tissues; carcino genesis (experimental and clinical observations); reproductive effects including fetotoxicity and teratogenicity; mutagenesis; Yusho disease and occurrence of cancer; and other health effects including enzyme induction, changes in immunocompetence, and porphyria. Or. Matanoski's treatment of epidemiological observat ions constituted an independent section of the draft report. Draft sections from the Category 1 team were then re viewed for content, conclusions, and opinions by the members of a scientific team of pharmacologists snd toxicologists designated as the Category II team; or. f.G. Standaert (Georgetown univer sity), Or. A. Alvares (uniformed Services university of the Health Sciences), Or. J.A. Thomas (west Virginia university), and Dr. P.E. Enterline (University of Pittsburgh). Or. Enterline was the prime reviewer of the epidemiological contribution made by Or. natanooki. Comments and critique from Category II team members, singly and as a group, were then transmitted to the Category I teas for consideration, leading to revisions and amplifications HONS 221938 19 that are in place in the m*l draft of this study. Comments and suggestions from scientists representing the sponsor* of this.study. EEI and NMA, wars also considsrsd. In ths final vsrsion of ths study, to the estent possible, a Motion on summary and opinion is appandsd to saeh discussion of a potsntial human health sffset attributable to PCB eaposure. Ths primary responsibility for each of these sections is assumed by the Category I team, even though the con tent may have benefltted from useful contributions by Category It personnel. B. Commercial PCB Kistursa Polychlorinated biphenyls (PCBs) are members of a class of non-polar chlorinated hydrocarbons based on the biphenyl nucleus, in which multiple chlorine atoms are substituted on MOMS 221939 20 either or both the primed and unprimed aromatic ring*. Cartain individual members of tha PCS family hava baan praparad in a relatively pura state, with substitution of ring positions by chlorine ranging from dlchloro isoaars (symbol 1 rad as 2-CB) up to tha nonochloro (5-C8) and daeachloro (10-C8) darivativas. Commercially, k-CBs vara marketed in tha united Statas undar tha trada narna of Aroelors. Thay vara also manufaeturad abroad undar tha tradenames "Phtnoclor* and "Pyralene" (franca), "Clophan* (Carmany), and Kanachlor (Japan). Thay ara comprised of mixturaa of chlorinatad biphanyls. Tha last two digits of tha U.5. commarcial nama danota tha pareantaga of chlorina in aach mistura, a , Aroclor 1242 contains 42% by waight of Cl corraspendlng to an avaraga of approximataly thraa chlorlnas par blphanyl molacula. Likewise, Aroclor 1254, Clophan A50, and Kanachlor 500 all contain 54% chlorine corresponding to five chlorina atoms par molecule on the average. Commercially useful mixtures of PC8S hava bean widely distributed ever the world in tha past few decades, usually in applications that have precluded excessive exposures of user populations* Oowever, because of the great chemical stability of these polychlorinated molecules, their persistence in the environment after accidental release can be lengthy leading to possible exposures of people and biota in tha biosphere. Tha results of these exposuree, as wall as those of personnel occu pationally exposed to fCSs in the course of chemical synthesis HONS 221940 21 iri manufacturing operations, art of great importance from the standpoint of potentially harmful health effects that might occur on an acute or chronic basis. c. PCB impurities Commercial PCB mixtures are truly complex, containing variable numbers and amounts of congeners within a given family of compounds, and traces of impurities, all of which are potsn- ttally toxic to humans and animals. Impurities that have been identified in PCBs as manufactured are polychlorinated derivatives of napthalene (PCNs), terphenyls (PCTs), methylbiphenyls. and dibenzofurans (PCOPs). The occurrence of PCDFs is particularly noteworthy in view of the higher toxicity for certain congeners, rslativs to PCBs, It is Important to note that there ere theoretically 135 poaaible PCDr congeners, a faw of which ars believed to be highly tosic. While reviewing PCB toxicological or epldeeiologicel date, s number of fectora related to the actual material involved oust be considered. The PCDF content of commercial PCBa varies< for Arociora tbe reported range la 0-2 ppm of total PCDF congeners. For europesn end Japanese PCM, the reported range for PCDF con tent la 5-20 ppm. The impurity levels can also be effected by espeeure to high temperatures and oxygen. For esample, Aroclor 1214 is converted to 2-2% PCDFs at 550-400 degrees C. These Mao conditions result in the formation of polychlorinated gueterphenyls (FCQa). HOMS 221941 23 II. Yusho Episode In 1968 * matt outbreak of food poisoning occurred in japan, following ingestion of cooking oil contaminated with PCBs and other compounds, that aroused worldwide concern over the potential human health effects from exposure to KBs. However, this poisoning, which became known as Yusho disease, differs sig nificantly in several ways from occupational exposure to PCBs in the united states so that data from the Yusho incident cannot be extrapolated to indicate the effects of PCBs in industrial situations, . Recent studies of the rice oil involved in the Yusho poisoning show that the oil contained relatively large amounts of other chlorinated hydrocarbons such as pCOPs and PCQs (see Burstsune e al., 1*76; and dayabuchl e aK, 1979), The rice oil that caused the diseese was found to contain about 1000 ppm of PCBs, 5 ppm of PCDFs, end 1000 ppm of PCQst ths amounts of the latter two classes of chlorinated hydrocarbons in the rice oil are higher than in the Aroclors used in the United States, tlayabuchi reanslysed the intake data for the Yusho patient, and calculated that the average intakd for the mean latent period was PCI 4*6 mg, PCDP 2.5 mg, and PCQ 439 *9) the smallest intake by e patient was estimated to be 111, 0.4, and 10S mg respectively. KB concentrations in the tissues of Yusho patients were much lower than those of aaymptoutic individuals with body MONS 221942 24 Durdens of PCS* resulting from occupational exposure. Fur ther, PCS fractions of blood, tissues, and breast milk of Yusho patients yielded gas chromatographic patterns showing a larger amount of late-eluting peaks than do PCS fractions of tissues of individuals subject to other types of PCS exposure (Koda and Masuda, 1975). These patterns have never been observed in indi viduals (human or animal) exposed to PCSs in other situations, They are unique to Yusho disease. Also, PCDPs have been found in tissues of Yusho patients. Further evidence for the uniqueness of the syndrome in humans exposed to the Yusho oil is furnished in two recent studies. Hayabuchl it il. (1911) in follow-up studios on these patients five or more years after the poisoning found signifi cant positive correlations for the years 1973-1979 between blood concentrations of PCM and the total amount of rice oil con sumed, but not with the dosage of rice oil consumed per unit of body weight per day* Kashi no to at al^, (1991) found that Yusho is quite different from ordinary PCS toxicity in the sense that, even 12 years aeter the first outbreak, PCQs have been found in the patients' blood and both PCQs and PCOrs have been found In their tissues and organa. St is obvious from this brief review that Yusho cannot be considered a model to reflect the possible effects of the PCB exposure in man. Although much can be learned from the Yusho HONS 221943 25 Incident, it would be misleading to attempt to interpret the observations on Yusho patients as valid signs and symptoms of overexposure to PCBs or to attempt to quantify the possible effects of PCB exposure based on Yusho disease. a. yusho Disease Yusho disease is characterised by the ingestion of a mixture of chlorinated hydrocarbons containing PCBs in large aeounts over a relatively short period of time (latent period from start of ingestion to onset of the disease averaged 71 days)* in contrast, the studies of PCB exposure in workers in the United States have been concerned with the possible effects of chronic exposure to small amounts of PCBs through inhalation or shin contact. The principal signs of Yusho disease are skin conditions such as acneform eruptions, pigmentation of the skin and nails, and hypersecretion of the Meibomian glands. Chloracne and hyper secretion of the Meibomian glands are believed now to be caused predominantly by pCDPs. ttyperplgmentation of the skin is observed rarely, if ever, in human populations with heavy occupational exposure to primarily PCBs. The aetionm of PCDPs appear to differ in several ways from theme of the PCBs. Xuratsune jt il. (1*7) showed, for example, that the liver appears to concentrate PCDPs selectively relative to PCBS. it was also found that relative to PCBs, the concentration of PCDPs was about 250 times higher in the rice oil than in unused Kanechlor-400. Additionally, the PCDPs appear to HONS 221944 26 - be highly toxic, at least in ths rabbit; a single oral dose of 0.5-1 mg/kg of the tri- and tetrachlorodibemofurans caused sevre_and often lethal necrosis in the rabbit (Hofmann, 19SS; Bauer et^ aK, 1961). B. Yuaho Oisease and Liver function In view of the effect of pCBs on the liver of the rat and the highly toxic action of PCDfs on the liver of the rabbit, it was anticipated that the Yusho patient would have severe liver damage, but such has not been found. In their review of Yusho disease, Kuratsune et_ al, (1972) list "the subjective symptoms of Yusho as stated by 169 patients*; 11% report jaundice. Data to confirm the patients' subjective symptoms* are not provided, nor is the presence of this 'symptom* confirmed by other statements of clinical findings. Prof. Urabe (Chief of the Study Group) did not list jaundice as a sign or' symptom of Yusho disease and the diagnostic criteria adopted in 1972 do not make reference to jaundiee or the need for a liver function test in these patients (see Kuratsune et al., 1976). The following two papers on Yusho disease and liver function ere in Japanese end the brief summary given below is taken from the report of Kuratsune at a^. (1976). Okmere and Kstsukl (1969) > They examined 24 patients soon after tbe onset of the disease; MOMS 221945 27 (U There wart no objective sign* of livtr disorders; (11) No patients wart jaundiced and only three had palpable livers (in one patient examinations of a liver biopsy showed marked hypertrophy of the smooth endoplasmic reticulum). Okunara (19T2M Liver function tests were performed in 39 Yusho patients with various subjective symptoms. An increase in lactic dehydroQenase (LDH-S) and in thymol turbidity titer was observed in some of the severe cases, "but no definite evidence for liver disorders was obtained " in a follow-up study of 121 Yusho patients the mean arum bilirubin was 0.4* 09/IOO ml compared with 0.17 m^/loo ml la control patients (Birayams at al., 1974). The difference was statistically significant and the authors surest that there may be accelerated bilirubin disposal from the blood. It may be concluded that the Japanese findin9S do not provide evidence for the developawnt of hepatocellular injury or jaundice in patients with Yusho disease. C. Yusho Plsease and Carcinogenlclty Urabe and co-workers (1979) report that SI of 737 Yusho patients la the Fukuoka district had died and they list the cause f death for 31 of the patients. There were 11 deaths (35.4%) from neoplasms whleh they state is substantially hotter than the Will rate that is "the mortality rate from neoplaama in the MONS 221946 - 28 same prefecture Chi* y*r.* A further analysis is not provided. The following malignant neoplasias wars listed as the causa of death* for tna 11 patiants with canear. No. of Casas Stomach Canear Stomach Canear a Livar Canear 2 1,1 var Canear a Livar Cirrhosis 2* Lung Canear 2* Lung Tumor 1 Braast canear 1 Malignant Lymphoma _2 TOTALi 11 *Autopslad information on aga and othar relevant epidemiological data are not givon, and even a tentative conclusion regarding Yuaho disease and any malignancy must await further analysis. MONS 221947 29 III. Body Burdens, Metabolism, and Kinetics K. introduction The degree of chlorination (two to 10 Atoms of Cl per pCl molacule) And the positions of thS chlorins substituente on tb biphenyl rings both exert a profound influsncs on how mam malian systems hsndls Any given PCS molsculs. Ttts degree And position of chlorinstion plAy a msjor rols in determining ths P*thwAys for metabolism And sliminstion of ths psrsnt molsculss And thsir metabolites by sniasl modsIs And ths human. Thsss Structural factors also bsar on lipid solubility of ths molsculss, and thsrsfors influsncs to sons mutant ths kinetics of PCS tissus distribution and storage. Ths following ssctions daal with ths praamnt stats of knovlege on thasa PCS handling mechanisms eieployad by animal isodals and tha human, raeogniiing that thsra is a strong linkage in tha dynamic procassss beginning with exposurt and ending in excretion. Thasa topics will bo treated in thras groupingai (1) distribution and storaga of PCS natabolitaa in tissuasi (2) metabolism and excretion) and (3) kinetics or the dynamics of PCS turnover in animal medals and ths human. Presently, same generalisations emerge with regard to PCS struc ture versus resetivity relationships end mechanisms for handling PCla in test animal systems that make reasonable extrapolation tm potential events in tha human organism possible, even when direct evidence for actions of a given compound or PCS mixture is human populations is not available. MOHS 2219*8 JO Additional attention has been diraetad to avallabla information on tha actions of PCDFs in animal modal* and tha human, and to a variaty of biochaoical affacta racordad for PCS* and thair metabolites in aammallan aystama. PCDFs may ba contaminanta of aoma commareially uaad pCBs. Although 10-20 ppm of thaaa contaminant* hava baan found in pell manufaoturad in Europa and Japan, only traca amount* on tha ordar of ona or two microi)rams of total PCDP congener* par gram of PC> hava baan raportad in tha Amarican manufacturad mixture Aroclor 1254 (Bowes al., 1575). B. PCI Distribution and Storaoe in Tlssuaa A eonsldarabla body of litaratura axists on studlas of tha tiaa dapandanca of tha distribution, aovamant, and stor age of PCSs and thair matabolltas in th# tisauas of experimon- tal animal modal* and of humans, following axposuras to chlori- natad biphanyl* aa pura compounds or olituras. In taat animal modal* using uniabalad or radiolahalad or PCSa, con trol lad axposuras wars generally by tha oral routa (stomach tuba, or in tha food) or by intravenous injection, followed by study of the changing distribution of tha agent and its metabo- litas in tha circulating blood, in tissues, in bile fluid, and in excreta aa a function of elapsed tiaa after dosing. In the human, axposuras with resulting body burdens of PCBs ware gen erally of the subehronlo type steaming either from massive poi soning events, as in tha rusho events, from chronic occupational axposuras in air and via shin contact, and vis PCI contaminants in air, water, food, and surface contacts in tha ambient. Humana HONS 221949 31 tty also have been exposed to PCBs occupstionaliy m the chemical genufacturing procsss, in ths manufacture of cspseitors, and in ms nanufacturs and rapsir of transformers. Until recently. |everal microscope immersion oils contained 30-40% PCBa as Aroeior 1294. causing potential exposures of students, pathologists, fcicroscopists, ete.j the degree oi exposure is low and the peneBxstion through shin from these products may not be as extensive pa in large scale manufacturing processes. In human studies, PCB distribution and storage in readily obtained tissues was generally followed epideaiologicslly la exposed populations by monitoring levels in blood, sometimes IS mother's milk as a function of time and sometimes by measuring PCBs in adipose and other tissue samples obtained clinically and post mortem. Animal nodal mesults The picture of distribution and storage of PCM and their metabolites in tissues over time has been developed most eomplstely from controlled dose experiments in animal models. Generally, rats and mice were the animals of choice for this work (burse it ii., 1974) Oeyer it il., 1910) Guiney et al., 1971) Hattewe and Andereon, 1979) Morales and Matthews, 197ft hlbro and Pishboin, 1972) burse at al., 1974), but the dog, as soil am the'monkey, has also been used (bsu et al., I979a> Milling at al., 1979) Sipes at al., 1910). The dynamics of tissue distribution vary with different isomers and congeners, 4hd depend in large measure on whether or not the specific PCb HONS 221950 32 molecular structure allows rapid metabolism and excretion of polar metabolites vis bile* feces, and urins (Milling et al., 1979; Safa et al., 1975; Sipss it il., 19#Q Matthews et al., 197#j Guiney et_ al., 197#; Guzslian, 1979) or slower metabo lism with retention of parent cosipounds and metabolites in tissues. M will be discussed in the following section, metabolic transformation in the liver is particularly facile for those PCBs with lower chlorine content (2-CB through i-CB, i.e. 2-4 chlorines per PCB molecule) and with adjacent ring carbon atoms unsubstituted by chlorine atoms (Matthews and Tuey, 19IOt SundStrom et al., 197i Katoet al., 1910; Jensen and Sundstram et al., 1974b| Ghiasuddin et al., 1974) Matthews st si., 197B). for many PCB molecules in which metabolic transformation and excretion is not excessively rapid, the dy namic distribution of parent compounds and metabolites in tis sues following dosing has been studied carefully (Misutanl at al., 1990i Safe it il., 1973i Sipes et al., 1910). The fol lowing generalIsatione appear valid in animal models for struc tures ranging from 1-CS to S-CB and higher. Plrst, the PCBs are readily absorbed from the gut following oral administration and appear rapidly in the blood stream (Jtlbro and flshbeln, 1972) Berlin et al., 1973; Chen and Matthews, 1974). Within minutes to hours, the materials largely clear from the blood and accumulate in the liver and in nuaela tlaaea (Berlin et al., 1973f Burse et al., 1974t Chan and Mat thews, 1974). However, traces of PCBs have been found in the MOMS 221951 33 blood of humans, probably by redistribution from other tissues, years after exposure. The liver is the primary locus for metab olism of the PCBSi especially for reactive species* leading to mixtures of parent molecules and metabolites that then either translocate to other tissues or are excreted by both bile/gut, lumen/feees, and urinary pathways. Ae translocation froo liver and muscle occurs in the rodent model and other species over time periods ranging froo hours to many days* the ultimate depots for major amounts of the non-polar pels and their polar Mtabolites appear to be adipose tissue and skin (Berlin et a^.. 1975) Hansen, 1979) Guiney jt jl., 1J7I| Burae et al.. 1974). DM general distribution pathway in rodents may therefore be characterised as sequential migration from gut and bloodstream entry points to liver and muscle tissues, in a rapid procesa, and thence to depot storage in body fat and skin. When the PCB structure is such as to permit ready metabolism to polar hydroxy, dihydroxy or diol derivatives, the metabolic process may be closely linked in tine with excretion of the metabolites (Jensen and Sundstrom, 1974| Lay et al., 1979) Matthews and Tuey, 1910) Matthews t il., 197Bj Matthews and Anderses, 1979), Animal studies on urinary and fecal ex cretion of Pda (Gusellan, 1979) Matthews and Anderson, 197S) Berlin et al., 197S) Lay et al., 1979) Chen et al., 1976) van Hiller et al., 1973), and ratee of elimination of PCBs from liver Into bile end then into gut/fsees, show that the larger HONS 221952 u proportion of excretion in rodents is by fecal elimination (Kato et al., 19S0; Ley et ai^., i979f Chen et el., 197*? Ven Miller et el^.. 1979? Chen end lietthewe, 1974) of polar metab olites, mostly glucuronidee, eliminated via the bile. The dynamics of distribution and elimination ot PCBe in two monkey species have been etudied (Hsu, et al.. 1975a? Sipes et al., 1910; Hsu et_ ml., 197 5b), and are found to follow a similarly complex pathway, but with wider tissue dietnbution ultimately than that seen In the rat. in our opinion, this difference may relate in part to the ability to analyse more tlesues in larger animals. With fat tissues pres ent in only small proportions in the infsnt Rhesus monkey, the ultimate depots Included bone marrow and the adrenal glands, in addition to skin (Hsu et al., 1975a). Long-term studies involving chronic administration of PCBS at low dosage levels to aniaul models for significant fractions of their lifetimes, with determinations of total bur dens and tissue distributions achieved over time periods of one to two years of ingestion, are lacking. Human Body Burden Results from tpldemloloelcal Studies Experimental data on body burdens and tissue distribu tions of PCts in humans as s result of precisely-measured in takes are not available. However, there are several population sectors for which exposures to PCts can be at least roughly esti mated, and from which tissue samples (blood, subcutaneous and other fetty tissue, etc.) have been taken to obtain indices of HONS 221953 35 - liody burden. These sectors include: (l) humsns occupationally posed to PCBs during years in which they were employed in uflutacturinq processes (Karppanen et, aU, 1972: Hasegawa t al., 1972; Kitamura et al,.. 1973: ouw e_t a_l.. 1976; Pischbein et al., 1979; Wolff et_ a_l., 1911; Maroni et al^., 1981a. b; Smith et al., 3.981a, b; Chase et, a^.. 1981); (2) humans accidentally poisoned by 8C>s ingested in contaminated Coods. as in the YUsho experience In 1988 end in corresponding ingestions of contaminated rice oil in Taiwan (Chen, 1980; CPA summary, 1980); and (3) humans living in areas in which PCBs have somehow entered the food chain or water supply in measurable amounts, leading to longtsrm, low-level body burdens in edults that may also be present lit the human milk supply Cor transmission to infants (Humphrey, 1979, 1980; Kuwsbara et al., 1979a Kuwabara et al., 1979b; Nes and oaviea, 1979; watanabe et al., 1980). An additional source of exposure that is mors difficult to charaeterlss quantitatively atarns from the exposure of families to eonteoineted clothing of PCS workers. Survey work has bean dons in ell of these popula tion asetors worldwide. The results are sketchy, but tentative qualitative generalisations can be drswn. Blood or plasms levels of PCBs ere most readily followed in potentially exposed population data using highly sensitive analytical techniques such as gas chromatography and mass spectrometry, for occupationally exposed people nilOSH, 1177; Smith at el., 1910s) values ranging from 10 ppb up to a exiaum of 3330 pph have been observed, with the additional MONS 221954 36 qualitative finding from Japan*** reference* that the half-life Cor disappearance of PCBe Cron blood following cessation of exposure ranges fra* three to 30 months, PCB blood levels were higher with increased duration of exposure, for rusho victims ;n Japan, with blood staples taken five to seven years following exposur* to PCBS, in the 1973*1975 tia* frame (NtOSK, 1977) values in the range 3-33 ppb were observed. Enhancement factors over control group levels (mean, 3 ppb) as great as 10 were calcu lated, but the observed blood levels were atill much lower than levels found in Japanese capacitor workers. It is of interest to not* the observation of Humphrey (1975) on the very slow clearance of PCBe from the tissues of humans exposed by eating fish. In general populations, blood plasma or serum levels of PCBs in the rang* 5-29 ppb have been found (HIOBH, summary p, 36). . A current and wml1--documented study of body burden* of PCBs in persons employed for many years in capacitor manu facturing (Wolff *t el., 1911) is of special value from the standpoint of its correlations of tissue concentrations with extent of exposures, with highly chlorinated PCBs (H-fCBS), plasma concentrations of 1-54B ppb in exposed personnel corre lated with total aoosmsiated exposure time* for the lees highly chlorlnstsd KBS OPCBS), plasma lsvola in tha rang* 6-2530 ppb corralatad better with specific tasks of individual* working with thooo 2-CB to 4--CB molecule*. Also observed in this study was a correlation of lsvnla in plsasa with level# in adipose MONS 221955 37 tissue Cor each data of PCBa, with H-pCBs and L-PCBa taken aa ssparato cissies, and an ovarall adipoaa/plaana partition coef ficient of 190. Tha lavala of PCBa and matabolitaa in aubcutanaoua fat In huaana hava alao baan aurvayad in genarsl populations (rilOSK, Jp77), in groups such at Yuaho patiants with high axposuraa, and in aoma occupationally axposad indlviduala. For the ganaral population, lavala in fat range froa lata than 1 ppm to graatar than 2 ppa. For Yuaho indlviduala. alavatad fat PCB lavala in tha range 13-75 ppa hava baan obaarvad. corraapondlng to peak anhaneaaant factora aa high aa 30 ovar tha population at larga. it aBould alao bo notad that tha apaetrua of coapounda In huaan tlaauaa la not naeaaaarily idantlcal with tha apaetrua in tha alatura to which a givan population waa axposad (Kuwabara at al., 1971a). Rangaa of adipoaa tlaaua PCI lavala in occupationally aapoaad indlviduala hava baan raportad aa 160-63S ppa (Rarppanon at al.. 1972). 1-13.6 ppai (Chaaa at al.. 19B1). and 2-271 ppa (Wolff at al., 19B1)* Special aurvaya hava baan aada of PCB lavala In tha ilk of lactating huaan aothara (Maa and Daviea, 1979 watanaba at al.. i9B0t MIOdB auaaary) and of lavala in huaan aabryonic and fatal tlaauaa reaulting froa in utaro tranafar froa Yuaho teaalaa (NXOM, 1977). Huaan ailk aaaplaa with valuaa of PCBa la tha range 0.001-0.1 ppa hava baan obaarvad. Clearly, conoantratlona in ailk are higher than thoae in blood priaarlly baaauaa ailk la rich in fat. Organa froa tha aabryonic and HONS 221956 - 3a ^etal tissue displayed PCB levels in the range 0.002-0.750 pp for wheia tissues, with fat derived from these organa yielding levels in the range 0.06-1.14 ppm. C. PCS Metabolism and excretion hniaai eiperiaents involving exposure by feeding, in tubation, or injection of purified PCS isomers in teat eniaal models have yielded iom important generalisations on the mechanisms employed by mammalian species to aetabolixe PCSa to more polar derivatives, and to excrete both parent compounds and metabolites. Beginning with reedy absorption from the qut and transfer to circulating blood-, or with dlreet injection in to the bloodstream, a given PCS molecule ultimately reaches the liver where major aetabolie setlone are initiated. The process es of metabolism and eseretion as a result of theme actions are coddles, and dependent on the molecular structure of the pcs. General features of these process#a include the following polntai (1) Variable amounts of PCS metabolites are excreted via the fecee after delivery to the put lumen via the bile flow pethwey. Unchanged PCSs can occur and be discharged in silk. Relatively lesser amounts arm excreted es polar metabolites In urine then in feoea in moat animal medals (Sato at al.. ISIOi Ur at al., 19T9| Chen at al., I97fi Van Killer at el., 197Si Chen and Matthews, 19743. (2) Ketabolitas are formed in patterns that differ quantitatively or qualitatively among mammalian species. They era generally formed by oxidative processes that are thought HONS 221^57 39 to involve an arena oxide formation that results in monohydroxylation, dihydroxylation, hydtoxylation and methylation, or diol formation accompanied by partial reduction of an aromatic ring <Berlin st 1 ., 1975? Lay t al_.. 1979 ? Lucier et al., 1971? Milling e al., 1979? Sundatrom et al., 1976? Gardner at aU , 1973? Chen et rl., 1976? Matthews et aK, 1978, van Miller et el., 1975? Meu et aU, 1975a? Heu et al., 1975b? Bursa at al_., 1976). evidence alao exiata for dechlorination of a PCB in ehe proceaa of metaboliaa {Rato et al., 1960? Hutsinger et al., 1976b). For aome PCI atructuree, the proceaa of oxidative metab oliaa may be cloaely followed by excretion vie the liver-bilefecea pathway (Chen end Matthewa, 1974). (3) Compounda with lower levela of chlorination (2-CB to 3 or 4~CB) generally undergo metaboliaa more readily, and faater than the more highly chlorinated PCBa. The more highly chlorinated PCBa may peraiat in tieauea for yeara because they are not metabolised. Indeed, 10-CB la virtually inert. (4) In the case of metabolism by oxidative pathways, the moot facile process involving formation of hydroxylated products ooeurs when one or both aromatic rings contains adjacent pairs ot ring carbon a tome (called vicinal ring atoma) that are amoebatltutcd by chlorine atoaM. in the absence ot unsubstituted vicinal positions, direct hydroaylation can occur in the ring, hot with greater difficulty (Gayer aK, i960? Matthews and Tmey, i960). HONS 221958 40 The importune* of vicinal unsubstituted positions on PCS rings in facilitating oxidative metabolism in th# liv#r is explained by a mechanism that involves an arana okid# intermediata (Daly a_t al_., 1972). when aithar or both of tha vicinal positions contain chlorine, reaction rates will b# low#r, but th# mechanise is not entirely ruled out. Additional molecular rearrangements, including the so-called nxii (National Institutes of Health) shift of a ring substituent (Daly at al. 1972), may be involved. Less is known about mechanises of direct enxymatie hydroxylation that do not proceed through an arena oxide inter mediate. -6 (5) Hydroxylated metabolites of the PCBs and their conjugates will generally display different orders of toxicity than those shown by the parent aolecules. (#) A general point of Interest with respect to PCS metabolites lies in the observation that they are usually more polar than their parent compounds. Conjugation of the hydroxy and dibydroxy metabolites as glucuronldes or sulfates can occur, Isadinf to polar conjugates that can readily be excreted. The polar character of metabolites, in contrast with the non-polar HONS 221959 41 Characteristics of ths starting PCBs. can lead to differing dis tribution, storage, and excretion patterns for the two claaaas Of chemical compound!. Polar metabolites ara not readily par titioned into fat or raabaorbad from tha urinary or gastrointsstinal tract!. Therefore thay ara excreted relatively rapidly. D. PCB Kinetics Profilas of tha dynamic growth and dacay of PCB/matabolita coneantrationa in aach ksy tissua can ba drawn from eontrollad toxicological axparimanta. Tha distribution of a givan PCB and its matabolitaa in tha blood, tisauaa, and axcrata of taat animals is followed at a function of time after administration. Tissues ara viawed as body compartments into which materials ara delivered from tha arterial blood supply, in which tome matabollc proceaaea may occur, and from which materials are dslivarad into tha venous drainage systems. A collection of such compartments communicating with tha blood supply and eontrollad by rates of flow through the compartments, with postulated equilibration of any givan chemical in a compartment with its venous blood flow, constitutes an appropriate modeling system for correlating PCI distribution, storage, metabolism, and excretion kinetics in n animal over time. This multi-compartment model ham bean oploysd by Matthews end co-workers end others (Anderson at si., 1*77 j Bungay at sl_., 1979 Tuey and Matthews, 1977t Luts at al., 1*771, to sort out the kinetics of specific PCB isomers in rodent models. The PCB administration can be either direct MOMS 2219*0 - 42 - injection of PCI into the blood circulation, or its absorp tion into blood from the gut after feeding or intubation of the-compound. Excretory pathways are via the liver/bila/gut route or the blood/kidney/urinary elimination system. The success of a model equation system in fitting analytical data Cor a given PCI and predicting the shape of its coneentrstion versus time eurve for each organ or compart ment depends in large measure on several factors, including: (1) the assignment of suitable values for distribution coef ficients of PCS compounds in each compartment; (2) the diffsrential blood flow to various orgsns; and (3) the clearance from organs and the body. This fitting process hss now been carried out for s number of PCSs for which kinetic data are available (Anderson n il. 1977; Chakraborty, 1971). The goodness of fit of the model to each set of PCS kinetic data available attests to the validity of the assumption that mate rials partition at equilibrium between blood and tissue ac cording to purely physical properties Involving solubility parameters of the chemicals. c. Miscellaneous Biochemical Effects of PCSs todies of the actions of PCSs in animal models and humans eaposed to theme chemical agents accidentally or in the occupationsl setting have revealed e variety of biochemical offsets on mammalian organisms. Some, such as alteration of drug metabolism by virtue of PCS induction of mieroeemel mixed function oxidases (MPO), are treeted elsewhere in this documen HOMS 221961 4] gtlpr effects appear to bt unrelated to MFO actions, and have ^n da tact ad in the course of acuta or chrome to* icolog leal ggpertments with laboratory animal modals or epidemiological ^rvays of axpoaad human populations. in an animal study (Bastomsky at aK, 1975) aimad at Probing tha previous avidanca on reduced sarum bilirubin lavals ^ ifus ho patiants, it was found that Aroclor 1234-treated rats amoved incraasad livar microsomal protain, as axpaetad, but with so significant elevation m livar bilirubin UDP-glucuronyl trans ferase activity that could have accounted for reduced sarum levels. Other studies (Grots il.. 1973) Cake e al., 1979) Save shown enhanced levels of this transferase activity. At pret est therefore, the mechanism underlying the hypoblllrublneaia fie Yusho patients remains speculative. Prom epidemiological studies of Yusho patients (Strik, 1979), a rather general biochemical finding has been the obser vation of porphyrins in urine and porphyrin accumulation in liver, ea a result of exposure to chlorinated hydrocarbons Including PCbe. Chronic hepatic porphyria is the designated condition, which increases with exposure and can therefore'be taken as an indicator of the extent of Kl exposure. Porphyria is diseussed elsewhere in this text (section XI). h biochemical factor that nay bear on the toxicity of KBs in certain sensitive human populations, e.j., fetuses, neoheteo' ensyme deficient edults, etc., is related to the ability to excrete the toxic phenolic metabolites rapidly and efficiently. MOMS 221962 - 44 - Sine* a common rout* of excretion involve* preliminary conjuga tion of the phenolic hydroxyl group* with glucuronic acid in th* oody, or sulfate conjugation, it has b*n pointed out (Calabrese, 1977b) that human groups that are biochemically deficient in th* ability to conjugate could be predisposed to accumulate PCBa and metabolites because of this deficiency. A more serious consequence of altered liver capebillty would be a reduced capacity to deal with arena oxide Intermediate* effec tively. An interesting biochemical defect In human lymphocytes has been studied (Lee and Park, 1910) that can be attributed to direct action of PCS* on those whit* blood cells. for both human lymphocytes and monocytes. It has been found that incuba tion of the cells with Aroclor 1234 in culture medium causes a decrease in their ability to take up glucose from the medium. A non-aetabollsable analog of glucose, 2-deoxyglucose, was used to detect the biochemical defect, which was attributed to PCB exposure but which may well be more general for any organic ehealeal that concentrates In the fat of the cell wall, it say entail direct action of KIs on an active transport process in cell membranes. In this regard, liver glucose-4-phosphatas* h*< been found to be inhibited in rats fed various Aroclor mixtures (Lltterest et aj., 1972). The processes by which PCB pr*treatment influences rates of protein and nucleic acid (RllA) synthesis and turnover in rat liver tissues have been investigated systematically MONS 221963 45 URrbonn*, 1979a, o, c, ), using radiolabeled substrates. it jp, clear that livac tissue, i vivo and in. vitro, raaponds to jC* treatment (Phenochlor 0P6) by ineraasmg tha protein synthesis Is livar microsomal fractions in a proeass that is both aga and aa> dependent. Concomitant meraasas in livar fat ara also paan ijn vivo, as wall as changas In lavals of AHA synthasis in yarious livar fractions and incraasaa m livar weights. From the turnover experiments in rats, it is also obsarvad that micro somal membrane protain metabolism is anhancad by ingastion of Kanoehior DPS. Soma further biochemical affaets of PCB exposures on tne human ara saan in workers occupationally axpoaed to thasa sbemicals for extended periods of time (Smith at al., 1979). The findings, as yet unexplained In terms of requisite dosages or underlying mechanisms, ars thati (1) the circulating tri glyceride levels in blood plasma are elevated for exposed workers over controls, but are still within normal levels; and (2) tha circulating levels of high density lipoprotein ara lowered in axpoaed groups of workers. Another biochemical effect seen in PCS-treated rats is worthy of note, sines it relates to an impairment of excretion ot an important drug and its metabolltss (Scbmoldt at al., 1979). Xm the Histar rat pretraated with Aroclor 1248, the drug digitmain and Its metabolites were blocked to a significant degree sxerstion vis the bile. The results suggest that the MOMS 221964 block*?* is due at Isast in part to a PC*-induced impairment of the cleavage of on* of th* sugars from diqitoxin. Finally, th* action of PCS* leading to induction of mixed function oxidases (UFOs) in the liver, with elevation of associated cytochromes P-430 or P-44i, has potential conse quences. These are discussed elsewhere (section XI). F. Some Observations on Polychlorinated Dibenxofuran* The pCDfs are of special interest since they are known to be highly toxic in their own right, and the degree to which, as contaminants, they add to th* potencies of PCI mixtures in production of adverse health effects in animal models and humans has not been fully evaluated. However* toxicological studies in animals with PCOFs containing one to four or more Cl atoms per mol ecule (Morita and Olshl, 1977 Goldstein *t *1., 1974* veerkamp *t al., 1981 > have shown that the PCDPa are qualitatively quite simi lar to their structural PC* analogs with respect to properties of tissue distribution, metabolism, and excretion, in the mouse, the heavily chlorinated isomers localise in liver, spleen, and fat (Norita and Oiehi, 1977), with a half-life far clearance from the body of about two weeks. In the rat, metabolism oc curs by oxidatlvo pathways lsadlng to mono- and dihydroxylated derivatives (Veerkamp $ al., 1991), with a wide variation in ring position by the hydroxy function among the lower chlori nated PCOFs. The octaehloro derivative yields no aetabolle products In tissues or excreta (Veerkamp et al., 1991). In MONS 221965 47 the chick (Goldstein tt al*. 1976), the 2,J,7,8-tetraehlorodibensofuran (TCDF) has been shown eo be relatively poor in enzyme induction. However. Goldstein et al. (1978. 1979a) have shown tbat 21J7,8-TCDF is a potent inducer of cytochrome P-450 and aryl hydrocarbon hydroxylase. Some important data on PCOf metabolise and excretion in the human were obtained (Rappe et si,.. 1979) by analysis of liver tissue from two deceased patients in the Yusho disease group in japan. From the differences in PCDF structural rela tionships in the contaminated rice oil and in the PCDF fractions Isolated from the livers, inferences eould be drawn with respect to PCDF structure (all containing four to sis chlorine atoms per solecule) retained by the liver versus those that had disappeared from liver by procesaea of matabollsa/elimlnation. In striking parallelism with PCI disposition in mammalian tissuea, it was found that none of the PCDFs retained in liver had two vicinal unaubstitutsd (by Cl) positions in either aromatic ring. Apparent ly. all such molecules had been sufficiently susceptible to oxida tive catabolism to be hydroaylated and excreted from liver in the bile. The above observations are not to be taken as allinclusive with respect to the body of information that must be developed in the toxicology of the PCDFs. This elass of com pounds, even at low contaminant levels, is an important contrib utor to the total spectrum of toxic effects from commercial pci lxtures. MONS 221966 48 - C, Summary and Opinion Soma general reflections and opinions can reasonably bs drawn from the previous discussion regarding the use of animal-derived biochemical and Kinetic information to predict certain events and hazards in human pCB intoxications. (1) Pathways of absorption, distribution, metabolism, and excretion have been explored fairly extensively in animal models. Prom the speeies variability seen, coupled with limited observations in the human, educated guesses and predictions can be made on the occurrence of certain tosie effects and processes in the human. (2) Mathematical analyses of kinetic data from animal modeling experiments lead to seme generalisations (Luts et a_l., 197?) that eould apply to PCI turnover kinetics in the humam (1) kinetic rate constants for metabolism of PCSs by the liver decrease as the degree of chlorination increases! (2) rate con stants for biliary clearance of PCI metabolites from the liver are nearly the same for all PCIsi (3) urinary clearance rates for PCIs decrease as the degree of ehlorination of the parent moleeuies increases! and, (4) for each PCI, the value of the distribution coefficient between fat and blood is greater than that in any other major tissue, indicating that the fat compart ment of all tissues may constitute the major PCI depot. <3) Kinetic models derived from animal data may be use ful for prediction of time courses of action in the human once MOMS ZZ1967 49 - edition*! data on metabolism and clearance rates for individual in human tissues are obtained. (4) Some general PCB structure versus activity rela tionships have emerged from animal studies, particularly rodents, lhat can have useful predictive power for the human. (5) There is some relevance of the features of the Oeerption/distribution/metabolism/elearanee processes discussed la. this section to the toxicology of PCBs in animals and humans, for example: (a) The possibility that an arena oxide intermedi ate ean occur in PCB metabolism has special significance in terms of potential reactions with protein, MlA, or ona to cause tissue damage or damage to a cell's nuclear functions. (b) The retention of PCBs in adipose or other jtlseue ean have major significance by creating reservoirs from which materiel ean be leeched over tine for reaction at other tissue sites. (e) There is little evidence in humane for acute cytotoxicity of the kind usually associated with reaetive metabolites. Bather, some of the adverse effects of PCBs, , Cbloracne, could atom from the physical presence of unreeeted materiel in the cells along with oils end/or sebaceous metariels pf the akin. MOWS 221968 51 - IV. General Toaicity A. Snr<1 Considerations Any attempt to undertake a systematic evaluation of the fcOJ.city of PCBs is confounded by a number And variety of factors that complicate the interpretation of the findings and limit their generalization. Therefore, these factors should be recog nised at the outset of consideration of the available body of jeosicological literature. The more important of these factors re listed as follows! (a) The multiplicity of commercial produets of both 7*S. and foreign manufacture; (b) The multiplicity of isomeric forms of PCBs in jBOMereltl products; (c) Qualitative and quantitative differences in metab olism of different isomers within the same species; (d) Qualitative end quantitative differences in metab olism of the earn* isomer between species; (e) Differences In rates of metabolism of different Homers within the same speeiss; <f) Diffaranees in rates of metabolism of the same learner between spmeies; (g) Differences in the biological half-livea of different Isomers within the same species; (h) Diffsrsneee in the biologiesl half-life of the Mas isomer between species; HOMS 221969 52 ti) The presence in commercial products of Lmpuritiss of much greater toxicity than that of PCBSj (3) Tho variability batwaan commercial products of tha same typa U ,e,, saaa degree of chlorination) in tha con centration of impuritias of mueh greater toxicity than that of PCBsi ik) Tha variability between commercial products of the different types U.e., different degrees of chlorination) in the concentrations of impurities of much grester toxicity chan that of pCBsj and (1) Differences between species in susceptibility to the toxic action of <i) individual isomers and their metab olites, and (ii) the impurities that may be present in com mercial products. The preceding factors may underlie the conclusion reached by the Panel of haiardous Trace Substances <19721 that "[tlhere is no consistent relationship between toxicity and degree of chlorination which is valid for different species and dlffsrent routes of exposure." To this might be added the ob servation that there is often no consistent relationship between the results of investigations on products of the same degree of chlorination from dlffsrent manufacturers* These observations constitute caveats that should be borne in mind as individual toxicological experiments and results are evaluated, l. impurities in Commercial Products The work of Von and his associates (Von and Keenan, lB70r Von et el., 1970 Von and Beams, 1971) lad to a recognition MOMS 221970 - 53 fthe significant role pUyd by traces of impurities in compreial PCS* in influencing the epperent toxicity of the Letter. 14 studies involving three commercial PCBe of the seme degree of Ifelonnation, these investigators found marked differences in gtsieity that were traced to the presence, in two of the products, pr small amounts of chlorinated dibensofurans (PCDrel and chloHnated naphthalenes. The PCDFs are related closely, both struc(firally and toxicologically, to the chlorinated dibensodioxins. |be 2,3,7,9-tetrachlorodibenso-p-dioxin isomer is an extremely potent toxicant in mammals, especially for the fetus. The ehlofclnated naphthalenes are less toxic than the chlorinated dioxins, Set nevertheless cause ehloracne and other symptoms in man Elailar to those produced by poors. The extant of the contribution made by contaminants to the toxicity of eomswrcial PCBs is uncertain, but the consensus Is that it is substantial. There seems little doubt that the akin lesions, including ehloraene, are caused by PCDFs. The Panel on Hasardous Trace Substances (1972) states that the PCDFs *are probably the chief if not exclusive cause of ehloracne in Ban.* Pishbeln (1974), in his review of the toxicity of chlo rinated biphenyls, observes that *[lliver damage and skin lesions are believed to be caused prlmerily by chlorinated dlbenxofuran contaminants and to a minor extent by KB itself.* Furthermore, lose the chlorinated dlbentodlexlns exhibit pronounced embryofcmsicity, it is not unreasonable to expeet that the PCDFs share this property and, hence, are largely responsible for the fetal MOMS 2271 54 - deaths and resorptions that have baan observed experimentally with commercial pCBa. . An appreciation of tha rola played by eontaminanta m tha toxicity of comma reial PCBa ia important for two rea- sona. Pirst, it may explain dlacrapaneiaa between the results of atudiaa of apparently aimilar commercial produeta. Second, it pointa up the difficulty of attempting to uae pCB tiaaue levela to correlate the reaulta of laboratory atudiaa with ob- aervationa of occupationally or environmentally exposed popu lations. for example, some animal populations in the environ, ment appear to be unaffected by PCI tissue levels that are equal to or greater than those associated with adverse effects on comparable species in the laboratory. C. General Toxicology 1. Acute Toilclty The Aroclors of the PCI class have a low order of acute toaielty. The acute oral U)90s for rate ranqe from 1-10 g/hg, The LOSOs by single application to the shin of rabbits ara approximately 1-3 g/fcg. Oral and dermal LD30 data have been summarised by rishboln (1974), Kimbrough at al. (197B), and the Panel on ttasardous Trace Substances (1973). 3* Subchronic and Chronic Toxicity (a) General Subchronic and chronic toxicity are grouped together for purposes of this dlaeusslon sines the effects of chronic HONS 221972 ss - vpOSur to PCBs are essentially extensions of those observed ^rtTM repeated exposures of shorter duration. There ara numerous published atudiaa m vhich commerlelal PC3a (Aroclors) have baan administered by various routaa [for varying parioda of time co most coanon mammalian apaeiaa of {Laboratory animal a. Out of this maae of observations, ona may BSsntify two principal claaaaa of biological of facts of these abstances. Thaaa claaaaa ara (a) altarations in tha Uvar, and akin loaiona. (bI Alterations in tha Livar Enlargement of tha livar, both in abaoluta tarma and a a parcantago of body weight, haa boon obaarvad consistently Bh. aost apaeiaa consequent to rapaatad aaposura to PCSs, although is moro pronouncad in rodents than in others* This phenomenon its been reported for mica (Kimbrough and Cinder, 1974), rata IfBruckner at al*, 1973, 1974a, b), guinea pigs (Voe and Van ^Dciol-erootanhuia, 1973), rabbits (Hollar and Zinkl, 1973), dogs (Galandra, 1979), and monkeys (Alien tt tl., 1973). Early enlargement of the liver is primarily the result of an increase in the site of the hepetoeyte associated with an increase in tha tmount of the smooth endoplasmic reticulum (SER). These develop* Mnta are associated also with increased ensymetie activity of the liver (Bruckner at al,, 1973). A detailed discussion oe the affects of pCBs on liver 1* toot animal systems is given in saetion VI. HONS 221973 I (c) Skin Laaiona Cutaneous affects from repeated exposure to commer cial PCSs can be elicited by feeding to monkeys or skin appli cation to rabbits, although the results are somewhat more dramatic in the former. The results of those animal studios are discussed in section V. (d) Miscellaneous effects Hyperplasia and dysplasia of the gastric mucosa have been observed in monkeys fed a diet containing J00 ppm of Aroclor 1241 for throe months (Allen and Norback, 1973). Gas trointestinal lesions do not appear to oeeur in rodents, except at very large single deees by mouth {Kimbrough, 1979), A dietary concentration of 2.5 ppm of Aroclor 1249 produced alterations in the menstrual eyeles of adult, female rhesus monkeys (Allen at al., 1979). Menses were prolonged, and there was an increase in menstrual bleeding, nepotic porphyria has been demonstrated in mice after feeding Aroclor 1254 (Kimbrough and binder, 1974), in rats after feeding Aroclors 1254 or 1240 (Kimbrough, et al., 1972), and in rabbits after repeated skin application of Aroclor 1240 (voe and teems, 1971). (Jrinary excretion of eoproporphyrm was increased in rats fed Aroclor 1242 (truckner et al., 1974), and both urinary and fecal excretion of porphyrins was increased in rabbits receiving repeated skin applications of Aroclor 1240 (voe and Booms, 1971). othsr offsets rsported for one speeies or another include structural changes in the kidney (Vos and Seems, 1971 Bruckner at al., 1974a, b), hematologic alteration! NOUS 221974 - 57 ^ruekner d aU. 19744. b). and thymic atrophy toqathar with i Jdoction in tha numbar of qarmmal eentar* m tha spleen and g^ph nodes (Vos and Beams, 1971), 0. Summary and Opinion Voluminous lite:.ture establishes that commercial CCla are capable of producinq a variety of bioloqieal affects xnen administered in larqe quantities to eaperimental animals. majority of these effects can be qrouped into two cateqorias. gamely, those involvinq the skin and those involvinq the liver. K number of miscellaneous effects that have been observed in one species or another can be considered secondary to the action of the substances on the liver. In qeneral, these effects are only Slidtad by relatively hlqh dosaqes of the PCBs, reflectinq the 1&W order of acute toxicity of the u.S. commercial mixtures. There is a eonsldsrable ranqe of spmeles susceptibility to the bioloqieal activity of PCBs as measured by the aixa of the doeaqe, the duration of the exposure, and the severity of the effect, nink appear to be the most susceptible, monkeys somewhat leas so, and rodents the most resistant. There la no basis for a judqment as to irtiicti species most accurately serves as a nodal for man* A comparison of the observations on humans in the Yuaho Incident with those on monkeys fed relatively smell amounts of PCBs hsm lsd some investiqators to conclude that tha latter species is an appropriate surroqete for men. Althouqh there are Some similarities between Yusho disease and tha findinqs in monkeys, they are not sufficient to justify such a conclusion. MONS 221975 There ia evidence throughout the literature that some n{ the biological effects observed experimentally with commercial PCS mixtures are caused not by PCM themselves but by other chlorinated aromatic compounds present as impurities, such as the pCDPa. The significance of this finding is that PCB levels resulting from occupational or environmental expo sures cannot be interpreted in the same way as thoee observed in experimental animals. A broader implication of this cir cumstance is that the results of laboratory studies are not necessarily predictive of what may be expected from inciden tal exposures since the nature of the exposure may have dif fered in the two instences. As is always the case in experimental toxicology, the validity of test results as predictors of hasard to man must await confirmation or denial by observations of exposed human populations. rertunately, the reports of actual injury to man from PCS exposure are few, although extensive epidemio logical surveys have been conducted and others are in progress. An evaluation of the epidemiology of exposure to PCBs is the subject of section XXX of this report. Still other sections of eht report deal with specific potential health effects in greeter detail. HONS 221976 - S9 V. Skin and Other Cutaneous rmu Epithelial and follicular hyperplasia and hyper keratosis have boon reported Co occur following tha application of PCB* on tha akin of rabbits (Vos and Baams, 1971), skin losions hava also baan obsarvad in rats and quinea piqs from tha Ipplication of PCBa. Rap*atad application of Aroclor 1260 to tha skin of rabbits causad thickeninq of tha akin as a result of hyperplasia and hyprkaratosis of tha epithelium (vos and Baams, 1971). Cutaneous affects bav# baan elicited in mala rhesus oonksys fad a diet contalninq 300 ppm Aroclor 1241. within on* month the animals lost con*idarable hair from tha head, neck, and back {Allan at l., 1973, 197S), Similar effects hava baan obsarvad In female rhesus monkeys fad a diet contalninq 25 ppm Aroelor 1241 for two months (Allan M al^, 1974). Within six masks tha animals boqan to loss hair and developed obvious siqns of adama of tha lips and ayalids. Small pustulas lnvolvinq hair folllclas appaarad about tha mouth, chaaks, and naek. Abraham and Allan (1973) showed that thm infant monkey was able to tolarata doaas of PCM that produea extra*# morbidity in adult aonkays. nay suqqaatad that thara may b* variations in absorp tion, distribution, metabolism, atoraq*, and axcration in adult mi Infant monkeys that may account for these differ#ness. Follicular hyperkeratosis is an important feature of tbs occupational dlaaasa known as sens, which is charaetarixad by the appearance of papulae, comedones, and cysts, industrial HONS 221977 60 - dermatoeia of the acneform type has been observed among workers xooaed to chlorinated hydrocarbons {Jones and Aldan. 193#; flayers and Silverberg, 1931; Maroni jt il,, 1911). Savon casts of chloraene of the face and head have been reported emong i* chemical operators exposed fro* 5-19 months intermittently to low concentrations of chlorinated biphenyls (neiga and Albom, 1954). Pueeinelll (1954) and Hofmen at al. (19*2) report chloraene in several capacitor workers, whereas Smith at al. (1911) noted that none of the capacitor workers examined in this recent survey were found to have acneform lesions sug gestive of ehloraene. The aenefona eruptions that occur in the skin of both monkeys end rabbits may be caused by a squamous setaplastie change in the epithelium lining the sebaceous glands, which result in a ehange in the character of the accretion from nor mal oily to keratlnaceous. This condition frequently results in plugging and rupture of the glands with consequent inflam matory reactions (acne). The question of whether a similar condition can occur in nan from exposure to PCM will be dealt with in another section of this report* Xt baa been suggeeted that the eutaneous eruptions that occur in both animals and nan from exposure to commercial prepsTstiono of PCM may be due to certain impurities. Chemical analysis of tbs PCM that contaminated tbs rice oil that caused the Yusho disease in japan showed high levels of polychlorinated dlbensofurano (Ituratsune. 197#). HONS 221978 - 61 - vl. Effect of peas on Liver A. hpiflMHtll Data 1. Livtf Wight The admimstration of ?CBs nay indues an increase in (ivtr weight (Table 2). The effect is more prominent at the plgher dose levels; the lower doses of PCBs do not increase fiver weight. The detailed date of Kimbrough et_ _al_. (1972) (fere not included in the table. They found that Aroclor 12(0. administered with the diet in doses of 500 and 1000 ppm for eight months, significantly increased liver weight in male and female KatSt doses of 20 and 100 ppai were effective only in male rats. Aroclor 1234 increases liver weight in both male and female rats St doses of 20. 100, and 500 ppai. Although the data in Table 2 illustrate ths effeet obtained in subehronie and chronic studies, it should be noted that liver weight may also be increased in acute toxicity studies. PCS congeners (pants-, hexa-, and heptaehlorobiphenyla) given in a high single dose of 50 mg/kg, can increase liver weight in the rats in most but not all tests, liver triglycerides, cholesterol, and phospholipids were increased (Yoshihara at al., 1979). In the monkey a single oral dose of 1.3 g or 3.0 g/kg of Aroelor 1254 produced slight enlargeaent of the liver in 4 days (Allen, Sorback, and >su, 1974). The increase in liver weight is correlated with hepatic cell hypertrophy and an increase in smooth endoplasmic reticulum MONS 221979 -41 Taftia 1 tffaet at KJa an 1.1vat walaM a4 Marvhalaav valfft* Ot--f MUiniN mam IMlM U Mia a Na)ar llatalorisai lU4U<a ilaMraua* t (.lataa, iria, kfMUl 11*4 ftMilaa La lata Hawanu MIMlI aanaatt. at al., K. (t ci 1*4 a* 1M af a 4aya V i IN 4ar* * calla avallaa. trail*# puilta I ! i Mallei a* al. 14 miia + malar 12*4, U44 la ppa i pm malar lias 144, i*. i pm li amta 14 ~|--"1 14 MM. 4 4 4 UltMMit a al.. un malar 1141, 1144 1244, 1244 M4 M 1 4.1 allaa a itfl, 4.11 la. 4iat malar 1141, 1244, 1242 inMMa at al., um> 144 M/1 Juaalar 1141 2T r at tl., 14T4 >a pm s pm 4mta imt. 1,4,4 * rat 4aa*lata, vaaaatatiaa* 4 as^atSa ."laaraaaa 11*14 ita lutaa xv ataia HONS 2219*0 - -4 J* TMla 2 CCOKTtBUIO) af *Oa an llvar MtiM m aoraftalaav mm at ai.. Araalar 1241. 1014 Ma at al., imlai UU kMMfclara10M*rl lalln 4 IUUi liTl UMltt 1214 imtac 1242 U4414I 1221 Ulaa at al.. 1*11 laaalaa U4t Mitt MM Mtfkt Clrnmi laeraaaa ctaaat Itutlaa la |<U ICaattaMt) natar Nutoloy- ini finainy* im pyn u *a 1* aaatha ftaklaa U biuu 120 lUMl 4 I a mat o taiaaya* itayatoaytaa. vaeualataa eytafiaa. duiMtitiiao a ail4 etianyaa fOittlt 4ayaa caeiaa. nacroaia 1M * Ii41m la tfea Makar 4111444 >4H4- TtNi aaaaaaia Salary** Hayataortaa. aana aa tiatalayleal 1M ran MM IP 4*rt ** * tUait*4 tayau- oytaa. aa aaanaia ** ` MOMS 2219SI Livar Laaioaa la Albino Rata Traatad with Aroclora for 1 faara (Data fraa Lavinakaa, 1991) Diat laval, MM Control Mo. anioala amanlnad 1) vacuolar eOanf# rocal nocroaia roeal lynpdoid Infiltration Focal hypertrophy bapatocytaa Modular hyporplaaia n ' 1 hyporplaaia Cholanplobaparnna Mapatoeallular oaroinoMa 1 1 1 1 S * Aroc lor 1242 1 ID ID# 12 29 1C 7 D .9 11 D tD D 21 D 11 D 11 1 0 1 9 1 D Arcelor 1294 1 ID 1DD 10 2C 79 11 2D 14 01 C1 0D 0D 00 24 11 1 1 14 14 14 4 2 0 Tba rfaulta of thla atody vara praaaatod in a MMMarlrod for* by calandra ililil and ttara latar raanalyaad and tabulator ov Levinakaa <19411 Aroeior 12 AO > 10 >00 21 IS 17 4J 01 1 11 D1 t7 01 00 00 IS 9 t 0 9 t 12 7 4 0 HONS 221982 s; rat, rabbit, and monhay (Voa at^al., 1972; Allan and ^ealiamson, 1973; Bruclcnac a *1.. 1974a; Allan, Norback, and Hsu, ft 4, Allan, Caritana, and Barsotti, 1974). Ecobichon and Comeau U^74a, b) found that tha affact of PCBs adminiatarad intrapennaally on livar weight and on hapatic ancymaa associated with batic andoplaamic radculum waa related to tha poaition of chlorina aubatitutlon on tha biphanyl nuelaua. however, all K'the congeners and iaoaara admin iatarad at a doaa of SO mg/leg ^trsperi tone ally for thraa daya producad an increase m amooth gpdoplasmic, lipid droplata and microbodiaa, although tha guanti^tiva raaponaa variad Utansell and Eeobichon, 1974). 2. Canaral fllatology Tha adainiatration of PCBa to aspariaantal animals will ftoduca hiatopathological changaa in tha livar. Tha main affacta Mtainad ara tha production of anlargad hapatocytaa, fat droplata. Sad alight dagraa of nacrosis* tha oecurranca of thaaa changaa dapand particularly on tha doaa of tha PCI and to some mutant on tha particular Aroclor (Tables 2 and 2A). Necrosis aaama to ba *ra aavara in tha rabbit than in tha rat. In ganaral, tha pBrphological changaa obaarvad in tha livar of PCB-traatad animals ara similar to thosa found aftar traaemant with othar chlorinatad kydroearbone. in a data Had study, Kimbrough at H. (1972) found that |>Molor 12*0 (20, 100, S00, and 1000 ppai) and Aroclor 1234 ( 20, 100. f*ad 900 ppa), glvan in tha dint of rata for aight months, produced HONS 221983 66 - enlarged liver cell* and cytoplasmic inclusions. At the higher dotes, there wee evidence of lipid accumulation, which wee eesocieted with a foamy cytoplasm, and pigment accumulation in the Kupffer cells. The pigment gave a posi tive Prussian-blue reaction, indicating the presence of hemosiderin. Studies of eats four to sis months after eaposure to different dosee of Aroclors 1011 and 1242 indicated that the morphological changes are reversible and disappear gradually after dosing is stoppedt the hepatocytet were still larger than controls, but the frequency of vacuolated eytoplasm or inclueions within the cytoplaem had decreased (urse at al., 1974). Aroclor 1294 was evaluated by the National Cancer Institute (1979). Pischer rats receiving 29 ppm in the diet for eight weeks had enlarged livers, but without evidence of histological abnormality. The administrations of dosee of 29, 50, and 100 ppm for 104-109 weeks did not Increase the frequency of liver lesions such as congestion, inflammation, necrosis, or angiectasia. 3. Adanoflbroala hdenofibroois (synonymst bile duet proliferation, bile duet adenomatosis, cbolangloflbrosls, fibroadenoma) has been observed In some rats receiving pCBs. Adenofibroeia is generally regarded as a benign lesion. In their review of experimental tumors, Stewart and Snell (1997) stated that there Is no convincing evidence that adenoflbroala is a precaneeroue lesion. MOMS 221984 67 It should be noted, however, that Reuber (1969), studying 2acatamidofluorene and 2-diaeetamidofluorene, suggested that adanofibrosis Is a pracancarous lasion for tha development of cholang loearcinoma, (1) Studias In mica. Kimbrough and Linder (19741 obsarvad foci of adanofIbrosis in tha liver of soma nea with 300 pp of Aroclor 1234 in tha diat for 11 months Ito at ai. (1974) comment that ehay did not obsarva cholanqiofibrosis in slca receiving Kanaehlor. (ii) Studias in rats. Kimbrough st al. (1972) obsarvad adanofibrosis in rats trastsd with Aroclor 1260 and 1234* tha affact was obsarvad st tha higher doaa lavals and particularly in animals receiving Aroclor 1234. Whan tha feeding of 500 ppm of Aroclor 1234 was discontinued and tha animals studied up to 10 additional months, tha fat and liver content of PCS remained high and tha adanofibrosis persisted (Kimbrough at al., 1971). In a later paper involving treatment with Aroclor 1260 at 100 ppm for 21 months, mention is only made that a few rats showed areas of adanofibrosis, indicating a low degree of response, but data are not tabulated (Kimbrough at al., 1975). In further studies by tha same group adanofibrosis was not ob served in rats fed Aroclor 1016 or 1242 (100 ppm) for up to 10 oaths (lures at al., 1974). In a study with three Aroclora, administration of 100 ppm in tha diet for 24 months produced a low incidence of HOMS 221985 - SI - cholangiohepatoma (Table 2A), but concentrations of 1 ppm or 10 ppm wore without affect (Calandra, 1974; Levinskaa, 1911). Treatment did not significantly affect ductal hyperplasia. The study of the National Cancer institute (1971) did not observe adenoflbroals in rats receiving Aroclor 1254 at dosea of 23, 30, and 100 ppm for 104*103 weeks. in studies with various Ranechlora, ito et aK (1974) administered Ranechlor 500. 400. and 300 in the diet at concentrations of 1000, 300, and 100 ppm. At the concentra tion of 1000 ppm of the Ranechlora. the incidence of cholangiofibrosis ranged from 13 to 304 in the ratei cholangiofibroais did not occur at levels of 300 or 100 ppm. Riaura et al. (1971) alao reported cholengiofibroale in rate treated with Ranechlor 400. 4. Hyperplastic Pool and nodular Hyperplasia in the Liver Hyperplastic foci or hyperplastic areas represent minimal changes in the hepetocytee. Such foci or areas of hy perplastic changes are uncommon in untrsated young rata, but increase with age. The hyperplastic areas or foci may cooslet with nodular hyperplasia and/or hepatocellular carcinoma. The signlfiosnee of hyperplastic foci is that they may be part of a spectrum capable of progressing to a nodule (Squire and Cavitt, 1975). The hyperplastic nodule (nodular hyperplasia, neoplaetie nodule, hepatoma) is generally as large or larger than the srsa of several lobules, and the lesion is sometimes elevated HONS 22198b - 69 - the surface of the liver, The lesion is frequently rt^grred to aa a neoplastic nodula and soma conaidar it to ba a manifestation of a carcinogenic process, the aarliar stages Pjfwhieh nay ba represented by tha hyparplaatie foei discussed Jftffove, Tha uaa of thaa* tarns in tha Utaratura is confusing, s aona who uaa tha word "hyparplaatie nodula* raised tha salon to ba part of tha naoplaatie process whereas others Consider it to ba unrelated to neoplasia. Sons investigators M tha tarns adenoma or hepatoaa to designate tha lesion, replying that it is a benign neoplaan. Despite the differing terminology, it nay be considered that the hyperplastic foci and nodular hyperplasia (neoplastie Modules) occurring in the liver are benign lesions rather than mrclMsaas. However, such nodules aay be part of a sequence of faeoplastle changes that eventually progress on to hepatocellular esreinoeas. Although the data on hyperplastic foci and nodular typarplaaia are discussed in this section and hepatocarcinogenef 1 are discussed in section vtll, the experimental data on the ine,, dance of benign and aallgnant lesions are given in the sane table so that the overall biological effect of the treataent can be observed as a unit. U Studies in nice. Ito at al. (1973) observed sdolar hyperplasia in nice only at the highest dose level of tinsehlor 500. (negasahi at al., 1972, reported the sane data.) areas Kanechlor 500 produced nodular hyperplasia at 500 ppa, leaser doses were not active and Kanechlor 400 or Kanechlor 300 MONS 221987 - 70 - was inactive at ail doses studied (Table 3)* There was toee v-rdence that the administration of Kanechlor 500 increased tne nodular hyperplastic response induced by or p isomers of benzene hezachloride. Kimbrough and Linder (1974) observed adenofibrosis and hepatomas in nine of 24 mice fed Aroclor 1254 (300 ppm in the diet) for 11 months* in animals fed Aroclor for only sis months followed by a five month recovery there was no adenofibrosis and the incidence of hepatoma was only 1/24 mice, (11) Studies in rats. Repllnger e eK (1971) did not observe hepatic lesions in rats receiving different Aroclors for 11 months* however, re-*valuation of the slides indicated a significant increase of nodular hyperplasia in the treated animals (see National Cancer institute, 197i). Ito et al. (1974) observed nodular hyperplasia in rats receiving 100, SOO, or 1000 ppm of Kanechlor 500i a lesser effect was observed with Kanschlor 400 and there was no signi ficant effect of Kanechlor 300. Kimbrough et al. (1975) reported a significant in crease in the incidence of hyperplastic foci or areas and neo plastic nodules in female rats given loo ppm of Aroclor 1210, mixed with the diet for 21 months (table 4). In another study, the dietary administration of 100 ppm of Aroelor 1242, 1254, and 1200 for 24 months increased the incidence of nodular hy perplasia (Table 2A)i a lesser effect was obtained with 10 ppm. HONS 221980 71 TAaLE 3 i Incidanea of Livar Lasiona in Mai* Mica . Traatad with PCBi for 24 Waaks (Oata of Ito at al, 1973) ppai in diat Incidanea Nodular Hyparplaaia Hapatoca Uular Carcinoma tknachlor SOO ganaetilor 400 fcaaachlor 300 Controls 500 7/12 250 0 100 0 SOO 0/12 250 0 100 0 500 0/12 290 0 100 0 - 0/ 5/12 0 0 0/12 0 0 0/12 0 0 0/4 HONS 221989 '72 TABLE 4 Incidence of Liver Lesions m Female Rees Treated with Aroclor 1250 (Data from Kimbrough at al., 1975) Lesion hyperplastic foci or areas .isoplastic Nodules Hepatocellular Carcinoma Incidence Controls Experimental 29/173 0/173 1/173 192/194 144/194 26/194 HONS 221990 -73- TABLE S incidanca of Livar Las ions in Mala and Fatnaia Rats Traatad with Arocior 1242, 12S4 and 1260 100 ppm in Oiat for 24 months (Data from Calandra, 1975) nodular hyparplaaia Bapatonaa apatocallular carcinoma 1242* 6/20 2/20 0/20 Arocior 1234** 13/27 4/27 0/27 12(0 7/27 S/27 0/27 *10 aalaa and 10 faaalas **13 aalaa and 14 faaulaa MOMS 221991 -74 TABLE * Incidence of Liver Lesions in Male and Female Rata Treated with Aroelor 1254 (Data from National Cancer Institute, 1978) Number of animals neeropsied Hyperplastic foci or areas Adenoma, NOS* Hepatocellular carcinoma Low Dose Males_______________ remalaa Mid Do so High Dose Low Mid Dose Dose Hicjh Dose 24 24 24 24 22 24 58 00 01 12 1 2 8 9 17 01 2 00 : * Hyperplastic foci, hepatocellular adenomas or carcinomas were not diagnosed in tha controls, + Not otharwlso specified ** Ae defined in report HONS 221992 - 75 - gl 1 ppe did not produce a positive response (Calandra, 1976; ^glnskas, 1911). All throe Aroclors produced an increased pugDer of hepatomas at the- high dose (Table 5). There was no Aidence of meeastaeis or invaeivenese, and the lesions were |g;arded by the pathologists as benign tueors. The results of a bioassay of Aroclor 1254 for carcinogpilextv. using dosoe of 23, 50, and 100 ppa in the diet, are Bluaiarised Table 6 (National cancer Institute, 1979). Their See of terns is confusing, for although they use the words `nodular (yperplasia* in their table, they state in the tost that `the roes of nodular hyperplasia appaered to be aicroscopicaliy Bellar to what is currently tented 'foeal areas of cellular Iteration.1* Thus, we have used the tons `hyperplastic foci or reas* in Table 4 to describe their results, it is evident frost (be data in Table 4 that the hyperplastic foci were present in a Boee-relatod frequency. Although the Incidence of the hyper* (lactic foci did not differ significantly froa the controls, this Incidence appeared to be related to treataent. The biological (ignifIcance of the increase in *focal areas of cellular aItsra don* is not clear as relatively few adeneaas were found. both the above studies (Klabrough et al., 1973r National Cancer institute, 197) deaonstrate an increase in proliferative Steioao of the livert the effect is greater with Aroclor 1240 bsa with Aroclor 1234. (ill) Studies in docs. Hepatic nodular hyperplasia iid not occur in the dogs receiving dietary levels of 1, 10, or 100 MONS 221993 76 ppm of Aroelor 1242, 1254, or 1260, respectively, for two years (Calandra, 1976). Each treatment qroup consisted of eight doqs (four fainala and four mala), 5. Summary and Comment Tha administration of hiqh doaaa of pels to animals can produca hapatlc enlargement and an lneraaaa in liver weights, which is aaaociaead with an incraaaa in smooth endoplaamic ratlculum, Othar affacta include a alight degree of nacroaia and tha praaanca of fat droplata and a vacuolated cytoplasm. These changes, which are similar to those found after treatment with other chlorinated hydrocarbons, are readily induced by high doses of PCIi, but are absent when lower doses of PCts are given. The response appears to be greater with increased chlorination of the biphenyl nucleus but, depending on dose, even the high chlorinated derivatives may not produce a positive response. Treatment with PCls usually increases the occurrence of hyperplastic foci. The nodular hyperplasia, neoplastic nodules or hepatomas have been reported to be-increased in some studies, but other evaluations have not confirmed these effects. Tha effsets of PCls on the occurrence of nodular hyperplasia, neoplastic nodules, hepatomas, or edenofibrosis is highly variable same studios have reported a positive effect whereas others failed to show an effect of treatment. Again the change in histological response or in frequency of benign hepatic tumors is related to both the dose of PC* administered and the degree of chlorination of the pcs. HONS 221994 - 77 - Oats on hepatocellular carcinoma in PCS-treated animals ftre discussed in section vin. B. clinical Data 1. Liver function in PCl-axpoaed Workers Based on results in animals, it was expected that if jCls produced a significant degree of injury in man, it would .be- to the liver. Such has not been the case, as the clinical studies summarized below have provided little evidence for the occurrence of hepatic dysfunctions in PCB-exposed workers even though the Blood .tvel of PC* may be relatively high. (i) Ouw et el. (1970 studied liver functions in 34 workers exposed to Aroclor 1242 for one month up to 21 yearst 31 wore exposed for more then one year end 1C for five or more years. Scattered Individual abnormal test results were obtained! serum bilirubin was normal and in all 34 subjects, alkaline phoephatase was elevated in one of 34 subjects and serum transaminase (SCPT) V was Increased in five tests.* There was no relationship of the results to the blood level of PCI and the mean of each hepatic function test for the whols group was within normal limits, bsp */ The abbreviations used in this section are as follows* SOOT serum glutamic oxaloacetic transaminase SCPT serum glutamic pyruvic transaminase SOOT serum gamma glutamyltranapeptidase LDQ serum laetie dehydrogenase AST sspertste aminotransferase ALT serum alanine aminotransferase SOCT serum ornlthin-carbamoyltranaferase UP - brcmeulfonpbthaleln HONS 221995 79 - teats war# also performed on seven workers with relatively nigh blood PCDi four of the seven testa were sightly above the normal limit of 51 but. as the authors state, sinee other conditions such as fever may increase BSP retention, these resulte by them selves could not be taken as proof of hepatic damaga. The asp test results did not show a significant correlation with blood PCS levels or the length of exposure (five to 23 years) to pcb. (ii) flachbeln at al. (1979) studied liver func tion tests in 321 workers exposed to PCIs in an electrical manu facturing plant for less than five years to more than 25 years. The percent of tests that gave an abnormal test result was SCOT 2.21# SGPT 7.21# LOB 2.59, alkaline phosphatase 1.21# and senm bilirubin $.3, and indicated a "very low prevalence of abnormal liver findings." There wss no comment or analysis to state that a certain number of the subjects showed a pattern of abnormal liver function tests indicative of hepatic dysfunction. These data can be taken to represent a series of random test results that might be expected in a population of 321 individuals rang ing in age from less than 30 years to over 70 years. Control subjects or non-expomed workers were not included for compari son. There wee perhaps some Indication of a relationship of SCOT levels to plasma levels of pets# but the two ssposure categories of PCS levels are too broad and require a finer analysis. (ill) taker at al. (1900) studied liver function in l4t individuals with various degress of ssposure to PCtSi the HONS 22199* ?9 g^n PCI Mrun levels for the four cost groups varied from 17.4 to 75.1 ppb. There was no change in liver function tssts moor, SGPT, LDH, alkaline phosphatase, or strum bilirubin) in Ration to PCS blood levels in tithtr drinkers or nondrinksrs of dtcohol. Strum GGTP (gamma glutamyl trtnsptptidast) corrtiattd mxtf strum pet, but a corralatlon did not exist when alcohol (linkers wtrt rtmovtd from the analysis. (tv) Maronj tt al. (1911a, b) studied llvtr function fcm so vorltors exposed to PCBS for an average of 12 years and ported that IS Individuals had an abnormal liver finding as Hedged by elinical examination or by laboratory tests. Inspection of the data shows relatively few instances mf abnormal liver function tests. The aost frequently altered laboratory tssts were as follovet . of 10 subjects with increase of SCCT activity 7 of 10 subjects with increased serum amino transferase activity (AST or ALT) of to subjects with increase of SOCT activity. It is evident from their data that many of the changes are slight, and as test results from oontrol subjects were not Included, we do not know what the normal test variations nsy be for 90 control subjects of a similar ago* Further, examination of the data for the 14 subjects with clinical hepatomegaly shows only one subject with an abnormal test in three types of tests (SCOT, AST/ alt, and OCT); only two of the subjects gave a positive response in two of HONS 221991 - 80 - eh* e*at typos; tight subject* had an abnormality in only on# e*at-f thra* aubjtct* had normal taat rasults. Sarum bilirubin and aiJcalmt phosphataa* activity war* within tha normal rang* in all aubjaeta. Saaad on tha abov* raviaw, it it avldant that only on* oftha 10 aubjaeta ahowad a pattern of taat raaulta indicativ* of abnormal llvar function; tha othar taat raaulta raflact only random variationa from normal. naroni at al. alao raportad that tha moan laval of oloodKla in tha 16 workers with abnormal llvar finding* waa aignifieantly higher than that of 64 workara without abnormal llvar finding*, but tha rang** for tha two group* ahow eonaidrabla overlapping and tha two aubjaeta with tha highaat blood PCS lavala had normal llvar function taat*. Tha only control wa can uaa to evaluate the auggaatad relationship between PCI blood laval and llvar function are tha 10 subject* with chloracna; thaaa 10 Individuals had normal llvar taat rasults despitt tha fact that their mean blood PCS concentration was high and not significantly diffarant from tha maan blood PCS laval found In tha 16 workara discussad above. Thus, it cannot be said that this study demonstrates a relationship between a high blood PCS level end abnormal liver function tests, attaating furthar to the randomness of tha llvar function taat results In the study. (v) Smith at *1. (1961a, b, e) evaluated liver function tests in PCS-axposed saployeas from an alactrlcal manufacturing plant, a municipal alacferlc utility company, and MOWS 221998 81 ^mtivataly-ownad elactnc utility company, rtia data on SCOT m CGrr art difficult to avaluata as tha raaults of tha maa- art not gtvan, and tharafora may ba asaumad to ba Phm normal population lavalar cathar, tha authors sought JBrralations batwaan tha log of SCOT and got? with tha log of ggs lowar sarum PCSs and tha log of high aarum PCI*. Calcuia- SJtns includa simpla corralations, aaparata ragraaaiona with Kka confoundsra as pradictora, and squarad partial corralation. gus othar computations to aaa if associations axistad. Thair Fablas 6, 7, and 8 summariza many of thair calculations, and |Sta for transaminasaa from tabla 7 ara summarized below. Corralation With Sarum log L-PC1 Sarum log H-PCB llactrlc agulpmant company log SCOT log GGTP Sunicipal alactric utility company log scot log CCPT Erlrataly-ownad utility company log SOOT log CCTT (if statistically significant Vi not significant NS sig sig Sig NS NS NS NS Sig NS NS NS L-PCB lowar ehlorinatad biphanyls H-PCS - hlghar ehlorinatad biphanyls HQNS 221999 32 - Correlations (associations) were found at the equipnent company but the data cannot be examined to determine if the calculated value has any medieal siqnificancs. correla tions at the publiely-owned utility coapany were not eignificant. At the privately-owned utility company, the only positive findinq was a positive association of SCOT with serum L-PCI. It is not clear what the chanqe in this one test result means as the serum L-PCH were not significantly different between the exposed and nonexposed groups. The test results for total bilirubin, alkaline phosphastase, and lactic dehydrogenase are not discussed, and it is presumed that these measurements of liver function were not abnormal. 2. Liver Disease in PCS-Exposed Workers Medical examination of PCB-exposed workers has not shown the presence of liver disease, in the study of Pischbein et^ *1_. (1979), physical examination of 32* individuals (age less than 30 to over 70 years) revealed four individuals with abnormal liver site, two of whom had a history of heavy alcohol intaker one of the four had a slight elevation of one liver function test (SOOT of 5S) In another study of 14S individuals with varying de grees of PCS exposure, there was no evidence of liver disease as determined by medieel history end physical examinations (Baker et el., 19S0). Smith et al. (1991) did not find evidence for liver MOMS 222000 S3 - Sis**** in thir sublets, there being no significant findings on ^hytical examination of workers at an electrical equipment manu facturing plant who were heavily exposed to pCBs, or workers at ^municipal utility company or a private utility company who were leas heavily exposed. Deaths from cirrhosis of tha liver were not increased by exposure to PCB (Brown and Jones, 19SI); six deaths ware observed (three of the six consumed alcohol regularly) versus j'.i expected. 3, Summary and opinion The review of clinical data demonstrates that exposure to PCBs does not significantly affect liver function tests. Uver function remains normal in individuals with measurable, and freq* vientiy high levels of serua PCS. Also, exposure to PCBs does not result in the production of clinically detectable liver disease. The induction of ensyme systems in the liver and the biological significance of this process, as mediated by PCBs, are discussed in section XI. MOMS 222001 MOMS 222002 3 i Mi % Si ou p o ly c h lo rin a te d trip h a n y l), 5000 pp in the ( A lla n , C aratana, and S a r s o ttl, 1974). m o re t*4 / S X 86 (vi) Tha hyperplastic gastritis aay persist Cor over one yaar following diseoneinuanca of PCI exposure (Allan, 197$). A mixture of low chlorinated biphenyl (Clophen A-30) waa not obaarvad to produea gastric laalona in the aonkey (iatropoulos at_ aK, 1977). Tha findings of Allan at aK wars racantly confirmed and extandad by Backar _1. (1979). Their study involved six monkeys, one untreated and one each receiving a diet containing 3, 30, or 300 ag/kg of PCI (Aroclor 1262)j two monkeys received a diet containing 10 ag/kg. Monthly biopsies taken from tha greater curvature oC tha stomach showed a dramatic decrease in the number of parietal cells with a concomitant Increase in the number of aucous neck cells* The tyaogenle (chief) cells were also reduced in number, this was followed In all treated aniaale by a eucoua conversion of the gastric epithelium, with downgrowth of the gastric glands into the sutmucosa and the eventual formation of cysts* tt is noteworthy that the lesions were confined to the stomacht no changes were found in other regions of the gastrointestinal tract. The gastric changes can be described as a dyeplaetic growth pattern, but there Is no neoplastic transformation (Allen and norbaeh. 1973). Bowever, tha authore speculate thet they are 'suggestive* of an eventual neoplastic transformation. Analysis of tha rasults obtained In the aonkey indicates that tha PCS-induced morphologic changes in the gastric mucosa MOMS 222004 87 be specific co chit species and not predictive of possible Effects in man. (i) Evan within tha monkey a specificity of action ia praaant, aa tha lesion induead by PCS* 1a found only along tha graater curvatura of tha stomach; naithar tha cardiac nor pyloric portions wara affactad (Becker al., 1979). (11) Hypartrophy and hyparplaala of tha gaatnc mueoaa have not baan raportad In tha rodant (Allan and Abrahamson, 1973), rabbit (Voe. 1972). or in othar apaciaa (Vos and Koerman, 1970). Clinical findings to data hava not suggested or indicated that exposure to PCBs incraasas tha occurranea of cancer of tha atoaMch in tha human (sea also section VIII, relating to carcinogenicity). HONS 222005 - 89 VI11 Carcinogenesis; Experimental md Clinical A. Exptniwntil Studies All authors do not ass the words tumor igenesis and "toplasis to indicsts ths tarns type of rssponss. Tumor iqsniin is a general tsrm that rsfsrs to both benign growths and malig nant growths; compounds may affset ths occurrsncs of benign tumors without inducing eancsr. Neoplasia means simply a n*w growth. Ths tsrm 'neoplasia* can refer to a benign or malignant growth, oftentimes authors may combine data relative to benign and malignant growths so that when the terms tumorigenesis or neoplasia are used, they must be carefully defined. 1. Hepatocellular Carcinoma (i) Studies in mice, ito et al. (1973) ob served hepatocellular carcinomas in mice only in the high dose group given Kaneehlor 500 r lower doses of Kanechlor 500 or the other ranechlors did not produce a carcinogenic response (Table ]) The administration of 100 ppm of Aroelor 1254 in the diet for 11 months did not induce hepatocellular carcinomas in mice (Kimbrough a binder, 1974). (ii) Studies in rats. The administration of Kanechlor 400 for 400 days did not Induce hepatocellular carcino^i (Kimura a Baba, 1973), but the period of treatment may have been too brief to detect a carcinogenic effect. In a further study Kimura et al. (1970) administered Kanechlor to rats for six mont-s but duo to body weight changes a variable dosage schedule was employed. Pollowing the cessation of treatment, the rats were NONS 222006 90 - fed on * normal diet Cor 270-410 days> autopsy* aftar a total experimental period of 450-590 days* did not reveal hepatocel lular carcinoma in any of 12 rata. Ito at al. (174) traatad rats with diffarant dosaa of Kanachlor 500# 400, and 300 for pariods up to 52 weekar hepatocellular carcinomas wars not observed, but the duration of treatment was probably too short to rule out the poasibillty of a positive response. The three major studies pertaining to PCSs and hepa tic carcinoma in the rat are those of Kimbrough at al. (1975), Calandrs (1975), and the National cancer Institute (197). Kimbrough and co-workars, using the Sherman strain of rat, found that 100 ppm of Aroclor 12*0 in the diet for 21 months produced a significant increase in the incidence of hepatocel lular carcinoma in female rets (section VI, Table 4). Male rats were not studied. The administration of three different Aroclors at a dose of 100 ppm to rata for 24 months (Table 5) did not induce hepatocellular cardnos* (Calandrs, 1979). The author states that this negative finding was baaed on evaluation of the liver sections by three pathologists, who read the slides independently and separately. Be states further that Professor P. Pour re evaluated the Kimbrough slides and did not agree with the reported findings (so# else section VI, Table 2A>. The results of the National Cancer institute <197|> bloassay of Aroelor 1254 for possible carcinogenicity are shewn in section VI, Tsbls C. Fischer 344 rets were used end the PCt MONS 22200? 91 - ^Sur was administered at three dose levels <25, 50, and 100 ppm) gpths diet Cor 104-105 weeks. The effect of the treatment on oey weight and mortality at the higher dot* levels demonstrated ^at maximum tola rated doses warm used, thus providing a satisBetory test of carcinogenic potential. A sufficient number of ate of both saxes was available for meaningful statistical analyses of the incidence of late-developing tumors. Treatment as associated with only three hepatocellular carcinomas in male feats, which was not significantly different from the controls. nd it was concluded that Aroclor 1254 was not earelnogenie in the Sloasssy. (ill) Studies in does. Hepatocellular carcinoma did pot occur in dogs (four male and four female per group) receiving ft. 10. or 100 ppm of Aroclor 1242. 1254. and 1240. respectively, in their diets for two years (Calandra, 1575). (iv> Discussion. Date from the mouse provide only limited and restricted evidence for a carcinogenic effeet of the Japanese compound Kanechlor 500 (Table 3). Studies on the rat give conflicting results on hepatie eareinoma. (Section VI deals with the benign hepatie proliferative lesions found in the treat ed rats, which may or may not indicate earelnogenie potential.) Slabrough at a^. (1575) reported an increase of hepatocellular sssuinomss in feaale rats receiving Aroclor 1250, whersas the stadias of Calandra (1575) end the National Cancer Institute (197S) did not observe a significant inersaee in hepatocellular earelnomas in rata receiving different Arodors. Mhether the 22200s 92 divergent results sr related to the different strains of rets thst were used, represent differences In the effect of the two Aroelors, or are due to other factors Is not known, it Is ob vious, however, that in view of the differing results obtained it is not possible to extrapolste or project possible effects in nan. Hepatocellular carelnooas did not develop in dogs treated with Aroclor for two years. 2. Sladder Cancer Riebrough (1*72) observed bladder eancers in two rats fed 100 ppa of Aroclor 1210 for eight Months. In a later study with 200 rats receiving 100 ppa of Aroclor 1200 for 21 aonths the only bladder tuaor observed (a transitional cell papllloaa) was in a control aniaal, and it was concluded that "the occur* renee of the bladder tuaor in the previous experiaent was ap parently unrelated to tbe ingestion of Aroclor 1200" (Riabrough at al., 1973). mis type of variation deaonstrates the un reliability of attaching significance to saail changes in tuaor incidence in a given experiaent, particularly when the inci dence dees not show a statistically significant difference froa a control group. saiga or aallgnaat bladder tusrs did not occur in rats treated With Aroelors 1234 (23, 30, and 100 ppa) for 104 109 weeks (national cancer institute, 1970). The above stedles do not deaonstrate that adalnlstrat ion of Aroclor 1234 or Aroclor 1240 induces bladder cancer in the rat. HONS 222009 93 3. Stomach, Intestinal Tract Cancer Treatment of female rats with Arocior 1260 ( 100 ppm in (fiat) for 21 month* did not indue* tumor* in th* gastrointestinal (Tract (Kimbrough al., 1975), Tr*at**nt of rata with Arocior 1254 (25, SO, and 100 ppm HA th* diet) for 104-105 weeks did not indue* gastrointestinal Carcinomas (National Caneer Institute, 1971). Tumor* occurred In random manner as illustrated in Table 7. 4. Carcinogenesis - other Organ* Studies with PChs in relation to cancer of th* liver, gastrointestinal tract, and urinary bladder hav* been discussed separately above. In the studlee with PCI* other organs have been evaluated in detail without finding any effeet of ehronie administration of Arocior* on th* incidence of benign or malignant neoplasm*. The following appraisals refer to tumors of these other organs. Kimbrough *t aK (1975) found that th* chronic administration of Aroelor 1260 to rats did not affect the incidence of benign tumors or carcinoma* of th* thyroid gland, adrenal gland, uterus, lung, and other organa, frequently investigator* loot only for increases in tumor incidence, when in feet decreases are oftea obtained. It is worth noting that mammary adenocarcinoma Mevrred in 5/173 control animals versus an incidence of 1/164 in treated animals. If the incidence had been reversed, some authors may have commented or suggested that fees may increase the occurrence of mammary cancer, but tuch would not hav* been MQNS 222010 -* Incidence of Caatrointaatinal Carcinaaaa in Kata rraataa vita AroClar u (Data Croa National Cancer Inatltuta, LfTtl SUttt t rciaa Jajaaaa. earat Cocas, riaamauat wHr if rarcliwwaa 90501 H 0-- *KK. Ok-- auti ante ucUMaa MOMS 222011 95 the ease as Ch numb*r of mammary adenocarcinomas in control groups can vary signifieently from study to study, if th* incijnc* of spontaneous tumors can vary, then th* numb*r of malig nancies in th* traatad group will vary with *aeh *xp*rim*nt Independent of the treatment given. An additional Illustration of tumor variability is the incidence of ovarian granulosa theca cell tumors which was 5/149 in controls versus 0/10 in th* treated animals. In the National Cancer instituts (1970) study, th* chronic administrations of Aroclor 1254 was without effect on th* devslopewnt of benign or malignant neoplasms in ths various body organs of the rat (the liver, gastrointestinal tract, and urinary bladder were discussed separately above). In the study, interstitial ceil tumors of th* testes were present in nearly all control and traatsd animals, there being no effect of treatsent. Leukemias, which were the second most common neo plasms, were found in 13% of control males and 17% of control females. A statistically significant dose-related trend for leukemia was present in the treated males but not in th* femal* rats. Bovewer, direct dose comparisons between each treatsent group (male or female) and the control group were not statisti cally significant, so that an affect in males could not be elearly related to tho administration of Aroclor 1254. Adding the few lymphomas to the leukemias for the analyeis did not change the MOMS 222012 96 conclusion, Kimbrough et_ al_, (1975) also did not find a 119. mf icant affact of Aroelor 1260 on leukemia ineidanca (1/173 in controls varsus 0/184 in treated animals). It may be concludad from these studias that the chronic oral administration of high dosas of Aroclors 1360 or 1254 docs not induca baniqn or malignant tumors of tha thyroid gland, adranal gland, utarus, lung, hematopoietic systsm, pituitary gland, thymus, kidney, and othar organs in rats. S. Summary and Opinion Animal studias do not provide convincing evidence that PCBs indues liver cancer. Of tha major studies in tha rat, one has bean judged positive and two have been negative. Hepatic carcinoma was not produced in tha dog. Chronic administration of Aroclors in the rat did not indues bladder cancer, gastrointestinal carcinomas, or canoar of the thyroid gland, pituitary gland, adrenal gland, uterus, lung, hamatopoiatic system, or other organs. 8. Clinical Studies The studies of Brown and Jones (198U and Bertassl and co-workers (1981) have evaluated the relationship between exposure to PCBa and the subsequent development of cancer. Both analyses are retrospective mortality studies of workers to determine the cause of the death and, for malignancies, the speolfle typo of cancer causing the death) the deaths are designated as `observed cases." The person-years of exposure HONS 222013 - 97 - Qt eh* workers to PCB were and combined into calendar (1M periods and five-year age groups to calculate from mortality aaatisti.es the number of 'expeeted* deaths. The number of ob- aerved versus expected deaths was then compared. Background data relative to these studies are summarized briefly, as follows: (i) Brown and Jones (Ull). The authors analyzed 1|] known deaths occurring among 2,567 workers exposed to PCBs for 39,018 person-years, exposure to PCBs ranged from three months to over 20 years. The type of PCBs used at the plants were hroclor 1254, 1242, and 1016. (il) Bertazil et al. (18611. The authors analysed 27 deaths occurring In 1,310 workers exposed to PCBs for 20,565 person-years, determining 'observed* versus 'expected" rates for malignancies. Mortality was studied for a 2S-year period (1954*1978), Exposure up to 1964 was mainly to Aroclor 1254 and Pyrailn* 1476} starting in 1965 mixtures with 428 chlorine were used (mainly Pyrailn* 3010 and 3011). (iii) Behn et al. (1976, 1977). Thee* authors report two cases of malignant melanoma in 31.men exposed to Aroclor 1254. It is not clear from their studies if they are discussing aorbidity or mortality} Brown and Jones (1981) interpret the report as mortality. Pertinent data on the mortality from malignancies are summarised in Table 8 and art discussed below. MONS 222014 - 98 - All Baliqnanclss. Brown and Jones reported 39 ob served eases of cancer versus 43.8 expected caees, whereas Bertazzi at *1_. found a statistically significant increase m males, but not in female worksrs (Table 8). There wee no in. crease in the risk of mortality from all malignancies with length of exposure or with the number of years of employment (Brown and Jones, 1981). Rectum. The only statistically significant differ, enee observed in the study of Brown and Jones was for rectal cancer in females from plant 2 (Table 8). There was no significant finding for females in Plant 1, males In Plant 1 or 2, or for the combined data for males and females. The incidence of rectal cancer showed a slight, but statistically insignificant, Increase with increase in latency; no direct relationship with increased length of exposure is apparent. Bertassi at al. (1981) did not report a case of reetal cancer in PCB~exposed individuals. Stomach, Pancreas. The studies did not demonstrate an increased risk for stomach or pancreatic caneer (Table 8). Heoatocollular Carcinoma. Three cases of liver cancer were obeerved in the study of Brown and Jones (1981), but tho difference from the control rete was not reported to ho statistically significant (Table ). Bertassi and coworkere did not mention observing any ease of hepatic cancer, examination of the data for latency effect or for length of exposure to PCSs did not show any relationship to development of liver cancer (Brown and Jones, 1981). MOMS 222015 Ttaii l OtftjtM 4ra 1hctflc Tvwt af ?*ne*r (MftriMK af DbitrvM Omiu in fc workers W1UI tlHCtM 0*4 eft* k*(ar*nc* 1 2 2 Kj1lknknev 111 m "-*** CMM Isa ft,4 n f oftfrv* 3* i It--* *1* ? 1.12 2.12 1 XMtlM * ` i 4. SI 1 riyiMi 1) 4 4.14 PlftlMt 1) 1 4.S4 l * n.t 4 1.14 1 ItawM *.r 1 1.(4 1 rtMtMi m.r 1 l.M 2 01--tin 9rf*** (uracil, HMnw. tilliiy irHU H r 1 4.44 4* l tU< Cinimm n.t 2 1.4T 1 llMMIU 1 UWMU* 2* 2 *,r m T 2 4,14 2 4.44 2 4.41 1--m 1* 2 *.r 2 4.4* 44- US If 141 2S4 124 (4 12 144 * llitllticil Sinitiejne* N4 4*4 .94 N4 "4 *4 4*9.92 M4 N* M N4 *4 1(4 N4 44 N4 412 44 4 *4 4*9.991 - N4 - rt* M 1. M >. M 1. am. t IIMI M JMt, im hlUlHM *1.1 1*41 MM M *1., 1**1. UJT KmMNIiM wnirny r4lU lokMnM 4MUI/Wf*CtM 4Mtft* 1941 M llpUdiMI MOMS 222016 lymphatic and Hamatopoietic Cancar. the two itudiaa show diametrically opposite risk valus*. although nsittisr ia statistically significant (Tabla 8). . fialanoma. 9ahn at_ aK (1976, 1977) rspartad two casas of malignant malanosia occurring among 31 man who had haan exposed to Aroeior 1254 . Basad on tha Third National Cancar Survey incidanca ratal, Bahn rt al. calculata for a paraon-yeer analysis that only 0,04 malignant melanomas would ba expected, tha diffaranea being statistically significant (P"0.fl01). The extensive studies of Brown and Jonas and of Bertassi at al, fail to confirm tha ineraasad risk of mortality for malignant melanoma reported by Bahn and co-workers (Table 8), raising doubts about tha significance of tha Bahn studies, Evan an association with the low P value of 0.001 has not bean con firmed . Summary. The clinical evaluation of PCBs relative to cancar is currently basad on a limited amount of data, and any conclusion regarding their affects must ba regarded as tentative. Nevertheless, some detailed analyses are available and conclusions based on them, as listed below, are of aome significance, 1* Retrospectlve mortality studies have not demon strated a consistent relationship between exposure to PCBe aid the development of a particular type of cancer. 2. The clinical findings on hepatocellular carcinoma ara of greet interest as some experimental etudlaa raport an HONS 222017 101 - increase in liver cancer in rodents rsesiving PCS*. Although Brown and Jono* U9tl) observed three case* versus l.o? expected cases, the difference is not statistical!/ significant. Their analysis of PCB exposure and risk of mortality from liver cancer is also noteworthy since it did not demonstrate an effect of latency (nuaber of years from date first employed) or a relationship to increased duration of employment in jobs involving PCS exposure. These latter observations are, how ever, based on small numbers. Bettassi et_ al_. (14*1) did not report any significant relationship between PCS expoeure and liver cancer. Taken together these studies do not confirm the projection of a risk for liver cancer in humans based on the animal studiee. }. The SMR (Standard mortality Ratio) may vary widely in different studies# and emphasis should not be placed on an Increase in the SMR found in one study unless a significant change in SHR can be confirmed in several repeat studies, Por example# Brown and Jones found the SMR for lymphatic and hematopoietic malignancy to be decreased while Bertassi at al. reported en increase# although neither result was statistically significant (Table ). 4. Brows and Jones observed a statistically signi ficant Increase ia SMR for rectal cancer in women at one plant, but not In a different plant# and no significant effect in male workers st either plant was observed. Bertassi e al. HONS 222016 102 did not report any ractal cancar (Tabla 9). ovarali, thar*. Cora, a convincing damonatration oC ractal cancar a a ramie of axtandad axpoaura to PCS* ha* not b*an mad*. MOWS 222019 103 Reproductive Effects >n have appeared in the literature on nated biphenyls on reproduce ion in ton <1979) showed that female Spragueg Aroclor 1221, 1242, and 12(0 by gavaga 20 of pregnancy had no efface on eha if eha offspring aa judged by (a) normal lal appearance of ovariea and ueeri, and feeding SSO ppe of Aroclor 1254 for (7 lead In fewer lleeera, smaller lieeer by day ehree of ehe ria pupa. At 100 ppm Fib offspring was reduced. The pups s but appeared normal at weaning, tary level of 500 ppm <15.4 og/kg) for arkedly reduced litter aise and e ria and rib generation. Dietary 254 and 100 ppm Aroclor 1240 had no rats exposed through two generatione . dietary concentration of 2.5 ppm of oration in the menstrual cycle of ye. flenses were prolonged and menstrual .lien et al^., 1979). (1971) fed rata and dogs Aroclor 1242, f 1.0, 10.0, and 100 ppm. No adverse HONS 222020 104 affsct on reproduce ion wet obttrvtd in rat* given 1.0 and lo ppit Aroclor 1242, but there waa a dacraaaa in turvival of pupa at 100 ppm of Aroclor 1242, 1254, and 120 aa wall aa a dacraaaa m mating indicee. The affact of PC8a on reproduction in beagle doga and swine has baan studied by Carl a al. (1974). Aroclor 1254 interfered aignificantly with reproduction m doga at doaea above 2.5 mg/kg/day while m twin* 10.0 *g/kg/day lowered fertility and aurvivabillty of neonates. The reproduc tive effects in doga are questionable because of unexplained changes in the reproduction pattern among controls. 8. Teratogenicity 1. introduction Teratogenicity i* that property of an agent whereby it is capable of inducing congenital defects in the developing eabryo. Such agents that are cheelcal substances are known aa 'teratogens' and the defects they Induce are known as 'terata.* Although teratogenicity is considered generally to Involve only anatoeical defects, soae authorities regard functional or blocheelcal changes as aanlfeatation* of teratogenicity, h distinction must be sad* between teratogenicity and fetotoxiclty, i^e., toxicity to the fetus. The finding of deed or resorbing fetuses in the uterus of an experimental animal ia not evidence of a teratogenic action of the teat substance. Similarly, a aaaller site of the newborn is indicative of fstotosieity rather than teratogenicity. HONS 222021 105 A substance may appear to ba teratogenic if ie proguces saver* toxic affects on the pregnant female. Maternal Biaease and malnutrition affect the number and quality of the Offspring. Defects in the offspring that are secondary to toxic if facts of the substance on the mother are not considered terata. Teratogens produce their harmful effects during the period of formation of cells, tissues, and organa. Hence, once development of the fetus has been completed, a teratogenic vent can no longer occur. Chemical substances administered to the mother can be transmitted, together with their metabolites, Via the milk to the suckling young, and may produce toxic effects (n the latter. However, such effects are not indications of teratogenicity. Conventional tests for the detection of teratogenicity Involve administration of the test aubetanc* to pregnant females at repeated intervals throughout the period of organogenesis, a.^., days eix through 13 of the gestation in the rat. The treated female* are sacrificed on the day prior to parturition, and the fetuses removed from the uterus surgically for examination. Alternatively, the test substance may b* administered over rela tively long periods of tie#, and the animals allowed to bresd normally as in the usual on*- to three-generation reproduction studies. Tbs sppsarsne* of aslformed offspring smong ths euccsedlng generations would ba evidence of teratogenicity. in order for s chsaical substance to which the mother i* exposed to exsrt a direct action on the conceptus, it or on* HONS 222022 106 or more of ita metabolites must be able to croaa the placental barnar. Transplacental passage of PCBs has been demonstrated in several animal species (Allen et_ al_., 1990; Curley at al., 1973; Couvillion it il., 1976; Crant et il., 1971), and is known to occur in the human (Funatau at al_., 1972). 2. Mice PCBs were not teratogenic in mice at dosages up to soo mg/kg given on days one through six or days seven through ll of gestation (Toeruek, 1973). However, a recent study (Marks et al. 1991) with the hexachlorocongener 3,3',4,4,S,S -hexaehlorobiphenyl in mice at dosages in the range of 0.1-16 tsg/kg/day dur ing days six through 15 of gestation produced a significant in crease in fetal malformation, a significant decrease in average fetal weight, and an Increase in the percentage resorptions. Torok (1976) reported that oral administration of 375 mg/kg or 7SO mg/kg of 2,2'-diehlorobiphenyl to mice on days one through three of gestation resulted in prolongation of the interval between breeding and parturition, tie attributed this observation to delayed implantation. Although the treated animals had fewer litters and lesser mean litter sixes, there was no indication of teratogenicity. Some mice exposed to 3,4,3*a'-tetraehlorobiphenyl were reported to exhibit a *waltsing syndrome* (Oevis et al., 1979* Tllaon at al., 1979). Tha dosage was 33 mg/kg administered by gavage to the mothers on deys 10 through 16 of gestation. The HONS 222023 107 syndrome consisted of increased motor activity, nyperreflexie, no episodes of head bobbing and rotstlonsl movements that wars present up to st lssst sight months of ags. Not sll exposed mics wars sf(acted similarly, but avan those that did not exhibit the pyndrome showed diminished performance in various neurobehavioral testa Til son a al. (1979) refer to these observations as the behavioral teratology* of 4-CB. 3. Rets Thera are a plethora of studies in which the reproduc tive affects of feeding various Aroclors to rats have been in vestigated (Calandra, 197Sj Gellert and Wilson, 1979* Keplingar at al., 1971) Keplingar at al., 1973r Linder at al., 19741 Villeneuve at al., 1971a), Collectively, these studies reported fetotosleity as the dooage was inersased, but no teratogenicity was demonstrated. It may be useful to note the order of magnitude of the dosages involved. Vllleneuve at al. (1971a) found no effect from the administration of dosages of up to 100 mg/kg per day orally to pregnant females from the sixth through the fifteenth day of gestation, ultrastrueturel lesions in thyroid follicular cells snd a reduction in serum thyroid hormones have been reported in neonatal and weanling rets whoee mothers had been fed a diet containing 90 ppm or 900 ppm of Aroclor 1294 throughout the period of gestation (Collins and Capen, 1910). The authors suggest that alterations in thyroid structure and function in the fetus or neonate may be related to subsequent disturbances in growth or development. HONS 222024 - 109 - 4. Poq In the study conducted by Carl et ai. (1974), preg nant bitches were given dosages of 0.2S, 1.0, or 5.0 ng/kg of Aroclor 1254 from the day of breeding to the day on which thsy wore nocropsied. At 5.0 mg/kg, there was an increase in the percentage of resorptions, a decrease in the number of live pups per litter at birth, and a reduction in the percentage of those surviving to two weeks. The terata observed consisted of enlarged fontanelles, cleft palates, and superfluous pha langes. This dosage was said to limit diet consumption severely. The authors state that one litter of the controls 'may have had a genetic defect that caused an unusually high incidence of terata.' 5. Swine Earl et si. (1974) included miniature swine (normal strain) in the investigation described immedlataly above. Preg nant sows were given dally oral dosages of 1 mg/kg, 10 mg/kg, or 30 mg/kg of Aroclor 1254. Dosing began 21 days before breed ing and was continued until the day of neeropsy. The authors concluded that dose-related effects were seen at all treatment levels as evidenced by decreases in the nuaber of pregnancies, number of live pigs farrowed per litter, and percentage of live offspring after two weeks of age. Syndactyly and cleft palats* were observed in the young of sown receiving 10 eg/kg, and patent fontanelles and cleft pslstss in the offspring of those receiving 30 ng/kg. As in the case of the dogs, the higher dosages caused a narked reduction in food consumption. HONS 222025 109 6. Monkeys In a study reported by Allan at al. (1974), six adult, female rhesus monkeys wars fad a diat containing 25 ppm of Aroclo? 1248 Cor two months. During this pariod, all animals davalopad characteristic signs of toxicity, although thay main tained a regular menstrual cycle. One animal died. At the beginning of the fifth month, or three months after discontinu ance of exposure to the test substance, an attempt was made to breed the survivors. Three animals appeared to conceive, but only one succeeded in carrying her fetus to term. Although this infant was well developed, its body weight was considerably lower than that of the average rhesus Infant, examination of the tissues showed no gross or microscopic lesions. In a second study by the Wisconsin group (Barsottl et al., 1878) involving II adult, female rhesus monkeys, nine were fed a diet containing 2.5 ppm, and nine were fed a diet containing S ppm of Aroclor 1248. After seven months on these diets, the eight surviving animals from the 2.5 ppm group and eight from the 5 ppm group were sated with control males. Ml animals in the 2,5 ppm group became pregnant, but three of these resorbed their embryost the remaining five gave birth to live infanta* in the 5 ppm group six animals became pregnant. These impregnations resulted in three abortions, one resorption, one stillbirth (suffocation during difficult delivery), and one un complicated birth. At birth, the six infants were small) how ever, other than their small stature and focal areas of dermal MOHS 110 hYP*rpigmsntation, thsir general appsarancs, hemograms, and osseous davalopmant as aval.uatad radiographically were normal. Tha adult, faaala rhaaua monkeys that vara tha ori ginal subjects m tha study discussed above ware fad tha diata containing 2.5 ppm or 5 ppm of Aroclor 1241 for aix montha prior to braading, throughout gaatatlon, and for thraa month! aftar dalivary for a total of about IS months (hilan at al., 1980). Only IS famalaa wars brad, inasmuch as ons had diad and another was dropped froai tha study for soma rsason not explained. About one year aftar discontinuance of the Aroclorcontaining diats, tha animals wara brad again to control males. All of tha seven survivors in tha S ppm group conceived, but only four gave birth to live infants, in tha 2.5 ppm group, one animal had an abortion and tha remaining seven had uncom plicated deliveries. Apart from their somewhat smaller site compared to the young of the control animals, the infants appeared normal. Analyses of adipose tissue from two stillborn infants of mothers in tha 5 ppm group showed the presence of PCSs, but histological evaluation of adipose and other tlsauea hewnad no abnormal1ties. 7. Clinical Data ronatsu at al. (1972) studied in detail four babies born to mothers who had ingested rice oil contaminated with a heat-exchange fluid containing pete, PCOFs, and PCOs. The mothers wara among tha population exposed in the 'Yuaho* s pi sods. Three of tha four bablea exhibited soma evidence of intrauterine salnutrition or retardation of growth, and all four had dark brown HONS 222027 - Ill - piqmantation of tha ikm chat vai moat pronounead at tha gamfcalia, axillaa, and naar tha fingarnails. Tha aama pigmsntation ^aa notad-on tha lips, gums, and palata. Hhlli ona or mors of tha infanta displayed othar clinical signs, no naurological or eardiovaaeular abnormalitlaa, nor any malformations wars obaarvad. Bba oigmantation of tha akin and mucous mambranaa diaappaarad within two to fiva months of aga in all caaaa. > Summary and Opinion (a) In a variaty of tasts, eonuaareial PCS mixtures L(kroclors) a howad no taratoganie activity in mica, rata, rabbits, and monkaya. (b) Earl at al. (1974) hava not damonatratad convinc ingly a taratoganie action of Aroclor 1254 in dogs or awlna. An avalnation of thalr work auffart from a paucity of Information and tha posaibls praaanco of a ganatlc dafact in tha dog colony. Tha publlshsd abstract tanda to ba mlalaading. Examination of tha unpubliahad manuscript shows that tha authors did not ragard tha two lowtr deaagas aa taratoganie for aithar apaclaa. Tha highsst doaa la said to Halt food consumption savaraly in both paclas. Tharafora, it la llkaly that tha dafseta obaarvad in tha offspring war* tha rasult of aavara natarnal malnutrition, anaan at al. (1975) failad to find taratoganie affacta in awina whan tha ootMra woes fad a dlat containing aoma 20 ppm of Aroelor 1242 throughout gustation and nursing. (a) Tbs obosrvations of Collins and Capon (1910) on tltrsatruetural aitarationa in tha thyroid glands of parlnatal HONS 222028 112 rats who mother* wsre exposed to Aroelor 1254 ere indicate* of functional changes rather then of teratogenicity. (d) The occurrence of e "waltzing syndrome* in mice exposed prenetelly to 3,4 *J',4'-tetrechlorobiphenyl might rep resent e true ttratogsnie effect (Oevis at el., 1979). Thu phenomenon usually results from e structural or functional defect of the middle ear. The dosege used to produce the syn drome is relatively high. While the exposed animals were not uniformly affected Insofar as the overt signs are concerned, Til son et al. (1979) presented evidence to show a wider pre valence of more subtle nsuro-behavioral effects, it is not known whether this condition could b induced by a commercial PCS mixture. (e) The scientific literature presently supports the conclusion that PCls present no appreciable risk of teratogeni city for humane, in our opinion, in view of the essentially negative teet results in four teat species and the questionable positive findings In the dog and in swine. C. retotoxicity Rabbits given 1.0 mg/kg of Aroelor 1254 daily for 2S days of goatatlon hod no offset on the developing fetus but doses of 12.5 to 30 mg/kg were fetotoxlc. hats appear to be more resistant than rabbits, as dosss up to 100 mg/kg do not cause fetal deaths or malformations (villsnsuvm at el., 197lei. Bmbryotoxlc affects of kanechlor 300 and 500 wars produced in HONS 222029 113 fprsgue-Dawley JCL rats when fed at levels of SQQ ppm in the gist throughout gestation (Shiote, 197(b). Diets containing 0 ppm of Aroelor 1248 were fetotoxic to rhesus monkeys. fetuses end neonates of mothers with Yusho disease gpve developed some of the characteristic signs of disease as gprsaule of transfer of pC8s to the fetus and infant through the placenta and breast feeding (Yanashita, 1977; Katsuda, et al.. 1978; Yakushijji jt il,, 1978). Studies in mice on the tranefer of PCBa to fetuses and offspring indicate that the amount transferred depends upon the ehesiical structure of the individual compounds and the position of the chlorine atoms within the chemical structure (Matsuda et al., 1978, 1979). Aroelors 1242 and 1294 are potent inducers of hepatic microsomal ensymes. A single intraperitoneal injection of 100 mgAg of Aroclor 1242 to rats increased liver weight, total microsomal activity, as measured by hydroxylation of acetani lide and N-demethylatlon of aminopyrene, and hepatic cytochrome P-490 (Bruckner et al., 1973) Tbs breakdown of endogenous sub stances such as progesterone, estrediol, and testosterone haa been shown to be increased in animals pretreated with chlori nated biphenyls (Orberg, 1978). It ia possible that alterations in the metabolism of the endogenous substances by PCBa may upset the normal balance that is essential for implantation of the fertilise* ova in tbo uterus (Smitb, 1981). Peeding a PCI alsture containing got chlorine significantly increased the uterine weight of guinea pigs (Vos, 1972). HONS 222030 - 114 Yamashita (1977) studied the clinical features of PCS, PCDP, and PCO md uetd fetopathy in four babies born from mothers poisoned by contaminated rice oil. There was intra uterine retardation of growth, dark brown pigmentation on the skin and mucous membranes, edematous face, and exopthalmus, m some cases the retardation persisted for many months but the infanta eventually gained their weight for the age group. Although over 100 nursing mothers residing in Michi gan during 1977-1978 had residues of PCBs in breast milk rang ing from l.o ppm to over 3 ppm, there have been no reports of serious adverse effects on reproduction or infant mortality (Wicklier, 1911), Summary and Opinion 1. It is apparent from studies on humans and animals that certain classes of polychlorinated biphenyls are more tosic than others and that the degree of chlorination is one of the determinant factors in their toxicity. Out, as stated previously undsr cutaneous toxicity, the presence of contami nants may be responsible for the adverse effects on reproduction Oishl et al. t1971, 1980) compared the activities of PCBs and dtbensofurana in rats and found that dibensofursns markedly depressed body weight, decreased weights of tha thymus, ventral prostrate, end seminal vesicles and reduced hemoglobin and hemat ocrlt values, whils PCBs had littls or no offset. HONS 222031 115 2. On the question of fetotoxieity in pCB-exposed (tin, positive results ere seen in certain test ammaia (rets, doqs, rabbits) when the PCBs are administered at relatively hiqh doses (qreater than 10 mq/kq) to preqnant animals. In the human, the only reported evidence for fetotoxieity in exposed popula tions sterna from the unique Yusho event, in which causation may not be linked to PCBs. Ho such reports have been made on other exposed human papulations, suqqestinq the absence of this effect in the human under occupational exposure conditions. HONS 222032 - 117 X. .`lutegenesi i A. General _ The term "mutagenesis* refers to any process that reduces e permanent change (mutation) in the genetic composition a.a cell, thereby causing that cell to differ In a consistent pay from its parent. If a mutation occurs in a germ cell, the bffsprlng resulting from the union of that cell with another Will nave an altered genetic composition that will persist in the germ line unless the alteration is lethal, nutations occur spontaneously through unknown mechanisms, but they also may be caused by radiation or chemical substances (mutagens). While in a strict sense the term 'mutation* applies only to changes in the DMA at the molecular level, it is considered broedly to include alterstions in the number and structure of chromosomes. Mutagenicity is the property of an agent, chemical or physical, to induce nutations. Chemical substances may oe tested for mutagenicity by a variety of methods, among which are those that employ (s> bacterial test systems, (b) cytogenetic analysis i_n vivo, (cl cytogenetic analysis ^in vitro, and (d> dominant lethality in a rodent. a. Sacteriai Test systems The 'Ames test" is the moet populsr test of eutagenssls employing a bacterial taet aystea. It ia a ao-called "backward* autatien system that uses s series of autsnt strains of salmonella typhlmurlam that have lost the ability to synthsairs the emlno MOMS 222033 118 acid histidine, Hence, they can grow only if exogenous hutidin* ia supplied. A mutation ha* occurred if, after exposure to eh* chemical substance, eh* organisms regain eh* ability eo qrow in eh* absence of histidine. Aroclora 1221, 1234, and 1260 showed little muta genic activity in the Ames east (Wyndham et al., 197) with indications ehat Aroclora with lower chlorine contents are weakly positive in the Salmonella tsst systems. However, these results must be discounted since they could not be repli cated (MeNahon et al_., 1979; Safe, 1910). As a general finding, Heddl* and truce (1977), Heflahon jt il. (1979), Schoeny *t_ al. (1979), and s*8* (1910) war* unable to find evidence of muta genicity of tCBs in bacterial teat systems. C. Cytogenetic Analysis in vivo In this procedure, the experimental animal ia treated with the test substance and, after a suitable period of time, sacrificed for examination of rapidly dividing tissues, tons marrow and the seminiferous tubules are generally the most frequently used tissues for this purpose. It is customary to inject the aniswls with colchicine several hours before sacri fice in order to promote the accumulation of cells in the meta phase stays of division. In this stage, the chromosome can b* examined more readily for abnormalities. In two investigations, PCS* wore judged not to have produced chromosomal abnormalitiea. Dikahith et al. (1975) MONS 222034 -119- exasined seminiferous tubules of rets at different intervale after daily doeaqes of SO eg/kg of Aroclor 1254, Green at al_, (1975a) examined both bone marrow end spermatogoniai cells of rata after either a single dose of 5000 mg/kg of Aroclor 1242 , or four daily doses of 500 mg/kg. In all cases, it wea concluded that no significant chromosomal damage bad occurred. The micronueleus test is a test for agents that tend to break chromosomes (clastogens). A micronueleus is a fragment of chromatin that has broken away from a chromosome during cell division and has failed to be included in either of the daughter nuclei. The phenomenon can be observed beat in newly formed erythrocytes since these stain differently from the mature erythrocytea in that they exhibit polychromaaie for a period of 24 hours or so. Furthermore, the nucleus has been extruded at the last maturation division so that the micronuelei, which remain behind, are readily visible in an otherwise chromatinfree cell, riicronuclai occur in a small fraction of normal red cella, but their incidence is increased by the action of clastogens. The test is carried out by administering the agent to the test animal, and examining the polychromatic erythrocytes in bone marrow smears after some interval of time has been allowed for mieronuelei to form. addle and Bruce (1977) reported Aroclor 1254 as nega tive in a micronueleus test. HONS 222035 120 - 0. cytogenetic Analyst* in Vitro Hoopingarner et al., (1972) act ivated cultured human lymphocytes with phytohemagglutinin and treated the* with loo ppm of Aroclor 1254 at various ataqes of a division cycle. The cells then were examined for chromosomal aberrations for ths different stag* treatments. Aroclor 1254 had no apparent effect on chromosomal integrity as measured by cytological evidence. E. Dominant Lethality in Rodents A dominant lethal mutation is on* that occurs in a gens cell. While It does not impair the function of that cell, it kills the fertilized ovum or the developing embryo. Nice and rats are the preferred experimental species, in its aim* plest form, the test consists of treating males with the sus pected mutagen, mating them with normal females, and counting the number of viable offspring. The test could be used to detect dominant lethal mutations in females, but it would be difficult to rule out adverse effects on the embryo that might be secondary to non-genetie effects on the mother. Creen et al, (1973b) concluded that Aroclors 1242 and 1234 were not mutagenic since they failed to induce domi nant lsthal mutations in rats, in similar studies reported both by Keplinger et al. (1972) and Calsndra (1974), Aroclors 1242, 1234, and 1240 were administered to male, albino mice in a single intraperltoneal dosage of aither 300 mg/kg or 1000 mg/kg. Subsequent matings of these animals to control females HONS 222036 121 shoved no effect of treatment on eh* number of implantation or -sorption sites, number of viable embryos, or preimplantation loaa . F. Summary and opinion There ia no evidence from i_n vivo tost systems that any commarcial PCS mixture la mutagenic. Tha aama obsarvation holds trua for tha bulk of tha investigations employing i_n vitro techniques. In our opinion, tharafora, it ia quits unlikaly that tha PCls as a class avoka mutagenic activity in tha human, aithar acutaly or chronically. Sines chamieal mutagenesis and carcinogenesis oftan corralata for a given aetiva chamieal, this opinion is rainforcad by tha assantially naqativa findings on earcinoganasls in populations occupationally exposed to PCBs (sections vrrr and XIIK HONS 222037 123 XI. other Health Effects A, Smyrna Induction 1. tntrodaction Moat chemicals that art allowed to antar tha body ara Converted by tha body to a variety of diffarant chemical entities. In thia manner, food becomes transformed into energy. Chemicals, jthar than food or thoaa that ara naturally prasant in tha body, that ara introduead into tha body ara generally eallad *xenobiotlea,* and thay alao ara frequently convartad by tha body to deri vatives of ths original compounds. Tha convarsion procaasas ara regulated by tha ensyaatie systaas generally taraad biotranaforaatlon systems. Although thara ara a multltuda of xenobiotlc substancas to which humans ara exposed, thara ara only a few diffarant ensymo ays tans lnvolvad, Tha body basically biotransfotias cheatgala by oxidising, raduelng, hydrolysing, or containing (conjugating) tha agant with othar chaaicala. Although aaeh of thaaa systaas la important, of particular intaraat hara ara thoaa systaas that rasuit in convarsion of tha original compound to tha osidissd derivatives. tt is not uneoaaon for tha body to raaet to soma xenbiotic compounds that it normally biotranafoems by ineraaaing its ability to parfora tha biotranaformation function by producing an lncraasa in tha amount of snsymas available. This process, which is eallad induction* of tha enkyma system, affectively makes the body mors capable of bio transforming not only tha com pound that initlstsd tha Induction but also all othar compounds HONS 222038 - 124 - Chat are oxidized by the itat enzymatic system. In this manner it is feasible for a given xenobiotie agent to indue* * bio transformation system that affects th* ability of th* body to biotransform not only th* original compound but also a large numbor of othor xenobiotics as well as aom* naturally existing chemicals within th* body. Shortly, it will b* shown that th* PCBs in general hav* b*n described as being effective, that is, potent inducers of major oxidative biotrensformation sys tems in experimental animals and in th* human, via induction of enzymes, th* concentration of various normally occurring chemicals may be altered. The scientific evidence associated with these subjects will be evelueted in terms of the aveilabl* current literature. _ The major oxidative biotranaformation system in th* body, as far ea xenobiotics are concerned, is present in great est activity in th* liver and ie present in lesser activity in moat other tissues. In experimental studies* the liver gen erally serves as a monitor of drug or chemical effect on th* oxidising enxymes. The ensymes ere located in th* 'microsomal* fraction of the liver cells. This is a fraction of the cell that can be obtained by proper ultracentrifugation techniques. The biotranaformation system of interest is known as the 'microsomal mixed function oxidase system* (MfO). Functionally this system operates to incorporate oxygen into th* xenobiotic agent via a series of ensymatic actions. The system does this by making an 'active* oxygen atom available via a hemeprotein enxyme* This hemeprotein 1s in fact a family of proteins MONS 222039 125 - llectiveiy identified as "cytochrome P-450.* The ability gpthe enxyme to oparate as an oxidative system is dependent ^^eha existence of savaral naturally occurring substances . in particular, on ths axistanca and quantity of available --tachroms P-450 in tha microsomal fraction of tha livar. Microsomal P-450 can bo moaaurad diractly or indiractly 01rtq various subatratoa. Dlract moasuramant of P-430 ia baaad mm aaasuramant of tha protain systam from which thaso ansymas ibtainod thair name, that is. whan tha ansymas ara roducad and fombintd with carbon monox ida thay axhibit, in a apmctrophotomtttr, maximal absorption of light anargy at tha wavolangths of 430 nanomatora, hanea tha nama cytochroma P-430 systam. Tha ^*430 systam can also ba maasurod in tanss of its activity on spscific aubstratos auch as sthylmorphint and antipyrina. Induction of this systam is aaasurad in tanas of an ineroasa in p-430 and/or its activity (based on units of protoin par S'amplo of aicrosomas). Invastigations of ansyma induction have separated tbe P-430 ansymas into two qroups, identified as P-430 and P-440 troupe, on tha basis that various components of tha P-430 group of ansymas ara "induced" to different degrees by different xonoblotic agents. Tbe P-430 ansymas ara those that ara mainly induced by tbe barbiturates, whereas tha P-440 ansymas are mainly induced by 3-metbylcbolenthrene and show maximal absorption at 440 nanometers. The literature includes studies that suggest that the p-440 ansymas as well as the P-430 ensymea are Induced MOMS 222040 by certain PCBs although there appears to ba soma species and tissue specieicity in their inductive properties. Investigations of the effects of PCBs on cytochrome P-450* have centered on two areas of interest. One involved the induction mechanism via the use of either a commercially available sample of a single PCB congener ' iuch as 2,4,S,2',4a, S1-hexachlorobiphenyl) that wss synthetically prepared and could be tagged with a radioactive atom to facilitate analy tical work. Generally, a group of eiperimental animals (rats) was administered the PCB. Samples wers then obtained at vari ous levels. Livers were then examined directly for the quan tity of cytochrome P-430 or indirectly for P-430 and P-44B activity via its ensymatic action on various substrates. The liver may also be esamined histologically and for evidence of : the state of protein synthesis. Induction of the P-4S0 enzymes in the human is estimated by measuring the plasma elimination rate (plasaw half-life) of anfeipyrine in controls as compared to exposed subjects, hntipyrlne is a drug that is completely absorbed when given orally and completely metabolized by the liver p-430 microsomal system. The second eres of interest concerned the ebility of the liver microsomal system to biotrensfons PCI. Of perticuiar Interest mem the nsture of the intermediate and final products of the biotrsnaformation process. This subject ia important in understanding the toxicology of the PCBs because of the follow ing hypothesesi MOWS 222041 - 127 - (a) Certain pCBe indue* th* microsomal mixed fjntion flRdation systems thereby influencing not only their own diabolism but- also the metabolism and time course of action ^-available endogenous hormones as well as other xenobiotics Including drugs) administered to humans. (b> Certain pCBs or contaminants of commercial Reparations of PCBs may lead to the formation of intermediate Boxide type derivatives, and these derivatives can covalently Bid to macromolecules In th* liver thereby leading to hepatic Bxlclty. 2. induction of Liver Enxymes Various studies have reported on the effect of short Bn espoaure of rats to mixtures of chlorinated biphenyls. Qm such study by Ecobichon at el. (1974) used the Aroclore Identified as Aroclor 1014. 1221. 1242. and 1294, and another Btndy by a French investigstor. Narbonne (1910). used a Prench preparation known aa phenoclor OP*, in both studias the sample Mterlel consisted of e mixture of congeners of the chlorinated biphenyls. These studies showed that when rets ware administered 10 ppm of the PCla in thmir diet for only ono day, the'livers from the animals showed induction of F-490, aniline hydroxylase, end aminopyrlne-ii-deeethylam*. the Induction of these enxymes use maximum in about firm days, if the rets were given 10 ppm of the PCBs in tbe diet for eight consecutive days, induction oc curred in throe to five days end to a lesser extent over the remeln- MONS 222042 128 ing eight-day interval. In the Ecobishon study, intraperitoneai injection of the Aroclors in doses of SO rttg/fcg was made for three consecutive days. Animals wars saeriflead 96 hours later. Mixed function oxidative eniymes wars found to be inducad in tha livar. Tha graatast induction was saan with tha mora highly chlorinated Aroclors. Tha conjugation eniyme induction occurrad rapidly on exposure to tha Aroclors, and particularly to those Aroclors that arc mora highly chlori nated. Tha PCBs used in these studies ware coautareial grade. In order to batter understand which of tha P-450 cytochromes are inducad by tha PCBs* Ryan aK ( 1979) treated groups of rats with Aroclor 1254, phenobarbital, or 3-methylcholanthrene. The livers ware used to prepare three different P-450 fractions on the basis of differing molecular weighte and they identified the three fractions as P-450a P-430o and P450c. All thres of the P-450S were obtained from the PCItreated animals. P-430a and P-4S0b were obtained from tha phenobarbital-traatad rats and P-430a and P-450e were isolated from tha 3-methylcholanthrene-treated rats. (P-450e is prob ably equivalent to P-441). Therefore, this study showed that the Aroclor induced at least three identified cytochromes including the type induced by phenobarbital and the type induced by 3-methylcholanthrene. in 1910 Parkinson at al. investigated the validity of the concepts that were current at that time regarding the structure-activity relationship between specific PCB congeners HOMS 222043 -129- |p hepatic enxyme induction. The study was designed to yield Me structure versus activity data. Sasically, they conducted lapariments-in rets using eight synthetic PCS congeners plus phenoflhrbital end methylcholanthrene es enzyme inducers. They con cluded that in order tor a PCB to induce a methylcholanthrenegype or e mixed-type liver enzyme system, the PCS would have gis contain chlorine subetituted at specific positions on the Bwnyl rings, whereas the PCI inducers of the phenotoarbitel |ype had multiple diverse structures that could not readily be Betined. Whether PCSe are administered for as short s time as pee to three days or whether they are administered dally for up to a yesr, various liver ensymes appear to be induced, but the IBsnome non of induction does not seem to be specifically very harmful to the animals. Allen and Abrahamson (1979) fed rats diets containing 100 ppto of Aroclor 1141, 1134, and 1140 for 13, 24, and 31 weeks. The growth rate of these rats was comparable to the controls but the test animals did show liver hypertrophy, some focal cellular degeneration, and an increase in serum lipids. In general, the effects were no greater in those animals that received the diet for a year than in those that received the diet for 11 weeks. Alvareo at si, (1973) published results from eaperiaants that Involved treatment of rats with Aroclor 1134. Intraperltoneal administration of 13 mg/kg/day for six days HOMS 222044 130 produc'd a tripling of cytochrome p-448 content of the livers end e 10-Cold increese in the enzyme ectivity involving benzo(e)pyrene hydroxylation (which is e typicel J-methyleholenthrene type of induction), es well es en increese in ethylmorphme-Hdemethyletion (a typieel phenobarbitcl type of induction). They therefore concluded thet Aroclor 1354 induced e mixture of both P-448 end P-450, In 1977, elveres end Keppee described some edditlonal work that showed the ability of Aroclor 1354 to cross the placental barrier of the rat, to be transmitted to the neonatal ret through the mother's milk, end to cause increases in blotransformat ion enzymes in the fetus end newborn. Goldstein at al. (1971, 1979) attempted to resolve the question of whether pure PCS congeners had enzyme-inducing properties that were different from those produced by commercial preparations of the single congeners or the PCS commercial mix tures (such as Aroclor 1334). These authors synthesized a `pure* sample of 2,4,3,2*,4*,3*-hesachlorobiphenyl and snowed that it had different enzyme induction properties than did the seas commercially obtainable, specially prepared, congener that was reported to be *99% pure.* The difference in the Induction capability of the two preparations was primarily in regard to the induction of P-441 cytochromes in which the synthetically pure isomer, at doses of 330 mg/kg administered to fsaale rats, induced aryl hydrocarbon hydrozylase (AHKi s P-448 enzyme system) only five-foldt whereas the commercial isomer at a does of S0ng/kq produced a 30-fold increase of AMR. Also, a GC-MS analysis MOWS 222045 - 131 - oC the two preparations of hexachlorobiphenyi showed that the commercial preparation contained four contaminants that wars not prasant in tha pura congener. two of thasa contaminants wars idantifiad aa a tn* and a tetrachlorodibantofuran (TCDF). rCDF was than shown to bo a potant inducsr of AHH and cytochroma P-448, Tha ED (offactivo dosa, SOI of tast animals) for TCDF rat Smyrna induction was found to ba 0,5 uq/kq for thraa days, Tharofora, tha conclusion was that avan a 994 pura conqonor that was coouaarcially obtainabla can contain sufficiant dibanzofuran to altar tha enzyme induction action. In ona raport, Alvaros at_ al^ (1977) had studiad altaratlons in druq aatabolisa in both rats and humans. In tha rat study Aroclor 1018 alicltad a bsrbitursta typa of Induction of hapstic onsymas. That Aroclor did not induce cytochroma P-448) however Aroclor 1254 did induce cytochrome P-448. The human study involved five workers in a capaeitor osnufacturinq plant who handled primarily Aroclor 1018. Those exposed workers showed a low half-life (10.8 hours) of antipyrlna as compared to control non-ezposed subjects (who showed a half-life of IS.8 hours). The volume of distribution of the druq in the two qroups was not different, so the com~ parison of the half-lives of the druq in the two qroups is valid. Thus, sniyma induction occurs in the human in response Co occupational exposure to Aroclor 1018 and the induction MOMS 222046 132 as measured by antipyrine metabolism is a P-450 type of induction. In 1915 Bickers at al. reported on the affacta on livar enzymes associated with topical administration of aion oils (aa used m microscopy), Thaaa Limtnion oila were known to contain approximately 301 PCBa. One to 10 microltterj of the oila ware applied daily for aia daya to the shaved backs of rata and tha animals ware sacrificed on the seventh day. The authors found that both akin and livar enzymes ware induced. In a second experiment 10 microliters of the oil were topically administered on one occasion only, and the animals were sacri ficed at various intervals following application of the oil. p-450 and liver monoasygenases were Induced (including benzo* a-pyrene hydrosylase, a P-441 enzyme system) showing maximal effect in two daya with a slow return to normal by 2* days, in this study there must have been very large differences between indivlduala in the control group because their data show very large differences between groups with only a 95* significance. The laawrsion oils currently marketed in the u.s. do not contain PCSs. 3. Metabolites of PCa Shineda and Sato (1910) studied the reactive metabo lites of PCS metabolism. Their work Involved the use of isotops labeled PCS congeners. This work suggaata that PCS epoxides ay be the activated fonts that covalently bind the mecroooie- eules in the liver cells. A haaachloroblphanyl congener HOMS 222047 13 3 - <2,4.5.2'.4',5'-haxaehlorobiphanyl) that haa no adjacent unchiorinata<1 atom* In tha biphenyl rinq and that cannot ba converted to tha apoxXda w* found not to ba covalently bound although accumu lation of this PCB in tha llvar was found to occur. Othar pCBa fho covalant binding that is principally with microsomal protains rathar than tha ribosomal RN*f a conclusion basad on th# finding that various protaasas would solublllza th* radioactivity of tha labalad atom. Treatment of th* animala with phenobarbltal produced 1 Ivors that showed good covalant binding to th* PCS, but treatment of the animals with mathylcholanthrane produced livers with poor pcs binding capability. Th* authors concluded that PCS ape*id*a war* formed by th* monoasygenas* system end these epos Ids* were responsible for th* binding of th* compound to microsomal proteins. Their conclusions are baeed on indirect findings. 4. interactions Based on th* Induction of enzymes by PCS* On* report (Murphy at el.* 1979) described studies that tha authors claimed indicated th* ezlstenc* of a drug interaction In the form of potentiated lethality of fluroxen* In Aroclor pratraated anieela. Til* authors did shew that th* Aroclora Induced hepetlc enzymes* Their method of measuring anzyms induction was to measure the metabolism of warfarin by livsrs of tha Aroclortrsatsd animals according to e procedure that they had developed and that thay claimed could differentiate between Induction of P-4S0 a* compared to P-440. Thoy found that Aroelor 1294 in rata mainly induced cytochrome P-441 where** Aroclor 1240 induced mainly MOMS 222048 cytochrome P-450. The authors than indicated that both Aroclor* cauaad animal* to ahov incraaaad lethality on aubaequent adminiatratlon of fluroxen*. We have difficulty interpreting thia article. We do not believe that the concluaiona are supported by the data that ar* givn. In one case involving Aroclor 1240 the data are not given in the table and in the other case the data obtained following administration of fluroxen* do not appear to be different from the control data. 5, Ensvmea Other Than Cytochromes Affected by PCfla Two additional reports deal with an action cf the Aroclor* on ATPae* activity. On* of th**e report* (Lee and Park. 1979) used cultured huaien Lymphocytes and showed a doeeresponse relation for Aroclor 1254 and inhibition of mitochon drial respiration. Prea> thl* effect they indicated that there may be a decrease in Adenosine triphosphate (ATP) concentration, w* can see no way to evaluate tdiat this report means since the concentration* of the Aroclor used ar* not correlated with concentrations that eight be involved in intact biological syatasw. The ether report {Laftocca and Carlson, 1979) indicat ed that the Aroclor* produced in vitro inhibition of rat magnesiuai ATPas* activity at a concentration of 30 ppn. A wak correlation ves found between increasing inhibition and increaaiog chlorination. A strong correlation wes found between PCS-induced inhibition of the ATPas** and decreasing aqueoue solubility. W* do not know what these results signify HONS 222049 us 9thr chan chat they seem seem to be incidental findings many other chlorinated hydrocarbons do the aame thing, $. Summary and Opinion The available data from experimental studies on animals ana man indicate that the commercially available preparations of the PCBs (Aroclors) as well as some highly purified PCB congeners act to induce some of the hepatic ensymes. Considerable effort has been devoted to determine which of the microsomal ensymes are Induced by the Aroclora. There are some data that indicate that the predominant induction occurs for the p-450 type of cytochromes (identified as a phenobarhltal-type of induction). When experi ments are conducted with the 'more pure* congeners there is very little evidence for induction of any enryme systems other than the P-4S0 cytochromes. In general, induction is greatest with the most highly chlorinated derivatives, but the least chlorinated deriv atives also induce the P-4S0 cytochromes. The subject of whether the 'pure* congeners of the PCBs have less action on the cytochrome systems than the commercial ateriala may be only of academic Interest, since the preparations that are avsilable to industry and the public are the commercial preparations such as the Aroclora. It should be recognised that authors tend to demeribm effects due to PCBs whereas they are usually referring to effects of Aroclora (such as Aroclor 1254), which are mlstures of PCBs plus various trace contaminants. The commerclally-available preparations of the PCBs are capable of inducing certain hepatic ensymes in the rat and there is one report suggesting that occupational exposure to HONS 222050 commercial PCB* may indue* a hepatic enxym*. Thar* ara no data ufgaatin? that th* overall health of th* animal* or man ia in fluenced aa a conaequenc* of PCB-induced mieroaomal ensymea. Althouqh it ia auq9*at*d by aom* people that chan9in9 the meta bolic tranaformat ion capability ia inherently detrimental to the animal, there ia no raal evidence to aupport auch a hypotheaia. when ensymea ara induced and they are then involved in the bioactivatlon of aenobiotic aqenta, auch *nayme induction could be harmful dependinq on the doaaqe sequence and the Inherent toxicoloqic propertiea of any specific aqent. On the other hand, if th* ensymea that are induced are involved in blolnactivatlon of xenobiotie compound*, then induction may be beneficial to the animal aqaln dependin* on the doaaqe aequence and inherent toaicoloqic propertiea of any apeeiflc aqent. There ia no qood ex perimental or clinical evidence that PCI* may act throuqh their ensyme induction capability to affect 'hormone* level* and reault in harmful effect* on th* body. B. PCI ffacta on Immunocompetenc* A few report* appeared prior to 1970 that *u99**t*d Indirectly that PCI* may Influence immunoeoopetenc*. in 1970, VO* and looman allowed that when chick* war* fed 400 ppm PCS for CO day* they showed atrophy of the aplenic pulp and lymphoid neeroel*. (Chick* at hiqher doaea all died durlnq th* teat.) The chick* alao ahowed porphyria and liver necroaia. in 1971, Wo* and Beam* reported that commercial PCI aamplaa applied to HONS 222051 137 the akin of rabbit* daily five timaa weekly (or 38 day* (21 applications each containing 118 mg PCI) produced histologic atrophy of tha cortax of the thymus and a reduction in the mbr of germinal centers in the spleen. At this time the animals showed marked chloracne of the skin, increased (seal coproporphyrin and protoporphyrin, as wall as liver and kidnay daeaga. The authors stated that these effects were strong in. dieators of an immunosuppressive action of the PCI*. In 1977, Loose and co-worker* fed Aroclor 1242 to ice for six weeks. The animals were then lmmunogenically stimulated with sheep red blood cells ss an antigen and the antibody response was measured. The method of measuring anti body activity Involved plaque-cell estimation in the spleen and the measurement of the plasma imounoproteins. Positive findings were obtained as compared to controls and the author* particularly remarked about the reduced IgA levels found in tha PCI-treated animals. It was also noted that clinically subtoxic levels of Aroclor 1242 were profoundly lmmunoeuppresslva. Thasa authors also cite the work of Holler and Thigpen (immunosuppres sion by a PCI to pooudorablem virus in rabbits). Vo* and van Drlel-Grootinhuls (1--unosupresslon by PC! in guine* pigs), and mend and Trainer (increased mortality in ducklings that had bean previously exposed to Aroclor 1254 and then inoculated with duck bopotitis virus). MOHS 2220*2 138 In 1978, Loos* nd co-work*rs studied th* effects of PCBs on ho*t resistance systems. Mice that wars fed diets con taining 167 ppm Aroclor 1342 for three waeks and for six weak* exhibited increased sensitivity to salmonella endotoxin and a decreased survival time to inoculation with malaria. Thus they concluded that host resistance wee impaired by prior treat ment with PC8*. Also in 1978, Thomas and Hindsdill reported on studiei in which they fed monkeys 2.5 to 5.0 ppm PCI (Aroe lor 1248). After six months th* monkey* developed chiorecne, alopecia, and facial edema. After 11 month* control and treated monkeys were tested with antigen* (sheep red blood cell* and tatanua toxoid). Th# only positiv# finding was in tha 5.0 ppm monkeys who showed significantly lowar antisheap rad call antlbodias as c(Spared tor controls. No offset was obtainad regarding tha antibody rasponsa to tatanua toxoid. These authors also fed mice up to 1000 ppm of th* PCS for three to five weeks without evidence of overt toxicity, but thee* animal* did ehow a higher mortality whan challanged with tha pathogen salmonella tvPhlmurlum a* compered with tha controls* In 1980, Oiahi and Hlraga reportad on thair studio# in which they had given mice KIs (commercial product) by oral intu bation oaoo weakly for four wasks. othar groups of nlca wars fed COr (chlorinated dibonsofuren) or COO (chlorinated dibenso-p-dioaln). Only th* group* of animals that had received 10 or 100 HONS 222053 - 139 pgAg cor ahowad decreased thymus weiqhts. All groups war* ph* Hanged with endotoxin and aqain only tha CDP-pretreated pniaala ahowad incraaaad lathality coopered with tha controls, jt It notaworthy that tha authors found no daatha In thalr con trol anil**la qlvan andotoain, a finding chat raiags doubt about Chair experimental daaign. in thla atudy tha PCS pratraatad aniaala did not ahow incraaaad auscaptibility to endotoxin. in tha same year (1980) imaniahi at al. ahowad that mica fad PCBa for 21 daya at 100, 200, or 400 ug/gm wara aiqnificantly mora auacaptlbla to harpaa aiaplax virus and alactroaalia virus khan wara aniagls fad a pCB-fraa diat. In 1981, Chang at aH raportad on tha iaaunologlc evaluation of patiants from Taiwan who davsiopad an acna-lika kin diaaasa, toraad Yu-Chang disaasa, that was ralatad to tha oonsuaption of riea-bran oil contaainatad with PCBs, PCOrs, and PCOs (in an aeeidant vary slailar to Yuaho). Tha authors had 30 sueh patiants who showad avaraga whola blood PCI lavals of 49 ppb, with a ranga of 19 to 98 ppb, plus an additional control group of 23 haalthy parsons aatchad according to aga and sax who showad no datactabla lavals of PCI in thair blood. Tha patiants had dacraaaad concentrations of IgA and lqn lamina globulin but not igO. Thalr study of subpopulatlona of lymphocytas showad that tha paraantaga of B calls was not affactad by tha disaaoo hot tha parcantaga of sooa spacias of T calls was dacraaaad as coopared to tha controls. HONS ZZZ054 140 Environmental chemical affects on immunocompetence have been extensively reviewed by Faith, Luatar, and Voa (1980). A number of studies cited by them found PCSa to be imnunoluppreaaive in various species (from ducklings and chicks to mice and monkeys), in some cases at dose levels that produce little affeet other than hepatocyte hypertrophy. Only one study (Street and Sharma, 1975), which involved feeding low levels (0.18 to 6.5 mg/Vg/day) of Aroclor 1254 to rabbits, showed no significant effect on humoral or cell mediated re sponse our review of the Street and Sharma report indicated that there was a dose-related trend toward immunosuppression in their animals end at the higher doses (2.1 and 6,5 mg/Vg/day) for four to eight weeks the animals showed significant increase in liver weight. Tits Faith, Luatar, and Voe review lists several general factors (nutritional statue, hormonal levels, and amounts of iswinoregulatory proteins such as alpha-fetoprotein) that influence immune function. Therefore those studies in which immune function wee studied following exposure to levels of the FCls that resulted in overt toxicity are meaningless from an immmotoxlcologlc viewpoint. In contrast, immunosuppression at dosage levels that do not produce general toxicity would be significant. lysrv and opinion The overall eoncluaion that can ba reached in regard to the studies on the effects of FCe on ixwinocompetance isi HONS 222055 with exposure condition* that lead to general toxicity, fepunoaupprejsion nay be demonstrable, but it may be indirectly ^duced; <21 with experimental conditiona wherein only subclimcal fexicity is observed, such as hepatocyte hypertrophy, there is the feasibility that immunosuppression is also produced> and (3) under fllll lower PCS exposure conditions it is impossible that lamunoIpppresaion is involved, perhaps the best study to estimate a noIffect dose for exposure to PCSe would be the Thomas and Hindsdili fl97t) study which suggests that six months' exposure to between |2S and S ppm of PCIs in the daily diet of monkeys is a threshold rbr effects on the immune system. Unfortunately, there are few data lireetly concerned with the dose-response relationship for effects th* PCts on the lnmune system In animal models or tho human. C. porphyria Th* administration of PCSs to rats will produce a delayed type of porphyria, l.t., deposition of porphyrin* and their degra dation products in tlaauea and excreta. Although th* mechanism of action of th* PCS* is unknown, it apparently differs from that of othsr porphyrogenlc compounds such as hexachlorobansen* or isopropylaeetamide. It has boon thought that tha effect of peas in animals may indicate that theme rospounds can induce conditiona such as porphyria cutmmma tarda in man, but clinical data have not shown this to occur in PCa-exposed workers. t1) experimental pats. The fecal content of coproporpbyrln and protoporphyrin of rabbits was increased by Aroclor 12SQ HONS 222056 142 and by hexachlorobiphenyl, but the difference was statisti cally significant only for coproporphyrin (Voa et al., l72b]. Bruckner at aK (1974) obaarvad an incraaaad excretion of uri nary coproporphyrin in rata given Aroclor 1242. S or 25 ppm for two, four, and six months. Goldstein at al. (1974) emphasised the delayed onsst of the PCB-induced porphyriaj rata fad 100 ppm of Aroclor 1254 became porphyric after two or seven months of treatment. Although the excretion of coproporphyrin and other porphyrins was increased, the largest elevation was in the uroporphyrin fraction. There was also a marked accumulation of uroporphyrin in the liver. The studies of Goldstein at al_. suggest that PCBe may effect uroporphyrin formation or utilisation. The r induction of delta-amlnolevullnlc synthetase (ALA synthetase, a rate-limiting ensyme In heme synthesis) does not appear to be the mechanism by which porphyria Is induced by PCI, as it is for many porphyrogenlc chemicals. In their studies the in crease in ALA synthetase activity was probably secondary to the porphyria. Also, Aroclor acts to increase liver cytochrome P-450 rather than to decrease it. Sesachlorohensene is known to Induce a delayed type of hepatic porphyria similar to that produced by Aroclor 1254. However, the two responses apparently differ signifi cantly as Goldstein et al. reported that the rats fed PCBs did not exhibit the nervous or cutaneous eigne associated with hexachlorobensene poisoning. HONS 222057 143 (ll) Clinical Studies. Son* of the yuaho patients ingesting rica oil contaminated with PCBs reported pigmentation of tha akin and naiia, but there were no atudiea to evaluate a poaaible relationahip of the reported symptoms to any change in porphyrin metabolism (Kuratsune, 1972). Smith at (1981 a,b,e) determined urinary coproporphyrin. uroporphyrin and porphobilinogen in PCB-exposed workers; they did not find a correlation between the urinary porphyrins and the serum level of the lower chlorinated PCBa or the higher chlorinated PCBs. The subjects did not have any recognisable dysfunction and there was no elinieally apparent Illness with high levels of PCB exposure or with high serum PCB. Other investigations evaluating the health effects of PCB exposure have not reported eases of porphyrin-related disease or casee of porphyrin cutanea tarda (Fischbein at al. 1979* Maroni et al., 1991). The observation that PCBs increase ALA synthetase in aniaals raises the possibility that PCBs can cause an attack of porphyria in patients suffering from acuta, intermittent porphyria. Bowever, a ease of this type has not been reported in the aedlcal literature. As noted above in studies on the rat, the action of PCBs appears to differ from that of other porphyric agents. MOMS 222058 14$ XII. Epidemiology Although caae reports of toxic effects. especially afcm lesions related to exposure to chlorinated organic chemicals, have bean recorded almoet from the beginning of their use tVones and Aldan, 1936) few epidemiological studies appeared Until the accidental axpoaura of a large Japanese population eo Kla, PCOPa, and PCQa from the contamination of rice oil. Since that time, numeroua studies have been undertaken to determine the health effects related to exposure to PCBs in the workplace Snd general environment. It must be remembered that there were problems In these studies In assessing the effects because some of the environmental exposures may have Involved PCBs that had been altered by processing at high temperatures (Brown, J.P., Jr. bfcal., 19S1). The niabers of Individuals exposed occupationally are relatively small, although some may represent the heaviest and most protracted exposures of any reported, and their added burden of PCBs from the workplace must be compared to the back ground levels that are currently preaent in all populations. Many of the commonest changes noted In biochemical and other medical measurements obtained in screening surveys have not yet been associated with any subsequent development of disease. la order to evaluate the epidemiological studies that assessed the effects of PCBs, we will discuss the results of Mortality data, morbidity data, and screening surveys separately even though many studies include data on several outcomes. MONS 222059 146 A. Mortality Studies in 1968i an unknown number of parsons in tha wsstarn part of Japan ingested riea oil containing Kaneehlor 400 that was contain mat ad with polycnlor inatad dibenzofurana (PCOFa) in amounts 250 tinea mors than tha usual levels in japsnssa pCBa (IAAC, 1978) and mors than 1000 times tha usual lavals in u.S. Aroclors. By 1977, 1665 eaaas of *Yusho* had baan recognized basad on symptoms of ocular dlsturbaneas, skin lasiona, pri marily subjective neurological symptoma and blood PCS lavals (urabe, 1979). Fifty-one daaths hava occurrad in thaaa patlanta and tha cauaaa hava basn raportad to includa 1ivar cancars and lyaphomas. However, thara hava baan no rsports on tha numbers of axpactad daaths by specific causes baaad on tna usual death ratss In similar Japanese populations. Tha distri bution of eausas say simply represent tha usual distribution of daaths found in the age groups characteristic of Yusho patients, and so it Is impossible to assess tha aortality patterns of these cases at tha present ties. arteis1 at aK (1981) hava reported a study of 1,310 workers, predominantly women, who, beginning In 1946, initially ware exposed to Aroclor 1254 and Pyralene 1476 end subsequently were exposed to mixtures with 42% chlorine content. Mortality dete were collected on all individuals with six months or more of employment over a 23-year period ending in 1978, The total num ber of daaths (27) was msall but thara was an excess of mortality NOUS 222060 147 In female workers compared to the general population, which is un usual for any working group. This study demonstrates a signifi cant excess for all neoplasms for the combined sexes and an excess specifically of lymphomas. it is difficult to interpret these Seta since the type of cancer incriminated seems to differ from that of other studies. Further, the data of Brown and Jones <1981) ("see below, and also the compilation in Table 8, section viln on porkers in two manufacturing plants do not confirm a finding of scess malignancies in PC8-eaposed personnel. The unusual two fold excess in mortality of female workers in the Bertaaai et al. study deserves further attention. A retrospective cohort mortality etudy of 3,587 workers in two electrical capacitor manufacturing plants that had used PCBs for over 30 years, identified 183 deaths (Brown and Jones, 1M1), The type of PCBs used over the years had varied and in clude Aroclors 1354, 1343, and 1018. The overall mortality and total cancer mortality were low, but there were three-fold ex cesses of cancers of both the rectum and the liver (with a total of seven deaths) although the results were not statistically signi ficant. The only significant excess was that of the subset of rectal cancers in femalsa in Plant 3, The standardised mortality ratios (SNfta) for rectal cancer, liver cancer, or cirrhosis did not Increase with increasing latency or duration of employment. Unless one can denonstrats that the risk of cancer increases in association with increasing duration of employment, which serves MONS 222061 148 as a proxy measure of dost, it is difficult to suggest that tha agent is possibly causativa for the diaaaaa. Although this study has dsvotsd stnet attention to details such as tha completeness of identification of workers and ascertainment of outcome it has not verified the diagnosis of cases nor investigated the presence of confounding vari ables. Rectal cancers are often misclaesified by location in the intestinal tract. The claaeification 'liver cancers* may include cancers of the gall bladder and biliary system as well as metastatic lesions to the liver froai cancers at other sites. Therefore when one has an excess of liver cancers, verification of specific site within the liver system as well as identifi cation of primary liver lesions is extreawly important, espe cially since the number of desthe from this cause is smell. The investigators have not verified the diagnosis of either liver or rectal cencere. Since alcohol is considered a fre quent etiologiesl agent for cirrhosis of the liver and possibly for liver cancer, eome information on consumption would be relevant as s confounding variable, no data on possible con founding variables have been reported in the paper. TIM mortality data from the occupational groups and the Yusho patients are baaed on very ssmII numbers of deaths and at present do not confirm a carcinogenic effect in nan. The observation of excess liver cancer deathe in workers occu pationally exposed to PCBs is of major interest sines the liver MONS 222062 149 vta a target site for changes in miiali and tinea nan has demonstrated avidsnes of aubclimcal al carat ions in liver junction, if livar eanears ara to ba evaluated, the diagnosis of. primary cancers of the hepatic cells must be confirmed n the mortality studies since the number of cancers in the group will be vary small. The available data demonstrate no consistency in the cancer mortality patterns in the studies and no data on a possible relationship of cancers to dose pf PC8s. t. Morbidity or Incidence Data Shin Skin lesions have been reported in association with sposure to chlorinated aromatic compounds since the early 1900's (Jones and Alden, 193d)* Taylor has emphasised that acneform eruptions are more frequent with the chloronaphthalenes and the dibensofurans and that the variation in the quantity of these sub stances that may be present as contaminants in PCBs nay account for differsnees in reporting of akin eruptions with eiposures. Taylor has also reported that the acnegenic capacity of various compounds changed according to their form (ftasi> liquid, or solid) and the degree of chlorination (Taylor, 1979). These factors may also influence the presence of reported skin disorders in studies. Met only the frequency but the characteristics of skin lesions hawe differed in the various studies. Jones and klden's arly description of tbe lesions they associated with chlorinated biphenyls included `blackheads* or 'carbon-colored* comedones MONS 222063 - 150 - soaatimas diatnbutad in unusual araas of tha body and offtan associated with cyitic araaa and yallow pus (Jonas and Aldan, 1936). Taylor noted that tha cystic swelling and hyperseere- eion of tha meibomian glands ara important charactariatica of tha chloracnagenic affaet of pCls comparad to othar similar chamicala. Thasa wars tha typical lasions raportad By neigs at al. in aavan of 14 workers aapoasd to a pcs vapor leak from a haat exchanger in a plant In Connactleut (neigs at al., 1954). Tha exposure to vapors was intarmittant but of extendad duration. Liver function tasts wara normal in moat of thasa workers and no PCI lavals in individuals wars obtainad, although an air sample prior to tha onsat of skin disaaaa was 100 ug par m^, which was within tho accaptad standards. Tha pstiants who war* initially dsscrlbod with Yusho disaasa had lasions similar to that daacribad abova in about 334 and a brownish pigmentation of tha skin and nails in 10% of pstiants. Thasa frsqusnclss wars incraasad aubaaquantly to includa about 70 to IS% of pstiants bacausa of naw dafinitions of charactaristlcs of disaaso or dalayad development of tha signs. Tha ayaa wars also involved. exhibiting swallinq of tha uppar lids, hyparamia of tha conjunctiva and aya discharge (kuratsune, 1073). Pigmentation of tha akin and aya discharges also occurrad in nawboms of affsctad mothars. no comparison groups hava baan inoiudad in thasa studlas of Yusho pstiants. Whara tha lasions ars pathognomic of pct-relatsd disaasa this may not ba nacassary MOHS 22206% - 151 - }yt when the lesions ars more general, comparison groups ars fcsential. There ware histopatholoqical changes in five patients utopsied mat saem to be associated with contaminated rice oil B^eation. These changes included hyperkeratosis of hair follicles Uml increased melanin pigment in the basal layer of the epidermis kJUlC, 1970. Three out of the five cases also had proliferation mt ductal epithelium of esophageal glands, it would have been mlpful if these pathological assessments had been made blindly a that qualitative judgments such as "increased melanin" eould have been compared in exposed and non-exposed groups. Correlating Chase pathological findings with changing levels of PCls, peers, Cad PCQs would also have been helpful but there are no reported eta relating to these issues in the papers available, it is Cairn that the amount of used Kanechlor in the rice oil consumed By the patients was between 0.5 and 3.0 g, which would indicate a pci exposure similar to levels in occupational settings. Kara et al. in two separate papers (1974. 1975) have described the skin lesions in workers in a capacitor factory where Kanechlor had been used. The serum PCM of all workers ranged from 7 to 300 ppb but it is not known how these values serrelated with the presence of skin lesions (Mrs et al,, 1974) era et al., 1975). Discontinuance of the exposure not only decreased the overall PCI level to 759 of the original value hut the skin lesions disappeared to "veetigial markings on a few individuals* The summary of the report does not indicate MONS 222065 the correlation of the blood PC and skin lesions although there are data in this paper on the half-life of PCls in relation to duration of exposure. Hasegawa has reviewed the health of workers in five plants whose industrial process Included exposure to Kaneehlor {Hasegawa at a^. , 1972). The industries included capacitor manufacture, PCI Manufacture, and biphenyl recovery. The vapor concentrations ranged from 13 to 9<S ug/s3. Skin lesions ware reported to be unrelated to blood PCls but generally related to direct skin contact. The average blood PCS level was 370 ppb. The principal dermal findings included brown chroaodermatosis of the dorsal joints of hands, fingers and nail beds and acne. There were no further descriptions of the latter lesions so that the presence of chloracne could not be confirmed, but the brown skin discoloration certainly is typical of the Japanese worker reports. Xltamura et al. described 13 workers from an electri cal capacitor aanufacturlng plant (Kitamura et al., 1973). The lesions in 10 of the workers described in this group are even more vague. They did not include the typical coloration of nails) chloracne was not directly diagnosed) and the follicular lesions did not ooour at points of contact with PCls. Proa the description of the study it is not clear that the author's conclusions that the skin lesions were due to PCBs was justified without further Information on the usual frequency of similar types of skin lesions in normal populations or a description of typical chloracne. The blood PCI level in this group was a20 ppb average. MOWS 222066 153 I nous et 1_. studied the health of workers who wore Imposed to Kanechlor 500 in a thread-glossing factory < moue at jkl., 1975). Tha frequency of akin laaiona waa low. The blood fCia ware over 50 ppb in seven out of 54 individuals atudiad. OBa paraon had rapraaantativa chloracna with blood PCSs of 190-210 pb. Ouw a al_. described one caaa of chloracna anong 34 worKara exposed to Aroclor 1243 In capacitor manufacture (Ouw gt al., 1976). The average blood PCS waa 400 ppb. In addition Cive workers cooplalned of ecieaatous rash but there was no de scription of lesions. Seven out of IS process workers and six Sut of 19 lepregnation rooe workers coaplained of burning and irritation of the eyas. face, and skin. It is difficult to raconolle these coaplaints with level of exposure alnee it should have Seen higher in the latter group of workers than the former. How ever, Aroclor concentrations in air as high as 2220 ug/e3 were oeasured. The investigators indicated that the "dermatological complaints* occur more often among workers with highar 'blood Aroclor levels" but they also indicate there is no clear corre lation. it is difficult to be sure of the true evening of dermatitis as elicited by history when the answers can be biased and the authors do not indicate which cases are related to physi cal findings only. As part of a health haxard evaluation at a facility that manufactured electrical distribution equipment* nlOSS studied the MONS 222067 1S4 - health of eight workers and found no symptoms or physical aicjns of chloracne (NIOSH, 1977). There were several subjects who reported skin rashes but not those typiesl of PCB exposure. The mean PCB level in blood wse 98 ppb with the highest vein* being 286 ppb. Another health haiard evaluation was done after an Ac cidental spill of PCBs (NIOSH, 19B0) In this situation there were no signs of chloracne. However, the mesn blood PCB level of exposed workers was only 6.4 ppoj this was below the mean for unexpoaed workers. Humphrey studied the PCB level of indi viduals on the basis of fish consumption (Humphrey, 1975). He found that the PCB level was correlated with fish consumption with mean blood levels ranging from 46 ppb to 82 ppb and a masimum individual level of 366 ppb. There were no skin lesions or other health problems associated with PCBs. A medical and biochemical survey was made of 120 male workers esposed to PCBs in the maintenance of railroad cars and locomotives (Chase at al., 19B1). Among the esposed group of If workers the 'medical histories and physical findings* revealed 'several cases of chloracne* -- 'with none being found in the other groupe.* No further details are given as to whether the conditions were currently active, nor was there a description of the lesions. It would be of interest to confirm these cases am true chloracne since the current mean plasma PCB level in the esposed group is only 33.4 ppb (range 10-312 ppb), a very low level of PCBs to be associated with chloracne. HOMS 222068 1SS - Flachbein e id. (1979) completed a medical aurvey of Capacitor manufacturing workers who were self-selected for physi cal and bio-chemical axaminationa. A high proportion (45-SS*) of Doth male end female worker! complained of akin disorders with III giving a history of acne beginning after the onset of expo sure. 'Dermatologic findings* ware present on physical examina tion in jf to 41% of female and male workers, respectively, owever, these lesions included 'erythema, swelling, dryness, and thicksning,* which would not be lesions characteristic of K1 exposure. Five percent of the study population tied acne fora eruptions. There is no mention of whether these were typical Of chloracne or were the usual acne lesions found in any eedical survey. Since skin lesions are common In the general population and since the population was self-selected initially it is diffi cult to evaluate these findings. The average lower sea hcmologues in plasma wore 124 ppb and of higher pcae, 4 ppb. The authors report that the skin findings were correlated with plasma (f-scas. Unfortunately, if the examinations were done with the observer knowing the job held by the participant, all results can be biased, since reporting sight be related to the job held and the PCI levels were related to job. There was no note of skin hyper pigmentation but 1st of workers had eye abnormalities including 'injected conjunctiva and palpebral hyperpigmentation and edema.* Again, it is not clear how frequently these leelone would heve keen reported in normal subjects had examinations been done without knowledge of exposure categories. MONS 222069 156 Maroni ejt al. (1961) recently reported on two groups 0( workers who wore exposed to PCBs in the manufacture of capacitors on* group (A) hed been exposed to both 54t end 42% chlorinated biphenyls. Although the levels of the trlchlorineted chemical were similar in current employees in the two plants (121 ppb uj and 137 ppb (S)), the levels of pentachiorinated agent differed (249 ppb (A) and 68 ppb (8)). it is of intereet that 10 cases of acne and folliculitis appeared in the two plants and at least four were entirely typical of the condition. All four typical cases occurred in nine eaployees who had worked m a high power capacitor impregnation area of Plant A where levels of pentachiorinated biphenyls were high. Their mean blood PCI was 450 ppb, a value not different from that of the five un affected workers but certainly higher than the overall levels in the two plants, naroni et el. also noted two cases of bleeding hemangiomas, but one had existed from birth and the only difference in his condition wss that bleeding had taken place after the Job startad and the lesion was excised. The other patient had bleeding from the tongue and a cavernous hemangioma was discovered as well as chronic myelocytic leukemia. Case reports such as this and particularly the unusual circum stances surrounding multiple conditions in one patient in the second case make such findings difficult to interpret. The re ports of chloracne appear valid and suggest a problem. taker et al. examined sludge users, workers in a ca pacitor plant, workers' families, and community non-sludge user* HONS 222070 157 - taker at al. * 1910). Since Che sludge contained pci*, it we* It that ice use as fertiliser might seriously affect the PCB svel m the blood. Ths level of Aroclor 1242 ranged froa 7.2 o 49.4 ppo and for Aroclor 1254 froa 10.1 to 24.5 ppb, with he lowest levels being found m sludge users and the highest avals in workers. No cases of ehloracne or other syaptoas of toaiciey were noted but only two PCI values were above 200 ppb. Saith at al. examined workers involved in the maintenance, repair, and overhaul of electrical tranaformers and measured levels of PCIa by job (Saith at al.. 1911). The aean serua levels of L-PCM in the municipal utility workers wars ll to 3* ppb with a aaxiaua of 59 ppb. and of H-PCBs of 1 to 24 ppb with a aaxiaua of 74 ppb. In the privately-owned facility workera had siallar value* with 1^PCB level* between 19 to 22 ppb with a aaxiaua of 52 ppb. and B-PCI level* between 4 and 31 ppb with a aaxiaua of 250 ppb. There was no significant difference in either place in the frequency of akin lesion* between those with less than 10 ppb and those with greater than 10 ppb n-PCBs. There was a significant excess of ayaptoa* of ay* irritation in on* and a history of bronchitis and loss of aasll in the other aaong those with serua levels of I-PCI* greater than or equal to io ppb coopered to less than 10 ppb. however, sine* these are subjective measures of disease and sine* workers aay have been influenced to report subjective ayaptoas differently depending on job it is iapossibl* to evaluate the iaportance of these observations. HONS 222071 Smith t al. reported on the physical findings and symptoms in 197 workers who manufactured electrical equipnent. The serum levels of L-PCSS in the workers varied by Joo. with the geometric means ranging froa 89 to 502 ppb, the highest levels (2400 to 2330 ppb) being found in the department where capacitors ware processed, finished, and tested, and in a department that had assigned work throughout the plant. The geometric mean level of H-PCBs ranged from 22 to SI ppb, with the highest values (150 to 250 ppb) In these departments. This plant had always used 42% chlorinated biphenyls, both Aroclor 1242 and 1018. Although there were some symptom* of skin and eye lesions (darkening of akin and nails, skin rash, and irri tated eyes) that appeared to be different between the groups with L-PCB 200 ppb greater than or equal to 200 ppb compared to thoee with lower values, these differences disappeared when the comparisons were corrected for age and Job. Thus one can conclude that symptoms were primarily related to age and Job with the latter association being either real or biased. The symptoms were not related to the body burden of PCBs indepen dent of job. Ho evidence of skin lesions suggestive of chloracne was found on physical examination, in spite of same extraordinarily high PCB blood lavmls. In a preliminary report. Bahn (1975) indicatad the incidence of cancer in 54 enployeea exposed to Aroclor 1254 in a research and development laboratory and 55 refinery workers HONS 222072 - 159 - ftlth * similar exposure from the seae area. The investigator Reported a significant axcasa in the incidence of melanoma of Ithe akin as well as pancreatic cancer based on expected cancer yttsa from the Third National Cancer Survey, in a subsequent letter to the New England Journal of Medicine, Bahn et al. have reported only on the excess of melanoma (Bahn et_ al.. 1970. Mien Lawrence criticised the study on the basis of the fact that individuals could have been exposed to aultiple chemicals In the laboratory environaent (Lawrence, 1977), Bahn and col leagues suggested that the reason for emphasising the melanoma fish was the biological plausibility of such an association whereas an excess risk of pancrestic cancers could have indiested an association with aultiple chemicals (Bahn et al., 1977). The investigators themselves have discussed several of. the flaws of this study. Information on true exposure is lialted and perhaps sore Importantly one-fourth of the exposed vorkere had to be omitted. The author has also suggested that she underestiaated the death ratio by including individuals during their early years of eaployment when there had not been a sufficiently loag latency from the time of first exposure of KB to the expected time of cancer development. There are other problems with this study related to the identification of easos in the exposed population and the comparability of ease ascertainment in the Third Rational cancer Burvey date. Apparently the investigators identified cases HONS 222073 - 160 - without attempting to validate tha accuracy of diagnosis, pancreatic cancer it very difficult to recognize and diagnose. The diagnose* of the two cans need to be validated from hospi. tai records in order to make them comparable to data from the survey. 5km cancers such as melanomas may be diagnosed in doctors' offices. Thus. the lesions could be missed in the cancer survey data where records were obtained primarily from hospitals but identified in populations with routine medical care. It would be necessary to vslidate the cases in this study through the use of hospital and pathology records and then to compare these cases to a comparable group of employed individuals who have had active medleal surveillance by physi cians. In summary# the data on skin lesion* in relation to PCI exposures have indicated a remarkable consistency, individ uals who have a body burden indicated by a blood level of 200 or more ppb PCIa have an increased risk of chloracne. There is little evidence of risk below this level and those studies that do suggest a risk at lower levels usually do not have a compari son group or they have not collected the data in a manner such that bias might be avoided. The data also suggest that typical skin leaiona nay occur more frequently in workers exposed to PCIs that have been heated and to PCS* that have 54% or more chlorination, since the skin lesiona occur more frequently after heating# it is possible that chloracne is actually due MONS 222074 - 161 - to som alteration or contamination of the PCBs with non Icnegenic materials such as dibenzofurans, as found in tha susno incidant. Symptoms of chloracna art reported frequently won? those who use Kanechlor; this could be related to level |f exposure or its high level of PCDPs relative to pels, such possibility could not be evaluated with the information m these papers. The relationship to direct skin exposure could |1so not be evaluated. C. Biochemical Changes and Liver function Extensive studies of liver function have been included among the recent papers on PCM. Som of these are summarised in Sable 9. The early study of Meigs at al. involving a PCI leak Srom a heat exchanger indicated that there were no abnormalitlea la seven workers with chloracna except for some transient changes in liver function teats in one worker (Meigs at al., 1954). These Changes could not be definitely attributed to PCM. The study of Raaegawa at al. of 99 workers in six indus trial plants in Japan indicated that increases could occur in ensymes such as SOOT. SOFT and decreases in blood cholinesterase (Msegawa it il.( 1973). The authors regarded the changes in liver function as mild and not clinically significant, titamura il, (1973) indicated that in the 13 capacitor workers the hepatic function testa were normal. HONS 222075 SlH*7 He. Subject! Hettfaea at a).,, M 1*77 Table btacbeatca) Smilei '7 tanaet eat liver Ficnaa *verefa Date ebb SCOT Carraletlaa r alevatiea wttb Mm SCbT CCTb tt UK llltrMX Tat. 17b * H.T. b.T. H.T. a.T milt cHoliMitart.* lita^a at il .1) 1*7) Qua at al., 117* 7 HI OSH 1*77 7 Fiichtele at aLJ71 1171 Tat. m Tat. *M Tat. . l* 174 MM haaatlc fKttaa tattt aeraal a.T. a.T. a.T, a.T. a.T. a.T. bats. Haas. a.T. feta. a.T. tturm. IwrM I lM mmI 7.71 7.71 l.tl I.7S 7.SI R atar at a)., 1Mb at Slutfe Tat. atart lb iaitan It earbar Tea. 77 Caaaaiitr Hi Carre la tlaai tu bCb |7, Ob.) 7t,l IM.il Maaa 11.* IU.I) 14.4 07.b) Maaa naaa Haaa Haaa after earrettlea al cabal toreai at al., !M1 bb Liver aaaara. 14 Liver none. 44 ia 711 HI Mb Tat. 414 la *7 HI IT* Tat. 7* 7 ? ' SOI alee. Mara. 7 bealtlva attaclatlaa abaanal liver flablaft a4 Kbt T Haaa Hera. iv iaiirai la S7 paretot Ha caavariiea treat- He cerrvc 11 on coafauMiea >ar Tablet 4aet)rfM itb aea-brinaert be atbar variable controlitu m-tCb met la aaalriit Hatataaatalr Ml Sifal 11cast 11 miner fCti ia liver catat HONS 222076 TAHU (coatimMtl Hiochaaical ftudiaa of lot*-- nd Liaac function (continued! Study M. fekjKU *ri|i On* ** MOI ClWM ( !., IN IMI Tat. (aamt T aawt M.44 d#-m) II. 4 (M-*7) PM. Salt* at *)., I** Lo 4-MI M/al Mm (Ml **) HI n-t Mi. Salt* at at., llk 47 Aufe.la HI 44 Aria, ta HI II-J4 a^al 4-14 If.*) ag/al 4-11 mm Mm Am. IhmIiiII Salt* at a!.. I 1 I MM Sattk at at., IMIc *14 La HI 47 Am*.la HI 44 Arl*. la Ml Mm Am. Mat Am. Kraut at 1., 4M 17 .* atcraa./l H.T. ().* 1*7. ) Carralattaa or alaaatlan (t* am MAT IA U LIH III India Mm Mm mm Mm mm MM MM Mm tat Mat Mm Am. mm Mm Mm Nii Am. Mat Mm Mm mm mm mm Mm Mat mm Mm Mm Mm Mm Mm Mm Mm Mm Mm Mm Mm Mm Mm Mm Mm Mm Nil H.T. H.T. MM Carrot tad Tar Of Hat atlar riu factor t alcaaal CaraaUtlaa lac luaa carractiaai Analytu aack AC4 laMMHMnt af atkar HONS 222077 164 Ouv a_t ol. taatad the liver function of capacitor workara through tha uaa of biochemical markera and found tha ovarall taat data for tha group to ba normal (Ouv at al., 1976), Tha BSP livar function taat waa eonductad only on individuala with blood PCBa above 500 ppbi four out of aavan workara wara abova normal lavala. but It ia not claar whether thaaa valuaa wara abova tha range of arror of tha taat or whathar thara wara othar factora that might have lnfluancad tha reaulta. It ia mdicatad that tha blood KB laval and tha BSP taat do not corralata. NIOSH (1977) avaluatad tha livar function of aavan of aight workara axpoaad to KBa in tha aanufactura of alactrlcal iqulpiant. Tha lavala of SCOT, 3GPT, alkaline phoaphataae. and total bilirubin war# normal in a group of aavan workara with a mean PCS laval of 99 ppb. riachbein at al. (1979) examined a group of 321 work ara from two capacitor manufacturing planta. Tha workara had moan lavala of L-KBa of 124 ppb and n-KBa of 49 ppb. k aaall proportion of tha workara had abnoraalitiaa in tha biochemical toata. Two percent had abnormally high lavala of SCOT. 79 high lavala of S09V, 2% high lavala of CCTP, 19 high lavala of alka line phoapbataae, and 29 high lavala of LOI. However, thara wara no abnormally high lavala of bilirubin. Tha reaulta of thia atudy hava not been corrected for important confounding variablea euch HONS 222078 165 as ago, alcohol intake, and other diaaaaaa currently or m the paat (e.. hepatitis) tnat may influence theae findings. There la no unexposed group for coapariion. The investigators have not preaented data correlating increasing onayme levels to in creasing PCS levels, which would be an appropriate method of presenting the relationship between two variables that are con tinuous. The study does include a comparison of the data di chotomized by two levels of SCOT, loss than SO and greater than SO i.u. and two levels of both lower and higher homologuoa of PCBs. Those data indicated significant differencea between toe proportion of Individuals with high and normal SCOT levels for l-PCSs greater than 73 ppb compared to lower levela and for i^PCIa greater than 200 ppb compared to lower levels* It ia not clear whether these PCS levels were selected after examining the data, in which case the concluslona would be questionable. The If individuals involved in a PCS spill (MOSS, 1910) had normal liver function testa that included total bili rubin, transaminase, alkaline phosphatase, and lactic dehydroge nase. The triglyceride changes could not be evaluated by the investigators because of inappropriate test procedures. Choles terol levels were normal. This group had very low blood PCS levela of f.4 ppb as a mean value, a level lower than that of non-expomad groups. laker at al. (1990) studied PCI levels in users of PCI-contaminated sludge as a fertiliser compared to workera in HONS 222079 - 166 KB-usin9 facility, their Camillas, and non-sludge uaars in ttia community. The PCB laval variad from 17,4 to 75.1 ppb m the four groups with tha lowest laval being found In tha sludge uaars. Thara were no signs of changing lavala of SCOT, SGPT, alkaline phosphatasa, LDH, or bilirubin in ralation to blood PCBs in drinkers and non-drlnkars of alcohol. Tha GCTP laval corralatad with PCB laval in tha total population but, whan alcohol consuaiars wara removed, tha correlation disappeared. Karoni ejt al. (1911) studied liver abnormalities in 80 workers from a capacitor manufacturing and tasting plant. Siitean workers (20%) had aaymptoaiatic liver abnormalities. Over 10% of these had enlarged livers. Among this group tha moat frequent ensyme elevations were the gamma glutamyl transpeptldase (GCTP) in half the cases, the transaminases in 44% and the ornitbin-carbamoyl-tranaferase (50CT) in ]|% of cases with enlarged livers. The mean L-KB level was significantly higher in workers with abnormal liver findings compared to con trols (213 to 92 ppb), mean S-KB level was significantly higher (JOB to 17% ppb), and total mean PCB level was significantly higher (324 to 29% ppb). The levels o% KBs in these workers are high compared to values from many of the exposures reeantly reported. It is interesting that the authors report that al though there is an association between liver disease and PCBs there was no such association for chloracne, but the number of cases was smaller for the latter parameter. HONS 222080 167 Chase et el. (1981) (ittintd the rum PCS lvla and the biochemical markers of liver and lipid activity in 120 maintnanc workers who had had varying exposures to PCBa in their work. Plaama PCBa war* correlated with SCOT and, attar adjuatmg for ago. tha corralatlon batwaan thaaa two variablaa la atlll significant. Thara la no significant corralatlon batwaan plaaM PCBa and CCTP or SGPT. If thla corralatlon ia corract it fiaa oceurrad with lavala of PCBa in tha blood of exposed workara 01.4 ppb) that ara lower than thoaa found in othar atudlaa relating aubclinical ehangaa in livar function with pcaa (NIosh, 1977). However, without eorractiona tor othar potentially con founding variablaa auch aa alcohol intake and tha hiatory of othar dlaaaaaa auch aa hepatitla, it ia difficult to aaaaaa tha finding. Recantly, NXOSI haa completed three atudiaa rapraaentlng eroaa-aactional medical aurveya in two groupa, individ uals working in capacitor manufacturing (Smith at al., 1911a) and individuals working in maintenance and repair of electrical transformers (Smith at nl., 1911b). The third study combined the data from each study in an overall analysis. in the capeeitor manufacturing group there were 224 participants for whom b>KBs end a-PCBa were detarmined, aa well aa biochemical studies. Several simple correlations were cal culated and* for all those that were significant, multiple 'agression aquations were developed using all other predictor HONS 222081 168 variables tor whicn information waa available. Thia included drug in taka, smoking history, other biochemical markers, age, aai, and othara. Serum H-PCS waa significantly correlated with SCOT and CGTP. There ware, however, no clinical findings sug gestive of liver diaeaae and no indication that the levela of theae enzymes ware abnormally high. Expoauraa in thia plant ware high with plaama PCS lavala being eight to SO tinea the level found in the community. Smith t al. (1981b) have reported in the aurvey in formation on 93 individuala who were about equally dietributed between a nunieipal electric eyatem and a privately-owned elec tric utility company. The levela of H-PCBa and t^-PCBa are elmilar in the two facilitiaa. There were very few ensyne testa related to liver function that were significantly correlated with PCS levels. The only significant correlation waa a positive relationship between L-PCts and SOOT for the private company. Smith at al. (1981) subsequently reanalysed the data for the three sites presenting partial correlations for L-PCBa and a-PCls independently without correcting the level for alter nate homologous ainee they were closely interrelated, under these circumstances, there is not only a positive correlation between tl-PCBo and SOOT and GOT* at the manufacturing plant but also a correlation with L-PCB and GCTP. The positive correlation between L-PCB and SOOT still remained after corrections for the private utility company. Combining the data for all sites it ia HONS 222082 U9 p0tad that log SCOT and log GGTP demonstrate both significant gnd homogeneous trends in relation Co log L-PCB laval. Only log BOOT is ralaCad to log H-PCA and in this eaaa the trand Cor all Site* is homoganaoua but not significant, rn tnaaa analyses, tba only confounding vinablas eonaidarad were aga and aaa for pne study sita whereat the analysaa in the pravioua papara con trol! ad multiple varlablaa such as smoking and othar dlsaasas. feadueing tha number of variables and incraaaing tha number of subjaeta available for study may have aceountad for tha changas In tha ralationship with biochemical markers and symptoms to tha levels of PCBa. Because of tha many changes in relationship, it is difficult to indicate precisely the association between spe cific liver eniymea and specific homologues of PCBs. it does appear that in these studies one or sore ensyae levels within normal ranges may be related to one or morn types of PCBs In the Mood. in order to identify the anxyme system that la induced by the various chlorinated forms of biphenyls, klvarea et_ ai. (1977) tasted the induction of liver cytochrome P-490 and P-441 By Aroelor 1014 in rsts and in workers occupationally exposed to the agent. In retB, the lower ehlorinsted PCB elicited a barbi turate typo of offset on the oxidative anxyme system inducing cytochrome P-490, ethylmorphine-N-demethylase, and microsomal pro tein. Unlike Aroelor 1294, which induces both P-490 and P-440, the rate with Aroelor 1014 showed little effect on benso<a)pyrene HONS 222083 - 170 - hydroxyl**# activity, which aureate llttl* induction of p.g by th* chMieal. Th t**t* in expoaed worker* war* conducted ~by determining th* half-life of eh* antlpyrln* wnoa* aetaboliea is etimulated by th* barbiturate claaa of inducing aubatane**. Th* worker* had a aigniflcantly ahorter n*tabolle half-life of th* drug than th* control* auepeatinp that th* Aroclor 1016 had induced cytochroe* P-430. In a atudy of 3I coeeunity reaidenta in a town that had high level* of PCS* in fish, kriaa at *1. (1911) found a correlation b*tw**n PCBs aa **aaur*d apainat Aroclor 1260 and GGTP. Thar* w*r* no correlation# with other llv*r ensyeea. Correction# w*r* **d* for a*v*ral other variable* auch aa ape. aex, fiah and alcohol conaueption, and obealty. In aueeary, th* data fro* th* atudiea of liver enxyxea and function auppeat that th* population* expoaed to PCS* uaually do not have clinical liver diaeaae, although in on* atudy ther* waa aayeptoaatic hepatomegaly <a* Table 9). rew of th* early atudiea allow ua to aeparata the varioua homolopuea of peta in order to correlate ensye* reaponae to level of chlorina tion of PCle. Recent atudiea auppeat that SCOT and/or GGTP are th* aoat aenaitiv* aarkera of chanp* in th* liver enxye* ayateea related to PCB expoaure. in the atudiea that included eatenaive teetin? of all ensyee ayatee# aa well aa charactarisation of th* PCBa, the data have lnconaiatenciea that do net allow ua to judp* clearly the level or the apecific type of HONS 222084 - 171 K that la ralatad to ineraaaad lavala of apaeifie livar anlymaa. Many of tha atudiaa hava not corraeead for othar con founding variafilaa aueh aa alcohol conauaptlon. Tha data ara augqaatlva that thara ara chanpaa in ona or mora livar aniymaa ralatad to PCS axpoauia chat ara not aaaoeiatad with diaaaaa and may occur at lavala oalow thoaa at whieh ehloracna occur. D. Lipid Hatabollam Tha lon^-tarm atudiaa of patianta with Tuaho diaaaaa haa ravaalad aavaral othar abnormalitiaa. amon? whieh warm alavatad blood tri^lycaridaa (Uraba at. al^. 1979). in raeant raporta of indivlduala axpoaad to PCha, aaaaaaaant of lipid aataboliaa haa lndicatad iom abnoraalitiaa, but in ganaral no clinical nanifaatationa of thaaa abnormalitiaa auch aa ineraaaad riaka of cardioaaacular diaaaaa haaa baan notad. Some of thaaa atudiaa ara avaaaari aad in Tabla 10. HONS 222085 Takla ! UHJ StaQItt $to4r Mir Naartfa Carratattaa or alawtlaa af llpli* Sakjactt Oaaa Mk TrlflycirlPw Chela*tarat N-Chal. tout _*- ____________________________________________________________________________ NaU*Mt >t at., ** Tat. 3701 fiacr. acr. O.T. Oacr 1*11 Hin it at., 1*73 IIS Tat. 7-300 lacr. h.t. O.T. O.T. iwTtiiimir *t al. . 37 Tat. 4 O.T. Omul O.T. O.T, FlichhalH at *1. 421 i*n u 124 hi 40 tipartii ti 1 illwa aaraal 10. IS 17.01 Hi cMarlsaa lilt caatral. Ha correction far caafauaHia^ varWbl Mar at al- IMO * tiutff* atart 1* tartan 1* tartar faa. 22 cavity Tat. 17.4 7S.1 33.4 14.4 HI (10.1) 2*.$l 14.0 (12.0) Pm. - >. M|. H.T (NS) Coaaana for n-pcb on Mlyiaa aaljr aa non Hcohal Hrlatars No attar variables caatralla*. 1! H 1 balth at H r lMla 22* La SO-MU ap/al HI 22-11 SIT Camctaa far oiaar variable* HONS 222086 Study Huatoar Sub)act* Avarapa Ooaa ppb TAILS 10 (continued) Lipid ItuJm Corralation or alavation of lipid* Trial ycaridaa Cholaatarol N-Chol. L-Choi. MOL- LOL- Hots* Salts at *1-. 1 MIS 47 Sail. 44 Fr1. La Ml LO HI Salts at *1., UIU (ftawMlyu* of papart tbaua) Capacltar La HI Fb, ut. Frl*. ut. LO HI La HI (rain at > 4H ll-a af/at 4-24 Haas Fa*. 11-23 4-31 Fat. MBS. Maas Fat. Man* Poll NMt Naas 17. t alcraa/L. Mm (3.7-147.1) Man* Poi. Naas Mas Poll Nana Fat. Fa*. nan* Fat. Ml- Nan* Nana Itaia Nana Nana ai Mono Naaa saa. Haas Mono iMaa Nan* Mans on* Mono Mono Mas Nan* Fotltlv* corral*!tom carrtctad <#r athar nriablat. Includad favor caafsundtns v*ri4blti MONS 222087 174 Haaagawa a_l. (197 2) had not'd chan?" in lipid nataboliaa of Yuaho patianta aa aanifaatad by dacraaaaa in tna blood lavala of cholaatarol, triglyearidaa, phoapholiplda and bata-lipoprotaina. Othar atudiaa auch aa that of Kara at al. ( 197 3) on Yuaho patianta had not'd alavatad triglyearidaa in 551 of aubjacta who had blood PCBa abova 50 ppb. Tha lattat data wara not corractad for any riak faetora auch aa aga or waight. Bungarnar at a^L. (1973) Indicat'd noraal cholaatarol lavala in 37 rafuaa workara who had a aaan PCB laval of 4 ppb. Fiachbaln at a^L. (1979) haa axaninad lipid aatabolisa in 321 capacitor workara. cholaatarol lavala of 300 or aora a9/100 *1 vara found in 17,% of workara and triglycarida lavala of 200 or aora ag/100 al vara rapertad in 10,9% of tha popular tion, Tha total lipida vara alavatad (abova 1 g/100 al) in 3.4% of tha population. Thaaa aatabolic paraaatara, hovavar, ara influancad by aga, partonal habit*, and tha praaanca of othar ditaatat; it la tharafora ataantlal that tha data ba coaparad to a population with ainilar aga and aaa diatribution and that confounding variablaa ba eontrollad bafora ona can aaaaaa tha rola of PCBa in thaaa obaarvad changaa. Sinca thaaa conpari- aona vara not nada, no conclualona can ba dram froa thaaa obaarvatiOM* In tba atudy of Bakar at al. (1910) in which PCB- contaainatad aludga uaara vara coaparad to aapoaad workara, tha it faailiaa, and coaaunlty control', thara waa a highly aignificanc HONS 222088 175 Jbaitlve correlation of plasma triglycerides and serua h-pcb. jtjie correlation was strengthened when aieohol consumers were joaoved. There was a negative correlation of HDL cholesterol vfth H-PCBS that was not statistically significant. The investi gators suggested that the seen level of serua PCI in fasting Subjects with hypertriglycerideaia was only 25.0 ppb whieh is lower than the levels at whieh this abnormality was noted in previous studies (50-200 ppb, NI03H document). It is not clear, however, whether the other studies with higher levels have used total pels, whereas this study used only tt-PCls in the correla tion analyses. The ft-PCls constitute 35 to 591 of the total aean pets in the groups. Personal characteristics aay influence triglyceride levels# and many factors were apparently considered by these investigators Including age, aes, and drinking habits. Those lipid abnormalities aay be occurring at the lower PCI iiaits# or even below those Halts reported previously. Chase at al. (lfll) in their study of aalntonanee workers exposed to PC1s found that levels of plaaaa PCts were significantly correlated with triglycerides but not with eholostsrol. Adjusting for age or length of employment dees not change the significance of this correlation. The triglycerides are not slgnifleaatly correlated with fat PCS levels. As mentioned pre viously the levels of plasma PCBs in this group of workers is low 03.4 ppb). MOWS 222089 - 176 - Smith at al. (1981a), in the study of 224 workers fro* a capacitor manufacturing plant, found that aarua PCBa wart corralattd with maaauraa of lipid metabolism. Corractiona wara mada for raiavant variablaa auch aa smoking, history of diabetes and haart diaaasa, drug usa, and othars. Tha partial eorrelationa indicated a significant correlation between aarua h-pcb level and total cholesterol and trlglycaridaa and s significant negative correlation of plasma trlglycaridaa with serua l-pcb levels. Whan the levels of H-PCB and L-PCB were coabined the correlation was positive aa seen in other studies where total PCBa have been eaaained. There were no signs of clinical dis ease in relation to the elevated lipids. It was noted that several of the lipid measurements were correlated with gctp level. As the authors suggested, this may indicate that PCBa induce hepatic microsomal entymea, aa has been found in labo ratory animals and man, and these in turn may increase synthesis of specific lipids. Smith et al. (lMlb) in a health study of 93 workers divided between a public and private utility plant found corralations of lipid metabolites with PCS levels that conflicted with data from the previous study. Triglycerides were positively correlated with H-PCBa in one facility and negatively correlated with H-PCBa in tbe other. Both correlations were significant even after correction for multiple variables. Both triglycerides and cboleeterol were poeitively aesociated with L-PCBa in only MONS 222090 177 - facility van though tha iavala of tha biphenyl* in tha good wara aiailar m tha two populations. High danaity l1poBptalna wara negatively correlated with H-PCSa in only one igtablnhaent. in thia case, tha othar facility also demonprated a aiailar nagativa ralationahip but tha laval of tha gtrrelation waa aueh lower. Saith at al_. (lMle) have combined tha data froa tha aa two atudiaa and correetad tha raaulta for only aga. sea, Bad study aita. Undar thaaa circmaataneaa thara wara laaa con flicting date in tha corralationa. Only ona significant corre lation with L-PCB waa notad and that waa a positive correlation VItb cholaatarol at tha private utility. Both cholesterol and Jog triglyceride ware aaeociated with 8-PCBe at the equipment hanufseturing site. Triglycerides and i*Kl wore poeitively correlated and KDL-choleaterol and H-PCB negatively correlated at the municipal utility eite. Combining the data froa all atedy sites indicated that log triglyceride was significantly aaeociated with both L-PCB and H-PCB but the trend for all sites was homogeneous only with L-PCB. Log HDL-choleaterol was significantly and negatively associated with H-rcia and thia trend was eonalatant serosa ell altaa. there waa no significant relationship of KB* with total cholesterol. Krelsa at al. (1M1) have studied a community where Mfh levels of Kit and DOT wore founds in fiah. Among the 4 SB participants, there was a positive correlation between cholesterol MONS 222091 - 178 - and PCBs measured as Aroelor 1260. There was no additional contribution by aarun triglyceride or HOt^eholeaterol to the prediction of serum PCB in multiple regression analysis. in summary, the studies In aan suggest that thara it fraquantly a poaitiva corralatlon between PCBs in blood and triglyceride lavala, although thara ara many atudiaa that damonatrata no relationship. Tha eorralation ia oftan to tha higher hoaologues of PCBa and occura in some caaaa with blood lavala o H-PCB at 25 ppb or below. Tha data associating hdlcholaatarol and H-PCBa ara not aa oftan significantly eorralatad, but whan thay ara, tha ralationahlp la negative. Lover lavala of HDt-eholaatarol may ba an laiportant rlak factor for coronary heart dlaaaaa but thara la no evidence of a ralationahlp of these lipid findings to clinical dlMaaa in thsaa studies. Tha variation in tha presence of lipid abnormalities in relation to PCBa In tha atudiaa and tha variation in tha specific lipid changes observed would suggest that thara aay be a confounding variable that haa been ignored and that ia influencing these relationships. A positive correlation of blood lipids with plasma PCS levels could in part be a consequence of the tendeney of PCBa to distribute equally among all lipid pools in the body. B. asproductive Iftacts very few papers have addressed the problems of human reproductive affects related to PCB ingestion. Tha early paper MONS 222092 - 179 by Rurataune (1972) on the Tuaho patients had indicated tnat out of 11 women patlanea and two of the wivae of patients who were-v*poad at any tint during pregnancy, there ware 10 live born and two aelllborn infanta and three of the hv oorn War* small Cor chair age. Tha auehora do not provida comparison figures on reproductive outcomes for that araa of Japan ao that it la iapoaaLbla to aaaaaa tha meaning of thaaa figures. it ia claar. however, that for all baniea whose raeorda were reviewed, akin staining and aya discharge wara usually present. xreiaa ac al. (1991) simply indleatad that thara waa no aaaoeiation of miscarriage, atill birth or Infant daath rata lndapandant of age affacta in a study of a community with high PCS levels. in 9n* eral, tha data on reproductive affacta froa exposure to PCie are iialtad. T. Hematology and I--unology Host of tho atudiaa of hematological affacta have found iio abnormalltiaa and thaaa obaervationa have boon aada in aimple statements. The atudiaa of Ritamura at al. (1973), Biaagarner at al. (1973), Rarppanan and Rolho (1973), Plaebboin at al. (1979), iakar at al. (1990), and Haronl at al. (1991) have'not revealed any abnormalities of hemoglobin or laukocytes. Ouw at al. (1976) reported several protein and globulin teats on exposed workers that were higher or lover than the reported normal. However, the overall levels of globulins were not different in two groups of workers with high and low exposures, in the Initial abstract MONS 222093 - 180 - relating Co the Baker al. (1910) study, the authors reported increased hematocrit and hemoglobin in relation to PCS levels controlled for age. The second complete report corrects for several other variables that may account for the difference m results, in the three reported studies of Smith et al. (1981), the investigators looked at red cell count, white cell count, hemoglobin, and hematocrit and found no significant correlation with either t^PCS or S-PCS when corrected for confounding vari ables. in the latter studies they have also examined the corre lation of total protein, albumin, and the various globulin frac tions and found no significant correlations after correcting for other factors. In general, thera srs no recont studies that suggest abnormalities of the homo system In man related to levels of PCSs. In addition, the Smith et al. (lfsib) study of workers in electrical utilities showed no significant variation in pCBe related to urinary porphyrins, porphobilinogen, or 17-kotosteroida or 17-hydroxyateroida. G. Other Factors Kreias at al. (1M1) in the study of a PCS-exposed com munity found ineraased diastolic blood praaaure to be correlated with PCS ievele even after the corrsction for other variables. No comparison data for a control group were given. The study of workers in the equipment manufacturing plant also demonstrated MONS 222094 - 181 - Correlation between diastolic blood praaaura and H-pca but ffcla disappeared whan corractad for age. Other invaatioators Jfeve not found thia relationship, to tha diffaranca may ba laaaoclstad with an unrecognised intarralatad varlabla or a fchance aaaoclation ralatad to tha multiplicity of factora that Hava baan examined. warahaw at aK suggested that werkara in a capacitor ;benutacturlng plant (population of riachbeln at al.I had de greased vital capacity and raatrletiva impainaant of lung func tion in tha abaanea of signs of radiographic change (Warahaw at hi.. 1979). They have coaparad tha PVC to that of other worker populationa in pravloua haxardoua axpoaura atudlea aa wall aa to a non-aaoking normal population. Ilia reported percent abnor mality of PCI workers la 141 compared to 9.M cited for non smoking populationa. Hie coaparlaona do not Indicate that they have been controlled for smoking hablta and sax. Host atudlaa have reported no clinical diaeaae in PC9axpeaad populationa with the exception of ruaho diaeaae and chloracne (Karppanen # aJu* Humphrey. Smith at al.j Chaae at al. t Kralaa at_ al_.). Some have reported a yaptoms that are difficult to evaluate ainee moot are aubjectlve and could be related to worker blaa. riachbeln at a^. auggesttd that neurological syaptoma ware incraaaed but there la no alallar group with which to compare werkara and than aeka thia aaaeaaaent. smith at al. HONS 222095 - 182 (1981) in the study of the combined work sites found that couch ing st work snd irritated eyes were relsted to both L-PCI nd S-PCB. Loss of appetite end peripheral 'tingling* were associated only with L-PCB. History of skin rash was associated only with H-PCB. Many of these differences were not observed when individual work site data were enslyxed separately. The lack of a difference in each site nay result becauss jobs were included as a eonfounder variable. Most studies hsvs not tvsn reported any symptoms or history of disease (Baker et al. and Kreiss e_t al. 1 In all studies reviewed there was little evidence of clinical disease with the exception of chloracne and thia condi tion seeaed to be aost frequent under specific conditions of exposure. The other eoaaon but not consistent findings were abnormalities of lipid metabolic, especially blood triglyceride levels, and abnormalities of liver ensymes, especially SCOT and GOT?, which wore related to levels of PCBs. The lipid and liver changes appeared to occur at lower levels than the skin manifes tations and were not associated with ellnical disease or symptoms. HONS 222096 -181icefully submitted, T^fk,-lovii. nJ. fn.D. MOHS 222097 -1B5- XIII. REFERENCES 1. . XN. J.R. and AJRAHAMSON, L.J. (1979). 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Covalent binding of polychlori nated biphenyla to ret liver aicroaonee. Toxicol. Aoel. Pharmacol. 99, 490-500. SHIOTA, k. (1974b). EUbryotoxle effecta of polychlorinated bi phenyla (Kanachiora 300 and 900) in rata, okaliana Pol. anat. Jon. i3, 93-104. S2PB4, I.0. 1* (19S0). 4.4'-dichiorobiphanyli Oiatribution. metabolism. and exeretlon in the dot and the aoohey. Toxicol. Appl. Pharmacol. 51. 9S4-943. SMITH, A.S.. SCHLOHNBB, J.. LOMJtT. L.X., SNAUMOOO, A.N.. LI00, R.H., TAMAItA. S.. STRUMSB. W., JOMSfl, M. , end OIUCCX. C.J. (lfdla). Croee-eeetionel medical aurvey of a group of workers oocmpetiomally exposed to polychlorinated biphenyla (PCBs) et en eleetrleal equipment menufeaturing plant* Draft report prepared by National Institute for Occupational Safety end Health, 01vi sion of Surveillaneo. Hexard Evaluations end Plaid Studlea. Cincinnati, OH, and Lipid Reeaarch Canter, University of Cin cinnati Nodical Centar, Cincinnati. OH. (91 pages, 12 tables, 4 figures.) M0NS 222113 -201- SMlTH, A.B., SCHLOFMER, J., LOWRY, L.K., SMALLWOOD, A.W. , LIOO, R.H., TANAKA, 3., STRINGER, W. , JONES, M., HERVIN, R., and OLUtCX, C.J. (1981b). Croii*Metionil ntdictl survey of two group* of workers occupationally exposed to polychlori nated biphenyl* (PCBe) in the maintonaneo. repair, and overhaul uf alactneal tran*formers, Draft report prepared by National rnstitut* for Occupational Safety and Health. Division of Sur veillance, Hacard Evaluations and Field Studies. Cincinnati, OH, and Lipid Research Center, university of Cincinnati Medical Center, Cincinnati, OH. 08 pages, 14 tables.) SMITH, A.9., SCHLOEMEA, J. , LOWRY, L.K., SMALLWOOD, A.W.. LIGO, R.N., TANAKA, S., STRINGER, W., JONES, M., HERVIN. R.. and GLUECK, C.J. (1981c). Metabolic end heelth consequences of occupational espoaura to polychlorinated biphenyls (PCS*). Draft report prepared by National Institute for Occupational Safaty and Health, Division of Surveillance, Hacard Evalua tions and Field Studies, Cincinnati, OH, and Lipid Research Center, University of Cincinnati Medical Cantar, Cincinnati, OH. (SS pages, including 8 tables.) SMITH, A.8. at al, (1978). Lipid lipoprotein alteration! Occupational espoaura to polychlorinated biphenyl. Clin. Rea. 38, S49A. WITH, D.M. (1988). The effect of the tins of estrogen in jection on implantation in ovariectoaiaed pregnant mica. J. Endo.. 41, 11-15. SQUIRE, R.A. and LEVITT. M.8. (1975). Classification of specific hepatocellular lesions. Cancer Rea. 35, 3314-3333. STEWART, H.L. and SNELL, K.C. (1997), The hietopathology of experimental tuaore of the liver of the rati A critical review of the hlatopathogeneele. Acta Unlo Internationalla Contra Caaerue 13. 770. STREET, J-C. and SOARMA, R.P. (1975). Altention of Induced cellular and humoral immune response by pesticides and chemi cals of environmental concern) Quantitative studies of iamunoeuppreeeiom by DOT, Aroclor 1354, carbaryl, carbofuran, and methylparathioo. Toalcoi. Aoml. Pharmacol. 33,. SS7-803. STRIK, J.J.T.N.A. (1979). Porphyrins In urine as an indication of aapoeura to chlorinated hydrocarbons. N.Y. Aced. Sciences- SUNSETROM, 0. Rt El* 11*78). The metabolism of chloroblphemyls - A review, chamaehara 5, 387-298. TAYLOR, J.8. (1979). Environmental chloracnat Update and overview. Ann. N.r. Acad. Sciences 330. 295-307. THOMAS, P.T. and HINOSDILL, R.D. (197S). Effect of polychlor inated biphenyls on the Immune responses of rhesus monkeys and mica. Tori col. Agi^ Pharmacol. 44, Si. HONS 222114 -202- TriSOH, K-A., DAVIS, G.J., hcLACHLAH. J.A., and LUCIEA, G.W. (1979). The effects of polychlorinated biphenyls given pre natally on the neurcbehavioral development of miee. Environ. Rea. 19. 499-474. ------ TOERUEK, P. (1973). Effect of PCB on the developing mouse. Chanosphere 2. 173. TORQK, P. ( 1979). Delayad pregnancy in JMRI rale a tmtd with PC9 2,2'-dichlorobiphonyi. Bull. Environ. Contaa. Toxicol. 19. 33-39. ------------- ------- -*"*----- -- TUEY, O.B. and MATTHEWS, H.B. (1977). Pharmacokinetica of 3,3',3,s'-tetraeniorobiphenyl in tha mala rat. Drua. Hatab. DiaP. 5. 494. URASE. H., KAOA, H., and A3AHI, M. (1979). praaant atata of ruaho patianta. Ann. tt.Y. Acad. Sciancaa 330. 373-379. VAH MILLER. J.P. at al. (1979). Distribution and nmtaboliaa of 3H-3,9,3*.5'-tatrachXorobiphanyl in rata. Proe- Soc. Exp. Biol, Had. ME, 93. VEERKAMP, w. at 1. (19*1). Tha metaboUai of seme chlorinated dibenxofurana ay rata. Chsmpabhsrs 10(4). 397-403. VILLEMEUVE, D.C., ORAST. D.L., RHESA. K., CLROO, D.J., SAER. K.. PHILLIPS, W.E.J. (1971a). Tha fatotoxleity ef a polychlorinatad biphenyl mixture (Aroclor 1294) in tha rabbit and in tha rat. Environ. Phvaiol. 97-71. VOS, J.O. (1972). Toxicology of PCOa for naaaala and for birda. Environ. Health Peresact. 103-117. VOS, J.O. and ROMAS, J.H. (1970). Comp*TM*!** toxicologic atudy with polychlorinatad biphenyls in chicken* with special rafaranca to porphyria, edema formation, liver necrosis, and tissue residues. Toxicol. Anal. Pharmacol. ^7, 959-99S. VOS, J.O. and BUMS, S.S. (1971). Dermal toxicity studios of technical polychlorinatad biphenyls and fractions thereof la rabbits. Toxiool. Pharmacol. , 917-933. VOS, J.O. and VAS ORIRL-OROOTttfRUlf. L. (1972). PCS-induced uppraaalaa of tha humoral and call-mediated immunity in ^ilnea pigs. Sf^. TgHl Scytrom. i- 2*9-303. VOS, J.O. and HOttSSOOM-RAM, E. (1972). Comparative toxicity atudy of 3,4,3,3' ,4* ,3'-hexachloroblphenyl and a polychlorinatad biphanyl mixture la rabbits. Toxicol. Annl. Pharmacol. 23, 343. MOMS 222115 -203- V08. J.G.. KOEMAN. J.K.. VAN OCR MAAS. H.L.. TEN WOEVER DC gRAUW, K.C.. and OE VOS, R,H. (1970). Identification end oiicological evaluation of chlorinated dibemofuran and chlorinated naphthalan# in two commercial polychlorinated biphenyla. Pd. Cosmet. Toricol. 8. 635-633. KATANABE. I. et al. (1980). Distribution differences between polychlorinated terphenyla and polychlorinated biphenyls in human tissues. Bull. Environ. Contain. Toxicol. 2i. 810-815. KICKI2ER. T.M. et al. (1981). Polychlorinated biphenyl con tamination of nursing mothers' milk in Michigan. Am. J. Public Health 71, 132-137. ~ WOLTP. M.S., riSCHBElN, A., THORNTOIf, J., RICE, L. . LILIS. 9.. and SEX.XKOFP. I.G. (1981). Body burden of polychlorinated jiphenyls among persona employed In capacitor manufacturing, iubmitted for publication to Int. Arch. Oceup. Environ. Hlth. Preeented in part at the XXX International Congreee on Occupa tional Health. Dubrovnik. Sept.. 1978. tnmOKAM, C., DEVENXSK, J. and SAXE. 8. (1976). The in vitro metabolism, mecromolecular binding, and bacterial mutagenicity of 4-chlorobiphenyl. a model PCS eubatrate. Ree. Commun a CHm Pathol. Pharmacol. ^5, 563-S70. YAKU8HIJJI, T. et al. (1978). Long-term studlee of the exeretion of polychlorinated biphenyla through the anther's milk of an occupationally exposed worker. Arch Environ. Contan. Toxicol. 7. 493-504. YAMA6HXTA, P. (1977). Clinical feature# of polychlorobiphenyls {PCB)-Induced fetopathy. Pediatrician 6, 20-27. Y08HXKAIIA. 8. a^. (1979). Toxicological aaeeeement of highly chlorinated biphenyl congeners retained in the Yueho patients. <2lSSStf&3ft i* 531-538. HONS 222116 -205XIV. Oloiufy of Tmn or abbreviations alkaline phosphatase bromsulfonphthalein livar function teat gamma glutamyl tranapeptldaae PCte with high degrees of chlorination PCts with lower degrees of chlorination lactic dehydrogenase polychlorinated biphenyls polychlorinated dibenxofurane polychlorinated naphthalenee polychlorinated quaterphenyls polychlorinated terphenyle sema glutaaic oxalic traneaaioaee eerua glutaaic pyruvic traneeainaee aerua ornithine carbaaoyl traneferaee the dleeaee noted in Japan following huaan ingestion of cooking oil contaainated with PCte. PCDrs, and PCQs. parental teet anlaale litters derived froa first generation anlaale at their first (a) and second (b) matings HOMS 22211? CURRICULA VITAS CATSCORY I TtAM HONS 222liS 1 of CUWICULUM VITAE OF M. VI CTOt A. DIUJ, BWCATIOM oeDolor of Science (*.S.) degree, Long I* lend Deivaroity, 1931. Doctor of Fhlloeephy {Ph.O.) degree, Prlocetoe Dolvareity, 19*1. Doeter of Medicine (H.D.) degree, Tele Uoiverelty School of Medicine, 19**. PgLOTWHfT Inetrocter la Phereecology, College of Ffcyolclene eed Sergeone, Callable Oelreralty, 19*3. Ieetroctor le Fhoraocology, Telo Delverelty School ef Medicine, 19**-*7. AMleteet Frofeeeor of Fhereecology, Tele Delverelty School of Medicine, 19*7-**. Ftofeooor ef Phereocelogy, Voyaa ffeiverelty College ef Medicine, 19**-S3. Aaaedcte Ttyelclda, Detroit leeelrlag loepital, 19*9-33. Director of Idecatlee, -- ef leten Coaelttee. Detroit lecelvleg Soegltel, 19*9-93. Director of tfologloal leeeerch, 0. D. Seerle * Co., 1953-70. Leetarer, Dogemoet of Thereecology, Mortheeoten Oelrcrtley Moditel School, 1994-47. Director Of SclentIfle ead Frefeeelceal Affaire, 0. D. Scoria t CO., 197^7*. leeteror fa Fhereecology, Deleerelty ef Illlaola College of MOdltint, 1994-75. Feefeeeev of Fheeaeaology, Delverolty of Illlnolo College of Madldae, 197**. Directors Drill, Frlaoa, leye, loaaie i Shaffer, lee.. IS9ft-. *0*S 222119 Curricula* Vicii of Dr. Victor A. Drill 2 of * fmussiohai. socim MpgiiSHiys Alpha Oae$a Alpho. Aoerlcea Association for the Study of Liver Olaeaaaa. Aeerieaa Chenlcal Society, Division of Medicinal Chewiatry. Aoerlcea Fertility Society. Aoerlcea Fhyelological Society. Aaerlcaa Society for Cllaicnl niarwocolegy taf Therapeutics. Aaerlcaa Society fer Fhanacelogy aad byarlaaitil Therapeutics. International Society of Reproductive Medietas. Mew Terk Acadewy of Scieeeoo. Peclfie Cooot Fertility Society, loyal Society of Nedlciao. SIm U. Society fer toporlooecal Blolegy eed Nediciee. Society of Teleology, Oietlagwlahed Fallow, Society of Tool oology. Fellow of the latloaol laoearth Cowweil, Morthwooteto Valvatiicy Medical School, 1942-43. Fellow, Sow Tort Acaday of Sciaaaao. Fallow, loyal Soelecy of Nodi alaw. Seoorary Mat, latarmatioaal TmLlf Fleaoiaa leeaarch Association. iaworary Mar, Fhanacelogy Society of Towaswala. Jaaohao Fallow, Frlacecea University, 1941-42. Froaidoat. Society ef Towleslogy, 1172-73. MOMS 222120 Curriculum vicaa of Dr. Victor A. Drill 3 of - ftOKSSIQWAL ACTIVITIES IMcr. Endocrine Panel, Cancar Chaaocharayy National Sarwica Caatar, National Cancar Inatltuta, 1936-62. Conaultant, National Cancar Inatltuta, 1963-67. Haabar. Board of Director*. Barran Foundation. 1971-72. Haabar. Drug Naaaarch Board, National Naaaarch Council-National Acadany of Sclancaa, 1971-76. Haabar, Organiaatlon Conaittaa for tha Syuyoalta on tha Future of Aalaal Call*. Hod*la and Syataaa In Naaaarch, Daueloyaunt, Education and Tooting, Inatltuta of Laboratory Aalaal Neeourcoa, National Naaaarch Council-National Acadaay of Sclancaa. 1974-76. Haabar, Sclane* Advleory Board, National Cantor for Toxicological Naaaarch, 19 73-76. Haabar, Board of Director*, International Faally Planning Naaaarch Aaaaclatloa, 196^79. (Vlco-Praaldast, 1972-74.) Co-Chalmaa, The Third Conference oo Cutaaooua Tonicity, (ayanaorad by tha Aaarlcaa Hadical Aaaoclatlon and Society af Toxicology), Nay 1^16, 1976, Vaahlagtoa. DC. Co-Chairaan, Tha Fourth Conferaoca on Cotanoooo Toxicity, (eponaorad by tha Aaarlcaa Hadical Aaaoclatlon aod Society af Toxicology), Nay 9-U, 1979, Washington, DC. PgiUCATICHS: 9000 Drill, F.A., Editor. Fhaiascology la Hadlclna, NeCrao-ttlll, Near Torh. Flrat tdltioa, 1934 Second Editioa. 1M Drill'a PhnaaologF la Hodlniao, HeOrar-UU, No* Toth, edited by 1.1. DIFelan. Third Iditlon, 1963 Fourth Bdltiaa. 1971 Drill, U., Oral Coatracaatlraa. HeCraa-liU, New Tork, 1966. Drill, F A., Faraaaaloxia Hadlee. La Fraaaa Hadlee Haalcaaa, lUa, edited By 1.1. DiFalaa, 1961. Trattato di Fafocoloxln dl Drill. Ficcio Editor*. fador*. Italy, edited by J.B. DiFalaa. vole. 1 aad 2, 1971. MOMS 222121 Curricula vitra of Or. Vlecor A. Drill 4 of 4 TOBlICATIOMt >OOtS (continue) A. Cmto* a Pu, 7.A. Drill, H. Haraahl, V. lodrlguaa and A.7. Scholl?, Mltor*. Mcwt Adrancct in ft--n Aoproductlon. Pncitllan of tha Flrot International Cm|thi on Imm Reproduction, Alo da Jaaalro, Braall, Nov. 11*14,-197*, lacaryta Madlca ICS Na. 170, Excerpta Medlca, Aaatardan, 1974. Drill, v.a., end F. Lexer, Cutaaooua Toaidtr. Acadaalc Praaa, Nan York, 1977. Drill, 7,A., and F. Lexer, Currant Coacaata la Cuttnaua Taalcltr. Acadaalc Fraaa, N lark, 1940, mucATiowsi umi Author ar co-author of appro*loatoly 1M poyora la the adaatlflc lltaratura. (Ilhllofrapb? arallabla upon re^uaat.) Birth datat Jm 10, 191* Harrlad i SoptaMi U, 19A0 (Bath Cralf) Chlldzaot Crai* A. Otoooahar 30, 1943) Richard . (March 13, 1945) Cary A. 0*1? 14, 1947) Aagcat 1, 19BO MOHS 222122 1 3f ) CtJUXCUUJM VITA! OF da. simon l. miss OUCATIOW lactialor of Art* (A.I.) dafraa, UnlTaraicy of California C Loo Angola#, 1*A3. Haacar of Area (M.A.) dagraa, OaivaralEy of California at Loo Angola#, 1**4. Doctor of Fhllooaphr (Fh.D.) fagrao, Onlvaralcy of CallfonU or Loo Angolaa, 1*47. WTLOTWIff march Choalat, Maahattaa taglMorlag Dlatrlct. 1**4-**. Uitntttr, Dofiitioit of Chitotry, Oklnnltr lochaatar, 1*46-31. llooolon teouNk tmd AHalatrotlao. Iml Mafleal loooorch Uacleou, 1*51-7*. loooorch Scionclot; 1931-3*. loo*, fhfilol KutrtaciT HfUliit 1MMJ, Chaim, Ffcyolaloglcal Scloocoo llopinc, 1*45-70. Chaim, fail wootol lloocloacoo Dopormt, 1*70-79. "--g'-g Otrwcor; Drill, Frlooo, lay*, Tniio aa4 Shoffar, lac., 1900-. Tha toolary of cho llpa U DXotmi Maflaal Society VittiaitM Inaf--y of Srliaa HONS 22*123 Curriculum vitae of Dr. Seymour L. Frlaaa l of HOWOM Adjunct Profaaoor, Department of Pharmacology, Uniformed 3erricon Ijnlverelty of the Health Sclencee. The Mdlcal Schaal. 1977-. Honorary Chair, Inaeieuto of Blophyelce, Unlvaralty of Iraail at Rio da Janeiro, aa Chief of tho Laboratory of Moleeular Pharxacolor* 19*1-. W' Phi Bata Kappa Du Pone fallow la Cheaiatry, 194^47. Preeldenc, Society af Toxicalo(y, 1973-7*. Naabar, Ultorial Board, Toxlcolorr aad Applied fhatmacolorr. 19**-**; Aaaaelata tdltor, 1970-79, Maker, editorial Board, Toxlcoa. 19*5-, Makar, Ultorial Board, Toxic Subaeanceo Joutual. 197*-. Makar, Ultorial Board, Perpoactlraa la Toxlcolorr. 1*7*-, Mter. Scloatlflc Adrloary Board, Chtecal laduotty laocltuto of Toxicalofj, 197*-. Praaldaat, Aaerlcaa Board of Taxlcolofy, Iaa., MTV. Preoldeac, tacaxxaciaaal Daloa af Toadcalefy, 19X>-. Dlatlafalakad Mlw Award, Society af Toxicology, 19*1. yipfuiromL icttnmi Makar, CiatttM aa ToaleoLoxy, Aaaaakly af Ufa Sclaacaa, Maclaaal loader af Sclaacao-lUtloaal Kaoaank Cowell. 19*7-7*. CUee-Oialrmaa, 19M-71.) Spoil'BlelexrVlUtleaal Aaraaaatlee aad Space Afaecy. 197^75. Mater, Toxicolaxy leferaatiae frepa Cotet tea, iHcMly of Ufa Balaaaaa. Parlrwl Baoaarek Coaacll-Xatleaal Imtai af Tdaaaaw. 1*71-77. (Chairman, 1*74-77.) Mater, 4d Baa Adrloary CaaBlttae ax Carton Maoxlda, Dapartaoot af laaltk, IdaeatUx awl Welfare, U.S. Pu*Ua Baaltk Baarlaa, Bxraaa af Coaaalcy Bariroaaaatal Maataaaat, 1*73. Oulna, Sclaatlfte Paaal far the NASA Apollo-Soyaa Teat Prafra, 1*74-73. HOMS 22212* ricuiu vit Siynouf L. Fria : of i g^npSIOHAL ACTIVITIES (continued! MMhar, EarlroMMncal Protection Agancy-Naeional Acadnay of Sclancaa Adrianry Cosictaa on Tolerance for the Peetlclde Leptophoa, 1974. Adrlcor. Sub-Coonletae on Protraa Davelopoant and Adnlalatraelon, l4<rlw CoHlccaa on cha National Cantor for Toxicological Rasaarch, National Acadaay of Sclancoa-Natloaal Raaaarch Council. 1976-. Maher, Bureau of Blaaadlcal Sclancaa (Cooauaar Product Safety CoMlaalon) Rarlav Coonlttae, National Acedany of SclenceaRatloaal Raaaarch Covine 11, 1977-71. llalaon Rapraaaatatlva, Department of Da fanaa. to cha Iateragaacy Taetiag CoMlctaa, Adrlaory to cha Adnlalttrttor of cha larlroiaaneal Protaccloa Agency for cha tonic Suhatameaa Control Ace, 197^79. PUBLICATIONS Author or co-awthar of approximately 130 papara la cha aelaatlflc literature, (Bibliography arallakla upon rogucac.) PM* nr DfTmst AW cohpttpci Taetiology af iaduatrial and allltary chalcala: aaurnaueeular phaiaecnlogy and tanicology; ancyna klnotlca and nttiwlai of action; phyataloyy and pathology of ehaaaracoptora; chonical klnotlca; baserd aaaooanooe and aafacy cvnloatlon; regulation of ton&e auhatancao; hyparbarle eoalcology and phyalalogy, Sink data! Jolyl. 1922 HMTladt inly 11, 1933 (Mary inganla Tartar) Children; Philip L. (Saaaftor 29. 1934) Martin C. (Mowhar 23, 1934) at addranat 4322 Lana Oak Court lathnada, M> 20034 Drill, Prlaaa, laya, Loanda 4 Shaffar, lac. Snita 204 1901 North Part Mynr Drlva ArUngtoo, tt 22209 laalaaaa talaphonni (703)327-4430 Augnae 1, 1910 MONS 222125 1 of J CURRICULUM VITAS OF OR. HARRY W. HAYS EDUCATION Bachelor of Seloneo (B.S.) degree, Frankla A Harebell Callage. 1933. (Uitir of Science (H.S.) degree, Princeton Ualvaralty, 1937. Doctor of Fhiloeephy (Ph.D.) degree, Princeton Uolvaealty, 193t, PTLOYMPT laaearth Pfcetaacologlat, CX1A Pharmaceutical Coagany, 1939-41. Aaeociaee Frofooaor of Pharaecelogy, Wayne State Unleereity Collage of Hadlciaa, 1940-57. Director. Adrlaory Cantor on Toxlcelegy, Rational Acedany of SeleneeoRatlaaal Raeearch CmicU. 1937-00, Director, Faetlcldae Ragnlation Dixielee, 0.9. Department of Agriculture, 199*-70. Staff Officer, Rational Progren Staff, 0>S. Depnrtncnt of Agriculture, 1970-00. Director; Drill, Frlaoa, Inyo, Tnnala A Staffer, lac., 1990-. pRoiissiowAi socitn HuaniMipf Anertcon Conformce of Oeieinooarel Xadeetrlal Ryglanlata. taerlcaa loalaty of Ptarmoeelegy mi Ixperlnantal Therapeutiea. Soalaty for ^arlawntal Ilology and Medicine, loalery of Toaftcologgr. Editor, Teoicelagy and Applied Ptaxnecology, 1939-00. Praaldenc, Society of Toxicology, 1904-03. HONS 222126 Curriculum Vitaa of Or. Harry W, Hay* 2 of ] HOMOM (continued) Hlatorlaa, Socialy of Toaleolofy, 1973-. Marie Award, Soclaty of Toaleolofy, 1977. Dl*eln(ul<had Fallow Award, Soclacy of Toaleolofy, 1940. Fraaldaoe, Toaleolofy Laboratory Aeeradltacioa Board, 1940-. fboussiomal activttibs Maabor, Conic too oa Cutnaoua laalth ami Cooaatlea, Aaarleaa Nodical Aaaoclatioa, 1941-49, (Otalnao, Loflalatlra aod Ualaoa Subeonietaa, 1944-49.) Maabar, Fr*ira Conlecac for Syupoaia oa Cutaoawua Toalciry, Soclaty of Toaleolofy, 1944-79, Maabar. Conlccaa oa Cortlflcatloa of Toaicoloflata aod Aacradicatloo of Laboracor1*, Soclacy of Toaleolofy, 1973-79. Maabor, Zatarafooey Collaborative Croup oa Isrlroaaautal Careiaofoaoata, etloaal Caacor leacltata, 1973-79. Hafer, Chaalcal Solacclaa Martlet Croup, Wat local Caacor laacltuta, 1974-79. Maabor, Baa Stadlaa Ganltcoo, 9.S. Dapa racet of Aftlaultan, 1974-79. Maabor, Tadaleal Adrlaory Conit tea to 9.S. Doportnet of ebo Any oa eta dcodllcariaaciac yrafm, 1977-74. Maabor, tt.S. dalofaclaa c* the Jolac FA0/WB/W1F Conference oa Hyaotadaa, Nairobi, faaya, 1977, Oulaa, lavia Coniccoo, luraoc of Sloaadlral Srlaaaaa, riaaiaor Fradacta Safety fiHaalaa, 1977-74. Maabor, ConcU^acAccradltatiac, Aaarleaa Aaooclaclaa for laboratory CBlblIafrapbyTc^lIo*ta"^4tTMoootnt^~ ** MOMS 222127 CufTlxulua Vlca* of 0t. Harry W- Hay* J of 3 qt sfkial intctist and coMyrrmct Hataral toxicanta la food: food addltlvaa; toxlcolotr of paatlcidoa 4 lnduatrial chlcala; reflation of paatlcldaa; hatard aaaaaaaant and aafary evaluation. PtASONAL tlrcti data: Karrlad: Children: Hoao addraaa: Oetober 23, 1)09 Doceabar 1*. 1)33 (Elaa C. Uct) Thoaae Oratory 3)00 Vateoo Placa Waahln|tea, K 20014 Buaiaaaa addraaa: Drill, rrlaaa. Hay#, Local# 4 Shaffer, lac. Suite 204 1)01 (forth Fort Wyor Orlva Azllatcoa. VA 2220) ualaaaa telephone: (703)327-4430 Aaguat 1, 1)10 HOMS 222128 1 of & anuuon.UK mAi or DR. TED A. LOOMIS EDUCATION Bachelor of Sclaoca (I.S.) diftH, DUmaltf of Waohlagtoo. 1939. Itutir of Sdanca (M. S.) degree, Uolvaralty of luffala, 1941. Doctor of PMloaophy (Pfc.D.) dagrta, Uolraraity of Buffalo, 1943. Doctor of Madldnc (M.D.) da*roo, Tala Oaivonlty School of Madldnc, 1944, WWW latara, Karloo loafleal, U.S. MUt laalth Samoa, Saaccla, ha, 1944-47. Aaolataoc Profaaaor, Dap orfoot of Vhonocology, hlwtlqr of Uoahlogtoo School of Hadldno, 1947-49. Aoooaloto frofooaor, Dap a moot of lliimcilop, oolvoralty of Uaahlostou School of Wadldoa, 1949-53. Capcalo, 0,1. Amp Hailtal Cocfo (Active Doty), 1993-99. Aoaoclato Frofacaot of rhonacolofy ao4 Suto Tooleolotlac, Ualvanity of Waohlap too School of Wadialoe, 1999-57. Profaaoor of Fhanaoology cod Itoto Tosloalo|lat, felvorolty of Vaohloftoo School of Nodlcloo, 1957-74. Profaaoor of Phonaaology aod Torn!oa lap, DWlvonlty of Hoot tattoo School of Wadi>1ao. 1974-. Dlroatovi Drill, Prlooa, layo, till 4 Shoffar, loa., 1910-. nenutma. soexm t--rnsas loorim Society for Phonooaloty aod Wpirimtl Tharafoutlaa. Soclaty far *t--|mmlloloiy aod Mediclea. Soolocy of ToBlcolocy. Hoatara Phanocolofy Soolocy. MONS 222129 Curricula* Vltaa of Dr. ltd A. Looola 2 of & Dlploaata, National Board of Nodical baalaara. Blaclngulohod Fallow. Saclacy of toxicology. Frooldont, Soclacy of Toxicology, 19*9-70. Fraaldaac, tfaatoro Pharmacology Soelacy, 19*9-70. Itad plant. Toxicology tducodoo Award, Sodaty of Toxicology and Fon* for Advmcaaanc of Toxicology, 197*. womiioKAt AcnriTiig MaaOor, Cowlctoa on Taxto for latosleacloo, Kotiooal Safaty Council, 1951-. MaHhar, Xdltorlal Board, Cllal&al Fharoaeoloar and TWaooudco. Maatar, Agricultural Addaory Board oa Faadaldaa aod laaactlddca, Stata of Waadagtoo. 1943-77. Nadir, Addaory Conic tao Tituaou for lafory tralaatlaa, O.t. Food awl Drag Addalatrxdaa, 1HM9. (Mar, Addoory Caalitaa, Faadaldaa tagolaelaa Btvtoloa, 0.1. Dapartoaot of AgrlMlM*. 19**-70. Nxdtr, Fharmacalagy Toxicology Iadov Contlttoo, Vatloaal laatltsta of gaoaral Hodlral gclaotaa, latlawl laotltxtaa of Boalcfc, 19*4-70. laiwkAfflUata, Bagloaal Frioato Cootor, Ooivaralty of Vaafclagtao, 19*^. Molar, naioaaalagj Taalralagy TfUilip Catnictao, latlawl Zaotieoto of antral mHtal Idooooa, latlml laodtvtoo of Iwlcfc. 1970-74. MMar, riwUtn for tAaotlflaadoo of laa--rrt Ooadi la Motor B^gly. fcgfoil^ aod 9r*n KoaltA SctootM Vtody Soatloo, Sadronaotal Cootrol IMalltntln, Cnwtr Fracactloo aod MNwaul laoltli Bardaa. Mila ladle* fardeo, 0.5. Ooparroaot of halt*, Idoaatlao. mi Malfara, 1970. IM, Addaory Caaoittaa to Iadov lira 0oo of J.l.yi, Agrlaolmral Mao iota* Bardaa, O.t. Papaiaoal af Agrlamleara, 197(^73. Caoaoltaat, CrltarU far a to Ffcaotl. ratloaol Taodcx MOWS 222130 Curriculum Vina of Or. Ted A. Loobi* 3 of . MOfISSIOMAL ACTIVITIES (continue) Conaultaat, Criteria for a RecomMnded_ Standard: Occupational tarpoaura to for--ldahyda. National Institute for Occupational Safety and Haalth, 197*. Hb*r, CoMlttee on Haalth Hazards of Pyrolyela Product* of Polymer*. National Notarial* Advisory Board. National Roaoarch Council-National Academy of Sclancaa, 1973-70. H*afcer. Comic tea on Chronic Toalclty Tooting, Advisory Center on Toslcology, National Raaaarch Council-National Academy of Sclancaa, 197*. Penalise, Committea on Harlas Bcoayacan* Analyila (New York light Project), 1970-77. Member, Advisory Beard, Sprloger-Verlag Raadhuch Sarlaa, 197]-. Mamber, Editorial Board, Combustion Toxicology. 1973-. Chairman. CoMlttaa for Pear Barlow of NASA Ufa Sclancaa Propotala, Pharmacology-Toxicology Sactlaa, Amarlcaa Institute of Blalogical Sclancaa, 1971. Member, CoMltteo oa Sub-Chronic Toxicity Taat Protacoln, U.S. InTlrni--raT Protection Agoncy, 1979. Mambnr, Scientific lariam Panel far laalth Raaaarch, U.S. tarimi--aral Procaetlan Agency, 1990. ppiLianowi 1000 Uaontlala of ToxtcolOP. Lao * Ptblger, Philadelphia. Pint Ultima, 1909 Saaaad Ultlam, 197* Third Ultlam, 1979 pgiLicanc. PAWM Uclwr mr m mmrter of approximately 100 papera la the aclaatlflc literature. (UhUefrapby arallabla upon rmgnoat). MONS 222131 Currieulun Vitae of Or. Tad A. loonla * of 4 ai|aa fir OtClAL nTTIMST AMP COMfETIWCE Dovelapnant of biological and chmlcal oathodology for toslclty tasting; clinical and foranalc toxicology Including evaluation of cauo*affact relationships and intarpratatlon of clinical analytical findings; development and presentation of apodal prograaa and Instructional notarial# In toxicology for Industry, educational institutions, and attorneys; offsets of alcohol and drugs on autonob 11# driving. Including blood and breath casts for intoxication; anlaal and clinical drug and paatlclda tonicslogy. rtmoNAi data Birth data: April 2*, 1917 Married: Much 19, 1944 (Marlon Adana) Children; lolls J. (Mo*star 13, 1944) Baafcy A, (Huaiat 7, 193)) Rons address 2707 teat lacksr goad Clinton, tt 91234 Bualaaaa address: Drill, rrlann, Inyo, Loonla 4 Shaffar, Inc. Suita 204 1901 Barth fort Myur Drive Arlington, W 2220* Bnslaaaa talaphono; (703)327-4430 August 1, 1910 MOHS 222132 1 of ] CURRICULUM VITAX or OR. c. BOYD SHATTER PUCATIOH Bach*lor of Sclmco (1.3.) degree. Lebanon Valley College, 1931. Doctor of nilloeophy (Hi.Di) degree, Princeton University, 19*1. BgLOYMBfT Sector fellow, Chwlcal Bygtoaa Fellowship, Holloa Institute of Industrial Research, 1941-32. Chief Industrial Toxicologist, Central Nodical hmaant, Aaarlcaa Cyanwid Coapeay. 1932-31, Olractor of Rnvironnental Raaltb, Control Medical Departaoat. Aaarlcaa Cysnwid Canaan?, 1939-44. Director of Toniealogy, Central Nodical Dopemoot, Aaarlean Cyaawld fnon iny. 1944-79, Dlractar af Corporate Toxicology, frrnrnnnanrsl Servleaa Division, Anarlcan Cyansald Canpony, 1979-90. (Makar af corporate Label CotBtctoa af Aaarlcaa Cyanwid Csapany, 1937-dO( Cholrnoa, 1943-90.) Director; Drill, Frtaaa, lay*, Insale 4 Shaffer, laa., 1990-, rjQfMtiomi can Iadnstrlal Ryglana Aaoorlatlan. Society af and Sapor ital Iborapoutlea. tealacy fo* Bporlaatll Slelogy sad Medicine, lottery af Toatoology, The Society of tha lias XI. Adj wet Aaaoolata Profaoaor of lavtroaaontal Madlelaa, Dapareaaot of Raviroaaaatal Madlclna, Now Tarh University Medical Cantor, 1939-10. MOMS 222133 Currleulv* Vita* of Or. C. Boyd Shaffer 2 of i HOWOM (continued) Chalraan, Cordon laaaareh Conference on Toxicology and 'Safaty Iwaluatlon, 1942. Certified by cho Aaarleoo Board of Induatrial Hygiene, toe.. la cha TOXICOLOGICAL ASPECTS of Induatrlal Hyglana. Praaldont, Soeloty of Toxicology, 1942-43. Editor, Toxlcolotr and AgoHad Fhataacoloxy. 1945-47. Dt*tlo|lahad Fallow Award, Soelaty of Toxleolagy. 1910. piorosioKAL Acrmno ni tmoi association ChNlcal Manufacturer* Aaeoelacioa (Fonarly Manufacturing Chaalata Aaaaalatloa) Lakalt and Praeautlomary Information Caaalcceo (Naahar alaca 19Mt Ckalrwa, 1945-47). Incarconltcaa Tank Crap aa Traaaportatlaa laaarda, 1945. (Vraca, wick lapat tm cka Oraay. tka K| OwCard Hanoi aad tka MCA Cana Information cL* --al) Tranepertatlee laaarda Information Committee, 1947-49. (Wrote a proyooal aa Traaafartatlaa laaarda Iafaraatlaa S7a far awkaiaalaa ta cka 0.1. Dapai feat af Traaapertxtloo.) Todc labataacaa Caatral Crawa, 1971-74. (Ckalraaa, 1972-74. Praaaacad tka ICA taaclaaay aa Toxic Sukacaaaaa Caatral laflalatlaa kafara CoaBltteae af bath laaaaa af Caatraaa darlaf tka tteaa aaaalaaa af Caacraaa awar which thla laclalatlaa waa eaaaldarad.) Qilunl lagmlatiaaa Adwlaary Canaletto**1974-77 (OaliHa). HaManal Agrtoalcnral Oilrala Aaaaalatloa krlnaatal Adwlaary Caaalctaa (Ckalraaa. 1972-74). Naalar, Camttaa aa Toxicalogy, Ratloaal Acadnay of Sdaaraa-latioaal taaaarek Caaacll, 1949-75. HONS 222134 itrteul.ua Vitoa of . C. Boyd Shaffar J 3C ' ffl^ftSSIOWAl ACTIVtTIIS IS COVIRHHPCT (coatlnuod) Mater, Standarda Adnoory Comlttaa for Haaardoua Nataruia Latelias. 1974-75. (Convonod by tha Occupational Safaty and laalch Adnlnlttratloa of tha C.S. Dapartnaut of Labor.) Advlaor on niaaroua oeeaalona, 1972-71, to tha Datamation froa tha 0.S. Daparcount of Tranaportatloo to aaatlnga of the Croup of lapportauro on tha Foefcaging of Dangaroua Gooda of tha Coanlttaa of loparta on cha Traaapore of Dangaroua Coodo. (Boatings hold oni-annually In Canava, Swltearland, undar tha ouaplcao af tha leouonlc and Social Council of tha Oaltad Rations.) HBLICATIQHI . Author or eo-author of approalnotaly 40 popora In tha aclantlfle llcaratura. (bibliography available upon raguaat.) nm <ncm armrsT amp cowirmci tasoarch doalgn; eanlcalogy of aynttetla organic laduatrlal chanlrola; toslcology * aynttetla organic peotlcldaa; aafoty rraluatlon; procautlansry latellag af haasrdana laduatrlal ehanleala; praeantlanary Labeling hanaahald prodneta undar tte fadami laaardoaa Rutetanaaa Aaf pmasntlanary 1 atellaa of paatlaldao undar tte Federal Inaoatlalda Fungldda, and Rodaatlclda Act; rofnlatlan of rhmlrala undo* tte Toma Sutetancaa Control Aett tranaportatloo of batardaua natarlalai praparatlao. aubnlaslao, and foilan up of food addltlva patltlona. llrth datni Hamad i Chlldmni Ainot It, 1917 3mm 14, 1941 (Mary Louiao Stooer) T ill b. (terror 20, 1942) Million A. (Dainabar 17, 1943) 2370 Rt Oaaan bird. A-M2 Itnnrt, fb 33494 2940 Fona*uld Court *---- r- m 21401 Drill, maaa, Raya, lewda 4 Shaffar, Ue. Suita 204 1901 March Fan Mpnr Drlm Arlington, 94 22209 (703)327-4430 Auguat 1. 19bO MOMS 222135 CURRICULUM VITAE Mvlflvfl Elizabeth Matanoskl (Nee Murray) .:gelal Security 140 034-22*2128 tc* Of Birth: Salem, Massachusetts Oat* of Birth: a^st 2fi, 1930 Obcatlon: Punehard Hi oh School. Andover, Mast.. 1947 Radcllff* Collar. Cambridge, Mats., 1947-1951 Johns Hook Ins School of Madldna. Baltimore, Md.. 1951-1955 Johns Hopkins School of Hygiene 1 Rutile Health, Baltlmora, Md., 1940-1944 Degrees; Radcliffa Collage, A,B. in Chemistry, 1951 Johns Hopkins School of Medicine, M.O., 1955 Johns Hopkins School of Hygiene I Public Health, N.R.H. 1982; Dr.P.H. 1984 Research Presentation for deoree of Doctor of Medicine, "Prleery Biliary Cirrhosis In Children and Adults" Certified a Specialist in General Preventive Medicine by the American Board of Preventive Medicine, Decoder 1973 felloe of the American College of Preventive Medicine, April 28. 1975 Honors: Matter of the Alpha Chapter of the Delta Omeea Honorary Society, May 1980 Genevieve m. Metanoski, m.o., Dr.P.H. Professor The Johns Hopkins University School of Hygiene I Public Health Department of Epidemiology Room 2401 615 North ttlfe Street Baltimore, Maryland 21208 Telephone Nos.: (301) 955*3483 (301) 955-3892 NONS 222136 POSITIONS: Prof**r: John* Hockin* School of Hygiene & Public Health July 1, 1976 to pr*i*nt Associate Professor: Johns Hopkins School of Health Services September 1973-Jun# 1978 Associate Professor: University of Maryland Dental School October 1970 to present Coordinator 6 Evaluator of Special Projects: Evaluation 4 Biostatistics Center of the Regional Medical Program Mareh 1970 to 1973 Associate Professor: Deoament of Preventive Medicine University of Maryland 1970 to present Associate Professor of Epidemiology Johns Hopkins School of Hygiene 4 Public Health July 1, 1989 to present Instructor In Department of Preventive Medicine: University of Maryland 1987-1989 Training Fellowship in Public Health: Johns Hopkins School of Huolene 4 Public Health 1982*1984 Assistant Professor of Epldorfolooy: Johns Hopkins School of Hygiene 4 Public Health 1984.1989 Instructor in Epldaariology Johns Hopkins School of Hygiene 4 Public Health 1959-1984 Pediatrician Out-Patient Deoartimnt: Johns Hopkins Hospital 1957 to present Research Assistant In Epidemiology; Johns Hopkins School of Hygiene 4 Public Health 1957-1959 Assistant Resident in Pediatrics: Johns Hopkins Hospital 1958-1957 Intarn in Pediatrics Johns Hopkins Hospital 1955-1958 Research Assistant Johns Hopkins School of Medicine 1955 MONS 222137 CURRICULA VITAS CATEGORY II TEAM HONS 222138 cum aunt vitai Alvito Patar Alvorca, Ph.D. on: Doconbor 23, 1*33: Boahay, India Cltltanahip: u.*.a. . Harriad: eve ehildrao Idyciclon: Unlvaraity of Boahay, India, 1*31-1*31 >.Se. Datcaa: Major in Choniacry; Minor is Fhyclea, 1*33 1.3c.(Inch) Degree: in Choaical Technology, 1*37 Unlvaraity of Detroit. 1*51-i960; M.S. Degree; Major la llochoaietry; Minor la Chaaietry, 1941 Unlvaraity of Chicago, 1*40-1*43 Ph.D. Degree: Pharaacology, 19M Protont, Addraaa, Da pa mant of Pharaacology Uniformed Services Unlvaraity of tha Health Sclaaeos 4301 Joooo >rld|a load Bathaada, Maryload 20*14 Telephone: (203) 293-122* Aptoutanotaj 1. Poot-dactoral Fallow) Oapartaont of Pharmacology, Ualvoralty af Nlaaoaota Nadiaal School, Hlaaoapolla, Hina. 1943-1**7. 2. Scalar loaoarah Biochemist: Wallcoaa laaaareh Lehoraterlaa. Barrow|ha Walloon and Co., Tuchahae, R.T. 1M7-1970. 3. laaaareh Aoaoclatai Tha lochafallot Unlvaraity, Haw Toth, R.T. 1970-1971. 4. Aaalataat Prafaaaon Tha loekafallot Unlvaraity, Raw Tart, R.T. 1971-1975. 3. Aaalataat Profaaaori Dapartnant of Pharnacaloty, Catnall Unlvaraity Wadi til Callage, Raw Tart, R.T. 1972-1973. 4. Adjnat fieri ta-Profaaaor: Dapartaant of Pharaacology, Coraall Unlvaraity Madlcal College, Raw Tart, R.T. 1973-1977. 7. Aaaoclata Profaaoari Tha lochafallot Unlvaraity, Raw Tort, R.T. 1973-1977. 4. Adjnat Prafaaaari The locfcafallar Unlvaraity, Row Tart, R.T. 1977-197*. 9. Aaaoclata Prafaaaari Dapcrtnat of Pharmacology, Uniformed Sarvtcaa Unlvaraity af tha laalth Sclaacaa, Bathaada, Maryland. 1977-1974. 10. Prafaaaari Dapartaant af Pharmacology, Uniformed Sarvlcoa Unlvaraity af tha laalth Sclaacaa, Bathaada, Maryland. 1974-praaant. HONS 222139 2 I. Awards: Irua T. Hlrechl Scholar. 1474-1971 National Institutes of Health Career Devaloyaent Award C. Professional Soclatlaai Sl|M XI Aaerlceo Aaaoelatloa far tha Advaacaaaet of Scleuca How torh Acady of Sclaaeaa Aaerlceo society of Pharaacalagy aad Ixyerlaeutal Therapeutics Aaerlcaa Soclaty of Biological Chaalita Aaarlcae Society for Cllalcal Pharaacalagy aad Therapeutics Toxicology Soctloa, lotorsatloeal tJaloa af Pharmacology (1UPHA1) Society of Toxicology D. Medical School aad University Activities! 1. Lectures la Nodical Pharmacology Course 2. Hlalcowraa la Toxicology far lad year aadieel students J. Graduate Itidat Advisory Cuwaittoo 4. Meager> faculty Senate, 1971-M 5. Chatraaai Crievecaa Coaaittoa, faeulty Souata. 1979-BO 4. Meageri Keeearch Proyeoel Merit lavlaw coaaittoa, 1979-12. 7. Meager: llahaxarda, Ceatrolled Sugetaaceo, aad Bangoroua Materlala CoMlttoe, 19B1-B4. I. Craduate Studacta ae^ Theses: Julia L. Ilaaaaa. "Altaratloaa la haaa eetahallaa Induced by gold." 1979. f. Maaearahieai 1. Meager, Itearlag COMlttee, ItirhMlnal Phaiaaaolagy Dlecuaaui 8rOf, Mew Tarfe Acadvy af Sciaecoe, 1974-1977. 2. Ad hoc reviewer far llochoalcsl Pharmacology, Nelecular Pharmacology. Life Sciaecoe, Scleata, Cllalcal Pharmacology aad Therapeutics, aad Jowraal af Pharmacology aad layerlaaetal Tharayeutica. 3. Mo^er, Uorkgrouy af the Hatiouol Covloaiac ae Olgestlvo Dlaaeaee, 1977-1971. 4. Maagor, gdltarlal Boardai Cllalcal Pharmacology aad therapeutics Pharaacalagy Journal af Euvlraaaaucal Pathology aad Toxlcalogy MONS 222140 3- C. Pittltlpwt (Invlead ipulat) 1. Flrot Iotornotlonol Syapoalua la Nlcroaoaao aad Drug Oxidations, lothaada, Maryland, 1999. 2. lotamatlonal synpoalua on Drug Toloraaea. Addiction. AAuoa aad Nathadona Traatamt. Haw Orlaaaa, Lonalaaa. 1971. 3. Sacond lataraatloaal Synpoalun aa Mlcroaoaaa aad Drag Oxldatloaa. Stanford, California, 1972. 4. ID* Syagoaluai taaetloa Maehaolana af Cytochroaa P*430 aad Ralatad Inaynaa, StocUtola, Swadoa, 197). ). UgjoKa Coaforaaca on lypaotica aad Sadatlvaa. Calmtoo, Hlehigan, 1974. 9. Xuropaan Soclaty of 9adlatrie todaerlaalagp, Aaanal Haatlag, Mrlla, Moot Caraaap, 1979. 7. Third lataraatloaal Syagoolua on Mteraaoaaa aad Drug OUdatloao, Sarila, tfaot Caraaap, 1979. . Cordon laooareh Confaraaca - Brag Hatakallaa, Plymouth, Haw laagrtlrt, 1979, 9. PaaCth Boar Lodgo Confaraaca on Cllalcal Phamoealagp, Platbaad Laka Ladga, Maataaa. 1979. 10. Gordon laaoarak Coaforoaaa - Taadaalogp, ftidal1 Oalaa Acadaap, Bov la^aklco, 1977. 11. lynpoalun on Dng Dlavooltlon la Man, Saraaota, Florida, 1977. 12. 1 ragBlan n Taflaaara af Ontrltlonal footora on Toslcalagj, latamattonal Coagraaa af Phtmacolony. Parla. Pranaa, 1979. 13. Synaalw an Aaaaaanaat af Dng datafcallan u Man, 19. Zasarnatlaaal raafaranca on Critical Currant lanas U aolraanantal Baalth laaarda, Tol-dnrly, taraal, 1979. 13. taoanth gunpaw Harhahog la Brag Hatakalion. Xarlafc, Bnltaarlaad, 1999. 19. Uarkabog aa tha Caadtaad Iffoeto af Xaaahlatlca, gatlaaal laaaarch Cowell, Ottana, Canaan, 1991. 17. Cardan Confaraaca on Food and nutrition, 1992. MOMS 2221*1 PUBLICATIONS: McKutlck VA. Hurriy GE. Paaltr RC. Wtbb CM: Musical murmurs, Bull of Johns Hook ms Hospital 97:136, 1955 Price WH, Matanoskl GH. Morrison 0. Prewar A, uaqnar Q: 7h# fractionation of saromueoUs from human strum. Bull of Johns Hankins Hasp. 108:227, 1961 Price UH, Matanoskl GH. Prewar a, Ractor L: Seromucoid fraction patterns of individual with pnaunonia or Itukamia. J Genoral Physiolooy 5-205, 1962 Matanoskl GH. Prlca HH, Farancz C: Ep1damloloqy of streptococcal Inflation* in rtitumatic and non-rheumatic familial. 1. ObJ act Was. plan of study, and comparatlva fraouoncy of stmtococcal Isolations, Amer. J. Epid. 87:179-189, 1968 Matanoskl GH. Prlca WH, Farancz C: Eoldonlolooy of stradtococcal inflations in rheunatic and nonrheimtie familla*. II. The intar-ralationshio of stradtococcal infactions to aao, family transmission and tyoa of Group A. Amtr. J, Eoid. 87:190-206, 1968 Matanoskl GH. Prlca WH, Farancz C: Eoldemioloqy of stradtococcal inflations in rheuattic and non-rhataaatic faari 11 as. III. Comparison of tha i swine rasponsa to stradtococcal infactions in tha two populations. Amur. J. Eoid, 87:207-225, 1968 Matanoskl GH. Prlca WH, Farancz C: Eoidanioloqy of streptococcal Infactions in rheusetic and nonrtiai-- tlr fasti Has. IV. Tha affact of tonsillactomy on stradtococcal Infactions. Amor. J, Epid, 87:226-236. 1968 Matanoskl GW: Tha rola of thp tonsils in straotococcal Infections: A comparison of tonslllactomisad childran and siblina controls. Amar. J. Eoid. 91:278-291, 1972 Maunoski GH. Saltsar R, Sartuall P2. Olamond EL. Elliott EA: Channinq brands In mortality of specialists and U.S. whita malts. Procaadinos and abstracts of papers presented at tha seventh annual maotino of tha Society for Eoldemiolooic Research, Berkeley, California, Juno 19-22, 1974 *0*$ 222142 Rlngelberg ML* Matinoskl GW, Klinbell AW: Oental carfas-experienct _ in three generations of families, Journal of Public Health Dent 34:3, 0*9*1 174-1 SO. Siaaar 1974 Matanoskl GM. Seltser R, Sartuell PE, Diamond EL, Elliott EA: Tt current Mortality rates of radiologists and other physician speciallots: Deaths free ill causes an* cancer. Auer. J. Epld. WJljJ, 189-191, March 1975 Matanoskl GW. Seltser R, Sartwell PE, Qlimond EL, Elliott EA: The current eortality rates of radiologists and other physician specialists: Specific causes of deeth. Amor. J. Eold. 101:3. 199-210, March 1971 ----- Matanoskl GW. Sertuell PE, Elliott EA: Letter: Hodgkin's disease aortaTTty aacni physicians. Lancet U92S, 197S Metanostl GW. Landau E, Elliott E: Epidemiology studies - Pilot Study of cancer Mortality Near a Chemical Plant and Other Industries In laltimore, U.5. Environmental Protection Agency. Office of Toale Substances, Washington, O.C. 20410, Msy 1979, Final Roeort Mstanotkl GH. Hendorson Ml, Stine X, Ceurpas C, Hepner R, Walker 5: The effectiveness of phonocardlotcan screening for the detection of haert disease in school-age children. AJP|7:7, 609-411, July 1977 Matanosfcl GW. Landu C, Elliott E: "Progress in a Coaunlty Arsenic stuay^n Toale Substances in the Air Envlrwant. Air Pollution Control Association, Pittsburgh, 1977 Kaszuba Ai, Mitanoikl 6M. filbton fi: Evaluation of the Eaergency Ooperaant as a site for Hypertension Screening. JACEP 7:2, peges SI-61, February 1979 Mak H. Flvm JP9. Mtanoall GN: Oo AMnlstratlva guidelines Modify the Application 1m Cl Meal lenefit of Heme Oxygen? Abstnct. Marl can Revleu of Aesplmtory Disease, Suppliant 119^, April 1979 MOHS 222143 -4 H. fiM of Sclaatlflc Iatimt: (a) factor* influencing th# aaeaboliaa and actio* of drugo> ooviroRMBcal chaaicala aoc carcinogen*. <b) lataractlona bacveaa nutritional factor* aad drug aataboUaa. (e) glochoaical and toxicological affacta of covlroaOMtal chaaicala aad earclao|aaa. (d) Boavy natal toxicity. (a) Iffacta of foreign choalcal* o* haan blaayathaaia tad ha** aataboliaa. <f) Mlcroooaal hoaoprotalno: differoacao la conpoaltlon aad tunwxar rataa; regulation by drug*, cblorlaatad hydrocarbon* aad carclaogoaa. HONS 222144 -5- AIVTTP UTIK ALVAJItt Lite of Publlcatlonoi 1. Aivaraa, a. p. : utlllxation af vuua and by-producta af tha fatty oil industry. bnabay Tachnoloolst. 9i 1-4. 19*7, 2. Harbor. L, I.. A. P. Aivaraa. A. I. Jacobana and *. j. viaaki rf - fKt of barblturle acid and tnlartatraeyellnb upon growth, anon la concantration and vtraaaa activity on tha yaatraiataatlaal tract of ehlcka. Journal of autriei--. ai 1-1. 19*1. 1. Aivaraa. A. p.. L. I. Aarbar and W. j. viaofci Bffaot of barbituric acid, chlortatraeyellaa and carbohydrataa upon ymvth and yaatrolataatinal uraaaa activity of eblcfco. J-----' af Butrltloa. Ji *3-9*, 19*4. . Aivaraa. a. f., a. r. aandriekaon and . j. viaaAi tffacta af lao- nlaxid. chlortatraeyclina and coppar upon yrovth and yaatrolntaatlnal uraaao activity of chleAa. Journal of utrltlon. 93> 79-43. 19*4. 9. MandrleAaon, ft. p,, A. p. Aivaraa and *. j. Vloaki tffacta of chlortotracyullJM and lonalaald on body wlfkt pain and intaotlnal una hydrolyala of rata. Journal of natrltloa. Mi *9-70 19*4. *. tabora. Jon j,, a. p. Aivaraa. C. Alapal and j. T. nelauphllai Brain obolaatorol Si Bffaot of aobadullnf an tha rtorol louarlny capability of nothylphonldato (Bltalln). PraaBodlnaa of tbo toolatv of aaorlnontnl iloloov and nodlrlno. 1301 37-41. 19*1. 7. Andora. u. ., a. P. Aivaraa. and 0. J. Wnnar1n*> Inhibition of dru* notabollna. IXi notabolitos of 2-41othyl aainnotbyl 2,2dlptaoaylvaloroto BO. (or 929-A). Wolooular Pbarnoooloav. i> 32B-334, 19*. , Ji 921-92*. 19*7. la hydraay lotion by hopotla dru*bltal and 3-notbylaholanthraoo- *ad UnUrtlory ................... HOWS 222145 Ha t4noski GM. Sal tsar R, Sartwall PE, diamond E, Elliott E: ' RTsks of Radiologists Ov*r Savon Qacadts. Abstract prtsantad it - SER Stating, Mom hivan. Connaceicut, 1979 Katmoski GW. Payton AJ: A Cohort Study of Canetr Mortality in virologists. "" Abstrict orasantad it tha first Annual NIOSH Scientific Symposium 1978. Toxicological 1 Carcinogenic Health Hazards in tha Workolace. Pithotox puhllshars, 1979 Smdlar OP. Matanoski GM. Comstock GW: Haalth Consequences of Nasooharyngai) Radium Irradiation. Abstract orasantad at SER moating, Nn H*van. Connacticut, Juna <979. Anar. J. Eoid. 110:3, page 158, Saotambar 1979 Matanoski GW. Landau E, Tonaseia J, Lazar C, Elliott EA. McEnroe W. UaHng R, Saiftar J: Lung Caneer/Mortality in Proximity to a Pasticida Plant. EPA 560/i1-60-013 (Eoldomlolooy Studios), U.5. Environmantal Pro taction Agancy, Washington, O.C., March 1980 (in intarim raoort) Mak H, Flynn JPG, Matanoski GH: Do Clinical Guldalinas Modify tha Application and Benefit of Homo Oxygon? Maryland Stata Modical Journal by tha Madleal and Chirgrgieal Faculty of tha Stata of Maryland, Saltimora, Maryland, March 1980 Farancz C, Matanoski GM, Wilson PO, Rubin JO, Halil CA, Gutbarlat R: Matarnai Hormon* fheraoy and Conganital Haart Oisaasa. Taratology 21:2. 225-239, April 1900 Massay RK, Crochetlere CA, Matanoski GW: Haoatologic Valuas in Sanzana Exposad Workars. Journal of Environmantal Pathology and Toxicology 5 2. 315-521, Pathotox, January 1981 ~ Matanoski GH. Billings CE, Lavina MS, Laos PJ, EIHott EA: Investigation of Haalth Hazards In tha Painting Tradas Industry Raoort, Unoublishad raport to NIOSH, Tha Johns Hoofclns Uni varsity, School of Hyglana and Public Haalth, Saltimora, Maryland, January 198Q Matanoski GM, Watt S: Occupation and Environmantal Exposures and tha Risk or Conganital Haart Otfaets. Abstract orasantad at SER Moating, Minneapolis, Mlnnasota, Juna 1980 Altar NJ, Garaty RJ, Sampt inar RE, Small mood L. Tabor E, Matanoski GM. Ntthanaon 8: Coamnlty Acoulrad 8on-A- Mon-0 Hopatltls. Abstract orasantad at SER Moating, Mlnnaapolls, Mlnnasota, Juna 1980 Sandler 0* Matanoski GM. Comstock 6, Mttchnil T: H*alth Consaquancas of tha NasopharyngSaT Radlvaa Exposura. Symposlia* on Biologic Effacts, Imaging Taehniguas and Dosimetry of Ionizing Radiation. HHS PuOlicatlon (FQA) 80-8128 HONS 222146 Sandler 0?, Comstock GW, Matanoski GH: Neoplasms Following Low-Dose Radius Irradiation of the Nasopharynx. Submitted to JNCI, September 1980 Son* Metals and Metalic Compounds, rntamational Agency for Research on Cancer Monographs on tho Evaluation of tho Carcinogenic Risk of Chemicals to Huaansi Volume 23., JuWet, 1980 Matanoski GH: Risk of Cancer Associated with Occupational Exposure in Radiologists and Other Radiation Workers. Proceedings of the 1980 International Symposiw on Cancer, September 1A-18, 1980. Cancer - Achievements, Challenges and Prospects for the 1980s, Volume l_:2*1 -254, Grime and Stratton, 1981 Matanoski GM, Landau E, TonascU J, Lazar C, Elliott EA, McEnroe W, ' '" EThg Cancer Mortality in an Industrial Area of Baltimore, Environmental Research 25:8-28, 1981 Matanoski GM. Elliott EA: Bladder cancer Epidemiology. Epidemiologic Reviews Vol. 3: 1981 (In Press) MOMS 222187 CONSULTANT ACTIVITIES: Parodontal Qlseases Advisory Conmittaa, National Instl tuta of Oantal Rasaarch, January 1975-Jgna 30, 1978 Subeawiuto* on Adult Health, nodical and Chlruroical Faculty of the StAto of Maryland, September 1975-Juno 1978 Program Oavoloomtnt Board, American Public Health Association. 1977-1978 Food and Orug Amain 1 strati on Biometric and Epidemiological Mathodology Advisory CoMilttoo, Bureau of Orugs, HEH Rockville, Maryland, Nov--Oar 1978-danuary 1978 Air Quality Control Advisory Council, Maryland Stata Oapartmant of Montal Hygiene, March 1978-present Technical Panel on Envlronaental Hazards. American Public Health Association, 1978-1981 Cantor for Olsoase Control, Berylllua Mooting, Atlanta, Georgia, October 1978 Central Maryland Health Systaae, Che1 naan. Technical Advisory Group on Maternal I Child Health, Novoeher 1978*1979 Craniofacial AnoMalles Program, HIM, HEW , Docaafcer 1978 Syavoslua on Potentiation of beMW Response to Vaccines, NIAID. HIM. February 1979 U.S. Army Envlromaantet Hygiene Agency, Residency Advisory Comltteo, Edgowood Arsenal, Maryland* 1978-present Food and Omg Adrlnl strati on. Anesthetic 1 Life Support Orugs Advisory Covlttee, March 1979*1988 Hiau Health Studies Program, Division of Slowitnc and Environmental Research, Oept.ef Energy specialCoMlttee: Consultant to prepare a special report for HQf Secretary Cali fane Review experimental and apidaelologtcai date on the carcinogenicity of beryl 11t*. Center for Olsoase Control, Atlante, Georgia, October 9, 1978 HOMS 222148 ONSULTANT AMO MEMBER: Seienee Projaction Paper Canwnttte. CSR, Inc. Public Matting - A Proposed Federal Radiation Rasaareh Amanda hold in tna Jack Masur Aduitoritmi, Clinical Cantor, NlH. Bathasda, Maryland, March 10-11, 1900 Mnbtr oftha Preventive Madlclna and Public Maalth fast Combi ttee of tha National Beard of Madieal Examiners, 1900-1904 Member of the International Agency for Research on Cancer (lARC) working Group on tim Evaluation of tha Carcinogenic Risk of Chemicals to humps: Same Metals. World Health Organization, Lyon, France, October 23-30, 1979 Member of the AUA Review Cased ttee for the Radiological and Environmental Research Olvislon, Argome National Laboratory, July 1, 19*0-June jq, 19U Participant in the 1900 International Symooslua on Cancer presented by Sloan-Kettarlng Cancer Center with the American Cancer Society and the National Cancer Institute, New fork. New York Conference entitled; 'Cancer 1900: Achievements, Challenges, Prospects' Or, Matanoskl Lecture*. 'Risk of Cancer Associated with OeeuMtlonal Exposure in Radiologists and Other Radiation workers" September 14-10, 1900 Participant and discussant in the joint U.S.A.-Camrtslon of the European Countries Sorlner on Ambient and Biological Monitoring, Luxembourg, December 8-12, 1900 Member of tne Medical Radiation Advisory CoMrittao, Burets of Radiological Health, 19B1- HONS 222109 -9- pjofrsional societies: tairfcin Association for the Advaneenent of Science Amrican Public Health Association New lork Academy of Sciences Sodaty for Epidemiolopieal feseareh International EoideMiolopieal Association Association of Teachers of Preventive Medicine American College of Preventive Medicine ABEAACH INTERESTS: Cancer risks fro* occupational and environmental exposures to radiation and other aptnts; evaluation of health propria*; fasilydated population studies; dental disease; especially oral cancer and the role of iveunolopy in periodontal disease; rhaimatlc fever and streptococcal infections; infant Mortality and eonpenltal eel formations. CURRENT RESEARCH: Epidemiol ay of infant Mortality and congenital msI forestions: survival rates folloarinp dlapnosls of onl cancer-relation to type; factors associated with risk of oral cancer; physician Mortality in relation to radiation exposurt; cancar Mortality in vlroloplsts and votarinarians; occupational risk fro* exposure to dyes and synthdtlc rgpber; health hazards fro* paint teal 1 cation; atloloplcal factors in nultiple Myeloma; envlnw--ntel risks fro* exposure to arsnnlc ; tho effocts of exoosuro to low-levels of radiation in a population of shipyard vorears. HOMS 222150  10. Alvar**. A. P., G. Schilling, w. Levin and a. Kunttaan, Altaration of tha ilcroH*il haaoprotain by l-**thylcholanthr*n*t effect* of athionin* and actincnycin 0. Journal of Phamcolaw and tkoarinancal Therapeutic*. lilt 417-424, 1944. 11- lavin. w., A. P. Alvar**, M. Jacobson, and I. luntaim Cffaet of terag* of froaan livar eicroaanal preparation* on th* hydrmylation of t*to*t*ron* and pentobarbital and th* *-d*n*thylation of athylnerphin*. Iloch--leal Pharmacology, 141 **3-a*9. 11. Kuntraan, A., W. Lav in, G, SchilUn* and A. p. Alvoraai Tha af fect* of 3-aathylcholanthrana and phenebarbital on livar aierocnal haneprotelns and on tha hydroxylation of banrpyrana. tn wicroao-- and Pro* 0ui4atl*a*. Acad--tc Praaa. *av rork, 3t3*3, 194*. 13. Alvar**, A. P., G. Schilling, W. Lavin, k. Kunttaan. L- Brand and L. C. Mark, Cycaohron* P-4S0 and b* in Iwan livar *icroaon*a. clinical Pharuacolouv and Tharaoeutica. JOt 45S-4S9, 194*. 14. Alvar**, A. P., G. Schilling, A. Garbut and R. biotnani Stodla* m tha hyUrexylatioa of 3,4 bonipywno by hepatic aicroaaaaai effect of allwin on th* rata of bydrocylatloa of 3,4-banapyt***. llnrh--1r*l Phyacoly^ 191 1449-149S, 1*70. 15. Alvar**. A. P. and C. J. Waring TVwdttrata kiaatlca of drug* ootaboUsing anayw *y*-- of hepatic olero*--*. holacular pmruaoaloov. 4. 204-212, 1*70. It. Lavin, w., A. P. Alvar** and R. B*fn Olatrlbutlon of radioaetiv* hanopcotaia and 00-blndlng pigaant in rough and woth andoplMBie raticulia of rat liv*r. Archive* of *inchani*try and Rlonhwlca. lift 130-231, 1*70. 17. Alvar**, A. P,, G. Schilling and C. Lavlnt Spaoia* difference* in th* Induction of ainoocal b***prot*ia and 3,4 b*nrpy*na hyhydronylao* by phonobarfcltol and 3-nthylchol anthten*. Journal of Phamaooloav and txearinantal Thara*utic. 17$. 4-11, 1*70. IS. tnMa, 1.. e. S. Li abac. A. P. Alvina, w. Levin and R. flintwn hhnnol to hngntic nierooann. It* lncroaan by athanel nifUn. bloctwtoal Phnnacolocy, 20. 22S-232, 1*71. If. Alvina, A. P., a. Schilling, and R. Kun'twn. Alteration in tha ntwmnoal hwiifnriln and tha kinetic* of 3,4 hcnipyrana hydronylaea induced by 3-notnylcho lanthr--. Tin* cour** *tody and affect* *f purooycin. Lif* Sclancc*. 1> 129-134, 1*71. HONS 2221S1 7 20. Kunttmon, *# * F. Uwm and a. Larin i tffKU of iadveara of ifvor leroacoti uyM on tha ganpaaitlon of mlcroaomal hanoprotaln. Mvawcaa In CvtoBHarmacoloav. vol. r, tdo. r. Clamantl and 1*71. Caccaralll, Rartn Froaa, a. y., dm. 241-24*. 21. Uvuiii a. F., S. Schilling, w. bavin ud R. --------- r Inability of ivbttitut u altar tha eirboi hmx14 and tthyl lanrrranlfl* dlffaranca tpactr* of aicroaenal hamoprotain. Journal of Pharmacology and Prparlnantal Tharanaotlea, 17*i 1-10, 1*71. 22. Kltanl. t. Jt. I. airaroa, I. soom and it. xtf*ui Preparation and propmrtlas of a Mlmbllisod fan of gyrnahrrn* F-4o frca chick anbryo liror microomos. molocular Pharmacology. 7i 230-2*2, 1*71. " 33. Larin. w.. it. icuntnnn, it. F. airaraa and It. a. Cooaoy chroma tography of radioactira nicronomnl Impnulu am diathyianlnoatltyl ealluloaa. Halacmlar Pharnacalogr. 7i *00-310, 1*71. 24. Nltwl, F., IU ViiMhHttt. k. 9. ilTUH. k. Mind and it. bf*ut Interaction of oytaahrona F-430 ritb antlbodiaa rniaod tftlut a aolubillsad P-atO propagation tram hnpa*i* micraanaa. wolocmlar Pharmacology. 7, M*-4M, 1**1. 21. klrarae, a. f. and k. xappoai Infloanoo of iknakiiUul on tha matabcliom and annltoaie affaot of nothodona m rata. Journal of laboratory and Cllnienl dodleina. 7t 430-434, 1**2. 24. Larin, W., a. a. Cammoy, a. *. airoroo, I. Mrtiu and a. Ttppati Induct lam of bamaoCalpyTMa hydronylano in tmn dUn. icionco. 17*i 41^420, 1**2. 2*. hlraroo, k. F. and a. Inppaoi tt* inflmanom of phonoborbital on tbm in Titn and in rim aetaboliam of oathaiinma in rata. la . 1, runta 1*73. 21, aiva d and matbyl F-430 and tk* i' 1400, 1*72. 2*. *--tjfci R. a., l. Oanmi, a. f. Uwm and a. a. cooaoyi tffoot of Moym --Jir am tm Mtnnoliam of bomao(a) pyrame and 3`aalbjl I *m--lijlMlniimihi tin U tk* input and fatal rat. SMBEJtfaiCdU. U' **-** 19Ta- HONS 222152 JO * ticker*, 0. A., L. C. fUrber, a. Ufpu ana a. p. Alvar**t *olychlorin*tad biphenyl* Comparative affects of hiyh M lav ehlorine-centainlny Aroelorc on haptlc nlrad function oaldaa*. waaaageh Ca^un|c*tlona U> Chclcal Pathcloev an* MwaacolowI Ji 5Q3-S13, 1*71. Jl. Alvar*o. A. p., C. J. Parll an4 s. J. Nannarlnfi Inauction of dcuyaatatellM. VI. Effects of phanoberbltal M J-aathylcbolantftrane aAlniatraticn on r lenamrl rlm i*ya* tyiwi of rouh ana Maoth hepatic airrnf--. Bioohaaieal rhimcolow. 2, 1017-104*, 1073. J2. Ivaro*. A. p., A. Pappas, * Levin an4 A. . Coaneyi Ia4uclbllity of benae<a)pyrene hyOruaylaa* in Emm akin bp polycyclic hydro carbono. Clinical Pham*co low ana Theraaoatlaa. Mi 10-40, 197 J. 13. Alvarse, A. P., A. Kappas, . Levin A. I. Cooney i InAuctlon of aryl hydrocarbon hydronyl*** in In Mlcrnaata ana Dry Ovidatlona. Us. A. w. laeabrook, j. a. dilates and a. c. Lai fin. villlaaa an* wilAina Co., Aaicinora, HA., ppa. 304-3*0, 1*73. 34. maiov. a. t.. a. Tianff, o. I. nruahlaa. t. MUnaa, o. a. aichara, A. p. Altar** an4 A. Kappaai Dray-induced altaration* *f ataraiA horaona aetaboliaa la mm. *a>*la *f the n*v Tart fi4ir f Xlancaa. 213 140-134. 1*73. 13. kltarea. A. P-, 0. A, Sicken phenyl* A amt type af A. of liter. fwwtdton tf the Mtioaal 13311331, 1*73. Klyahlerinatad blP-44* i* the of eiaBM. 701 14. Alrarsa. A. P. ana p. Slakwitst eel eloetropboraaia of partially parifla4 aytoahre-- P-430 traa liver alcntena at variouslytrantai rats. Aidehtaal ana AtoaOvaictl aaaaarcb CMimi iriini 341 *33-43*.. 1*7J. 37. i. A.. A. P. A1teres, o. A. Makars. a. Levin ana A. Conaayi of a utiaineyan aatalmMalny auyai la haaa akin. I UTM*r M _____ "itm -- sa. , 0. A., A. KAppna, ana A. p. Altaraai Diffaranena in induct* bility of -nit inarms and hepatic any Mtobollaiat wpai ana jnihriMa P-4SO by poirntWlnaraa bipbsnyla ana 1.1,1-trlchloro- 3,3-bia(p-abloropkawyl)athana (DOT). ~ ~ '" IMi 300-30*. 1*74. ` MOMS 222153 9 39. Uvun. ft. P., 0. ft. lickart and A. Kipped Induction of irufin*r anaynea and aryl hydrocarbon hynroaylaa* by ai- eroacopo u*r*lo oil. Life Polanco*. lt 933-440, 1974. 40. Alvaroa, A. F.. j. Cohn and A. Kappa a< Studio* on th* affact* of ethyl narcury on ethylaorphina K-iaaathyU** and anllina hy- dromylaaa aetlvitiaa and on the contortion of eytochroaa p-430 to eytochroaa P-420. Drue (totaboll and Oiaaaaitiaa. 2i 239 244, 1974. " 41. ftltaraa. a. p. t Micro aoael anayaa induction by druyo and antlrenaaatal cnmical*. In cyanotic*. Ida. r. main, t. Inroad. X. ftickala, ft. 0. Rudsik and >. Sorad. lalatad Prtaa, M. T.. I. I., pp, 143-241, 1979. 42. kickora. o. ft., j. tlanan. ft. Kappa* and A. p. Altaraa> Micro- aeopo liataion ailai tffacta of akin appllcatlaa on cutanaoo* aad hepatic druv aataboliiinf oasyaaa. ftiochaaical Pharaacoloot. lit 779-791, 1973. 43. Kappa a. ft. and ft. P. ftltaraat mam tha Uvar Natabollaaa faraim tubatanca*. Scimtific American. 2331 23-31, 1971. 44. ftltaraa, ft. P., a. Kapalaor, a. laoaa aad ft. Kaypaai 0ro aatabollaa in aonal childron, load pnlaoaad children, aad nocaal adalta. Clinical Pharaacalort aad Tharapautica. 17 179-193, 1979, 49. ftltaraa, ft. P. and ft. Kappaat Tadartlan of aryl hydrocarbon hy droxylaaa Wf polyaklarinatad biphenyl a in tha foata-pUeantftl unit and naonatal liter* duriav lactation. W9 lettara, 301 173-174, 1979. 44. ftltaraa, ft. 9. and J. Cahat Klaatroa eranapart chain and eytochrono* in microacaaa from aalaalo and plant*. I. OMtaat- Call lioloot Data amah. P. t, ftlHaaa aad 0. 0. Kata, ad*., fadacatian of J^arloaa aeietiaa far ttparlaaatal Btalavy, Bothaada, Hi., pp. 399-243, 1974. 47. ftltaraa, ft. 9. and J. Qahai Klactraa Tranapeat chain aad cytarNriawa in microemae from aaiaala aad plant*. IX. Propactiaa. Call Kialort Data tank. P. L. ftllmaa aad 0. 9. Kata, ada., Podaratiaa of Jtaacleaa aociatia* far npw laaai al tioloyy, Bath*ada. Mi., pp. >43-349, 1974. 44. Andaman, C. 9., ft. . ftltaraa, 9. 9aaaa aad ft. Kappa* Drag oaidctlca rata* la haradltary hepatic porphyrin. Clinical Pharaa- 49. ftltaraa, ft. P., ft. Plaabhaia, I. Satan. K. I. ftadamaa aad ft. Kappaat Land iatmioatiaai Kffacta oa eytaalraa P-490 aadUtad hepatic aicrooaml osidatiaaa. Clinical Phamanalocy and Tharaaamtia*. 19t 193-190, 1979. MOMS 222154 -u- 30. Chw|. R. L., *. w. Wood, w. j. oi*M, A. . Cmtj, K. I. Marion. J. IIMan in* a. P. Alvaraa* Aadpyrlna: Itadlolanuaoaaaoy la pluaa and lollvo tollowUi adainlacration of , high 4 low ooaa * * Clinical Phanacoloav and Tharanoutlca. 20: 219-224, 1974. 31. Alvarao, A. r., K. I. Andaman, A. I. CoaMy u4 A. (ayyo: tntiraccloni batvein nutritional Inc torn u4 ln| hlacnaafomaclona af <hQ national Atadaav of klinc... tj* 32. Kappaa, a. ana a. P. Alvaraa: Raw cha liver aatabollcoa toraifn ubatancai. In 0""|p *>lTTlll~IT "rf *M *------ *" Haalth and Olaaaaa. 14. A. J. Vaador- H. I. Praonm aa4 Co, , San Praaclaco. pp 40-40, 1074. 3}. Pantuck, t. j., K.-C. Ralao. a. I. Cianay, V. a. Garland, a. Kappai, K. I. Andaman and A. P. Alvaraa: Ufoct at eharcnnl-broUad boat on phaaacatla notaboilin la nan. Iclanca. 104: 10SS-1057, 1074. 34. Kappaa, A., K. t. Andaraoo, a. . fomy, and A. P. Alvaraa: la (lumen of dlotary proto la and carbohydrate an antlpyrlno and tbaophyllioo notaballan In nan. Clinical Phamaaoloar and Thoraaoutlta. 20* 3). roomy, A. a., I. J. Pantuck. K.-C. laiaa. V, A. Garland, K. I. Andaman, A. P. Alvaraa and A. tappoa* (nbanaod pkamiotin notaballan la hunan mbJ acta fad charcoal-Orallad boat. Clinical miffnlttT mi T1lT"~........ M* 433-442, 1074. 34. Kappaa, A., I. L. 1rodlow, 0. K. tlabnra and A. P. Alvaraa: Induction at 0 dafleioncy of otarald 4k-4a-ra4otaaa activity la llvor by a parybyrlaataalc drag. Journal of Clinical Iavooclnatlm. 30: 139 144, 1077. 37. raonay. a. a., !. J. Pantuck, K.-C. Ralao, . Kuntmon, A. P. Alvina and A. Kappaa* tafuloelm at drug notaballan la nan by anvirm- aantal tkaluli and diet. Todaratim Procaadlaai. 14A7-1432, 197 7. 34. 1 ttlanlotary affacta of pnlychlarlaotnd blphoayla m P-430 and P-414 andlirod nlataaaanl oxldailm. la 30. Andaman, K. t., a. Plocbbaln, D. Itaotbun. I. *0000, A. F. Alvoroi ad A. Kappaa* Plmblan fran airborne land In a firm* rm|a- Aa unaoual axpoaura to a toxic boavy natal. The Anatlcan Journal i Radlclna. *Jt 304-112, 1077. 0, Alvarna. A. P. mt A. Kappaa* Tho ladoclaa propartlaa of polyehlorinatod blphoayla (PCba) aa hepatic naaaaiyiaaaaaa. In Prmnodlat. J apkaaaa.^m^iw!*"' ai,," HONS 222155 1L (1. * A. P. Alvaraa. * C. Aadaraon, V, A. Garland, C, j. Paatuck aa4 A, I. Conaay: Tha rogulatioa of hmaa drug aacaballaa by nutritional foctoro. In Procoodlata of tljj, Third Intoraacional lwaal on Mlcrononoo and Prut Onldationa. Porgaaen Praaa, n. I, 703-70S, 1977, 1, Conaay, a. I. J. Pantuck. t. Cuottaaa, A. Eappoa, K. t. Aadorooo and A. r. Alvaraa: Nutrition and chonlcol hlatraaafamacloaa in banana. 1^ Proceedlane of. (ho Poor Lodaa Confaronca so 7hmacs1oar, cilaleal Fharaacalegy aod Therapeutic* - 11, Alvaraa, A. P., A. riaehboln, X. E. Andaraon and A. Layyaai Alter- aclona In drug netaboliea in varkero occupationally axyoond cn Mlychlarlaatad biphenyl* (PCI*), Clinical Phornncolonv and Thoroeoutlca. UO-14*. 1*77. A. Cohn, J. A., A. P. Alvaraa aad A, Eappaoi On (ha occurrence of crteckrona P-430 aad aryl hydnearhaa hydronylaao la ra( brain. '"YfMl at fawrltttil Hodlclna. lilt 1407-1411, 1977. *3. Alvarao, A. P. aad A. Eappaat lataroganalcy of cytockroaa P-430* induead by poiyeklorlaacod blphoayla. /fmtl Si. Halmlcal aaHSIlt 121> *373-071. 1977. M. riachbalg. A., A, 9. Alvaraa, E. I. Andaraon. a. Ianna and A. fappnn Land latanleatlaa aaoag doaalltlon vorkarai Tha efface of land oa the hnpatle cytothrona MJf ayoton In nan. Journal Tenicoloaar and Invln--intal lenlth. if 431-137, 1977. *7. Aadaraea, E. I., C. K. Poteraen, A. P. Alvaraa aad A. Kagpaet Oxidative drag aacabellan and tadatlblllty by phaaehatbieal in oiekl^cell " il* 3*0-37. 1977. H. Eappae, A., A. P. Alvaraa, K. t. Andaman. K. J. Pantncb, C. 1. Paacuek, K. Chang aad A. I. Conaayi Effect of charcoal-broiled beef on antlyyrlae aad thaephyllfaa na(abelian. SUA&Sii 21i 443-490, 1*7*. *9, riachheii. A.. I. . Bam. I, Bewidev, A. P. Alvaraa, t. Sanaa, A. tagged. J. tfafnar. . . limbers aad I. J. telihetfi Lead hacard aaaeg liaanrtin II lading aa elevated eubuny lino la Ban Toft City. I. Kata J----i * 2|l 1330-123*, 1*7*. 70. Elaaaaa, J. L., aad A. P. Alvaraai Altnraciow ladaaad U baaa peataay narynaa aad aanaatjl--* *7 gold. Phamecolonr J4* 1170-11**, 1*70. HOMS 222156 -12- 71. Alvarao, A. P.: Interaction* baevacn aaviroaaoetal ehealcda and drus blot ran* (o mat laa* la aaa. Clinical Phamacokiiietlea. I.: 442-477, 1*7*. 72. Comay. A. I., E. J. Paatuck. C. >. Paatuck. N. Bouain|. D. H. Jartaa. J. C. Fortaar. A. P. Alvarao, K. E. Aadaraoe and A. Kappa*: Role of eavlrooaaat ind diet la the regulation of huaaa drug aataboliaa la 3a laductios gj Drug Httabolloa. p. K. J. Varies Proaa. Nsw Tork, pp. Jbl-404, 1*74. 7). Alvaro*. A. P., A. Kappa*. K. E. Aadaraos, E. J. Paatuck aatf A. H. Caooay: Micrltloeal factor* rasulatla| 4ru| blot rasa fora* c Lon in mm. la Advances la Phatnacalaav sag, Tharaaeutlea. Val. . Ed., C. Olive, Portaana Proa*. N. T. pp. *J-J1, 1979. 74, Alvaros, A. P., E. J. Paatuck, K. E. Aadarsaa, A. Kappa* and A. H. Comay: Ugulstlan of drug aataboliaa la nan by iart ~r naani il factors. Ia procoedlags at the fyaaoalua m Ores Dlaaealtioo la non. Dtu Hatabollaa levleue.Ts liPltt. 1979. 73, Saaaa, 1., A. Kappas, S. E. laiaatola aad a. P. Alvarao: loan biosynthesis aad irsf aataboliaa la ales with boredltarp baas* lytic aamda: Was axyganssa ladoctlaa aa aa adaptive raapaaaa for cytoakraaa P-430 la ckreelc boaelyala. Jouraal lielocical CbaaAatrr. 23*: 729-733. 1979. 74. Alversa, A, P. aad A. Kappas: Lead aad polyeklartaatad blpbanyla: Effects of bans aad deep aataboliaa. Ia preceediago of the Plaeoaltlaa lg IJ^, Drug Naeabollaa lavlaw*. 77. Alvareo, A. P., A. Kappas, J. L. Ilaeaan, E. K. aaderaon, C. a. Paatock, I. J. Paatuck, K.-C. lalaa. . A. Garland aad A. 1. Cooney: latraladividual verlatloao la dreg dlapoaitlaa. dialed *11111trim ML Tharaaeutlea. 21* *07-*19, 1979. 7S. Al' A. P.l Ilea of di aad carelaagan* la liver lataatlaa. ismrt of the mml SSMtUia. a -- 0. sToapertaaac afiaaltk. Education, aad Halfera. Pel. IT, Pert 21, pp. 93-U3. 1979. 79. paras, A. P., J. L. Sleanm, a^ E. K. Tan*: XaduclbLllty of th* baaao(o)pyvsaa by polyehlertaatad blpbeayla (Pda) la liver and ln| amnanaal properatloaa free rata aad rabbits. Ia Wlcro- pp^?207^18l0^*fadaajc^raasT'K^l^T******^ M. aaaaa, J. 1.. and A. P. Alversa: lane aataboliaa ia the fotoplacaatal salt a^ aaoeatal livers during laetatiaa. Effect o< geld aadlm thlonalat*. Jouraal o Ph*rantslory pad Inserl- watil Tharaaeutlea. 21*i 250-23*7 1900. MOMS 222157 -13- II. llong, T.-S., J. U Unim and A. P. Alvaro*: Inhibition of pulenory eyeoohroac P-*30 and bonto(a)pyrafM hydroxyls** la rabbles by polyehlorlnatod blphanyla (PCIa). Ilochasleal and Hophyaleal Kfoareh Co--uwleatlowo. 9} 117*3-17*9. 1940. |2. Alvaraa, A. P., f, J. Paatuck, a. K. Conway and A. Kappaa: Cffoeta of anvlronaoatal faetora and nutrition on huaan drug aatabollan. In Swan toldjrnloloig and Anlnal Laboratory CoTrslatlona In Chaalcal Carelnoaanaala. oo. 33-72. Ablas Publlahina Corn.. B.J., ltlO. 3, Cooney, A. I., E. J. Paatuak, C. . Paatuck, J. C. Portnar. A. P. Alvaraa, K. E. Anderson and A. Kappasi Variability lo huaan drug aatabollan. In Procaadlana of tha World Coofaranea on Clinical Pharmacology and Tharaaauclc*. pp. 31-42, Macmillan Publiabaro.. London, 19P0. I*. Uoag, t.-H. and A. P. Alvaraa: Selective loos of pulaoaary cytochroa P-*30t In rabblto pratrantad with polychlorinated blphanyla. Journal of lloloalcal Chaniatrr. 2J4: 7334-73*2, LM1. 3. Alvaraa, A. P.: Cytschronsa P-*SO: Monarch highlights of tho loot ern daeadas. Orns Mtsboltan EarIowa. U' *M-*J*. M. Alvaro*. A. P., J. L. Elasnaa, T. -M. (long and A. Kappas: Pslycklorlsatod blphaaylsi Spaclaa and tlsaua apaolflaltlas of tha Induction of aoaooxygaaaoaa la rata, nlca, rabbits, and hunans. Is proceeding* of workshop as lb Combined Iffim Tf wtUotlas. Rational Maaarch Count 11, Canada, la press. (Apis Milliftra) venom on ths cowroa of odjwwi and doprooalon of drag aatabnllsn Is tho rat. la proao. M. Alvar**, A. P., T. HL tag and 3. L. Elaanaat Polychlorinated blphanyla ladueibls aanaasypasaaaa In rabbits and nlca: Spaclao and argan apaolflcltlao, fUritlt In prana. HONS 22215a -1 CURRICULUM VITAE NAME: SIRTHiMTE : (t*T1irU\CE CITIZENSHIP: SOCIAL SECURITY NUMSER: JUSTNESS ADDRESS: HOME ADDRESS: Philip E. Enterline A/25/21 Kictanning. Pa U.S.A. 181-K-S618 A315 Crabtree Hell. CSPH ISO DeSoto Street Plttaburgh, PA 1S261 ]2 St. Clair Drlva Plttaburgh, PA 1522S TELEPHONE: 412/624-3013 TELEPHONE: 412/343-1330 UdiiritiAuua 19JS-42 Graduate 1941-S4 1935-40 EDUCATION AMP TRAINING Voetaioettr Collaga 88a (1942) Econoalea American Unlveralty Aaerleen Unlveralty HA (1954) Ph.D. (1944) Stattacle* Oeawgraphy (Dr. Frank Lonme APPOINTMENTS AW POSITIONS 1940-45 1945-47 1947 - 4ata 1*75 Amrlcan Unlveralty Profeeeorial Laeturar Unlveralty of Plttaburgh Unlveralty of Michigan Profaaaor of Blootatlatlea Faculty, Suaaar Saaalon oo Health Cara Orgaolaatlon fe'ltaaialc Poeltlona 1942-45 19*455--5S0O U.S. Any U.S. Public Health Service Stetiecielea MOMS 222169 2 1910-54 1954*59 1959*61 1961-65 U.S. Public Health Service Aaat. Chief Prapraa Anelyaia Section Tuberculoala end Chranlc Dlaaaaaa " Chief Statistician Heart DLataaa Control I'ruprae " Chief. Morbidity and Health Staeiatlca Ireneh, Pubiie Health Kathode " Chief. Iloaetrica and Social Scudlea Ireneh, Occupational Health MEKEKSHIP In PtortSStOHAL OtCAHIIATIOHS 1946 - praaaat Aaerlcen Public Health Aaaaeladoa 1946 - praeant Amt lean StetletlealAeeeeladoa {Treasurer Pph. Chap tar 1972*74 Council Haaber 1971-7]) 1969 - praaaat Intarnetleael lpidaalelo|ical Asaocladoa 1971 * praaaat Society for Oceupatiaeel and Eavlranaaotal Health 1955 1972 1977 1957 1957 1931 1979-91 Pellaw, Aaerlean Pubiie Heelth Association Elected Follow, Morican Steele deal Association Plttabur|h Scatlade lee of the Tear Of Oeperreeatal Superior Sarrlco Award IV Dopertweetel Holoaa - Arthur S. Plowing Award for Tan Meet Outerand1m Toum Mm la Covaranwnt PI CeMB Hu (letieeal Social Science Honor Socioty) Haaber, Editorial Seard, Aaericen irrlaa of laaplretory Dtaaaaa HONS 222160 e--china (eurroot) Bootatlatlco 211 goatatlatlt* 216 goatatlttlct 219 -3PPOFESSIONAL ACTIVITIES Frlntlplaa of Statlatleal Reasoning Introduction to Saapllnf Vital and Hodleal Care Statlstlea ffanarch and Train in* (1947 - data! Cranta and Contract a Tara Tod oral Cranta Tltla 1944-74 1472-73 1971-73 Tralalat H Public Haalth Statlatlea Tralalat In InduatrUl lloatatlatlca Train Inf in Had lea 1 Cara Stacladca 1949-76 1474-77 Study of Cho Cffacto of National Haalth Iaauraaca la Quaboc Plooalat Croat on Childhood Load Po loan lag 1977-41 Caacar la Artonic Eryoaod Pofulatloat Sourea NTS NtCSS HOUR NCSSR N* MCI Non Fad oral Contracts 1979-40 laolth of thrkaro la Hlaoral Vbol aad Fibrous Glass Manufacturing 1974-40 Mortality of Nlckal tfcrbaro Nuatlagton, V, Vo. 1973- Swrvoillaaco of Soalth of Chaoleal tferksra Saar Pork Tana 1901- Itortsllty Anas Sooltor tfcrkaro 1901-42 Crosa-f actional Study of Pulaoaory Function la Alcoa Arkaaaas tfcrkaro nm MOST. ALLOCS 3SSLL oil )OA ALCOA Othar Woo-moral -- HO, MS Aaounc $134,18 3 $161,406 $274,374 $7*6,532 $ 71,790 $313,470 $303,339 $104,351 $ 36,60* $*50,377 $ 3*. 386 l. Othar Soooorch oai Tralalao o^iw atn-tat-- 1WO-4J hool Unbar, 0.1. loar4 of CItU Sinlci Emlaaro Sti(lotUUa) 1444-70 Soalth SorrUos Untrek Stair Sootloa, ISMA 1447-40to Soalth Advisory Conlttsa, Notloaal laraoa for BeoaoaU loooorch 1447-72 Advisory Fallow, Halloa Zaotltato aad lodaotrlal Srslaao Pondst too MOMS 222161 -4- 1970-72 1972-75 1972-74 1974-76 197 5-79 1979-80 1979 1979- Hoalth Sorvleca Oeaonatratlona Study Section. i:S71* National Advisory Food and Orup Committee, FDA Psnol on Chromium. Cm It too nn liolopieel Effaeta 0f Atmoapherle Pollutant*, Nattonel Ac ad mi y of SeLanca* Chairman. Advlaory Conilttao on Longitudinal Study of Subattrlnors, U. S. Navy Pulmonary Dlaooaos Advlaory Commit too. 101LII Took Fore* on tho tpldealolopy of Respiratory Dlaaaso. :atlai Chairman. Commlttao oa Occupational Apents Lltaracura Rovlever-tpldanioloay-J- of Occupational MmitcUi* Aaaociato Diroe tor, Cantor for Environmental Epldaiolo|y Sarvlca (currant) 1. Departmental: Chairman (1976-data) School: Mmber, Dmam'a Cabinet 3. Local and Stata; Cranta tavlav Commlttao, Pannaylvania Coal Horkaro Respiratory Dlaaaso rropru FWUaTIflW I. Refereed at tie loo Enterlino, Philip I., and Samar, Hor hart I: Commit y-vida X-ray aurvaya, vi, Record a and Upnvte, Pub, Health Hop, 66:1613-1624. (December 7, 1951) . Entarllna, Philip t: Croup Cheat X-ray bnmlmationa and the Tuboreuloala Oaath lata. Pub. Hoalth lap. 67:762-766 (Amp. 1932). Payua, Hounid H., tutorllaa, Philip I., and Houck, Julia: A Study of tha Pooltlvo *------6--im"- P lad lap a for 1941 tfcahlaptoa Hooa Survey. Am. Rav. The. 66:346-366 (Ham. 1931). Imam, lfcltar H., amd Intarllna, Philip I: Dnlayad Hood Super OotoratnotlonsEvmluatlaa of o liood Paranrvatlvo. Pub. Raalth lap. 69:240-246 Qfcrch 1934) . Aadoroom, Mbart J., latorllno, Philip I., and Tumor, Otto D. Undotec tod Tuboreuloala la Varloua leoaaale Groupa. Am. lav. The. 70:393-600 (Oct. 1934). Aadoroom, Robert J., tatorlime, Philip I., Hill, Rank J., and Roberta, Jaan: Ao tvoluotloa of Tukorculoola Detect tom by Chmmc X-ray Survaye. Pub. Health Up. 69:1033-1060 (Hov. 1934). Kurlender, AraeU I.. Rill, Elisabeth , amd Interline, Philip U Ao Evaluation of Some Calmly Uaad Sermonlap Taeta for Heart Dleoeea amd Hyportanslon. J. Chr. Ole. 2:427-439 (Oct. 1933). HONS 222162 ;*rllne, Fhlltp E.. and Stewart. WilluB : Geographic patterns in Deaths ro* Coronary lltirc Dlsaasa. Pub. Health Rap. 71:8*9-855 (Sape. 1956). it wort, Will las H.. an* Entorlln*. Philip C; Ecology and Coronary Heart J. Chr. Dla. 6:86-89 (July 19J7). jrodaur, Arsand_ E.. Baker. Jana* ?.. and Cntarllna. Philip E: Saw on Chest Photofluorograms and Dlegnosable Heart Disease. ud. Thar., and Hue. Mod. 7*: 226*233 (Aug. 1937). Abnormalities An, J. Roent, Cntarllna. Philip t. , snd Kordan, Barnard: surveys of Tuberculosis and Heart Disease. (Oct. 1958). A Controlled Evaluation of Mass Pub, Health Rep. 73:867-873 Eatarllna. Philip E., and Capt, Katharine G: A Validation of Interaction Provided by Household Respondents In Health Surveys. An. J. Pub. Health *9)203-212 (rab. 1959). Zukol. Will lea j,. Levis, Robert H., Enter line, Philip !.. Painter, Robert C.. Raison, Lloyd S., Fawcett, Robert M.. Meredith. Alla F., and Peterson, Bwtrica. A Short-Ten Coneunlty Study of the Epldanlology of Coronary Heart Disease. An. J. Pub. Health 49:1930-2039 (Doc, 1939). Sauer, Herbert 1,, and Interline. Philip E: Are Geographic Variatlone la Death lotae for the Card levaocular Dlseasaa Real? J. Chr. Die. 10:313-32* (Dec. 1939). Interline, Philip t., liUl, Arthur I., Sauer, Herbert l.. and Hymen, Merton: Death Rateo for Coronary Hanrt Diaeaaaa In Hatropolltan and Othor Aroaa. Peb. Health Rep. 73:739-764 (Atig. I960). Maredlth, Alla P., tatorllao, Philip t., potoraen, lentrice, end Pskovor, Jean C; An Ipldeelelogic Diet Study In North Dakota. J. an. Dletet. Aaeoc. 37 :339-3*3 (Oet. 1940). Interline. Philip I., and Stewart, Will las K: Eat lest ad Morbidity in the On itad Stataa baaod on Moethly Laker Force Report. Pub. Health lap. 73: 1131-1160 (Dee. 1960). Interline, Philip Ii Caweee of Death Raeponolblo for Roe set Incroaooo in San Mortality Dlffarsntiala la the Onited States. Milbaak Ha. Pond (hurt. 39:312-328 (April 1961). BetKllas, Philip t: Hhrk Uti Due te Illneee la Selected Oecupetlona and Induacrlee. J. Oecep. Med. 3:403-411 3apt. 1941). towert. Will ion 1., end Merlin, Philip I) Effects of the notional Sarvtca an Phyalnlena UtlllMtlae end Health la and Men. Hew b|Us* J. of Mad. 163:1187-119* 9m. 1961). Merlin, Philip I., and Stewart, Will in I: Haalth Program itfiirtaati to Offaec Effeeta an Lamia af Living. An. J. Pub. Haalth. 32:401-409 Otorch 1962). Cooper, w. Clark, Marlin, Philip 1.. and Werdsa, Eleioe T: Minting Occupational Disease Hnsards Through Medical Care Plena. Pub. Health tap. 77:1063-1070 (Dee. 1962). Interline, Philip t., and HeKievor, Mgan* F: Dif foroet ini Mortality Proa Luag Cancer by occupation. J. Oeeup. Mod. 3:263-290 (Juno 1963). MOMS 222163 6 Syue, 5. Leonard, llyuan, Herron J.. end Interline. Philip t: Son* Socul end Cultural Factor* Aetoc toted with ch* Occurrence of Coronary Heart Dlteaee. J. Chr. Dlt. 17:377-1*9 (1966). Enterlln*, Philip C; Sick Abaence for Hn end Uonen by Marital Statu*. AMA Arch. Environ. Health. *:*66-470 (March 1966). Encerllne. Philip E: Mortality Rate* Aaong Coal Miner*. An. J. Public Health. 5*:75*-76t (May 19t*) . Enter line. Philip E: Uork Los* Du* to Illneea In Cereals Western Nation*. Men* *n Onderning. Qlep 1966). Enter line, Philip E: Uork Loee Du* to Ulnae*. Monthly Labor Review. 87:11*1-11*3 (jOct. 1966). Enterllne, Philip > flak Abeenee In Cartatn Ueetarn Countries. Ind. Nad. end Surgery 33:738-761 (Oct. 1966). Enterlln*. Philip t; The E*t lost Ion of Expected late* In Occupational Dlaaaa* Epidemiology. Pub. Health lap. 79:973-97* (Hew. 1964). Syuo, 5. Leonard. Hyuan, Merton H.t and Batarlls*. P.E.: Sociocultural rector* end Coronary Heart Dleeaa*. Sociological In*. Vol. 36. lie. 1. (Winter. 1966). Syno. S. Leonard, Hyuan, Morten M.. Interline, Philip t: Cultural Mobility end tha Occurrence of Coronary Heart Dlanaan. J. of Haaith and Hunan Behavior Vol. 6 (Winter, 1965). Aahford, J.H., Enter Una, Philip *: Radiologic Cleeelf leaden of the Pnaunoconioaaa. Arch, of Invlron. Hick. Vol. 12, (March 1966). Enter Una, Philip El Social Caueee of Sick Abeenee. Arch, of Environ. Kith. Vol. 12, (April, 1966). Enterlln*, Philip I; Tha Effect* of Occupation on Chronic Hooplrecory Dlooneo. Arch. Environ. Ilth. Vol. 16, 119-200 Con. 1967). btnllae, Philip I. end Lnlahnrt, H.S.; The inletlonehlp between Coel Mining and Chronla Henapeclf 1c Hoop Intory Diaaaoa. An. 1. of Pub. Hoolth Vol. S7, Ho. 3, 6*6-69S Ohnk 1967). btnllae, Philip g. end Kendrick, Mildred A: Aeboocoe-Duat Expeeurea at Variona Laval* and Hartal Ity. Arch. Environ. Rltk. Val. 13, 1*1-1*6 (teg. 1967). Herevil*. 1. end Entnrllne, Philip ft Lung Canc teang tha Java. An. J. of Pub. Hltb. Vel. 60, Ha. 2 (Tab. 1970). btnllno, Philip t: Validating Threehald* Doing Induetrial Record*. J. af Scaup. Ned. val. 13, Ha. 1 (Pab. 1970). Eaterllaa. Philip K: Epldanielegy af Ceal rkar'* Pamaaranlnel*. Ind. Mod. aad Sucg. Val. 39, 113-117 Obreh 1970). Haruaa, I. aad totorllaa, PhUip E; Lung Cancnr teang tha Jm end Jon-Jew* of pitteburgh. Auer. J, of Epld. v*l. 91. Ho. 6, 333-367 (April 1970). HONS 222164 -7 interline, thill* I.. DaCoufle. Pierre, and Handero:\ VivUn: Mortality in ;Latlon to Occupational Expo aura In cha Atbeito* industry, j. Oecup. Kcd. /al. 1*. n*. 12 (Dec. 1972). 'atariina. Philip E., DaCoufla. P. and Mendanon. V: Respiratory Oncer la delation to Occupational Expotures Anong Retired Atbettot Worker a. Brit. j. taduatr. Mad.. Vol. 30. 162-16* (1972). tntarline. Philip E.. McDonald, J.C., McDonald, A.O., and Seltar, V: rite Effect* of "Prea" Medical Care on cha Practice of Medicine - The Quebec Experience. New England J. of Mad. 221:1152-1155 (May 31, 1973). tteDonald, A.D., McDonald, J.C., Stelnueti. M., Enter Una. P.E., and Salter V: Phyalclan Service In Mantreel before National Health tnauranca. Mad leal Cara 11 (July-Auguet 1973). Hatoereon, V., end Enterliae. F.E.: An Unueuel Mortality Experience In Cotton TeztUo Darker*. j. Oecup. Mod., Vol. 13, No. 9 September 1973), Eaterline, P.E., Salter, V., McDonald. A.D., and McDonald. J.C.: the Distribution of Medical Services Before end After 'Tree" Medical Cara--The Quebec Experience. Now England J, Of Mad, 189:1174-1178 (Nov. 1973). atarllne. t. t. and Headarena V: Tyro of Aabeetoc and Booplrttory Cancer la tha Aabaato* taduatry. Areh. lav Iron. Kith., Vol. 2A (Nov. 1973), latorllaa, t.E., McDonald, J.C., IfeBaeall, A.D. oad Hander ten, v.: Phyalclan** Harking Moure oad Petlaat* Soon Bofaro end After National Hnaith Inouraace. Medical Caro, Vol. 13, to. I. Ctabrnary 1979). latarllna, Philip t: loaplratory Cancer Among Chronat* Wtorkert. J. Oceup. Had., Vol. It;323 (Aug. 1974). Inter lino. Philip B. and Hendoreon, V; Martdllty and torhidlty Exparlaoce of Eat trad plbroua Cleat tor her a. Arch, of tovlron. Kith.. Vol. 30 (March 1973). McDonald, A.D., McDonald, J.C. Saltar, V. ead latarllna, P.t.; Ef facte of quaboc Medicare on Phytictea canonisation for Selected Synptone. Nov Eng. J. of Mod. 291:*49-432 (Dope. 20 1974. Enterliae, Philip E: Pitfalls la tpIdHieingLeal Eeeeareh. J. of Oecup. Hod. Vol. II; 130-13* (torch 1979. Interline, Philip li 1stlasting laalch Elaha la Stud lee af the Health If feet* of Atbeotoo. to. tor. of topintwy Diaooao, Vol. 113 (1971). Place, S., tour11m, Philip I., taderaan, V., oad Varner, Michael, 0: Mortality Experience la toiatlea to a Mae on* id Arsenic Trlonlde Expoacre. Envlroouentel Health Pnrapenttmo. Vhl. 19*127-130 (tog. 1977). McDonald, J.C., toBanald, A.D., and EnterHas, P.E.; Som Efface* of Madtcoro la ^inboe (ttudaa ear l'aaauranea-nclcdlo due Quebec) toelologle at Socletea. IX, 1, pp. 31-73 Spring 1977), tlcci. t.. Interline, p.t.. landarson. V: "Contacts *tth Pharaaelata bafera sad After "Free" Medical Can -- tha Qn**v* Experience," Medical Cara. Vol. 14. Da. 3, torch 1979. HONS 222165 -3- Pinto, S.. Henderson. V. and En tar Una. ?: Mortality Experience ot Arinlc Expo tad VJorkcrs. Arch, of Environ. Hlth. pp. 325-331, Mov/Dac. 1978. Marsh, C. and P.E. Entarllna: a Mat hod for Verifying tha Coaplatanas* 0f Cohort a Utad In Occupational Mortality Studiat. J. of Occup. Mad., Vol. 2t 10, pp. 665-470. October 1979. Entarllna, P.I.; Aceribucabtlity In cha Faca of Uncertainty, CHEST. Vol. 78. p. 377S-379S, Suppliant August 1980. ' 2. Proceedings Entarllna, Philip E: A Controlled Evaluation of Caaafindlng by Cheat X-ray. Proeaadlnga of tha Hatlonal Tubarculoala Association (Map 1957). Entarllna, Philip Ei Trend a and VarUtlona In Sick Absence in tha United Scat* Proceed Inga of tha Second Int'l Conf, on Sick Abo. Statlatica. Anatardaa, Tha Kae her Unde (AprU 22, 1965). Entarllna, Philip Is Mortality Anong Asbaatoa Product a Markers in tha Unltad Stataa. Annala of t ha N.Y. Acad, of Scl. Vol. 132 (Doc. 1965). Interline, Philip E: Tha Statlatlclan In Epldaalaloglc taaaarch, Tha Procaadlngn ot tha Canadian Aeaoc. of Taochora of Sac. and Prev. Mad., Annual Maatlag. (June 3 and A, 19M). Entarllna, Philip E: Asbaatoa Duac Ineranenta and Mortality fron Two Dtaanaes. Procaadlngn of tbo Soeond Int'l Conf. on llologlcol Effocta of Asbaatoa. Oraadan, Conan, (April 19M) . Entarllna, Philip E: tec ant Oovslopnonca la Sick Aboanca Ststlatlca, Trans act Iona of tho 33rd Mooting of tbo Induotrlal Nygino foundation of Anar lea, lac. (Oct. I960). Entarllna, Philip 1: Statistical Studlaa of U.S. Asbaatoa Products Uorkars. Proc sad lags of fibrous Dust Saninar - Malian Institute, Pittsburgh, PA (Hot. 22, 19M). Entarllna, Philip X., Saltar, Vara, McDonald, A.D., and McDonald, j.C.s Doctor Viaita la Various Incoua Croups Prior ta Canadian Kadicara. TTt----- *1ngi of tho VI Couf. of the Int'l Xpldniologlcal Asooclation. Prlnootan, Tugoalnrla, (Aug. 1971). McDonald, J.D., MeDoanId, A.D., Stalanots, Eatarllao, P. and Saltar, V: Usrk at Physicians Is Nentraal. Procoodlngt sf tha VI Conf. of tho Int'l XpldoniolagiMl Assoc 1st loo. Prlnestan, Yugoolsris (Aug. 1971) . newline, Philip I. and Hhill, N: Asbaatasia In Aabaatna Cast Worker*, frof and Inga af tha LAIC Harking Croup to Aaaooa tho Uo logleal Effects of Aobostos. Lyou, franco (Oct. 1972). Entarllna, Philip Si A Ravlou of Mortality Data for AnarIcon Cool Minora. Annals of tha l.Y. Acad* of Scl., Vol. 200 (Dae. 19, 1972). Eatarllae, P.X. Praaaadioga af tha Third Anneal Industry-Cavemant Coefer*Asbeetoe lnfornatlan Asaaclstlon of North Ineriea. (tape. S-9, 1976) pp. M- Intar Ilia, P.X.: Proceedings of tho la cardapextsaatal Itorkar' Conpanastion : fores Confaranca on Occupational Diseases and Ibrharo Conpanastion, U.S. Governsent Printing office. (1976) pp. 13-15. HONS 222166 -9 itullfl*. P.E.. Place, S,, and Henderson, v.: cancer Among Arsenic Exposed tptluti In e Copper Seeltur. Proceedings of che Air Pollution Control AssocUtIon, feeton, Kov. 8-9, 1976. Goterllne. P.rT: Epidemiology In Studies, of Occupational Heeleh. Proceedings of the Annual AHA Congress on Occupetionel Health, Septsebcr 90, 1977. toterllne, P. E.: Epldoniologleal Methods for Establishing Dose-Response golstlonshlp* in Asbescos-Du*t Related Diseases. Proceedings of the Asbestos Jympoolun, Johannesburg, South Africa, October 4, 1977. BStsrltns. P.E. : Epldeelologle Methods In Industry. Procosdlngs of tho ITAI Health Protection Seminar, Copenhegea, Denmark, June 29, 1977, or line, P.E, end Marsh, C.M.; Environmental end Mortality of Markers from e Fibrous Close Plant. Proceedings of tho Socloty for Occupetionel end avlronmoncel Health, Ueahlngton, DC, December 6, 1977. I&terllao, P.E. and C. Marsh: Environment end Mortality of Morkera from a Flbroua Claao Plant. In Dusts end Dleeeeee, 1979. Interline, P.E,: Some obsmrvatlene on Geographic Tar la done In Mortality. Procondlngo of che 13 th Annual Conference on Traco Substance# la Environmental Health, Columbia. Missouri, June 3, 1979, pp. 19-27, Interllao, P.1,: Anbeatoo and Health Panel lenerke, 4th Industry end Government Conference, Asbeetoe Inf ernet Lon Aeooclatlon, Sept. 19-20, 1979, Arlington, va. fetterline, P.E. and C. Norsk: tfertallty of Markers in tho Men-Mode Miners 1 Fiber Industry, Proceed Inge of tho Symposium on tho Biological Effects of Hlnoral Fibers, IAHC, Lyon, Ftonce, September 23-27, 1979. Interline, P.I.: Sorting Out Multiple Caueol rectors In Individual Cases, Procondlngo of tho Socloty for Occupetloanl end Environmental Health, tbohlngten. DC, Daeembar 4, 1979. Henderson, V, and P.E. Intorlloei Aebeecoe Exposure; Tectore Associated with Ixceee Caneor and Inspiratory Diseoeo Mortality. Amnola of Pf Academy of Sc loneee, Vol. 33, pp. U7-121, Decembor 14, 1979. Interline, P.I.: txtropeladen from Oecupmdonol Studios--A Substitute for Environmental tpidemlalogy. Proceedings of tho First Annual Symposium on Cnrlroanancal Epidemiology, Pittsburgh, pa., April 21, 19d0. Intorllno, 9,1.i Doe of tho tatloaal Booth Indot la Occupational Zpldmlclogy, Peased Inge of the Public Heelth Conference on Record end Stadetlao, *-g--` 5, 19M. Interline, T.t. end 0, Marsbi reality Among Markers in a Mlckal Refinery end Menu feecuring Plant In Moot Virginia, USA. Proceed Inge of the 2nd Intornntlonsl Hlckol Conferonce on Environmental end Occupetionel Tonlcology of Hlckol, Suessee Melee, United Kingdom, September 3, 1910. Enter line, P.I.: Preport loo of Cancer Duo to Expoouro to Aaboetoe. Proceedings of tho ConSoronco on thn quantification of Oeeupadonel Caneec. anbury Cantor, Cold Spring Sorbor Laboratory, March 30, 1901. MOMS 222167 10 Entarllna, p.E. : Epldcalolotlc taii* for tha Anbaato* Standard. ProcauJ.rv* of tha Sacond Annual Synpoilum on Envlronmantal Epidonlolo|v, Pltt'.burjh, ?' April 28. 1981. ' Entarllna. P.E. and C.M. Mar*h; Mlaslni ftacord* in Occupational niic** Epldtalology. Proceed in|i of tha 1981 Anar lean Oceuatlonal Haalth Conftranea Atlanta. CA April 29. 1981. ' 1. Abstract* Entarllna, P.E.: Faetora Aaaoelotad with CaagrapHlc Olffaraneaa In DaatH* fro* Coronary Haart Dlaaaaa. Circulation 14 (Nov. 1958) . Syna, S. laonard. Hyoan, Mar ton M.. and Entarllna, Philip E: Soaa Soeial and Cultural Faetora Aaaoclatad with tha Incldanca of Coronary Haart Dlsaaaa. Circulation. (Oe. 1981). Entarllna. Philip E. and Nanaa, Nlcholaa Et Sax Dlffarontlals in Mortality In En|land and Ualaa and In tha Unitad Stataa. Population Indax (July 196]) . 4, Othar Entarllna, Philip E,* Hauardlns tha Slab. (Editorial) J. of Anar. Mad leal Aaaoc. Vol. 198, No. 5, 0*r 2, 1988). Entarllna, Philip It Aabaatoa and Public Haalth (Editorlal) . J. of Anar. Had leal Aaaoclatlon, Vol. 201, No. 12, 148-147 9 opt. 18, 1987). Entarllna, Philip I, i (Manhar af CoMlttaa) Standard a for Epldwlolotlc Survaya In Chronic Inaplratoty Dlaaaaa. National Tubarculoala and taapirstory Dlaaaaa Aaaaelatlon. Nan York (1989). La Inhart, U.I., Dayla, H.H., Entarllna, Philip t., HanacHal, A,, and Kandrick, H,A.; Pnawoconloaia la Appalachian lltunlaoua Goal Minor*. U. S. Dapt. af laalth, Educatloa, and Ualfara, Pub. Iltb. tarvlca, Publ. No. 2000, (1989). Entarllna, Philip E. and Jacabaan, H.: "Epldanlalapy" in Hadielna In tha Hlnlng ladnacxlsa, ---------- Nodical Boaka, loadou. 1973 (J. lagan Ed.) Entarllaa, P.E.s Tffacca af Chrenina Conpauada an Bunaa laalth" In roport on Chranlaa prapnrad by chn National Baaaarch Council, National Acadany af Sclancn. tteahlagcon, D.C., 1974. atarllaa, P.E. t dditarlal) Aabaataa aad Cancan The Intornattonal Lag. An. lav. of Eaap. Dia., Val. 1U *975-978 (Daaanbor 1978). Entarllaa, P.E., HeDonald, A. and Me Donald, J.i Sona af facta af Quabac Haalth Iaauroaaa. ROBB Baaaarch Dlgaat S ariaa, nth Puh. Ba, (IU) 79-3328, January 1979. MOWS 222168 -L- CURRICULUM VITAE Nam: Frank G. Standaert Horn Address. 520S Stone Trail Drive Bothnia*. Maryland 20617 Business Address: Business Telephone: Btrthdata: 3*00 Reservoir Road, M.U hash 1n*tOft. D.C. 20007 (202} 625-7635 Noveober 12. 1929 11 rthplaca: Paterson, Now Jersey Citizenship: U.5.A, Narital Status: Married, 3 sons Education: Hervard Coll#9*. 1*47-1*11, A.I. (eua laudo), Chemistry Comal 1 University Nodical Coll#**, 1951-1955, tt.O. Apoolntmnts and Posit Iona: Tho John* Hopkins Hospital Intomo (nodi el no) 1*95-1*16 Comoll Unlvorslty Nodi col Coll#*# Research Fallon, 1*56-1997 Instructor In Phemecolo*y, 1*59-1*60 Assistant *ref#stor of Pharmcolofy, 1960-1964 Assoclot# Professor of Pheratcoloty, 1*66-1967 Goor*otown University Schools of Medicine and Oootlstry Schorl* Foundation Professor and Cholnwn of Phomocoloty, 1967- Tho Murrey ontf loonlo 6u**onholo Oontal Clinic Lecturer u tho staff, 1960-1967 ovol Nodical Rosoorch Institute. lethosOo, Naryland ftoost Scientist, 1967-1*70 halter Need Ar^r Inotltvte of Denul Nesoarch Consultant-lecturer, 1966-1*72 Naval Oontal School Consult ant-lecturer, 1970-1971 HONS 222169 -2- Appointments and Positions (Continued): -U. S. Government: National (nstitutas of Health Pharmacology and Endoerinology Fellowship Review Committee, 19(8-1971 Neurological 01 sordart Program Project Review Comlttae, 1971-1 975' Chairman 1973-1975 ' Pharmacology Toiicology Program Project Review Comlttae, 1976-19(0; Chairman, 1977-1980 fourty International Fellowship Review Commit too, 1975, 1976, 1979 (Chelmen), 1981 (Chelmen) Biotechnology Resources Review Comlttae. 1981* hiC05 Comlttae to review Antloplleptlc Drug Development Program, 1961-1987 Veteren's Admlnlstratlon Went Review loard, NeuroOlology, 1974-1977 Chelmen, 1976-1977 Consultant, 1977 Congress of the United Stetes Comil ss Ion on tho Fedorel Orug Approve! Procoil 1911- Fedorel Trade Collision Consultent 1971-1976} 1978 Occupotlonel Sefety end Hooltti Administration Consultant 1974 Prl veto: Notlonol Reseerch Council Comitted on Toslcology, 1971-1977 Ponel on Anticholinesterase Chemicals, 1911Olvlslon of llologor and Agriculture, Representative frm American Society for Ptiaraocology end Experimental Therapy, 1987-1977 Safe Orlnklng hater Comlttae (consultant) 1978 Pesticide Infomatlen Review A Evaluation Committee 1977-1981 Common on Military Environmental Problmas, (Choiman) 1910-1981 Comlttot on Recomendetlons for u. S. Amy Basic Scientific Research 1961- American Heart Association National Capitol Affiliate HI* School Research Comlttae, 1970-1972 Chairman, 1971-1972 Research Comities, 1972-1977 Board of Directors, 1972-1978 Middle Atlantic Rational Heart Comlttoe Research Review end Certification Subeomlttoo. 1979-1981 U.S. Phormcopolal Convention, 1970- Exxon Health Research. Board of Scientific Advisors. 1981* MONS 222170 2- Professlonal Societies: American Society for Pharmacology and Experimental Therapeutics Cowlttoo on Intersociety Relations 1966>1964 Representative to Oiv. of Biol, and Agriculture, tws-NRC, 1966-1977 Representative to Publications Comalttoe of Federation of Aneriean Societies for Experimental Biology, 1970*1976 Educational and Professional Affairs Coamlttae, 1971*1974; 1979Subcomalttee on Sraduate Convocation Program, Chairman 19 72*1974 Program Cotmtutae (ad hoc member), 1964Ad Hoc Comalttoe on Teaching of Pharmacology, 1970-1971 Task Force In Support of Training and Research, 1973-1976 Secretary-Treasurer, 1976-1977 Comaltteo for Liaison with Society of Toxicology (Chairman) 1976-1978 Long Range Planning Comal tteo, 1979* ; (Chairman) 1979-1941 Federation of American Societies for Cxperlemntal Biology Publications Coamlttee, 1970-1974, Chairman, 1971-1974 Life Sciences Research Office-Panel for evaluation of health hatards of irradiated beef 1977-1976, Long Range Planning Croup, 1960 Treasurer Elect 1941 Association for Nodical School Pharmacology, 1964Councillor, 1974-1975 Secretary, 197S-1976 Society of Toxicology Coamlttee on Ethics of Animal and Human Experimentation (Co-Chairman, 1974-1974) Toxlcology-40's Commission, 1979 Sign* il 1960Vice President, Cornell Nodicol subchapter, 1966-1967 Executive Coamlttoo, Georgetown chapter, 1970-1973 The how Torfc state Society for Nodical Research Vice Presidoflt, 1961 Vico President and Treasurer, 1966-1967 Editorial Positions! ^jawtiwaiif* T*r"*',a Field Editor, HourepMmacology, 1971-1974 Guest Field Editor, 1974- c,",< ,*'m" Science; Anestheslolodr (id hoc) Fellowships and Awards; U.S.P.H.S. Career Development Awardee, 1961-1965, 1966-1967 Golden Apple Award, 1964 MOHS 222171 4 HI Harv Service: U. S. Nivy, 19S7.19S9, Lt. (M.C.) U.S.N.R.. Stationed at Naval Medical Institute. Bethesda, Niryland Professional SocitIts; American Anoeiation of Dental School* American Association for Laboratory Animal Science American Association of University Professors American Medical Association (Faculty Affiliate) American Society for Cllnicil Pharmacology end Therapeutics American Society for Pharmacology *"d Experimental Therapeutics Allocution of Dental Pharmacology and Therapeutic* Teachers Allocution for Medical School Pharmacology Drug Information Association The Harvey Society New fork Academic of Sciences S19** *1 Society for Experimental Biology and Medicine Society for Neuroscience Society of Toxicology The Peripatetic Society Professional licenses: District of Coluafcla Maryland New font Publications: See appended list HOMS 2221^2 "3 8ICU0GHAPHT FRANK G. STANDAERT 1. Roberti, J., F.G. Standaert, T.l. Kin and W.F. Rlktr, Jr.; The initiation . and pharmacologic reactivity of a ventricular pacemaker in tha intact r animal. J. Pharmacol. Exp. Th*r. 117: 374-384, 1958. 2, Rlktr, w.F., J, Robert*, F.G, Standaert and H. Fujimere: The motor nerv* terminal at the primary focut for drug-induced facilitation of neur muscular transmission. J. Pharmacol. Exp. Thor. 131: 286-312, 1997. 3. Standaert, F.G.. H.c. Sudduth and N.v. Hudak: A toxicological study of hydraulic fluids cellulube 950A, kolube 220 and houghto-safe 1099. MI Research Report m 93 01 00.03.01, 1996. 4, Fries*. 3.L.. F.G. Standaert and L.J. Reber: Convultant activities of aminocyclanol derivatives at influenced by stereochemical configurations (24321). Proc. Soc. Eap. Biol. N.T. 99: 277-280, 1996. 9. Barr, 1.1., B.E. Shepp, N, Tareloner and F.G. Standaert: Physiologic responses to stressful stratosphere flights. J. Avlat, Ned. 30: 334-343, 1999. 6. Priest, S,l., F.G. Standaert, E.R. Miltcoaft, R.F, Nigral 11, J,0. Chan ley and h. Sobotka; Some pharmacologic properties of holothurln, an active neuro toxin from the tea cucuamer. J. Pharmacol. Exp. Thor. 126 : 323-329, 1999. 7, Standaert, F.G.: Effect of pH on twitch facilitating potency of 3-hydroxyphenyl-trlethylammonium Ion, Proc. Soc. Exp. Biol. N.T. 102: 138-139, 1999. I, Frlets, S.L., F.G. Standaert, 6. Wltkop, R.C. Durant and L.J, Reber: Some toxicologic proportion of a no* series of aryl ethars derlvtd from trans2-amlnocyclohexanol. Toxicol. Appl. Pharmacol, h 609-617, 1999. 9. Standaert, F.G,, 5,L. Frlest and R.O. Ooty: Comperatlvo ganglion-blocking potencies of tn geometric isomers of teo cyclic 1,2-amlno-alcohols. J. Nod, ChdBk Jk 491-466, 1999. 10. Sudduth, H.O, and F.G. Standaert: Inhalation toxicity studies on a triaryl phosphate hydraulic fluid, M] Research Report HE 009. 04-0001. 03, 1999. 11. Standaert. F.G. and S.U Frless: Sterle configuration and the activity at the mem*Hen neurtmucular Junction of cyclic amlnoalcohol derivatives. J, Pharmacol. Exp. Thor. 29: 99-64, 1960. 12. Frless. S.L.. F.G. Stsndeert, E.R. Whiteox*. R.F. Nigral 11. J.O. Chanel y and Harry Sobotka: Some pherswcologic properties of holothurln a, a glyeosidic mixture from the sea cucimter. Am. N.T. Acad. Sci. 90: 693-901, 1960. MONS 222173 *rr' 13* Fries*, S.L., U> Reber. W.C. Thommesan. L.J. Graenbaum, F.G. Stlndlirt and w.V. Hudak: Toxicological prooartta* and stareo-chomical eonftqUr|. tton in derivatives of the tropano! series. Toxicol. Appl. Pharmacol. M. frit**, S.L., L.J. Gratnbaum, F.G. Standaert and U.C. Thomnmsen: Central activity woted in the eat by emransliomeri of 1,2-am1nocyelohxano1 derivatives. Toxicol. Appl. Pharmacol. 3; 636-653, 1161. 15. Standaert. F.G.: Evidence for a pratynaotlc action of d-tubocurarme and tucclnylcholln* at tha naamllan neuromuscular Junction. Proe, 16th bo*t-grad. Assertly Anesthesiology N.Y. 23-25, Oac. 1M2. l$. ftikar. u.F. and F.G. Standaart: Pharmacologic aspect* of neuramuscul*r transmission. Recant problems of phamacology. Academy of Medical Sciences of the USSR. Institute of Pharmacology and Chemotherapy. Vol. III., pp. US-137. Ed. by O.A. Karfcevleh. Moscow. 1463. 17. Standaart, F.G.: Pott-tetanic repetitive activity In the eat soleut nerve. Its origin, course and mechanism of generation. J. Gen. Physiol. 47: 53-60, 1963. 16. Standaart, F.G.: The action of d-tubocurarlne on the motor nerve tenetn*1. J. Pharmacol. Exp. Thor. 143 "111-166. 1964. 19. Standaart, P.6.: The mechanism* of poet-tetanic potentiation in cat soleut and gastrocnemius auscles. J. Gen. Physiol. 47: 967-1001, 1964. 20. Standaart. F.G. and J.E. Adams: The action* of sued nyl choline on the motor nerve terminal. J. Pharmacol. Exp. Thar. 149; 113, 1965. 21. Hiker, W.F., Jr. and F.G. Standaart: The action of faellitatory drugs and acetylcholine on neuromuscular transmission. Ann. N.T. Acad. Set. 135: 163-176, 1966. 22. Standaart, F.G,, 6. Levitt and J. Roberts: Antagonism of digitalis arrhythm: by pronothalol--a neural phenomenon? Nature 210: 742, 1966, 23. Raines, A. and F.G. Standaert; Pro- and post-junctionel effects of dipnanyi. hydemteln at the cat soleut neuroaiscular junction. J. Pharmacol. Exp. Thor. 361-366, 1966. 24. Standaart, F 6, and J. Roberts: A neural action of pronethelol. Ann. n.t. Acad. $d. 1309: IIS-620. 1967. 26. Ralnee. A. and F.6. Standaert: An effact of dlphonyIhydantoIn on tha post* tetanic hyperpelarlxatlon of intramedullary nerve terminals. J. Pharmacol Exp. Thor. m-. 591-597, 1967. 26. Roberts, J., 6. Levitt and F.6. Standaert: Autonomic nervous systam control of cardiac rhythm. Nature 214; 912. 1967. MONS 22217b -7- 27. Standaort, F.G. and M.F. Piker: The consequences of cholinergic drug actions on motor ntrve ttmnnals, Ann. N.T. Acid. Sel. 144: 517-533, 1961. ----- 28. Raymond. L. and F.G. Standaert: Thf respiratory offcctt of carbon dioxide In the cit. Anesthesiology 28: 974-980, 1967. 29. Raines. A.. 8. Levitt and F.G. Standaert: Tht ffct of spinal section on ventricular rhythm disorders induced by ouabain. Arch. Int. Pharmacodvn 170 : 485-490, 1967. 30. Levitt, 8., A, Aalnes. Y.J, Sohn, F.G. Standaert: The physiologic and pharmacologic basis for the sleep regiment In myocardial Infarction. Lancet. Letter to the Editor, June 15, 1988. 31. Utublasa, J.E. and F.G. Standaert: The effects of local anesthetics on motor nerve terminals. J. Pharmacol. Csp. Ther, 159 : 353-361, 1968. 32. Eager, R., L. NeCarty, F.G. Standaert: The pharmacology of 2-ailrldlnyl ethanol. J. Pharmacol* Esp. Ther, 166: 205-216, 1969. 33. Raines, A. and F.6. Standaert: The effects of anticonvulsant drugs on nerve terminals. Epilepsia JO: 211-227, 1989. 34. Levitt., 8., A. Raines, 0. Haros, and F.6. Standaert: The capacity of h-1 sopropyl-p-nltro-phenylathanolmsl np (IN8EA) to Influence the course of ouabeln-inducod cardlotoxlclty in the cat. European J. Pharmacol. 8 : 217-222. 1989. 35. Standaort. F.6., 8. Levitt, J. Roberts and A. Raines: Antagonism of ventricular arrhythmia induced by digitalis--a neural phenomenon. Europaan J. niarmocol. %i 209-218. 1989. 38. Gil 11s, R.A., John A. Quest and F.G. Standaert: Depression by reflexes of the pressor and cardlotoxlc responses to ouebaln. J, Pharmecol. Exp. Ther. J70: 294-302. 1989. 37. Sohn. T.J., A. Rolnee, F.6. Standaert and I. Levitt: The effect of diphenylthlohydentoln (DPH) on digitalls-induced cardiac arrhythmia. Arch, Inti. Phermecoleglet U_: 244, 1989. 38. Levitt, I., A. Rolen, T.J, Sohn, F.6. Standaert and J.W. Hlrshfald: The nervous systsm es a site of action of digitalis and anti arrhythmic drugs. Haunt Sinai J. Ned. 37: 227, 1970. 39. Standaert, f.t. and P. Dttwller: The neuromuscular pharmacology of feral no-3-acetate and gwmlne-3, -18-dlacotato. J. Pharmacol. Exp. ther. V71: 223-243, 1970. 40. Standaort. F.8.: The idoal compendia: Rut is H? (Speaking from tno standpoint of a ndlcal oducator) Drug Information lullotln 4: 204-206, 1970. HONS 222175 -3- -41. Ralnas, A.. I. Lavltt, F.G. Standaort and V.J. Sohn: The influence of sympethotle nervous activity on the anti arrhythmic efficacy of diphenyl, hydontoln. European J. Pharmacol. Ih 293*297, 19 70. *2. Gillis, R.A., J.R. McClellan, T.s. Sever end F.G. Standaort: Daprasnon of eerdlee sympathetic nerve activity by dlphtnylhydentoln. J. Pharmacol Exp. Thor. J73- 599*610, 1971. ' 0` 43. Gil lit, R.A., R.A. Olonne end F.G. Stendeert.: Suppression by elonidine (ST-ISS) of digitalis-induced arrhythmias. J. Pharmacol. Exp. Ther. 182: 218.226, 1972. 44. Glllls. R.A., A. Re 1 net. r.J. Sohn. I. Levitt end F.G. Stendeert: Hours. excitatory effects of digitalis end their role In the development of cardiac arrhythmias. J. Pharmacol. Exp. ther. 163: 154.168. 1972. 45. Glllls. R.A., f.h. Levine. H. Thibodeaux, a. Raines end F.G. Stendeert: A cooper Ison of mothyllldocalno end Hdocaine on arrhythmias pro* ducad by coronary occlusion In the dog. Circulation 7: 697.703. 1973. 46. Standaort. F.G.: Mechanism of action of muscle relaxants. 1973 Locturas. Amer. Soc. Anestheslol. 117-1 to 117*3. 47. Soteropoulos. G.S. and F.G. Standaort*. neuromuscular effects of morphine end naloxone. J. Pharmacol. Exp. Ther. 114: 138-142, 1973. 48. Hoefcmen, T.B., K.L. Oretchen and F.G. Stendeert: Miniature end-plate potentials recorded from mammalian myoneural Junctions in vivo. Science 183: 213-215, 1974. ----------- 49. Glllls, R.A., O.E. Evans, A. Raines, B. Levitt and F.G, Stendeert: Sleeo end ventricular premature beets (Letter to the Editor) Circulation $0. S63-B84, 1974. 50. Standiort, F.G., K.L. Oretchen, L.R.Sklrboll end v.H. Morgenroth. Ill: The effects of cyclic nucleotides on meawlian motor nerve terminals, j, Pharmacol. Exp. Thor. 199; 944, 1978. 51. Stendeert. F.G., k.l. Oretchen, L.8. Skirboli end v.H. norgenrotn. in. The role of cyclic nucleotides In neuromuscular transmission. J. Pharmacol. Exp. Ther. J99: 553, 1978. 52. Orptchon, K.L., F.g, Stendeert, V.H. Morgenroth, lit end L.R. SkirboK Evldenct for a prejunctional rolo of cyclic nucleotides in neuromus cular transmission. Nature 284: 78-81, 1978. $3, Oretchen, K.L., V.H. Morgenroth, III, F.G. Standaort and L.F. Halts: Aiathloprlne: effects on neuromuscular transmission. Anesthesiology 45: 604-809, 1978. HONS 222176 -9- 54. Dretchen, x.l., F.G. Standaert and A. Raines; Effects of phenytoin on the cyclic nucleotide system in the motor nerve terminal. Eplltptla. 18(31: 337-342, 1*77. 55. Standaert, F.G.: Interactions anon? neuromuscular 0locking agents and other drugs. Refnsher Courses in Anesthesiology. Ed. S.G. Hershey; J.l. Li ppencott, Philadelphia, Vol. 6, 111-124, 1978. SI. Sklrboll, L.R., F.G. Standaert and K.L. Cretehen: Effects of calcium on a cyclic nucleotide system In soleus motor nenre terminals. Eur. J. Pharmacol.. S4: 295-291, 1979. 57. Standaert, F.G. and X.L. Dretchen; Cyclic mideotldes and neuromuscular transmission. Fed. Free.. 38 : 2183-2192, 1979. 58. Standaert, f.g. and K.L. Oretchen: Cyclic nucleotides In neuromuscular transmission. Aneath. Analg., 10: 91-99, 1981. 59. Standaert, F.G.: The Release of Transmitter at the Neuromuscular Junction. 8r1t. J. Aneesth., 1982, (Submitted). 10. Standaert. F.G. and K.O. looher: tourmmtscular Slocking drugs. In: CMC Handbook on Pharmacology and Aging. Ed. N.J. Roberts: P. Goldberg, CRC Press, d. Palm Mach, 1982, (Submitted). MOMS 222177 -10 A8ST8ACTS K Standaort, F.G.: The action of d-tubocurarine on the motor nerve termini! Fed. Proe. 20: 304, 19(1. " ' 2, Stands art, F.G.: Mechanise of post-tetanic Potentiation (PTP) tn cat slow ind fast muscles. Fed. Ppoc. 22: 309, 1983. 3. Levitt, 8., A. Raines, J. Roberts ano F.G. Standaort; Antagonism of dijltalls arrhythmia: a neural phenomenon. Fd. Proe. 28; 402, 1982. <. Raines, A,, 8. Levitt and F.G, Standaort: Factors influencing oiohenyihydantoin antagonism of ouabaln-1nduced ventricular arrhythmia in tne cat. The Pharmacologist 9: 237, 1987. S. Lavltt, 8., A. Ralnas, 0. Mores and F.G. Standaort: Antagonism of ouabain- induced ventricular tachycardia (VT) and death by large doses of h-itoorapyi p-nltrophenyl ethanol ami ne (INPCA) in the cat. Fad. Proe. 27 : 348, 1988. 8. Sohn, r.J., A. Raines, F.G. Standaort and 8. Levitt: Anti arrhythmic prop erties of sodium S,8-d1phony1-2-thlehydantoln (DPTMJ. The Pharmacologist 10: 221. 19M. 7. Gil Us. R.A. and F.G. Standaort: Effect of carotid sinus and vagal nerve section on seme cardiovascular rsponses induced by ouabain. The Pharma cologist 10: 220. 1981. 8. Oetwller, P. and F.G. Standaort: The action of genuine nonoecetato (GMA) on cat soleua muscles and nerves- Fed. Proe. 28: 899, 1989. 9. Glllls, R.A., 8. Levitt, A. Raines, T.J. Sohn and F.G. Staneaart: Effect of ouabain on sympathetic, vagus and phrenic nerve activity. The Pharmacologist 244, 1989. 10. Glllls, R.A., J. R. McClellan, T.S. Sauer and F. 6. Standaort: Effect of dlphony1hydantoin on spontaneous sympathetic nerve activity. Pharmacolo gist 1: 304, 1970. 11. Glllls, R.A.. F.H. Levine. H. Thibodeaus. A. Raines and F.G. Standaort: Effect of methyl 11docalne on arrhythmias produced by coronary occlusion In the deg. Free. Fifth International Congress on Pharmacology, 1972. 12. Hoakmee, T.8., t.L. Oretchen and F.G. Staneaart: in vivo intracellular recording of miniature endplate potentials from tne cat soleus muscle. Fed. Free. 32: 771, 1973. 13. Standaort, F.G., V. M. Morgenroth, III, L.R. SklrboU and K.L. Oretchen; Cyclic nucleotides and neuromuscular transmission: prejunctional affects of cyclic nucleotides. Pharmacologist II: 193, 1978. MOHS 222178 11- 14. Morgonroth III, V.H., L.R. Sk'rboll, K.L. Oretchen and F.u, Standaert: Cyclic nucleotides end nturo*jscular transmission; prejunctional offaett of raagents tnat affect cyclic nucleotide systems, Pharmacol091st 18; 193, 1976. -- 15. Skirooll. L.A., K.L. Oretchen, F.G, Standaert and V.H. Morgenroth. Ill; Cyclic nucleotides and neuromuscular transititlon: prejunctional affects of antagonists of calcium flux. Pharmacologist Id; 193, 1976. 16. Oretcnen, K.L., F.G. Standaert. V.H. Morgenroth, III and L.R. Skirboll: Cyclic nucleotides and neuromuscular transmission; prejunctional effects of physostigmlne; innioition of phospftodlesterast? Pharmacolooist ]8: 193. 1976. 17. Sklreol 1, L.R., L. lalier, M. tadarola, F.G. Standaert. V.H. Morgenroth, III and K.L. Oretchen; The effects of eelefum. magnesium, lanthanum tetraetnylamenium and amlnopyrfdlnet on the cyclic nucleotide system in the motor nerve terminal. Fed. Free. 36: 976. 1976. 18. Standaert, F.G.: Structure, function and pharmacology of notor nerve terminals. In American Society of Anesthesiology: workshop on neure- mscular junction--a caaprehenslve revlee. 6. J. Saverese; Boston, March, 1977. 19. Curley. w.H,, K.A. Scaooaticcl, A. McGee. t.L. Oretchen, and F.G. Standaert: Cyclic AMP phosphodiesterase from cat sciatic nerve. Fed. Free. 31: 272, 1979. 20. Oretchen, K.L.. A.A, Howard, F.G. Standaert and C.s. Bade: Differential effects of acetylcholine and edrophonium on motor nerve endings. Sec. Iteuroscl. Adit. S: 479, 1979. 21. Curley, W.H., K.L. Oretchen and F.G. Standeert: Inhibition by Fhysesttgmine of Neural cAMF Phosphodiosterasd. Fed. Free. Sh 410, 1960. 22. Standaert, F.G.: Reuronscular Transmission - Whet Is a cholinergic rec^torT Lectures Amer. Sec. Anesthesia. 333-1 to 133-4, i960. 23. Day. N.S., Oretchen, K.L. and Standaert, F.6.; Comparison of Norcuron and Pancuronium on Neuromuscular Transmission. Fed. Free. 141: 260. 1901. 24. Oretchen. K.L. and Standaert. F.6.; Cyclic nueloot Idas and antimyasthenic drugs. N.T. Acad. Scl. (In Press) HONS 222179 CURRICULUM VITAE fl^ICE AQORESS-. ppNf ACORESS: yxtw! John Arltn Thomas Dtrtmant of pharmacology and Toxicology host Virginia unlvaralty Madlcal Cantar Morgantown, watt Virginia 26306 Talaonona- (30*) 293-32*9 661 vallay via* Straat Morgantown, wait Virginia 26303 Talaonona: (30*) 399-1*29 La croaaa, Wisconsin April 6. 1933 PORTION: La Crosaa Rublic School, La Cross*. Wisconsin 1933-1930 Univarsity or wisconsin-La Crosaa, La Cross*, Wisconsin 1931-1933; 1933-1936 Stata Unlvaralty of Iowa, low* City, Iowa 1936-1961 ffcAOEMIC DECREES: S.S., Unlvaralty of Wisconsin, 1936 M.A., Ststa univarsity of Iowa, 1931 Ph.O., Stata unlvaralty of Iowa, 1961 MARITAL STATUS: Marriad (1937): on* son - 001 Jun* 12. 1962; on* daughtar - 001 May 31, 196* MILITARY SERVICE: Mon-coMissionad Offictr (Sargaant) U.s. Aray - 1933-1933 Aaarican Ragistry of Physical Tharseists-Ststa Unlvaralty of Iowa-1937 (inactiva) Aaarican Acadaay of Toxicologie Sciancas Oioloaata, 1912-1913 honors ano PWEtST^NAu HtCQCNITi5n7 2 Oean's Lilt*, University of wisconiin . n c*:sje Camne Aiona, Scianca Honorary, Unlvariity gf Pre-ooctoral Faliowsnio*, university of i0w| " Poraign Tnvtl Awaro. Amarican Sociaty for Pharmacology ano Exparimantal Tharapautics Maxlco City, Maxico; San Paulo, Brazil. 1966 Chairman, Endocrina Pharmacology, American Sociaty for Pharmacology ano Exoarimnti1 Tharapautics (univarsity of Minneiot*, 1966) Chairman, Enaocrlna Pharmacology, Fedaritio*. of Amarican Sociaty for Exparimancii Biology (Atlantic City, n.j.) 197i Co-Chairman, Llvar Microsomal Entymat, Sociaty for Toxicology (Nam Torn, ha* vork) 1973 visiting Profasaor and Senior Rasaarcn Advisor, faculty of Maoiclna, university of Ottawa, Ontario, Canada 1971 McLaughlin Award > Outstanding Taacning Award, west Virginia university School of Medicine (Shared Award) 1971 Adjunct Professor, Departwant of Allied Health Sciences, Kent State University 1973-Dresent Outstanding Teaching Award 1973-1974 west Virginia University Co-Chairman, Endocrine Pharmacology, American Society for Pharmacology and Experimental Therapeutics (University of Montreal, 1974) Co-Chairman, Endocrine Pharmacology, American Society for Pharmacology and Experimental Therapeutics (university of California, 1975) U,S. Environmental Protection Agency * Certi ficate of Scientific Service, 1977 McLaughlin Awsrda - Outstanding Teaching Award, vest Virginia University School of Medicine, (Shared Award), 1977 National Academy of Science Travel Award, XII International Cancer Congress, Suenos Aires, Argentina, 1978 Co-Organizer, Epidemiology of Toxicology, ASPET/SOT Joint Meeting, (University of Texes, 1978) Maurice 0, Craff Distinguished Alumni Awero (University of *isconsin-La Crosse), 197a Co-Organizer, n.I.E.h.S. - sponsored Target Organ Toxicity, The Endocrines Symposium, Rest Virginia univarsity, 1980 Organizar, ASPCT/SQT - Sponsorad Symoosium. "innovating moosIs in Taratooaniclty" (Unlvariity of Louisville), 1902 HQNS 222181 3 Research Associate, State University or ioa, 1998-1999 visiting Senior Scientist - travenol Laooratories. Chicago, Illinois 1982 tEACHlNp 855 I5TANT5HIPS AND ACAOEMIC APPOINTMENTS; ' Teecning Assistant, Qepertment of Physiology, Scnooi of neoicine, State university or Iowa, 1980 Instructor, Department of Physiology, School of Medicine, State University of Iowa,1981 Assistant Professor, Oepertnent of Phr*a- cology. university of Virglnio Scnooi of MeoiCina. 1981-198* . Associate Professor, Department of Physio logy -Pharmacology, Creighton university, School of Medicine, 1988-1987 Associate Professor, Department of Pharmacology, west Virginia university School of Meoicine, 1967-196? visiting Professor ana Acting Chairmen, Department of Pharmacology, Pahlavi University School of Medicine, Shiraz, Iran, 1970 Professor, Oeoartment of Pharmacology and Toxicology, east Virginia University School of Meoicine, 1970-present ADMINISTPATIVE EXPERIENCE AND CURRENT RESPOHSI8IL1TIES; Associate Dean of Administration, east Virginia University School of Meoicine, 1979-present Assistant Oeen of Administration, east Virginia university School of Medicine, 1979-1979 American Asociation of Medical Colleges Executive Development Seminar Program, 1976,(m.i.t. Sloan School of Management) fiscal Officer, east Virginia university School of Medicine. 1979-present Promotion and Tenure, Peat Virginia university School of Medicine,1979-present Chief dents and Contracts Officer, vest University School of Medicine,1973-present Affirmative Action Liaison, west Virginia University School of Medicine,1979-present Academic Review, west Virginia university School of Medicine, 1979-present lomedicel Research dent Support Officer. Root Virginia University School of Meoiclne, 1979-present Facilities and Scheduling, vest Virginia University School of Medicine 1973-ortsent HONS 222182 a RESEARCH ACTIVITIES flNO INTERESTS: Co-Investigator, National Cancer Institute, (Prostate Cancer) 1970-oresent ' Enoocrins Pharmacology/Physic I -- . Aeoroouctive System Tonicity Orug-Hormone Interactions Heavy Metai Toxicity (Zinc MstsDoli**) Pesticide Toxicity Conaoal Toxicants Anti-androgenic Agents Phthalste Acio Estars organization): American Sociaty for Pharmacology ano Exoerieental Therapeutics Enoocrlna Sociaty Sociaty of Toxicoiogy "astern Pharmacology Sociaty Sigma xi American School Health Association, aiactao Fallow, 197i national Society for Medical Research act Virginia Association of Academic Oaans Association of American Medical Colleges- raprasantatlva PRESENT COMMITTEES-. 'Executive Faculty Committee. 197) Medical School Promotions Coeaittaa 1973 * Med leal Scnoool Adsiissions Coeaittee 1973 - Sul ftrSr&Sittee for Sasic Sciences Chaireen, 197) - Medical Cantar Planning Coaalttae Cheirein, 197* . Educational prograa Coeeittaa, 1973 Learning Resources coeeittaa, 197* . Senior ieneuet Coeaittee. 197* Association of Aaericon'Medical Collages Planning Coordinator, 1973 Faculty Council - School of Dentistry - 1974 Medical Student Financial Aids Coaalttae 1977 Aawrlean Society for Pheraecology and Cxoeri- aentsl Theraoeutica - Coeaittee on Environaental Pharmacology, 1973 coaouter uaera coeaittee 1979 Medical Scnool-Hoapital Liaison to Student tody Coeaittee. 1979 Dissertation coaaitteea, 1949 Post-doctoral Training Grant (Cnoocrinology> 1977 nsf Coeaittee to Stimulate Coaoetltlva Re search in east Virginia, Chalraan, 1971 a.v.U, Medical Center Siohaiaros Coaalttae, c-i 1990 - MOHS 222183 5 SLCTCP LIST OF PAST AnO PRESENT CONSULTANTSHIP5 flNp flQvISQftV HOLES: 1 Environmental Protection Agency National Cancer Institute Committaa on Carcinogenesis university Park Press. Baltimore, narylano mason Research institute, eorchester, h*s*. asha-pma Lecturer on Prug Abuse Encyclopedia Britannica Ao hoc Reviewer - Journal of Animal science Editorial Board - Journal of Toxicology ano AoollaO Pharmacology 197J-19B1 Clinical Pharmacology - Texas Allergy Re search Foundation Ba*tar-Travenol LSDoretories - Chicago. Illinois world Health Organization - Narcotic Oivision Ad hoc Reviewer - Science J5 hoc Reviewer - American j. School Health Id Hoc Reviewer - American j. Physiology Id hoc Reviewer - Journal of National Cancer Institute Clement Associates, Inc. Scientific Regu latory Consultants, Washington, P.C. Editorial Board, Technomic Publishing com pany (Health Science Oivision) westport,ct National Institute Arthritis, Metabolic, and Digestive Piseesee union carbide Corporation, south Charleston, e.vs. American Public Health Association Urban * Schwerzenberg Medical Puelisners, Baltimore, Maryland National Sclanca Foundation-Regulatory Bio logy Program Editorial Board, J. Toxicology and Environmental Health Editorial Board, Perspectives in Toxicology Raven Press, New York, New vork Professionel Consultants in Occupational Health, Inc. (Washington, O.C. Ad hoc Reviewer - Proceedings Society Experi mental Biology end Medicine Ad Hoc Reviewer Ancrology National Toxicology Program (ntp) Board of Scientific Counselors Exxon Corparstion, Newark, n.j. Syntax Research (Oivision of Syntsx(USA], Inc.), Polo Alto, Cslifornle Ag Hge Reviewer National Prostatic cancer "Project MOMS 222184 I 6 5LCTE0 LIST OF PAST COMMITTEES ANO Offices (ChWONOlCCICJl,Presiaent - Virginia Academy of Science*, Mtoical Sciences, 1964 Secretary - Virginia Academy of Science*, Magical Sciences, 1962*1963 Research Fellowship Committee, university of Virginia, 1962.196a Sacratary-Traasurar, Society of Sigma *1. Creignton university, 1965-1967 sacratary, Sociaty of Sigma *1 - att Virginia university 1969 Curriculum Commlttae, vast Virginia univirity Senool of Maaiclna, 1967-1969 Faculty Senate (*VU), 1969-197i; 1973-1976 Faculty Sanata committee (wvu) on **moeranio ang Conatituanciaa, 1970-1971 Maoical Senool Promotions Committaa Iwvu), 1969-1973; Chairman 1970-1973 Medical Senool Admissions Committaa (*vu), 1969-1973; viea Chairman 1970-1973 Pra-Madical Adviaory Croup 0*vu), 1970-1979 Basic Sclanca Aomlnistrstor for vast Virginia Univarslty Camorenens iva Cancar Cantar Olractor of Cradusta Stuolas in Pnarmscology (RVU) 1967-1973 President's (east Virginia university) Task Force Committaa on North central Accredi tation, 1972-1976 President's aq hoc Council far vest Virginia university Raseeren and Craouate education, 1972-1974 Co-Oiractor, USPHS Training Crant in Pharma cology, 1967-1973 Medical Canter Long Mange Planning Committee (avu), 1966-1974 American School Health Association committee on Orug Adusa, 1970-1973 Faculty Promotions and Tenure Committaa l*vu School of Pharmacy) 1972-1974 Craouata Faculty, Kant State university, 1975 Board of examiners, univarslty of Madras, India Board of Examiners, university of Qtta*a, Canada Search Committaa for University comptroller (mvU) Chairman, 197$ Research Strategy Committee (wvu), Chairman. 1977-1978 By-Ls*s Committaa. Rest Virginia university School of Medicine, 1978 HONS 222185 7 Selected lilt of Past Committee* and Office* (Chronological): Vacuity of Hotoouetl Physiology, Institute of Biological Sciences, a*t Virginia Univeralty 1967 Radiation and Iiotooa Committee, 1968 Cancar Pellovsnip ana Raaaarcn Committee, 1968 Faculty Promotions and Tanura Committea - Oaoartmant of Pharmacology, 1970-1978 Intar-Olaclolinary Advisory committee - Master's Program in hurting, 1972-1974 Unlvartlty Energy Committee, 1977-1979 Executive Committee of tna Gerontology Center 1978-1980 metis Committee*, 1968 HONS 222186 a PUBLICATIONS (includlna 123 research osoars/ooows/ehapters/revit.* , . taoes/Fllns/eedU ; lot aastrectsj: ------------------------------- CiuCose Tolerance In Rheumatoid Arthritis, J.A. Thomas, and v.Q.Piul Clinical Chemistry *: 336, 1936 (Abstract). ' Effect cT 2^50 megacycle Micro-eves In Oogs, Rats ana Larvae of Common fruit Fly, C.D. Seerle et.al., Biol. Effects of Microwave Radiation > 187, 1*61. i' Carbonyarate metabolism in Patients -1th Rheumatoid Arthritis as Determines oy Oral and Iv Glucose Tolerance. J,A. Thomas, m.a. Thesis. State university of Iowa, 1938. * Effect of Mieroaeve Irradiation on Spermatogenesis ano Accessory Sc Organs In the Male Albino Rot. J.A. Thornes, Ooctoral Olssortation. Staruniversity of love, 1961. Dissertation Abstracts 2: 107, 1961 (Abstract). The Effects of Mlcroveve irreolatlon on Spermatogenesis ano Accesory Sa< Organs in the Male Albino Ret, J.A. Thomas, ano j.O. Thompson, Federation Proceedings 22.: *01, 1961 (Abatrect). Alterations In Glucagon Response In Allosan Oiebetlc Orchldectomiaed Rats by 17-ethyl-19-nortestosterone end Estradiol Bentoote. J.A, Thomas, Federation Proceedings i: 199, 1962 (Abstract). Effect of 17-athyl-19-nortestosterone on Blood Glucose In the AHoxsn Olapetic Rat. J.A. Thomas. Virginia Journal of Sclenee 13: 293, 1963 (Abatrect). Maoiflcetion of Glucagon-induced Hyperglycemia by various steroidal Agents, J.A. Thoees. Metabolism^ 207, 1963. The influenca of 19-nortattoaterona Oarlvatlves on Glycogen and Phosphorylese Activity in Noaogenates of Mouse Hepatic Tissue. j.A.Thcmas end j.Lomes, federation proceedings 22* 551* 1**5 (Abstract). The fffact of Several Steroidal Agents on Liver Phosphorylese Activity. j.A. Thomas, Virginia Journal of Science. ^ei 331, 1963 (Abstract). Norathendrolono-inductd Changes in Hepatic Phosphorylese Activity, j.a. Thomas. Metabolise 2* 63, 1966. Effect of Teateaterene Analogues on Ses Aecestory Gland Fructose Levels in the Orehidbctbdised Mouse. j.A.Theeet, Federation Proceedings 22' 1966 (Abetreat). Action of Noyothondrolono or Testosterone on House Ses Accessory Orga^ Fructose Levels. A.J. Strauss and J.A. Thoees, Virginia journal of Science 22: 3AS, 196A (Abstract). The Action of Androgenic Steroids on Some Aapeeta of Accessory Se* C:;a* MetsDolism. j.A. Thoeoe, Virginia Journal of Scisncs 3*6, 196e (Abstract). Structural Modifications of the Testostarona Molecule sno its influa-c* on Fructose Secretion in Sai Accessory Organs of Raproouctlon in tne Cestrete Nouea. J.A. Thonaa, The Pharmacologist ; 169, 196A (Abstract MONS 2221S? 9 indications (cant. ): ie Effect of Steroids on Mouse Sox Accessory fpuctoss Levels. J.A. .tomss ana a.j. Strauss. Acta Endocrinologies (CdPtnhegtn) <19, 19;;. jadoganouj Histamine in Mole Organs of Aeprocuctlon. t.a. Assaykeen ana j.A. Thomas, Endocrinology 7: 839, 196S. ffect of Slmulianeously Injectec Testosterone ano Testosterone Analogues jn Sex Accessory, Organ Fructose. J.A. Thoiaas, Federation Proceedings 24- *38, 196 3 (Aostract). -- The Antagonistic Action of Estrogens on the Testosterone Oependent process of Sex Accessory Organ Fructose Formation. J.A. Thomas, The Pharmacologist 7: U), 1983 (Aoatreet). Fructose Levels in Sex Accessory Organs of Msture Coloon nsasters. J.a. Thornes ana ft.v. Anorevs, Enoocrinology 7^: 11a7, 1963. Antagonistic Action or Noretnynoorel on the Testosterone Oependent Process of Fructose Formation In Mouse Sex Accessory Organs, j.a. Thomas sod E.T. Knych.Jr.i Acta Enoocr inologlca (Copennsgen) 244, 1966 tht ^ vivo and in vitro Incorporation of 32p in Mouse Prostate elands. E.T. Knycn, Jr., snd J.A. Thoooa, Federation Proceedings 22: 31*, 1966 (Abstract). Inhibitory Effects of Estrogens on the Teetoeterone-Oependent Process of Sex Accessory Fructose Secretion. J.A. Thooes end E.T. Knych, Jr., Endocrinology 7; 1084, 1944. Sooe Actions of Asserolne on Sex Accessory Organ Fructose Secretion, j.a. Thoees, The Pharmacologist 201, 1944 (Abstract)* Further Studies on the Influence of Estrogens on Androgen Oependent Fructose Formation in Sex Accessory Organs. J.A. Thooes end E.T. Kynen Jr., Acte Endocrinologies (Copenhagen) 22; 433, 1964. Effects of Cyclohsxioide on Salivary Gland Protein MetaDolls*. j.a. Thooes snd m.f. Hill, Anatomical Record 137; J91, 1947 (Abstract). Action of Cyclohexlmide on Prostate Gland Fructose, j.a. Thomas, Federation Proceedings 2&! *** 1947 (Abstract). Effect of Reserpine on Prostate Gland Fructose. J.A. Thomas, N.v. Andrews end m.f. hiii, Acta Endocrinologlca (Copenhagen) 22`- 399, 1947. Effect of Scllvsrlsdenectomy upon Gonadal Activity in Mela Rata. J.a. Thomas end M.F. Hill, Archives on Oral liology i: 921, 1947. Action of Cyclohexlmide on the Submaxillery Glands in Normal and Castrate Mice. M.F, Hill end J,A. Thornes, European Journal of Pharmacology 1.: 4)4, 1967. HONS 222188 PuBli:*tlof (cont 10 Some Aspects of Prostata Clana metabolism following tn 0*loistriti-^ .. Cyciohasieids. J.A. Thoas, The Pharmacologist 9: 232. 1997 (Abstract;. Effect of Cyclohaaimide on mous Sei Accessory Organs, j.a. Thomas, European Journal Pnsrmscology 2: 127, 1997. Efffet of E*ogtnous Oope*ine on at Aoranal Ascorbic Acid. a.8. King *no j.a. Thomas, journal of Pharmacology ana E*perlm#ntsl Tharipautlcs i?9- 19. 1*99. ----- Sa Accassory fructost: An Evaluation of Blocnamlcal Tacnnlauas. J.a. Thomas, m. Mewhinney and w. mason, Procaaolngs Soclaty of Cioarimantai Biology and Medicine 127: 930,1999. Relationship of **aia Sa* Hormona to Phosphorylatad and Nononosonorylataa fructose. J.A. Thomas and m.c. Maahlnnay, federation Procaaolngs 21: 62*. 1998 (Abstract). Action of Tastostarona Analoguas on Prostata Gland PhosohoryIstad ana Non-phospnorylstad Pructosa. m.c. Maahlnnay ano J.A. Thomas, Tha Pharmacologist 22*, 1998 (Abstract). Effact of Tastostarona and Cstrogan on tna Activity of Alkaline ano acia Phosphatase in Mouse Sea Accassory Organs. t.T. Knych, jr., and j.a. Thomas, Tna Pharmacologist ifl: 22*, 1998 (Abstract). Changes in Submaxillary Gland Protein and Nucleic Acids following fthionine Administration. J.A. Thomas, a. mason and m.c. Mewhinney, Journal of Dental Research *: 192, 1999 Hormonal Regulation of free fructose and fructose Phoapnata Esters in Prostata Clanda of mieo. J.A, Thomas, m. maohinnay, C. manger and C.T. Knych, Jr., federation Proceedings jjs 77*, 1989 (Abstract). Effect of a Single Injection of Testosterone and/or Ethinyl Estradiol upon House Prostata Gland fructose Levels. J.A. Thomas, m. Mewhinney ana E.T. Knych, Jr., Acta Endocrinologies (Copenhagen) 319, 1989. Action of Synthetic Steroids on tha uptake of Teetosterone-l,2-h3 by Mouse Prostata Glands. J.A.Thomas, E.T. Knych, Jr., and m.g. Mewhinney. IV International Pharmacology Congress Proceeding (losol, Switzerland) o- 398, 1989 (Abstract). factors Affecting the Uptake and Subcellulsr Distribution of Radioactive Tastostarona in Sas Accessory Organa of Mico. C.T. Knycn, Jr., J.a. Thoaao end C. Smith, The Pharmacologist ii*. 292, 1989 (Abstract). Effect of 19*ntretarolds on the uptake of Tritiotod Tastostarona by Proatsto Glands of mice. J.A, Thoaos, The Pharmacologist 292, 1999 (Abatroot). effect of Reeerplnm and Cyeiohawimlda on Heioaa Levels of nouso 8raln. C.R. Monger, J.A. Thomoo and T.J, Lte, The Pharmacologist H,.- 290, 1999 (Abstract). Effoct of Roserpina on tno Uptake of Teatosterone-1,2-m* by Mouse Prostata Gland. J.A. Thomas, E.T. Knycn, Jr., m.c. maonlnnoy, Europaan Journal of Pharaaeology 391, 1999. HONS 2221*9 ^LIGATIONS (cent.): 11 iubcellular OItributlon of Radioactivity In tn# Prostata eland Following r Single injection of Testosterone-1,2-hJ. j.a. Thomas, C.C. Soitn *.C. Mavhinnay and E.T. Knych, Jr., Acta EndocriftOlogiCi 3: JOJ, 1970. action of various 19-norstoroids on the uotaka of Radioactive Testosterone by Se* Accaasory Organa of tha Mouse. J.A. Tnoaaa, E.T. <nych, Jr., M-C. **a-nlnnay ano S.R. Smith, Eurooaan Journal of snarmacology 9= 23S, 1970. ^olatlonahio of Fructose and Fructose Phosohate Esters In Accaaaory Sox Jrgana of tna Mouse. m.g. M*ehinnay, E.T. Knych, Jr., and J.A. Thomas, journal of Endocrinology (Britain) : 9*9, 1970. uotaka of 2-deoyglucose-Ci4 (2dG) or 3-o-oethyi-glucose-el* (3oG) by Guinea Pig Saminal vaslclaa In vitro, m.G. Mavhinnay, J.A. Thomas and E.T. Knycn, Jr., Federation Proceedings Q: 782, 1970 (Abstract). uotaka of Cl4-2-daoxyglucosa and Cl4-3-0-athyl*glueoaa by tha Rat vantral Proatata In vitro, m.g. Maninnay, J.F. Laa, C.C. Smith, and j.A. Tnoaaa, Tha Pnarmacologiat 1^: 2*1, 1970 (Abstract). Cniymatie Measurement of Proatata Cland Fructoaa. J.A Thomas, m.g. Mavhinnay ano C.R. aangar, Journal Reproduction and Fortuity 21: 22, 1970. Aaalallatlon of Nonutilixsble Clucoaaa by Sx Accaaaory Organa in vitro. M.C. Mahlnnay, O.F. Mila* and J.A. moose, Federation Proceedings 2&: 344, 1971 (Abstract). uotaka of Non.utilitabla Sugars by Guinao Pig Sadinal vaaiclas A*J, vitro. m.g. Mavhinnay and J.A. Thomas, Journal PharMCology and Experimental Thorapautica AT?; **7, 1971. Tha Abuaa of Madicinal Products. J.A. rnoaios and G.N. Knotts, American Journal of School Hoelth a^: 233, 1971. . mov oo Oral Contraceptives *erh? m.G. Mavhinnay, J.A. Thodas and G.A. Knotts, American Journal School Health *^: 901, 1971. uptake of TritiuO'Cebeled Tastostarona by Rat Femur: Effect of oisusa ano Ago. m.a, Grant, J.A. Undaay and J.a. moots, Canadian Journal of Physiology and Phoroocoldgy 717, 1971. Formation of Radioactive Cyclic 3', S' Adenosine Monophosphate (c-amp) Froo H'.Adanoalna by Mouaa Proatata Glands A2. liSl* Carol C. Saith, j.a. Thooaa and m.g. Mavhinnay, Tha Pharmacologist 1?: 287, 1971 (Abstract). Oistributlon of Non-utilixeble nasoaaa and Aolno Acids in Evartad Saainai vaaical Sac of tna Guinao Pig, m.g. Maoninnty, J.A. Thooaa and C.C. Saith, ma Pharoacologiat A2: 30B, i97i (Abstract). Effect of Cstrogan Pre-treatment on tna Uptake and Siotrsnsforoetion of Tcstosterone-l,2-H3 by Mouse Prostata Glands. J.a. Thooaa, m.t. Soith, C.C. Soith and m.g. Mavhinnay, The Pharoacologiat il: 2B4, 1971 (Abstract), MOMS 222190 12 The Action ot Testosterone on tne Assimilation 0f Non-utllizaola e^Ca. by the Prostate. J.A. Thomas, m.c. mavhinney, T.j. L# ano C.C. Su*r* Journal of Pharmacology and Experimental Therapeutics 179: *99, 1971/ Pesticides and the environment. 0. Taylor, J. Stevens ano J.A. Thomas American Journal of Scnool Health 92, 1972. ` Localization of Q0T-hj in Mala Reproductive Organs and Its Actions con Anorogenlc Function. m.T. Smith, J.A. Thomas, C.C. Smith, m.g. Ma*ni,,,,.. ano J.J. McPhlllips. Society of Toxicology, nth Annual Meeting, *arcn 1972, 0. 101 (Abstract). * Action of Oieldrln on the uptake of Testosterone-1,2-h) oy Prostate Clanos of tne mala mouse. J.a. Thornes, m.T. Smith, m.g. Mamnney ano J.J. McPhlllips, Society of Toxicology, 11th Annuel Masting, March 1972 p. 103 (Abstract), ' Effect of Testosterone or Olhydrotestosterone on the In vitro Synthesis of Labelled Cyclic Adenosine Nucleotide (c-amp-h)) by~?ai"Accessory Organs of Reproduction, C.C. Smitn, j.a. Tnomee, m.g. Meohlnnay ano j.. Lloyd. Federation Proceedings 399, 1972 (Abstract). ' Effect of Testosterone on Cyclic Adenosine Monophosphate-H? (c-amo.mJ) and Adenyl Cyclase Activity in Rat Seminal vesicles, r.l. Slngnal, J.A. Thomas m.R. Parulskar ano C.m. Ling, v International Congress of Pharmacology, p. 219, July 1972 (Abstract). Assimilation of Adenosine-**) end Its Conversion to Cyclic Adenosine Nucleotloe (c-Amo-hJ) by Normal or Hyperplastic Proatatee of Oogs In vitro, m.c. Maahlnney, C.G. Smith, j.a, Thomas ano O.F. Milam, iv international Congress of Endocrinology, 0. 379, June 1972 (Abstract). Cherectsrlstles of Hsxoas Uptake by the Prostate Gland, m.c. Mawhinney, J.A. Thornes, C.C, Smith end 0,F. Milam, invoetlgetlvs urology 9: a39, 1972. - " Failure of Seta-adrenarolc Slocking Agents to Alter Estrogenic induction of uterine Enzymes. R.l. Slngnal, J.A. Thomas, and m.R. Parulskar, Li fa Sciences 299, 1972. Relationship of Pituitary Hormones end Androgens on Prostate clano Metabolism. J.A. Thomas, m.c. Meohlnnay ano J.R. Lloyd, Proceedings 1st Annual carcinogenesis Symposium, p. 41, October 1-a, 1972 (Abstract). Effects of 00T an Radioactive uoteke from Testosterone-1,2-h) by Mousa Prostate Glenda, m.t. Smith, J.A. Thomas, C.C. Smith, m.g. Mevninnay a-: J.w. Lloyd, Teaicelegy and Applied Pharmacology 22: 199, 1972. Currant Assessment of Marijuana. J.A. Thomas, m.t. Smith and G.R. American Journal of School Health 2>. 392, 1972. uterine c-amm-h) after Estradiol and/or Propranolol. J.a. Thomas, e. Czap ano R.L. Slngnal, Hormonsa ano Metabolic Research * 313, 197?. Adenosine uptake and Metabolism of Cyclle 3*, S'-Aoenoslne Monophase-i* by Normal ano Hyperplastic Dog Prostate Glands, m.g. Meehlnney, C.C. ^ Smith, j.a. Thomas and O.F. Milea, investigative urology 2a3, 19 . MOMS 222191 IfrllQtiorn ( con t ) ; 13 utostarona: Stimulation of fldanyi Cyclist ana c-amp.h) Formation in It Samlnal vaalcias. J.A. Thomas ano a.l. Slngn*;. aiocnamicai fcarmscology 307, 1973. a formation ano Distribution of Cyclic 3* , S'-aaanoslna M0nooh0*onat* f tna Evartad Culnaa Pig Saninai vaalcla Sac. C.C. Smith, m.c. whlnnty, s.l. Slngnai. ana J.A. Thomaa. Invaatlgatlva urology 278, atrlbutlon of C^-Aiflha.jwinoButvrlc Acid, Cl4-J-o-athylgiucosa (o C14 Insulin in Evartad Saislnal vaalcla Sacs. **.5. nawhinnay. J.A. da*, C.C. Smith ano O.F. Milam, Invastlgativa urology j2, 1973. tabollc Charactarlstics of Hyparplaatlc Oog Prostata Glands, m.c. owninnay, f.l. Schwartz, J.A. Thomas, L.S. Ollvar, E. Zaps and J.w. |oyd. Procaadlngs Annual Amarlcan Urology Association, 1973 (Abstract). nataneas with Apusa Potantlal at tha Elamantary and High School Laval. &A. Thomas, m.c. Mswhinnay ano c.A. Knotts. Clinical Padiatrica 12: 17, *73. ffacts of chronically AOmlnlstarad Oaltal-tetrahydrocannabinol on feranal and Conaaal Activity of Mala flats. C.M. Ling, J.A. Thomas, O.S. |har ano a.l. Slngnai. intamatlonal Journal of Clinical Pharmacology 7: 1973. " |tlona of tha HorblclOa 2,*,3-T on th uptake and ilotranaformation of latosterone-1,2-hJ by tha Mouse Prostata Clano. J.w. tloyO, J.A. Romas ano m.c. Mawhlnnoy. Archlvaa of Cnvlronmontsl Health : 217, 197j. [[fact of Prolactin on tha In vitro Accuaulatlon of Trltiatad Satoatarona (T-J) by tna Frostaca Gland. J.w. Lloyd, J.A. Thomas. SL. Koanan and 8. Araatan, Federation Procaadlngs 31: 298,1973 [Abstract). boa Inhibitory Actions of Morphlna on Saw Accassory Gland Matabolisn. I.A. Thomas, m.c. Mswhinnay and J.A. Lloyd. Proc. Sociaty of Toxicology, !2th Annual Masting, p. 29, 1973 (Abstract). Amo Actions of Orgsnochlorlbo Pastlcldas on Sax Accassory Organs of Mproouctlon. J.A. Thomaa and J.w. Lloyd, in PCSTICIOCS Amo ThE SviPONMCNT: A CONTINUING CONTAOVCASY, p. IT, Symposium Spaclallst, publ. larth Miami, Florida, 1973. iffacts of 2,a,S-T and Othar Organochlorldas on tha Matabolism of Bstoatarona-ltl-H3 by Nolo Orgona of Reproduction. J.w. Lloyd, J.A. Komas, m.c. Mawhlnndy, and C.5. Olarlngtr, Sociaty of Toxicology, 12th fcnual Mooting^ p. 9, 1973 (Abstract). IPdrogan Motabalism by tho Cplthallum or Muaelo Ltytra of tho Guinea Pig aaoinoi vssielaa. F.L. Schwartz, J.A. Thomas, J.*. Lloyd and m.c. pwhinnay. The Pharmscologiat 237, 1973 (Abstract). Ta Effact of Taatoatarona on th Concantratlon ATP in Accoaadry Sax Bgena of tna Culnaa Pig and Pat. m.c. Mawhlnnoy, L.C. Ollvar, J.A. Romas, c.j. Malanga and J.W. Lldyd. Tha Phsroacaldglat 13: 234, 1973 bstract). HOMS 222192 PUBLICATIONS (continued): LA Differential Response of Either Bovin* or Ovine Prolactin on Testostorone-H? Metabolism in various Looat of tn* Pat Prostata cianc e.4. Zaoo* J.A. Tho**, m.g. M*wninn*y ana J.n. Lloyd. Th* ' Pnsrmscologist l^ 234, 1973 {Abstract). Effect of Bovin* Prolactin on Androgon Accumulation by tha mous* Proscit* Clano. 6. J. Kaanan, J.A. Thom**, **.G. M*wnlnnsy ano J.a. LloyO. Th* ' Pharmacologist l^,: 234, 1973 (Abstract). Inriusnc* of Carbaryl on Androgan Mitabollsm in tha Prostata Clano mg Livar. C.S. Olarlngar, J.A. Thomas- and R.E. Stltzal. Th* pharmacologist 224, 1973 (Abstract). Distribution of Padloactivity in moi* Reproductive Organs Artar tn* Aoministration of Either Carbary 1-Cl* or OOT-hJ. j.a. Thomas, L.C. Scnain, ano C.S. Olarlngar. Tha Pharmacologist 227, 1973 (Abstract). factors Affactlng Cyclic Adanoslna Monophosonata (c-amp) l*v*1s in th* Prostrata elands of tha flodant. J.a. Lloyd. J.A. Thomaa. and m.c, Hawhinnay. Th* Pharmacologist l; 231, 1973 (Abstract). Androgan* and Cycllc-AHP in th* Guinea Pig' Samlnal v*aicla. C.C. Smith, J.A. Thomas and m.c. m*ninnay. Tha Pharmacologist 13*231. 1973 (Abstract). Actions of Morphlna on Mala Sax Accessory Organs of Reproduction. J.t. Oomorosky, J.A. Thomaa, J.w. Lloyd and m.C. M**nlnn*y. Life Sclancaa 13* 794, 1973. A Olffaranca in th* in vitro Accumulation and Metabolism of T*stoat*ron*>l,2-HP By tn* Nat Prostate Clano felloelng Incubation ltn Ovlna or Bovin* Prolactin. J.a. Lloyd, J.A. Thomas and m.c. Mahinn*y. Steroids jji 473, 19T3. H*aos* and Amino Acid Assimilation by th* epithelium and Muscle of th* Guinea Pig Seminal vaaicla. M.C. M**hlnn*y, J.T. Oomorosky, C.C. Smith. J.a. Thomas* J.w. Lloyd, journal Pharmacology and Experimental Therapeutics 17: *30, 1973. Actions of Oisldrln on the Accumulation and llotransformation of Radioactive Testosterone by Mouse Prostate Glands. J.A. Thomas, J.. Lloyd, m.c. Mooninney and C.C. Smith. Toxicology ano Applied Pharmacology 523, 1973. Th* uae end Abuee ef Anabolic Steroids. J.A. Thomas, C.A. Knotts and c.s. Erickson. Journal of Alconol and Orug Education 31, 1973. Relationship of Pituitary Hormonas and Androgons on Proatat* Clano Metabolism. J.A. Thoaas. 2nd Annuel Collaborative Carcinogenesis Conference, p. 3*, November 23~29, 1973 (Abstract). Passage of Substances Into the Lumen of the isolated Seminal vaslcla 3*: of th* Guinea Pig. J.A. Thomas, m.c. Mhlnnay end J.a. Lloyd, urologies international!* 1*9* 197*. NONS 222193 j&l Icatlons (eont ): 15 lie 3*, S'-Guanosine Monopnosenate (cCMP) and Cyclic 3',S'-Adenosine .wriopnosonata (camp) Laval* in Mouia Sax Accaaaory Organa. E.A. Zaps, j.A. Tnomas and a.*. Planing. FeOeration Proceedings 33; 521, 1574 Abstract). ;rract* of Prolactin mo Taatoatarona on Mouse Prostata Gland and Saninal /aside. E.J. Keenan and J.A. Thomas, Federation Procaaolngt 33- 283, t?7* (Abstract!. --" Tha Effact of Prolactin on Androgan Asslnllatlon by EDithallui* and Muscle if tna Guinea Pig Saninal vatida. J.A. Bells, P.i. Scn.artz, J.A. Thome* ind M.C. naninnay. Federation Procaadlnga 32: 283, 177a (Abstract). ETfact of Paratnion on tha nota*a and Matabolisn of Androgans In ftoaant Sax Accassory Organs. J.A. Thonas and L.C. Senain. Toxicology and Applied Pnarnacology, 9: 53 , 197*. Effects of Carbaryl on tna Matabolisn of Androgans in tna Prostata ana Livar of tna mous*. C.S. Olaringar and J.A. Thones. Environnantal Rasaaren 2' 381, 197*. Prostatic and Hepatic Tastostarona-1,2-3m Matabolisn as Affactad by 00T Pra-traatnant in tna Mousa. J.x. Lloyd, J.A. Thonas, and m.c. Maahlnnay. Toxicology and Appiiad Pnarnacology jj: 2*8, 197*. Effacts of Carbaryl on Mouse Organa of Reoroductlon. J.A. Thonas, C.S. Olaringar and L.C. Senain. Toxicology and Applied Pnarnacology ZB: 1*2, 197*. Pnarnacology of Morphine and Heroin, m.c. Maahlnnay, C.R. Knotts and J.A. Thonas, Journal of Alcohol and Orug Abuse, 23(3), 197*. Androgan Asslnllatlon by nornal and Hyperplastic Oog Prostata elands. m.c. Maahlnnay, F.L. Schwartz, J.A. Thonas and J.a. Lloyd. Invostigative jrology 1^.: 17, 197*. Androgan Asslnllatlon by Eplthallun and Muscle of the Culnaa Pig Saninal vesicle, m.c. Maahlnnay, ?.L. Schaartz, J.A. Thonas, J.A. Balls and J.a. Lloyo. Journal of Phernacology end Experieantal Therapeutics 188: 32*, 197*. effects of Acetylcholine or isoproterenol on Sax Accassory Gland Levels Af cgmp or camp In vitro. C.A. Zapp and J.A. Thonas. The Pharnacologist, ill 310. 197* (Abstract). Effacts of Croocryptlno and Prolactin on the Mouse Anterior Prostata Clano and Sonlnol vaslela. E.J. Kaanan and J.A. Thonas. The Pharnacologist. 279, 197* (Abstract). Action of Prolaetin on Oxygen Consunptlon by Mala Guinea Pig Sax Accessory Organs. J.a. Bells, O.f. Milan, J.A. Thonas and m.c. Maenlnnoy, The Pharnacologist. 275, l*7* (Abstract). Relationship of Prolactin to Oxidative and Reductive Matabolisn of Testosterone by Guinea Pig Sax Accassory Organs, m.c. Me*hinney, J.A. Bells, F.L. Schwartz, C.S. Olaringar and J.a. Thonas. The Pharnacologist. Id: 273. 197a (Abstract). HONS 222194 Publication (cont. ): IS Interaction of Oleldrin and Paratnlon on Androgen Metabolism in tn Prostata and on Hpatic P-*SO Activity in Mica. J.A. Thomas l.g. Scntit m.O. Colby *no *.J. Canady, rna Pharmacologist. l: 229, 197* (Abstractj Synergistic Effect of Prolactin and Testosterone on Pat Prostata CU"C sno ivucitlc Acia Levels. m.s.p. Manandhar, J.A, Thomas, m.g. Mawninrty E.J. Kaanan *no E.a. Zaop. Tha Pharmacologist. 1: !7S, 197* (Abstract>. failure of Parathion to Altar mcic Mousa Paproductlva Organ Activity. j.a. Thomas and m.c. Mawninnay. Toxicology sno Appiiao Pharmacoloov 29' 13*. 197* (Abstract) -- Cystic Dilatation of Sax Accassory Organs In common ano Inbrto Syrian namstars. J.A. Balls, f.l. Schwartz, J.A, Thomas, J.a. Lloyd, j.r. Oomorosky, c-S. Olarlngar and m.g, Mawninnay. Journal of Garontolocv z?- JB2, i97*. * 4-' Tha Toxic Effacts of Marcury. E.a. Zaoo, C.A. Knotts ano J.a, Thomas. Clinical Padlatrics. 12*. 9, 197a, Effacts of Thiophanata and Tniophanate-Methyi on tha Mala Paproductlva Systam of tha Mousa. J.a. Thomas and L.C. Schaln. Toxicology and Appiiao Pharmacology, 129, 197*. Hormonal Influanca on Prostata Organ Cyclic Cuanoslna Monopnospnata (cCMP) and Cyclic Adsnosina Nonophosonata (cAMP). j.a. Thosas and m.s.p. Manandhar. Proc. xxvi Intarnatlonsl Congrass Physiological Sclancas, haw Oalhl, Octobar 197* (Abstract) Effacts of Psaticidaa on tha Mala Paproductlva Systam. j.a. Thomas ano L.C. Schaln. Proc, Sstallita Symposlum*xxvi Intarnatlonal Congrass of Physiological Sclancas, Ludhiana, India, Octobar 197A. Tha Effacts of Testosterone snd/or Prolactin on tha Incorporation of AH-thymldlna Into ONA in tha Pot Prostata eland n vivo, m.s.p. Manandhar and J.A. Thomas. Procaodings xl Intarnatlonsl Cancer Congress. Florence, Italy, October 1974 (Abstract). Action of Pesticides end Other Orugs on the Mele Paproductlva Systam. J.A. Thomas. Environmental Health Effects Peseerch Series. (Nat'l. Tech, inform. Serv. 09297311 - December 1974). Effect of Prolectin an Androgen Metabolism by the Guinea Pig Sax Accessary Organs, m.c. Mamhinney, J.A. bells, J.A. Thomas, and J.. Lloyd. Journal of Pharmacology end Experimental Therapeutics, 192: 2<*2. 1979. Effect of Prolactin and/or Testosterens on Cyclic amp in tha Pat Pros*.**.: Gland. J.A. Thomas and m.s.p. Manandhar. Hormone and Mataeollc Research, t 929, 1974. Chsngse in Carebral Cortical Cyclic amp Formation in the Pet After ic- ? and Chronic Treatment with Morphine. Kh.S. Shanid-Selles, t.K, colesenti, c.p. Craig and J.A. Thomas. Faderstlon Proceadlnga, 2*: 1979 (Abstract). MONS 222195 jffrllcatlons (coot.); 17 igsponse of the Rt Prostata Gland Following tn Aoniniatration of irolactin. j.A. Thomas, m.s.p. wananonar and m.c. Mawhinney. 3rd Annual :arclnoganaaia Confaranca, Fao. 2-9, 197a (Abstract). Effects of Narcotics on tn Mala Reprboucttve System. J.A. Thomas ana J. jambroswy. Procaaoinga Tomcology Society, lath Annual Maatina. o. 97 <arcn 1979 (Aostract). v' Jlratnlon-Olalorin intaractiona on Androgan Metabolism in tn Mouse. l.C. Sfehain ano J.A, Thomas, Procaaoinga Sociaty Toxicology, lath Annual mating, p. 71, March 1979 (Aostract). Uomium Pollution and Its Impact on Body Metabolism. R.u. Slngnal, A. derail, J.A. Tnomes, and G.R. Knotts. Contemoorary Education, *6: loo, 1579. Effects of Prolactin and/or rastostarona on Nucleic Acid levels in prostata elands of Normal and Castratad Rats. J.A. Thooaa and m.s.p, <anandhar. Journal of Endocrinoiogy (Britain), 65,: 149, 1979, Effects of Morphlna upon tha Foroatlon of Jh-cAMP in Prostata Glands of the Mouaa. J.A. Thomas, J.T. Ooobrosky, m.c. Mawhinney, and Kh.S. Hossaini. Llfa Sclancas, 1197, 1979. Effact of Mfthadona on tha Mala Reproductive System. J.A. Thomas and J.T. OombrosMy. Arehlvaa Intarnatlonalas da Pharmscodynamle at da Thersple, 2J2; 219, ^979. Effacts of Olaldrln on tha uptake and Motabollso of Testosterone-1,2-Jh Rodant Sax Aecassory Organs. L.C. Schaln and J.A. Thoaas. Environaantai Rasaarch, 9: 29, 1979. Tha Effacts of Tastoatarona and Prolactin or Growth Horaona on tha Aeeassory Sax Organa of Castrata Mica. C.J. Kaanan and J.A. Thoaas. Journal of Endocrinology (Britain), 6*: 111, 1979. Stimulation of Mousa Aecassory Sox Organa by Prolactin. E.J. Kaanan and j.A. Thomas. Federation Procaaoinga, 2*: JO*, 1979 (Abstract). Effacts of trgocryptlno on Accessory Sox Organ Function in mio Mica. E.J. Kaanan, v.O. Edvards, E.A. Zapp and J.A, Thomas. Tha Pharmacologist. 2*2, 1979 (Abstract). Effacts of Oiathvlstllbostrol or Estradiol-.17|ota on tha Aecassory Sa> Organs of Molt Mica. J.A. Thomas, M.S.P. Monanonsr and E.J. Koansn. Tha Pharmacolaglst, 2*2, 1979 (Abstract). Soma Phsrmaealogleal Aspoets of tha Antihistsmlnas. E.A, Zapp, C.R. Knotts and J.A. Thomas. Clinical Padlatrlcs, i*: 1119, 1979. Androgans and Cstrogans in tna Plasms and Prostatic Tissue of Normal Cogs and Oogs with Benign Prostatic Hypartrophy. J.w. Lloyd, J.A. Thomas and M.c. Mtwhlnnay. Investigative urology, iis 220, 1973. HONS 222196 Interaction of CirOaryl ana Oitldrin on tno Motaaoliti* of 3H-T*stoat*ron*. l.G. Schein, J.A. Thoaaa, P.A. Kiase and e.O. Edward*. Proceeoings ISth Annual Toaicoiogy Socloty, p. iso, 197$ (Aoatract). conolnad Effact* of Parathion and CarOaryl on tho 8iotran*formation of Jh-Teatoatoront in tho Mai* Mouse. J.A. Thomas and L.C. Sentin. Proceeoings 15tn Annual Society Toalcology, p. ISO. 197* (Aoatract). Effect of various Carcinogen* (Cmba, Enu) on festoaterone-^H M*taoolisn and Ona Synthesis in the Rat Prostate Gland, w.O. Edwards ano j.a. Thomas, Proceedings isth Annual Society Toxicology, p. i*i, 197* (Abstract). An interaction Between Prolactin ano Oihydrotostosterone (omT) in tn aat Prostata Gland and Sealnel veslelss. E.J. aeenan, p.a. kiss* and j.a. Thomas, federation Proceedings, ): 220, 197* (Abstract). further Studies an the Pale af Cycllc-Adsnoslns-3',3'-*onaphasoh|te (camp) in Male Mouse Sea Accessory Organs. C.A. Zaps, J.A. Thornes ano J.E. Jones, federation Proceedings, 777, 1774 (Abstract). Some Pharmacological Aspects of Morphine end Methadone, j.a. Thom**, Kh.S. Shanld-Salles, B.K. Colasanti end I. Area ten, Proc. 7th Pahlavl Meolcal Congress, p. 243, April 1974, Shiraz, Iran (Abstract). Oleldrln and Parethlon interaction in tho Prostate and Liver of the Mouse. L.C. Schein and J.A. Thom**, Journal Toaicology and Environmental Health ,: 827, 1774. Influence of Prolaetin uoon Nucleic Aeld Matabollsm in Accessory Sea Organs of Male Mice. E.J. Keenan and J.A. Thomas, Proceedings SSth Annual Endroclnology Masting, p. 328, Juno 1774 (Abstract). Effeet of Isoproterenol and Acetylcholine Treatment in vitro on Cyclic Nucleotides in Mouse Sea Accessory Organs. C.A. Zeop end j.a. Thomas, Biochemical Pharmacology, 7i7, 1774. Effect of Prolactin on the Metabolism of Androgens by the Net ventral Prostate Gland n m.S.p. Men*noner end J.a. Thomas. Investigative urology, 20, 1774. Effects of Prolactin and/or Olhydrotestosterono upon the Nat Prostata Gland. J.A. Thmmat, m.S.p. Menendhar, E.J. Keanen, s.O. Edweros ano Kies*, urologica lnternetlonells 21* 243, 1774. Seizure Disorders In Children end Orugs used in the Management of Cplleeey. J.A. Thomas, C.N. Knotts, American journal of School hoU~. 4: *42, 1770. A Difference In the Nesponses of the Mouse Prostste Gland and Seminal vesicles to Prolactin, p.a. Kleaa, E.J. Keenan, e.O. Edweros ano Thornes. The Pharmacologist, ifi 2*7, 1774 (Abstract). MOMS 22219? Publication (cent.): 19 perturbation by Orgenochlorlna Pesticioes of 3m.testosterone Metabolis* In Roaent Hepatic Microtomes and Prostate Glano in_ vitro, m.p. oonovan, J.A. Thomas, L.C. Scnein, ana p.a. Kim. Th Pharmacologist 18: 23a ' 1976 (Aoatract). 5ff*ct of oiazinon, Paratnlon ana Caroaryl on tha in vitro Metabolism of H-testostaront oy Roflant Prostata Clanos and Meoatrc Microsomal Enzymes. l.C. Scnain, j.A. Thomas, m.p. Oonovan and p.a. xiasa. The Pharmacologist, 20, 1976 (Abstract). Scatchard Plot Analysis of Anorogan Binding In tha Male Guinea Pig. f.l. Schwartz, J.A. Thomas, C.l. Robinette sno m.s. Mawhinnay. rna Pharmacologist, 230 , 1976 (Aostract). Oihydrotastostarons ano Catradlol-17 Bata Receptors in tha Rat vantral Prostata and Seminal vaslcla. C.t. Roblnatta, J.A. Thomas ad m.g. Mawhlnnay. Tha Pharmacologist, 18: 2*9. 1976 (Abstract). Effects of Myposia and Erythropoietin on Murlna Solanlc Ornithine Oacarbosylasa Activity. M.NUson, j. Contrara and J.A. Thomas. Tha Pharmacologist, 216, 1976 (Abstract). Cyclic AMP-lnducad Changes In tha EEC and Bahavlor Effacts of Morohina In tha Rat. Kh.s. Shehld-Ssllea, 8.K. colasantl, C.R. Craig and J.A. Thomas. Tha Pharmacologist l^t 212, 1976 (Abstract). Crgoeryptlna and mala Aeaasory Sax Organ function. E.J. Kaanan and J.A. Thomas. Proeaadlngs 20th Annual eastern Pharmacology Soelaty, victoria, British Columbia, Jan, 28-29, 1977 (Abstract). Staroidophilic Proteins In Cytoplasm of tha Mouse Prostata Gland, m.p. Oonovan, J.A. Thomas and L.C. Schtln. federation Proceedings, 38: 3**. 1977 (Abstract). Cffacts of Prolaetln on the Oorsolateral Lobe of the Rat Prostata Clone. j.A. Thomas and m.S.p, Menendhar, Invaatlgativa urology, 398, 1977. Proposod Modal for Assessing Antl-prostetle Orugs Using a Transolsnt System, j.A. Thomee, P.R. felloe and w.O. Edvards. The Pharmacologist, 188, 1977 (Abstract). Effacts of Pesticides on Steroid Hormone Binding in Cytoplasm of Roaant Tissues. L.C. Scftaln, j.A. Thomas and m.p. Oonovan. Society of Toxicology Proceedings, p9j, March, 1977 (Abstract). Soma Actions of Parathlon and/or Oleldrln on Androgen Metabolism, j.A. Thomas, L.C. Scheln and m.p. Oonovan, Environmental Research, lj: sal, 1977. Morphine Anelgeela and Tolerance: A Possible Role of Cyclic amp. m.p. Oonovan, G.m. Ling and J.A. Thomas, v.h.O. Bulletin of Narcotics, : 9, 1977. Effacts of Aging on ONA and 01hydrotestosterone-3M formation In Rat vantral Proatataa In !) and Ventral Prostata Transplants. J.A. Thomas no *.0. Edvards. taperimtntai Gerontology, 3*: 303, 1977. MONS 222198 Publications (com.): 20 Coeoint: Old Qrug, me* Problems. C.f. xaglay and j.a. rmomss( ii*:.-,. Journal of School Health, *J.: too, 1977. Effacts or Androgens and/or Prolactin on ventral Prostata Transplant. .0. Edeards and J.A. Thomas, Urologies Intarnstlonalls, 3: 303 , i?tt a blocnemlcal Basis ror Insecticide-induced Changes In tna miu Reproductive System. J.A. Thomas, m.p. Oonovan anc t.C. Scnain. procaaolngs 17th Annual Soclaty of Toxicology, ol*9, 1978 (Aostraett. Effects of Zinc and Other metal Ions on tha n vitro Blnoing of Ancroge-'i to Cytoplasmic Proteins of mouse Prostata clano. m.p. oonovan, l.o. Schaln and J.A, Thomas, Procaaolngs 17th Annual Soclaty of Toxicology. 0183, 1978 (Abstract). Ability of Parathion (P) To Loser Plasma Testosterone and Comoatitively Inhibit Binding of Olhydrotastoaterone-Jw (OhT-Jm) to mouse Prostate Receptors. t.C. Schaln, m.p. Oonovan and J.A. Thomas- federation Proceedings J7: 288, 1978 (Abstract). gffaets of Androgans on Isooroterenol-Induceo increases In mouse Accessory Sea Organ Cyclic amp in vitro. E.a. Zaoo and J.a. Thomas, Sloehemical Pharmacology, J7: *aT, 1978. Charaetarlaatlsn of Cytoplasmic Binding of Olhyorotaatosterone by th Prostata Gland and Other Tissues of the Mouse. t.C. Seheln, m.p. Oonovan and J.A. Thornes, Toaleelogy and Applied Pharmacology, ai 1*7, if7*. 0i*(2*ethylhexyl) Phthelete (OCHPJ - A Report on its Biological Effects (revlea). J.A, Thornes, T.O. Oerby, R.E. sellIn, p.j. cervln and t. mertls. Toxicology and Applied Pheraecology AJi 1*27, 1978. Some Toxieologieel Effects of fluorocarbon Aerosols. J.A, Thomas ano C.f. Kagley, The American Journal of School Health, a: *43****, 1978. involvement of Brain Cyclic amp in tho Acute and Chronic Effects of Morpnlno in tho Rot. Khedijeh S. Shsnid-Sallei, Brenda k. Colasanti, e.e. Craig end J.a. Theaea, Pharmacology ^7: 128, 1978. Tho Structure of u.S. Modlccl School Govtrncnet c Octormined by Their 8y*teac. J.A. Thoaot end J.K. Jente. map Notte (Menadement Advancement Program), American Asamcletlon of Medleel Collages, Summer, 1978. Role of Epidemiology In Toxicology. J.A. Thempa. federation Proceedings 21: 187J, 19T9. Cffeete mt PeetieIdes on Metabolism of Storiod Hormone 8y Rodent Llvtr MicrosomdB. M.P. Donovpn, L.G. Schaln end J.a. Thornes. Journal of Environmental Patheiogy end Toxicology, **7, 1978. Some Phermeoelogle Aepeete of flourldee in Oentistry. R.a. Greet sno Themes. Rest Vlrglnle Otntel Journal, 22* 1S79. uptake ef Redleeetlve Zlne (*sZn) Into Rodent Sex Accessory Tissuss. m.p. Oonovan end J.a. Thoaot, federation Proceeding# 2i 271, 1979. HONS 222199 Plications (cont. ): 21 aceharin. P.A. relict ana j.a. Thomas, American Journal of School altn, at: 39*, 1979. ffects of Monoetnylheayl Pnthelate (mehp) on Pregnant Babbit* ana Their ffsoring. j.a. Thomas, P.R. Felice, p.k. Cuota, L.C. Schaih ana A.e. :Cafferty, Pro'catdings 18th Annual Society of Toaicoiogy 33.: *5, 1979- allure of wonoetnylneiyl Phthelate (mehp) n Offspring of Rabbits. J.A. Thomas, L.C. cCafferty, p.p. Felice, ana m.p. Oonovan. narmacology 51.: 523, 1979. to Cause Teratogenic Effects Schein, p.k. Cuota, R.E. Toxicology and Aoolleo loalstrlbution of uonoethyihe*yl Phthalata (memp) In Pregnant Aabblts no Neonatal Pets. J.A. Thomas, L. Mortis, S- clovenetto, A.E. MoCsfferty no m.p, oonovan. Feaeretlon Proceedings 29:525, 1980 (Abstract). ffects of Zinc Ion on Fructose In the Male Sex Accessory Organs of the louse. Michael p. Oonovan and John A. Thomas. Federation Proceedings 39: <98, 1980 (Abstract). ione Antianarogenlc Actions of Zinc Ion In tha Mouse, m.p. Oonovan and ].A, Thomas, Proceeding 19tn Annual Society of Toxicology, 1980 : Abstract). inhibition of Androgen*Reeeptor Interaction In Mouse Prostate Cland jytosol by Olvelont Metal Ions, m.p, Oonovan, L.C. Schein and J.A. Thomas. Molecular Pharmacology 22: 154, 1980. Effect of Prolactin end Testosterone Administration on the Maintenance of ventral Prostate Transplants Into Intact or Gonadeetomized Male and famola Syngeneic Pats. w.O. Edwards and J.A. Thomas. Urological 'nternatlonells : a, 1980. . *eet of Pharmacology Doses of Sea Steroids on Endogenous Zinc in Rodent Accessory Sex Organs, m.p. oonovan and J.A. Thomas, The Pharmacologist, 22: 269 1980 (Abstract). Morphologic and Metabolic Characteristics of ventral, Oorsal, Lateral ana anterior Prostate Lobe Treneplents in Petst Effects of Testosterone sna Prolactin. w.D. Edwards and J.A. Thomas, Hormone Research, 22: 28-29, 1980. Interaction of Cadmium and Zinc In Intact end Castrate Rata, m.p. Oonovan, m.p. weslkes, and J.A. Thomas. Federation Proceedings, *: 939, 1981 (Abstract). Effect of Cadmium on the Subcelluler Distribution of Endogenous Zinc In Fetal end Maternal Rabbit Liver, m.p. wsalkes, j.u. Sell, end J.a. Thomas. Federation Procaedlngs, A: 701, 1981 (Abstract). Failure of Monethyihexyl Phthalata (m|hp) to Affect Conedsl Zinc or Ona or RNA Levels In the Mouse, k.a. Curto and J.a. Thomas. Proc. Soe. to*. 1: 103, 1981 (Abstract). Reproductive Hazards and Environmental Chemicals. J.A. Thornes. Toxic Substances Journal, 2:31*> 1981- MOHS 222200 22 Publication! (contJ: Effect of Monoethylhe*y1 ^theiiti (MCHP) on th# Asslallatlon of tinc^J oy Rodent Reproductive Organs In vitro. J.a. Thoeas, k.a. Curto mo * a waalkes. Eighth international Congress of Pharmacology, Tokyo, Japan, If81 (Abstract). Effect of Prolactin on Ona Synthesis and Growth of tna Accessory 5a* Organs in wale Mice. C.J. Keenan, Patricia A. Kiase ana j.a. rnoes. Journal of endocrinology 108:170.173. 1981. Introductory Remarks:The Tastes. J.A. Thoaas- Environmental Healtn Perspectives 21;3"*> effects of Cyproterone Acetate on Rat ventral Prostata Transplant Growth. J.A. Thodss, w.O. Cowards and R.R. failed. Cndoerlnologia eiperlMntalls, 1.*171, 1981. Interaction *atwaen Prolactin and Anorogena In the Accessory se* Organs of Male Mice. C.J. Keenan, Patricia A. Kiase and J.A. Thoas. Journal of enoserlnology, 90:323, 1981. MQNS 222201 23 ARTICLES IN PRESS: Effact of Pesticides on Metabolism of Sterlod Hormones oy Rodent Liver Mierosames. m.p. oonovan, l.C. Schein and j.a. Thomas, Journal of Toxicology and Environmental Health __s 1982. Effects of Pesticides on ^H-oihydrotestosterone Binding to Cytoaol Proteins rro* various Tissues of tna Mouse. l.C. Scnain, m.r. Donovan, j.a. Thoaas and P.R. Falica, Journal of Environmental Pathology ana Toxicology . 1982. Endocrino Toxicology. J.A. Tho*es and J.U. Ball, ^n methooS In TOXICOLOGY, A. aallaca Hayaa, Edit., Raven Praaa __ :____, 1982. pituitary Hormones, J.A.Thornes, n pharmacology ano therapeutics, S.n. cnao and R.P. MaicKal, edit., C.v. Moaoy and Co, 1982. Mala Coneoal Hormones and Anabolic starolda, J,a. Thomas, in pmarhacolocy anO therapeutics, S.n. Pradhan and R.P. Meiekel, adit., C.v. Moaby ana Cd. 1982. Elaetroflharatlc Analyaia of 3H-Oihydrotestosterone Binding In tna Cytoplasm of the Mouaa Prostata Gland and tna Effacts of Pastlcldas. Pat Felice, m.p. Oonovan and J.A, Thoaas. Journal of Environmental Pathology and Toxicology, __ , 1982. Effaet of Diethylheayl Phthelete (OEMP) or aonoethylhexyi Phthalata (mEHP) on Mouaa Reproductive Organa, k.a. Cur to and J.A. Thoaas. Toxicology and Applied Pharmacology1982. Toxicity and Matadollaa of m*mp - A Survay of Racant Lltaratura. J.A. Thoaas and S. Northup. J. Toxicol. Environ. Haaltn ___ : , 1982. Asaaasaant of Gonadal Toxicity From Chemical Exooaura in tha *ork Placa. Proceedings Canadian Sociaty of Toxicology i . 1982. NONS 222202 Articles In Press (cent.): MEMP/OEHPtGonadal Toxicity and grreets an Rodent Accessory Sex Organs. Jonn a, Thoeas, Karen a, Curto ana Michael J. Thoeas. Environeentai wealth Perspectives :__ . 1982. failure of Phthalate Ada Esters (PAC) To Stieuiate Lioid Peroxidation Rat Reproductive Organs, a.c. Brogan, 111, k.a. Curto and J.A. Thoaat Procaeolngs 19th Annual Saelaty of Toxicology (Abstract) 1982. Further Studies on the Effects of the Phthalate Acid Esters (PAE) on a Male Reproductive Organs, k.a. Curto, R.c. necafforty, m.p, Oonovan a J.A. Thoeas. Procaeolngs 19th Annual Society of Toxicology (Abstract) 1982- Cean>lu-Induced Prostate Metallothloneln in the Rabbit, m.p. waal*ts, m.p. Oonovan and J.a. Thoeas. Tha Prostate, 1982. Effects of Lead on tha Mala Reproductive. Tract. J.A. Thoeas ana e.c. irogen, III, Aeerlcan journal Industrial Medicine __ :__ . 192. Enhenceaent of Iron*lnduced Testicular Lipid Peroxidation (lp) 8y 0i*(2-Ethylhexyl) Phthalate (OCHP) or Oietery Zinc Oefleleney. w.C. Brogan, ill, K.A. Curto, and J.A. Thpaaa. federation Proceedings (Abstract), 1912. MOHS 222203 -25- B0CK5 aNO CHAPTERS: SVNCPSIS OF ENOOCfllNC PHARMACOLOGY. j.a. Thomas ana m.c. Mi.hinnty, university Part* Prass, Baltimore, *arylano, 197?, Cyclic 3' . 5'-Acenosina Monoonosonata-Adtny1 Cyclase System in Prostate Clanos ana o:n*r Anorogan-Oaoanoant Tissues, R.l. Singnal. J.a. Thomas ana O.J.8. Sutherland, AH normal anO ABNORMAL GROWTH QF The PROSTATE. Cnaotar 25, o. **5, C.C. Thomas mg Co. , PuOl., 1974. Soe AetiOhs of Prolactin on the M*t*oolism 0# Tstost*rona-*3 in Prostata Clanos of tna Rat ana Oog In vitro, j.a. Thomas, m.C. Mehirnt ano J.w. Hoy0, in normal ang asnormTl dAOwTH OF th* PROSTATE. Chapter 21, p. 53* i C.C. Thomas ano Co., pudl., 197*. MOLECULAR MECHANISMS OF C0NAQAL HORMONE ACTION - Advances In Sax Mormon* Research, volume I. J.a. Thomas ana R.l. Singnal, aoltors, university Park Press, Baltimore, Maryland, 1973. Effect of Pesticides on the Reproductive System, j.a. Thomas, in MOLECULAR MECHANISMS ON CONAOAL HORMONE ACTION - Advances In 5*7 mormon* Research, j.a. Thomas end R.l. Singnal, editors, university Park Press, Baltimore, Maryland, 1979. introduction to the Endracrine*. J.A. Thomas and J.C. Jon#*, in the essentials of pharmacology, John A. Bavan, editor. Harper enoTTow, 197*. Pituitary Hormones, J.A Thomae and J.C, Jonae, in The ESSENTIALS OF pharmacology, John A. Bavan, editor, Haroer end Row, 1974. Thyroid and Anti-Thyroid Oruge. J.C. Jonas and J.a, Thoaaa, in the ESSENTIALS of pharmacology, j.a. Sevan, sditor, Haroer and flow, 1976. Insulin and Oral MypoQlyeemlc Drugs. J.A. Thoaaa and J.C. Jones, In the ESSENTIALS OF PHARMACOLOGY, j.a, Bavan, aCltar, Herder and Row, lTT*. Adrenal Cortical Steroids. J.C. Jones and J.a. Thoest, An the essentials OF PHARMACOLOGY. John A. Seven, editor, Harper end Row, i976. Androgens and Estrogens. J.C. Jonas and J.A. Thoaaa, in THE ESSENTIALS CF PHARMACOLOGY, John A, Sevan, editor, Haroer end Row, 1776. Orel Contreeeotlvee. J.A. Thomas and J.C. Jones, AS. ESSENTIALS OF PHARMACOLOGY, John A. Sevan, editor, Heroer end Row, 1976. CELLULAR MCGMAMISMS MOOUIATINC GONAOAL ACTION - Advened* in Sex hormom* fleeeercn, volume II. R.L. Singhei end J.a. Thoaaa, editors, university Perk Press, Beltisore, Maryland, 1976. Prolactin influences Uoon Androgen Action In Hale Accessory Sex Organ*. j.a. Thomas and E.J. Keenan, An CELLULAR MECHANISMS mOOULATInG GONAOAl action - Advances in Sex Hormone Reseercn. vol. II, oo. *23-*70. R.L. Slnghal and J.A. Thoaea, editors, university Perk Press, Beltieore, Maryland, 1976. nons 222204 26 aoom and Chaotart (eont.): REGULATORY MfCHAMSNS AfPECTINC CONAQAL HORMONE ACTION - Advances in 3fl Horoona Rasaareh vol. III. J.A. Thoaas and A.).. Slngnal, adit., university Par* Press, Baltiaore, Maryland, 197*. Effect of Narcotics on the Reproductive Systaa, J.A. Thoaas. x.s. Shanid-Sallas ana m.p. Oonovan, in REGULATORY mechanisms aepectinc GQnaoal hormone action - Advancas in Sex noraona Rasaaren, vol. Ill, Thoaas and R.L. Singnal, aoltors, Unlvarsity Parte Rrass, Baitlaora, Maryland, 1977. :.a. Effects of Leao on tna Raoroouetlva Systea. J-u. Ball and J.A. mo*as i* BASIC ano clinical toxicology or LCAO, R.L. singnal ano j.a. rttoae*. ~' adit., uroan a Schwartanbarg Radical Rubllanara, Baltiaore, Marylano, 19*0. BASIC ANO CLINICAL TOXICOLOGY Of LEAO, R.L. Slnghal and J.A. Thomas, adit., urban 4 Schwartanbarg Mtdleal Publishers, Baltiaore, Marylano. 19 BO. Soae Proteln-Haevy natal Intaractlons In tha Rodtnt Prostata Call. j.a. Thoaas, m.p. Oonovan and m,p. waalkas In TmC PROSTATIC CELL. Murony, G.P., Sandbarg, A.A. and Karr, J.R. adit., A.R. Lias Publlshars, 19B1. Introduction to Endocrlno Tharaoy- J.A. Thoaas in NOOERN pharmacology, C.R. Craig, ono R.K. Stitxal, aolt., Llttla Brawn Publ. 19B1. Eatrogona, Oral Contracaotlvas and Progostlns. J.A Thoaea in mooirn pharmacology, c.R. Craig and R.C. Stitxal, adit., Llttla Brown pud. :?8i. Thyroid and Parathyroid. J.A. Thoaas, Ifi NOOERN PHARMACOLOGY, c.R. C:ais and R.C. Stitxal, adit., Llttla Brown Publ. 19B1. HONS 222205 AuOIO-VlSUAL MATERIALS: -2 7- Slology sno Drugs, J.A. Tho*s, 38 minutes, black ana ehitt: vtaoo rao, k.V.u. filo, i72. Pharmacologic.Actions of C.N.S. Oopresssnts (Pharmacology laboratory exercise). j.a. Thomas ana m.c. Hswninney, a? minutes, black ana nite: vioeo Tase, e.v.u. fiim, 1973. Pharmacology of Pituitary Hormones, j.a. Thomas, 38 minutes aualo tape cassette, Meolcal Science Taoe Library, hew York, n.y., 1774. Pharmacology of ThyroiO Hormones, Antl-Thyrolo Orugs ana Parathyraia *orone. j.a. Thomas, 38 minutes, auOio taoe cassette, Medical Science Taoa Library, he* York, n.y., 1974. Insulin ana Mycaglyeemle Agents, J.A. Thomas, 34 mlnutas audio taoa cassatta, nodical Science Taoa Library, Nae York, n.y., 1974. Pharmacological use of Aorenoeartlcal Steroids, j.a. Thomas, 49 minutes audio tape cassette, medical Science Tape Library, Nee York, n.y., 1974. Pharmacological use of Androgens and Estrogens, J.A. Thomas. 52 mlnutas audio teoe eessette. Medical Science Tape Library, Nee York, n.y., 1974. Oral Contraceptives, J.a. Thomas, 30 minutes audio taoa eassatta, Medical Science Tape Library, no* Vork, n.y., 197A. Histopathology of the human Prostate, m.t. smith and J.a. Thornes (108-2* * 2" photomicrograph aat of light and CM slldas) Toehnomies Publishing Company (Health Sclanca Oivision), eoetport, conn., 1977. MOMS 222206 Cwa siAiE myosity library -28. manuscripts submitteo ano/QR in preparation; Effect Of MCA on tna ONA Syntha*l*. *H.Testosterone Metabolise. *na Noronology in the Rat Prostata. w.o. Edward* ano J.a, moaas. Alteration* in JH-Tastostarona Metabolise, Ona Synthesis, and Moranoiogy in tn Rat Prostata following Treateant witn collaganata and/or Carcinogens (0M8A and mca). w.O. Edward* and J.A. Thomas. Effaet of 0M8A on tna weights, ona synthasis, 3M.ra*tostarona Mataooll**, and Histology in tna Rat Prostata. J.A. mcaas ano w.o. Edward*. Influence of Donor Mo*t Aga on vantral Prostata Transplant Survival. o Edward* and J.A. moots. ' Effaet of Enu on th* Morphology and Metabolisa of Tastostarona-^n in tna Rat Prostata, w.o. Edward* and J.a. Thoaas. Horaonal Influanca upon tna Morphology of Rat vantral Prostata Transplants. w.O. Edward* and J.a. Tnoaaa. Ergacryptlnt and Prolactin influence* upon Mole Accessory Sa> Organa. C.J.- Keenan, p.a. Klass and j.a. Thoaas. TEXT800K or ENOOCRINC PHARMACOLOGY, J.A. Thoaas and E.J. waanan. urban t Sahwaraanoarg Medical Pwblisnera, baltlaare, Motylana (in preparation}, Effect* of Paatlcidaa on ^M-Oihydrotastottarona Rinding to Cytoaol Protein in various Tlaaua* of the House. L.6. Scnain, m.p. Donovan ano j.a. Thoaas. me Induction of Tuaors in Rat vantral Proatste Epithelial Tranaalants. w.o. Edwards and j.a, Thoaas. Allergic Reactions Caused by Horaones or Horaone-liMe Oruga. j.a. Mecovarn, c.R. Knotts and J.a. Thoaas. Soaa Protaln.Msawy Metal Interactions in tna Rat Proatstlc Call. j.a. Thoaaa, m.p. Donovan and m. sealkee. induction of Matallathlanain in the Ret Main by Coppar-lPplantatlon :ut not by cobalt-laalantatlan. m.p. wealkes, S.m. Reas, C.R. Craig ano J.-. Thoaas. HOMS 22220*