Document Neq1ZqMmXod8wgY8k3DagZ6zb

OFFICE OF ENFORCEMENT Monsanto Industrial Chemicals Company 800 N. Lindbergh Boulevard S t. Louis, Missouri 63166 ^ 22-Vi*i5 Gentlemen: * Recent governmental sampling data Indicate the presence of Polychlorinated Biphenyls (PCBs) and comparable chemical substances in the a ir , in water bodies, and in fish in several areas of the country. In order to determine the nature and extent of the possible adverse e ffe c ts resulting from the presence of PCB compounds in the environment, the Environmehtal Protection Agency (EPA), in cooperation with other federal and State agencies, is attempting to determine the sources and amounts of PCBs entering the environment. I t is important that th is e ffo rt be carried out without delay. I t is our understanding that your company handles PCB compounds or mixtures or comparable chemical substances in it s operations. I am therefore requesting, pursuant to the authority provided by Section 308 of the Federal Water Pollution Control A ct, as amended, 33 U .S .C . 1318, and Section 11A of the Clean Air A ct, as amended, A2 U .S .C . 1857c-9, that your company furnish EPA with information pertaining to your use and handling of PCBs and comparable chemical substances. In addition to a general description, which should include information as to sources, quantities, uses, and ultimate disposition, you should respond in d etail to the enclosed questions. I f any question la not applicable to your company or operations, please so indicate by responding "not ap plicable." * The information requested herein must be provided notwithstanding i t s possible characterization as confidential information or trade ' secrets. tShould you so request, however, any information (other than efflu e n t or emission data) which the Administrator of this Agency determines .to constitute methods or processes en titled to protection n. as trade secrets w ill be maintained procedures specified in AO CFR Part a2^s-confid ential, pursuant to i\ ADM 0 0 6 2 9 0 I 213 v 1. * * i c 2 Within 14 dava of receipt of this le t t e r , your company must ^provide a l l information concerning your current status and a c tiv itie s and covering the'twelve nonth period immediately preceding receipt of 3_ i f c " i H r t e r . `-- Within 30 days following receipt of this le t t e r , your company oust provide a l l information for a l l of the prior years indicated. The information required herein should be sent directly to the address indicated below. I f you have any questions you may c e ll "the pe'rson indicated below or Mr. Blake A. B iles of our o ffice iu.*202>.755-*731. ' <.* "! We appreciate your prompt cooperation in th is matter. Enclosure Regional Contact: - ' v. - * Mr. Earl J . Stepiirnfcbf D irector, Enforcement Division Environmental Protection Agency 1735 Baltimore Kansas C ity , Missouri 64108 Telephone: (816) 374-2576 t .v /' t -1 j ADM 0 0 6 2 9 1 i 214 cc POLYCHLORINATED BIPHENYL (PCB) COMPOUNDS OR MIXTURES providWeitihlinl 14 days of receipt of this le tte r , your company must information concerning your current status and a c tiv itie s W covering the^tvelve month period immediately preceding receipt of this letter. ^ Within 30 days following receipt of th is le t t e r , your company must provide a l l information for a ll of the prior years Indicated. FOR PURPOSES OF THIS LETTER, THE PHRASE "PCB COMPOUND OR MIXTURE" INCLUDES ALL CHEMICAL SUBSTANCES KNOWN OR BELIEVED BY YOU TO BE PCB COMPOUNDS OR MIXTURES OR OF A SIMILAR CHEMICAL NATURE, IRRESPECTIVE OF TRADE NAME, AND SPECIFICALLY INCLUDING V CHLORINATED TERPHENYLS.. 1. For each PCB compound or mixture produced or iaaxLaihy your company, for each company f a c il it y , during each year of 1971^ 1972, 1973. 197A. and the f ir s t two quarters of 1975: . a The to ta l amount or Imported. of each PCB compound or mixture produced b The name and address of each of your company's f a c ilit ie s which handle PCB compounds or mixtures, (including production f a c il it i e s and wholesale and r e ta il o u tle ts), and the . + amount of each PCB compound or mixture distributed through each f a c il it y . e . The name and address of each customer of each PCB compound . or mixture, obtained by the amount of each customer each PCB compound or mixture from each f a c i l i t y , and each ^*-^^.9USvtpmesc ' e.:ileiivery^p,oint(s) OT-the t S'ceiph'- 9f 'each" PCB' "" compound or mixture. ; 2. For each PCB compound or mixture Incorporated by your company into i t s products, for each company f a c i l i t y , during each year of 1971, 1972, 1973, 1974, and the f i r s t two quarters of 1975: .x a . A description of each products b . .For eah product the to tal amount incorporated of each PCB compound or mixture. i jp jj,< ADM 006292 215 cc "21 (continued) ~t r . For each product the name and address of each source from which~ymir company obtained each PCB compound or mixture, and the amount ^of each PCB compound or mixture obtained from each source. d . The name and address of each of your company's fa c ilitie s which handle such products (including production fa c ilit ie s and wholesale and r e ta il o u tle ts), and the amount of each product distributed through each f a c i l i t y . e . The name and address of each customer of each product, and the amount of each product obtained by each customer from each f a c i l i t y . For consumer products l i s t only the to tal production of each product at each f a c il it y and the total number of customers. Do not provide the name and address of each customer of consumer products. 3. For each PCB compound or mixture used by your company in its operations other than for incorporation into it s products, for each company f a c il it y , during each year of 1971, 1972, 1973, 1974, and the f ir s t two quarters of 1975: # a. A description of each use. b . For each use the to tal amount of each PCB compound or mixture c . For each use the name and address of each source from vhich . your_ companywpbtaiflsd ^eacb^EfB. fcgippund iOr-m ixtureandv the^-v amount of each PCB compound or mixture obtained from each source. 4. A For each PCB compound or mixture reclaimed by your company, for e'ach company f a c ilit y , during each year of 1971, 1972, 1973, 1974, and the f ir s t two quarters of 1975: s . A description of each method,!of reclamation. bi For each method of reclamation, the to ta l amount of each PCB compound or mixture reclaimed. e . The to ta l amount of each PCB compound or mixture reclaimed. ADM 0 0 6 2 9 3 t 216 d. Th4 name and[ address of each source from which your company obtained PCB compounds^or mixtures, and the amount of each PCB compound or mixture obtainedfrom X " ba'ch source. *" - e . For each method, of reclamation, the location of every reclamation s it e , the name and address of each party Involved in the reclamation of each PCB compound or mixture, and the amount of each PCB compound or mixture reclaimed by each party. For each PCB compound or mixture disposed of by your company (with or without the involvement of other p a rtie s), for each tompany f a c i l i t y , during each year of 1971, 1972, 1973, 1974, and the f i r s t two quarters of 1975: a . A description of each method of disposal. b . For each method of disposal the to ta l amount of each PCB compound or mixture disposed. c . The to ta l amount of each PCB compound or mixture disposed. d The name and address of each source from which your company obtained PCB compounds or mixtures, and the amount of each PCB compound or mixture*obtained from each source. e . For each method of disposal, the location of every disposal s it e , the name and address of each party Involved in the disposal of each PCB compound or mixture, and the amount of each PCB "'a"^ci^buhd''Of-ttmure^diap'6ed ~bf*~iy~eeeh;'p'art'y7"'' "" r ' v - The composition by chemical name and percent by weight * of each PCB compound or mixture -produced, imported, so ld , reclaimed, used, and/or.disposed of by your company since January l t 1971. The results of any and a l l sampling-and analysis performed by your company, i t s agents or contractors since January 1, 1971, concerning the following: a . Concentrations of PCB compounds or mixtures in the effluent of any discharges by the company (into waters of the United States or Publicly Owned Treatment Works) or in the emissions of the company into the a ir . ADM 0 0 6 2 9 4 217 4 v .- b . Th? flow and/or composition of any discharges or emissions " bjTthe company (into waters of the United States or Publicly O^aied Treatment Works, or into the air) which contain PCB --compounds or mixtures. c . Concentrations of PCB compounds or mixtures in receiving waters (both upstream and downstream) of any discharges by the company which contain PCB compounds or mixtures and concentrations of PCB compounds or mixtures in the air in the area of the company. 8. The methods by which PCB compounds or mixtures are transported to , by, and/or from your company, including: a . A description of esch method of transportation, and the form in which PCB compounds or mixtures are trans ported by each method. Where different methods of trans portation are used at d ifferent f a c ilit ie s specify which transportation method is used at each f a c il it y . b . The names and addresses of a l l known transporters of PCB compounds or mixtures. 9. A ll occasions (including s p ills ) of which you are aware on which / PCB compounds or mixtures have or may have been Introduced into . the environment. In p articular, describe such occasions Insofar as 'they Involved PCB compounds or mixtures in their liquid sta te , as incorporated into closed systems, or as Incorporated into open systems. For each occasion, Indicate name and address of party Involved; dates, time, and location of the discharge or 10 A description of any adverse health or environmental effects which you know or believe to have resulted from the introduction ' o f PCl compounds or mixtures into the environment. Indicate any sp e c ific occasions including dates, times, locations, amounts, v and parties Involved for which such e ffe c ts are known. *r 11. Any and. a l l other information which you possess concerning: / a . The production, importation, reclamation, use, distribution, and disposal of PCB compounds or mixtures. 1 AOM 006295 218 b. Ttb discharge of PCB compounds or mixtures into the environment. In addition to the above, EPA would appreciate receiving any other Information which you possess concerning the distribution and discharge of PCB compounds or-.mixtures by sources other than your company, Including your company's customers and sources. * < -V V .. " ~ -* A \ >A' AOM 006296 Monsanto c rt} j mah( i wocation* D ^ v id W ood*St i8*B2SO c OAT| uajcer Ofl*oberrr3 0 , 1975 *=f-E P A COMMENTS ON EPA LETTER REC'D 10-17 TO W. B . Papageorge B2SK IN - 10 V. 1/7 1 . B i l l , t h i s seems t o be a new v e r s i o n . 2 . Page 1 . C l . Terphenyls s p e c ific a lly m entioned. 3 . a) P r o d u c tio n reco rd s answer 1 ( a ) . b) Remember we warehoused PCBs f o r s h o r t p e r io d 1974 ahead labor co n tra ct renew al. c) Q u e stio n l c r a is e s a problem th a t has been a t bach o f my m in d. #2 r e p o r t i s supposed t o show " s h ip t o " a d d r e s s , b u t i f t h i s i s c a s e , why do 3 rd p a r t y W/GE shipm ents appear under " b i l l to " lo c a tio n s . 4 . Q2 a) No problem b) No problem c) No problem d) No problem e) P o lic y - Hanley le v e l? 5 . Q3-No problem exce p t 71/72 6 . Q4-No re cla m a tio n . 7 . Q 5-a) No problem b) D i f f i c u l t . Can s p l i t D ielec/H T/Pydraul 1 B u t some r e tu r n s m ix tu re s o f .o il/ P C B , e t c . c) Can do. .` d) D i f f i c u l t e) D i f f i c u l t . / ` 9^ 8 . Q6 -- A v a i l a b l e .% 9 . Q7 - a ) G u ess we have b) Gu ess we have c) G uess we have 006288 1 0 . Q8 - a) B u lk R a i l Bulk R - 3 accounts Drum - S p e c i f y drum c o n s t r u c t i o n b) E . M. P o tte r 220 cc * 1 1 . Q9 - S h o u ld answer from our a c t i v i t y ? - ri - * - - , - 1 2 . Q10 - NoneP^YUsho?* C lo r a c n e * y e a r s ago - Dangerous Q u e s tio n . 1 3 . Q l l - a) M ig h t g e t HUB a g a in ? b) S h o u ld w r it e t h i s one v e r y c a r e f u l l y - can make some p o s it iv e p o in ts in t h is s e c t io n . /deb D a v id Wood .1 / / a^ f t4 r ADM 0 0 6 2 8 9 221 c5 * t MonsontU;rUs / MONSANTOiNQUSrniALCxCMICAL*CO. 00 N. liAtatrn IJwU*ir 63S t . L o w i t . U i i t t w r i CA m** au H4-I000 Dcsbr 11. 1975 \ Mr. Earl J . Stephenson Diractor, Enforcement Division Environmental Protection Agency 1735 Baltimore Kansas C ity . Missouri 64108 ' * .' Dear Mr. Stephenson: * f Attached is a response to the questionnaire which accompanied Mr. Stanley Legro's le tte r dated October 17, 1975. To the best o f my knowledge and b e lie f, the information contained in this response represents the best information available to Monsanto. I f I can be of further assistance, please le t ac know. Sincerely, ~vi f S ') W. B. Tapageo'rge " Manage:', Prsduct A cceptability Process Chemicals Division it Attachment CC: Mr. Stanley W. Logro' US Environmental Protection Agency c 401 ` " *!" S tre e t, SW V*ishi ngcc.n, O.C. .0*<o0 #All *.l Mm'. I4f 241 ACM 0071 cC ' POLYCHLORINATED BIPHENYL (PCS) COMPOUNDS OR MIXTURES Za response the phrase "PCB compound or mixture1* includes those m aterials liste d ' under Base Products in E xhib it A. 1 (s) Monsanto In d u strial Chemicals Company does noe import PCB . compounds or mixtures. Amounts produced for 1971, 1972, 1973, 1974 and the f i r s t three quarters o f 1975 are included la Exhibit C. (b) Production- f a c i l i t i e ? : - . ^ V o r 1971 and 1922 Monsanto Company Box 249 Anniston, Alabama 36201 For 1971 to present Monsanto Company Route 3 Sauget, I lli n o i s 62201 i ;:The amounts'produced at the Anniston, Alabama plant are shown on E xhibit 0 . The Sauget, I llin o is u n it produced the amounts shown on E xhibit E. Wholesale and r e t a il o u tlets are not used. < (c) See E xhib it P for 1971, Exhibit C for 1972, Exhibit H for 1973 * ' i r o a 197^. and E xhibit I for "the'SrthistohY^'Aiibem 1975. The PCB compounds or mixtures xr.vfaoiliJyr.ari^listcd in Exhibi t 0. The remaining were shipped from the Sauget, Illin o is ' 2 . (a) Sea E xhib it A - pages 2, 3 and 4 and E x h ib it B. i** Cb) See E xhib it A - pages 2, 3 and 4. . (c) The PCB compounds or mixtures used were produced by Monsontc. See 1(b). (d) Production f a c i l i t i e s are those shown under 1(b) and for 1971 and 1972 also included Monsanto Company, 1700 South Second S tr e e t, S t . Louis. Missouri 63177. Products distributed `through Exhibit ZMt.onsAaniltoP*sy Anniston, Alabama u nit !r.ul j r".iuct:: vr-re dist arc ribu shown on ted through the S t . Louis, Missouri f a c i l i t y . Remainder o f products d istrib u ted through the Sauget, I lli n o i s u n it. Amounts d istrib u arc shown on the exh ib its lis te d in 2c below. 242 aO* 007 1 ; V r *. ^ c - .i ...' - -- --T- x c tc *> -a- .. . () Sm Exhibit F for 1971, Exhibit G for 1972, Exhibit H for 1973 aad 1974 and Exhibit X for 197S. The products'obtained frca ther Anniston, Alabama f a c ilit y are lis te d in Exhibit 0. The Pydraul products originated a t the S t . Lou is, Missouri unit: The remaining were shipped from the Saugee, I llin o is f a c il it y . We do not manufacture consumer products containing PCS compounds or mixtures. 3 . (a) During 1971 and 1972 PCS compounds or mixtures ware used as heae transfer flu id s , hydraulic flu id s and in transformers and capacitors. Ouring the la tte r part o f 1972, 1973, 1974 and 1975 PCS compounds or. mixtures are only present in transformers and capacitors. (b) See Exhibit J . Amounts shown era for to ta l Monsanto Company usage. No records are available to determine sp e cific company f a c i l i t y . Inerteen was used in transform ers. Pydrauls in a ir compressors. Therminols in in d u stria l heat transfer systems. (c) The PC3 products were a l l produced by Monsanto Company. s p e c ific sources are shown on E xhib it J . .4 PCS compounds or mixtures are not reclaim ed. The: t I 5 . (a) During 1971 and 1972 so lid waste m aterial contaminated with PCB compounds or mixtures were buried in a secure la n d fill located within a fenced area on property owned by Monsanto Company at the Anniston, Alabama f a c i l i t y . Sim ilar waste has . also been buried in a secure la n d f ill located on Monsanto Company property at the Sauget, I llin o is f a c i l i t y during the period 1971 - 1973. liq u id wastes have been disposed by incineration for the period 1971 - 1975 in a high temperature unit located ;.i ` the-Sauge-fe,,illinoiv_.faC^ ilij:y %_, During 1975 so lid waste was sect to Texas E co lo gists, P .' 6 . ~Box' ib^T'Robstowh;v'Texa3 (b) Waste m aterials containing PCS compounds or mixtures are received from many sources. Thu type o f PCS compound or mixture in the waste is unknown. The concentration is also unhnown. Solid waste is estimated as-`containing levels ranging from the ppm le v e l to S0\ by weight. Liquid waste is estimated to contain about 901 PCS compound or m ixture. For amounts disposed sec Exhibit K. Noto the amounts shown re fe r to the to ta l weight o f wasto. The actual PCS content is unknown. (c) Sou Exhibit r. for to ta l waste dicpoccd. Concentration and type o f PCS compound or mixture are unknown. 243 AO* o o n - (d) Sm E xh ib it L.' Total amounts o f vast are shown, Concentration and type o f PCS compound or mixture ara unknown. (4) Saa 5a for name and lo ca tio n . Saa E xh ib it K for amount disposed. 4 . Saa Exhibit A. Monsanto Company doas not import or ra c la is PCS compounds or m ixtures. Composition o f disposed material is unknown but can range froa ppa level to 100% by weight PCS. 7 . (a) See E xhibit M for Sauget, I lli n o i s f a c i l i t y waste e fflu e n t analyses. See Exhibit N for Anniston. Alabama f a c il it y water a fflu e n t analyses. .,For PCS emissions to the atmosphere at the Sauget. I llin o is f a c ilit y sea Exhibit 0 . Analyses of a ir emissions were nat^.made a t the A w iscon , Alabama f a c i l i t y . (b) Sea Exhibits M. N and 0 . ,* (c) No information 'is available regarding the Anniston. Alabama f a c i l i t y . No information is availab le re la tin g to PCB con- san itatio n in the a ir in the area o f the Sauget. I llin o is f a c ilit y Samples o f the M ississippi River ware taken in 1972. wart as follow s: R e s u*lt s Sample Date 11 20 //13 30 //77 22 12/12/72 9 L o c a tio n T .B . Bridge (downstream) Ch N. a( uoinpf s to1r1fe 1a R.mo)Rcki s v e B r r idge (ups t r e a m , Analytical blank value at"10?010<7^i:000=1-7^ b /1 PCB 0.000 0.000 1 2 2 - 0. 000' 0.0002 - 0. 000' 8 . (a) PCI compounds or mixtures arc liq u id s and are transported in bulk or in ste e l drums. / (b) See Exhibit P for transporters c f PCB compounds o r' mixtures from Monsanto f a c i l i t i e s . Transporters of material returned for disposal can bo any common c a rr ie r serving tho S t. Louis. ' Missouri area. tr - v f , Monsanto Company is noe aware o f any occasion in which PCS compounds or mixtures wars introducsd into tht snvironasnt which is not alraaly known to representatives o f the Environmental Protaction Agency. Examples include the contamination o f fish meal in North Carolina, ths drainaga o f flu id from a transformer in tra n s it in Tannassas ' and ths leakage o f flu id from a damaged transformer in ths Duwamishwaterway in Washington. 10. Monsanto Company is not aware o f any health or environmental e ffe c ts resu ltin g from the introduction of PCS compounds or mixturas into the environment which has not bean reported in the s c ie n t ific and popular prtsa and alraady.Xhewa to. representatives o f the Environmental Protection Agency. * * *ee 11. (a) Monsanto Company has received reports that about 1800 drums, o f PCS compounds or mixtures are being offered by a company located in the northeastern U .S . for sale for any a p p lica tio n . This information was received from Hr. Robert Lahaa, Hub Fabric Leather Company, 7 Charlton S tre e t, E verett, Massachusetts 02J4P; . This has been discussed with a representative o f the Environmental Protection Agency. * Recently Pyramid Chemical Sales Company, 103S V irg in ia Drive, Fort Washington, Pennsylvania 1S034 has advertised the a v a ila b ility for any application o f Aroclor 1221, Axoclor 1232 and A rd o r 5460. A representative of the Environmental Protection Agency has been informed. *^Sr, :SU. 245 AOM 007 C V REPORT TO MONSANTO COMPANY TWO-YEAR CIHNARRAOONLCBICLINOOORRRA1A2L6T0TSOXICITY WITH NOVEMBER 12, 1971 IBT NO. B7298 L Introduction At the request of Monsanto Company, a two-year chronic oral toxicity study was conducted using albino rats to determ ine the potential toxicity of A roclor 1260, Lot No. AK-3. The following report presents the results of this investigation. 000082*0 c 372 262 ruL^i-ual B I^P - T C S T c . 2 n . Summary A two-year chronic toxicity study was conducted using albino rats fed diets containing 1 (T-I). 10 (T-II), or 100 (T-III) ppm Aroclor 1260. Food consumption and body weight gains were not altered at any level of A roclor 1260 fed. The number of animals dying and the time at which the deaths occurred did not vary among the test and control groups. Hem atological and clinical blood chemistry studies conducted after 3i 6, 9, 12 IS or 24 months did not reveal any affects related to Aroclo 1260. Urine analyses failed to reveal any differences between test and control animals. At sacrifice after 3, 6, or 12 months on test organ weights organ to body weight and organ to brain weight ratios disclosed several randomly occurring intergroup differences. The lack of any consistent dose related response and the absence of any deleterious histopathologic change confirrr that these differences were not related to the ingestion of Aroclor 1260. At the final sacrifice after 24 months on test, the liver weights and liver to body weight or brain weight ratios were significantly elevated in the rats from the T-UX group. Histologic examination of the livers from the T-IU group revealed several animals with vacuolar change. This lesion is morphologically indicative of fatty degeneration. Specific fat tains confIi-ned the presence of fat in these vacuoles. Focal hypertrophy and focal hyperplasia were also found in the livers from animals fed Aroclc 1260. AOM 003721 263 000083 cc H yperplasia of the urinary bladder was found in an animal from the control group but not in any of the test anim als. The incidences and types of all tumors were about the same in all groups, including the control group, and are considered normal for rats of this age. Respectfully submitted, INDUSTRIAL BIO-TEST LABORATORIES, INC. R eport p rep ared by AIP^hs.itsliiTsptoaSxnimtciiTttyho,xiBc.oSlo. gist /PJReport approved by: SRJaea/mmt\bTosroxCBi.rcoitpuylpanL*ead. er SPeacutlioLn, HWeardig, hTt,oxPihc.oDlo.gy M an--La1.geKr,ep^Tl--ioq'xgipcror,loPgyh. D7 November 12, 1971 lam tsjn a OM 00372 000084 c m . Procedure c. A. Experim ental Animals ! The anim als employed in the test were Charles River stra in ' albino ra ts. Four hundred rats (200 m ales and 200 fem ales) were selected for the experiment, ear-punched with the animal number assigned and housed individually in standard wire-bottom ed steel rat cages. Each cage bore a color-coded card identifying the rat with r e spect to project-num ber, dose level assignm ent, individual anim al number and sex. B. Organization of Groups A structural outline of the experim ent is given in Table L Grcuo Control T-I T-II T-IU TABLE I TEST MATERIAL: A roclor 1260 Two-Year Chronic Oral Toxicity Study - Albino Rats Outline of Experiment MNuamleber ox AFneimmaalles Diefotaorrry.) Level 50 50 None Administered 50 50 l 50 50 10 50 SO 100 Charles River Breeding Laboratories, North Wilmington, M ass. ACH CC3722 265 000085 Q c cC. Diets, Feeding and Food Consumption AH diets were prepared in the central diet room of this laboratory. The basic ration from which all diets were constructed was a standard, pulverized stock rat ration*. The diet for any given test group was prepared by blending the calculated amount of A rodor 1260 with a pra-weighed portion of the stock ration in a Hobart m ixer. . Fresh diets were prepared each week and every rat was offered an amount of food sufficient for ad libitum feeding. Food consumption was recorded for five rats of each sex in ever} group weekly for the first three months and monthly for the next nine months. Thereafter, periodic spot checks were made. D. Bodv Weights and Weight Cains Initially, the.body weight of each rat in every group was deter* C mined and recorded. Thereafter, individual weighings were made weekly for the first 13 weeks and m onthly thereafter until the conclusion of the investigation.________ __________ ________ ___________ E. M ortality and Reactions * " - Checks for m ortality and abnormal behavioral reactions were .made daily throughout the investigation. 7-7* F. Hematologic Studies and Urine Analyses Blood studies, including determ inations of hemoglobin concentrations, hem otocrit value, erythrocyte count and both total and differential * Purina Rat Chow, Ralston Purina Co. , St. Louis, Mo. i aD* Co37 266 00008G o rf leukocyte counts, were conducted upon five m ales and five females from both the control and 100 ppm groups. Urine analyses for the presence of glucose, albumin, m icro scopic elem ents, and determ inations of pH and specific gravity w ere con ducted upon urine sam ples at the same time intervals and from the sam e anim als as those employed for the blood studies. These studies w ere conducted after 3, 6, 9, 12, 18, and 24 m onths of feeding. G. Clinical Blood Chem istry Studies Determ inations of blood urea nitrogen concentration (BUN), serum alkaline phosphatase activity (SAP), fasted blood glucose .concen tration and serum glutam ic-pyruvic transam inase activity (SGPT) were conducted a fter 3, 6, 9, 12, 18, and 24 months of feeding upon the sam e rats as were the routine blood studies. -- H. Pathologic Studies - --When an anim al succumbed during the test period, a gross autopsy was perform ed. In those cases when postm ortem autolysis was not ad vanced, representative tissues were taken and preserved in ten percent form alin solution for possible future histopathologic study. A fter 3, 6, and 12 months of testing, five anim als of each sex from each group were sacrificed and subjected to complete gross pathologic exam inations. AOH 0 0 3 7 2 267 000087 C <r. Absolute organ weights w ere recorded and organ to body weight and organ to brain weight ratio* computed. The following organs w ere included: liver, kidneys, spleen, gonads, heart and brain. These data w ere then subjected to statistical analysis. An Analysis of Variance was conducted first and significant effects disclosed by that treatment were further studied by "f'-tests. Complete m icroscopic examinations were conducted upon the tissu es and organs from all control and 100 ppm group rats sacrificed a fte r 3, 6, o r 12 months of testing. The following tissues and organs w er included in the examinations: heart, trachea, lungs, liver, pancreas, esophagus, stomach, sm all intestine (duodenum, jejunum and ileum), caecum, colon, spleen, lymph nodes, kidneys, urinary bladder, gonads, prostate gland, seminal vesicles, uterus, pituitary gland, adrenal glands, salivary glands, thyroid gland, parathyroid glands, skeletal muscle, ; sternum , bone, peripheral nerve, spinal cord and brain (cerebrum, cerebellum and pons). The aforementioned tissues were prepared and stained with Hematoxylin-Eosin stain. I~ A fter two years of feeding, all surviving anim als were sacrific* e d and subjected to complete gross pathologic exam ination. The absolute weights of the liver, kidneys, spleen, gonads, heart and brain were recorded immediately after sacrifice. AOH 00372 268 000083 I c( M icroscopic examinations were conducted upon tissues and organs from selected anim als dying during the experiment and upon all anim als from the final sacrifice. Tissues and organs examined were the same as those previous m entioned. L Tumor Incidence and Classification A tabulation of the incidence of tum or formation in each group was m ade at the conclusion of the investigation. In addition, tum or data for individual animals including location, weight, sire and pathologic classification were recorded. ACM CC3727 269 000089 cc IV. R esults A. Bedv Weights and Weight Cains The m ala and fem ale body weight data are assem bled in Table II. The data in this table also include the 3, 12 and 24 month total weight gains. T here were no significant effects due to ingestion of the compound \ AO CO 270 0000:)) C t k lietary Level of Aroclor 1260 (ppm) Sex Control M F 1N > --*-J M F 10 hi F too M F TABLE II TEST MATERIAL: A roclor 1260 Two-Year Chronic Oral Toxicity Study - Albino Rate Body Weight and Total Weight Gain Data Summary of Mean Valuee I Body Weight 90-Day (grams! Total Weight Week: Gain 0 1 2 3 4 5 6 7 8 9 10 12 13I I i f i r a m s / 133 203 245 313 362 373 391 409 424 440 440 449 467 474 136 178 190 219 244 254 259 265 270 276 281 278 290 288 341 152 133 192 250 322 361 374 394 416 428 448 450 474 479 490 136 167 189 218 241 252 256 261 268 273 277 281 290 288 357 152 133 204 245 317 368 382 400 417 436 448 461 467 475 481 136 174 190 217 242 254 260 263 268 274 281 279 285 288 348 152 133 208 247 319 363 375 394 425 437 451 460 479 486 500 136 173 IBS 222 240 253 258 262 265 267 270 275 275 280 367 144 >o :x oo 9t If 000091  Dietary Level of Aroclor 1260 (ppm) Sex Control M F I !: N> ro 1 10 M F M F 100 M F TABLE II continued TEST MATERIAL: A roclor 1260 T w o-Y ear C hronic O ral Toxicity Study - Albino Rata Body W eight and Total W eight Gain Data 45 Summary of Mean Values Body Weight (grams) Month: 6 7 B9 i 10 II 498 533 565 593 622 642 667 688 297 310 322 333 345 359 374 383 516 547 578 600 628 643 68 688 298 307 314 321 333 340 353 367 496 526 551 581 606 633 660 685 291 306 314 331 340 358 370 381 522 555 580 607 633 650 00 707 289 302 307 314 326 333 342 347 12-Monlh Total Weight Gain 12 (grams /rat) 701 568 390 254 699 * 379 566 243 709 576 388 252 717 584 363 227 000092 o>3: Uooi .1 t Dietary Level of A roclor 1260 (ppm) Sex Control M F 1M F 10 hi F 100 M F TAEiLE II continued TEST MATERIAL: A roclor 1260 Two-Year Chronic Oral Toxicity Study - Albino R ats Body Weight and Total Weight Gain Data Summary of Mean Values Body Weight 24 - Monili (grams) Total Weigh Month: 11 14 15 16 17 18 19 20 21 22 23 24 Ga in 728 426 746 444 759 466 768 481 769 500 767 515 760 533 758 547 739 * 726 551 550 687 564 642 551 721 390 740 427 760 466 768 433 776 445 774 762 476 481 753 493 733 514 718 530 715 484 654 525 509 415 521 3B5 ^ 728 416 745 434 776 482 761 449 768 473 780 508 774 519 761 530 735 536 715 542 683 536 645 584 746 380 760 386 772 417 775 414 774 435 769 453 760 471 750 481 733 500 714 507 711 485 64 1 537 512 448 508 401 inx> oUOi O O C 27 3 B. Food Consumption The data obtained from the food consumption m easurem ents V conducted during the first 12 m onths of feeding are sum m arised in Table II] These data revealed no significant difference between test and control rats. The periodic checks conducted during the rem ainder of the investigation also revealed no outstanding differences between test and control animals. ( A> CC 372 00 274 (f TABLE III TEST MATERIAL: A roclor 1260 Tw o-Y ear Chronic O ral Toxicity Study - Albino Rata i ^' ( Food Consumption Data Summary of Mean Values i Food Consumption I ietary Level of Aroclor 1260 (ppm) Sex 1 2 3 4 (grams/rat/s Weel 567 n days) 89 Average Food Consumption ! 10 11 12 13 ( g r a m s / ra t/ seven days Control M 94 160 175 163 137 137 225 197 204 188 191 194 196 F 73 140 144 107 104 133 208 154 165 151 146 150 151 174 140 1 M 118 154 151 169 201 116 200 198 201 193 189 187 194 F 95 118 97 139 160 107 162 139 165 149 150 143 147 175 136 10 M 106 146 144 142 190 136 196 214 214 192 191 199 200 F 94 124 128 124 179 90 190 167 155 151 150 149 152 175 143 100 M F 121 89 150 93 156 123 117 151 187 151 124 101 121 193 190 136 196 140 186 144 184 144 199 147 189 146 163 135 o>X oou> O 275 A ietary Level of Aroclor 1260 (ppm) Sex 4 Coni rol M 196 F 148 1 M 196 F 148 10 M 186 F 142 100 M 179 F 156 TABLE III continued TEST MATERIAL: A roclor 1260 Tw o-Y ear Chronic O ral Toxicity Study - Albino Rata Food Consumption Data Summary of Mean Values Food Consumption (grams /rat/seven days) Average Food Month: Consumption 5 6 7 B 9 10 11 12 (grams/rat/seven days) 189 168 147 163 184 179 170 187 154 136 121 138 152 160 141 127 176 142 200 189 192 179 181 182 172 184 163 141 163 160 153 157 143 132 186 151 191 188 193 197 197 168 164 196 138 145 144 144 151 136 139 141 186 142 170 180 188 186 ` 166 181 188 180 127 147 144 134 132 162 149 139 180 143 vo** oo u\ 00 276 CC C . M ortality and Reactions A frequency distribution of natural deaths occurring during the investigation appears in Table IV. No untoward behavioral reactions were noted among any of the anim als employed in the investigation. AOH CC37 00 277 f-- D iet(aprpymL) evel Control 1 10 100 Sex MF MF MF MF TABLE IV TEST MATERIAL: A ro d o r 1260 Two-Year Chronic Ora! Toxicity Study - Albino Rats M ortality Data 1 Frequency Distribution of Deaths 1-3 4-6 7 F -9 requency 10-12 MD oi snttrh1i bs3:u-1t i5o n of Deaths 16-18 19-21 22-24 N uTmobtaelr DTeeasdted* 00 00 00 21 31 75 67 93 25/35 19/35 00 00 01 21 43 73 56 58 2169//3355 01 01 00 23 42 74 58 63 2197//3355 * 01 02 02 02 23 85 67 94 2293//3355 Does not in elude the five anim ale of each ex from every group sacrificed for interim pathologic tudic o. 1200 "u* 15 D. Hematologic and Clinical Blood1C hem istry Studies Mean male and female hematologic and clinical blood chem istry data a re sum m arised in Tables V through EC. Values for all param eters investigated were within the norm al range for the albino rat. No significant differences between test and contre values were observed. ACM CC373 0 0 ' 279 i * TEST OC 280 DLieevtaerly (ppm ) Control 100 Sex 3 M 14.0 F 9. 1 M 10.8 F 13.2 TABLE V TEST MATERIAL: A roclor 1260 Two-Year Chronic O ral Toxicity Study - Albino Rata Hematologic Data Summary of Mean Valuea T o t(athl 6 oLuMesuao9knnotdhcs:y/mtemC1^2o)unt 18 24 3 6 E(rmy tihllMri9ooocnnyst/htme; mC^ou) nt 12 18 IS .4 10. 1 11. 1 9.9 11.2 8. 1 8.2 8.7 8.8 7.6 9.4 6.7 7.6 8. 8 7.6 7.5 7.7 7. 3 7.8 7.7 13. 1 7.9 8.2 7.9 12.8 8.6 6.5 7.8 8.4 7.4 7.5 8.1 8.0 7.6 8.0 7. 3 7.5 7. 3 7.5 7.4 24 6.5 7.6 6.4 O 's CD ta o:% oo il .iI fr D(pLipeemvtae)rly Sex 3 Control M F 17. 1 16.9 100 M 16l 1 F 16. 3 TABLE VI TEST MATERIAL: Aroclor 1260 Two-Year Chronic Oral Toxicity Study - Albino Rats Hematologic Data Summary of Mean Values Hem 6 oglo(gbM/i91no0nC0thom:n lc)e n t r a t i o 12 n 18 24 3 H 6 e mMaCtoMon9ctrhi;t Valu 12 17.7 15.7 17.6 16. 1 13.6 51 49 48 50 17.4 14. 1 16.7 16.4 14.6 50 47 43 46 17. 14.0 15.3 15.9 14.5 17.0 13.7 15.6 15. 3 12.9 49 47 43 43 48 47 41 44 18 41 42 41 39 o> ^5 mto Uit 24 jf 35 38 38 32 ACM CC3735 o r*. D(Lpipeevmtae)rly Sex 3 Control M 62.0 F 83.0 100 M 85.8 F 92.0 TABLE VII TEST MATERIAL: A roclor 1260 Two-Year Chronic Oral Toxicity Study - Albino Rata Hematologic Data Summary of Mean Values 6 DLiyff9mMerpoehnnotthci:aylte1Ls2eukocyt1e8 Count (Num 24 ber of Coll 3 per 6 H u n9dNreeduM)troonp1t2hhi:ls 18 86.6 80.4 78. 8 79.0 65.4 16.0 11.4 18.6 20.6 20.0 86.6 66. 8 89.0 70. 2 61.4 15.4 11.6 11.8 10.0 29.2 A* 32. 2 36.0 85.4 83.4 72. 4 73. 8 66.6 89.6 78.8 82.2 80.6 65.6 12.6 13.8 15.8 22.6 24.6 31.6 7.6 10.0 19.4 17.0 17.4 34. 2 tt V } >o ooK>J 00 282 T7 / t Dietary Level Sex 3 Control M 0.6 F 0.6 M 0.0 100 F 0 .0 V TABLI VII continued TEST MATERIAL: A roclor 1260 Two-Year Chronic Oral Toxicity Study - Albino Rata ( ''Y t Hematologic Data 1 Summary of Mean Values 6 DMif9Mofenoroencntyhtti:easl12Leukocy1t8e Count (Number 24 of Cells 3 per 6 HEuonsdinroedp)hils M9 onth: 12 18 24 I i I V 0.0 0.0 0.4 0. 2 1.2 1.4 2.0 1.0 0. 2 1.6 i 0.0 0.0 0.0 0.2 1.0 1.0 1.8 1.4 0.2 0. 6 1.6 oO CoO 0.0 0.0 0.0 0.4 0. 8 0.0 0.0 0.0 0.4 0.2 1.4 0.8 0.8 1.0 1.2 1. 0* 0.4 0.4 0.8 0.8 1.6 o c oo t o TABLE! VII continued TEST MATERIAL; A roclor 1260 Two-Year Chronic Oral Toxicity Study - Albino Rats Hematologic Data Summary of Mean Values D(Lpipeemvtae)rly Sex 3 Differential 6 L e u k o c y teB aCsMo9ouopnnhttihl(s;N u m b er of 12 Celle per Hundred) 18 24 Control M 0.0 F 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 100 M 0.2 0.0 0.0 0.0 0.0 0.0 / F 0.0 0.0 ' 0.0 0.0 0.0 0.0 oo O ACM 003 O N) NU f ? S' Dietary (Lpepvmel) Sex 3 Control M 38 F 33 M 33 100 F 29 TABLE VIII TEST MATERIAL: Aroclor 1260 Two-Year Chronic Oral Toxicity Study - Albino Rata Clinical Blood Chem istry Data Summary of Mean Values 6 STerraunm(sDaMGam9dolienunttahUas:mneiitcAs)-1cP2tyivriutvyic 18 24 36 48 45 45 42 36 17 15 39 38 42 32 30 14 16 B lo oCdo n(Umcregensat r%Na)tiitor on g e n 9 M12onth; 18 24 12 10 14 15 15 9 13 11 39 42 43 31 36 37 50 40 32 33 14 15 17 16 16 15 15 15 14 13 12 14 I O ACM CC37S L D(Lpipeevmtae)rly Sex 3 * Control M F 128 130 l 100 M 118 F 117 TABLE IX TEST MATERIAL* A roclor 1260 Two-Year Chronic O ral Toxicity Study - Albino Rata Clinical Blood Chem istry Data Summary of Mean Values 6 FasCteodn(MmcB9eoglnonsot%trhda):tGiolnu1c2ose 18 24 3 S erum (Kin 6 gA-AlkAraMm9clitosnitnvertiohtPny: g1h2oUspnhitas)taIBse 123 89 118 US 88 138 99 92 134 109 28.6 24.7 21.5 20. 3 16.2 18.9 17.8 10.6 11.9 16.8 24 22. 3 20. 2 iii 118 116 135 146 98 116 US 138 146 94 37.8 21.8 21.9 23.9 11.9 16. 1 12.0 12. 1 7.6 11.7 7.8 12. 4 riCOO WO* NU Cc . Urine Analyses M e u m ale and female urine analyses data are sum m arized in Table X through XIL Determinations for glucose concentration were negative for all rats at every interval of examination. No'differences were noted between the urine from control and test anim als at the intervals of examination. ACM 0C3 00 I tr D(Lpipeevmtae)rly Sex 3 Control Mn Fn 100 Mn Fn r TABLE X TEST MATERIAL: A roclor 1260 Two-Year Chronic Oral Toxicity Study - Albino Rata Urine Analyses Data Summary of Mean Values 6 GMl9uocnoths:e 12 nnn nnn IB 24 nn nn 3 6 A9Mlbounmthi:n12 nn11 nnnn n n n nn n n n nn n11t hnnn 10 24 42 43 t 42 4 1 43 4 1 44 444424nIK3( 5=es--=yt:nm331r00e0ao00gcrtaeoettt;ooiv1tlh503ee00a0sn00smmm5tgh0gg/0a1//n101m0003g000m/1mmml0gll0u/uur1mirr0niiln0neoeumrilneurine E IL 03 Y> m Ln ^ ACM 0037VO f I D(Lpipeevmtae)rly Sex 3 Control M F N N 100 MN FN u TABLE XI TEST MATERIAL: A roclor 1260 Two-Year Chronic O ral Toxicity Study - Albino Rata Urine Analyeea Data Summary of Mean Values 6 M icrMos9ocnotphi:c E lem ents 12 18 NNNN NNNt 24 41 t 3 6 9MPonth:12 18 24 77677 6 8 a7 B6 6 N N N N1 N N N t1 77676 6 78676 6 Key: <3 i lINs=s tN5raotrcome;1a0llepsear tlhoawn p5opweerr lfoiweldpow er field O^ 44 32 *s m10ortoe 1th5apner15lopwerpolowwerpofiweeldr field l o n u I 0rv0 289 O D(Lpiepevmtae)rly Control 100 Sex M F M F O TAfaLE XII TEST MATERIAL: A roclor 1260 Two-Year Chronic Oral Toxicity Study - Albino Rata Urine Analyaea Data Summary of Mean Values 3 6 Spe9ciMficonGthr:avity 12 1.029 1.022 1.033 1.027 1.020 1.019 1.025 1.024 1.021 1.025 1.031 1.030 1.016 1.023 1.035 1.029 18 1.042 1.032 | 1.043 1.028 I o n 24 I .0S1 1.039 1.039 * 1.045 290 O >a*T Oou> .V W tf^ B >0 T E S T ^C 30 F . Pathologic Studies 1. Three-Month Sacrifice a. Gross Pathologic Findings No outstanding differences w ere noted between test and control rats upon gross pathological examination. b. Organ Weight and Organ to 3odv and Organ to 3 ram Weignt Ratio Data The results of the statistical analyses conducted on absolute organ weights, organ to body weight and organ to brain weight ratios are sum m arized in Tables XIII through XVIII. Significant differences between a. test group and the control group are designated by asterisks following the test values. Organ weights, organ to body weight and organ to brain weight ratios disclosed several randomly occurring intergroup difference The lack of any consistent dose related response and the absence of any deleterious, histopathologic change confirm that these differences w ere not related to the ingestion of Aroclor 1260. AOH C037V 0 291 nnn/ t .s' QO TABLE XIII TEST MATERIAL: A roclor 1260 Two-Year Chronic Oral Toxicity Study - Albino Rata Organ Weight and Ratio Data Three-Month Sacrifice Summary of Mean Value Organ: Liver DAireotac(prloopyfmr L)1_e2_v6_e0_l_________ MalOer_g_a_n_(g_W)_ Feiegmhtale_______O__rgMana/lDeo(_dg_y_/1_0_W_0eFigeg)mhtaRleatio O r gMa na/lBe r_a_i_(n_g_/Wg_)Fe iegmh ta Ratio le Control 21.4 13.0 4.13 4.16 10.3 6.82 1 VKrOoJ 10 100 20.4 24.0** 29.5** 13.2 12.2 14.5 3.90 4.48 5.73** 4.59 9.98 3.61 : 11.8 4.58 14.4** 6.86 6.38 7.72 ** S tatistically significant difference at^ the 99 percent confidence level n k ) Oou vO/> I m tf o % DAireota(cprlooypfmr L)1e2v6e0l Control 1 10 100 o TABLE XIV TEST MATERIAL; A roclor 1260 Two*Yer Chronic O ral Toxicity Study - Albino R ats Organ Weight and Ratio Data Three-Month Sacrifice ' Summary of Mean Values Organ: Kidneys M alOesr_g_a_n_(g_W)_ Feiegmhta le O s_______ rgMana/lBeso(_dg__y/1_0_W_0 eFgige)mht Ratio ales 4.03 2.49 0.782 0.802 4.37 2.62 0.838 0.911 4.00 2.61 0.747 0.782 4.00 2.52 0.779 0.793 O r gMa na/lBe sr_a_l_(n_g_/Wg_)Fe iegmh ta Ratio les 1.95 1.31 2.14 1.36 1.96 1.37 1.96 1.35 li n o ACH lyoj oo <% 00 294 % Dieta A roc rlooyfr Level 1260 (ppm) Control 1 10 100 nolra Looi O TABLE XV TEST MATERIAL: A roclor 1260 Two-Year Chronic Oral Toxicity Study - Albino Rats Organ Weight and Ratio Data Three-Month Sacrifice ; Summary of Mean Values Oirgan: Spleen O rgan(gW) eight Males Females 0.766 0.578 0.846 0.516 0.838 0.632 0.718 0.556 Organ/Body Weight Ratio (g/100 g) Males Females 0. 150 0.184 0.161 0.180 0.156 0.189 0.140 0.177 O rgan/B raln Weight Ratio (g/g) Males Fem ales 0.371 0.302 0.412 0.269 0.411 0.331 0.352 0.297 V V 1 t I ! I V * f Dietary Level of A roclor 1260 (PPm) Control l 10 100 TABLE XVI TEST MATERIAL] A roclor 1260 T w o -Y ear Chronic Oral Toxicity Study - A lbino Rata Organ Weight and Ratio Data Three-Month Sacrifice ; Summary of Mean Values Organ: Gonad Organ Weight (g) Males Females 3.60 0.114 3.67 0.128 3.83 0.121 3.71 0.138 Organ/Body Weight Ratio (g/100 g) Males Females 0.698 0.0370 0.704 0.0450 0.715 0.0368 0.725 0.0429 Organ/Braln Weight Ratio lg/g) Males Fem ales 1.74 0.0599 1.80 0.0666 1.89 0.0636 1.81 0.0728 .v I !i V rKj. i a O LA ADM 003753 f r 0u TABLE XVI! i TEST MATERIAL: A roclor 1260 Two-Year Chronic Oral Toxicity Study - Albino Rata Organ Weight and Ratio Data. % Three-Month Sacrifice Summary of Mean Valuea Organ: Heart I I V C DAireotac(prlooypfmr L)1e2v6e0l M Org ale* an(gW) eight Fema le s O rgMana/lBeso(dg y/1 0W0 eFgige) hmt Ratio ales O rg an /B r M ales a l(ng /Wg )Fe iegmh ta lReas t i o Control 1.59 1.05 0.307 0.339 0.767 0.551 1 1.57 1.01 0.300 0.353 0.765 0.526 10 1. SB 1.04 0.296 0.311 0.781 0.546 100 O O 1.52 0.946 0.298 0.297 0.743 0.505 AOM 00375 ft I uc ACM 0C3755 OO T ABLE XVIII TEST MATERIAL: A ro d o r 1260 Two-Y#r Chronic O ral Toxicity Study - Albino Rata Organ Weight and Ratio Data Three-Month Sacrifice Summary of Mean Values Organ:. Brain DAireotacrlooyfr Level 1260 <PPTMi________ Organ Weight Male (g) Fem ale* O'rgMana/lBeao(dgy/10W0eFgige)mht Ratio ales FoifnSalacBroifdiyceWd eRigahtats M ales (> F em ales i, Control 2.07 1.91 0.402 0.616 518 314 i 1 2.05 1.92 0.392 0.672 523 287 10 2.04 1.91 0.380 0.572 536 337 100 2.05 1.89 0.400 0.593 517 321 O r I OJ luit. /'"'N L O' 3i*J**\*aL 5 TES T JiM A O iv u ti, c il c . Histopathologic Findings Histopathologic examination of tissues and organs taken from all animals from both the control and 100 ppm groups was conducted. noted. Tables XIX and X X list all histopathologic changes - . A ll of the lesions noted in the m icroscopic examina- tion of tissues were those of spontaneous disease and are not unusual for the albino rat. The most frequent findings were lesions in the trachea and lungs, indicating chronic murine pneumonia. These oc curred in the control as well as the rats fed A rocior 1260. ADM C037 00 298 I fuLt'iC'ueJ' I C 3 I Z J& u iiiA + C i. Jru z. c 33 TAB LZ XIX TEST MATERIAL: A ro clo r 1260 Two-Year Chronic Oral Toxicity Study - Albino Rata Histopathologic Changes Three-Month Sacrifice Croup: Control NAunmi mb earl sof 5 Males 5 Fem ales Or^an Examined LTur ancgh e a Urinary bladder Lung Findings HTCyrhadprcoeishnrepiecailstairesseisap ira to ry Chdroisneicasree sp ira to ry Incidence i 3i ACveraradgee 1.0 11 .. 00 i 1.0 All other tissues and organs were normal histologically. Grading System 542301......000005*ss*emmssmexlioivtglirddenheerimtmeraeatel ADM 003757 299 OC rb i 'Jc. XS :? TABLE XX TEST MATERIAL: A roclor 1260 Taro-Year Chronic O ral Toxicity Study * Albino Rata Histopathologic Changes Three-Month Sacrifice Croup: 100 ppm NAu nmi mb earl so i 5 Males 5 Fem ales Orsan Examined LTur ancgh e a LTur ancgh e a Kidney Findings TCrhardcoihnseeicaitsiresesp ira to ry FTCorhacridncoaihflnsieeillcyatirtsmiaresetpishoponiirda to ry Incidence - AGverardaeg < 4 1.0 2 1.0 3 1.0 2 1.0 1 1.0 All other tissues and organs were normal histologically. Grading System 452301......000005=aa*a emsmmsexlioiivtglnrddeheiermmteraaatle AOM 003 75 00 300 Cy- ^ " : l 40 2. Six-Month Sacrifice a. Gross Pathologie Findings No outstanding differences were noted between test and control anim als. b . Organ Weight and Organ to Body and Organ to 3rain Weight Ratio Data The results of the statistical analyses conducted on absolute organ weights, organ to body weight and organ to brain weight ratios are summarized in Tables XX I through X X V I. Organ weights, organ to body weight and organ to brain weight ratios disclosed several randomly occurring intergroup differences. The lack of any consistent dose related response and the absence of any deleterious histopathologic change confirm that these differences were not related to the ingestion of Aroclor 1260. 0C375 301 0c t DAireotac(prlooypfmr L)1e2v6e0l Control 1 10 100 TABLE XXI TEST MATERIAL: A roclor 1260 Two-Year Chronic Oral Toxicity Study > Albino Rata Organ Weight and Ratio Data Six-Month Sacrifice Summary of Mean Values Organ: Liver * M Orga ales n(gW) Feiegmhtale 22.9 13. 1 14.8** 15.1 19.0> 10.5** 24.4 11.6 O rgMana/lOeso(gd/y10W0eFgieg)mhtaRleatio 3.74 3.77 2.92** 3-74 3.31* 3.08* 4.69* 4.03 O r gMa na/lBe sr a l(ng /Wg )Fe iegmh ta Ratio les 11.7 6.71 7.05** 7.86 9.45* 6.07 12.3 6 . 17 :>SSttaattiissttiiccaallllyy ssiiggnniiffiiccaanntt ddiiffffeerreennccee aatt tthhee 9959 ppeerrcceenntt ccoonnffiiddeennccee lleevveell.. KOto) 92 TOO r oO TABLE XXII TEST MATERIAL: A ro d o r 1260 Tw o-Y ear Chronic Oral Toxicity Study - Albino Rata Organ Weight and Ratio Data Six-Month Sacrifice Summary of Mean Valuea Organ: Kidneys DAireota(dprooypfmr L)1e2v6e0l Organ Weight Male (6) Fem ales O rgMana/lBeso(dgy/10W0 eFgige)mht Ratio ales O rgan/B raln Weight Ratio M ales <g/g>F em ales Control 4.04 2.79 0.664 0.806 2 t 06 1.43 1 3.64 2.73 0.716 0.674*. 1.73 1.42 10 3.85 2.35 0.670 0.684* 1.92 1.36 oo 100 3.92 2.35 0.753 0.814 1.97 1.25 u> ou> * S t a t i s t i c a l l y s ig n i fi c a n t d i f f e r e n c e at the 95 p e r c e n t c o n fid e n c e l e v e l . E L tn mtn ACM 0C37. f' t A t o oo % DAireotac(prlooypfmr L)1e2v6e0l Control 1 10 100 TA6 LE XXIII TEST MATERIAL: A roclor 1260 Two-Year Chronic Oral Toxicity Study - Albino Rata Organ Weight and Ratio Data Six-Month Sacrifice Summary of Mean Values Organ: Spleen Organ Weight M ales (g) Fem ales 0.752 0.684 0.754 0.908 0.836 0.566* 0.636 0.443* O rgMa na/lDe so(dgy/ 1 0W0 eFgige)mh t aRleastio 0.122 0.196 0.148* 0.220 0.146* 0.167 0.122 0.151 O rgan/B rain Weight Ratio M ales (g/glF em ales 0.384 0. 350 0.359 0.472 0.416 0.327 0.320 0.236* I r i I i i yi vl o S tatistically significant difference at the 95 percent confidence level. 14 AOM 0037 t/ o % DAireotac rl ooyfr Level 1260 (ppm) Control 1 10 100 o TABLE XXIV TEST MATERIAL: A roclor 1260 T w o-Y ear C hronic O ral Toxicity Study - Albino Rata Organ Weight and Ratio Data Six-Month Sacrifice Summary of Mean Values Organ: Gonada o O rgan(gW) eight Males Females 3.55 0.0960 3.23 0. 120 * 3.56 0.0968 3.53 0.0710* O rgan/B o(dg/y10W0egig)ht Ratio Males Females 0.593 0.0279 0.636 0.0297 0.620 0.0287 0.686 0.0250 O rgan/B ral(ng/Wg)eight R atio Males Fem ales 1.81 0.0492 1.54 0.0625* 1.77 0.0560 1.77 0.0378* * S t a t i s t i c a lly s ig n ific a n t d iff e r e n c e at the 95 p e r c e n t c o n fid e n ce le v e l. % J* I ( 1 KtyIi ACM GC3 r- t I Q TC''V,rPyf` TABLE XXV TEST MATERIAL: A roclor 1260 Two-Year Chronic O ral Toxicity Study - Albino Rate Organ Weight and Ratio Data Six-Month Sacrifice Summary of Mean Valuea Organ: Heart D 'A ireotc(aplroopyfmr L)1e2v6e0l Control 1 10 ICO Organ Weight M alea (s) F em ales 1.70 1.05 1.45 1.12 1.63 1.05 1.49 1.06 Organ/Body Weight Ratio M ales(g/100Fge)m ales 0.282 0.302 0.286 0.277 0.283 0.307 0.286 0.368** O rg an /B ra M ales l(ng/Wg)Feiegmhta Ratio les 0.867 0.538 0.690 0.583 0.810 0.606 0.749 0.564 O OtJ OT oG\ OOb* * S tatistically significant difference at the 99 percent confidence level. nu * * DAireotac(prlooypfmr L)1e2v6e0l Cont rol 1 10 100 TABLE XXVI TEST MATERIAL: A roclor 1260 *Two-Year Chronic O ral Toxicity Study Albino Rate Organ Weight and Ratio Data Six-Month Sacrifice Summary of Mean Values Organ: Brain Organ Weight M alet (g) Fem ale* 1.96 1.95 2.10 1.92 2.01 1.73 1.99 1.88 O rgMana/lBeso(dgy/10W0eFgieg)mhtaRleastio 0.320 0.560 0.412* 0.474* 0.349 0.504 0.382 0.650* Foinf aSlacBroidfiyceWd eRigahtt** Male* ` (e) Fem ale* 613 348 509 405 575 . 343 522 289 * S t a t i s t i c a lly s ig n ific a n t d iff e r e n c e at tho 95 p e r c e n t co n fid e n ce l e v e l .  t id u liu a l 'TEST t. jna. c 4- c. Histopathologic Findings Histopathologic examination of tissues and organs taken from a ll anim als from both the control and 100 ppm groups was conducted. Tables X X V II and XXVIH list all histopathologic changes noted, A ll of the lesions noted in the microscopic examination of tissues were those of spontaneous disease and are not unusual for the albino rat. The most frequent findings were lesions in the trachea and lungs, indicating chronic murine pneumonia. These occurred in the eontr< as well as the rats fed Aroclor 1260. ACM 0C37 bt> 0 ( 308 lu*l B I sr J*ttf. 43 TABLE XXVII TEST MATERIAL: A roclor 1260 Two-Year Chronic Oral Toxicity Study - Albino Rats Histopathologic Changes Six-Month Sacrifice Group: Control NAunmimbearlsof 5 Males 5 Females Organ Examined Trachea Lung SLkiveelertal m uscle LLTuirvanecgrh e a Kidney Findings HTFFFFooooryaccccpcaaaaehllllreepiptnmirnetafireilcsiaauchmmheoimotlniaasinttiigosintis HHPFF oeoyyrccppiaaceellhrreeitonmrmlafaiilcnaaahgmei timitsiast i o n Incidence ' AGvreardage 22211l : 011111......550000 2lll1 20111.....55000 Ail other tissues and organs were normal histologically. Grading System 245301......000005 *a*aa mmemsselxiioivtglnrddehieemrtmeraaetle r ACM 0C37 0 0 309  J 'mZ*m,yUC3. TABLE XXVIII #; TEST MATERIAL: A roclor 1260 Tw o-Y ear Chronic O ral Toxicity Study - Albino Rata Histopathologic Changes Sbc-Month Sacrifice Group: 100 ppm NAunmimbearlsof 5 Males 5 Females Orcan Examined Trachea Lung L iv er LTur ancgh e a Liver Kidney Findings HHFFFToooryyacccppcaaaeehlllrreeepptmmirentaireiisciaauchhmeoiotlniasintgisitis. FFooccaall ptrnaecuhmeiotnisitis HHFF ooyyccppaaeellrreenpmmee priiiaahcrhi toilsa n g i t i s Incidence 244111 . 222311 AGv er ar da ge 200111......055500 030011......550550 All other tissues and organs were normal histologically. Grading System 234501......00050 0a*aa*amemsselmxiiivtglnordeheidmrtmeeareal te 9 A0f* CC370 310 00 nd^iiiual TEST JsJuyiaJo^uci, J*c 50 3* TwclvcMonth Sacrifice a G ro ss Pathologic Findings Gross pathologic findings among test animals were significantly different from those noted in control anim als. b. Organ Weight and Ratio Data The m ean organ weight and ratio data collected a t ti twelve month sacrifice are presented in Tables XXDC through XXXIV. v. S tatistically significant differet nces a re designated by asterisks following the test group value. Organ weights, organ to body weight and organ to br weight ratios disclosed several randomly occurring intergroup differences The lack of any consistent dose related response and. the absence of any deleterious histopathologic change confirm that these differences were not related to the ingestion of Aroclor 1260. ACH 00376 311 0 t' o D ieta(prpymL) evel Cont rol l 10 100 oo TABLE XXIX TEST MATERIAL: A roclor 1260 Two-Year Chronic Oral Toxicity Study - Albino Rata Twelve-Month Sacrifice Organ Weight and Ratio Data Summary of Mean Values Organ: Liver Organ Weight M ales (g) F em ales OMrgaalne/sB(od/y1 0W0 geF)ige mht Ratio ales O rgan/B raln Weight Ratio Males (g/g) Fem ales 22.1 15.5 3.79 3.52 10.8 7.72 17.1* 10.7* 2.79** 3.01* 9.23 5.76 20.0 13.6 3.30 3.54 10.8 7.28 28.8* 14. 1 4.26 3.79 13.4* 8.52 a as O ufO-> To* OOta _ Statistically significant difference at the 95 percent confidence level Statistically significant difference at the 99 percent confidence level t D iet(aprpymL) evel Cont rol l 10 too TABLE XXX TEST MATERIAL: A roclor 1260 Two-Year Chronic Oral Toxicity Study - Albino Rato Twelve-Month Sacrifice Organ Weight and Ratio Data Summary of Mean Values Organ: Kidneys Org an Weight M ales (g) F em alcs Organ/Body Weight Ratio M ales (g/ `oo gF>em ales Organ/B rain Weight Ratio Males (g^g)F em alcs 4.04 3. 19 0.692 0.738 1.97 1.58 3.84 2.58** 0.625 0.724 2.06 1.39 oo 2.78* 0.660 0.736 2.16 1.48 5.11* 2.81 0.758 0.755 2.38* 1.69 Vc c ri + Statistically significant difference at the 95 percent confidence level, os Statistically significant difference at the 99 percent confidence level. o o u> ,Vo* U> o o t/ Dietary Level (ppm ) Cont rol 1 10 100 TABLE XXXI TEST MATERIAL: A roclor 1260 Two-Year Chronic O ral Toxicity Study - Albino Rata Twelve-Month Sacrifice Organ Weight and Ratio Data Summary of Mean Valuea Organ: Spleen M a O les r g a n(gW) eight Fem a le a OMrgaalne/sB(ogd/y1 0W0 egFi)gemht Ratio alea O rgan/B Malea ra(ign/gW) eight Fem a Ratio les 0.778 0.796 0.756 0.460* 0.836 0.578 0.785 0.474* 0.133 0.183 0.122 0.129* 0.1J9 0.150 0.116 0.127* 0.380 0.396 0.408 0.247* 0.457 0. 308 0.365 0.284 a O u> .u Vat OO Statistically significant difference at the 95 percent confidence level* ! '\ f\ o Dietary Level (ppm! Cont rol 1 10 100 oo TABLE XXXII TEST MATERIAL: Aroclor 1260 Two-Year Chronic O ral Toxicity Study - Albino Rats Twelve-Month Sacrifice Organ Weight and Ratio Data Summary of Mean Values Organ: Gonads . O rgan(gW) eight Males F crnalci O rgan/B(ogd/1y0W0 egi)ght Ratio Males Females O rgan/B ra(ign/gW) eight Ratio Males F em ales 3.46 3.38 3.51 4.03** 0. 116 0. 103 0. 1 12 0.088* 0.596 0.551 0.578 0.598 0.0275 0.0287 0.0294 0.0238 1.70 0.0574 1.82 0.0552 1.89 0.0584 1.88 0.0527 * Statistically significant difference at the 95 percent confidence level. Statistically significant difference at the 99 percent confidence level. ^ v% ootjj 315 D ieta(prpymL)evel Cont rol 1 10 100 f rf o TABLE XXXIII TEST MATERIAL: A ro c lo r'1260 Two-Year Chronic O ral Toxicity Study - Albino Rate Twelve-Month Sacrifice Organ Weight and Ratio Data Summary of Mean Values Organ: Heart M Org ales a n(gW) eight Fem a le s OMrgaalne/sB(ogd/1y0W0 egFi)gehmt Ratio ales O rgan/B M ales r a(lng/gW) Feiegmhta Ratio les 1.71 1.23 0.293 0.287 0.835 0.611 1.68 1.07 0.273 0.301 0.902 0.575 1.59 1.16 0.261 0.307 0.845 0.620 1.86 1.27 0.275 0.340 0.868 0.760 316 vo o o i o Dietary Level (ppm) Cont rol 1 10 100 TABLE XXXIV TEST MATERIAL; Aroclor 1260 Two-Year Chronic Oral Toxicity Study - Albino Rata Organ Weight and Ratio Data Twelve-Month Sacrifice Summary of Mean Values Org an Weight Males (g) Fem ale* Organ: Drain Organ/Rody Weight Ratio (g/100 g) Malea Females Final Body Weight of Sacrificed Rats (grams) Malea Females 2.04 2.02 0.349 0.460 584 439 1.87 1.86 0. 304 0.522 616 356 1.88 1.90 0.310 0.493 607 385 2 . 1 5 1.67 * 0.318 0.449 675 372 Statistically significant difference at the 99 percent confidence leve!. OO vr> \ oo ; 317 V% nui h O' cc C . Histopathologic Findings Histopathologic examination of tissues taken from each r a t sacrificed from the control and 100 ppm groups after twelve m onths of testing was conducted. Tables XXXV and XXXVI list all hisopathologic changes noted. All of the lesions noted in the m icroscopic exam ination of tissues w ere those of spontaneous disease and are not unusual for the albino rat. The m ost frequent findings were lesions in the trachea and lungs, indicating chronic murine pneumonia. These occurred in the contr as well as the rats fed Aroclor 1260. AOf*. C03776 318 ooc TABLE XXXV TEST MATERIAL: A roclor 1260 Two-Year Chronic Oral Toxicity Study Albino Rats Histopathologic Changes Twelve-Month Sacrifice Croup: Control NAunmimbearlsof 5 Males 5 Females O rian Examined TL ur ancgh e a Urinary Bladder LTur ancgh e a Colon Findings TC C rhadalrccoisuhnelieuacisstriese s p ir a t o ry TCP arhdarrcaoishsneiieatciestsiersesp ira to ry Incidence i 2l l 11 AGver;j 1. i1.. 1. 11.. All other tissues and organs were normal histologicaily. Grading System 452301......005000 *s=s emsmmsexliioivtglnrddeheiermtmeraaetle AC C03777 00 3 1 9 I JtvLui'+id B r5 r 'j*e . ( 'i'i TABLE XXXVI TEST MATERIAL: A roclor 1260 Two-Year Chronic Oral Toxicity Study - Albino Rats Histopathologic Changes Twelve-Month Sacrifice Croup: 100 ppm NAumnibmera..l.so.. 5 Males Orsan Examined TL ur ancgh e a Kidney Liver 5 Females TL ur ancgh e a Findings VTFCorhardiaccrnacioaunsfhnloiedleilalotcayirsmtrameirstecipcoshhenpaolnilirdsgaetoorfy TCrhdaricoshneeiacisteirse sp ira to ry Incidence i 3 1 1 l l AGverar<; l.C l.C l.C l.C l.C l.Q All other tissues and organs were normal histologically. Grading System 243501......000050 ****ss mmesmselxiioivtglnrddehieemrtmeraaetle ACM 0C3778 320 OC B T 5 T jVic 1 to 4. Final Sacrifice a. Cross Pathologic Fir.dir.es Gross pathologic fundings among test animals were not significantly different from those noted in control anim als. b. Organ Weight and Ratio Data The mean organ weight and ratio data collected at the final sacrifice are presented in Tables XXXVII through XLII. Statistically significant differences are designated by asterisks following the test group value. f Absolute liver weights and liver to body weight or liver o to brain weight ratios w ere significantly elevated in those rats fed 100 ppm A roclor 1260. Other organ weights, organ to body weight and organ to bra weight ratios disclosed several randomly occurring intergroup differences, The lack of any consistent dose related response and the absence of any deleterious histopathologic change confirm that these differences were not related to the ingestion of A roclor 1260 O ADM 0C 37 321 0( BIb TEST A>. CO3 ieta(prypmL) evel onlrol 1 10 00 TABLE XXXVII ' TEST MATERIAL: A roclor 1260 Tw o-Y ear Chronic O ral Toxicity Study - Albino Rata O rgan Weight iand Ratio Data Summary of Mean Values ' Final Sacrifice Organ: Liver Org an Weight M alea (g) F em ales O rgan/B(ogd/IyOWOge)ight R atio Males Fem ales 22 0 16. 3 3.47 3.05 22.0 16.6 3.40 3.35 24. 1 18. 1 2. 87* 3. 19 29.9** 2 2 .7++ * 4.67++ 4.42+* * SSttaattiissttiiccaallllyy ssiiggnniiffiiccaanntt ddiiffffeerreennccee aatt tthhee 9959 ppeerrcceenntt ccoonnffiiddeennccee lleevveell i Organ/B rain Weight Ratio Males (g/e) Fem ales 10. 10 8.42 9.93 8.62 11. 20 9. 26 13.40 + 11.60 O' r d h cia(prypmL) evel lonlrol 1 10 100 o TABLE XXXIX TEST MATERIAL: A roclor 1260 Two-Year Chronic Oral Toxicity Study - Albino Rata Organ Weight and Ratio Data Summary of Mean Values Final Sacrifice Organ: Spleen Organ Weight M ales (c) F em ales Organ/Body Weight Ratio M ales /100 g) F em ales 1. 15 0.96 0. 182 0. 181 1. 17 0. 72 0. 178 0. MB 1.09 0. 83 0. l i t 0. 142 0.89 0.75 0. 138 0. 146 "* * Organ/B rain Weight Ratio Males (g/g) Fem ales 0.520 0.492 0.529 0. 370 0.509 0. 428 0.400 0. 379 O * LJ Q to * 1 U> Uooi / \ D ietaInrynmLlevel Control 1 10 100 TABLE XL TEST MATERIAL: A roclor 1260 Two-Year Chronic Oral Toxicity Study - Albino Rata O rgan Weight iand Ratio Data Summary of Mean Values Final Sacrifice Organ: Gonada M ales O r g a(ng) W eight Fe m ales 2.52 0. 123 OMraglaens /Biogd/IyOWOge)igFhet R m atio ales 0. 397 0.0222 3.56* 0. 140 0.550* 0.0317 3. 36* 0. 177 0. 400 0.0338 2.97 0. 113 0.464 0.0229 O > S tatistically significant difference at the 95 percent confidence level. aNu.>j AOM 003782 o O rgan M ales /B (rga/ifni) W eight Ratio Fem ales 1. IS 0.0628 1.61* 0.0718o 1.56* 0.0900 1.33 0.0584 t \ r' f \ oo D ie ta(prypmL)e v el Coni rol ; 1 10 100 TABLE XLI TEST MATERIAL: A roclor 1260 Two-Yer Chronic Oral Toxicity Study - Albino Rat Organ W eight land Ratio Data Summary of Mean Values 1 Final Sacrifice Organ: Heart Organ Weight M ales (g) Fem ales Organ/B(occ/JiyooWge)ight Ratio Males Fem ales 1. 87 1.54 0. 294 0. 288 1.98 1.45 0.304 0.294 1.90 1.58 0.225** 0.279 2.00 1.49 0.313 0.288 O Statistically significant difference at the 99 percent confidence level. Organ/B rain Weight Ratio t Males (/) Fem ales 0. 860 0. 795 0.893 0.747 0.884 0.809 0.904 0.764 325 KoJ O IW >*vc. UI c. Histopathologic Findings Histopathologic examination of tissues and organs taken from all anim als sacrificed after 24 m onths on test was conducted. Tables XLIII through XLVI list all histopathologic chans noted." Table XLVI2 contains the results of the histopathologic exam inatic of the urinary bladders. Significant liver injury was found in anim als fed 100 pprr A roclor 1260 (T-III). The compound associated lesions consisted of vacuc change, focal hypertrophy and focal hyperplasia. In addition, there w ere lesions of inflammation, necrosis, fibrosis and minor degeneration in this group which, although seen in the controls and low er test groups, w ere me severe and frequent in the T-III group. The vacuolar change was not seen in the control anim als but was observed occasionally in livers from T -I (1ppm) and T-U (10 ppm) anim als. It was frequent in the T-III anim als. This lesion is morphologic indicative of fatty degeneration. Form alin*frozen sections of livers from represenative anim als which displayed vacuolar changes were stained with Oil Red 0 to reveal the presence of fat. The vacuolar lesion in the cytoplat of these cells was positively identified as fat. The hypertrophic change found in the liver was focal and often lim ited to the central lobular area where groups of cells were swollen to two or three times their norm al size with clear pink homogenous cytopla: The hyperplasia was associated with the same cells and appeared to be an ACM C0376<, Q l 326 c wo extension of the hypertrophic lesion. The hyperplastic cells were also usually hypertrophic. The most severe exam ples of hyperplasia appear as nodular growths with limited com pression of the surrounding norm al hepatic tissue. The minor lesions of degeneration, hepatitis, ductule c proliferation, necrosis and focal lymphoid infiltration seen in the control anim als and the T -Iand T-H groups are lesions of spontaneous disease a; are not related to the Aroclor 1260. This level of liver disease is not uni in old anim als. Hyperplasia of the urinary bladder was found in an anim from the control group. This finding was not present in any of the ra ts it A roclor 1260. All of the other lesions in other tissues found in these anir a re related to spontaneous disease and they are not unusual for old ra ts. VDDoiepnteloorvmiannaatrey,. PAGamtohreodrloiocnga, insCtCs. oVl.leMge., oPf h. D. ACM CC37 327 oc !n o oo D iet(aprpymL) evel Control 1 10 too TABLE XLH TEST MATERIAL: A roclor 1260 Two-Year Chronic Oral Toxicity Study - Albino Rats * O rgan Weight iand Ratio Data Summary of Mean Values Final Sacrifice Organ Weight M ales (g) Fem ales Organ: Drain OrMgaanle/Ds fogd/1y0W0 egFi)gehmt Ratio ale SaFcMriinafailecl seBdodAyniWmeaFilgeahmt(gaolrfeasm a) 2. 18 1.95 0. 342 0. 362 642 551 2.21 1.94 0.343 0.407 654 525 2. 15 1.96 0.255#* 0.347 845** 584 2.22 1.95 0. 346 0.378 641 644 I I iiiI i S tatistically significant difference at the 99 percent confidence level. 3 328 ADM 003786 oO' 6Zi 0 0 Number of Animals 11 M a l e s >n oo Oj o TAPLE XLIII TEST MATERIAL: A ro d o r 1260 Two-Year Chronic O ral Toxicity Study - Albino Rate Histopathologic Changes Final Sacrifice Group: Control Organ Examined Heart Trachea Ling Liver Stomach Spleen Kidney Testes Prostate Adrenal Gland Brain Eye Findings Chronic focal myocarditis Tracheitis Chronic respiratory disease Focal degeneration Ductile hyperplasia Chronic gastritis Hemosiderosis Chronic nephritis Testicular degeneration Periarteritis TInefllaanmgmi eacttiaosni s Nodular hyperplasia Focal fatty change Focal encephalitis Inflammation Incidence 3 3 91* 2 1 3 8 2 2 1 1 1 1 1 2 o 14 I A Gv er raadgee 1.0 1.0 1.0 1.0 1.0 1.01.0 1.0 1.0 1.0 1.0 i1..O0 1.0 i.O 1.0 o TEST AO#* CO 3788 t O TABLE XLIII continued TEST MATERIAL; Aroclor 1260 Two-Year Chronic Oral Toxicity Study - Albino Rata Histopathologic Changes Final Sacrifice Group: Control NAunmimbaerIsof Organ Examined Findings Incidence H Females HTLLurievanacgerhrt ea Stomach SUCKptoicdlleorneunensy Ova ry Adrenal Gland Salivary Gland CCTAHMCNCFDCFPFoohorhhahyucoeeacccrrrrasrcnmtocooaoaatatnr-ilhlnnnlinslotltiheiieiiispihllccctcsoyiyiieetdhdmsmisfgpnreyisoesaepaprvpcsotphshaeaip-tsohotclrriiiipiurrssisddmitalqotiatiuslyiisosannaoirramffcyiiclalotthrdrurdaaaisnsitttiiegeiooasepnnsi teh e l i u m NCTheolrdaounnlagicriehfciytbaprsoeirsspislaasniad atrophy All other tissues and organs were norm al hilolnir.illw 7 196324325331111 491 O AGvreardage e 022111111111111...............500000000000000 1.0 11..00 ^*{> o i< 7 O NAunmimbearlsof 11 Males >o oo TABLE XLIV TEST MATERIAL: A roclor 1260 Two-Year Chronic O ral Toxicity Study - Albino Rata Histopathologic Changes Final Sacrifice Group: I ppm * Organ Examined HTLLurievanagcerrht ea SSKTPLtpyaeiodlmnsemntcepeeanryhscehaNsode SPermositnaatle V esicle Findings CCHTCF1FACCTIoohhrhohceceaccrrurnmmrsoocoaaottgeihnlnloonneciieissishsufcccciiitocedldticaoiafprfnecsoaoernraerrlcrcsootpdiaaipgsnshtleliiitagrgsrssmpisaettaitnyrsonieortcrciyarsaetridaoditnsiitteiiass s e PIInneffrllaaiammrmmteaarttiiitooinsn . Incidence 14720111 42711111 o 'V A vGerraadgee 222232111111111...............000000000000000* 331 fr O Number of Animal s 11 M a l e s 14 F e m a l e s o ouUK>>i nX* Uoo) o TABLE XLIV continued TEST MATERIAL: A roclor 1260 Two-Year Chronic O ral Toxicity Study - Albino Rats Histopathologic Changes Final Sacrifice Group: 1 ppm ' Organ Examined Adrenal Gland Heart Trachea 1-unjj Liver 9 Stomach Findings Nodular hyperoplasia Focal fatty change C h ro n ic focal m y o c arr d i t i s Chronic focal myocarditis Tracheitis Chronic respiratory disease Focal fibrosis Focal lymphoid infiltration Ductile hyperplasia Congestion Vacuolar change (fatty) Chronic gastritis Acanthosis Incidence 2 2 3 1 9 13 1 1 1 1 2 o Average Grade 1.0 1.0 1.0 3. O' 1.0 1.0 1.0 1.0 0. b 1.0 2. 0 1.0 1.0 tt Number of Animals 1-1 F e m a l e s >n X oo TABLE XLIV continued TEST MATERIAL: A roclor 1260 Two-Year Chronic O ral Toxicity Study - Albino Rata Histopathologic Changes Final Sacrifice Group: I ppm > Organ Examined Stomach Colon Spleen Lymph Node Kidney Uterus Adrenal Gland Findings Ulceration and acanthosis Para sites Hemosiderosis llype rpla s ia Congestion Chronic nephritis Vacuolar change (fatty) Metritis Telangiectasis Nodular hyperplasia Congestion Incidence n43ii1ii 93 1 All other tissues and organa were norm al histologically 0. 5 : ntinitn >I Grading System >A i % i i Average Gra 1111....0000 1.0 21111.....00000 I. 0 eec 000 r 334 Number of Animals 7 Males O 14 F e m a le * o TABLE XLV TEST MATERIAL: A roclor 1260 Two-Year Chronic O ral Toxicity Study - Albino Rat Histopathologic Change Final Sacrifice G ro u p : 10 p pm < Organ Examined Heart Trachea Lung Liver Stomach Spleen Kid ney Prostate Adrenal Gland Findings Chronic focal myocarditis Tracheitis SCuhprpounrica tirvees ppinr eaut omroynidai s e a s e Vacuolar change (fatty) Chronic gastritis Acanthosis Hemosiderosis Chronic nephritis NInofdlaumlamr ahtyiopne r p l a s i a Incidence 3 2 5 1 2 1 2 63 2 1 Ilea rt Trachea Lung Chronic focal myocarditis Thracheitits Chronic respiratory disease 3 8 14 Average Grade 1.0 1.0 1.0 3. 0 1.0 1.0 1.0 1.0 1.0 1.0 . 1.0 IIIl \I 1.0 11 .. 00 X f S r r TABLE X*LV continued TEST MATERIAL: A roclor 1260 Tw o-Y ear Chronic O ral Toxicity Study - Albino Rata Histopathologic Changes Final Sacrifice Group: 10 ppm * NAunmi mb earl sof Organ Examined Findings Incidence 335 H Females o> OCU O0U-al Ui Liver Pancreas Stomach Spleen Kidney Ute rus Pituitary Adrenal Gland Vacuolar change (fatty) Focal hyperplasia Chronic focal pancreatitis Periarteritis Acanthosi s Hemosiderosis Chronic nephritis Metritis Congestion Telangiectasis Nodular hyperplasia Congestion i i i i i 1120 . 7 1 71 1 All other tissues and organs were norm al histologically. CD L1 min 'c Average Grade 1.0 1.0 3.0 3.0 1.0 . 1.0 1.0 2.0 1i ..o0 1.0 1.0 U& -tnI ( o o TABf LE XLVI o. TEST MATERIAL: A roclor 1260 Two-Year Chronic O ral Toxicity Study - Albino Rats Histopathologic Changes Final Sacrifice Group: 100 ppm Number of A n i m a l s _________ O r g a n E x a m i n e d _____________________ F in d in g s Average Incidence_______________ G r a d e 10 M a le s OO Heart Trachea Lung Liver PS taonmc raccAh i Spleen Kidney 1 Chronic focal myocarditis Tracheitis Chronic respiratory disease Congestion Vacuolar change (fatty) Focal degeneration Congestion Centrolobular hypertrophy Telangiectasis Chronic focal pancreatitis Inflammation Acanthosis 1lc m o aide ro a is Focal lymphoid infiltration Calcified concretions in pelvis 5 6 91 2 1 3 2 1 2 2 2 71 1 1.0 1.0 2.0 1. 0 2.0 1.0 2.0 1.0 1.0 1.0 2.0 11..00 1.0 1.0 1.0 ACM .0037 f r'- Number of Animals 10 M ales TABLE XLVI continued TEST MATERIAL: A roclor 1260 Tw o-Y ear Chronic O ral Toxicity Study - Albino Rata Histopathologic Changea Final Sacrifice Group: 100 ppm* Organ Examined Kidney (continued) Teste s TP rhoysmt autse Adrenal Gland . Findings Calcified concretions in pelvis Aspermia CInyfslta m m a tio n Telangiectasis Nodular hyperplasia Incidence 1 1 1 31 1 15 F e m a l e OO--> vjCo Co ~ o Oo tJ Heart Trachea Lung Liver Chronic focal myocarditis Tracheitis Chronic respiratory disease CE do ne mg eastio n Vacuolar change (fatty) 5 8 11 1 1 5 1 I II Average Grade 11 ..00 1.0 11 ..00 1. 0 \IiiI1 1.0 1.0 11 ..00 1.0 1.0 ^-v1j f r o TABLE XI LVI continued TEST MATERIAL: A roclor 1260 Two-Year Chronic O ral Toxicity Study - Albino Rats Histopathologic Changes Final Sacrifice Group: 100 ppm< Number of * A n i m a l s _________ O r g a n E x a m i n e d _____________________ F in d in g s _______________________________ Incidence ACf* CO 37So 15 F e m a l e s co Liver (continued) Pancreas SKpildeneeny Uterus Pituitary Adrenal Gland Pa ratliyroid Focal hyperplasia Chronic inflammation of liver capsule Centrolobular hypertrophy Necrosis Ductile cell hyperplasia portal fibrosis and widespread eosinophil inclusions in hep.itucyte cytoplasm Chronic focal pancreatitis and periarteritis Hemosiderosis Chronic nephritis Metritis Congestion Telangiectasis Nodular hyperplasia Congestion 1l y p t M p l a s i a 42511 s 1 69711181 Average _________ G r a d e 21111.....00000 3.0 11111211........00000000 I II i I t (r Group c T-I * (1 ppm ) (T1*0IIp p m ) T-III (100 ppm) tfABLE XLVII TEST MATERIAL: A roclor 1260 Two-Year Chronic Oral Toxicity Study - Albino R aft Histopathologic Changes of the Urinary Bladder Final Sacrifice Sex Number Examined Findings* M F i1i4 Proteinaceous plug (34) Focal epithelial hyperplasia (62) MF 1110 Proteinaceous plug (86, 105, and 107) None MF 174 Proteinaceous plug (187) None MF 1104 Proteinaceous plug (271) None * Individual animal numbers are shown in parentheses. Grading System <1.0 - m i n i m a l o r t r a c e 4.0= severe 2.0 = mild 5.0 = extreme 3.0 = moderate oo Incidence ii 3 - I< - 1 Average Grade 1.0 - - ACM c JKO M O IW - I S J V G. Detailed Description of Tumor Findincs Tumor data for individual animals including location, weight and pathologic classification are presented in Tables XLVIL through LI. Nona of these tumors could be related to the ingestion of Aroclc 1260 and are considered normal for a random population of rats this age AD* 003 0( 340 341 r !c o !Aa*nnudimmSbaeetxir l-M 2-M ;6-F 17-F !8-F 50-F 52-F 5 9 -f i. ;> 64-F ^oo i Location Abdomen Panereaa Abdomen Lymph node Abdomen Abdomen Abdomen AAbddreonmaelngland Abdomen I O TABLE XLVIII TEST MATERIAL: Aroclor 1260 Tw o-Y ear Chronic O ral Toxicity Study - Albino Rata Description of Tumor Findings Group: Control W eight 11.76 6345..9089 - mm 88.92 Size <c m )________________________ 85 xx 12 xx 22 - 2x2x1 2x2x3 -_ . 13x11x4 C lassificatio n Mammary fibroadenoma A denocarcino m a MM aamm mm aarryy ffiibbrrooaaddeennoommaa Reticulum cell sarcoma M ammary fibroadenoma M ammary fibroadenoma Mammary fibroadenoma MPhacmocmharorymfoicbyrotoamdeanom a F ibroadenom a , f MTooennstths 24 24 24 24 24 7 24 24 24 ir o Animal NanudmSbeexr rij; 99-M 127-F i 128-F 118-F kT1. 342 O 51-F : co 152-F Xr> o Location Pituitary AP ibtduoitmareyn AP ibtduoitmareyn APibtduoitma eryn Ovary Abdomen Abdomen TABLE XLDC * TEST MATERIAL: A roclor 1260 Two-Year Chronic O ral Toxicity Study - Albino Rata Description of Tumor Findings Group; ! ppm 1 (Wg reaimg hat) - 25.00 .60.- 80*'' 20.07 a 14.89 540.00 Size (cm) - 6x3x1 5 x 6 x 2 - - 13 X 15 X 2 ' C larification 'Chromophobe adenoma 1/ MCharmommoapryhofbiebraodaedneonmoma a ^1CMharmommoapryhofbiebraodaedneonmoma a 'ii MCy.harm!ommoaprhyofbiebraodaedneonmoma a '"Adenoma * Mammary fibroadenoma Mammary fibroadenoma MTooennstths 20 24 21 124 24 24 22 (r O O TABLEL Q TEST MATERIAL: A roclor 1260 Two-Year Chronic O ral Toxicity Study - Albino Rata Description of Tumor Findings Group: 10 ppm NaAnundmimSbeaexlr_________ Location_________ (Wgreaimghst) ______ S(cimze)___________________C lassification____________________MTooennstths ' 205-F 208-F 213-F 216-F Abdomen Pituitary Abdomen Right shoulder 190. 00 - 138.00 9x5x4 - ^ `Mammary fibroadenoma i*Chromophobe adenoma i Mammary fibroadenoma ^ Subcutaneous tumor 24 24 24 23 220-F AP ibtduoitmareyn 9 .-5 7 _ - /`'MChaommmopahryobfeibardoeandoemnoam a 24 221-F SAurbebdgmoimoanxenillary 14.44 29.0 2x3x1 3x5x2 i Fibroadenoma * Mammary fibroadenoma 24 n< 0( 343 f I e a2NAn2uVnd-miFmSbeaexlr 233-F 234-F Location Lereftgifoenm oral Pituitary AP abndeo mr eean o I TABLE L continued TEST MATERIAL: Aroclor 1260 Two-Year Chronic O ral Toxicity Study - Albino Rata Description of Tumor Findings Group: 10 ppm i (Wg reaimg hat) 56. 00 S(cimze) 6x8x2 C lassificatio n i f Subcutaneous tumor - - K Chromophobe adenoma 60. 82 6 x 4 x 3 ^'IMslaemt mcealrlyadfiebnroomadaenom a 9 i i MTooennatth s 6 24 24 11 I1 5\t1i% 9 344 oc 01 looo*>i 345 & aNAnudnmimSbeeaxlr 244-M 264-M 281 -F i 293-F 294-F 301,F. D Location Pancreas Pancreas Abdomen Liver Acbadvoimtyinal Liver ( 0 1 TABLE LI TEST MATERIAL Aroclor 1260 Two-Year.Chronic O ral TojdcUy Study - Albino Rata Description oi Tumor Findings Group: 100 ppm I (Wd reaimg hst) - 35.04 50.75 S(cimze) - " - 6x4x2 6x4x3 C lassificatio n 1 Adenoma /Islet cell adenoma / Mammary fibroadenoma Lymphosarcoma ^ Fibroma i - Lymphosarcoma r i) MTooennstths 24 21 24 23 24 ** c \ [ h VV ' 23 i< & KaAmunimimSbeeaxlr ' 302-F 308-F ' 311-F 312-M 314-F 1 Location Lymph node Pituitary Abdomen Pituitary Abdomen t r- Cf i TABLE LI continued TEST MATERIAL: Aroclor 1260 Two-Year Chronic O ral Toxicity Study - Albino Rate Deflcription of Tumor Findings Group: 100 ppm j (Wgreaimgh*t) - M e 00 O 26.00 Size 41 xx 32 xx 12 5x4x3 C lassificatio n Lymphosarcoma ^'Chromophobe adenoma ^(MMaammmm aarryy ffiibbrrooaaddeennoommaa . //Chromophobe adenoma S Mammary fibroadenoma f MTooennatlhs 24 24 24 24 24 o * n o /f Bl CiT TEST J. .U REPORT TO MONSANTO COMPANY TWO - YEAR CHIRANORANOLICCBLIONORORAR1L2A5TT4OSXICITY WITH NOVEMBER 12, 1971 1BT NO. B7298 L Introduction At the request of Monsanto Company, a tw o-year chronic o ral toxicity study was conducted using albino rats to determ ine the potential toxicity of Aroclor 1254, Lot No. AK-38. The following report represent: the results of this investigation. ACM 00 35** 347 00 k.T 5T CjriC . 2. Summary A tw o-year chronic toxicity study was conducted using albino rats fed diets containing 1 (T-I), 10 (T-II) or 100 (T - III) ppm A roclor 1254. Food consum ption was not altered in any test group. Body weight gains of te st and control anim als did not differ after 3 or 12 months of testing. A fter 24 m onths fem ales fed 100 ppm A roclor 1254 had gained less w eight than the control fem ales. Weight gains of the male rats did not differ from the controls. The number of anim als dying and the time at which death occurred did not differ among test and control groups. Hem atological and clinical blood chem istry studies conducted after 3, 6, 9. 12. 18, or 24 months did not reveal any affects related to A roclor 1254. U rine analyses failed to reveal any difference between test and -control rats. . ! At sa c rific e after 3, 6, or 12 months on te st, organ w eights, organ to body weight and organ to brain weight ratios disclosed several random ly occurring intergroup differences. The lack of any consistent dose related response and the absence of any deleterious histopathologic change confirm that these differences were not related to the ingestion of Aroclor 1254. At and liv in both the final sacrifice after 24 months on te st, the absolute liver w eight er to body weight or brain weight ratios were significantly elevated T-I1I m ales and fem ales. Histologic exam inations of the liv e rs i i* fro m the T -III group revealed several anim als v. ilh vacuolar change. ^ AOK 0035 4 348 oc rT i T 3 T his lesion is m orphologically indicative- of fatty degeneration. Specific fat stains confirm ed the presence of fat in these vacuoles. Focal h y p ertro p and focal hyperplasia were also found in the livers from anim als fed A roclor 1254. H yperplasia of the urinary bladder was found in anim als from the contr: group and from each of the test groups. This hyperplasia was usually associated with cystitis. None of the tum ors found could be related to the ingestion of A roclor 1254 and are considered norm al for a random population of rats this age. Respectfully submitted, INDUSTRIAL BIO-TEST LABORATORIES. INC R epo rt p rep ared by: ARPhastisliiTsptoaSxnt.itcSiTtmyoixtihc,olBog.Sis.t R eport approved by: JSRaearnthveTp3'iroxGBi.croitPuyplanLkeader SPeacutlioLn. HWeardig, hTt,oxPiici.oDlo.gy Novem ber 12, 1971 bb:hp Manager, Toxicology ACM OC 3 OC 349 E I0 T E S T Jdyudyuai. Jt%c. C III. Procedure A. Experim ental Animals The anim als employed in the test w ere C harles River Strain* albino rats. F our hundred rats (200 male and 200 female) were selected for the experim ent, ear-punched with the anim al num ber assigned and housed individually in standard w ire-bottom ed steel rat cages. Each cage bore a color-coded card identifying the rat with respect to project number, dietary level assignment, individual number and sex. B. O rganization of Groups A stru ctural outline of the experim ent is given in Table I. TABLE I TEST MATERIAL: A roclor 1254 Two-Year Chronic O ral Toxicity Study - Albino Rats Outline of Experim ent Grouo NMuamleber of FAenmimalaelss D ie(toaorym)L evel C o n tro l 50 50 None A dm inistered T -I 50 50 1 T -II 50 50 T - m 50 50 100 * Charles R iver Breeding Laboratories, North Wilmington, M ass. mx 350 0 r 0354 8 I TEST cI.*:. 5 C. Dicta, Feeding and Food Consumption All diets were prepared in the central diet room of this laboratory. The basic ration from which all diets were constructed was a standard, pulverized stock ra t ration*. The diet for any given te st group was prepared by blending the calculated amount of Aroclor 1254 with a pre-w eighed portion of the stock ration in a Hobart m ixer. F resh diets were prepared each week and every rat was offered an amount of food sufficient for ad libitum feeding. Food consumption was recorded for five rats of each sex in every, group weekly for the first three months and monthly for the next nine months. Thereafter, periodic spot checks were made. D. Body W eights and '''eight Gains Initially, the body weight of each rat in every group was deter* mined and recorded. Thereafter, individual weighings were made weekly for the firs t 13 weeks and monthly th erea fte r until the conclusior--n of the investigation. E. M ortality and Reactions Checks for m ortality and abnorm al behavioral reactions w ere m ade daily throughout the investigation. F. Hem atologic Studies and Urine Analyses *' j11 Blood studies, including determ inations of hemoglobin concentra- tion, hem atocrit value, erythrocyte count and both total and differential * Purina Rat Chow. Ralston Purina Co. St. Louis. Mo. AO* 0 0 3. 0 ' 351  ! C N T E S T aAsiyutA, !!&. c 6 leukocyte counts, were conducted upon five m ales and five females from both the control and 100 ppm groups. e U rine analyses for the presence of glucose, albumin, m icro scopic elem ents, and determ inations of pH and specific gravity w ere con ducted upon urine samples at the same time intervals and from the same anim als as those employed for the blood studies. These studies were conducted after 3, 6, 9, 12, 18, and 24 months of feeding. G. Clinical Blood Chem istry Studies Determ inations of blood urea nitrogen concentration (BUN), serum alkaline phosphatase activity (SAP), fasted blood glucose concen tration and serum glutamic-pyruvic transam inase activity (SGPT) were conducted a fter 3, 6, 9, 12, 18, and 24 m onths of feeding upon the sam e rats as were the routine blood studies. H. Pathologic Studies When an anim al succumbed during the test period, a gross autopsy was perform ed. In those case when postm ortem autolysis was not ad vanced, representative tissues were taken and preserved in ten percent formalin solution for possible future histopathologic study. A fter 3, 6, and 12 months of testing, five anim als of each sex fro m each group were sacrificed and subjected to complete gross pathologic exam inations. Absolute organ weights were recorded and organ to body weight and organ to brain weight ratios computed. The following organs were ADM 0 0 3 5 Ol 3 5 2 BI O T 5 S T 2s*yuiio*us. !c. / included: liver, kidneys, spleen, gonads, heart and brain. These data w ere then subjected to statistical analysis. An Analysis of Variance was conducted first and significant effects disclosed by that treatm ent were further studies by "t"-tests. Complete m icroscopic examinations w ere conducted upon the tissu e s and organs from all control and TOO ppm group anim als sacrificed a fte r 3, 6, or 12 m onths of testing. The following tissu es and organs w ere included in the examinations: heart, trachea, lungs, liver, pancreas, esophagus, stomach, sm all intestine (duodenum, jejunum and ileum), caecun colon, spleen, lymph nodes, kidneys, urinary bladder, gonads, prostate gland, sem inal vesicles, uterus, pituitary gland, adrenal glands, salivary glands, thyroid gland, parathyroid glands, skeletal m uscle, sternum , b one, p erip h eral n erve, spinal cord and b rain .(cereb ru m , cerebellum and pons). The aforementioned tissues were prepared and stained with Hematoxyiin-Eosin stain. A fter two years of feeding, all surviving anim als were sacrificed and subjected to complete gross pathologic exam ination. The absolute weights of the liver, kidneys, spleen, gonads, h eart and brain were recorded immediately after sacrifice. M icroscopic examinations were conducted upon tissues and organs from selected anim als dying during the experim ent and upon all anim als frorr the final sacrifice. ACM 0C3f> OC 353 -at 0 I C TEST *atU*i. /** ( 8 Tissues and organa examined were the sam e as those previousl m entioned. L . Tumor Incidence and Classification A tabulation of the incidence of tum or form ation in each group w as m ade at the conclusion of the investigation. In addition, tum or data for individual anim als including location, weight, size and pathologic classification were recorded. i tiI 1 AC* C03552 354 0( a` CO C r IV. Resulta A. Body Weights and Weight Caina The male and female body weight data are assem bled in Table II. The data in this table also ineludc the 3, 12 and 24 month total weight gains. ACh OC3553 355 Of ( rf DAiert(oapcrpylmorL) e1v2eSl-lof Sex Control MF 1 MF 10 M F 100 MF O o >a uLc>nn 3ooUaLUHi>i TABLE II TEST MATERIAL: A roclor 1254 Two-Year Chronic Oral Toxicity Study - Albino Rats Body Weight and Total Weight Gain Data Summary of Mean Values 0 12 34 5 B(u6Wgdr/eaemWks:e7)ight 8 9 10 II 12 13 113336 210738 214950 321193 234642 235743 239519 420659 422740 424706 428410 424798 426970 427848 113363 210716 215930 231223 233654 234763 234968 422550 4 36 259 425707 427700 428713 429709 528059 113363 210719 215914 325 220 375 243 236943 402 2,89 4 10 293 428312 425732 427706 428748 429840 250888 113363 210774 26 197 232243 234652 235745 229756 421990 428218 424608 427500 427649 428707 428860 (Tgor9taGa0ml-aDiWsna/ yeraigt}ht 315121 31769 317562 315134 it f o DAiert<oaPrc*ylomrL) e1v2e5l4 of Sex Control MF 1 MF 10 MF 100 M F 4 429978 522829 532009 429925 utn> TABLE II continued TEST MATERIAL: A roclor 1254 Two-Year Chronic Oral Toxicity Study - Albino Rats Body W eight ar.d Total Weight Gain Data Summary of Mean Values 5 6 7 Bo(dMg/r8oaWnmtehai:)ght 9 10 II 533103 536252 539333 632125 642 359 636747 638883 525905 538017 630242 633333 635480 638504 731657 536078 539213 . 632310 634412 636574 638617 730800 532010 534016 536162 532816 630286 632372 634420 12 T(gort1aa1Glm-aMWisn/oerniagtthh)t 730910 525648 732850 529442 726 392 525963 636447 52131| -^ ..ia , ADM. OC. tr dietary Level of A roclor 1254 Sex 'Jonlrol M F 1M F 10 M F 100 M F TABLE II continued TEST MATERIAL A roclor 1254 Two-Year Chronic Oral Toxicity Study - Albino Rats ii l I Body Weight and Total Weight Gain Data Summary of Mean Values 13 14 15 16 Rudy Weight (grains) Monili: 17 18 19 20 21 22 23 4- Month Total Weight Gaii 24 (g ra m s /ra t) 728 426 746 4 14 476569 768 481 769 500 767 515 760 533 758 547 739 551 726 550 687 564 642 551 509 4 15 760 401 780 426 807 476 800 483 802 493 795 510 786 521 756329 750 537 728 542 715 553 656 540 523 404 746 774 824 780 804 *826 823 821 813 800 767 762 421 433 485 466 475 481 485 492 298 . 500 471 500 629 364 688 714 735 730 733 726 716 700 685 652 628 656 360 367 392 374 381 394 393 398 401 400 395 411 523 275* ^ Statistically significant at the 99 percent confidence limit. ui CO a DM 0 0 3 5 5 5 c B. Food Consumption The data obtained from the food consumption m easurem ents conducted during the firs t 12 m onths of feeding are su m m arised in T able HI. These data revealed no significant difference between test and control rats. The periodic checks conducted during the rem ainder of the investigation also revealed no outstanding differences between test and control anim als. A D H CC355t OC 3 5 9 ff r ,dual B I C/ T E S T J^yta^es. 0035* TABLE III TEST MATERIAL: A roclor 1254 Two-Year Chronic Oral Toxicity Study - Albino Rata Food Consumption Data Summary of Mean Valuea Dietary Level of Aroclor 1251 ______ 2_J________ Sex Food Consumption (gram s/rat/seven days) 5 6 We7ek: 8 9 10 11 Coni rol MF 9743 116400 117445 116037 110347 113337 220258 115947 210645 115818 119416 115904 115916 1 MF m87 114178 115068 116188 111438 220134 116005 119337 218 149 114846 114844 114877 114869 10 MF .19106 113099 110478 111644 112613 212913 201 159 113949 211464 119510 115912 210502 119499 100 MF 116 89 14712 19683 185 129 231 129 119805 114869 114968 114855 197 139 113879 114869 . 121 193 uj O oCT\ ACvoenrsaugme pFtiooond 117440 113724 118316 187 152 * ADM 0035 TABLE III continued TEST MATERIAL: A roclor 1254 Tw o-Y ear Chronic O ral Toxicily Study - Albino Rata Food Consumption Data Summary of Mean Values DAietraor1cynlopLrnel1v2e5l4of Sex 4 5 6 (g rFa7omods /rCMaotofn/tnssteuhvm:epntid9oanys) 10 11 12 (g ra mACsvo/ernnrsautg/msoepvFl eioononddavs) Cont rol MF 119468 118549 116368 112417 16) 138 118542 117609 114710 118277 117462 1 MF 114819 118519 118447 119682 119405 115900 115917 115223 112960 118465 10 MF 190 119 119318 118498 119468 119500 118485 119318 118462 163 149 114847 1*00 MF 114789 114618 114940 116729 116837 115812 114987 114810 118378 11488) ta i (. i ir C. M ortality and Reactions A frequency distribution of natural deaths occurring during the investigation! appears in Table IV, No untoward behavioral reactions were noted among any of the anim als employed in the investigation. ACM CC3 OC 362 (r O D iet(aprpymL) eve! Control 1 IO 100 Sex MF MF MF MF V TADLE IV 1* TEST MATERIAL: A roclor 1254 Two-Year Chronic Oral Toxicily Study - Albino Rata 1t M ortality Data Frequency Distribution of Deaths ii 1-5 4-6 7 - F 9 re q uency 10-12 MDoisnttrh1ibs3:u-1ti5o n of Dcatlie 16-18 19-21 22-24 N uTmobtaelr DTeeasdt_e_d_' 00 00 00 21 3i 75 67 93 2159//3355 02 00 00 21 52 61 85 93 3104//3355 00 01- 01 41 23 53 48 170 22 72 // 33 55 01 00 21 43 42 52 47 69 22 73 // 33 55 * Does not in elude the five anim als of each sex from every group sacrificed for interim pathologic Studie 3. oLu\ ACH C03S6C cL I O l 5 T c. 13 D. H em atologic arid C linical Blood C hem istry Studies Mean m ale and female hematologic and clinical blood chem istry data a re su m m arised in Tables V through EC. Values for all param eters investigated w ere within the norm al range for the albino rat. Ho significant differences between test and control values were observed. O O i AOM C 03S6l 00 364 f\ t o D(Lipeentvamerlly Control 0 ' o TABLE V TEST MATERIAL: A roclor 1254 Tw o-Y ear Chronic O ral Toxicity Study - Albino R ats Hematologic Data Summary of Mean Values Sex 3 T 6 o t(athl oLu9esMaunkodonscthy/1:tm2emC-*o)un1t8 24 3 6 E9r(ymtlhlrlMiooconynati/elmi1:2Cmo^u)nt 18 M 14.0 15.4 10. 1 11. 1 9.9 11.2 8. 1 8.2 8.7 8. 8 7.6 F . 9. 1 9.4 6.7 7.6 8.8 7.6 7.5 7.7 7.3 . 7.8 7. 7 24 6.5 100 M 15. 1 15.2 10.9 11.0 9.8 10.2 7.5 7.7 8. 1 7.7 8.0 8.0 F 11.6 12.2 7.3 8.7 6.6 11.8 7.5 7.6 7.7 6.9 7.3 6.4 0* OD I I r\ ! ACH 003562 00 365 / TABLE VI TEST MATERIAL: A roclor 1254 Tw o-Y ear Chronic O ral Toxicity Study - Albino Rate Hematologic Data Summary of Mean Values D(Lipceplvmaer)ly Sex 3 Hem 6 o g lo(b9giMn/ 1o0Cn0tohmn:1c2l)e n t r a t i1o8n 24 3 Control M F 17. 1 17.7 15.7 17.6 16. 1 13.6 51 16.9 17.4 14. 1 16.7 16.4 14.6 50 H em atocrit Valu 6 9 1M(o%n)th1:2 18 49 48 50 41 47 43 . 46 42 100 M 15.6 17.6 13.8 15.6 15.7 15.3 47 47 42 44 41 F 16.5 17.8 13.9 14.5 14.5 12.7 48 47 42 40 37 24 35 38 40 32 On LJ ( I tItI I% rc PStOO fr oo @ D(Lipeentvamerlly Control TABLE VII TEST MATERIAL; A roclor 1254 Tw o-Y ear Chronic Oral Toxicity Study - Albino Rats Hematologic Data Summary of Mean Values i Sex 3 6 DLify9fmeMrpeohnnotticha1y:l2teLseuko1c8yte Count 24 (Number 1 of Cells 6 Np9eeMru tHor onuptnh1hd:2irles d ) 18 24 M 82.0 86.6 80. 4 78. 8 79.0 65.4 16.0 11.4 18.6 20.6 20. 0 32. 2 F 81.0 86.6 86.8 89.0 70.2 61.4 15.4 11.6 11.8 . 10.0 29.2 36.0 100 M 88.2 79.6 85.8 85.2 69.8 68.0 10. 8 20.2 I ) . 8 14.2 29.0 30.2 F 92.2 92.0 79.6 84.6 79.0 61.0 7.4 7.8 20.2 15.0 20.4 37.6 i I < III OCO I ADM 00356** ooo D(Lineeptvmaer)ly Control Sex 3 M F 0.6 0.6 TABLE Vll continued TEST MATERIAL A roclor 1254 Tw o-Y ear Chronic O ral Toxicity Study - Albino Rats Hematologic Data Summary of Mean Values 1 6 D iMf9feMorneoonncityliiat:1el2s Leukocyte 18 Count 24 (Number 3 of C 6 ells Ep9oeMsrinoHonupthnh1:d2ilrsed) 18 0.0 0.0 0.4 0.2 1.2 1.4 2.0 1.0 0. 2 0. 8 0.0 0.0 0.2 1.0 1.0 1.8 1.4 0.2 0.6 24 1.6 1.6 100 M 0 .0 0 .0 0.0 0.0 0. 8 1.0 0.2 0.4 0.6 1.2 1.0 F 0.0 0.0 0.0 0.0 0.0 1.0 0.4 0.2 0.2 0.4 0.6 0.4 oO oo ADM 0C356 I I/ r O D(Lipeeptvmaer)ly Control Sex M F 100 M F TADLE VII continued TEST MATERIAL: A roclor 1254 / Tw o-Y ear Chronic O ral Toxicity Study - Albino Rata Hematologic Data Summary of Mean Values 3 D ifferen tial 6 L e u k o c y te9 C oBunMatsoo(npNlhhui:mls ber 12 of Celia por Hundred) IR ____ 24 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 oO AOM 003 O o o TABLE VIII TEST MATERIAL: A roclor 1254 Two-Year Chronic Oral Toxicity Study - Albino Rata Hematologic Data Summary of Mean Values i DL(ipeeptvmaer)ly Sex 3 6 STerrua9mns(aGDmalMudinot1oaa2nmUstehnic;iAt-sP)cy1ti8rvuivtyic 24 3 6 BlooCdo9nU(Mmcrcegonasnttrh*No1/:.t2)iitorongen18 Control M F 38 33 48 39 45 38 45 42 42 32 36 30 17 14 15 16 12 15 10 9 14 13 100 M 33 32 43 ' 50 38 41 14 15 13 12 11 F 32 46 49 61 46 78 16 15 13 14 13 24 15 11 15 15 'S nu K v K o ACM GC3567 r 4 r o oo Dietary Level (ppm) Control Sex M F TABLE IX TEST MATERIAL: A roclor 1254 Two-Year Chronic Oral Toxicity Study - Albino Rata Hematologic Data Summary of Mean Values Fasted Blood Glucoao Concentration S e r u m A lkaAlcintioviPtyh o s p h a t a s e (mg* (Klng-Armstrong Units) 1 6 9 Month1;2 18 24 3 6 9 Month1:2 18 24 128 123 89 88 138 99 28.6 24.7 21.5 20. 3 16.2 130 118 115 92 134 109 18.9 17.8 10.6 11.9 16. 8 20. 2 100 M 109 113 129 128 124 115 35.4 23.2 27.4 27. 1 14.6 23.5 F 120 10? 124 113 132 107 17. 1 18. 1 19.3 16.7 10.0 21.6 IIUI*NV ru K i v*. ACM 0 0 3 5 6 6 IuN. BIOVf S T 3nc. vi* 26 E. U rine Analyses Mean male and female urine analyses data are sum m arised in ; Table* X through XIX. No differences were noted between the urine from control and test animals at the intervals of examination. \ 00ACM C03 569 372 rf J*JuU**i BlOO bSr JsJcytcJaucu 'Jc* TABLE X TEST MATERIAL: A roclor 1254 Two-Year Chronic Oral Toxicity Study - Albino Rata Urine Analyaea Data Summary of Mean Values D(Lipeeptvmaerlly Sex 3 6 9GMlounctohs: e 12 18 24 3 6 9AMlbuonmthin:12 18 24 Control M F n n n n n n nn n *n nn nn n n 1 n 1 42 43 n t 42 M n n n n n n n n t t t 42 100 F n n n n n n n n t t t 43 Key: nt 4I 44423! === == tn31r0ea00gctaeott;oiv1l03ee00s0amrtgnhg/a/n11000300mmml lguur/i1rn0ine0em l m30o0reto th5a0n0 m50g0/ m10g0 /ml0l0umrilneurin u e r in e tv ZiZ t?COu tr 0 GO TABLE XI TEST MATERIAL: A roclor 1254 Tw o-Y ear Chronic O ral Toxicity Study - Albino Rata Urine Analyses Data Summary of Mean Values vavor.iy St-x 3 6 M icro sc 9 Mo poincthE:1l2e m en ts 18 24 3 6 9 MopnHth:12 18 24 r. i : *^ n n n n n n n 1 7 7 t t88 6 7 77 86 6 6 .* *i n n n t t 7 7 6 7 6 6 n n N t t 8 8 7 7 6 6 V CP OH , 1C7a1l t\ CoD +121 1 ==i! iNt51nr0aolsocrlaomel1i;av0ISlolpepteser rtlohlowawn p5poowpweerer rfloifewiledlpdo w er field I J : m ore than 15 per low power field f0s0i AHH 00357 Oo \ DiLineoptvmacr)ly Control Sex M F M 100 F TABLE XII TEST MATERIAL: Aroclor 1254 Two-Year Chronic O ral Toxicity Study - Albino Rats Urine Analyses Data Summary of Mean Values 3 6 S 9 p e c iMf iconGthr:a v i t y12 1.029 1.022 1.033 1.027 1.020 1.019 1.025 1.024 1.018 1.021 1.029 1.027 1.020 1.018 1.023 1.022 18 1.042 1.032 1.037 1.029 24 1.051 1.039 1.027 1.031 t o ?sto'j wgr >4 j f M^ I c ww F. Pathologic Studies 1. Three Month Sacrifice a. Gross Pathologic Finding No outstanding differences were noted between test and control rats upon gross pathological examination. b. OOrrggaann tWo e5igrhatinanVd.'cOigrigttanRatotio3oDdavtaand The results of the statistical analyses conducted on absolute organ w eights, organ to body weight and organ to brain weight ratio s are sum m arized in Tables XIII through XVIII. Significant differences between a test group and the control group are designated by asterisks following the test values. Organ weights, organ to body weight and organ to brain weight ratios disclosed several randomly occurring intergroup differences. The lack of any consistent dose related response and the absence of any deleterious histopathologic change confirm that these differences were not related to the ingestion of Aroclor 1254. A O h C03573 0 ( 376 t TABLE XIII TEST MATERIAL: A roclor 1254 Tw o-Y ear Chronic O ral Toxicity Study - Albino Rata Organ Weight and Ratio Data Three-Month Sacrifice Summary of Mean Values Organ: Liver !I; DAireota(cprloyopfmr L)1e2v5e1l I: Control M Orga alca n(gW) eight Fcma lc a 21.4 13.0 O r gMa na/lBe so( dg y/ 1 0W0 eFigge) hmt Ratio ales 4.13 4.16 O rg an /B r M ales a l(nc /Wg )Fe iegmh ta lRe ast i o 10.3 6.82 1 24.0 13.5 4.34 4.34 11.7 6.85 10 22.8 13. 1 4.59 4.29 10.9 6.85 Q 100 28.0* 13.8 5.25 4.89 u> sj * SS ttaattiissttiiccaallllyy significant significant difference difference at at the the 95 99 percent percent confidence confidence level. level. 14.6** 7. 11 I seoo B10X-TEST ACM OC357i 0 0 378 D u t a r yof L evel A ro(cplopmr l1_2_5_4____ C o n tro l 1 10 100 TABLE XIV TEST MATERIAL: A roclor 1254 Two-Year Chronic Oral Toxicity Study - Albino Rats Organ Weight and Ratio Data Three-Month Sacrifice Summary of Mean Values Organ: Kidney* I M a lOesr_g_a_n_(g_W)_ Feiegmhta le s ________O_r_gMa na/lDe so(_dg__/y1_0_W_0 eFgieg)mht aRleast_io______O__r_gMa na/lBesr_a_i_(n_g_/W_g)Feiegmhta Ratio les 4.03 2.49 ' 0.782 0.802 .1.9 5 1.31 4.30 2.62 0.778 0.845 2.09 1.32 4.05 2.61 4.21 2.74 . 0.821 0.792 0.852 0.975 1.94 1.36 2.19 1.42 K yK* M t/ Diet A ro ac(prloonyfmr L)1e2v5e4l C o n tro l 1 10 100 TADLlE XV TEST MATERIAL: A roclor 1254 Tw o-Y ear Chronic Oral Toxicity Study - Albino Rats Organ Weight and Ratio Data Three-Month Sacrifice 1 Summary of Mean Values Organ: Spleen Organ Weight (g) Males Females 0.766 0.578 0.942 0.668 0.766 0.586 0.814 0.542 Organ/Body Weight Ratio {g/100 g) Males Females 0.150 0.184 0. 167 0.217 0.154 0.191 0.153 0.192 O rgan/B rain Weight Ratio (g/g) Males Female s 0.371 0.302 0.454 0. 338 0.368 0.308 0.425 0.281 ACM C03576 r"N r / Diet A ro a(cprlooypfmr L)1e2v5e4l Coni rol 1 10 100 TABLE XVI TEST MATERIAL: A roclor 1254 Tw o-Y ear Chronic Oral Toxicily Study - Albino Rata Organ Weight and Ratio Data Three-Month Sacrifice 1 Summary of Mean Values Organ: Gonads M Org ale* an(cW) eight F emale 3.60 0. 114 3.50 0.134 3.55 0.110 3.82 0. 120 O rgMana/lBeso(dc/y10W0eF0ige)mhtaRleastio 0.698 0.0370 0.637 0.0431 0.720 0.0361 0.718 0.0426 O r g an /B r M ales a iing /Wf i )Fe iegmh ta Ratio les 1.74 0.0599 1.70 0.0675 ` 1 .7 0 ' 0.0568 1.99 0.0618 08 0 0 - *ov AOM 0 0 3 5 7 8 r. r O D ietaroyf Level A ro c(plopmr )1254 C o n tro l 1 10 100 OO TABLE XVII TEST MATERIAL: A roclor 1254 Tw o-Y ear Chronic Oral Toxicity Study - Albino Rata Organ Weight and Ratio Data Three-Month Sacrifice j Summary of Mean Values Organ: Heart Organ Weight Malea (g) F e m a l e s 1.59 1.05 1.56 1.02 1.49 0.984 1.58 0.992 Organ/Body Weight Ratio M a l e s _(_g_/_*_0__0 Fge)m a l e s 0.307 0.339 0.283 0.332 0.302 0.322 0.297 0.352 O rgan/B rain Weight Ratio M a l e s (g' /g)F e m a l e s 0.767 0.551 0.756 0.516 0.713 0.515 0.817 0.512 r' r O nx U> 00 l DAireotac(prlooypfmr L)1e2v5e4l Cont rol l 10 100 TABLE XVIII TEST MATERIAL: A roclor 1254 Tw o-Y ear Chronic O ral Toxicity Study - Albino Rata Organ Weight and Ratio Data Three-Month Sacrifice .1 Summary of Mean Values M Org alca a n(gW) eight F em ale 2.07 1.91 Organ: Drain . Or gMa na/lDe so(dg y/1 0W0 eFgige) mh t aRl east io 0.402 0.616 Fifn Sa la M ales cBroi(fdgiyc) eWd eRigahtat Fem ales 518 314 2.07 1.99 0.376 0,647 553 311 2.09 1.91 0.424 0.625 499- 307 1.95 1.94 0.366 0.688 434 281 003579 /._ Bl q f SST JsS j*c. <jT l j: c Histopathologic Findings Histopathologie examination of tissues and organs taken from all anim als from both the control and 100 ppm groups was conducted. Tables XIX and XX list all histopathologic changes noted. All of the lesions noted in the m icroscopic exam ination of tissues were those of spontaneous disease and are not unusual for the albino rat. The most frequent findings were lesions in the trachea and lungs, indicating chronic murine pneumonia. These oc curred in the control as well as the rats fed A roclor 12S4. ADf* 0C358C 0 0 383 TABLE XIX TEST MATERIAL: A roclor 1254 Tw o-Y ear Chronic O ral Toxicity Study - Albino Rata Histopathologic Changes Three-Month Sacrifice Croup: Control NAunmimbearlsof O rcan Exam ined Findings Incidence AGverar- 5 Males LTurancgh ea TCdrhairscoehnaeiscietirse s p ira to ry U rinary Bladder Hyperplasia i l.C 3i ` 1l..C0 5 Fem ales Lung Cdhirsoenaisce re sp ira to ry 1 ' 1.0 Q ------------------------------------------------------------------------------------------All other tissues and organs were normal histologically. Grading Svstem 1 452301......00050O ==s=*= emmsmsexliiovitglnrcddheiemrmteraaetle O ACM 003 0 ( 384 TABLE XX TEST MATERIAL: A roclor 1254 Two-Year Chronic O ral Toxicity Study - Albino Rats Histopathologic Changes Three-Month Sacrifice Croup: 100 ppm NAunmimbearlsof --O rgan Examined.. ----------Findings Incidence . .A. Gverardagee 5 M ales LTurnacgh ea CTdhrairscoehnaeiscietirse s p ira to ry 1 3 1.0 1.0 5 Fem ales Trachea Tracheitis 1 1.0 All other tissues and organs were normal histologically. Grading System 045231......500000 ====== emmmssexliiiovtgnlrdedhieemrtmeraaetle \ c* oojsa o c 385 JtuUii'-** 0 I I c 3 l -T-i-->*-->uc.i, yc. 2. Six-Month Sacrifice a. Gross Pathologic Findings No outstanding differences were noted between test and control anim als. b. COrrgraann tWo eBigrhatinanVd.'eCirrrr.tanRatotioBDodavtaand The results of the statistical analyses conducted on absolut organ weights, organ to*body weight and organ to brain w eight'" ratios are sum m arized in Tables XXI through XXVL Organ weights, organ to bod/ weight and organ to brain weight ratios disclosed! several randomly occurring intergroup differences. The lack of any consistent dose related response and the absence of any deleterious histopathologic change confirm that these differences, w ere not related to the ingestion of A roclor 1254. AC* CC35 tr DAireotca(prioopyfmr L)1e2v5e4l Control 1 10 too -i TABLE XXII # TEST MATERIAL: A rocior 1254 Two-Year Chronic Oral Toxicity Study - Albino Rata Organ Weight and Ratio Data Six-Month Sacrifice Summary of Mean Values Organ: Kidneys Organ Weight M ales <) F em ales 4.04 2.79 3.80 2.58 3.22*' 2.50 3.23* 2.43 O r gMa na/lBe so{dy/1 0W0 eFgige)mht Ratio ales 0.664 0.806 0.715 0.784 0.703 0.780 0.700 0.861 O rgan/D rain Weight Ratio M ales (g/ g)F em ales 2.06 1.43 1.75* 1.39 1.57? 1.31 1.68* 1.25 : ! 0 C r\ aif. hIt1K. i V O Statistically significant difference at (lie 95 percent confidence level# I4 Af C0358 tr TA9LE XXI TEST MATERIAL: A roclor 1254 Tw o-Y ear Chronic Oral Toxicity Study - Albino Rata Organ Weight and Ratio Data Six-Month Sacrifice Summary of Mean Valuea Organ: Liver- DAireotca(orloonyfrritL)1e2v5e4l Organ Weight M ales <c) F em ales O rgan/Body W M alea( e /lo o eFbige)mht Ratio ales O rgan/B rain Weight Ratio M alea (g/ c)F em ales Cont rol 22.9 13.1 3.74 3.77 11.7 6.71 1 16.1** 10.3* . 3. Of** 3.11** 7.45** 5.54* 10 12.9** 9.54* 2 .94=* 6.29** 4.99* 100 19.2 12.4 4.14 4.40 10.0 6.39 ----- ,............. ......... * Statistically significant difference at the 95 percent confidence level. v< S t a t i s t i c a l l y significant d i f f e r e n c e at the 99 p e r c e n t confidence level. i% c ( fisI IILwLlh. y- V*. 35COO 00M r DA.rcotacHrlpooyfmr L)1e2v5e4l Cont rol 1 10 *100 TAD^E XXIII TEST MATERIAL: A roclor 1254 Tw o-Y ear Chronic O ral Toxicity Study - Albino Rata Organ Weight and Ratio Data Six-Month Sacrifice Summary of Mean Values. Organ: Spleen M O ale rg s a n(gWj Feiegmhtale s 0.752 0.684 0.830 0.602 0.588 0.594 0.684 0.512 O r gMa na/lDe so( dg y/ 1 0W0 eFgige) ht m Ratio ales 0. 122 0.196 6.155 0.182 0.128 0.184 0.150 0.180 O rg an /B r M ales a t(ng /Wg )Fe iegmh ta R atio les 0. 384 0. 350 0.384 0. 324 0.287 0.311 0.356 0.264 \ ! i ACM 003586 M OC358 OC 390 o DAireotca(olroonyfmr L)1e2v5e4l Cont rol 1 10 100 nto. o TADI.E XXIV i TEST MATERIAL: A roclor 1254 Two-Year Chronic Oral Toxicity Study - Albino Rats Organ Weight and Ratio Data Six-Month Sacrifice Summary of Mean Values Organ: Gonads o / Organ Weight M ales (c) F em ales 3.55 0.0960 3.67 0.0922 3.30 .0.0868 3.44 0.104 Organ/Body Weight Ratio M ales(g/100Fge)m ales 0.593 0.0279 O'. 691 0.0280 0.724 0.0272 0.747 0.0364 O rgan/B rain Weight Ratio M ales (g/ g)F em a le s 1.81 0.0492 1.70 0.0496 1.61 0.0454 1.79 0.0536 i i i\ iiitl t i ACM CC3 O DAireotacrloyofr Level 1254 Cont rol 1 10 100 O o TABLE XXV TEST MATERIAL: A roclor 1254 Tw o-Y ear Chronic O ral Toxicity Study - Albino Rata Organ Weight and Ratio Data Six-Month Sacrifice Summary of Mean Values Organ: Heart Organ Weight M alea (8) F em ales 1.70 1.05 1.58 1.04 1.44 1.03 1.40 1.02 O r gMa na/lBe so( dg y/ 1 0W0 eFgige)hmt Ratio ales 0.282 0.302 0.298 0.316 0.314 0.320 0.301 0.361 O rgan/B rain Weight Ratio M alet (/)F em ales 0.867 0.538 0.731 0.559 0.702 0.539 0.729 0.526 t O DA ireot ac rl ooyfr Level 1254 Cont rol 1 10 100 o TABLE XXVI I TEST MATERIAL: A roclor 1254 Two-Year Chronic Oral Toxicity Study - Albino Rat Organ Weight and Ratio Data Six-Month Sacrifice Summary of Mean Value Organ: Drain > O rgan W eight Male (C) Fem ale Organ/Dody Weight Ratio M ales(g/100Fge)m ales FoifnaSlacBroifdiyceWd eRigahtsts M ales (:) F em ales 1.96 1.95 0.320 0.560 613 348 2.16 1.86 0. 404* 0.562 534 331 2.05 1.91 0.447-* 0.593 459 322 1.92 1.94 0.414** 0.681*' 464 285 * SSttaattiissttiiccaallllyy ssiiggnniiffiiccaanntt ddiiffffeerreennccee aatt tthhee 9959 ppeerrcceenntt ccoonnffiiddeennccee lleevveell.. 392 ta K c. Histopathologie Findings Histopathologic examination of tissues and organs taken from a ll anim als from both the control and 100 ppm groups w as conducted. Tables XXVII and XXVIII list all histopathologic changes noted. All of the lesions noted in the m icroscopic exam ination of tissues w ere those of spontaneous disease and are not unusual for the albino rat. The m ost frequent findings w ere lesions in the trachea and lungs, indicating chronic murine pneumonia. These occurred in the control as w ell as the rats fed Aroclor 1254. AC* 0 0 3 * ^ 0 393 - u, < c TABLE XXVII TEST MATERIAL: A roclor 1254 Tw o-Y ear Chronic O ral Toxicity Study - Albino Rats Histopathologic Changes Six-Month Sacrifice Group: Control NAunmimbearlsof O rgan Exam ined Findings Incidence AGvrearda< 5 M ales o Trachea Lung SLkive leerta l M uscle HTFFF oooryacccpcaaaehlllr eeptpmiretnairiesciacuhhmeoiotlnai sni tgisi t i s Focal inflammation 22 21 * 11 ' 011111......550000 5 Fem ales LTLuirvanecgrh e a K id ney HHPF eoyyrcppiaceelhrr eetormmlaaciinaahgeiittiiss Focal inflammation 2111I * 211...500 01 ..50 All other tissues and organs were normal histologically. Grading System 01 ..05 s* msliignhimt al 2435 ....0000 s*> mmesexiovtlrddeeermeraete ikC* 0 0 3 * ^ 0 . 394 table xxvin TEST MATERIAL: A roclor 1254 Tw o-Y ear Chronic O ral Toxicity Study - Albino Rate Histopathologic Changes Six-Month Sacrifice Croup: 100 ppm NAunmimbearlsof Orca.n Exam ined Findings Incidence AGverardage 5 Males Trachea KLL uiidvnneger y FFTFFooooracccccaaaahllll etnpprienetaiprecsiuhhcmrheioitotilnsiasintigsitis 23l11 22001 .....00550 5 Fem ales LHTureanacgrht e a Kidney HFMFFoooyycccpoaaaeclllraenptrmrnedapeiictauhihsmreitioitsnisitis 341 21 * 30011 .....05500 All other tissues and organs were norm al histologically. Grading System 201...050 s=* mmsliiiglndhimt al 43..00 =s mseovdeererate 5.0 * extrem e ADM 003592 0( 395 l.uL-U-' * 1 ` ^ * ' = 3 1 - Jw c 3. Twelve-Month Sacrifice a. Gres Pathologic Findings Gross pathologic findings among test animals were not significantly different from those noted in control anim als. b. Organ Weight and Ratio Data The mean organ weight and ratio data collected at the 12-m onth sacrifice a re presented in Tables XXDC through XXXIV. Statistically significant differences. Are designated by asterisks following the test group value. Organ weights, organ to body weight and organ to b rain weight ratios disclosed several randomly occurring intergroup differences. The lack of any consistent dose related response and the absence of any deleterious histopathologic change confirm that these differences were not related to the ingestion of Aroclor 1254. *0* C J S 9 Ql 396 rr 9 TABLE XXIX TEST M ATERIAL: Aroclor 1254 Tw o-Y ear Chronic O ral Toxicity Study - Albino Rats '""S Twelve-Month Sacrifice Organ Weight and Ratio Data Summary of Mean Values Organ: Liver D iet(anryn nLl evel ______ M O ales _rg__a_n(_g_W)__eFigchmt a les O ___________ Mr g aa lne/sU_(_og_d/_1y_0_W_0_egFi)ge hmt Ratio O a l e s ___________ rg M an/B ales r a (ing/gW) Feiegmhta Ratio les Cont rol 22. 1 15.5 3.79 3.52 10.8 7.72 1 20.6 12.9 3.09* 3.41 9.89 7. 29 10 23.5 14.6 3.52 4.34 11.2 7.34 100 27. 1* 12. 2 4.58 + 3.43 12.7 6. 30 * S tatistically significant difference at the 95 percent confidence level. G--. *o 397 / D iet(aorpymL) evel Control l 10 100 TAB# LE XXX TEST MATERIAL: A roclor 1254 Tw o-Y ear Chronic O ral Toxicity Study - Albino Rats ^ Twelve-Month Sacrifice Organ Weight and Ratio Data Sum mary of Mean Values Organ: Kidneys Organ Weight M ales (g) Fem ales Organ/Body Weight Ratio M ales (g/100 gF)em ales O rgan/B raln Weight Ratio M ales (g/g)F e m a le s 4.04 3. 19 0.692 0.738 1.97 1.58 , 4.09 2.75 0.618 0.728 1.98 1.55 4.64 2.76 0.697 0.817 2.21 1. 39 4.39 2.78* 0.740 0.796 2.06 1.44 OCX. * S tatistically significant difference at the 95 percent confidence level u> CD I * r 1 $ 3 1 -^O I 0 7J"Vr",p"/ -=>"C D iet(aarnymL) evel C o n tro l 1 10 100 TABLE XXXI TEST MATERIAL: A roclor 1254 Tw o-Y ear Chronic O ral Toxicity Study - Albino Rata Twelve-Month Sacrifice Organ Weight and Ratio Data Summary of Mean Values Organ: Spleen Organ Weight M ales (g) F em ales Organ/Body Weight Ratio M ales (g/100 gF)em ales O rgan/B rain Weight Ratio Males (g/g) F em ales 0.778 0.714 0.904 0.754 0.796 0. 484* 0. 548 0.976 0.133 0. 107 0. 135 0. 126 0.183 0. 380 0.396 0.129 ' 0.344 0. 271 0. 161 0.430 0. 275 0. 280 0. 352 0.517 * S tatistically significant difference at the 95 percent confidence level. 1/1 399 rf D iet(anrnymL) evel Cont roi 1 10 100 TABLE XXXII TEST MATERIAL: A roclor 1254 Tw o-Y ear Chronic O ral Toxicity Study - Albino Rats Twelve-Month Sacrifice Organ Weight and Ratio Data Sum mary of Mean Values m Organ: Gonads Org an Weight M ales <g> F em ales OMrgaalne/sB(ogd/yio Wo egFi)ge mh t Ratio ales 3.46 0. 116 0.592 0.0275 3.68 0 .Ill 0.557 0.0294 3.68 0.0918 0. 550 0.0270 3. 56 0. 121 0.603 0.0334 O rgan/B raln Weight Ratio Males (g/g) Fem ales 1.70 0.0574 1.78 0.0624 1.75 0.0461 1.67 0.0624 E. tr.V n Ks I** fr 400 o Odc UUooii i4n* r i . J , ytC. ACH 003 D ieta(ornymLj evel Cont rol 1 10 too TABLE XXXIII TEST MATERIAL: A roclor 1254 Tw o-Y ear Chronic O ral Toxicity Study - Albino Rata Twelve-Month Sacrifice Organ Weight and Ratio Data Summary of Mean Values Organ: Heart Organ Weight M ales (g) F em ales Organ/Body Weight Ratio M ales (j;/100 gF)em ales O rgan/B rain W eight Ratio Males (g/g) Fem ales I . 71 1.23 0.293 0.286 1.68 1.13 0.255 0.301 1.84 1.08** 0.275 0.322 1.69 1. 14 0.284 0. 325 0.835 0.609 0.812 0.635 0.875 0.544* 0.795 0.589 /-V OCD S tatistically significant difference at the 95 percent confidence level* S tatistically significant difference at the 99 percent confidence level. f o D ieta(prnymL) evel Control 1 10 100 TABLE XXXIV TEST MATERIAL: A roclor 1254 Tw o-Y ear Chronic O ral Toxicity Study - Albino Rata Twelve-Month Sacrifice Organ Weight and Ratio Data i Summary of Mean Valuea Organ Weight Males (8) Fem ales Organ: Drain O rMgaanle/Bs (ocd/yioWo egFi)gehmt Ratio ale S aFcMriinafailecl seBdodAyniWmeaFitgeehmt(gaolrefasm s) 2.04 2.02 2.08 1.78 0. 35 0.474 0. 315 0.475 584 439 665 360 2. 10 1.99 2. 14 1.93 0. 315 0.591 0.361 0.552 669 338 596 355 * S tatistically significant difference at the 95 percent confidence level. O oK> ooIP iOr co i O - i c : i -T- a c c. Histopathologic Findings Histopathologic examination of tissues taken from each rat sacrificed from the control and 100 ppm groups a fte r 12 months of testing was conducted. T ables XXXV and XXXVI list a ll histopathologic changes noted. AC* CC3cCC 00 403  BI 0 ^ EST SMHiivuci. me. . TABLE XXXV TEST MATERIAL: A roclor 1254 Tw o-Year Chronic Oral Toxicity Study - Albino Rats Histopathologic Changes Twelve-Month Sacrifice Group: Control NAu nmi mb earl sof 5 M ales 5 Fem ales Ortran Examined TLurancgh ea U rinary Bladder LTurancgh ea Colon Findings TCCdrahalircscoeuhnaleiuscisetirse s p ira to ry TCdrhairscoehnaiescietrise s p ira to ry P a ra site s Incidence i 2i 1. ii AGv erar l.l ll ..ll l.l ll ..(l A ll other tissu es ar.d organs w ere norm al histologically. Grading System 423501......000005 =s==s= emsmmselxiioivtglnrddeheiermtmeraaetle l a CM 0C36C1 0 ( 404 illdi BI ^ / EST 3e c !'i TABLE XXXVI TEST MATERIAL: A roclor 1254 Tw o-Y ear Chronic Oral Toxicity Study - Albino Rata Histopathologic Changes Twelve-Month Sacrifice Group: 100 ppm NAumnibmear lsof EOxarmgainned Findir.es I n c i d e n c e "---ACv rear ac 5 Males Lung Chronic respiratory disease 4 1.0 5 F em ales AHTLurdeanracgerhnt eaal FTCCorhoacnrcoaghnleeismcittiyoirsoenscparidraittiosry d isea se 1111 1111 ....0000 All other tissues and organs were norm al histologically. Gradir.e Svstem 452301......000005 ====== emmsmsexlioiivtglnrddeheiemrtmeraaetle ACM 003ec o u 405 BI0 EST J^ s c 60 4. Final Sacrifice a G ross Pathologic Findings Gross pathologic findings among test anim als were not significantly different from those noted in control anim als, b. Organ V.'eight and Ratio Data The mean organ weight and ratio data collected at the final sacrifice are presented in Tables XXXVQ through XLII. Statistically significant differences, are designated by asterisks following the test group value. Absolute liver weight, liver to body weight and liv er to brain weight ratios were significantly elevated in both m ale and fem ale ra ts fed 100 ppm A roclor 1254. Other organ w eights, organ to body weight and organ to brain weight ratios disclos'ed sev eral randomly oc curring intergroup differences. The lack of any consistent dose related response and the absence of any deleterious histopathologic change confirm that these differences were not related to the ingestion of A roclor 1254. ACM 0C3tC 406 000 fr Dietary Level (ppm) Control 1 iO 100 TABLE XXXVII TEST MATERIAL: A roclor 1254 Two-Year Chronic Oral Toxicity Study - Albino Rata O rgan W eight iand Ratio Data Summary of Mean Values i Final Sacrifice Organ Weight (g) Malea F em ales Organ; Liver O rgan/B o(dgy/10W0 egig) ht R atio M ales F em ales 22.0 16. 3 3.47 3.05 19.5 16. 1 2.99 3. 10 23.9 19.5 3.21 3. 84* 30.2** 32.1 ** 4.75* 8.62** * Statistically algnificant difference at the 95 percent confidence level. * ** Statistically significant difference at the 99 percent confidence level. AUM 00360*1 O IrS. t:V w ' s ? itnn ic;- O rgan/D (rgal/ngl W eight R atio ^ M ales F em ales 10. 10 8.76* 8.42 8. 31 / - X1 11.40* 10. 30 14.10** 17. 10** 000 407 Q . Diet(aprpymL) evel Control 1 100 TABLE XXXVIII i TEST MATERIAL: A roclor 1254 Tw o-Y ear Chronic O ral Toxicity Study - Albino Rata Organ Weight and Ratio Data Summary of Mean Values Final Sacrifice i M ales O rg a(ng)W eight Fe m a le s Organ; Kidney OMraglaens /llu(tgly/10W0eigg)Fhte R m atio ales 5.57 3.48 0.877 0.646 5. 52 3.68 0.868 0.706 5.63 3.47 0.761 0.717 4.74 3.44 0.749 0.899* O rgan M ales /B r( ga i/ng ) W eight Ratio Fem ales f* . 2.57 1.79 2.48 1. 8 8 ^ 2.70 1. 84 2.21 1.82 * Statistically significant difference at the 05 percent confidence level. 000 408 a AOM ( l n u n c is D ieta(prypmL) evel Cont rol 1 10 100 TABLE XXXIX TEST MATERIAL: Aroclor 1254 Two-Year Chronic Oral Toxicity Study - Albino Rate O rgan W eight iand Ratio Data Summary of Mean Values Final Sacrifice Organ Weight M ales (C) F em ales Organ: Spleen - O rgan/Body Weight Ratio M ales (g/100 g)F em ales 1.15 0.96 0.182 0.181 1.26 1.06 0.189 0.237 1.57 0.86 0.220 0.175 1.04 0.66 0.164 0.174 * mto l l O rg an /B raln W eight R allo I Males (g/gi Fem ales 0.520 0.492 0.568 0.562 0.749 . 0.462 0.489 0.352 0 0 0 409 oo ooOaJ o *\ o D iet(aprpymL) evel Control 1 10 100 TABLE XL I TEST MATERIAL: A roclor 1254 Tw o-Y ear Chronic O ral Toxicity Study - Albino Rats O rgan Weight iand Ratio Data Summary of Mean Values Final Sacrifice j Organ: Gonads Organ Weight M ales (c) F em ales O rgan M ales / 0 <(Cdy/I\0V0egig)Fhte Ratio m ales 2.52 0.123 0.397 0.0222 3. 19 0.204 0.482 0.0390 # 3.28 0.135 0.4 15 0.0283 3.44 0.128 0.547 0.0316 C n is K*t>> V O r^an/B rain We iglit Ratio Males (/i Fema lea 1.15 0.0628 1.43 1.58* 0.0707 1.60* 0.0666 S tatistically significant difference at the 95 percent confidence level. ADM 0 0 3 6 0 7 c n OOU e o ts t1 r D iet(aproymLl evel Control 1 1 10 100 TADLE XL! T E S T M A T E R IA L : Aroclor 1254 Two-Year Chronic Oral Toxicity Study Albino Rata O rgan W eight iand Ratio Data Summary oi Mean Values Final Sacrifice Organ: Heart Organ Weight Males (c) Fem ales Organ M ales /H o(igly/1 W0 0eigg)Fh te mR aa tio les 1. 87 1.54 0. 294 0.288 1.98 1.55 0. 303 0.302 2.08 1.37 0. 279 0.282 1.94 1.50 0.304 0.386** *^_SSttaattiissttilccaallllyy ssiiggnniiffiiccaanntt ddiiffffeerreennccee aatt tthhee 9959 ppeerrcceenntt ccoonnffiiddeennccee lleevveell.. OO ADH 003606 I. nit. 1I O rgan/B rain Weight Ratio V* Males (/i Fem ales 0.860 0. 795 0. 889 0. 805 0.998* 0.727 0.909 0. 803 UO'l D ieta(prpymL) evel Control 1 10 100 TABLE XLII TEST MATERIAL: A roclor 1254 Tw o-Y ear Chronic Oral Toxicity Study - Albino Rat* Organ W eight iand Ratio Data Summary of Mean Value* Final Sacrifice I Organ Weight M ales | I) Fem ale* Organ; Brain O rMgaanle/Ds (ogd/1y0W0 egFi)gehmt Ratio ale SaFcMriinafalieclseBdodAyniWmeaFilcgsmht(agolrcfasm s) . 2. 18 1.95 0. 342 0. 362 642 551 2.22 1.94 0. 347 0. 376 656 540 2.08 . 1.88 0.279 0. 388 762 500 2. 13 1.88 0. 340 0. 486** 656 4 11** ** S tatistically significant difference at the 99 percent confidence level. O GQ a 0M 003609 1 to O OO T E S T Js^**v>vsz.~3`u.as, /ne ( 67 C. Histopatholocic Findincs Histopathologic examination of tissues and organs taken from all anim als sacrificed after 24 months on test was conducted. Tables XLIIt through XLVI list all histopathologic chan; noted. Table XLVU contains the results of the histopathologic exam inatio of the urinary bladders. ~ Significant liver injury was found in anim als fed 100 ppn A roclor 1254 (T-III). The compound associated lesions consisted of vacuolar change, focal hypertrophy and focal hyperplasia. In addition, there were lesions of inflammation, necrosis, fibrosis and m inor de* generation, w ere more severe and frequent in the T-III group.. The vacuolar change was not seen in the control anim als but was observed occasionally in liv ers from T -I (1 ppm) and T -II (10 ppm anim als. It was frequent in the T-III anim als. This lesion is m orphologic indicative of fatty degeneration. Form alin-frozen sections of livers from representative animals which displayed vacuolar changes were stained with Oil Red 0 to reveal the presence of fat. The vacuolar lesion in the cytoplai of these cells was positively idenified as fat. The hypertrophic changes found in the liver was f o ca l 4*a n d often lim ited to the central to two or three times their lobular norm al area sir.c whe with re groups of cells were clear pink homogeneous s wc yoItlole n plasm The hyperplasia was associated with the same cells and appeared ACH 00 36 1C o o c 413 cQ i O T c S T c 63 to be *n extension of the hypertrophic lesion. The hyperplistic cells were ilso usually hypertrophic. The m ost severe examples of hyperplasia appeared as nodular growths with lim ited com pression of the surrounding normal hepatic tissue. -> The minor lesions of degeneration, hepatitis, ductule cell proliferation, necrosis and focal lymphoid infiltration seen in the control anim als and the T-I and T -II grouos are lesions of soontaneous disease and are not related to the A roclor 1254. This level of liver disease is not unusual in rats of this age. Hyperplasia of the transitional epithelium was p resen t in the urinary bladder of animals from the control group and each of the test groups. This lesion was usually associated with cystitis. The m ost , ( . severe changes were associated with the presence of m ineralized calculi in the bladder lumen. All of the other lesions in other tissues found in these ( anim als are related to spontaneous disease and they are not unusual for old rats. DVDoiepntleoorvmiannaatreEy,. PACamothredorolioncga. insDtCs, oVl.leMg.e, oFf h. ACM CC3oll 0 0 0 414 r ' <r Number of Animals 11 Males - ooo > 5* ioio>ii TABLE XLIH T w o - YIe a r ITEST M A T E R I A L : A r o c l o r Chronic Oral Toxicily Study 1254 - Albino Rata Histopathologic Changes Final Sacrifico Organ Examined Group: Control , Findings i Incidence Heart Trachea Lung Liver i Stomach Spleen j Kidney Tc stes, < Prostate A<lrenal Gland D r a i n |1i1. E y9e 1 Chronic focal myocarditis Tracheitis Chronic respiratory disease Focal degeneration Jhiclilc hyperplasia Chronic gastritis Hemosiderosis ;j { Chronic nephritis Testicular degeneration Periarteritis . Inflammation Telangiectasis S Nodular hyperplasia * Focal fatty change ! 'Focal encephalitis Inflammation * ' 3 3 91 2 1 3 8' 22 1 1 1 2 K ** ii CP O -t itno Average Grade 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 l.o 1.0 ao 415 / NAunmimbearlsof 14 F em ales oX OOUarCJ-P- TABLEXLIII continued TEST MATERIAL: A roclor 1254 Tw o-Y ear Chronic Oral Toxicity Study - Albino Rata Histopathologic Changes Final Sacrifice Group: Control Organ Examined HTlL.uirevnaacgerhrt ea Stom ach SCKUpoitdlleeonrenuenys Ova ry Findings * CCTFDorhhuacrrccooatihnnlleieilccyi thmifrysoeppcshaepolriiprdmal atyisonoirfacyi latrdrdai ist tieiosans e MANHCFPohacoeecarrnmtoaanr-ilnolsttihiiisphctsoiieeddssgpeisaarvotsai-tstcriiusisstqoiuslaarmcohuasn ge ep ith eliu m CCF oyhcsr ota ln ilcy mn epphho irdi t6iisn f i l t r a t i o n Incidence 1763342235331111 O & oE r-sc nu AGvreardage e 022111111111111...............500000000000000 o-i si* 300 0 0 0 417 N.Au nmimb earlso f 14 Tc-malcs TABLE.XL.HI continued TEST MATERIAL: A roclor 1254 , Ttyo-Y ear .Chronic O ral Toxicity Study - Albino Rata Histopathologic Changes Final Sacrifice Group: Control* Organ Examined Adrenal Gland Salivary Gland Findings TNCPheholcrdaoounnclgaihcirreohcftiytnbaporsceoiayrspitsolamsaianad atrophy Incidence 9411 All other tissues and organs w ere norm al histologically. 01..50 ^*'msilingihmta! G ra23d..i0n0g==Smmy sioltddeemr a t e 45 ..00 == esexvtreerme e A0* 003614 I: co o icnn A vGerraadgee 1111 ....0000 -vj t Number o( Anirr *1s II Mali.fi pn3 oCj o * I TADLEXUV. TEST MATERIAL: A roclor 1254 Two-VeaT Chronic O ral Toxicity Study - Albino Rats Histopathologic Changes Final Sacrifice Group: I ppm 1 Organ Examined HT reaacr ht e a Lung Liver Pancreae Stomach Spleen Kidney Teste* Findings Chronic focal myocarditia Tracheitis Chronic respiratory disease Congestion Ductile hyperplasia Vacuolar change (fatty) Necrosis Chronic focal pancreatitis Periarteritis Chronic gastritis Acanthosis Ulcer HC he rmoonsi ci d ne er opshirsi t i s Testicular degeneration Incidence 5 6 91 1 1 1 2 1 2 2 1 5 B 2 t o c n I. A verage Grade titK; 1.0 1.0 1.0 01.. 05 1.0 / % 3.0 1.0 2.0 1.0 1.0 1.0 2. 0 2. 0 1.0 I-vi1 000 418 r \ TABLE XLIV continued TEST MATERIAL: A roclor 1254 Tw o-Y ear Chronic O ral Toxicity Study - Albino Rata Histopathologic Changes Final Sacrifice j Group: I ppm * NAunmimbearlsof ____ O rgan Exam ined_______ ____________Findings____________________________ Incidence 1I Males i Testes (continued) SAPPPearidmtorruaseiittnnthaaaaytrlleyrGoViledasniGdclleand PFiNICHnnoeooyffcrllndpaaaiguaemlmelrracpsmmtretaliaaarlohctstiniiytiiooiafpsinnce ar pt iloane i a 6222||| ex* 0 0 0 22 Fem ales HTlI..uirevanaccgrrht ea 40* 0 j ix CCTF ohhr acrr ooca lhnn iielcciytmilrsoepcsahploi rimadtlyonoricyi lalrrddai tsi lteiosans e 1116723 f p Hr.i iHn ____________ A vGerraadgee I. 0 2.0 2.0 2l1... 000 I.O l- I;- l li ^ 2111....0000 o-I isiu&l 3 I ACM 0 0 3 6 1 7 TABLE XLIV continued TEST MATERIAL: A roclor 1254 Tw o-Y ear Chronic O ral Toxicity Study - Albino Rats Histopathologic Changes Final Sacrifice Group: I ppm ' Num ber of Anirv. Organ Examined Findings Incidence 22 F ei.. ! s O Liver (continued) SSCKLtpoyiodllmemonenpeanyhchNode UP itteuriutsa r y Adrenal Gland VHHACCMTNNCDFPFFoooeoaohaouyebeecclcrnncrdcmcpsatoaaaautggucrrenillnlsooioeeellrtgeiaisspsslsifictcraisnttiiaselaeiihdsratefoosnhlctyelsscynnaceytirpiaamhoppfecsaishermchinipsrraasgpialnttealitigaiossoes(inanfiaatatyn)d acanthosis .KOU) .11 other tissu es and organs w ere norm al histologically, 242864833111 173I1 -'"`So rinu A vGerraadge 22111.....00000 2111111111..........0000000000* 1.0 K u 4--j tf TABLE XLV TEST MATERIAL: A roclor 1254 8 Two-Year Chronic O ral Toxicity Study - Albino Rats Histopathologic Changes Final Sacrifice Group: 10 ppm ' NAunmimbearl so__f______ O rgan Exam ined_________ _________ Findings________________ ______ Incidence_____________A_ vGerraadgee I2 Males HTLureanacgrht oa Liver e t .. SKSTPptiaiodulnemnlceeearnsyec ha s CCHTVPDCCTHCF nohrheyhhhaueaecrrcsrprrcmocouoooatuteiihnnmlnnnoorlceiiteiiisludccorcccaiioelntdhraipfrggnfieysoreaohceearpccshoynpsdaeapastehelrlrniirprgrsigampitaletteiaaitinsyssoone(oinrcfaarcyaanratetdtirdayodi)tanisictteiiasasnsteh o s i s 117927311l1l11 0022311111111.............0000000000550 Cn cc NJ ouoo> t/ Number of Animal'; 12 Male TABLE >XLV continued TEST MATERIAL: A roclor 1254 'T w o-Y ear Chronic O ral Toxicity Study - Albino Rats Histopathologic Changes Final Sacrifice Group: 10 ppm ' Organ Examined Testes (continued) Prostate Seminal Vesicle Adrenal Gland. Thyroid Gland Findings PInefrliaamr mt eartiitoi ns Inflammation Telangiectasis Focal fatty change Focal hyperplasia Incidence i 2 2 2 1 1 00A C0M 12 F cmales NK>) O I Heart Trachea Lung Liver Chronic focal myocarditis Tracheitis Chronic respiratory disease Focal lymphoid infiltration Vacuolar change (fatty) Nodular hyperplasia 3 7 12 4 1 1 IOV I i I Average Grade 3.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 3.0 1 /* o / TABLE- XLV continued TEST MATERIAL: A roclor 1254 Tw o-Year Chronic O ral Toxicity Study - Albino Rata Histopathologic Changes Final Sacrifice Group: 10 ppm * NAunmimbearlso__f______ O rgan Exam ined___________________ Findings__________________ _________ Incidence_____________A_ vGerraadgoe Liver (continued) SCKLpyoidlmleonepnenhy Node UP itteuriutsary ATPhadyrraemtnhuaysl rGoildanGd land HHCHCATDPMTAFHaoeoehedueybyepllcrnermcpspaataoanagtcreenninlotosieelrrogtgeismipsspiccmtiiitsselleaedihaaaoacnlsceysscntteriipaiaaoapfessishrciiisprsasilttaiiossina 2223911311111t 1111....0000 2111111111..........0000000000 o^;?eo^ wov OC"3 All other tissu es and organa w ere norm al histologically. UK> Gradini* Sx/str f AOM Number of Animals 11 Males O O oo K) rOo' TABLE XLVI TEST MATERIAL: A roclor 1254 Two-Year Chronic Oral Toxicity Study - Albino Rata Histopathologic Changes Final Sacrifice Group: 100 ppm* Organ Examined Heart Trachea Lung Liver Small Intestine Spleen Lymph Node Findings CT rharcohnei ci t ifsocal m y o c a r d i t i s ECdher omnai c r e s p i r a t o r y d i s e a s e Focal degeneration Vacuolar change (fatty) Ductile hyperplasia Hypertrophy Focal lymphoid infiltration Portal fibrosis Focal inflammation Hemosiderosis Congestion Incidence 43 1023333111 21 Average Grade 2. 0 1.0 1.0 2. 0 1i:.o0 1.0 2.0 1.0 2.0 1.0 1.0 1.0 I lr NAunmimbearl sof 1I Male* TABLE XLVI continued TEST MATERIAL: A roclor 1254 Two-Year Chronic O ral Toxicity Study - Albino Rate Histopathologic Changes Final Sacrifice Group: 100 ppm * Organ Examined KTAP reiddosrntseeetnaysatle Gland. Thyroid Gland Findings CCHPTInheoeyflrnlrpaaoigemannerrgipsmctitleeiaaorncslinetiitaaopissnhisritis Incidence e 52i1 1 IS Fem ales HTLureanacgrht ea Liver 1 OO CHCETFFdoohrhyaeccrrpcoomaaehllnnraiteihhcrcioyytifprppsoeheecsryraptprliloarmpashityaoyo*rcyarddisiteias se 16553111 A vOerraacglee 2111....0000 11..00 ^ 1.0 223111......000000 AOM OC 36 t TABLE XLVI continued TEST MATERIAL: A roclor 1254 Tw o-Y ear Chronic O ral Toxicity Study - Albino Rata Histopathologic Changes Final Sacrifice Group: 100 ppnv Number of Animal s IS Females Orpin Examined Liver (continued) ACM CC3o23 Stomach Spleen Kidney Uterus Pituitary Pituit Adrenal Gland O _______ Fi n d i n g s _________ Ductile hyperplasia Vacuolar change (fatty) Nodular hyperplasia Hepatoma Chronic gastritis Acanthosis Inflammation Ilemon idc 1osib Chronic nephritis Focal calcification Metritis Hyperplasia Nodular hyperplasia Telangiectasia Nodidar hyperplasia Congestion Incidence 10211 245511 343111 ju All other tissu es and organs w ere norm al histologica Uy. Grading System V A verage Grade 111111111111............000000000000 111...000 t.o no ,/ TABLE XLV1I TEST MATERIAL: A roclor 1254 Two-Year Chronic Oral Toxicily Study - Albino Rata Histopathologic Changes of the Urinary Bladder Final Sacrifice Group c Sex ENx aummibneerd Mn F 14 Findings * PFrooctaeli neapciethoeulsiapl lhugy p(e3r4p)l a s i a (62) (T1- pI pm) M 10 F 19 Proteinaceous plug (326) Diffuse epithelial hyperplasia associated with diffuse cystitis (377) T- II (10 ppm) M 13 F 13 Diffuse epithelial hyperplasia and papilloma associated with focal cystitis (417) Diffuse epithelial hyperplasia associated with diffuse c ys ti ti s ( 4 I 1)) None JO T- III (100 ppm) M 10 F 17 Focal epithelial hyperplasia associated with focal c y s t i t i s (4<J7) Focal epithelial hyperplasia (5) None ^ Individual animal numb era are shown in pa renthesis. -r Grading System 1.0 i minimal or trace 4.0 = sever** Incidence i i i i i i - i i \V -. L Average Grade i 3 4 2 2 1 - itnn i *V - oo : 5 V cyLztj'Xui. fnc. K %L C. Detailed Descrintion of Tumor Findings . Tumor data for individual anim als including location, w eight and pathologic classification are presented in Table XLVIII through LL None of these tumors could be related to the ingestion of A roclor 1254 and are considered norm al for a random population of rats this age. i ACM n iU i: ! (H 428 000 429 XaAnundmimSbecaxlr l-M 2-M 46-F 47- F 48- F 50-F 52- F Oo0--5 K> 9 - F F n*> loo &fvj -F ` Location Abdomen Pancreas Abdomen Lymph node Abdomen Abdomen Abdomen AA bddr eonmael ng la n d Abdomen Abdomen TADI^E XLV1II TEST MATERIAL: A roclor 1254 Two-Year Chronic O ral Toxicity Study - Albino Rata Deacription of Tumor Findings Group: Control (Wg reaimg hat) 11.76 64.98 35.09 - m* - 88.92 2 3 0 .no Size . (cm ) 85 xx 12 xx 22 2x2x1 2x2x3 - . 13x11x4 n v 11 .. C lassificatio n Mammary fibroadenoma A denocarcino m a MM aamm mm aarryy ffiibbrrooaaddeennoomm aa Reticulum cell sarcom a M ammary fibroadenoma Mammary fibroadenoma M ammary fibroadenoma MPhacmocmharroymfoicbyrotoamdeanom a F ibroadenom a MTooennstth s 24 24 24 24 24 7 24 24 24 Ir .!An'udnmimSheacxlr n-r * 12-F 13-F ** ocatlcn Abdomen Ahdonr cn Abdomen TABLE XLIX continued TEST MATERIAL: A roclor 1254 Two-Year Chronic Oral Toxicity Study - Albino Rata Description of Tumor Findings Group: 1 ppm (Wg reaimg hst) - Size (cm ) C lassificatio n ^ Mammary adenocarcinoma / - l Mammary fibroadenoma - [s Lipoma cf -li4t MT oeonsntths 24 24 24 r E Oo o> U> o If o uindmimSlia*elxr l-M 2-hi 3-F 4-F 5-F 6-F 7-F o 8 -F o>X 9-F oUOOi' TARLE XLIX TEST MATERIAL: A roclor 1254 TwoYer Chronic Oral Toxicity Study - Albino Rata Description of Tumor Findings Group: 1 ppm Location (Wg reaimg hst) Parathyroid gland Pituitary - Abdomen Abdomen AP abrdaotmhyenroid gland % 8-.9 7 Abdomen B. 86 ADrboedrgsoiamolnecnervic'al 20695.0 AP ibtduoitmaeryn > m Abdomen m Size (cm ) 2 x 2- x 2 3x2x2 13x8x2 . . . . as C lassificatio n v Adenoma ^ i' Chromophobe adenoma 1 M ammary fibroadenoma V'' i Mammary fibroadenoma V1AMdaemnommaaryu adenom a*, r I M am mary fibroadenom a \S- 'MFiabmromadaerynofmibaro;adenom a '# w: CMharmo mmoaprhyofbiob raodaedneonmo ma ^ a * r^rv% -* fit---*--i MTooennai 24 23 24 24 24 24 24 24 431 300z* C\nnudimmSbeaexlr 1- M 2-M 3-F 4-F 5-F 6-F 7-F 8-F 9-F 0*F ni, ooN . r. o TABLE L TEST MATERIAL! A roclor 1254 Tw o-Y ear Chronic Oral Toxicity Study - Albino Rata Description of Tumor Findings Group: 10 ppm Location (Wg reeigmht) Pancreas - Parathyroid gland - Abdomen TAhbydroomiden Abdomen m m AAbbddoommeenn 86 29 Pituitary - Abdomen 28 Pituitary m Adrenal gland 7.8 (Scimze) - 75 xx 85 xx 32 - 6x5x3 - 1/A.*den C lau lflc oma (-*' a tto n l/A denom a ^M ammary fibroadenoma 1 AMdaemnommaary fibroadenom a , Mammary fibroadenoma (/.F'Fibibrrooaaddeennoommaa * ' ('Chromophobe adenoma [/Fibroadenom a L"- [/Chromophobe adenoma (-- l/T elan g io m a / ( if a toa MTooennatth s 24 24 24 24 24 24 24 24 22 > min ^ I"' I t i i NaAnundmimSbecaxlr l-F 2-F 3-F 4-M 5-M 6-F 7-M 8-F OO U lo 9- F o 10-F Uooo*I Location Abdomen Abdomen Abdomen Pancreas Abdomen Abdomen Lymph node Pancreas Lymph node Abdomen D TABLE LI TEST MATERIAL: A roclor 1254 Tw o-Y ear Chronic Oral Toxicity Study - Albino Rata Description of Tumor Findings Group: 100 ppm (Wg reaimg hst) 48.12 m - * - m 13.0 m 52.0 Size _______ism l_______ 5x4x3 - 18x4x3 - 1x2x1 3x3x3 "l 8x5x2 Classification {/F ibrom a *s` Is M am m ary fibroadenom a is M am m ary fibroadenom a /Adenoma /- FlbroadenomA-^ |. M am m ary fibroadenom a t--l- Reticulum cell sarcom a y { /'A den ocarcinom a {/L ym phosarcom a V Fibroadenom a t-''"' VV /*y, MTooennstth s 24 24 24 24 24 24 13 24 24 24 oo 434 NaAnundmimSbeaexlr ll-F 12-F 13 - F M -F 15 - F Location Abdomen Abdomen Abdomen Abdomen Abdomen OO n2 I uOoLOu TABLE LI continued o TEST MATERIAL* A roclor 1254 Two-Yer Chronic Oral Toxlcliy Study - Albino Rata Deacription of Tumor Findings Group: 100 ppm (Wg reaimg hst) 141.9 42 209.0 14. 63 Size <cm ) 8x8X 2 6x 4x2 10 x 9 x 3 C lassificatio n K Mammary fibroadcnomaL/ * M am m ary fibroadenom a i^-- U Fibroadenoma / Mammary fibroadenoma V F ibroadenom a I* I I cj MTooennstths 24 24 24 24 24 . U)) B l C - T E S T 2.a-aoAoLyudi, c V REPORT TO MONSANTO COMPANY TWO-YEAR CHINAROARNLOBICCILNOOORRRA1AL2T4T2SOXICITY WITH NOVEMBER 12, 1971 EBT NO. B7298 I. Introduction At the request of Monsanto Company, a tw o-year chronic oral toxicity study was conducted using albino rats to determ ine the potential toxicity of A roclor 1242, Lot No. AK-255. The following report p resen ts the results of this investigation. CG3t>3 0 0 C 435 c.C ^ T E 5 T oa&iaLyLUi* IL Summary V A tw o-year chronic toxicity study w u conducted using albino rats fed diets containing 1 (T-I), 10 (T-II) or 100 (T-III) ppm Aroclor 1242. Food consumption and body weight gains were not altered at any t level of A roclor 1242 fed. The num ber of anim als dying and the time at which the deaths occurred did not vary iamong th test and control grouos. Hematological and clinical blood chem istry studies conducted after 3, 6, 9, 12, 18 or 24 months did not reveal any affects related to A roclor 1242. Urine analyses failed to reveal any differences between test and control animals. At sacrifice after 3, 6 or 12 months on te st, organ weights, organ to body weight and organ to brain weight ratios disclosed several ( random ly occurring intergroup differences. The lack of any consistent dose related response and the absence of any deleterious histopathologic change confirm that these differences were not related to the ingestion of A ro clo r 1242.1 At the final sacrifice after 24 months on test, the liver weights and liv er to body weight or brain weight ratios w ere significantly elevated in fem ales from the T-I1I group. Histologic exam ination of the livers from the T-UI roup revealed several anim als with vacuolar change. This lesion is morphologically indicative of fatty degeneration. Specific fat stains confirmed the presence of fat in these vacuoles. Focal hypertrophy and focal hyperplasia were also found in the livers from anim als fed A roclor 1242. ACM CC 36 33 001 436 b# ^Jma-uoI B I TEST JamaoLyuei, Sue. c H yperplasia. o the urinary bladder w u found in anim als from the control group and from each of the test groups. This hyperplasia was usually associated with cystitis. The incidences and types of all tumors were about the same in all groups, including the control group, and are considered normal for rats of this age. . Respectfully submitted, INDUSTRIAL BIO-TEST LABORATORIES, INC. R eport p rep ared by: ARPhasitsliiTsptoaSxnvitciSTtymoxitihc,olBo.gSis.t R eport approved by: SJRaeamnt iiToesroxBCi.rcoitPuyplanLkeadeLr tu*. SPeacutlioLn. Hberaidg,h7tT,/oxPihc.oDlo.gy MM .a nLa.g eKr ,e pTl ionxgiec or ,lo g y November 12, 1971 lm:bb :hpdcjl aDM 00363 0 0 1 437 B TEST cne. III. Procedure A. Experim ental Animals The anim als employed in the test were Charles River strain * albino ra ts . Four hundred rats (200 m ale and 200 fem ale) were selected for the experim ent, ear-punched with the anim al number assigned and housed individually in standard wire-bottomed steel rat cages. Each cage bore a color-coded card identifying the r a t with respect to project number, dietary level assignment, individual anim al number and sex. B. Organization of Groups A structural outline of the experim ent is given in Table I. TABLE I TEST MATERIAL: A roclor 1242 Two-Year Chronic Oral Toxicity Study - Albino Rats ; O nline .of.Experim ent Group MNuamleber of AFneimmaalles .Diet(aprpymL) evel Control 50 50 None Adm inistered T -I 50 50 1 T -U 50 50 10 T - m 50 50 100 * Charles River Breeding Laboratories, North Wilmington, Mass. AO* 003&3 10 0 438 B 1< y t S S T J.aio* aia***A, 2nc. c 5 C. D iets, Feeding and Food Consumption A ll diets w ere prepared in the central diet room of this laboratory. The basic ration from which all diets were constructed w as a standard, pulverized stock rat ration-. The diet for any given te s t group was prepared by blending the calculated amount of A roclor 1242 with a pre-w eighed portion of the stock ration in a Hobart m ixer. Fresh diets were prepared each week and every rat was offered an amount of food sufficient for ad libitum feeding. Food consumption was recorded for five rats of each sex in every group weekly for the first three months and m onthly for the next nine months. Thereafter, periodic spot checks were made. D. Body Weights and Weight Cains Initially, the body weight of each rat in every group was deter* m ined and recorded. Thereafter, individual weighings were made weekly fo r the firs t 13 weeks and monthly thereafter until the conclusion of the investigation. E. M ortality and Reactions Checks for m ortality and abnormal behavioral reactions were m ade daUy throughout the investigation. F. Hematologic Studies and Urine Analyses Blood studies, including determinations of hemoglobin concentra- tion, hem atocrit value, erythrocyte count and both total and differential * Purina Rat Chow, Ralston Purina Company, St. Louis, M issouri. ACK C 0 3 b 3 t 0 0 C 439 cy I W * I * W I ****** m*m** -- * > , y f | u c. v leukocyte counts, w ere conducted upon five m ales and five females from b oth the control and 100 ppm groups. U rine analyses for the presence of glucose, /albumin, m ic ro scopic elem ents, and determ inations of pH and specific gravity were con ducted upon urine sam ples at the same time intervals and from the same anim als as those employed for the blood studies. These studies w ere conducted after 3, 6, 9, 12, 18, and 24 month of feeding. C. Clinical Blood Chem istry Studies D eterm inations of blood urea nitrogen concentration (BUN), serum alkaline phosphatase activity (SAP), fasted blood glucose concen tration and serum glutam ic-pyruvic transam inase activity (SCPT) were ( conducted a fte r 3, 6, 9, 12, 18, and 24 m onths of feeding upon the sam e ra ts as were the routine blood studies. H. Pathologic Studies When an anim al succumbed during the test period, a gross autops; w as perform ed. In those cases when postm ortem autolysis was not ad vanced, representative tissues were taken and preserved in ten percent form alin solution for possible future histopathologic study. . A fter 3, 6, and 12 m onths of testing, five anim als of each sex from each group w ere sacrificed and subjected to complete gross pathologi exam inations. ACM CO 36 37 0 0 ( 440 c/* TES T JtaaoAai&uM. $%&. 7 A btolute organ weights were recorded and organ to body weight v and organ to brain weight ratios computed. The following organs were included: liver, kidneys, spleen, gonads, heart and brain. These data w ere then subjected to statistical analysis. An A nalysis of Variance was C conducted first and significant effects disclosed by that treatm ent were further studied by " f'-te sts. Complete m icroscopic examinations were conducted upon the tissu e s and organs from all control and 100 ppm group rats sa c rifice d a fte r 3, 6, or 12 months of testing. The following tissues and organs w er included in the exam inations: heart, trachea, lungs, liver, pancreas, m esophagus, stomach, sm all intestine (duodenum, jejunum and ileum ), i caecum , colon, spleen, lymph nodes, kidneys, urinary bladder? gonads, prostate gland, seminal vesicles, uterus, pituitary gland, adrenal glands, salivary glands, thyroid gland, parathyroid glands, skeletal m uscle, sternum , bone, peripheral nerve, spinal cord and brain (cerebrum , cerebellum and pons). The aforementioned tissues were prepared and stained with Hem atoxylin-Eosin stain. A fter two years of feeding, all surviving anim als were sacrificed and subjected to complete gross pathologic exam ination. The absolute weights of the liver, kidneys, spleen, gonads, heart and brain were recorded immediately after sacrifice. AO* 036 00( 441 Sndiulual BI &T TEST 2aa*aia*iM, S* c 8 M icroscopic examinations were conducted upon tissues and organs from selected anim als dying during the experim ent and upon all anim als from the final sacrifice. Tissues and organs examined were the same as those previously m entioned. I. Tumor Incidence and Classification A tabulation, of the incidence of tum or form ation in each group was made at the conclusion of the investigation. In addition, tumor data for individual animals including location, weight, size and pathologic classification were recorded. i AC* 0CJ6J 00' 442 J*LuliisL Bi tE S I 2 s i& 1& Lv U4 4, JtlC . c 9 IV. Result A. Bedv Weights and Weight Gains The m*.le and female body weight data are assem bled in Table II. * The data in this table also include the 3, 12 and 24 m onth total weight gains. There were no significant effects attributable to the ingestion of the compound. i AO* cn**/Q 00 443 Ir I TADLE II TEST MATERIAL: A roclor 1242 Two-Year Chronic Oral Toxicity Study - Albino Rats Body Weight and Total Weight Gain Data Summary of Mean Values dAiert(oapcrpylmo rL) e1v2e4l2of Sex 0 1 2 3 4 5 B6o(dWgyreaWem7ke:ai)ght8 5 10 11 12 13 T9o0ta-GDl aaWiyn eight (gram s/rat) Control MF 113363 210738 214950 321139 326442 235743 239519 420659 422740 424760 424810 424798 426970 427848 314512 i :I 10 100 MF . 113363 210753 215947 232296 326470 235773 236978 421972 423728 425810 426842 428814 429838 520928 MF 113363 210726 215916 32362 234642 235742 36982 48148 422768 425840 427815 428814 520800 520859 MF 113363 210733 214984 232250 235615 236746 237928 421960 427247 427359 425739 426857 427883 428867 317556 317469 315540 444 oo . OXU oo . * ISi*>.. t.tv r-v CD -nLH>n r c-- f bi OOt 145 TABLE II continued TEST MATERIAL: A roclor 1242 Two-Year Chronic Oral Toxicity Study - Albino Rata Body Weight and Total Weight Gain Data Summary of Mean Values j HAert(oapcrpylmorL) e1v2e4l2 of Sex 4 5 6 7 8Bo(MgdyroanmWthse):9ight 10 11 12 Control MF 429978 533130 536252 539333 632425 642 359 636774 638883 730910 1 MF 532052 535251' 538206 631343 634402 636555 639607 730817 734838 10 MF 522959 535123 537298 630303 632476 634514 637645 639753 730864 100 MF 259004 530373 532511 538303 630478 633630 636742 638868 711 379 n*j T( go1rt2aa-lGmMWaosin/nertiahgth)t K t 525648 621502 / 527438 527483 >OT OOl>i 'r lAiertoa rc(yplopmrLe)1v2e4l2 of Sex Control MF 1 MF 10 MF 100 MF TABLE II continued TEST MATERIAL: A roclor 1242 Two-Year Chronic Oral Toxicity Study - Albino Rata Ir .-. ! 03 Dody Weight and Total Weight Gain Data Summary of Mean Values i tmo 13 14 15 16 Body Weight (grama) 17 1M8onth: 19 20 21 T o2t4a-lMWoenitghht 22 23 24 (g ram s /r a t) 472268 744464 746569 748618 750609 756157 756303 755478 755319 575206 566847 654512 451059 767 428 748453 805 479 800 468 850040 581140 852030 583014 583052 800 538 583058 755329 632966 734903 740560 746223 744810 748642 748800 758050 758139 758209 573743 759367 753447 640111 472284 474278 476233 743657 747228 748346 748313 478340 748255 479150 744873 648552_ 519 349 to 446 BI0 *CTEST 2sh*ata*d& t. $to. c 13 V B. Food Consumption The data obtained from the food consumption m easurem ents conducted during the firs t 12 m onths of feeding a re su m m arised in T able III. These data revealed no significant difference between test L and control rats. The periodic checks conducted during the rem ainder of the investigation also revealed no outstanding differences between te st and control anim als. v 00ACf* <47 / 1 TABLE III TEST MATERIAL: A roclor 1242 Tw o-Y ear Chronic O ral Toxicity Study - Albino Rata Food Consumption Data Summary of Mean Values lAe traor(cyplopLmr e)1v2e4l2of Sex 1 2 3 4 ( 5 g rFa omosd/ 6 rCaWot/e7nsesekuv:mc pntidoany 8 s) 9 10 11 12 13 ACvoenrsaugme pFood (gram s/rat/se 1 Control p!|- 1 MF 9734 116400 117445 116037 110347 113337 222058 119547 210645 115818 119416 119540 115916 MF 19219 115049 116250 210614 112100 119616 210264 211307 213722 118450 114858 118498 114950 117440 113667 : 1 MF 19136 113124 114427 210311 120 1 10 119439 118032 118244 118646 119442 119463 119318 119434 117311 100 MF 117 89 114198 118259 230 189 19618 117142 119429 113752 212870 114952 114826 190 139 119400 113852 I1-. TO o m / -o -- 0X3* > rJ i rr TABLE III continued TEST MATERIAL: A roclor 1242 Tw o-Y ear Chronic O ral Toxicity Study - Albino Rats Food Consumption Data Summary of Mean Values AetraorcyloLr e1v2e4l2of (PPm > Sex 4 5 6 (g rFa moosd/ 7 rCMaoto/nsnsetuhvm:e 8 pntidoany 9 s) 10 11 12 (g ra mACsvo/ernarsatu/gmseepvFtieoononddayi Control ! : 1j ' 1 10 MF 119468 118594 116368 112417 116338 118542 117690 114710 118277 MF 118502 181 159 170 HI 115849 115900 118498 119436 119452 210589 MF 184 139 116447 113668 115917 119434 114858 119318 114826 113707 176 142 118508 114813 100 MF 116739 114912 116809 210408 119465 114846 118447 114867 114657 187 149 00 O Hmcn * tn AO' 00( 449 ST 1 3*c. K-S~ 10 C. M ortality and Reactions ' A frequency distribution of natural deaths occurring during the investigation appears in Table IV. No untoward behavioral reactions were noted among any of the anim als employed in the investigation. aCH OC 3o'* OIK 450 (f f D iet(aprpymL) evel Control 1 10 100 Sex MF MF MF MF TABLE IV TEST MATERIAL: A roclor 1242 Tw o-Y ear Chronic O ral Toxicity Study - Albino Rata O M ortality Data Frequency Distribution of Deaths mto Frequency Distribution of Deaths 1-3 4-6 7-9 10-12 M onth1s3:-15 01O'0 19-21 22-24 Total Dead Number Tested* t t00 00 00 21 31 75 67 93 2159 //33 55 21 00 01 11 33 23 47 58 2156//3355 00 01 01 22 01 72 55 85 2136//3355 * 00 01 00 31 23 64 78 10 9 22 95 // 33 55 * Does not include the five anim ale of each sex from every group sacrificed for interim pathologic studies. t AOK O i 451 BI0 TESTJaU *a{(**4i. 3*e. 18 D. Hem atologic and Clinical Blood C hem istry Studies data are Mean male and sum m arized in fem ale Tables hematologic and V through EC. clin ica*l blood chem istry Values for all param eters investigated w ere within the norm al range for the albino rat. No significant differences between test and control values were observed.. AC*  J u tte d BIO-TEST JaL tt D(Lpieepvtmaer)ly C o n tro l ii' 100 Sex 3 M 14.0 F 9. 1 M 15.6 F 15.6 TABLE V TEST MATERIAL: A roclor 1242 Tw o-Y ear Chronic O ral Toxicity Study - Albino Rata Hem atologic Data Sum m ary of Mean Values T o(tathl oLuesuaknodcsy/mtemC^o)unt 6 M onth: 9 12 18 15.4 10.1 II. 1 9.9 9.4 6.7 7.6 8.8 24 11.2 7.6 3 6 E(rmy tihlMlnioooncnsyth/tme: 9 mC ^o u) !2 nt 18 8. 1 8. 2 8.7 8. 8 7.6 7. 5 7.7 7. 3 7.8 7.7 10.4 9.7 12. 5 9.4 9.0 .7 .7 7.8 6. 2 9.3 6.4 7. 7 8.0 8.0 7.6 7.4 7.6 7.6 7. 1 7. 9 7.7 24 6.5 6. 8 7.0 7. 2 O N Ox D UUJl h vO rt / D(Lpieepvtmaer)ly 1' 1{1i :.Control i 100 TABLE VI TEST MATERIAL: A roclor 1242 Tw o-Y ear Chronic O ral Toxicity Study - Albino Rats Hematologic Data Summary of Mean Values Sex 3 H 6 e m o g l(ogb9M/i n1o0n0Cthom:nlc) entra 12 tio n 18 24 M 17. 1 17.7 15.7 17.6 16. 1 13. 6 Hem atocrit Value 36 9M(%on) th:12 18 51 49 48 50 41 F 16.9 17.4 14. 1 16.7 16.4 14.6 50 47 43 46 42 M 16.8 16.9 14.2 15.4 15.6 14.6 F 15.8 16. 1 13.6 15.7 15.5 14. 8 50 48 43 44 41 46 48 41 41 40 O nl/ii 24 35 38 37 37 G'-- >o u> jr* No D(Lpieepvtmaer)ly Control 100 TADLE VII TEST MATERIAL: A roclor 1242 Tw o-Y ear Chronic O ral Toxicity Study - Albino Rats v K 03 O Hematologic Data Summary of Mean Values min Differential Leukocyte Count (Number of Cells per Hundred) Sex 3 6 L y9mMpohnotchy: tes 12 18 24 r3 6 N9euMtroopnht1hi2:ls 18 24 M 82.0 86.6 80.4 78.8 79.0 65.4 16.0 11.4 18.6 20.6 20.0 32. 2 F 83.0 86.6 86.8 89.0 70. 2 61.4 15.4 11.6 11.8 10.0 29. 2 36.0 M 89.6 84.4 . 79.8 87.0 66.0 58.4 F 91.4 86.0 82.8 88.4 75.6 65.2 9.6 15. 2 18. 8 13. 2 33.0 38. 8 8.4 13.6 17.2 11. 2 23.0 33. 6 n o 45 5 or*> N IfoO>jJ tf D(Lpieepvtmaer)ly Control 100 Sex 3 M 0.6 F 0.6 M 0. 2 F 0.0 TABLE VII continued TEST MATERIAL: A roclor 1242 Tw o-Y ear Chronic O ral Toxicity Study - Albino Rats Hem atologic Data Sum mary of Mean Values 6 MDoiM9nffooecnryethtne:tsi a lL 12 euk o cyte IB Count (Number 24 of Cells 3 per 6 HEuonMsd9irnoeodnpt)hh:ils12 0.0 0.0 0.4 0. 2 1.2 1.4 2.0 1.0 0.2 0.0 0.0 0.0 0. 2 1.0 1.0 1.8 1.4 . 0.2 0.0 0.0 0.4 0.0 0. 8 0.0 0.0 0.2 0.0 0.2 0.6 0.4 1.4 1.4 0. 2 0.4 0.0 0.2 18 . 24 0. 8 1.6 0.6 1.6 1.0 2.0 1.4 1.0 GO >o* oo UI ot>J INvl S.u/uUal B I O b f AOM 0 0 3 6 D(Lipeeptvmaer)ly C o n tro l Sex M F M 100 F TADLE VII continued TE ST M ATERIAL: A roclor 1242 Tw o-Y ear Chronic O ral Toxicity Study - Albino Rata Hem atologic Data Sum m ary of Mean Values 1 3 D ifferential 6 L euko c y te C 9 oBunMatsoo(npNthhu*imls ber 12 of C ells per Hundred) 18 0 .0 0.0 0.0 0.0 .0 0.0 0.0 0.0 0.0 0.0 24 0.0 0.0 0.0 0.0 ' 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 ( if rv tf al B I 0 T E S T T A B L E VIII TEST MATERIAL: A roclor 1242 Tw o-Y ear Chronic Oral Toxicily Study - Albino Rats Clinical Blood C hem istry Data Summary of Mean Values Serum Glutam ic-Pyruvic DLieevtaerly (PPm > Sex 3 T ra6n(sDaMamdoienntaUh9s:neitAs)ctiv1it2y Control M F 38 33 48 45 39 . 38 45 42 18 31 32 24 36 30 3 6 BloodC9oUn(MrmceeoagnnstNtrh%1ai:2tt)rioongen 1 17 15 12 10 14 14 16 15 9 13 100 M 33 35 36 57 39 32 F 39 41 53 40 52 46 15 15 13 14 12 17 14 14 11 11 15 11 20 14 % X* cr N DL(ipeepvtmaer)ly Sex 3 Control M F 128 130 M 121 100 F 125 TABLE IX TEST MATERIAL: A roclor 1242 Tw o-Y ear Chronic Oral Toxicity Study - Albino Rata Clinical Blood C hem istry Data Summary of Mean Values 6 F asCteo-d(nM9mcBoeglnnsottohr%da:)tiGo1nl2ucose 18 123 89 88 138 118 115 92 134 24 99 109 3 S crum (Kin 6 gA-lAAk arc9MmltiinvoseitntrytoPhn:h1go2 sphatase Units) 18 28.6 24.7 21.5 20. 3 16. 2 18.9 17. 8 10.6 11.9 16. 8 24 22. 3 20. 2 123 129 145 125 115 118 124 121 135 116 26.4 23.2 17.4 25.8 16.7 13. 2 27.6 20. 3 9.6 11.7 11.6 14.2 C 459 o Uttv BI0 TE5TS ftdadu al 2aJ *ai&uM, c. 26 . Urine Analyses Mean male and female urine analyses data are summ arized in Tables X through XIL No differences were noted between the urine from control and test anim als at the intervals of examination. Ona. 00( 460 !f r oi 0 ACM TABLE X TEST MATERIAL: A roclor 1242 Two-Year Chronic Oral Toxicity Study - Albino Rata Urine Analyses Data Summary of Mean Values ii/ni D(Lpieepvtmaer)ly Sex 3 6 GMluocnot9she: 12 18 24 Control M n n n n nn F n n n n nn 3 6 AMlbou9nmthi:n 12 18 24 n n t . t +2 43 n n n n t 42 100 M n n n n nn F n n n n nn n n t t 4 1 44 n n t t t 3 444nKt213=es===yt:n331re0a00g00ctaeottt;ooiv1l50e3e000a00smmmtghgg/a//n11010030000mmmml llguuur/i1rrn0iinne0eem l urine 44 = m ore than 500 m g/100 m l urine ON TABLE XI TEST MATERIAL: A roclor 1242 Tw o-Y ear Chronic O ral Toxicity Study - Albino Rats U rine Analyses Data Summary of Mean Values r Va O vuNni. D(Lpieepvtmaer)ly .Control M icroscopic Elements Sex 3 6 Mo9nth: 12 18 24 M N N N N N +1 F NNNNt t 3 6 Mpo9Hnth: 12 18 24 7 7 6. 7 7 6 8 8 7 8 66 100 M N N N N Nt F N N N N Ni 7 7 7 8 6 6 7 7 6 7 66 t tKN23I =-e:==ytN:m51r0aootcortrmeoe;1a01tllh5epaspenser r1tlh5olawopnwep5rpoolpwowewerer rplfooifwewiledelpdrowfieerldfield C\ to NGO !f r BIO*TEST-/- CC3efc D(Lpieepvtmaer)ly Control 100 O o ot TABLE XII TEST MATERIAL: A roclor 1242 Tw o-Y ear Chronic Ora! Toxicity Study - Albino Rata U rine Analyses Data Summary of Mean Values Sex 3 6 S pecMifoincthG: ra 9 v ity 12 18 24 M 1.029 1.022 1.033 1.027 1.042 1.051 F 1.020 1.019 1.025 1.024 1.032 1.039 M 1.021 1.028 1.032 1.024 1.043 1.030 F 1.022 1.019 1.029 1.029 1.027 1.038 soIs DtvLuLual B1OC TEST 2aJ**aL>uu, C 30 t T. Pathologic Studies 1. Three-M onth Sacrifice j a. G ross Pathologic Findings Gross pathologic findings among test animals were not significantly different from those noted in control anim als. b. Organ Weight and Ratio Data The mean organ weight and ratio data collected at the three-m onth sacrifice are presented in Tables XIII through XVIII. * Statistically significant differences are designated by I asterisks following the test group value. Organ weights, organ to body weight and organ to b rain weight ratios disclosed several randomly occurring intergroup differences The lack of any consistent dose related response and the absence of any deleterious histopathologic change confirm that these differences were not related to the ingestion of A roclor 1242. ACM CG3fct 00I 464 f/ DAireot(caprioopyfmr L)1e2v4e2l C o n tro l 1 10 100 OC5 > TABLE Kill TEST MATERIAL: A rocior 1242 T w o-Y ear Chronic O ral Toxicity Study - Albino Rats Organ Weight and Ratio Data Three-M onth Sacrifice Sum mary of Mean Values Organ: Liver Organ Weight M ile s (e) F em a le s 21.4 13.0 22.3 12.4 23.3 14.4 25.5 14.0 Organ/Dody Weight Ratio M ales(g/100Fge)m ales 4.13 4.16 4.31 3.92 4.41 4.31 4.80 4.39 O rgan/B rain Weight Ratio M ales (g/g)F em ales 10.3 6.82 10.6 6 .5 9 11.9 7.93 15. 1 7.65 c ( I 465 if r D A ireot(caplropoymfr L)1e2v4e2l C o n tro l 1 10 100 TADLE XIV TEST MATERIAL: A roclor 1242 Two -Y ear Chronic O ral Toxicity Study - Albino Rats Organ Weight and Ratio Data Three-M onth Sacrifice Sum m ary of Mean Values Organ: Kidneys Organ Weight M alea (e) F em a le s 4.03 2.49 4.06 2.46 4.14 2.75 4.24 2.61 O r gMa na/lBe so( dg /y1 0W0 eFgi ge) mh t Ratio ales 0.782 0.802 0.784 0.772 0.786 0.827 0.795 0.817 O rgan/D rain Weight Ratio M ales (g/g)F em a le s 1.95 1.31 1.93 1.30 2.11 1.52 2.47 1.42 v- c f 00 465 O r> i f' i * */*' `mt? i-t T DAireotacrlooyfr Level 1242 (ppm) C o n tro l 1 10 100 G TABLE XV TEST MATERIAL: A roclor 1242 Tw o-Y ear Chronic O ral Toxicity Study - Albino Rats Organ Weight and Ratio Data Three-M onth Sacrifice Sum m ary of Mean Values Organ: Spleen M O rg ales a n(gW) eight Fem a le s 0.766 0.578 0.768 0.544 0.756 0.596 0.814 0.528 O rgan/B o(gd/y10W0 egig)ht R atio Males Fcmalca 0.150 0.184 0. 148 0.171 0. 143 0.179 0.154 0.166 O rg a n /B ra i(ng/Wg)eight R atio Males Female a 0.371 0.302 0.364 0.287 0.385 . 0.328 0.468 0.288 V cc: ad r.atb f rr Dietary Level A ro c(ploopfmr )1242 C o n tro l 1 10 100 . TABLE XV! TEST MATERIAL: A roclor 1242 Tw o-Y ear Chronic O ral Toxicity Study - Albino Rats Organ Weight and Ratio Data Three-M onth Sacrifice Sum m ary of Mean Values Organ: Gonads M O rg ales a n(gW) eight Fem a le s 3.60 0.114 3.51 0. 1430 3.5 0 0. 112 3.49 0.112 O r gMa na/lBe so( gd /y1 0W0 eFgieg) mh t Ratio ales 0.698 0.0370 0.681 0.0452 0.666 0.0336 0.656 0.0356 O r g an /B ra M ales i(ng /Wg )e*ig h t Fem a R atio les 1.74 0.0599 1.66 0.0758 1.78 0.0616 2.06 0.0619 * S tatistically significant difference at the 95 percent confidence level. /N (JIM 468 r TABLE XVII TEST MATERIAL: A roclor 1242 T w o-Y ear Chronic O ral Toxicity Study - Albino Rats Organ Weight and Ratio Data Three-M onth Sacrifice Sum m ary of Mean Values Organ: Heart Dietary Level A ro c loofr 1242 O rgan(gW) eight O rgan/B o(gd/y10W0 egig)ht R atio O rg a n /B ra i(ng/Wg)eight R atio (p p m ) _______________ M a l e s _______ F e m a l e s ___________ M a l e s _______ F e m a l e s ___________ M a l e s _______ F e m a l e s C o n tro l 1.59 1.05 0.307 0.339 0.767 0.551 1 1.58 1.02 0. 307 0.320 0.752 0. 540 10 1.55 1.10 0.295 0.331 0.788. 0.608 100 1.61 1.05 0.302 0.330 0.943 0.573 GG * CTt VO D"> t i i /r tr DAireotac(prloopyfmr L)1e2v4e2l C o n tro l 1 10 100 I TABLE XVIIt TEST MATERIAL: A roclor 1242 Tw o-Y ear Chronic O ral Toxicity Study - Albino Rat9 Organ Weight and Ratio Data Three-M onth Sacrifice Sum m ary of Mean Values Organ: Brain M a Org les an(gW) Feiegmhta le s O rgMana/lBeso(dgy/1 0W0eFgieg)mhtaRleastio MToaoflteaSsla cBroi(fdgiyc) eWd eRigahtsts Fem ales 2.07 1.91 2.12 1.89 0.402 0.616 0.410 0.597 518 314 520 318 1.97 1.81 0.375 0.545 527 334 1.82 1.83 0.345 0.576 534 319 ST JLiioxalafiti, ftc. 3 c. Histopathologie Findings Histopathologie examination of tissues and organs taken fro m a ll anim als fro m both the control and 100 ppm groups was conducted. T ables XIX and XX list all histopathologic changes noted. All of the lesions noted in the m icroscopic examination of tissues were those of spontaneous disease and are not unusual for the albino rat. The m ost frequent findings were lesions in the trachea and lungs, indicating chronic m urine pneumonia. These occurred in the control as well as the rats fed A roclor 1242. AC* C03te I 0 0 471 I D1O CT .E S T c 2c. 38 table xd: TEST MATERIAL: A ro d o r 1242 Tw o-Y ear Chronic O ral Toxicity Study - Albino Rats Histopathologic Changes . \ Three-M onth Sacrifice Croup: Control NAunmi mb earl sof 5 M ales 5 Fem ales Orean Examined LTurancgh e a U rinary Bladder Lung Findings TCdrhairscoehnaeiscietirse s p ira to ry H y p erp lasia Cdhirsoenaisce re s p ira to ry Incidence 1 31 .* 1 AGv rearda 1.0 r.o 1.0 1.0 All other tissues and organs w ere norm al histologically. Grading System 43201.....00500 ===== mmsmselioiivglnddehiermteraatle 5.0 = extrem e / a o m ccste? OOl 472 S I O f ' E S T JayuiLyiuu, c 35 TABLE XX TEST MATERIAL: A roclor 1242 Tw o-Y ear Chronic Oral Toxicity Study - Albino Rats Histopathologic Changes Three-M onth Sacrifice Group: 100 ppm NAunmi mb earl sof 5 M ales 5 Fem ales Organ Examined Trachea Lung Findings T rac h e itis CFdpohnicrsoeaeunlamiiscneotrneeirsasptiitriaatlo ry Incidence 2 2 1 ACverarca 1.0 1 .0m 1.0 All other tissues and organs were norm al histologically. Grading System 42301.....00005===== mmsmseloiiivglnddehiemrteraatle 5.0 = extrem e ACM 003 e7 0 473 ! fniiiit*1'1! Bl 0 T E S T JsIxvui/auU, ( 40 2. Six-Month Sacrifice a.. G ro ss Pathologic Findings No outstanding differences were noted between test and control anim als. b. OO rrgg aa nn tWo eBigrhatinanWd eOigrhgta nR atotioB ody Data and ~-- --------- The re su lts of-the statisticaL-anlayses-conducted-on ab- solute organ w eights, organ to body weight and organ to brain weight ratios are sum m arized in Tables XXI through XXVI. Organ weights, organ to body weight and organ to brain weight ratios disclosed several randomly occurring intergroup differences. The lack of any consistent dose related response and the absence of any deleterious histopathologic change confirm that these differences were not related to the ingestion of A roclor 1242. ACM 0C 3671 00( 474 (f r D ietaroyf L evel A ro (cplopmr )1242 C o n tro l 1 10 . 100 TABLE XXI TEST MATERIAL: A roclor 1242 Tw o-Y ear Chronic O ral Toxicity Study - Albino Rats Organ Weight and Ratio Data Six-Month Sacrifice Summary of Mean Values Organ: Liver O rgan Weight M ales (g) F em ales 22.9 13.1 13.8** 9.98* 22.3 13.2 22.0 11.7 O rgMana/lBeso(dg/y10W0 eFgieg)mhtaRleastio 3.74 3.77 2.85** 3.15 4.08 4.23 4.58* 3.70 O rgan/B rain Weight Ratio - M ales (g/g)F em ales 11.7 6.71 6.86** 5.76 11.0 6.95 % 10.8 5 .9 4 - * Statistically significant difference at the 95 percent confidence level, i Statistically significant difference at the 99 percent confidence level: 40M 003672 IwtJ-Sx. CO O m iHn t\ 00( 4 7 5 ( rr r T E S T Jaiaiabuc; 00( 476 Diet A ro a c rlooyfr Level 1242 ___ i Control 1 10 100 TABLE XXII TEST MATERIAL: A roclor 1242j T w o-Y ear Chronic O ral Toxicity Study Organ Weight and Ratio Data Six-Month Sacrifice A lb)in o { Rata i I<1! I Summary of Mean Values i Organ: Kidneys M a O le r s g a n(gW) eight Fem a l e s 4.04 2.79 3.51 2.44* 3.75 2.49* 3.54 2.33* O r gMa na/lBeAso( dg y/1 0W0 eFgi ge) hmt Ratio ales 0.664 0.806 i 0.728 0.774 |; 0.686 0.790 0.730 0.757 O rg an /B r M ales a i(ng /Wg )e ig h t Fem a R atio les 2.06 1.43 1.75 1.41 1.86 1.31 1.74 1.18 $ Statistically significant difference at the 95 percent confidence level. A0M 003673 tL*v> D3 K N f DAireot(caprloopymfr L)1e2v4e2l C o n tro l l 10 ' 100 TABLE XXIII TEST MATERIAL: A roclor 1242 Tw o-Y ear Chronic O ral Toxicity Study - Albino Rats Organ Weight and Ratio Data Six-Month Sacrifice Sum mary of Mean Values Organ: Spleen M a O le rg s a n(gW) Feiegmhta l e s 0.752 0.684 0.754 0.542* 0.796 0.622 0.584 0.488* O rgMana/lBeso(dgy/10W0eFigge)mhtaRleatio 0. 122 0.196 0.154 0.172 0.142 0.199 0. 120 0.159 O r g an /B r M ales a i(ng /Wg )e ig h t Fem a Ra les tio 0.384 0.350 0.375 0.313 0.394 0.327 0.288 0.248 * S tatistically significant difference at the 95 percent confidence level. tKt. u> mtn tk u4* LLV W O f aA / DAireota(cprloopyfmr L)1e2v4e2l C o n tro l 1 10 100 O CO TABLE XXIV TEST MATERIAL: A roclor 1242 Tw o-Y ear Chronic O ral Toxicity Study - Albino Rata Organ Weight and Ratio Data Six-Month Sacrifice Summary of Mean Values i Organ: Gonads M Org ales an(gW) Feiegmh t a le s 3.55 0.0960 3.44 0.0810 3.55 0.106 3.35 0.0772 O r gMa na/lBe so( gd /y1 0W0 eFgieg)mht Ratio ales 0.593 0.0279 0.716 0.0253 0.652 0.0335 0.697 0.0251 O rg an /B r M ales a i(ng /Wg )Fe iegmh ta R le atio s 1.81 0.0492 1.71 0.0468 1.76 0.0558 1.65 '0.0392 i c ( r 4. ** t/ .% D ieta A roc rlooyfr Level 1242 (ppm) I Control i 1 10 100 TABLE XXV TEST MATERIAL: A roclor 1242 Tw o-Y ear Chronic O ral Toxicity Study - Albino Rata Organ Weight and Ratio Data Six-Month Sacrifice 1 Sum mary of Mean Values Organ: Heart M a O rg les a n(gW) eight Fem a le s 1.70 1.05 1.49 1.03 1.46 1.06 1.42 0.970 O r'gMa na/lBe so(dg y/ 1 0W0 eFgieg)mht Ratio ales 0.282 0.302 0.309 0.325 0.267 0.335 0.293 0.314 O r g an /B ra M ales i(ng/Wgieight Fem a R le a s tio 0.867 0.538 0.741 0.595 0.722 0.558 0.700 0.492 \y ie;OD mln tru. tn 00 C 479 r o D ietaroyf L evel A roclor 1242 C o n tro l 1 10 100 OOz r vo:x TABLE XXV! TEST MATERIAL: A roclor 1242 Tw o-Y ear Chronic O ral Toxicity Study - Albino Rats Organ Weight and Ratio Data Six-Month Sacrifice j Sum mary of Mean Values Organ: Brain O rgan Weight M ales (e) F em ales 1.96 1.95 2.01 1.73 2.02 1.90 2.03 1.97 Organ/Body Weight Ratio M ales(g/100 Fge)m ales 0.320 0.560 0.415 0.546 0.369 0.597 0.416 0.635 FoifnSalacBroifdiyceWd eRigahtsts Males (y) Fem ales 613 348 484 317 548 318 488 310 I f AU) -fL--i4Ol4 !> r O4>' r n ** 7 7 B^ -TEST c$HC c. Histopathologic Findings Histopathologic examination of tissues and organs taken fro m all anim als from both the control and 100 ppm grou/ ps was conducted. Tables XXVII and XXVI2 list all histopathologic changes c noted. All of the lesions noted in the m icroscopic examination of tissues were those of spontaneous disease and are not unusual for the albino rat. The m ost frequent findings were lesions in the trachea and lungs, indicating chronic m urine pneumonia. These occurred in the control as well as the rats fed A roclor 1242. 1 AO* 003< 00 481 U n B *T S T J s^ uUauc, ne. c 45 TABLE XXVII TEST MATERIAL: A roclor 1242 T w o-Y ear C hronic O ral Toxicity Study - A/lbino Rats Histopathologic Changes Six-Month Sacrifice Group: Control NAumni.bmearlsof O rgan Exam ined Findincs Incidence 5 Males Trachea Ltmg SLkiveelertal M uscle FTFooracccaahll eptrinateicsuhmeiotnisitis HFF ooyccpaaellr eipnmefrliiaacmh oml aa ntigo int i s 2 21 2 11 ' 5 Females LLTuirvanecgrh e a Kidney HHPF eoyyrcppiaceelrhreetormmlaaciinaahgeiittiiss Focal pneumonitis 1. 21 1 1 AGv reards 11..05 0.5 l11...'00o 1.0 21..05 01..05 All other tissues and organs were norm al histologically. Grading System 24301.....00050 sss*s mmmsseliioivglnddehiemrteraa l te 5.0 * extrem e AC* CG3t>7S $iv4**a l BICT " T E S T ^a&e*af<n*td, 2*c. rv 49 \ TABLE XXVIII TEST MATERIAL: A roclor 1242 Two-Year Chronic O ral Toxicity Study - Albino Rats Histopathologic Changes Six-Month Sacrifice Croup: 100 ppm NAunmimbearlsof O rgan Exam ined Findings Incidence 5 Males Trachea Lung HFTF ooryaccpcaaehllreetpimrntaieiscauhme iot ni sitis 2223 5 F em ales LTurancgh ea HFF ooyccpaaellr etprmanceiauh me iot insitis 11 1- AGveraradge 0111....505 201...050 All other tissues and organs were norm al histologically. Grading System 452301......000005====== memsmselxiioivtglnrddehieemrtmeraaetle AC* GQ366C 0 0 ( 483 3,:<L u*L BIt - t e ST uW. Dn, e. so 3. Twelve-M onth Sacrifice -a .----G-r-o-s:-s--P--a-t-h-o-l-o-g-i-c--F-indings / G ross pathologic findings among test animals were not significantly different from those noted in control anim als. b. Organ Weight and Ratio Data The mean organ weight and ratio data collected at the tw elve-m onth sacrifice are presented in Tables XXIX through XXXIV, Statistically significant differenc'es are designated by asterisks following the test group value. " Organ weights, organ to body weight and organ.to brain weight ratios disclosed several randomly occurring intergroup differences. The lack of any consistent dose related response and the absence of any deleterious histopathologic change confirm that these differences were' not related to the ingestion of Aroclor 1242. *Cm 3 6 6 I 0( 484 i rr (0 TABLE XXIX TEST MATERIAL: A roclor 1242 Tw o-Y ear Chronic O ral Toxicily Study - Albino Rats Twelve-Month Sacrifice Organ Weight and Ratio Data Summary of Mean Values Organ: Liver 1 D ie t(aprpymL)_e_v_e_l_________ M aleOs_rg__a_n(_g_W)__eFigehmt a le s ___________OMrgaalne/sB_(_og_d/_1y_0_W0__egFi)egmht Ratio O a l e s ___________ rg M aanle/sB__r a__(i gn__/g_W)_ Fe iegmh ta Ratio les C o n tro l 22. 1 15.5 3.79 3.52 10. 8 7.72 1 22.7 13.7 3.45 3.33 10.4 7. 05 10 22.4 14.4 3.48 3.44 10.6 7.39 100 26. 3 14.4 3.78 3. 59 12.4 7. 16 OC 0L0O o-% oo IP ti -i LiH.l1 t rf .ttifiU il Qil T E S T Site. D ieta(prpymL) evel C o n tro l 1 10 100 TABLE XXX TEST MATERIAL: A roclor 1242 Tw o-Y ear Chronic O ral Toxicity Study - Albino Rats Twelve-Month Sacrifice Organ Weight and Ratio Data i Summary of Mean Values Organ: Kidneys M a O les rga n(gW) eight Fem a le s 4.04 3. 19 4. 31 2. 93 4.27 3.24 4.98* 3. 01 O Mrgaalne/sB(ogd/1y0W0 egFi)gehmt Ratio ales 0. 692 0. 738 0. 656 0.735 0.662 0.779 0.716 0.745 O rg M an/B ale s r a(ing/gW) eight Fema Ra les tio 1.97 1.58 1.97 1. 51 2.02 1.66 2. 33 1. 50 S tatistically significant difference at the 95 percent confidence level* O. --m ' ,i ^ 00 ) tA fVi tu f 0- r J, C 5 | ( 'J .fl ; ' " 7 r" ,r ' V '0,,C D ieta(prpymL) evel Cont rol 1 10 100 TABLE XXX! TEST MATERIAL: A roclor 1242 Tw o-Y ear Chronic O ral Toxicity Study - Albino Rats Twelve-Month Sacrifice Organ Weight and Ratio Data I Summary of Mean Values Organ: Spleen Organ Weight M ales (g) F em ales O Mrgaalne/sB(okd/ y i W oo egFi)egmht Ratio ales O rgan/B rain Weight Ratio Males (g/g) Fem ales 0. 788 0. 796 0. 133 0. 183 0. 380 0. 396 1.000* 0. 600 0. 152 0. 153 0.458 0. 307 0. 868 0.664 0. 136 0. 160 0.412 0. 341 0. 968 0. 570 0. 138 0. 145 0.454 0.285 O-- >nt rn * S t a t i s t i c a l l y sig n ific a n t d i f f e r e n c e at the 95 p e r c e n t con fid e n c e le v e l. CO'J ff D iet(aprpymL) evel Cont rol 1 10 100 TABLE XXXII TEST MATERIAL: A roclor 1242 Tw o-Y ear Chronic O ral Toxicily Study - Albino Rats Twelve-Month Sacrifice Organ Weight and Ratio Data i Summary of Mean Values Organ: Gonads Organ Weight M a l e s (g> F e m a l e s 3.46 0. 116 3.47 0.0938 3.00 0. 141 3.67* 0. 122 Organ/Dody Weight Ratio (g/100 g) Males Females 0. 596 0.0275 0. 529 0.0239 0. 457 0.0332 0. 531 0.0305 Organ/Drain Weight Ratio Males (g/c) F em ales 1.70 0.0574 1.59 0. 0483 1.40 0.0719 1.72 0. 0608 CuO* * S t a t i s t i c a l l y s ig n if ic a n t d i f f e r e n c e at the 95 p e r c e n t c o n fid e n c e level. to vo% oo mtn fv VA 000 (f D ieta(orpymL) evel C o n tro l 1 10 100 TAI3LE XXXIII TEST MATERIAL: A roclor 1242 Tw o-Y ear Chronic O ral Toxicity Study - Albino Rats Twelve-Month Sacrifice Organ Weight and Ratio Data i Summary of Mean Values Organ: Heart Organ Weight M ales (g) F em ales <OMrgaalne/sB(ogd/1y 0W0 egFi)gehmt Ratio ales O rgan/D rain Weight Ratio M ales C/) F em ales 1.71 1.23 0. 293 0. 286 0.835 0. 609 1.69 1. 18 0.258 0.298 0.776 0.610 1.68 1.29 0. 263 0.312 0.799 0.663 1.87 1. 19 0.268 0. 298 0. 878 0. 591 cl A rn Vi WOV ovOo y> UtA (< Gli.-7EST 490 Dietary Level (ppm) Control 1 10 100 TABLE XXXIV TEST MATERIAL: A roclor 1242 Tw o-Y ear Chronic O ral Toxicity Study - Albino Rats Twelve-Month Sacrifice Organ Weight and Ratio Data ' Summary of Mean Values Organ: Brain Organ Weight M ales (g) F em ales 2.04 2.02 2.19 1.95 Organ/Body Weight Ratio M a le s ( c / i o o gF)e m a l e s 0. 351 0.474 0.334 0.516 F inal Body Weight of Sacrificed Animals (g ra m s) Males * Females 584 439 660 431 2.11 1.95 0. 329 0.473 642 425 2. 14 2 .0 0 0.310 0. 508 98* -.409 ? S tatistically significant difference at the 95 percent confidence level. -- .1 ut O' ^io test V4 5 c. Histopathologic Findings Histopathologic examination of tissues taken from ea ra t sacrificed from the control and 100 ppm groups after twelve month: of testing was conducted. v Tables XXXV and XXXVI list all histopathologic chan; noted. All of the lesions noted in the m icroscopic exam inatio were those of spontaneous disease and cannot be related to the ingestion A roclor 1242. ( V 1. ooA 491 B7\ J T E S T 2aeyuiia^u, ne. K sa TABLE XXXV TEST MATERIAL: A roclor 1242 Two-Year Chronic Oral Toxicity Study - Albino Rats Histopathologic Changes Twelve-Month Sacrifice Group: Control N um ber of Animals Orean Examined Findi nc 5 Incidence 5 Males Trachea Lung Urinary Bladder T racheitis Chronic respiratory Cdailsceualus es i 2 1 5 Females Trachea Lung Colon Tracheitis Chronic respiratory disease Paras ites 1; 11 Av G 1 J 1 1 1 1 All other tissues and organs were normal histologically. Gradir? System 425301......000005 ====== mmmesslexiioivgtlnrddehieemrtmeraaetle \ ACM 0 0 3 6 0 9 00( 4 92 C < t a b l e XXXVI T E S T M ATERIAL: .A roclor 1242 Two-Year Chronic Oral Toxicity Study - Albino Rats Histopathologic Changes Twelve-Month Sacrifice Group: 100 ppm Number of Organ Animals Examined Findings Incidence 5 Males Trachea Lung PL ai vnecrr e a s Kidney Pituitary Adrenal 5 Females Trachea Lung Tracheitis CC oh nr ogneisct i or ens p i r a t o r y d i s e a s e Focal atrophy Focal lymphoid infiltration Chromophobe hyperplasia Nodular hyperplasia Hematocyst, Tracheitis Chronic respiratory disease 1 4 1 1 1 1 1 11 1 Ave G: 11.. 1. 1*. 1. 1. 1. 1. 1. 1. All other tissues and organs were normal histologically. Grading Svstem 432501......050000======mmssmeleioixvgnidtelhirdemrteermaatlee. 40* GC3 e o I 00( 494 J, Bl/-4*TESTsJaateUosu+i, Sru:. 60 4. Final Sacrifice a. Gross Pathologic Findings Gross pathologic findings among test animals were not significantly different from those noted in control anim als. b. Organ Weight and Ratio Data The mean organ weight and ratio data collected at the final sacrifice are presented in Tables XXXVII through XL!I. Statistically significant differences are designated by asterisks following the test group value. The absolute liver weight and liver to body or brain weigh ratio s w ere significantly evaluated in fem ale ra ts fed 100 ppm A roclor 1242. S tatistical evaluations of other organ weights, organ to body weight and orga .to brain weight ratios disclosed several randomly occurring intergroup dif ferences. The lack of any consistent dose related response indicates that these differences w ere not related to the ingestion of A roclor 1242. ADH CC369. O p 495 rtary Level - J e p jh )_________ Control 1 10 100 TABLE XXXVII TEST MATERIAL: Aroclo* 1242 Two-Year Chronic O ral Toxicity Study - Albino Rata Organ Weight and Ratio Data Summary of Mean Values Final Sacrifice Organ: Liver Organ Weight Males <g> F e m a l e s Organ /Body Weight Ratio (g/100 g) Male s Females 22.0 16.3 3.47 3.05 21.9 15.7 2. 93 3.00 22. 3 17. 1 3. 18 3. 19 25.6 22. 4** 3.95 4.82 +* & Statistically significant difference at the 99 percent confidence level. O V Organ/Brain Weight Ratio Males (g/g> Female s 10. 10 8. 4 ^ 9. 97 8.03 10. 20 8. 50 11.90 1 1 . 6 0 ** 496 Os eta(prpymL) evel C o n tro l 1 10 100 TABLE XXXVIII TEST MATERIAL: A roclor 1242 Tw o-Y ear Chronic O ral Toxicity Study - Albino Rata Organ Weight and Ratio Data Summary of Mean Values Final Sacrifice M ales O r g a(ng)W eight Fe m a les 5.57 3. 48 Organ: Kidneys Organ M ales /B o(dgy/1 0W0eigg)hFte mR aatlieos 0. 877 0.646 6. 13 3.45 0. 820 0.670 5.63 3.43 0. 816 0.644 5. 44 3.43 0. 835 0.725 i i ii f l O rgan/B M ales r(agi/ng )W eight Fe Ratio m ales 2. 57 I. 79 r*' 2.78 I . 76 2.56 1.71 2. 52 l. 79 L6t )0 Q > O' # < etary Level (ppTM) Control 1 10 100 OC xn VO CD oo t a b l e XXXIX TEST MATERIAL: A roclor 1242 Tw o-Y ear Chronic O ral Toxicity Study - Albino Rats Organ Weight and Ratio Data Summary of Mean Values Final Sacrifice Organ Weight M ales (B) F em ales Organ: Spleen O rgan /Body Weight Ratio M ales (g/100 g)F em ales 1. 15 0.96 0. J 82 0.181 1.26 0.81 0. 169 0. 158 1.08 0. 82 0. 158 0.153 ' 1.07 0.65 0. 165 0.140 - Organ /B rain Weight Ratio Males (g/g) Fem ale s 0.520 0 . 4 ^ 0.572 0. 145 0.495 0.409 0.499 0. 339 O f etary Level (ppTM) Control 1 10 100 oC TADLE XL TEST MATERIAL: A rocloi 1242 Tw o-Y ear Chronic O ral Toxicity Study - Albino Rat* Organ Weight and Ratio Data Summary of Mean Values Final Sacrifice Organ: Gonads Organ Weight M ale* <g) Fem ale* Organ/Dody Weight Ratio M ales (g/100 g)F em ales 2.52 0.123 0.397 0.0222 3.20 0. 102 0.424 0.0205 3.00 0.126 0.437 0.0237 3. 31 0.129 0.514 0.0278 i O rgan/B rain Weight Ratio * Males (g/g) Fem ales 1. 15 0. 0 6 2 ^ S 1.46 0.0523 1.40 0.0625 1.55 0.0671 O' ACM CC3 f/ t tary Level (ppm) C o n tro l 1 10 100 TABLE X LI TEST MATERIAL: A roclor 1242 Tw o-Year Chronic O ral Toxicity Study - Albino Rata Organ Weight and Ratio Data Summary of Mean Values Final Sacrifice Organ: Heart M ales O rga(ng)W eight Fem ale s O rgan/Bo(dgy/ioWoeigg)ht Ratio Males Fem ales 1.87 1.54 0.294 0.288 2.30* 1.51 0. 307 0.292 2.08* 1.59 0.303 0.298 2. 19* 1.41 0.335 0.303 SSttaaltli ssttiiccaallllyy ssiiggnniiffiiccaanntt ddiiffffeerreennccee aatt tthhee 9995 ppeerrcceenntt ccoonnffiiddeennccee lleevveell.. i j; t 1 J rL l |fc v O rgan/Brain Weight Ratio Males (g/g) Fem ales 0.860 1.040** 0 .7 9 ^ 0. 770 * 0.959* 1.010** 0. 788 0. 74 l * ADM 003697 O' til 00 5 00 r- TABLE XLII TEST MATERIAL: A roclor 1242 Two-Year Chronic Oral Toxicity Study - Albino Rats /*N. Organ Weight and Ratio Data Summary of Mean Values Final Sacrifice Organ: Brain D i e t a(prpymL)_e_v_e__l ______ Organ Weight Organ/Body Weight Ratio Final Body Weight of M a l e s _____(g_)___ F e m a l e s _____________M a l e s _(_g_/_1_0__0__gF) e' m a l e ______ S a cMr iafliecse d A n i m aFlcsm(agIreasm s ) Control . 2. 18 1. 9 5 0. 342 0. 302 642 551 1 2.20 1.96 0.294 0. 388 759 532 10 2. 18 2 ,0 1 0. J 13 0. 379 734 547 100 2.14 1.91 0.330 0.415 652 485 >o~x oouai a T0S 0 0 C, JfUL 67 c Histopathologic Findings v from all anim als Histopathologic sacrificed after 2e4xammionnatthis ono noft etsitswsu/aess and organs conducted. take Tables XLIII through XLVI list all histopathologic char, noted. Table XLVII contains the results of the histopathologic exam inati of the urinary bladders. Significant liver injury was found in animals fed 100 pp: A ro clo r 1242 (T<-UI). The compound associated lesions consisted of vacuolar change, focal hypertrophy and focal hyperplasia. In addition, tl were lesions of inflammation, necrosis, fibrosis and minor degeneration this group which, although seen in the controls and lower test groups, we m ore severe and frequent in the T-III group. The vacuolar change was not seen in the control animals but was observed occasionally in liv er from T -I (1 ppm) and T -II (10 ppm) anim als. The vacuolar change was observed frequently in the T-III anima This lesion is morphologically indicative of fatty degeneration. Form alin frozen sections of livers from representative anim als which displayed vacu olar changes were stained with Oil Red O to reveal the presence of fa: The vacuolar lesion in the cytoplasm of these cells was positively identifie as fat. The hypertrophic change found in the liver was focal and often lim ited to the central lobular area where groups of cells were swolle to two or three tim es their norm al size with clear pin* homogeneous cytop ACM OCJb'JS ooc 502 The hyperplasia was associated with the same cells and appeared to be . extension of the hypertrophic lesion. The hyperplastic cells were also usually hypertrophic. The most severe examples of hyperplasia appear, as nodular growths with limited compression of the surrounding normal hepatic tissue. The minor lesions of degeneration, hepatitis, ductule c proliferation, necrosis and focal lymphoid infiltration seen in the control animals and the T-1 and T-II groups are lesions of spontaneous disease a are not related to the Aroclor 1242. This level of liver disease is not unusual in old animals. Hyperplasia of the transitional epithelium was present in the u rin a ry bladder of animals from the control group and from each of the test groups. This lesion was usually associated with cystitis. All of the other lesions in the other tissues found in the animals are related to spontaneous disease and they are not unusual for rats of this age. VDDoeipnteloorvmiannaatreEy,. PACamothredoroliocnga, insDtCs. oVl.lMeg.e, oFfh. D. AQH C UOU 503 OOC 504 Number of Animals 1I Males n IT UoOl O TABLE XLIII TEST MATERIAL: Aroclor 1242 Two-Year Chronic Oral Toxicity Study - Albino Rats Histopathologic Changes Final Sacrifice Group: Control Organ Examined Heart Trachea Lung Liver Stomach Spleen Kidney Testes Prostate Adrenal Gland Ilrain Lye Findings Chronic focal myocarditis Tracheitis Chronic respiratory disease Focal degeneration Ductile hyperplasia Chronic gastritis 1l e m o s i d c r o s i s Chronic nephritis Testicular degeneration Periarteritis Inflammation Telangiectasis Nodular hyperplasia Focal fatty change Focal encephalitis Inilamma lion Incidence 3 3 91 2 I 3 8 2 2 1 I. 1 ft i c rt Average Grade 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 r> lii;- I O' xO Number of Animala 14 F e m a l e s IIDI' poX T A D L E X L ! continued TEST MATERIAL: Aroclor 1242 Two-Year Chronic Oral Toxicity Study - Albino Rats Histopathologic Changes Final Sacrifice Group: Control Organ Examined Heart Trachea Lung Liver Stomach Colon Spleen Uterus Kidney Ovary Findings Chronic focal myocarditis Tracheitis CF oh cr oa nl ilcy mr epshpoiirda tionrfyi l tdr ai st ieoans e Ductile hyperplasia Focal hepatitis Non-lipid vacuolar change Chronic gastritis Acanthosis - squamous epithelium Parasites 1I c i n o s i d c r o s i s Met ritis Chronic nephritis Focal lymphoid infiltration Cyst Incidence 7 9 133 2 1 2 3 5 1 4 63 1 1 Average Grade 2.0 1.0 l1.. 00 1.0 1.0 0. 5 1.0 1.0 - . 11.. 00 211... 000 1.0 Number of Animals 14 Fcmalcfl ` T A B L E XL1I! continued TEST MATERIAL: Aroclorl242 Two-Year Chronic Oral Toxicity Study - Albino Rats Histopathologic Changes Final Sacrifice Group: Control' Organ Examined Adrenal Gland Salivary Gland Findings Telangiectasis Nodular hyperplasia Chronic fibrosis and atrophy incidence 9. 4 1 All other tissues and organs were normal histologically. 0.5 = minimal 1.0 = slight Grading System 2. 0 = mild 3. 0 = m o d e r a t e 4.0 = severe 5.0 = extreme o o AUM 0 0 3 7 0 3 f Average Grade 1.0 1.0 1.0 t1 'tJKrr: Num ber of Animals 1 3 M a l e s O TABLE XLIV TEST MATERIAL: Aroclor 1242 Two-Year Chronic Oral Toxicity Study - Albino Rats Histopathologic Changes Final Sacrifice Group: I ppm < Organ Examined Heart Trachea Lung Liver Stomach Spleen Kidney Testes Prostate Adrenal Gland Findings Chronic focal myocarditis Tracheitis Chronic respiratory disease Focal lymphoid infiltration Cirrhosis Congestion Chronic gastritis and acanthosis 1l e m o s ido r o s i s Chronic nephritis Calcification Pc ria rtcritis Testicular degeneration Inflammation Telangiectasis Nodular hyperplasia Incidence s9 12 11 1 2 94 I 2 1 1 21 A vGerraadgee 1.0 2. 0 1.0 1.0 1.0 1.- 0 1.0 2. 0 2.0 1.0 2.0 1.0 4. 0 1.0 2. 0 507 t^ t* 0 \ TABLE XLIV continued TEST MATERIAL: Aroclor 1242 Two-Year Chronic Oral Toxicity Study - Albino Rata Histopathologic Changes Final Sacrifice Group: 1 ppm * Number of Animals Organ Examined Findings Incidence 14 F e m a l e s Heart Trachea Chronci focal myocarditis Tracheitis Lung Chronic respiratory disease Liver Ductile hyperplasia Pancreas Stomach Chronic focal pancreatitis Chronic gastritis Ulcerative gastritis Acanthosis Spleen Ileinosidcrosis o>X OO ooU o Kidney Uterus Adrenal Gland Chronic nephritis Met ritis Telangiectasis oU1 CO All other tissues and organs were norm al histologically. 6 7 13 3 2 2 1 2 8 6 1 10 Average G rade LO LO LO LO LO LO -.1.0 LO 2. 0 LO LO LO i Number of Animals 13 M al e s C CoCOVHTOD o D!u> ) TAI3LE XLV TEST MATERIAL: Aroclor 1242 Two- Year Chronic Oral Toxicity Study - Albino Rats Histopathologic Changes Final Sacrifice Group: 10 ppm * Organ Examined HTreaacrht ea Lung Liver Pancreas Stomach Spleen Kidney Testes Findings Chronic focal myocarditis Tracheitis Chronic respiratory disease Focal hypertrophy and hyperplasia 1l y p c r t r o p h y Vacuolar change (fatty) Ductile hyperplasia Chronic focal pancreatits Acantliosi a Inflammation, ulceration H eanmdo snicdcerroossiiss Chronic nephritis Testicular degeneration Periarteritis Incidence 67 9I 21 1 3 6I 7 10 2 3 r Average G rade 1.0 1.0 2. 0 1.0 ^ 1.0 ho 2.0 1.0 1.0 1.0 1.0 2. 0 3. 0 3. 0 ACM 000CC3707 TABLE XLV continue! TEST MATERIAL: Aroclor 1242 Two-Year Chronic Oral Toxicity Study - Albino Rats Histopathologic Changes Final Sacrifice Group: 10 ppm # NAunmimbearlso__f ______Organ Examined____________________ F ind ings_______ ___________________ Incidence 13 M a l e s 13 Females Prostate Adrenal Gland Heart Trachea Lung STtoonmgua ceh Spleen Lymph Node Kidney Uterus Adrenal Gland Inflammation Telangiectasis Medullary hyperplasia Nodular hyperplasia Chronic focal myocarditis Tracheitis Chronic respiratory disease CP he rr oi anritce rgiatsi st r i t i s and a c a n t h o s i s Ulceration Hemosiderosis ECdher omnai c n e p h r i t i s Metritis Telangiectasis Nodular hyperplasia 2 41 2 1 5 91 5 1 5 1 6 2 8 1 ^ A vGerraadgee 3. 0 1.0 ^ 1.0 1.0 1.0 1.0 2. 0 1.0 1.0 2.0 1.0 1.0 1.0 1.0 1.0 ff Number of Animals 6 Males TABLE XLVI TEST MATERIAL: Aroclor 1242 Two-Year Chronic Oral Toxicity Study - Albino Rats Histopathologic Changes Final Sacrifice Group: 100 ppm' Organ Examined Heart Trachea Lung Liver Pancreas Testes Stomach Spleen Lymph Node Kidney Findings Chronic focal myocarditis Tracheitis Chronic respiratory disease Focal degeneration Focal hypertrophy Hypertrophy Vacuolar change (fatty) Periarteritis CP eh rr oi anritce rgiat si st r i t i s and a c a n t h o s i s Periarteritis Hemosiderosis Periarteritis Chronic nephritis Incidence 3 63 1 1 1 3 1 3 1 1 1 1 4 Average Grade 1.0 2. 0 11.. 00 1.0 1.0 1.0 3. 0 21..00 2.0 1.0 3. 0 2. 0 AC* CC3 's Number of Animala 6 Males 14 F e m a l e s Ooo o> LTI DC NJ OO TABLE XLVI continued TEST MATERIAL: Aroclor 1242 Two-Year Chronic Oral Toxicity Study - Albino Rats Histopathologic Changes Final Sacrifice Group: 100 ppm* Organ Examined Prostate Adrenal Gland Salivary Gland Eye Findings Inflammation Focal fatty change Focal chronic inflammation inflammation Incidence 1 1 1 1 Heart Trachea Lung Liver Chronic focal myocarditis Tracheitis Chronic respiratory disease Focal degeneration FFoo ccaall hh yy pp ee rr pt rloaps ihay Hypertrophy Nodular hyperplasia Focal cho!angi<^icpatitis 4 8 6 3 2 2 3 1 1 V i1 c rc Average G r a d e-- a 31.. 00 1.0 /"s 1.0 1.0 1.0 1.0 1.0 11..00 2. 0 1.0 1.0 / TADLE XLVI continued TEST MATERIAL: Aroclor 1242 Two-Ycar Chronic Oral Toxicity Study - Albino Rats Histopathologie Changes Final Sacrifice Group: 100 ppm Number of Animals Organ Examined Findings 14 F e m a l e s ox3C> - Liver (continued) Pancreas Stomach Spleen Lymph Node Kidney Ute rus Adrenal Gland Focal hepatitis Hyperplasia Vacuolar change (fatty) Chronic focal pancreatitis Chronic gastritis Acanthosis Ulcerative gastritis Ulcer 1l e m o s i d e r o s i s Congestion Chronic nephritis Metritis Telangiectasis Nodidar hyperplasia Acanthosis j umeoo Uu-il All oilier tissues and organs were normal histologically. n c Grading System Incidence 1 I 11 1 22 1 1 4 1 7 2 8 41 Average Grade 1.0 3. 0 11..00 /""S. 1.0 1.0 1.0 1.0 2. 0 1.0 1.0 11..00 1.0 1.0 I t TABLE XLVII TEST MATERIAL: Aroclor 1242 Two-Year Chronic Oral Toxicity Study - Albino Rats Histopathologic Changes of the Urinary Bladder Final Sacrifice Group c Number Sex Examined Findings* M ii F 14 Proteinaceous plug (34) Focal epithelial hyperplasia (62) T-I (1 ppm ) M 12 F 13 Proteinaceous plug (582) Diffuse epithelial hyperplasia associated with diffuse cystitis (566) Diffuse epithelial hyperplasia associated with diffuse cystitis (580) None T- II M It Diffuse epithelial hyperplasia associated (10 ppm) with diffuse cystitis (651) C,**D>r Diffuse epithelial hyperplasia associated with diffuse cystitis and a proteinaceous plug (i>55) O CD rLn% T- III OooJ ' nJ x100 ppm) F M F 13 6 13 None Proteinaceous plug (744) Foctil epithelial hyperplasia (767) Individual animal numbers arc shown in pa renthescs. Grt^ilinp, S y s t e m 1.0 ? vninimal or trace 4.0 = severe Incidence i i i i i i i i i f. L tx> PS min Average Grade i . 2 1 3 1 r - 2 A. c G. Detailed Description of Tumor Findings Tumor data, for individual animals including location, weigh: and pathologic classification are presented in Table XLVIII through LI. None of these tumors could be related to the ingestion of Arocl 1242 and are considered normal for a random population of rats this ag< ACM C0371 00 515 VUl.' 516 Munmmbaelr ml Sex J-M 2-M 47 - F 48- F 50- F OO 52 - F *9-F 1-F n* OU^Oi Location Abdomen Pancreas Abdomen Lymph node Abdomen Abdomen Abdomen AA bddr eonmael ng l a n d Abdomen TABLE XLVIIl TEST MATERIAL: Aroclor 1242 Two-Year Chronic Oral Toxicity Study - Albino Rats Description of Tumor Findings Croup: Control Weight (grams) 11.76 63 45 .. 90 98 - 88.92 S(cimze) - 85 xx 12 xx 22 2x2x1 2x2x3 > * 13 x li x 4 Classification Mammary fibroadenoma Adenocarcinoma MM aammmmaarryy ffiibbrrooaaddeennoommaa Reticulum cell sarcoma Mammary fibroadenoma Mammary fibroadenoma Mammary fibroadenoma M1'laicmomcharroymfoicbyroloamdeanoma Fibroadenoma MTooennstth s 24 24 24 24 24 7 24 24 . 24 TAI3LE XL1X TEST MATERIAL: Aroclor 1242 Two-Year Chronic Oral Toxicity Study - Albino Rats Description of Tumor Findings Group: 1 ppm NAunmimbaelr Weight Size and Sex_________ Location___________ (grams)__________ (cm)__________________ Classification Moonnths _____________ T e s t 566-M Abdomen - Adenocarcinoma 24 569-M 604-F 609-F Spleen Abdomen Abdomen --15.00 5 x 3 x 1 Lymphosarcoma Mammary fibroadenoma Fibroadenoma 22 24 24 611-F Abdomen 5335..0500 5I xx 3l xx 1l FF ii bb rr oo aa dd ee nn oo mm aa 24 613-F OAvbadroymen - 3 x 2- x 1 GFirbarnoualdoesnaocmeall tumor 24 Q 15-F Abdomen 335.00 13 x 10 x 5 Mammary fibroadenoma 23 OO Ul AM 003715 f/ NaAnundmi mSb eaexlr 621 -F 627-F 628-F 630-M 631 -F 634 - F > s.r Location Abdomen Pituitary Abdomen Abdomen UAbtedroums en Abdomen AP ibtduoi tma er yn AUM 003716 TABLE XLIX continued TEST MATERIAL: Aroclor 1242 Two-Year Chronic Oral Toxicity Study - Albino Rats Description of Tumor Findings Group: 1 ppm (Wg reaimg hat) 18.00 115177..2900 44. 00 13. 41 39. 36 Size ______ Lsinl________ 1x3x3 - 6x3x3 97 xx 66 xx 42 3x2x1 6x5x3 6x5x4 Classification Fibroadenoma Chromophobe adenoma Fibroadenoma Mammary fibroadenoma Mammary fibroadenoma FF iibb rrooma dae n o m a Fibroadenoma CFihbrroomaodpehnoobmea adenoma MTooennstth 24 24 24 23 24 24 24 o> 518 NaAnundmimSbeaexlr 6-10- M 646-M ' 662-M 687- F 689- F 690-F <A95 -F OO - F OU Ln vo 1- F VUOOIj I TABLEL TEST MATERIAL: Aroclor 1242 Two-Year Chronic Oral Toxicity Study - Albino Rats Description of Tumor Findings Group: JO ppm Location Weight (g ram a )_____ Abdomen 129.0 AP adnrecnreaal sgland - AP ibtduoi tma er yn 280- .0 Pituitary - Abdomen - Pituitary - AAbbddoommeenn 233.. 9105 Abdomen 175. 0 Parathyroid gland - (Scimze) 9x7x3 -- - - 73 xx 63 xx 32 8x7x5 - Classification Fibroadenoma MIsleedtucllealrlyadtuemnoomr a CMharmommoaprhyofbiebraodaedneonmoma a Chromophobe adenoma Mammary adenocarcinoma Chromophobe adenoma . MMaammmmaarryy ffiibbrrooaaddeennoommaa Mammary fibroadenoma A d e n o m a MTooennstths 24 24 2242 24 24 24 24 24 24 t rf NaAnundmimSbeaexlr 707- F 708- F 71 1-F 7 12-F Location Abdomen Abdomen Abdomen Saubbdcoumtainneaolus, TABLE L continued TEST MATERIAL: Aroclor 1242 Two-Year Chronic Oral Toxicity Study - Albino Rats Description of Tumor Findings Group: 10 ppm (Wgreaimghat) 74. 6 189.0 6.96 155. 0 S(cizme) 7x6x3 5x4x1 3x2x1 II x 8 x 3 Classification Mammary fibroadenoma Mammary fibroadenoma Mammary fibroadenoma Fatty tissue fibroma O o LOtoH nu* OO !r*i %t MTooennatths 24 24 24 24 tUoI NaAnundmimSbeeaxlr 744-M 775-F 785-F 789-F 794-F Location Pancreas Ovary Pituitary Adrenal gland Abdomen TABLE LI TEST MATERIAL: Aroclor 1242 Two-Year Chronic Oral Toxicily Study - Albino Rats Description of Tumor Findings Group: 100 ppm ' (Wg reai mg hst) - 260. 0 (Scimze) - io X lo X 5 Classification Islet cell adenoma Granulosa cell tumor Chromophobe adenoma Medullary tumor Mammary fibroadenoma I wt ss* -IuhI MToeonnatht s 24 24 24 24 23 I r OO UK1) D> 4 <if)'