Document 93My9ZrB5yNv0M5d0qmNvav7D

AR226-2906 _______hag sdsJRistaggii orally so youag adolc Ie raca at repa?(l do iW&la of lCbr 1,000 ag/kg, 100 ag/kg or 10 g/kg for 10 day over 2-WRfc period. Clinical aigna obrvd included: waknew, Calad prlnal rea, lethargy, protrtlon, buap6d-pocur, cong*eioa chroBodcryorrha ani valghc lo. Conpound-induced macroccoptc and alcroBcople lloac ver preieat tn Cbil thyauB, <pleen, booe aarrow and kidaey of high-doM aaiiulf, BBC(U of th ortality aaen la the blghdo group, reversibility of thew leiioax conid not be adequately evaluated. No treatBeot-relaced lealona --re obaarved ia the lov or iatenwdiate doe group*. Staciatical analyala of clliaigal_laberator? Mliuraaenta data showed vlt^HHUBlBIHlHHID'0 that raf doed 10 tia l*vel of 100 g/kg and 1,000 ng/kg had bigtier! thaft noCMiery^lsyteTounta and haatos^fca_^ich appeared EO beiral-acadxb-'-tlie-'doll^ Racs dosed lth 1,000 ^^KW^IBBIBBiBHBlO14 ^S^^ ^^i?6* ^uota, alaoac twice ttr norialrangeeliaojBRedT^chtcontrola. tliea^.anlBala alao ahowed a threa-fold increase ia serua blood urna' oitrogeD nd increaaed hemoglobin, aerua glutaaic pyruvic traaaaaia^ activity, and creatlnlne. The 100 ag/kg created raca ahowd a light increaae ia arm total protela. An increaat in Company Sanitized. Does not contain TSCA CB! che relative number of neuCro^hlls (1,000 ag/kg group) aod a alight co moderate hypochrooia (100 og/kg sad 1000 ag/kg groups) was seen. In Cbe recovery groups, ^ slight Increase in serum creaciaine levels la the 100 ag/kg created racs wa observed* In the absence of this parameter being significantly differeotfprior to cfcp recovery period, the significance of the finding is questionable. No other differences clinical pathologic para--ter jstudies la the recovery were racs detected la (only I rat the was examined in the 1,000 ag/kg g^oup). Analysis of blood for or :aaofluorlde revealed a doae-related increase lo concentration following the 1 )tb dose (1, 30 79, and 197 ppa, exposures of 0, 10, 100, and j ,000 s-s/kg, : eapeccively) The8e values dropped to 0.5, 12, 25, and 25 ppo (1 rat), 0 to ,000 og/kg, respectively, 14 days after Che last creacaenc, indicating el i;araac froa the blood is relatively slow, Procedure; The test gmterlalL as an aqueous solution at con<--;n radons of either 102, 1Z or 0.12, was adainistftrad by totragastric intubation Co 3 groups oz young adult Crl:CD* ale rats, 10 r<its per group, 5 tiaes a week for 2 weeks at repeated dose evels of either 1*000 ag/kg, 100 ag/kg or 10 nig/kg; an additional group of 10 racs served as, cpncrola and was intubacad with distilled water. Two fcci rats at 1,000 we/kg died before the 6th <*ose and 1 before the 9th dose. F;.ve coafcrol aad 14 cJTsc rats were sacrificed approxiaately 4 hours after tii last dose Two ^se raes at 1,000 ag/kg died during the recovery period, "he reaalntng 5 controls and 11 test rats were observed over a 14-day racove: y period and then''acrlfIced. All racs were examined grossly, selected cii sues were weigfulid aiul selected tissue and organs were evaluated histolo) ically. Clinical pathology aeasureoents were taken on all surviving rats 4 hours after the ZOtb dose and after the 14-day recovery p-riod. Blood was a^so collected at the saae periods for fluorine analysis* - 2 - Company Sanitized. QQQS not conaain' Results: Dose (ag/kg/day) 1,000 100 No. of Doaea 10 10 Mor^ ' '^ 9/^0 0/^0 Clinical Signs First Week; Weakness and weight loss* Second Week; Weakness, stained per^neal area, lethargy, prostration, lumped posture and freight loss* Two rats died before the 6th dose and 1 died before the 9th dose. Becgviry Period; Weakness, congestion huaped posture, chrooodacryorrhea and . weight loss. Two rats died during the recovry period. First tffcdk; Slight weight loss. Second Week; Slight weight loss. Becovery Period; None* 10 10 First Week- Slight weight loss. Second^JWeek; Slight weight loss. Itecovery period; None, Pathologic Changes; See AppendixA (Pathology Report Ho. Clinical pathology; See Appendix B (Clinical Report forhj Fluorine Analysts; See AppendixC (Analytical Report job No - 3 - Company Sanitized. Does net contain TSCA C8t 5ejpore bys Reviewed by; Study Director Approved by: JAH:jrg:WP:1.22 Data laaugd: June 3. 1982 spore No. Section Supervisor ACH6 laveccigatlons - 4 - Company Sasltass. C-cas nsS cowsm TSCA GBf APPENDIX A E. L DU FONT OeNEMOURS S. COMPANY HASKKU. LABOftATOKY FOR TOXiCOLO^y ANO INDUSTRIAL MEOICINK [ El-KTON ROAO, NEWARK, DELAWARE 19711 CENTRAL. RESEARCH AND DEVELOPMENT OCPARTMENT Pathology Repoi I N11 UH| ^ -14008 Polymer Products Depar&nent & Chemical & Pigments Department Oral Subaeute Study in CPi> Rats I Aoril 21. 1982 Sunnnary j ' I , . Compound-Induced inacroflcjopic and microscopic lesions were present in the thymua (Lynphocytic depleeloq), spleen (Lynphocytic depletion), bone marrow (Hypocellularlty), and kidney a (Nephritis) of high-dose animals. Because of excessive mortality in the high-dose group, reversibility of these lesions was not adequately evaluated. Conpound-induced lesions yers not observed in the low or intermediate-dose groubs. Introduction Every animal (except 1^30p58) in this study was given a complete post- i mortem examination. Microscolc examinations were also performed on selected I I I-:: tissues from each available a limal.* Groups I (0 ing/kg), (1000 mg/kg), ^ ';,- I I I ;fci. (100 mg/kg), and IV (10 mi/kg) consisted of ten male rats each. Each --'' group had a 12 day feeding phase and a 14 day recovery phase except the * Adrenal Glands, Thyroid Gland, Parathyroid Glands, Esophagus, Stomach, Oueodenum, Ileum, Jejunum. Ce^um, Colon, Liver, Spleen, Bone Marrow; Thyaus, Heart, Sternum, Eyes, Brain, trachea. Lungs* Kidneys, Tesces and Bpididymides. - 5 - Company SanStized. Does not contain TSCA CBt high-dose group. Due to marxed clinical toxicity and early mortality in this i -" * group, only one rat survived the 14 day recovery period. Two additional high- dose rats survived for fchre^ and seven days in the recovery phase. Histomorphological lesions were tabulated by individual animal in Table I and were suiomaziz d in Tattle II. Results | i' <-' ' ' . Mscrescopically, coapo^ad-inducsd tissue alterations were restricted to the spleen (splenic atrophy!- 3 rats) and thymus (thymic atrophy - 3 rats) in the high-dose group. Both lesions were associated microscopically with mild Co severe lymphocytic depletion. Aniaals from all groups had multifocal areas of reddish-gray oottl^ag in the pulmonary.parenchyma. These lesions were associated hiatonorphologically with multifocal areas of granulomatous interstitial pneumonlcis. . . i Microscopically, compotlnd-induced lesions were present in the spleen (lyiBphocytic detletlon - 7o^9). bone marrow (hypocellularlty - 5 of 7), thynus (lymphocytic depletion - 5 of 8) fisd kidneys (purulent Cubuloister- i i . stifcial nephritis - 8 of 9),' of the high-dose group. Compound-induced lesions were not present in the other test groups. i. . The renal lesion in this study was rather unique in that there was selective coxiclty for the dllatal and collecting tubules and the medulla . " '-..: ! was more abverely affected than the cortex., TSe lesion was characterized by L degeneration and regeneration of the Cybular pitheliuni with tubular ^ ectasla. This was associated with a marked interstitial infiltration with neutrophils and edema fluid.: Occasionally, there were small foci of renal papillary necrosis assoelatejd with the neutrophllic exudate. One rat (if 301555 - 6 - Company Sanitized. Dess nss csntain TSCA C31 - Group II) that survived the 14-day recovery period did not have similar compound-induced lesions. \ There were several other!microscopic Inflammatory and/or degenerative lesions that were considered,;because of their common occurrence and/or ... ' their low frequency, to be" incidental spontaneous lesions In this group of : rats. ' '. WDK:WCK:vfd Report by; ^ . WlUlai/D" Kerns. D.V.M. Senior Research Pathologist Tf^Xw^ JWM^/ Approved by:; WUUaa C. Knrfuss, D.V.M. Manager, Pathology Division 7 - Company Sanitized. Does not contain TSCA CBI PAMOLOCT TABLE CODES * Tissue Accounting Code: L Lesion observed N So significaAS lesion observed 0 Tissue missing I Tissue insufficient for histomorphologic evaluation N Only one gland is present and it is normal Q Specimen quality is inadequate for an accurate assessmentiof subtle tissue alteration, other wise the tissue appears to be normal A Autolysia P Present ; ** Degree of Change: 1 - Minimal : 2 - Mild i ' 3 Moderate 4 " M&rked I 5 " Severe ! *** Mode of Death: S Sacrificed D Unscheduled (death - 8 - Company SaRitissd. BQSS rsoi sentain TSCA CBt 11-14008 Tlxauo*/ t)btiervott(in8< ElMCltlHK SYBT^ Groupi I Duel 0 M^ft Mode at Heaths S 8 8 8 8 8 P S S 8 H N M 1 vms UH (1 ^Z ^ 12 12 ! Recovery Djyci 0 1 1 0 t Mrt Ho. 301-. 144 S* S42 S4 5 6 6 6 4 * 4 S 1 6 Sil 26 26 U M SU H9 Thyroid Gland farjithyrold Gland (a) 1 OASTBO INTB8TIHAL 8KUTKM H U M 0 I M N 1 N 1 DON HNMMOIHONN BOOOO I N PurlusophiigttiN, gfanuluutoir. focal -- -- N H H M H N Btotiach 0 3 (ilamlulur, ulroaliy, dllfuaii o Uuuduimlu tu 1 luupi ? U) Jujuuum 6) 3 L'ucun % N Ciiliin (0 .0. l.lvur a 0 -- - HU M U KU M U u M N M NN N H N N N (1 H M H H H H -- W tt B It |i H ---N-M-U- N N N 0 -- MNHIHNUHUH Nu H M -- U U li r U H M M 11 11 H U M 1 nhi 04 MM -11 4 M 4 H Q Q < H (B yi S3 0 fJ6 0 0 3 i? 5" a? 0 > 0 " IfifiLaZk 8 S D B 1 M H 11 H I 000(0 12 12 10 1; S50 SS1 S52 55: 12 S54 S: OHINONUHUNJNINMtfOOU NNHLNH - - - 2 NNAIIHH NNNNHLNHNNMH H A N H I* UAUUU N N A N H H MQ M<} AN HH NQ HQ 1 0 1 r J l. 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Sscis nsi eoniaifi TSCA CSS ":: "\^;; ..',--"- ^-.:^ 1^. ^H1400fl* 1 (Continued ) - INDIVIDUAL ANIMAL 111STOPATniOUOT DATA TiBBuu*/ Obrarvotlono** flrouDi Doaal Mada of Daathi ftiSril D.. on RacowervDavi (ft Ho. 3ttl- 88 U H I? 12 0 B SB2 181 III 100 M/k 1 8 S 8 M H H li 12 H 2 ; 1 it ,...,,,S,8S,,,,.,,98f6fi...1,8H7...,51 BHDOCHINB SVB1BM Ailrenal (Jiuild ia) N N N H N N N Thyroid Olund ruratliyruld Glund (s) UASTBO iinaaTiH^ ^i>rw 000000 0 0 N 0 N 0 HO 1 ? >- BaapbttguB N H N H .N N N tjj ^, 1 PtirlaHopliBiltl*, grautMukou, focal . . - - ^ 0 0 t'^""c^^ M N 1 N N N N Ulunilulur, utiuphy, diffuiii - - - - O Ouujuiniui B) H H M H N M N < ll>i 0) lu|uiiun eu H H H N H N N li H H H H N N H 3. Cuiun NS" (.ulini & t,lvcr C3 Sg (0 3 a , 0 0 a B) H N H N H M H (1 H h H N M N N Q Q <) Q H H - 3' -1 CA P 0 .3 1 8 M 1 H 26 21 26 14 I 14 189 9 Sl N N N N N N 0 0 0 N N N - .,, N N N - - N H H N H H N N M M H M N M N It N N I Sfisa S - 10 ( N M H M li 12 12 H H ( 0 0 A A W. Ml 594 59S 16 I N N N 1 N 0 ONMHONOH -- N NNNM N M M N N N N MNH NNNHHNNNN N N <t qNHHNNQHNLNNN 380 VOS1 Ui-33iioo sou SSOQ -peagj^s AuedmoQ - frT - S- F e c - 1 i ; S j ^ ; . ; j --X -- K 1 = 5S e; & -- c -- --< B C "^ E -- - ??. tt B C -- --Bfx B < S -- " ~ = > -- ~ K g ? 5 ^^'SBp'*- : :" < C -. < s c i jRC -- B r- < in -- a B B--B ICB ft g ?. s 5 '< e " -- B !<*<&' fe 1 ? te s- c s o. &B - ^ 1 11 IS ^ c w j| I g ft s 5 if ^ 1 KIIXIwIX < XI 1 Z 1 -- 1 K 1 e ? S = B 5g s B ~ S B 1 V e ss S ? y s ; ^m69 ce f u s B 6 -- n S eo ? , ',, 5' = & ? " gs no K e < e B 1 " - '- K K a e3 ? fcgj & x? 52s' & r'^g5s-?i?! 1 e^ X a S eE t-" if K-- R Z -- -- Z 1 XI 1 Z> 1 X 1 Z 1 X 1 Z 1 -- 1 K ' ' ^o5x , , S - f6M XBI --ft XX 1 l 1 XI B X 1 -- t Z 1 K 1 X 1 f \ ?0= BSS.45 ' ' SS -a MX i xi u ^ 1 ( z i M i x 1 K 1 d 1 Z 1 1 ' ! k M B> E B SSg X B Z Z 1 XI 1 X < K 1 X SSK ? s ! 8 ? 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' " baswo*aa s a -4 .a u u 323-313 ; -- -- a >. .= u -- -< 3 ^ s " ^ 5 S " ' a g ^ ' 3z aficn* a y ' a ^ i ' ~ s 3SS5.2 a > = a " e> 5 z S - s 3 f-i " ^ " "3 ^ 91 a x * v*4uBcf-au>lx | ^ * a - - u a -- .-- 4 -- & -- a a u >fa<feUu^rU9a-o*geieg3uaoCI----z|>!>ifae.u-^^i=-i.e.3Maa---&a-fsuaatj a .bo 3 w ^w 3 a 1 ' SS'-g-'-S^23-31- ''i! (c =1 : - 15 - Company Sanitized. Does not contain TSCA CBI ^ ^ i! ix ix " S Sg i i 1 <ax i i MX 83S . . . z . , z (BX S ^ S <ax ^iS<^^J i o <a " ; eax N- 0 m 8 11 11 11 ' IX 1 I X 1 1 Z 1 1 X 1 ix i t a i x . as X - I> 11 11 C 31 1 1 Z 1 2 we i (1 . ix 1 > Z jl ** ^ j | ax *--< Mfl X -- 4 S--a =3 -- -- i " ; ea E 11 IX 1 1 X 1 11 IX 1 t Z 1 i a i i z i ii ix i i i i z i i I m i x i ii 1X1 1 > IX 1 i 9 I ^ i nx Ml 4 3 ' 11 IX 1 1 Z 1 i* ; S-85S*SU 9 S1 iar*;:" 'S :?5 . w ?|i3 S a s -- -- w a s S a ^ S IX:) 11 -- IZ 1 9 S . -S -: sSiS^ . 3. sa j H ill Is s^ 233 5 3 -- h e i ^ -'- H 1?2 =2 SS -- s araaa a3 -si; > cl fUit3 3a-i-.a a3"3 '3 ^!'uS --3<rxa<a J .1 A 2 3'fl 3 --B aa"~-a>-).3 --aa-aaaajar:-aj -a jw 333 a----a w 9 z--ana s : = b n zaai e = a--w*> x9 aa soa.---3 ?- 's ? -- -- f "^ 'a " ua-- > - .- -3 c -- a --s - & u 3 . 3- ^ S ^> - - ^ -- & a> s a -- -- - 16 - Company Sanitized. IJoes not contain TSCA CES a^ - ' ~ 11-14008 _ ' T' ' TABLE II SUMMARY OF HISTOPATHOLOGY DATA 214M1M 1 Group; Daya on Study; No. of Animals; TiBaue/Observation________Sex; EBOptiagus I 12 5 M (4) 26 __8___1_0___1U2 ___1_5 ___2_6 5 12 III 5 M M_____M M_____M__ (5) (2) (1) (4) (0) (1) (5) PeriesophagitiB, granuloniacous, foiial 0 0 0 0 1 -^0.-0^_,-_^0--0- Stomach ---------^----^- ^ ^ _ ^ . Glandular, atrophy, diffuse 0 1 ^r 00 000 00 : . (5) (5) (2) (1) (4) " :^ 1 0 :H6is||Aij^i^(l(jg^ Hep^i9 ./ . .^o^i^tilc."' . pUrulog^a^<^jiCOH3, " . . ' ..".- \ '.-T'J''' '.i f1''-.' .'.A 'yff ' '4. rf'" n " ;,-. .' ''.''.-.'' :_ 0 0 0 :NI<%^, .:^^^^.2^^ ^/'^ Lymphocytic, depletion, diffuse ' ' ' ' ,' - xi'-'^; ^_^. o q'' .,^),;(l).,;.^4),., 0 0 Bone Marrow (4) (4) (2) (1) (3) 2 1 3 1 0 0 0 Hypocellularlty. diffuse 0 0 00 'rhyroua (4) (5) (2) (0) (4) 1 1 3 0 0 Lymphocycic depletion, diffuse 0 0 0 0 Thyrousiti.s, pyogranulomatous, 2 0 2 1 0 Focal (0) (1) ::. . .- ' :' 0 ' - o. ^o' (0) (1) (I) (1) (5) ' ' 0 o ^ :^' "(5) ';< (1) (5) 0 0 0 0 0 0 1 00 <) " Number of tissues evaluatfcd ^i^l^is6^,:A^.:.,,^. ^JsM,^::^.;,^ ..^-^s<^^L ;^. ' l.i....,?- (,;&>. .,7,.rti,y.^?.l.^EB-];:, -' -'3. --".-' 1W1. 1i.1-^' L H-14008 TABLE II (Cointiiiued) SIIJMMABY OF HISTOP,&TH()LOGY DAl'A Group: I Days on Study: 12 26 No. of Animals: 5 5 Tissue/Observation Sex: H H II 8 10 12 15 26 2 1 4 1 1 M M M M M 12 I I I 5 M Lymph Node (Thymic) (4) (5) (2) (1) (4) (0) (1) (5) " '*'. " Lymphocytic hyperplasia, diffuse ---.----- Trachea Tracheitia, lymphocytic, focal ; 0 0 0 p 0 0 0 0 - (4) (4) <1) (.1) C4) CO) (D (4) " ' 0 0 ^:^0 0 1 0 0 2 - ^'K (ff Lungs; ': ' i "'. '' '"'" ' , '"'' . , .. ' . Pneumbnttis,,interstitial, ' .;;gr^ilc^t<)ii(fl^rffua;fc:|^Qcal- .' <5) (5) V;4 .': ' "- '2: .;' 7'2'v: ..^^ - :'. :' <1) : ^..?.:'i.: o ,^K- '"f '-''" .. S.^- "^ ,.W tS (U 3 '< M ' limeys "^:^y" ':' ..^^l,'^; '. , ;;^^^Ri^it^ia;e^,.tubHl^^ s ''. ~ .' ''-'.!i 'U-'. purulent, bilateral, inulclfocal 0 0 Nephritis, lymphocytic. Inter stitial, focal ^ 1 1 ..' ..'^ (t)'- 1 (1) 2 1 0 0 0 si. Tubular epithelium, basophllia ?' focal or multifocal 2 2 0 0 <D p. Nephrosis, multifocal, 0 0 unilateral 0 0 0 0 (0 03) Capsulitis, fibrinopurlent, 0 hemorrhagic, multlfocal, uni 8 lateral 0 0 0 0 3 5" 5-<" () " Number of tissues evaluated w g > r. : j j , ^ ^ ' - . ^ ' . ' " ^ . J '. '^ ^ ^ " :;s;-^;"^.' -.^- - >; . '" .&-LL^;, "^'' .. .. .- ,,,!;" '1 . ^',M:i';-f^AsSMr, '-w (4) .^.1 l^)^' 4 0 0 0 0 ^ .-.,;.JST. ;, 0) 0 J U) i 0 0 0 0 ':. - ^'^ '- ( .1 .,. 0) 0 i i 0 0 (5) ;-,^'2. ;. (5), 0 2 1 0 0 Group:____I Days on Study; 12 No. of Animals; 5 Ttasue/Obaervation________Sex; M 26 ___8____10___U12___1_5___2_6 5 2 I A 1 1 12 HI 5 M M M M_____M M______M I ; : : ; 1 to ': i Teatis (es); Semlniferoua tubular epithelium, atrophy, diffuse, bilateral Interstitial.cell hyperplasia, diffuse, bilateral Epidldymis (des): (5) (5) (I) (1) (A) (1) (!) 00 00000 0000000 (5) (5 10 10 0 Epidldymltia, interaitlal, | lymphocytic, focal, g unilateral ^ m P 10 00000 00 E N ----------------------------.--------------------------------------------------------------i___,-----.--.---------- ro a () Number of tissues evaluated 3 w-f a > o APPENDIX B E. 1. DU PONT DE NEMOURS 5 COMPANY HASKBLL LABORATORY POM ToxiCoijticY AND lNDUrnIAL MBDICINC ! ELKTON ROAD, NCWARK, OCLAWAMI lj711 ! CENTRAL RESEARCH AND DEVCLOPMtMT dePARTMBNT Subacute Oral Tend. Medical Research Project So Haakell Laboratory No. 14008 June 29, 1981 Blood s 10 times with1 10 nig/leg and examined. rats intragaatrically dosed it levels of 0 ing/kg (controls). rats dosed with 1000 ag/kg were After the tenth doae, bLood was taken from the tails of these rats for the measurement of erytb'ocytea (BBC), hemoglobin (Hb), mean corpuscular voluae (MCV), platelets, leucocytes (WBC) and relative number of neutrophils (Neut), lyiaphocytes (Lymph), eosinophil (Eosin), monocytes (Mono) and baaophila (Baso) . The hematocrit (fit)* aeon corpuscular hemoglobin (MCB) and mean corpuscular hemoglobin concentration (MGHC) were calculated from these data. Alkaline phosphatase CAP),, glutainic-pyruvic Cransaminase (GPI), glutami-c-oxaloacetic transaminale (GOT), urea nitrogen (BUN), creatinine (CHEAT), and total protein (TPROT) were also measured in the serum. Five rats from the 0 ag/kg, 10 mg/kg and 100 mg^kg groups and four, rats from the 1000 mg/kg group were then sacrificed for pafcaology. After a 14-day recovery period, the measurements were repeated oji the surviving rats in each group. j i B U The data were analysed statistically by a one-way analysi^^^vi Least significant difference a were calculated to compare preated racs with the controls when the ratio of variances Lffaraaes asoag tie groups. Significance was judged at the probability level. 0.05 The results of the clinical laboratory Table I; statistical analyst^ in Table II. mals are listed in the computer printout attache eaenta are summarized in ements on individual ani- to the report. ^Jftj--ta--ti--st--ic--al--a--n--aly--si--s --of--jjd--ieMledLvatetals sohofw1e0d0cihnagt/kgratasndd1o0s0ed0 10 times with nig/kg had higher TannocBaI^^yl^^cycecoTOS's and hematocrits which appeared to be related Co th I'l-se. These two .rou}pa also had a slightly lower MCH and MCHC when 20 Company Sanitised. Dees not contain TSCA CB? ,trol animals. Bats dosed with 1000 fflg/kg -- ^ang--ee^s--tab--Ils-h^e--dT--oy--th e - - COB r : ^u xols ^ . y60 The s c e ounts, animal - aS s, siost also twice the normal showed a three-fold increase in aerun BUN and increased hemoglobin, GpT and creatinine. The 100 mg/kg treated rats shoved a slight increase in serum ^ocal protein. Examination of the differential smears 9 lowed an Increase in .the relative nurAer of neutrophils in the 1000 iag/k{ group and a lighfc to moderate hypochromia in the 100 og/kg aad 1000 ag/kg grciipa. "; __ later, oniy one rat remained'in the 1000 mg/kgl reaeed group. Statistical analysis at this tine included fkg aad 10) og/kg dose levels, Other than a slight increase _ and|fmmimB in serum creatinine levels t: th<i 100 mg/ke-treatedrats. nodiaically significant difference betveiin the control rats preafced rats was coun^i for the other measurements Bade on the blooc aeport by; /lfi-ti,.:^&.^^fj^u^ Catherine C. Hatarese Technician CCM:JBB:tBjh Approved by; >^^(^k^M^' r\ \ I 'T^ ( John R. Bames '^--^ Chief, Clinical Pathology Section 21 - Company Qs^SSzM. Sess ^.Qi ssnSain TSCA CSB e d r> 000 e (N -< \0 '3- B >034<'r^OntCcs'1t0i0i-<(<T-C< eMtM\er.-i1-t 00""<>-|<-ITN<Crt>OI 0ft0 C a -l Of . -ii 00 a S o<a- <ci<oo & <o1>-f1t'04r-in.cN>rtOotrotrwtBBft-i'o<now^ori.^To^oo 1 r-l 1 ac ^ f> i 9in ir> 0 r 0 >oc4 0 NO'-Ai<or-nct>si<fiyai^u--><cO>Ot^C. 'i-lsoOiNi^--iai-oi<ms^ooo-A r-1 01 .CM i-ri --i c a- oo o ocn i ^.f.-ui.i orr ^tstc.stex<o- <oM-ia'oo o o ^ O 'ro.o<srs^rooi o ' s 0 0 3 09>00 1 ^ i-l<6 0 00 cor-^c-oehnCNMMfeootScc"><oconmen Oa00'-l<ff""(>Mooco*> -<u"i s r>< u J6 i Siw o <n^-o <o-< i^int-ir-.c^ooo'a'i-i'a'o-a'O^ciO'A'^OsO ^irt<^-c-i^<o c>ioc>t 0 -i -l 1-1 0 ri h 6fl ^ ^ r-i mneMO oim-<of>orn~e(^-Ofoft<"M<>-<0(0^Oir>0 0c^n>of\ti<-4M-(0m ? 0 0 N . I -4 Of ^ T \o cn g% in o o 0 <69> 5 0 o mr-i(ena mae' >ci-nOeiSo<-cipM<E<roktftOmoaion c,-r< icui'-fitooifl o ^ i tn 1 . 1. 'o ^ ea *> ID uej >>i4-r4 o o u inon^euc-31-i-iSEi^ u^w sas-e^uooo^.e ij^ocn UUj>d<U&Oejaf.4u0<0Hi-- ssso ^uSOBOOlU^.B. >>SS>SSai33Saei saOssOSUZU:sUaf<-I>O-iOzi^JOMSa<:uucaUE-i ki a "S B ^'- 9> ^ 0 0 B 10 4J S ^ ^M.e.ea<-i f-i CP r-i a - 111 -ri <J H 0} 0) o '-i ~-i^-Ol'M^e .--OSBO >> 1-1 B 0 <; 0 0 E- e-1 Z & Ci 0 3 Cd 06 5 b n - 22 Company Sanitized. Does nof contain TSCA CB( hJ 1*1 ( 0 0 o 0) w (U 3 faS- s a, 0 0 w (rt 3 a 0 <3 :3 ^?i (ii S" -fl 0 0 > 0 OB TABLE IT SUMMARY OF STATISTICAL ANALYSIS ON RATS INTUBATEP RBC Hb Hfc MCV MCH MCHC Platelet WBC Neut Lymph Eosin Mono AP GPT ! GOT BUN GREAT TPROT p* 23.) 13.1 30.4 3.4 5.2 18.1 1.9 9.4 24.1 15.7 1.0 5.3 5.5 3.8 1.6 122.0 34.2 5.2 10 moflta 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 F " Ratio of variance if? F* " Significant 2.89 fH Significant If 3'3.88 10 DAY "" --' - + 0 + 0 -IW"U mg/kg + + + 0 0 0 0 + 0 + + 0 0 0 + 0 0 0 + 0 0 0 + 0 + + 0 Vf 0.1 0.0 0.4 0.2 0.1 1.4 2.0 2.9 0.9 1.8 2 i.* 1.6 6.4 0.3 0.5 0.7 10.0 2.3 MSCO 10 ing/kg 0 0 0 0 0 0 0 0 0 0 0 0 - 0 0 0 0 0 (0) " Not significantly different than contr (+) " Significantly highi r than controls (-) - Significantly lower than controls MR: I COMPHD:!____ PERIOD:10 DAY TOKICOLOGIST: DASHIEL T | 14008 HASKELL CODE#: .. DPRTMMT.-?PD&CP - REPORT acTE: l8-Kay-8l CLINICAL LAB: MATARESE GROUP: 1CM DOSE; SAMPLE DATE: 15-MAT-81 ANIMALS: 301540 301541 301542 301543 301544 301545 301546 301547 301548 301549 AVG. S. D. S. 5. RBC MM/cn 6.91 6.67 6.41 6.64 6.77 6.35 6.47 6.87 6.86 6.46 6.641 0.208 0*066 Hb ef 15.2 15.2 14.6 15.9 15.1 14.1 15.3 15.8 16.0 15.4 15.26 0.59 0.19 SEX; MALE . SPECIES: RAT BIRTS DATE: 13-MAR-81 It HCV % /C!9fS 3^. 55. 39. 50. 37 58. 38. 58. 38. 57. 36. 57. 38. 58. 41. 59. "O. 59. 37. 57. 38J.2 57.6 1.5 1.2 0.5 0.4 MCH /sag 22. 23. 23. 24. 22. 22. 2<. 23. 23<- 24. 23.0 0.8 0.3 MCHC % 40. 39. 40. 41. 39. 39. l3. 39. 40. 45. PLAT H/CBl^l 1071. 105S. 1005. 698. 1180. 1167. 972. 1080. 1061. 1163. 40.0 1065.5 1.1 90.5 0.3 28.6 GROUP: 2M DOSE: 1000' MG/KG SAMPLE DATE: 15-MAY-81 SEX: HALS SPECIES: RAT BIRTH DATE: 13-MAP-Sl ANIMALf: 301550 301551 301553 30155't 301555 301557 301558 RBC MM/Cffl 7.57 7.21 8.53 8.29 7.66 9.29 8.25 Hb gf 16.5 15.4 18.3 17.8 16.8 20.5 18.1 AVQ. S. D* S. E. 8.114 0.698 0.264 17.63 1.63 0.61 Hfe % 45? 43, 501 .49? 45^ 55( 47^ 47*7 40 ^ HCV /cmc 59, 59. 59. 59. 58- 51. 5T 58.6 0.8 0.3- MCH /W 22. 21. 21. 22. 22. 2S. sz. 21.7 0.5 0*2 MCHC % 37. 36. 37. 36. 38. .3^. PLAT M/cnun 1351. 797. 822. 1210. 888. 1329. 802. 37.0 1028.4 0.8 256.4 0.3 96.9 24 Company Sanded. Does not contain TSCA CBl 14008 HASKELL CODEtf: DPaiMIT: PPD&CP HEPOST DATE: 9-Jun-8l CLINICAL LAB: MATARESE GHOUP; 1CH DOSE! CONTROL SAMPLE DATE: 15-MAY-81 : SEX: KALE SPECIES: RAT BiBTy'DATE: 13-MAR-81 ANIMALS: 301540 301541 301542 301543 301544 301545 301546 301547 301548 301549 AVG. 5. 0. S. E. WBC M/cffl 17.9 11.6 12.5 9.6 12.0 13.5 11.1 11.3 13.5 15.8 12.88 2.44 0.77 Neut % 18. 19. 15. 19. 17. 17. 19. 19. 12. 12. L'yp i % 7(6 75 82 73 78 48. 76 774 80J 80. Eoain % 0. 0. 0. 1. 0. 1. 1. 1. 1. 0. 16.7 74J5 0.5 2.8 9^7 0.5 0.9 3.1 0.2 Mono % 6. 6. 3. 7. 5. 4. 4. 3. 7. 8. 5.3 1.8 0.6 Bnao % 0. 0. 0. 0. 0. 0, 0. 0. 0. 0. 0.0 0.0 0*0 GROUP: 2M DOSE: 1000 MG/KG SAMPLE DATE: 15-MAY-81 ! SEX: MALE SPECIES: RAT BIBTB DATE: 13-MAR-81 ANIHALf: 301550 301551 301553 301554 301555 3^57 38 a . S. D. S. E. WBC M/CB 40.4 20.8 16.2 18.2 20.6 16.5 28.6 23.04 8.72 3.30 Neut % 36. 34. 24. 29. 32. 63. 45. 37.6 12.9 4.9 Lyap^ % i 56J 57J 71.) 61.; 63, 22.; 41.1 i . 53.io 16.It) 6.P Eoain % 0. 0. 1. 0. 0. 3. 2. 0.9 1.2 0.5 Mono % 8. 9. 4. 10. 5. 12. 12. 8.6 3.2 1.2 Baao % 0. 0. 0. 0. 0, 0. 0. 0,0 0.0 0.0 25 Company i ^^ZQ'S.QQS--^^, t t U j MR?:: HASgELI^i 14008 HASKELL CODES'. CO>MMPNPD:ND^--------^^----------1 DPHTOHT: PPD&CP PE;RRIIOODD:'fld DAT *" TOXICOLOGIST: DASHIELL REPORT DATE: 9-Jun-fll CLINICAL LAB: HATARESE GROUP: 3M DOSE: 100 fiG/Z5 SAMPLE DATE: 15-MAY-81 | SEXs HALE SPECIES: RAT BIRTH ;DATE:J3-M&B-81 WBC Neufc Lymph Eoain Mono Baso ANIMALS: M/CB % % < ( % 301582 9.7 18. 74. i ; 0. 301583 14.3 14. 1 79. 0. 301584 13.8 13. 83. 1, 301585 9.0 10. 88, 0. 301586 14.6 5. 88. 1. 301587 10.7 11. 87. ; 0. 301588 19.7 12. 84. 0. 301589 15.8 11. 84. 0. 301590 17.5 10. 85. 1, 301591 15.2 6. 91. 0. 8. 0. 7. 0. 3. 0. 2. 0. 6. 0. 2. 0. 4. 0. 5, 0. K..-;- 0. 3. 0. k- AVG. 14.03 11.0 84.: 0.3 4.4 0.0 S. D. 3.40 3.7 4.< 0.5 2.1 0.5 S. E. 1.08 1.2 ^ 0.2 0.7 0.0 GROUP: 4N DOSE: 10 MB/KG SAMPLE DATE: 15-MAX-81 m S S E X : SPECIES; RAT BIRTH DATE: 13-MAR-81 ANIMALS: 301592 301593 301594 301595 301596 301597 301598 301599 301600 301601 AVG. S. D. S. E. WBC M/ca 14.9 17.6 13.9 10.4 10.5 10.3 9.5 10.6 10.4 14.6 12.27 2.75 0.87 Neut % 12. 10. 22. 16. 22. 14. 9. 14. 15. 25. Lymph i 85. i 86. 69. ; 81.; 72. i 82. 85.J 80. 76. 70. , Eoain i 0. 0. 0. ,0. 2. 0. 0. 0. 1. 0. 15.9 78,^ 0.3 5.4 6.4J 0.7 1.7 2.0 0.2 Mono ( 3. 4. 9. 3. 4. 4. 6. 6. 8. 5. 5.2 ; 2.6 0.6 Baso K 0. 9. 0. 0. 0. 0. 0. 0, 0. 0, 0,0 <h0 0.0 26 - Company Sanltiaed. Does net contain TSCA CIS | | 14008 HASKELL CODE<P: DPHTMMT; PPD&CP ~ BEPOST DATE: l-Jun-81 CLINICAL LAB: MATARESE GROUP; 1C;M SAMPLE DAITE.' DOSE: 29-MAy^i V. CC NTROL . SEX: M1ALE SPECIES: RAT BIBTH DATE: 13-MAR-81 AWIMALtf: 301540 '. 301541 301542 301543 301544 301545 301546 301547 301548 301549 RBC MM/en 7.53 6.35 7.02 7.11 7.C2 Hb ^ 15.9 14.2 16,2 15.6 15.2 Hfe MCT r /cce MJM /nnng MCHC 5 PLAT M/cinm !2. 55< 2T. 38. 1220. i6. 57. 22. 40. 1062, (3. 61. 23. 38. 944. H. 57. 22. 38. 1142. (0. 57. 22. 38. 980. AVG. S. D. S. E. 7.006 0.423 0.189 15.42 0.78 0.35 10.4 57.4 22.0 38.4 1069.6 2.7 2.2 .0.7 0.9 113.7 1.2 1.0 0.3 0.4 50.9 [ GROUP; 2M DOSE: 10([>M0G/TC SAMPLE DATE: 29-MIAY-81 SEX; MALE SPECIES; RAT BIRTH DATE: 13-HAR-81 ANIMAL)?: 301550 301551 301553 301554 301555 301557 301558 RBC MM/em 6.25 Hb e3t 14.1 Hfc % i MCV /cnc MC /Bung f"CnC " E PLAT M/cmm ;7. 59. 23. 38. 1214. AVG. S. 0. S. E. 6.250 14.10 317.0 1 59.0 23.0 38.0 1214.0 ^?- ^ ^ _ Compaq sa.^ed. Dees ^ con^ TSCA CBE fa I MR:]------ COMPNOr PERIOD:*?0 DA? TOncOLOG1ST: DASHIEL STOL U : | i 1 GROUP: 3M DOSE: 10C) KSvfVQ SAMPLE DATE: 15-WAY-81 140 08 HASKELL CODEtf: DPRTwr: PPD&CP REPOlBT DATE: l8-May-8l CLINI[CAL LAB: MATARESE 1 IT^I fc 'SEC;: (ALE SPECIES: RAT BIRTH DATE; 13-MAR-81 AP GPT GO' BBN CHEAT TPSOT ANIMAU; IU IU IV W8% B8 gK 301582 225. 23. 7). 25.0 0.6 6.2 301583 235. 25. 7>. 24.0 0.3 5.7 301581 180. 14. 4). 20.0 0.6 6.0 301585 285. 19. 5).. 24.0 0.6 5.7 301586 220. 21. 5?. 19.0 0.6 6.2 301587 230. 16. 6). 21.0 0.5 6.1 301588 330. 19. 5. 21.0 0.6 6.4 301589 290. 25. 6>. 20.0 0.6 6.3 301590 240. 19. 5). 18.0 0.5 6.3 301591 225. 19. 45. 20.0 0.6 6.3 AVG. S. D. S. E. 246.0 43.3 13.7 20.0 3.6 1-1 5*5 11.4 3.6 21.20 2.35 0.74 0.56 0.10 0.03 6.12 0.25 0.08 GROUP; 4M DOSE: 10 ffi/KG SAMPLE DATE: 15-H1AT-81 SEX? MALE SPECIES: RAT BIRTH DA1E: 13-MAB-81 ANIMALf: 301592 301593 301594 301595 301596 301597 301598 301599 301600 301601 AVG. S. D. S. E. AP 6PT GCT BOH GREAT TPROT ID 10 10 OS% ss% eK 145. 17. 50. 20.0 0.5 6.1 280. 17. 50. 19.0 0.5 5.8 170. 19. CO. 25.0 0.6 5.8 195. 17. * 5. 21.0 0.7 -6.1 230. 21. 5, 22.0 0.5 5.8 170. 19. * 5. 20.0 0.6 5.7 205. 21. <5. 18.0 0.6 5.9 185. 19. SO. 21.0 0.7 5.5 250. 21. '5. 17.0 0.5 S.7 200. 19. '5. 22.0 0.6 5.6 203.0 40.6 12.8 19.0 1.6 ^ &- ^;' '1.0 20.50. 0.59 ^'5.80 ;5.2 2.27 0.06 '0.19 0.5 1.6 0.72 0.02 0.06 28 Company Sanitized. Does not contain TSCA CBf MR: COWS ____ PERIOD?TO DA1 TOXICOL^GIST: DASHIEL . W 14008 RASKELL CODEd: DPRTMHT: PPD&CP REPORT DATE: l8-May-8l CLINICAL UB: MATARESE GROUP: 104 DOSE: CONTROL SAMPLE DATE: 15-MAY-81 SEX: MALE SPECIES: RAT BIRTH DAm? 13-MAR-81 ANIMALf! 301540 301541 301542 301543 301544 301545 301546 301547 301518 301549 AP IU 195. 255. 265. 265. 185. 265. 325. 280. 240. 300. AVG.. S. D. S. E. 257.5 42.8 13.5 GPT 10 16. 19. 19. 23. 19. 17. 19. 17. 19. 21. 18.9 2.0 0.6 GOT IU 50, 65). 45* 601 50* 60. 501 45^ 504 55. BBH mgf 22.0 22.0 18.0 21.0 19.0 20.0 21.0 19,0 20.0 21.0 CHEAT TPROT , ttS^ '8% 6.7 ; 5,8 0,5 5.8 0.7 5.7 0.6 5.9 0.6 5.5 0.7 9 0.6' 6^0 0.7 6.2 0.6 5.0 0.5 5.9 53.JO '20.30 647 1.34 2,1 0.42 0.62 0.06 0.02 5.87 0,19 0.06 GROUP: 2M DOSE: 1000 MG/1CG SAMPLE DATE; 15-MAY-81 SEX: HALE SPECIES: RAT BIRTH DATE? 13-MAR-81 ANIMALS: 301550 301551 301553 301554 301555 301557 301558 AVG. S. 0. S. E. AP in 290. 395. 305. 240. 315. 210. 285. 291.4 58.9 22.2 GPT 10 19. 28. 19. 25. 28. 25. 19. 23.3 4.2 1,6 GOT' IU: 45J 65. 55. 60. 75. 70. 50. BUN a&f 74.0 61.0 66.0 79.0 91.0 106*0 66.0 GREAT OgK 1.1 1,0 0.9 1.2 1.3 0.9 0.9 TPor ' <E< 5.8 5.5 5,8 6.2 5-5 -^ 5-B oo.b 77.57 10,18 16.05 4^ 6.07 1*02 0.18 0.07; 5.76 0.24 0-09 23 - Co^y ^^ ^ ^ ^^ ^ ^ PERIOD:-TO DAY ToncoLocrsT: DASHIEL 14008 HASKELL CODE)!: DPRTMMT: PPD&CP REPORT DATE: l8-Mgy-8l CLINICAL LAB: MATABESE l-l GBOUP: 3MI DOSE: 100 HB/KG SAMPLE DATE: 15-MAY-81 SEX: MALE SPECIES: RAT BIBTH VATS: 13-MAR-81 ANIMALS: 301582 301583 301584 301585 301586 301587 301588 301589 301590 301591 RBC W./cm 7^9 7.01 6.72 7.27 7.20 6.65 7.79 7.41 7.49 7.10 Hb g% 16.2 16.0 15.0 15.5 15.8 14.6 .'.6 17.0 16.9 15.5 !.It MCV < /cne . 55. . 60. , 55. , 55. . 57. 57. ' ;" 55. ' . 57. , . 56. 57. MCH /mag 22. 23. 22. 21. 22. 22. 21. 23. 23, 22. MCHC % 39. 38. 40. 39. 38. 38. 39. 40. 39. 39. PLAT M/cnan 1021. 1322. 1307. 1089. 1101. 1021. 15C3. 1152. 1157. 1217. AVG. S. D. S. E. 7.213 0.356 0.113 15.91 0.79 0.25 40.8 ^.0 6.6 "6.6 22.1 38.9 1198.0 1.6 0.7 ' 0.7 148.7 0.5 0.2 0.2 47.0 GROUP: 4M DOSE: 10 MG/KG SAMPLE DATE; 15-MAY-81 [ SEX; MALE SPECIES: BAT BIRTH PAlE: 13-MAR-81 ANZMALf: 301592 301593 301594 301595 301596 301597 301598 301599 301600 301601 AVG. S. D. S. E. RBC MM/cm 6.78 6.84 6.21 6.89 6.64 6.76 7.10 6.12 6.63 6.41 6.638 0.308 0.098 Hb 8K 14.9 14.9 14.2 15.6 15.6 14.5 15.6 15.0 15.4 14.9 . 15.06 u^9 0.15 Ht \% 3( 3(, 3!. 3<. 3<. 3( 4C 3< 3 31 37 .9 1.5 0.5 MCV /cnc 56. 55. 56. 57. 59. 56. 56. 59. 58. 58. 57.0 1.4 0.4 MCH /Bag mac :"% 22. 39. 22. 39. 23. <M. 23. HO. 24. 40. 22. 39. 22. 39. 25. 42. 25. 40. ?'. ,40. -; ?*. 22.9 39.9 1.0 1.0 0.3 0.3 PLAT M/cina 1226. 1268. 983. 972. 992. 913. 941. 898. 1262. 1231. - 1068.9 156.2 49.4 30 - Company Sanitized. Does not contain TSCACBI MR:L COMPaD.-l PERIOD:TteC_O_V_ER_Y TmriCOLCC-^T; DASHIEL f l 14008i HASKBLL CODE<1: DPRTMNT;,PPD&CP & SEPOBT DATE: l-Jun-81 CLINICAI.. LAB: MATARESE GROUP; 3M DOSE; TOO MG/W SAMPLE '.-TE: 29-MAY-81 SEX; MALE SPECIES: RAT BIRTH DATE: 13-MAR-81 ^ HBC Hb ANIMALS: MM/cn S? 301582 MCW /eac MCT /Hms KCHC -< , PLAT M/cnm 301583 301584 i i 301585 i 301586 301587 301588 6.90 ^.^ Ht 58. ?2. 39. 1112. ^ 301589 7.18 6.80 15.1 IS.^t 39.. 54. 39 2.1,..- '39. 1292. 'S 301590 6.69 15.3 39 58. 23. 3S>. 1260. 59. 23. 39. 1020. ?c 301591 7.31 16.0 41 ' -i. 22. 39. 1238. AVG. S. D. S. B. 6.976 0.261 0.117 15.^ 0.34 0.15 39.6 Oi.9 0.4 56.S 2.2 1.0 ?2.2 . 0.8 0.4 39.0 1190.4 0.0 110.5 0,0 49.4 GROOP: 411 DOSE: SAMPLE DJITE: 29-MAT-81 AMIMALtf: 301592 301593 301594 301555 301C;96 301597 301598 301599 301600 301601 RBC MM/cm 7.11 -'.85 6.86 7.44 6.40 Hb ^ 15.4 15.0 15.2 16.4 14.7 AVG. S. D. S. E. 6.932 0.382 0.171 15.34 0.65 0.29 10 Mp/KG i "i MCV /cmc j i . ' i 39. 38 39^ 43.' 37.1 39.P 2.3 1.0 55. 56. 57. 58. 57. 56.6 1.1 0.5 SEXt ;HALE SPECIES: RAT BIRTH DATE: 13-MAR-81 MCH MCHC /me ' .. PLAT M/CHBl " . 22. 3. 22. 39. 22; ^ 22. 38. 23. . - y . ^. ? ? ^ 22.2 0^ 0,4 .,---; 0.2 0.3 980. 986. 1066. 1204. 1138. .C' 1074.8 97.0 43.4 31 Company ^SSK&. sd. Dses j;St ssHsaiii TsCA CBl mCO'M.VP^NSD:^gJJ| PERIOD:-RECOVERY TOXICJLOGIST: DASHIELL gASKJELLt1f:4008 HASKELL CODES'. DPRTONT; PPD&CP REPORT PATE: 9Jun-8l CLINICAL LAB: MATARESE GROUP: 1CM DOSE: COHT 10L SAMPLE DATE: 29-tWT-81 SEX: MALE . SPECIES: BAT BIRTH DATE: 13-MAR-81 ANIMALS: 301540 301541 301542 301543 301544 301545 301546 301547 301548 301549 AVG. S. D. S. E. WBC M/ca 12.3 15.4 10.3 14.9 13.2 13.22 2.06 0.92 Neut % Lyaplb % i '' EEooaain % ' \ 12. 84. 29. 67. 13. 82., ( 20. 75., 6. 90.; 16.0 79.P 00.6 8*9 8.6 00.5 3.9 4.0 00.2 Mono ? 4. 3. 5. 4. 3. 3.8 0.8 0.4 Baao % 0. 0. 0. 0. 0. 0.0 0.0 0.0 GROUP: 2M DOSE: 10001/KG SAMPLE DATE: 29-MAY-81 ; SEX: MALE SPECIES: RAT BIRTH DATE; 13-HAR-81 ANIMAL*: 301550 301551 301553 301554 301556 301557 301558 WBC M/cn Neut Lynpti Eosin 12.6 22. 67. 1. Mono % 10. Baao % 0. AVG. 12.60 22.0 67.6 1.0 10.0 0.0 S. D. S. E. 32 Company Sam-fesd. Does not ca^am TSCA CB1 FI CMORf.i'^l^--^--^J--^--^^--^--^U--S--K--El--ll^: mo08I DPBBMT; 8ASKELL CODE?: PPD&CP * PERIOD:TlECOVERy REPORT DATE^ 9-Jun-8l TQXICOLOSIST: DASHIELL CLINICAL LAB: HATARESE GROUP; 3M DOSE: 100 id/KG SAMPLE DATK; 29-MAY-81 SBX; KALg SPECIES; RAT BIRTB OATB; 13-MAR-81 ANIMALS: 301582 301583 301584 301585 301586 301587 301588 301589 301590 301591 AVG. 5. 0. S. E. WBC M/cn 13.1 18.6 15.2 10.8 10.9 13.72 3.27 1.46 Neut Lymph Eoain S % t ' 9. 87. ^ 1. 15. 81. 0. 17. 80. 0, 19. 75. 0. 14. 84, 0, 14.8 81.4 0.2 3.8 4.5 0.4 1,7 2.0 0.2 Mono % 3. 4. 3. 6. 2. 3.6 1.5 0.7 Baso % 0. 0. 0. 0. 0. 0.0 0.6 0.0 GROUP: 4M DOSE: TO MG/KG SAMPLE DATE: 29-MAY-81 SEX: MALE SPECIES: RAT BIRTH DATE: 13-MAR-81 ANIMAU; 301592 301593 301S9H 301595 301596 301597 301598 301599 301600 301601 AVG. 3. D. S. E. WBC M/CB Neut Lyapb Eosin % % % i 1 Mono % Baso % - . 10.4 23. 74. 1. 2. 0. 10.4 14. 82. ,! 1. 3. 0. 9.3 15. 76. 1. 8. 0. 12*0 27. 58. 2. ISr 0. 10.2 21. 73. 0. 6. 0. 10.46 20.0 72.6 1.0 6.4 0.0 0.97 5.5 8.9 0.7 4.4 0.0 0.44 2.4 4.0 0,3 2.0 0.0 33 CompaFiy SsnEtfcsd. Soss nss. cc^Eafs JSi :IjMB4 MMRR;^ HAggSLLff : 14008 HASKELL CODE)?: CCOOMPMMDPaND^1------------------rt OPBTMMT; PPD&CP PPERIOODD:"1TCCOvBH?^^^^^*1 REPORT DATE: 29-May-Sl TTOOXXIICCOLOGISTT DASHIEL CLINICAL LAB: MATARESE GROUP: 1C!M DOSE: coiniic3L SAMPLE DA TE: 29-?WY-SI ! ANIMALS: 301540 301541 301542 301543 301544 301545 301546 301547 301548 301549 AP IU 290. 300. 275. 225. 290. GPT IU 17. 19. 17. 21. 25. GOT pJ ' BUN Blg$ ! i y15-, 22.0 18.0 3$. 19.0 iO. 18.0 ro. 22.0 SEX: MALE SPECIES: PA1 BIRTH 3AiE: 13-MAR-81 GREAT ^ROT sgf ' 8^ 0.6 fi.3 0.6 16.1 0.6 ?6.5 0.6 '6.3 0.7 6.3 AVG. S. D. S. E. 276.0 29.9 13.4 19.8 3.3 1.5 7.0 19.80 16.8 2.05 7.5 0.92 0.62 0.02 0.01 J8.30 0.14 0.06 GROUP; 2M DOSE: 101)0 MG/KG SAMPLE DATE: 29-MAY-Bl ANIMALS: 301550 301551 301553 30'554 301555 301557 301558 AP IU 245. GPT io 14. GJ)I BON iro "S? 25. 29.0 i SE5K^ HAfeE SPECIES: RAT BBCTH SA-TE: 13-MAR-87 CSEAT ;TOSOT ass$ gl /,. . -.;---, 0.6 6.4 ' AVG. 5-. D. S. E. 245.0 14.0 5,0 29.00 0.64 6.40 ,.. 34 Company Sanitized. Does no} coniain TSCA CBI ^'^Mll^H^HIl M:RT:^ljBtfIHJLl CQMPND:HH---- HASgELL PERRIOIOD D.'.T-OTCEWCEOfl VER^^^^^ TOXJCOLOGIST: DASHIEL 14008 HASKELL CODE<(: DPRTMNT/; PPD&CP REPOJBT DATE: 29-May-8l CLINKAl. LAB; MATARESE GRODP: 3M DOSE: It 0' MGyfKQ SAMPLE DA'1rE; 29-t!ASr-8l SEX:: 'MAi LE SPECIES: RAT BIRTH ,D1 ATE: 13-MAR-81 ANIMALS: 301582 301583 301584 301585 301586 301587 301588 301589 301590 301591 AP GPT ( OT 10 IU Iff i 240. 14. S0< 275. , ...24. . 315. 245. 25. ?0. 240. 16. 0. 215. 17. 35- BON BgSC CREA' 'TpROT BKS^ 6< 15.0 20,0,. 19.0 18.0 21.0 0.8 6.1 0.7 ^6.5 0.'8 '^6.6 0.6 : ...6^ 0^ '"6.5 AVG. S. D. S. E. 243.0 21.4 9.6 18.6 4.4 2.0 'Mt.0 10.8 4.8 18.60 2.30 1.03 0.7? ;: 6.U2 0.05 .0.19 0.0^ 0.09 .:.? ' ^' -*.' i -, GROUP: 4M DOSE: .* . 10 MG/SG SSX,-, 'W^i SPECIES; RAT SAMPLE DATE; 29-MAY-81 BIBTH DATE; 13-MAR-81 ANIMALS: 301592 301593 30159't 301595 301596 301597 301598 301599 301600 301601 AVG. S. D. S. E. AP GPT QV W CHEAT. TPROT IU 10 W n^ "g? g? ' 180. 240. 210. 245. 210. 217.0 26.4 11.8 17. 19. 7. 21. 17. 18.2 1.8 0.8 ('0. ''0. *;0. (0. * 0. 2.0 8.4 3.7 IS.O 19.0 1^0 18.0 21.6 v^ao' 2.17 0.97 0.6 6.1 0.6 6.0 0.6 '- ^8.1 05 6.5 0.7 6.2 0.59'' 0.0& 0.03 ' " '6.18 0.19 0.09 . 35 Company Sanitized. Does not contain TSCA CBf 2^1 DCV 12-7* .APPENDIX C E. 1. DU PONT DE NEMOURS & COMPANY IHCaOKMUTW WiLMINGTON, DELAWARE 19898 fOLYMEW PRODUCTS DEPARTMENT EXPKKI MENTAL TATIOM ANALYTICAL REPORT September 16, 1981 CENTRAL RESEARC HASKELL LAB AND DEVELOPMENT DETERMINATION OFjFLUORININE RAT BLOOD (Job No. 812-668; PRAL Nps. 8i4-2101-2119.81-2419-?434.81-2611-2612; __________i|ithe o^studiesf------HIBHHu^6^08111'8 0^ ras tc 37 fBt blobd aanples'?Ubn>ltted 5/20/01 - 6T1.1/81 have been analyzed ToTrBiorine by the WickboXd Tor^ft procedure. The analyses were done by Erik Kissa at Jackson Lab (After prelinina.ry frieze-drying here), and results are given in the attached copy of his report, < ^ ^ S. S. Stafford Attachments jah Key Words: Analysis Wickbold Torch - 36 - Company SaifHSisscL Doss n&i coiRiasii TSGA C! "niere's a w- Ic of things w'm doing aomattiing about CH-l-l my. -W E. 1. OU FONT DENEMOURS 5 COMPANY WILMINGTON. DELAWARE 19398i CHCMICAL* AND PIGMENTS OCrAKTMCNT ; JACKSON LABOKATOKY : \ i^ Sally S. Stafford -"Polymers * & Plastics ' DespatQaesat Experiinental Station 2B9/212 September 1, 1981 FLUORINE IN RAT BLOOD CONTAINING The fluorine content of dried rat blood was determined by the oxyhydrogen torch method calibrated with p-fluorobenzoic acid (corrected for a blank and adjusted tp 100) fluorinj The results (see attacied pages}' surest thathej recovery rate is similar to that o^HI| ' ' ^f^^^^^^--^^--H--Bj^| HBHIHBr60' '' ~ Average F ppm ^Rate Saropled *0nly one rat survived 25* 25 12 0.5 Two fluorine values, seemingly out of line, were confirmed by duplicate analyses. standard deviation of the fluorine content ^f blood is larger' than that of the analytical method, indicating a large vana^ o' n of lu0i4,ne in blood from rat to rat. We need only about ^ 8-1 aa^iaiooit^for analyses. If a rat can donate this aaiiunt and reeover^jit may be better to sample the same rat p9;'i,odicicaalllly to follow the decrease of fluorine in blood with tine, ^^ ^v^^ E. Kissa Physical & Analytical EK:mml Attach. - 37 Company Sanitized. Doss noi contain TSCA CBI FLUORINE IN RAT BLOOD CCOTAINING PRAL Ho. 81-2101 81-2102 81-2103 81-2104 81-2105 81-2106 81-2107 81-2108 81-2109 81-2110 81-2111 81-2112 81-2113 81-2114 81-2115 81-2116 81-2117 81-2118 81-2119 Date Received 5/20/81 5/20/81 5/20/81 5/20/81 5/20/81 RAC if. 3(1540 3(1541 3(1542 3(1543 3C1545 Group. Tube ? I Tr'ie: I Tune ,2 I Tube 3 I Tube,^ I ;Tube.i:5 5/20/81 5/20/81 5/20/81 5/20/81 5/20/81 5/20/81 5/20/81 5/20/81 5/20/81 5/20/81 5/20/81 3C1550 3( 1551 3C1553 .-3C 1554 3C1582 3(1583 - 3C1584. 301585 301586 3D 1592 301593 II Tube .6 II Tube 7 II Tube 8 II Tube 9 HI Tube"10 III Tube11 til Tube 12 III, Tube 13 III Tube jl4 17 "': Ti*^l5 IV Tube 16 5/20/81 5/20/81 5/20/81 30]l594 IV 3o|l595 IV 3o!l596 IV Tube p Tube^8 Tube 19 81-2419 81-2420 81-2421 81-2422 81-2423 81-2424 6/1/81 6/1/81 6/1/81 6/1/81 6/1/81 6/1/81 303545 3013546 303S47 303548 30S549 I Tube: 1 I Tube 2 I Tube 3 I Tube 4 I Tube-5 301555 II Tube 6 i rxuurine 1.3 (b) Lioncenc, ag/icg r ' ' Grouo Averaae 1.2 X - 0.94 1.4 a " 0.52 0.6 0.2 212 190 K - 197 172 3 " 19.6 213 81 79 X- 79.4 78 0 2.7 S3 76 25.6 31.3, 29.8 ---. AJ f 16.7 22.8 21.7 X - 23.5 CT - 5.1 0.1 1.0 ? 0,48 w 0.5 0 - 0.34 0.5 " 0.3 ^ ' 23.1, 26.9 Avg. 25. ( - 38 QsmpQny Semijsgd. Doss RCS ^smaisi TSCA CBi FLUORINE IN RAT BLOOD COHTAIM Sample Designation (a) PRAL No. Date Received 81-2425 Jl-2426 81-2427 81-2428 81-2429 6/1/81 6/1/81 6/1/81 6/1/81 6/1/81 81-2430 81-2431 81-2432 81-2433 81-2434 6/1/81 6/1/81 6/1/81 6/1/81 6/1/81 81-2611 81-2612 6/11/81 6/11/81 Rat ffL Group. Tube 7 30158 1 30158 1 30158 30159 > 30159 L 30159 r 301598 30159 1 301601 30160 30427^ 30427^ III Tube 7 III Tube 8 III Tube 9 III Tube m III Tuba 11' iv Tube 12, IV Tube 13 , IV Tube 14 IV Tuba 15^ IV Tuba 16, Blank Blank Fluorine Content, ing/kg F (b) Group Average 20.4 31.0 22.8 27,7 25.6 X - 25.1 a -4.2 5.4 9.2 11.8 18.6 14.0 X - 11.8 0 - 5.0 0.0 0.2 (a) Sample Designation for| 0 Group Group II Group III Group I - control i - high. 1000 o^/kg Interaedlate.lpO IV a low, 10 og/kg [ i fflg/fcg For samples 81-2101 through -2119, recovery fclae w&s 4 hours, after dose 5/15/81. For samples 81-^419 through -2434, recovery cine was cbe final 14 days. Samples 51-2611 and 81-2612 we^e "blanks", blood from stock rats not pare of the study but dried and analyzed along with the others. (b) Total fluorine content, not corrected for inorganic' fluorine values which are probably Insignificant, i .^ - 39 Company Sanitised. Doss not contain TSCA CB1