Document Y00V6x5K1v9exZKNgvVe3yNE

EXHIBIT 2 The Toxicity of the Vapors of Aroclor 1242'and Aroclor 1254 J. F. TREON, Ph.D., F. P. CLEVELAND, M.D.. J. W. CAPPEL. and R. W. ATCHLEY The Raftering Laboratory. Department of Preventive Medicino and industrial Health College of Medicine, University of Cincinnati Reprinted from Amkkican Inuustimal Hvoiks'k Association Quactfrly, * 17:2, 21)4-213, June 10riS. _____ (Copyright, 1956, American Industrial llygicne Asftocintion) HONS Q9767S The Toxicity of the Vapors of Aroclor 1242*and Arochr 1254' J. F. TREON, Ph.D., F. P. CLEVELAND, M.D., J. W. CAPPEL. and R. W. ATCHLEY TKa Kettering Laboratory. Department of Preventive Medicine and Induxtiio! Health Collage of Medicine, University of Cincinnati Investigation ef ike phyeWogicnl re Aroclor 1242 per liter of air is equivalent sponse of animals to the inhalation of to 96.9 ppm by volume. two Aroclors, nnmely 1212 and 1251, was Aroclor 125-1, which corresponds to penta- undertaken because in the earlier literature1 ehlorobiphenyl, is a light, straw-colored, dealing with the toxic effects of A roclor*, viscous liquid. The positions of the chlorine no distinction line been drawn between the atoms have not been established. The mo toxie effects of chlorinated biphenyls and lecular weight of pentachlorobiphenyl is these of chlorinated naphthalenes, despite 226.44S, of which 54.3& Is chlorine. Ben- the differences in the chemical composition, ignus has reported that Aroclor 1264 con physical characteristics, and industrial ap tains 55.0 ^ 0.5`c of chlorine. Bulletin No. plications of these classes of compounds. In O-F-115 describes Aroclor 1254 a* having a tho case of the chlorinated biphenyls, at specific gravity at 25*.25*C of 1.538 to least, further toxicological investigation and 1.5-18; a distillation range of 3G5* to 390*C, consideration were required to demonstrate a refractive index (l)-linc at 2U"C) of 1.C39 the relationship between the extent of their to 3.C11. and .1 Pnvhnlt I'nivrr.-wj! vt..-v*f?v chlorination and their toxicity. al ICO* F of 1,00 to 2,500 seconds. The Properties vapor pressure at 150*C is about 1.3 mm, and at 200*0 is about 9 mm. The material A ROCLOR 1242 Is a light, straw-colored, mo is soluble in mo.<t organic substances, but il bile liquid. According to Uenigmis, of is insoluble in water and glycerine. At 745 Monsanto Chemical Company, it contains mm of mercury and 23eC the concentration 42.0 u: 0.5% of chlorine, an amount which of 1 mg of Ayoclor 1254 per liter 13 equiva corresponds to a chlorinated biphenyl with lent to 76.5 ppm by volume. three chlorine atoms in unnsslgnod posi tions. The physical and chemical properties Experimental Method are given in Monsanto Application Bulletin pxi'OSURE TO till: vator: In a preliminary No. O-P-115. Its *jxciftc gravity at 25/ experiment (No. 1) with the vapor of 25*C is 1.378 to 1.3S8: it has a distillation Aroclor 1242, a group of animals was con range of 325* to 3G0*C; a refractive index fined for seven hours on each of five days (P-line at 21>*C) of 1.C27 to 1.829; n Snyboll per week in a rectangular plywood chamber Universal viscosity at 100'F of 80 to 93 (volume 600 liters), of which the inner seconds, and a flush point (Cleveland Open mein) lining was coated with a baked chemi Cup) of 17G*-180*C. Its vapor pressure is cally resistant plastic, through which was about 4 mm at 150*C and about 30 mm at passed n stream of air laden with Aroclor 200 *C. Although insoluble in water and gly 1242 in u known concentration. The stream cerine, it is soluble in most organic sub of air. conditioned with respect In tempera stances. At 745 mm of mercury and 23*0, ture (.75* 3*F inside the chamber), dust the concentration of 1 ing of the vapor of and humidity, entered the vhnmW through rmntH at the >f*Ueth Annuel Mvetlnr if the 'AnmiU'am iMivemet. muir..\t Axmquatm*. I'hitaJelnMe, Apa ?. ms. , An "Ancmosiat," located at the center of its top, at the rate of 500 liters per minute, ns measured by an inclined manometer attached HONS 097660 to the Aroclor*, in another cham ber supplied only with condi tioned air. A second set of experiments with onch of the Aroclors at lower concentrations was eon- ducted in the same chambers. In tho third experiment with Aro clor 1242, which was heated to lITT*- 86* to G0*C, the air passed over the liquid at the rate of 800 liters per minute. In the second ex periment with Aroclor 1251, tho liquid wns maintained between 115* and 126*C while 700 liters of air per minute passed over its surface before entering the chamber. The animnls exposed in each of these experiments, as well u a second croup of controls, MwimNi Aiiimi of Ur wbHftriny Awilir, (Wkii. q<l|wirt fa iintNirtliii ii^ wIttHw ! implM. were confined In separata 600 liter chambers during a eevon hour period on each of five days per week during the week pre to ii venturimetcr (Fig. 1). The air was ceding the initial exposure of the test ani withdrawn by auction from the chamber mals to the vapor of the respective Aroclors. through an exit tube located on the rear In all experiments, the period of exposure wall near the door, equidistant from the or confinement (controls) wns seven hours aides. per day on five days per week for several AvocUir 1242 \vh volatilized from a wfwkv In nd ms*nn?c, tho original group heated shies well maintained at 122* to consisted of one cat, i\ guinea ten I 188*C. The air paused over the surface of mice, four rabbits, and ten rata. Among tho liquid before entering the chamber both the experimental and control groups, (Fitf. 1). several animals died from extraneous causes In a second similar experiment performed during the course of these experiments and on tho aiime Aroclor (No. 2>, the tempera were replaced very soon thereafter. In the Sm; ture of the liquid was kept at 100* to 105eC. While the second experiment with Aroclor 1242 was in progress, an experiment involv ing the vapor of Aroclor 1251 (No. 1) was carried out in a second chamber similar to the first except for the absence of a plastic inner lining. Tho rate at which air (lowed over liquid Aroclor 1251, which was main tained at 130* to 135*C, was 400 liters per minute. In order to accustom tho animnls to the cxpevimcntnl procedure, they wove kept in tholr respective chambers for seven hours on each of four consecutive days during the week prior to the introduction of the Aro clor vnpor into tho chnm!>er. For purposes of control (Xo. 1), a third grant) of animals was confined, throughout u like poriod be fore and during the period of the exposure second exiKdimcnt with Aroclor 3212, in the first experiment with Aroclor 1254. and In the comparable group of controls, repre sentative animals were killud throughout the experiment. 5IKTHOD ran THK DKTF.UMIN'ATIO.M OK THE AROCLORS in air: Those materials were de termined quantitatively by virtue of tho fact that, on thermal decomposition, they yield hydrochloric acid which with silver nitrate, forms a suspension, the density of which could t>e measured by means of the llockmnn si>ectrophot<>mcter at 500 mu. On each day, two samples of nir from each chamber were collected by passing air at the rate of ono litor per minute (for 16 min utes in the ense of the higher concentration* and for 15 minutes in ease of the lower con centrations) through a fused silica combus- tion furnn bubblers, 1 0.1 N midi mm outbid and 1G.25 era) strips die nine i> with a If* the fin ilia of R. ami ohm per ' bestos rrn midified l water phi- quartz till at 830rC, the pivtwr. absorbed midget bt MONS 097681 4 Mtlnr Clinm|lh tWMlt- nqMrlmcnt* Aiakn it tnt conhAArtKT*. In t HK Are kanltd to powwl ovur of MW liter* Mtond ex,ir 1201, the si-4 between ie 1M liter* wd over its tcrlntt the X|KMod in own, ak well of controls, rfanri* too Mr eoven of tro toy* r tcook prebo test milvo Aiwlon. of exposure erven hours for oovernl r.tol ttmip (>ire, ten el*. Amoutt tjnl group*, :rwtti eituse* tinwiil* find fter. In the r 1212, In r I'-'i, iimt *-rol., re|ii'c<#l'li,,ul the him or Tiir. U * <lov of tile fuct . they yield 'r nltnilo, t of Wllilll he Ihvkiiiiin 1 r fiten rnrh r sir nt I lie ; IS ininrural lun* - I,,er ten- ' romlill*- II i I i i ( i 1 Hf. 2. HvmUISfiar, furnace, and MfflpRnf levari. ff. 3. Sampflnfl Iowan. (Mi^al loblloiij tion furnace, mid (hen through two midget bubblers, in scries, each containing 10 ml of 0.1 N sodium hydroxide. A quartz tube (13 mm outside diameter, 7 mm inside diameter mid 16.23 inches in length) contained sev eral uli-ip* uf folded phitinum foil. The mid dle nine inches of Uio tube wore wrapped with a heating unit. The heating unit of the furnaco (Fig. 2) consisted of 20 feet of 11. and S., gauge 22, nicliromc wire (1 ohm per foot), and whs covered with nsbestos cement. The sample of air was hu midified by a cotton wick saturated with water placed 0.5 inch upstream from the quartz lid*. With thu furnace maintained at 850`C. (he Aroelor was decomposed in tho presence of 11-0 to form 1ICI; this was absorbed in 0.1 N sodium hydroxide in midget bubblers (Fig. 3) equipped with -frlttcd-gluas bubblers (Mine Safety Ap pliance Company No. 4.W7 i. The 0.1 N sodium hydroxide was pre pared by dinselvinjr 4.0 % of pellets (ACS specifications 0.01% G) In about 50 ml of double-distilled water. To this were added 10 p of arsenic trioxido (chloride-free) dis solved in water and filtered through What man No. 42 filler paper. The combined solu tions were diluted to 1,000 milliliters. The sample was tmnsforrnrl to n 25 ml graduated cylinder to which one drop of a solution of phcnolphthalcin was added (1 g of phcuolphlhalem dissolved in 100 ml of CP methanol. The solution was neutralized with 3X nitric acid (190 ml CP concen trated nitric acid diluted to 1,000 ml with double-distilled water) and diluted to 23 ml with double-distilled water. One ml of 3X nitric acid was added To obtain a pH of 1. After adding 1 ml of a solution of silvor nitrate (3 g of AffXOs diluted to 1,000 ml with double-distilled water), tho sus pension was mixed by inversion. After standing 30 minutes, the transmission of wave-length 500 mu was measured in n 50 cm cell by menus of a Heckman kpoctrophotometor which was set against n correspond ing celt containing a reagent blank. The nmuunl uf Aruciur was eatinjnuu uy means of a standardized cmre prernred from known quantities of sodium chloride. A curve presenting the transmission values at 60U m/A of suspensions prepared from sodium chloride ranging from 5.0 to 120 micrograms per 25 ml of final suspension is shown in Fig- 4. On the basis of 12.0fc of chlorine in Aroelor 1242 and 55.0% in Aro* clor 125 ), one microgrom of sodium chloride ia equivalent to 1.442 mtcrogvams of Avoch>r 1242 or to 1.1023 micioginnis of Aroclor 1254. experimental Results VJOrtality---akocloh 1242: No signs of A intoxication were observed in any of tho members of a group of 31 animals (Expcnine.it No, 1), all of which survived throughout a period of 24 days, on )7 of which thev were subjected to the inhalation of uir bearing 6.G micrograms of Avoolor 1212 per liter (0.83 ppm) for seven hours (Table 1). One cat, four guinea pigs, six mice, two rabbits, and eight rats survived without MONS 09 76S* sign* of Intoxication throughout * their npoNiirc (Experiment No. , ....____ t) for otven hourt on each of 83 t days over a period of 120 dnyi to , *** - air bearing tho vapor of Aroclor ( 1248 In'the concentration of mkrogrnms per liter (0.00 ppm). < Certain other survivors (two 1 guinea ptgn, three mice* one rab* ti bit, and two rate) were subjected to fewer periods of exposure (cf. a twm a ac aMa a t-MMMMM (i|MM * fWB, 0 t. n>l HM,| atwnua, a tM 0 tNM no*. mm ,Ksa Table I). The deaths from ex traneous causes among the ex posed animats were fewer than those which occurred among the corresponding group of controls (No. 1, Tabic 1). One cat, three mice, throe guinea pigs, throo rabbits, and eight rats survived following confinement for seven hours on 84 days over a period of 188 dags. In a chamber In FI*. 4. Standard carva far th* determination af Aroclar 1242 and . . AionUr I1S4. . which the air, conditioned with reaped to In another axperiment (No. 2, Table I-A) dust, humidity and tamperaturc, contained In which animals were exposed to air bear bo vapor of either Aroclur. Tea more survi ing Aroclor 1212 in the concentration of 1.9 vors (three guinea pigs, four mice, one rab* micrograms per liter (0.18 ppm) tor seven bit, and two rats) were subjected to fewer hours per day on 150 days over a period of periods of confinement (cf. Table I). 214 days, the incidence of mortality among Table I. Summary or Data ON r.IoKTAM'n Axiosr: Anim.m.s Mxi-osvo to tub Vapor or Arocuv; 121? ok AnOCLou 1251 in Am (Uighcr concentrations). Number of Animate that Survival Malarial Aracier I84d Amlar mt Aratlar 1H4 Central y/l MO ill S.4S arm .as Ml S.41 af Ktpatur* (hour*! IT s T It X 1 1! x 1 Hit Cats i 1 1 1 Guinea Rica a . S'.'.* '.'.* Mlea to >.v t`. Rabbi U 4 S' 4',* 4 lata ta is*.* IS* I tv No. 1 S 1 1 Hina af iKa animate wnii taptnrd an anlr n la U Sart *Ont af tha animal* vu Mimol an mI* It ta M dara Hina af Die animate w# apM*d an only to la IS dart -Five af th* mic* w*r* expmt'l an anlr T4 day* *Thwa a/ th* wlire wu *xpocd n mlr It ta 19 dart One af th* rabbit* vu axaattd an anty is dart Tasle I-A. ' orSummary Data on Mortality Among Animals Kxposed to inr Vapor OS' AROCLOR 1241! or AROCLOR 1251 in Am (I,ower concentrations) Number af Animate that Survived Malarial af Kxpaatm yf\. asm (Hanra) Catt Aratlar |>4t A ratter 1U4 Canteal l.d 140 1 MS isa T *41 i> x t 1 x T 1 1 I 'Oat at th* animate u tKpawd on aniy 24 ta SI Sara On* af llw mIimIi n tn*a**d enlr 41 la U dart *Om af ik* animate tn himmiI * aalr in w 1SS day* fittllHt Pig* Ml<* RabMte Rate No. d1 T*.*.* S' **.* *..* IS*.*,*.* 4 Id'.V.'..' S',*.* id* II* 10* t t t *Onr af IK* animate m mo4 an only I ta IS dart H>ni af IK* animate wm n ml/ lit la lit day* 'Om mamt re *nml an itlr II dara fa the \.,f. . On i..{ r. J. t !*; com,i.. cunti.,! .. I-A>. One , ,v- antiniiiv pern : . Aroclur j. tone v... . end >;iv i . the vaj-.y period i.j i. troop c f , - I*A>, u.i. . two raM.,' , out ihv ;1 seven h,..;,. days in ,-4 tinned ;,i<(one gnitif.4 one rat* , period of i I-A). X,. served am* mils. Mouru i guinea ji,nine sure, lur - over n j:-i\< Aroclor 1 micro^r.tr.:- other smitv; two rabbi exnnuu;iUt: sure (Till% from extra and t'orOrvi with llr tv pnrnhlc (T. One cut. rabbit*, tut* 2, Table I-. seven huur t period of -I 1251 In t lo per tiler, t` (three guir survived tt: poiMiie. Th- the expo-v*1 that envoi perimvid '*, HONS 097603 4 . UO Mt iilMfc I-A) l >lr banrlatim of 1.0 0 for imn 1 * prriod of :oiny umonff 1.U lUpl I I \ * -M1.14m H*. *" I I the various species, trith the exception of the fibbili (which died during on epidemic of pneumonia), wac no creator than that en- countered among a similarly constituted control group (Experiment No. 2, Table I-A). One cat, five guinea pigs, six mice and nlno rata survived throughout the entire period of (heir subjection to the vapor of Aroclor 1242. Seven additional survivors (one guinea pig, two mice, three rabbits, and one rat) wore exposed intermittently to the vapor of Aroclor 1242 over a shorter porlod of time (cf. Table I-A). Among the 1-A), one ent, five guinea pig*, four mice, two rabbits, and nine rats survived through-' out the entire period of conAncmcnt, for seven hours on each of 160 days over 213 ,days la a chamber, supplied with condi tioned air. Eleven other control animals (on, fulnaa pig, all nlebfkm rabblta. and ana rat) aurvivrd ifuHng a hort*r total porlod of Intermittent confinement (Table I-A). No algiu of lntoxiration were observed among experimental or control ani- mals. MORTALITY--AROCLOR 1254: One ent, three guinea pigs, four mice, two rabbits, and nlno rats survived throughout their expo sure, for seven hours on each of S3 days over a period of 121 days, to air containing Aroclor 1254 in the concentration of 5.40 micrograms per liter (0.41 ppm). Certain other animals (three guinea pigs, six mice. two rabbits, and one rnt) were killed for examination after 32 to 74 periods of expo sure (Table 1). The incidence of mortality from extraneous cnusca among the exposed and control animals (Experiment No. 1), with the exception of the rabbits, was com parable (Tabic I). - One cat, four guinea pigs, six mice, four rabbits, and 10 rats survived (Experiment 2, Tublo I-A) following their exposure for seven hours on each of 150 days over a period of 213 days to air containing Aroclor 1254 In the concentration of 1.5 micrograms per liter, (0.11 ppm). Eight other animals (three guinea pigs, four mice, and one rat) survived through 30 to 130 periods of ex posure. The incidence of fatalities among tho exposed group was slightly less than that encountered among the controls (Ex- pertinent 2, Table 1-A). ' "T ......... Tvr" Tails II. Thr Avi^scir Chances in Wkcut or Exrsni- MBKTiS N0 ^0Nt*01* Animals _________ (Higher concentration.) Iintlw mt Animal Miafer af A aimsla Aearajre Chang* hi Waicfat Awraia Kapni4 aa teltUI Weight Perrenlagaaf (k*> Initial Waighl Areefer 1*4* . I.CS 7/1 Eiperimeat Na. l Cat (luinra rfe Mcmim aMst Rat 1 10 4 IS uu + S.1 -94S - M S.s*< + s.l M# + 1.7 s.m + li Areefer l*4t . MS f/1 Experiment Na. S Cat Guinea Pi* Mm RaUSl Oat 1 a i is un S.4S4 mu un MU +n.i +M.4 +11.1 +isj +M.0 Areabe tSM (.40 vA CatwrtaitM Xa 1 Cm ' OlllNfS '' Mom tla bbit Rat 1 IS 4 It un +su MSS +4S.T S.SS1 +SS.S i.m +tt.T sjtr + s.t CenSHtoned Air - Cantreia experiment Ka. t Cat Uulnn Ma Mnuae Kai.UH Ifal 1 S 1 4 19 MM + S.S MIS +4C.I MIS +11.4 S.1S4 4-44.4 MU 4-14.4 Tabu: II-a. Tnr Average Chances jn Weight or the Sur vivors Among the original groups (Lower Concentrations) Spaataa < Animal ATerete Chang# Number in Weiclit Average ExpraiaeS aa at .Initial I'trtentiuieal Animal, (ig> Initial Weight P Arerfer lt4S l.t y/\ ExvrHment Nu. Cat Guinea Pic Moum Hat I S s I.TS0 SAM SOUS S.CI4 +114.0 + <1.1 + til + 19.* -- >4.04 Coes ->0.04 Areafer 1244 l.S *,/l Experiment No. t Cat Guinea Pic UauN ItaMrit Rat I 4 5 4 IS Mil Mil 0.0141 MM MSI + 111 + ill + ll.s + 44.4 + IS.7 ->0.01 >0.04 >0.91 >0.04 CanSitfencd Air . Central. . Experiment No. I Cat ClMMA tfc Moitb* iUl.bil Hal 1 I 4' S I.MI 9.400 0.0*47 MU MIS - 1.1 + lt.1 + 13.1 | 41.1 + I3.T . -- -- -- -- 'Inchidre twa aar^ repfeewureU. MUMS 0976*4 No general or specific sign* of IntoxicnUon were noted among the oxperlmenlyl anlmala during or ofter their c.t|i*ure. GROWTH: The portlnent dnto relating to the changes in weight of the animal# of the various groups oro presented in Table 11 ami Il-A. Although compnrnblo controls were not weighed riming the first experiment with Aroclor 12>12 (1? x 7.0 hrs.---8.G0 micro grams per liter) nil of the animals, except the guiiicn pigs, appeared to gain normal ly in weight during the period of exposure. Despite s small not loss by the guinea pigs in tins experiment, they were actually gain ing weight at the termination of the period of exposure. The animals exposed to the vapor of Aro clor 1242 In the concentration of 6.83 micrograms per liter (Experiment Xo. 2) or to Aroclor 1234 in the concentration of MO micrograms per liter (Experiment No. 1), with the exception of the guinea pigs that were exposed to the vapor of Aroclor 1204, grew equally ts well at the controls (Experiment Xo. 1, Tnblo II). The growth of tho surviving experimental animals in the groups initially exposed to tho lower concentrations of the vapor of Aroclor 1212 (Experiment No. 3. 1.0 micro* grume per Uter) and Ai-oclur 12GI (Experi ment No. 2, 1.8 micrograms per liter) was unaffected. Xo significant difference# in the average change in weight of the c*|>crimental and the control groups wore found by the two of the "t" test (Table Il-A). Weight of liver and ktdneys: The weights of the livers and kidneys and the relationship# of their weights to the body weights (expressed ns grams per 100 grams of body weight) of tho animals that sur vived following exposure to the vapor of Aroclor 1242 in tho concentration of 6.83 microgniros per liter, mo shown in Table HI, which alio gives the corresponding data on the controls. Comparison by the "F" tost of the variances of tho ratios of the livers or kidneys to the body weights of rats, guinea pigs and rabbits exposed to the va por of Aroclor 1242 (G.S3 niicrogrnms/ (iter), with those of the controls, revealed ho significant differences (P>0.05) ex cept In the case of the Uvers of the rats. Application of the **t" test to the mean values (Table 111) revealed no significant differences between the test and control groups of guinea pigs, rats, and rabbits. Comparable values for rats, guinea pigs and rabbits exposed to Aroclor 1251 in the concentration of 5.40 micrograms per liter * Tahle III. Summary or the Data on* the Rki.-xtioxfiiip or vm: Weight or rm: Liver or the Kidneys to tiik Body Weight or Animals Exposed to thi: Vafou or Aroclor 1242 ok Aroclor 1254 Aroclor 1242 - C.63 y i - 82 x 7 hr. Aroclor 1251 - 5.40 y, I - 83 x 7 hrs. _________ Controls - 0 y/l -31x7 hrs. Cmipwm4 Aivrbr 1349 Amk l ArwW 1913 Awltr ISM AiwIm 1714 Awtor lt&4 !t49 Amhi 1t4I AimIm IMS Ararlar 1914 Arvrlnr ISM A ltalar |4 Caniml Cinlrtl CwM Cantrai OmM Or*"" Liver Live* Uvtr Llvtr Liver Llvvr KMwr KMncra K itinera KIJmn KMnvn KtOnma Liver Llwr Llvtr KIJntrs KMnrri Kilnr* Sptcicv of Animal IUI Oiilnn Pit RabOtt Kat Gttlnva n* rubwt ni Guinea fir RabWt Kftt (IwImm rig RafcMt Hot . Guinea n* Rnt.tlt Rat Cwinea PI* KaiAU Average Oman WthrM a <S 11.1 s ts.s 9 I9L0 IS lt.l s tl.t 4 lt0.0 S I.SS 0.0 1M 10 LI f 4.0 4 1LS 10 L0 s S0.I 4 . ILLS 10 L0 s 4.S 4 1S.S Awnfr Italy Wtifht <> 94S 040 4.999 999 Oil Ml? *40 040 .0tt 930 Oil MOT 940 900 LOTS 140 OCO 0.900 Ratio ot Wolcht pi Oman X 100 to Hodr Wrlrht 4.04 4.00 0.04 Mi 4.01 010 0.719 0.900 0.400 0.770 0.000 0.404 i.li 4.01 SOI 0.907 0.791 0.004 l 1.2:91 0.4101 1.0090 S.SOM o.oooo 1.0132 0.5949 0.1337 0.417T 0.4100 0.0 til 0.9101 -- -- -- -- -- -- T 0.90-0.90 ^>0.90 0.10.4.20 <0.01 >0.50 sMQ >o.:o 0.40.0.50 >1.30 >0.10 >0.50 >0.50 -- __ -- -- -- -- Are nl.. v . the "\" vain. . nU . the uciy;,* writ? Mf*f . the cm;:,, hwly 10nK,,(|. . 4.13 v . tested Pig# ari l i dilferuu.. Tlu ,,:r. leaser n.>. . Alt* hit-jt v . bccmiM* .f resuiis :* . trillion*. Liver it to the r|>|m blood ini--.of certain . U) to the v The K> n i r Hours Imi IMniIi.n t( Aninu.t. CfttAKU in 110 CI4lH'- CUtlm- T Cat II I* r u i> 'IWtiwuiM*' MON3 097685 4 frl (Expcrir Hin ) was mm In the th jwrlvrere found lell-A). Nmri: The vyt nnd ilit ! 0 bedy r 100 grams U that *urto vn|ior of Inn of 6.83 im In Table rreapendinn i li)' llio "F" itios of the ght* of riits, t (o the va Mcregrams/ do, ramled >.) exvt the rata. the mean i significant and control I rnbbltn. guinea pig* 1251 In the per liter Kiini:y* to cum 1254 are also given in Table HI. Application of the '*!" tevt to the difference* in the mean value* which characterised the experimental and control auimntj* (Table III) shows that the weights of the Hvct-s of the exposed rats were significantly greater than those of the controls, the ratio of the liver to the. body weight of the former being 5.31 g per 300 g of body weight, that of the latter being 4.15 g per 100 grams. In all other instances tested (livers nnd kidneys of both guinea pigs and rabbits and kidneys of rnis) the differences were statistically insignificant. The organa of the animals exposed to the letter concentrations of the vapor of the Aroelovs were not examined in this manner because of the borderline character of tho results associated with the higher concen trations. ' Liver function; Data were obtained as to the apparent prothrombin activity of tha blood (measured by the method of Rato*) of certain animals'that had been exposed (1) to the vapor of Aroclor 12<i2, iu the con centration of G.S3 micvogrnms per liter; (2) te tho vapor of Aroclor 1251 in the cencen tmtion of 5.10 micrograms per liter; and (8> to conditioned air alonu. In Table IV the percentile relationships of the clotting power have been calculated arbitrarily by dividing 100 times the average dotting time of the blood of the control animals by the dotting time of the blood of the experi mental'animal* on the same day. No dimin ution in the clotting power of the blood, as n measure of tho impairment of the function of the liver, was induced by the exposure of the animals to the vapor of Aroclor 1242 in nir in the concentration of 6.83 micro grams per liter, or to the vapor of Aroclor 1254 in the concent ration of 5.40 micro grams per liter. This functional lest was not applied to animals subjected to the lower concentra tions, because of the negative results ob tained when the animals were subjected te the higher concentrations. Hematological results: Determine- Tarlk IV. Tub Effect or Exposure to the Vapor or Akoclok 1242 ox Apoclou 1254 in- Am fok Seven Hours Peh Dav on Fm: Days Pew Week Oral a Period or Several Months Upon the Ar- PARENT PltUTimOMBIX CONTKNTOF TIIK IJl.OOD OF CATS AND ItAODlTS ktlillm <vf TwlkrimWn Time" of Control ami Expvai`1 Anlmnii Kpre,x1 ArUn urlly In Term* of l'erfentaco ..f Uk*4 100 * Clotting Titnf of 1 llo*l of Control Anlmnla Tir rf Sr-'.f Exposure -- -- -- >:r: ,i : ---------- -- of Terloil After dotting Time of lllootl oi ripowd Ailmili Aroclor lt - C.S3 *,/l Kx|>erimrnt No. J l*crio4 . VT*t Drown Cot A-44S KtbfcUt (Averted 100.0 00.1 1IS.S 101.1 07.4 ' 11M 40.0 0S.S 10S.1 00.0 00.4 I0S.T lOM 104.4 Aroclor IIS4 0.40 -//I - Fxncrimrnt No. I .l' 14 S4 44 0 . Cot A-444 100.0 INS 114 IIS.0 I01.S ot.s 00.0 KitlilU (Averted 0M 40.4 01.0 44.4 44.0 loro m.i 41.4 OS.4 40.1 100.0 1 t 4 ' 10 IS so 01 4S so OS 'Drtormiiiolioii nidi IS 4r after Hud initod of iiiwuin PflimlMiiltn Midi 14 !> ifur Uni 1X11.4 t>( ni>oiiir M0NS 097686 - Tami V. .. T nrub Avebace Number* Erythihh'.ttki and Levcoctte, and the Average Concentration IlLovnor Hemoclooin in the rERi>UEKAL or K-Tinrii mental and Control Animal* CwnynMA* Awtor lid Aimtor III 0--trrti Ctoniiwtlii ili Mt ladwiit Nwabir t 1 1 tot*M c AmImwI ~diiiM pi* 1USW* OmIma PI* IUMI OiIim Pit lUMat KrrlHnmjrUvt |ThMauA| err rum* MSI MSS MSS S.4SS* i.n S.SM LtMMirUit ter mm* MM ),tZ7 IMII IMS* 1I4M llrmitoUai t/ISS ml 14.4* IU 144* IM 1S.I ViIin ilcwlniiw mi lhn Mitt rieUirf *r (Mtrak *Vb tlfffilflrtttlr then that yiel'l*! br eeatreh. (Ions of the number* of erythrocytes and first experiment with Aroclor 1254 (5.40 leucocyte* and of the hemoglobin content in microgrnms per liter), which were carried the peripheral blood of the guinea pii^i and out simultaneously, the deaths that occurred rabbits subjected to inhalation of the vapor among the test and control animal* wero of Aroclor 12-12 in the concentration of '6.83 the apparent result of an appreciable in microgrnms per liter, are given In Table cidence of pneumonia. The lesions of cer V, which also include* comparable results on tain of the animals were those of frank control animals. Application of tho "t" test, Dneumonia; in others such lesions were not to dlffortncM In tho mean values for tho sully developed. Degenerative changes in the experimental and control animals yielded vixeera wore usually found. In varying de borderline evidence of significant differ gree* f severity. In association with the ences In the number of leucocytes and in pnenmonU, hut in certain animal*, test and the concentration of the hemoglobin in tho control alike, the degenerative change* were blood of the guinen pigs. These differences moro evident than the pneumonia. The wore small and of opposite sign (the num similarity of the lesion* in test and control bers of leucocyte* in the blood of the test animals, and the lack of characteristic evi animal* were low. while the hemoglobin con dence of chemical pneumouitia, led to the tent was high)' a* v.vii iu being subject to rcaaimabJo, but m>v altogether cu`l;::!i, con individual variations, and they cannot bo clusion that all ot these fatalities resulted regarded as of physiological significance. from iiilorcurrcnt disemie among the ani Somewhat comparable result* were ob mal*. and not from Ihe effects of their ex tained when guinen pigs and rabbit* were posure to the Aroclor*. Kor practical pur subjected to Aroclor 1251 in the concentra poses, (hi* conclusion was subjected to tho tion of 6.40 microgrnms per liter. No physi critique of further experiment* involving ological significance is attached to tho more prolonged exposure of animal* to some lightly elevated hemoglobin content of the what lower concentrations. Except in the guinen pig*. ease of the rats exposed to Aroclor 1254, the Pathological findings : In all of the ex survivors subjected to tho higher concen periment*, animal* were killed from one to tration of either Aroclor hud normal vis 16 days after the final period of exposure. cera. . In tho first experiment with Aroclor 1242 All of tho animal* exposed to the vapor (8.00 microgrnms per liter), all of the ani of Aroclor 1242 iu the concentration of 1.8 mals were examined postmortem, ami since fnicrogr:iins tier liter were examined post gross examination of the viscera did not mortem, and the viscera of most of them reveal any significant alteration;}, the tis were examined microscopically. The few sue* of only representative animals (one death* among the exposed group were at eat, four guinea pigs, six mice, four rabbits tributed to incidental infectious pulmonary and six rats) were sectioned mid examiued disease. All exposed survivor*, except two microscopically. No abnormalities were rabbit* that had hepatic lesions of coccidio- found in the viscera of these animals. sis, had normal viscera. The control animals In the second experiment with Aroclor (Experiment No. 2) that died were found 1248 (0.83 microgrnms per liter), and in tho to have had pneumonia. Of those that sur- rive!. ,. # m*u. r I , mini. twitr>.j All ..f ; Ar*r? t l mien yr.,- mortvtn. * wvrr mapig th-,* phriii., j and it.K,> liver. U* doubt, :*. four m..chili* rtn.l that stirv guinea | . pvrinuai riscvia ar hepatic i. V*CUi4uli six hod r.i dSKMNrrat hfU MU p tried >f 1/ sierntiff vt-.riid fr< Hi gener.it of fatty i of lhc.a> rat* vv-, slightly { lesion* ui seventy ' killed amt the Inst | chronic ; had slight /JifCN.-v (except,tl rcncc of Aroclor microirrat tiont api periment; seven hot od of 21 Expert slightly 1242 (G> hour* pei periotl of basis of i tnlity, g MUNS 0976b7 rived, one rat, two guinea pigs, and one ment, liver function or hematological mouse had focal or diffuse cytoplasmic vacu- ehangee. LcbMUTIOM Iawmau elation of the hepatic echs. The remaining More prolonged *a|kwui of aiiiumS* in a control animnls had normal viscera. lower concentration of Aroclor 1212, (1.9 All of the animals exposed to the vapor of micrograms per Uteri ever the period of Aroclor 1254 in the concentration of 1.5 seven months was likewise without harm in t/m * mlcrograma per liter were examined post terms of growth, mortality and the absence mortem, and the viscera of most of them of pathological changes. were examined microscopically. A guinea* In view of this evidence it is suggested Plf that died exhibited chronic pyelone that the tentative allowable concentration of phritis, pulmonary hyperemia and edema, the vapor of Aroclor 1242 should be at least ILI and degenerative lesions in tho brain and two micrograms per liter (2 mg per cu liver. The visceral lesions were related, no meter), which is twice that recommended doubt, to the renal infection. Tho deaths of by the Americnn Conference of Govern I2&4 (MO ere carried four mice were attributable to acute bron mental Industrial Hygienists* for a chlorin chitis andpneumonia. The viscera of the eat ated diphenyl of unstated chlorine content. jil occurred that survived were normal. Of the seven The exposure of animals to tho vapor of limal* were r<lnblu in* guinea pigs that were living when the ex- Aroclor 1254 in the concentration of either perinicut wot terminated, three had normal 6.40 or 1.5 microgrnm* por liter failed to in of ccr- viscera and four had slight alterations of induce harmful effects in the form of re-, * af frank hepatic cells characterised by cytoplasmic tardation of growth (except in the ease of vaeuolatlon. Ten mice survived, and of these guinea pigs exposed to the higher concen MiteOw six had normal vieeera and four had slight tration), or of mortality, but bietopatho* degenerative ehangee In the liver. Four rab logic evidence of apparently reversible mi wilii the bits killed one to 15 days after the last hepatic cellular Injury was found in the hlm trt and T> tried of exposuve had diffuse hepatic do- animals. These findings cannot certainly be unm wro ijvncrntJon. The character of the lesions attributed to the effects of Aroclor 1254 be nutria. The varied from cloudy to hyaline or hydropic cause of the appreciable Incidence of pneu iml control degeneration and included varying degrees monia among both experimental and con IrrMic evi- of fatty metamorphosis. The other viscera trol animnls. When these nonspecific toxic , M lv tho of these ARhn*h> nv^vv.'l. A!! vf the chr.wjTC:-. iv. the viscera ef the r.iri:il.. vu- rtnin, ton* rats were examined and found to have associated with pneumonia, they were readi *.< rvKiiUvd lightly to moderately severe degenerative ly explained thereby, but they were also ri? the nni- lesions of tho liver. The lesions of greatest found in animals that had been exposed to <*r their cx- severity were found in the rat that was the vapor of Aroclor 1254 and were free of .vih-nl pur* in the killed and examined on the first day after pneumonia. That these may have repre the Inst period of exposure. Two rats had sented toxic effects of exposure to Aroclor '* involving imN to nmc* chronic pyelonephritis, and the remainder 1254 finds support in the fact that the livers had slight degeneration of the renal tubules. of the exposed rats 15.40 micrograms per *|t ||| the 'r I2.VI, the Ur I'unccii* Diseuttion: In terms of mortality, growth liter) were significantly heavier in i-ulalion (except that of guinea pigs) and non-occur to their body weight, than were those of rence of pathological changes, the vapor of control rats. It would appear that this ma noituiri vis* Aroclor 1242 in the concentration of 8.0 terial, which is reported to contain Vjrf of the vapor .'h f 1.9 |nt* i micrograms per liter (approachtar satura tion) appeared to be non-injurious to ex perimental animals subjected thereto for even hours on each of 17 days over a peri chlorine, is somewhat more toxic than is Aroclor 1242, which contains only 42'f of chlorine. Therefore it is suggested that the threshold concentration of 1 mg per cu meter 'f them 1 The few *t* n|- ! .!m->ttnry |\v *. 'v -hliw* ' * '`inalu *f touml ^ that ur* od of 24 days. Experimental animals subjected to but a alightly lower concentration of Aroclor 1242 (0.83 micrograms per titer) for seven hours per dny on each of 82 days over the period of 120 days suffered no injury on the basis of any of the following criteria: mor tality, growth, pathology, organ enlarge of air recommended tentatively for safe in dustrial practice by the American Confer ence of Governmental Industrial Hygien ists-1 is reasonable. Jt should be noted that it was nwc.-sary to heat these Avoclors in order to increase the rate of voiuUUxtttion sutttcicnUy to at tain the concentrations maintained in these HONS 097688 *1 .. experiments. To the extent that their Indus* trial usage is carried out at ordinary turn* peratures, the hasard of their inhalation nay well be slight or entirely absent sponsored by the Monsanto Chemical Com pany, whose flnnnrinl support is gratefully acUnowicdgcd, as is also their assistance in supplying the materials for investigation. Summery Prolonged Intermittent exposure of ani*mals to the va|>or of Aroclor 1242 (1.90 to. 6.G3 microgram* per liter) demonstrated' no Injury. Prolonged exposure to compa rable concentration* of Aroclor 1254 re sulted in reversible degenerative changes In certain viscera. The work described In this article was Reference* t. Diiskdi, C. Li ranker Okmillm en tke Pm. Ikb Sr*t*mi Tealehy el Certain ef the Chferinautf Hydrocarbon* wlUi SucKcetieae (r PtraiHiU* CancanIradon* in the Air el Werhmnw. J. 1*4. //*. A 7e*,, >1 :IU, 1*3*. t. Xatc. K.:Micnerethr*mMn Te*t with Capilltrr Whole llloud: MaJtMcatkm of Quick'* Quantitative Meih. 04. /liner. J. Cb*. /'*.. 105147, l0. h American Coarerenre o( (iavemiaeawl In4mtrtl Hrrleniftc. *n>ruh*hl Limit* fer 111*. AIM Artk. 1*4. ilra'th. ll:2t. 1111. .i t i MQNS 097689