Document a72d2Myb2y3ypqd6MV3LMJRX

FOR DD PONT SE ONLY AR226-2906 E. I. da Pont da Honours and Co., lac. Haskell Laboratory for Toxicology and Industrial Medicine Elkten Road,. P. 0. Box 50, Newjrk, Delaware 19711 HASKELL LABORATORY REPORT NO. 326-82 I ! K 5 H S 9 S S ^ ^ S & S B S 3 ~ "s edsdnlstsrcd orally to young adult CrlrCD* oftla rats at repeated dojie I W U i of either 1,000 mg/kg, 100 mg/kg or 10 ag/kg for 10 days oyer a 2-wepk period. Clinical signs observed included: weakness, stained perineal area,, lethargy, prostration, humped-posture, congestion, chroaodacryorrhea ami weight loss. Compound-induced macroscopic and microscopic lesions were present lb the thymus, spleen, bone marrow and kidneys of high-dose animals. Because of the mortality seen in the hlgh-dosa group, reversibility of these lesions could not be adequately evaluated. No treatment-related lesions were observed in the low or intermediate dose groups. I . ., . Statistical analysis of measurements data showed that rats dosed 10 times with _ _ _ lt lsvels of 100 mg/kg and 1,000 mg/kg had higher than normal srytnt^oyte counts and hsaatQcrias Which appeared to be ralaced to the doae? Rats dosed with 1,000 ag/kg' _ * higher leukocyte counts, almost twice the normal range eacaoxxsncd by Controls. Thesa .animals also showed e three-fold Increase in serum blO{ urfs' hitrogen anii;increased hemoglobin, serum glutamic pyruvic traasami , I* Activity, And creatinine. The 100 mg/kg treated rets showed a slight increase in serum total protein. An increase in - 1- Company Sanitized. Does not contain TSCA CBI { tI J Che relative number of neutrophils (1,000 ag/kg group) and a slight to moderate hypochromia (100 ag/kg and 1,000 mg/kg groups) was seen. In the recovery groups, 4 slight increase in serum creatinine levels in the 100 ag/kg treated rats was observed. In the absence of this parameter being significantly different prior to the recovery period, the significance of the finding is questionable. Ho other differences were detected in the 4c*l1 i4 n0*i4 caaal1 patholo^gaic _p_a_r__a_m_ete' r __ . studies . in ._ the recovery rats ._ (only 1 rat was examined in the 1,000 ag/kg group) Analysis of blood for organoflnorlde revealed a dose-related increase in concentration following the 10th dose (l, 30, 79, and 197 ppm, exposures of 0, 10, 100, and J ,000 ag/kg, respectively). These values dropped to O.S, 12, 25, end 25 ppm (l rat), 0 to 1,000 ag/kg, respectively, 14 days after the last treatment, indicating clearance from the blood is relatively slow. Procedure; The test materialL as an aqueous solution at conc^n rations of either 102, 12 or 0.12, was administered by letregastrie intubation to 3 groups of young adult Crl:CD*jaale rata, 10 nits per group, 5 times a week for 2 weeks at repeated doaa levels of either 1,000 mg/kg, 100 ag/kg or 10 mg/kg; an additional group of 110 rata served as, controls and was intubated with distilled water. TWo Cede rats at 1,000 mg/kg died before the 6th <ose and 1 before the 9th dose. Five control and 14 t i i f c rata were sacrificed approximately 4 hours after tjjie lest dose# Two t-fsc rats at 1,000 mg/kg died during the recovery period. The remaining 5 controls and 11 test rata were observed over a 14-day recovery period and then Sacrificed. All rata were examined grossly, selected tissues were weii^itd.aod selected tissue end 41organs ware evaluated histologically. Clinical pathology measurements were taken on all surviving rata hours after the IQtb' dose and after the 14-day recovery p.riod. Blood was also collactad at the same periods for fluorine analysis. i ! - 2Company Sanitized, Dees not contain TSC CIS Results: Dose (mg/kg/day) No. of Doses Mor 'M Clinical Signs 1.000 10 100 10 10 10 9 f\d o/|o 0/ First. Week: Weakness and weight loss. Second Week; Weakness, stained perineal area, lethargy, prostration, hasped posture and weight loss. Two rats. djLed before the 6th dose and 1 died before the 9th dose. Recovery Period; Weakness, congestion, huaped posture, chromodacryorrhea and weight loss TWo rats died during the recovery period. First Week: Slight weight loss. Second Week: Slight weight loss. Recovery Period: None. First Week? Slight weight loss. SecondWeek: Slight weight loss. Recovery Period: None. Pathologic Changes: See Appendix A (Pathology Report No. Clinical pathology: See Appejtdl* B (Clinical Report forjj Fluorine Analysis: See Appendix C (Analytical Report job No ^ Synonyn: Conpositlon.'* Purity Contaminants; - 3- Company Sanitized. Does not contain TSCA CBl JAH:jrg:WP:i. 2 2 -i:Approved by; I ; i : -gCs^Ad A K.-- ,,i V Gerald L. Kennedy. JrT Section Superviso)? Acute Investigations I I 4Company S, ;a't2 es noi contain TSCA C il APPENDIX A E. I. d u P o n t d e N e m o u r s 81 C o m p a n y H a s k e u . La b o r a t o r y fo r To xic o lo g y a n o In d u s t r ia l M e d ic in e i E ucTO * R o a o - N e w a r k , D e l a w a r e 19^11 c en tr al research a n d developm ent p| rartm ent PatholoEv Report No-6 - 0 a. f:'r* % Polymer Products D e p a r t & Chemical & PtLents . Oral Subacute Study in CD Rat- Summary 1 April 21. 1982 . Compound-induced nacroaqopic and microocopic lesions were present in the thymus (Lymphocytic depletfcxj), spleen ttm >hocytlc depletion), bone narrow (Hypocellularity). aod kidney, (Hephriti.) of high-dose enlmals. ,ecMse of excessive natality i,, the hiLdos. group, reversibility of these lesions ... not adequately evaluated. CoLpound-induced lesions were not observed in the low or intermediate-dose groups. Introduction Every animal (except #30^55) m tbi. study was gives . complete post mortem examination. Htcr.sc.Lic e x a c t i o n . wore .1,0 performed on selected f r m aach avaUabla Groups I (0 mg/kg), u (1000 ,,/kg,, III <100 mg/kg), and IV (10 m ^ ) collated of tsn mala rata each. Each group had a 12 day feeding phju. and a H .^recovery ph.se except the heart, S b rP* f " Ch^ i d C lenda, E ..p h .g ,, ,, s tM . c h , n y e s , TJin Brain, Trachea, L unUgsv, "Ki-dnseEylsa,a"T- es tes r and oEp,id Tidhyym^sid,e s . - 5Company Sanitized. Does not contain TSCA CBf udhtu high-dose group. Due to marked 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 thre| and seven days in the recovery phase. Bistomorphological lesions were tabulated by individual animal in Table I and were summaxlz d In Tajjle II. I Results "" | f . ` .i - - ' Macrescopically, compound-induced tissue alterations ware 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 to severe lymphocytic depletion. Animals from all groups had multifocal areas of reddish-gray mottling in the pulmonary'parenchyma. These lesions were associated hiatomorpho]ogically with multifocal areas of granulomatous interstitial pneumonitis. Microscopically, compound-induced lesions were present in the spleen (lymphocytic depletion - 7ctf 9), bone marrow (hypocellularity - 5 of 7), thymus (lymphocytic depletlcjn - 5 of 8) and kidneys (purulent tubulointer iI ' . stitlal nephritis - 8 of 9),! of the hlgh-dose group. Compound-induced lesions were not present in the othelr test groups. The renal lesion in this study Was rather unique in that there was selective toxicity for the dllatal and collecting; tubules and the medulla was more severely affected than the cortex. lesion was characterized by degeneration and regeneracin of the tubular epithelium with tubular ectasia. This was associated with a marked interstitial infiltration with neutrophils and edema fluid.: Occasionally, there were small foci of renal papillary necrosis associated with the aeutrphilic exudate. One rat (#301555 - 6- Company Sanitized. Boss not contain SCA CBl -r - Group II) that survived the 14-day recovery period did not have similar i compound-induced lesions. ( There were several other!microscopic inflammatory and/or degenerative lesions that were considered* because of their common occurrence and/or ' : '' ' yf|. their low frequency, to be incidental spontaneous lesions in this group of rats. i WDK:WCK:vfd } II Company Sanitized. Does not contain TSCA CBI PATHOLOGY TABLE CODES * Tissue Accounting Code: L x Lesion observed H No significant lesion observed 0 - Tissue missing 1 m Tissue insufficient for histomorphologic evaluatlonj N Only one gland is present end it is normal Q m Specimen quality is inadequate for an accurate assessment;of subtle tissue alteration, other* wise the tissue appears to be normal A Autolysis P Present . ** Degree of 1 - Minimal 2 - Mild 3 " Moderate 4 - Marked 5 Severe *** Mode of Death: : S Sacrificed | D ** Unscheduled.ideath i - a - Company Sanitised. Does not certain TSC CBt I I - 140(18 *M* I IHDIVIDOAL AHIHAi. lllaTWATIIOlOC DATA EPOCH!NK SVBTKH Croupi Hade of DDeaotnht!11-----B . 4 ___ a _ o /ha P8S p s 8 8 Seat' 1 ... . H N H M H M M H 'V 10 a i --M x i n }? 12 26 26 26 26 0 .. fl 0 -Jay.- j l f l .... }fl .- 4 i i _ -fL Jm . .a ;- . M L M .. ,4 J jiL Adrenal Gland (e) HN i MN H H i HH Thyroid Gland HH i H 1 U M0 0 H Parathyroid Gland (a) I OASTHO INTESTINAL 8VHTEH . VO 0 0 0 0NHO0 0 0 I Esophagus H N t N N N N 11 H H Perlusophugltle, gronuloaste local ---- - Btanech NMN HN H HN N H G lsndulur, atrophy, d iffu s a - - - - - - - - - - Uuudunuui 1Isuni Jujtimiai Cucura Colon l.lvur NN NNNN HN N H HN N HN H H H H H 1* H N N H u N H N H H HNHNHH 0H H NH H HH H h 2NH 4H 4N444M44 Company Saniazed. Does 3 O lUI&AAH f*W I HffilVIMKI. HISTOPtimucY DATA Part 2 1" Uyut i t i * --Tarite;---- ---------- |iuruIogruiiulp*touy, M u ltifo c a l U<H>utltU, lyapliucytlc, lo c a l 3W . - ---- -- 2- * -- 1 i zzi-- _Tt-- -----J L ' .J - -- f l -S -- a IIEHOKllETIC gyrif^ ttpleun H - - - - - ~ - - , Lyapliocytlc depletion. d iffu s e - HO* " 'I* Marrow j i M ypocoUuUrity, d iffu se ? u Thtitua f - lg e? iltym u altiu , pyugranulimutouu g rual -yt- Z.Z' NN N N "* h L L L N N 1. J. 0 L 2 2 4 1 - $ :3 5 ' `v H. H -M N % t LL 1. N N 4 0 :L Z - * . ii* .r ' 2. 2 2 1 -. N :* H .. L0 . ' 3 3 - * - L Lt 0 5 S - C 5 1) ih yo lc l.yinpli Node Lymphocytic liyporplusiu. ttj} d iffu s o S. HUjjliUfiiKKLEfAI. BVi'i'QM ,, V --- NN HH " "- (NQ> Heart Stornila HN HN IMN 1 N N H H M IN l N H N H - - B* 2 N N0 H MH N 0 0 H - --- --- - -- N N H Il N H N 1 0 u I N N II I H N N 0 N ? <O3-ft ac3> i-; 3ss-" mH o > O i lini' ,'fl !-,!' *:!< -- x 5 ** ;e O p IO I << < , |m X * 1- * .. I * XI i */ -'::3t- i a X IX III f.J;S5i!t T W * f (fiati**) RWBWi JlfflST&IBHflg.RftT* xx il a I ia X rm m X M* m X M m X t*o at X M0 <9* mi e m X M o 0 X toe x IJ X*-'..*. I - XX I al M I< II ca X Nmme mXM o ^1 atX M o vi 401019 miu.^. m--M ua a rti '1 5a !s moo ;'i o - tOoto to *toma 9>m o^- a9999932 io Iy s1 s 5} g| n 5 a aa aa >as o ua 2 Ai aWu: w w - awi3 wv >o% Je5 >* 22 * : 3a' 91 " 2 03 .is t-O' ~OS 2 '3:^ it."I ^A-tsa9o*ttat99ooo ^.-to >a1 aStW.taoo --Ata-*5o& trXaouo.t-atuo*o ttStaotoo-ottttaoaooo. tasS3<o o9oitof ttaaaoo* toawoto - a to ^ 1 ^ s a. Z to to fi -^| ilS 1 o Company Sanitized. Does not contain TSCA CBf - JJL - li. mammut ,T*Ut (Conttyi.^V animai Croupi Tlaauit*/ 8 8 8 8Moda of Uoaai'--------- -- Daathi'__ B -...S. --. s_____p___ BM/fc*_____ lui!.. , H -.,,li ,--JT. H H M -12 1 26 26 4 9'_UL_ Hacvary Payai 0 0 . - -JH l i ___ If fl fl N M~ M & Obaarvutlona** ~ .M 14 0 -lat>r wf-iS-41^ riait4-- j & . m : .m .m W m Kaphrtcta. tu tiu lo tn ta ra titia i, lym phocytic, neuprophill, u n ila t r a l, M > ltl|b c a l ' Nuphcoaia, u n ila t ir a l, M t(tlM l CupauUtis, fibtliipphruUnt, henarrliDHlc, unilateral, iucoi T 'r" y. : : l & v : VN. uiffutjQ, b iliiteral iiHarutltlal cull byparplaala, ditfuHu, bilateral _ Epidldynia (dea) ' L Epididywitia, inceratitlal. lymphocytic, unilatral. fnuul J OO3 ci $ nid ta 3O EOOS?! JW*-' x***r - t " " j V. CpiCI TABI.E I (Continued! INDIVIDUAL AH1HA1. tp a T n ftttlOliOCT DATA Part 5 Company Sanitized. Coes not contain TSCA CBS Bsopliugua Ul P u ria a o p lia g ltU , granulooatous. I fo c a l Stcoach D lunJulur, utiopliy, d lffu a a SuuJcimm 1lei'Bl le lumini (. DeLinn Bulini I.lvur N HNN NN N NN N HNN HHN HH HNNN NNN NN N NN N HHN NN QH h H N M H N N N Q 44NN4MN NHN NNN NHN NNN NNN 44N NN N NNA NH N NN N NH H LN4 NN NH NH NH NN NH t. 1I-14UOB D TAM.lt I (C o ntln im di IHDIVIMIAI. AWIMAI. HISTOFATIIOIOC HATA fart 6 Tiaauu*/ U b e ru v u tlo n "* Groupi III Doom ___ 100 -- / t a 1* Modo u f Daathi S B. s BS ff o S Sa - J L .l u i Paya on T oatt Hecovary Payai H _ 4 _ ____ * _ 12 >* 000 Hat Ho. 101-1 5B2 w SW H 0 BBS ? M HS H 26 SOI N 26 M SBB H U~ n BB9 N 26 14 JM M 76 U Ml 1 lla p a titla , uucrotlc. purutograniilffloatous, M u ltifo c a l - - - ' - - ' ' -, ' lla p a titla , lyaphocytlc, fo c a l .1 !im u n n ifn c atsTKq I Spleen N H NH HNNHNN I l.ynpliocytlc d o iila tlo n , d iffu s a - - - a a ' Bona Horrow i llypucul lu la r lt y , d iffu s a I 1 H I 1 N. 1 1 I H - - - ' - n m 0 _ Tliywuu NNN HN MN NH M Uyapliucytic da plotiou , d iffu s a - ' - a a. Tliyiuusl t la , pyugrunuloaatouu, lllllil - - Tliyuli- l.yraj.li NuJe l.yupliucyt lu liyputp iua ia . Jtflllo u Hus>J!L!!gMJ}^L uvai'im ' HHHNNHHN L N * * - -- --3 llu u ri HH 1 NN N H NHH i t NI 1N11 I N IV S M_ S H ___ IL ___ IPL P P 8 M 8 H 8 H R M s M 14 0 592 _ 1* 0 sa) - J L0 --<gtQf^A . -J L --yrr0, 12 0 -M S . 46 J* S97 6 26 -J A --1 * JJ L 26 26 . 6010 .. M Sl - 1- - 1- - H N N N N N' H H N N ' *" * - -- - _ M I H1 I MN 1HI '* " - - - - - - ... - N NM HHH NNNN * ** * - - -- H HNO HUN HUN - --- ------ I NHNHHI NNH H I I 1 I HN I NI Company Sanfizad, Ocss no! oonam TSCA CBS HltlVIPMAt. AW im i HlSTOPATROLOCY DATA Port 1 I&H8UV-/ O bservations** MKHVOUS SYSTEM Eyes B ruin Croup i ___ in Daaai Nod o f Doathi S ail Daya on T o a ti Recovery Davai Rot No. 301- 1 UH1 0 Ml ._--__S1I2fM8)t._ .nJSf 0 SA4 _--_IM1HSs?__ _1IM01M20s0_w_ta/kffaLI0ff -2. 91?5H98f----21M96a -_.31229M8f6t_-2J21UM596- K i 'N N N N NN N N H N H H NN N N NN RESPIRATORY SYSTE0 HTracheu - -1 - 2 1 H_G T ra c h e ltla , ly a p h o c y tlc , fo c a l Li Lungs L N NL L LNN NNN LL N LL Pneunonltlt. it e a L lt ls l, - 2 a. 1 3 2 2granulomatous, s u lc ilo c a l 2 SVST{!H 1UHUiiENITM. Kldnuy (u) 1.N e p h ritia , t u b u l o i n t e r u t it ia l, p u ru le n t, b l l u t u m l M u ltifo c a l NNLNNLL L N -- N u p lirlllu , lynpbucytic, In io r a tlila l focal 2- ,, 1 1, - - - - - - 12Tubular e p ith e liu m , b a a o p litllu , 1 -m u ltifo c a l o r fo c a l IV -- .. _______________ 10 jbm/ I ib ___ 8. . . 9 0 8 8 0 s a fl N t' t H N Pf M M M 19 19 19 .1912 --U 1fl__- W__ ft l - __ -32 f 9 t- --- 3 J? i0 21. - -- 5 12 ft - 8ft_- 26 19 32 2__ 70 MW 26 -329.. 26 ?6 . -fiftft--m 1NN l NNNNN N NNI NNI NI NI NL NNLNN I NH - 1 - - 1 - - . - am L NHNNL NL L L 2- - - - 1- 22 1 N L L NN L L L H N 11 Company Sanitized. Does not contain TSCA CBI 1ll-HOOB TABI.B I (C ontinued! IMniVltHUL AHimi. Part 6 TOltmumorivu*at/ long** ' III l -- ----------------------------------------------------- l o o j s a / h * 1B 3 8 S JL..... M If anDaya Hecovery Ho.tut T au t ... 1 1 ..... Oayai' - J L . 301-1I 582 T n in -J ? ____ f t _ . . - . M i , H * _n _ II 0 88 MM 2b 26 14 -- L L . 1 7 ..._ i! L N u p lir ltlu , tu b u lo in ta ra t i t 1*1,i lyapliocytlc, u a u tro p lilllu , u n ila te ra l, M ultifocal 8 8 M M II 26 26 26 i r 1 14 j m -M i Nupliruais, uni la ta r a l, m il tifu c a l - - - - - - - - -- C u pa ulltlu,fibrin op uru lun t, focalliuB orrtiogic, u n ila ta ta l, <n _- - - - ,, ' I Tuatia (uu) Bcwinlferuua tubular N N N M L N N N MN e p lcliu llu n , atrophy. UKtuuu, b ilu tu ra l - - - - -- - - In tt-tu c Itiu i c a ll liypurpluuiu, illltu u u , b llu iu tu l - - - - 1- . EpiUJ y a lllu , tiit r n tU 'll lyiN plm c/d, un llu r a ra l fin a l N MHH MHH H HN - - -_ . ---------------------------------- -------- VI______ 12 26 2146 26 *246s fi 5 M J! __n .. 1? . 0 -26M0Sf fiJ il ,, 0 -* H _U _ P JO M /ka _S__- - 1H? 0 .14 8 ___ L ___ & _ MMM s K -- 14_ -X L . 14 '-SL. 1 - 1- - - - - - - - - 2_ NNNHHN HNMN --- -- - - -- - - - - - - __ HNNNHN NHN - ___. - . N Company Sanitized. Does not contain TSCA CEE i %m ^ 11-14008 . TABLE II SUMMARY OP H1ST0PATH0L0GY DATA Group Days on Study: Mo. of Animals : Tlsaue/Qbservatlon________ Sex : I 12 5 M 26 5 M 8 10 11 12 15 26 M2 M1 4 M M1 1 M Esophagus (A) (5) (2) (1) (4) (0) CD Perlesophagltls, granulomatous, focal 0 0 00 100 Stomach (5) ( 5) (1) (1) (A) (0) (1) Glandular, atrophy, diffusa Liver Hepatitis ..nQcjrhtlc/ ' 00 (5) (5) 0 10 0 0 (2 ) (1) (A) (0) CD .wj p u r u l b ^ a ^ i ^ t p u s , pul|lfocal.-lp- _ o P0 1 0 -si; ;r' i # . " " b.i:;.).v fe .0 : 0 0 0 Spleen . ", '' :-xlA '*> : H : a> (1) (4) m 0 0 (l) 3 Lymphocytic, depletion, diffuse 0 0 213 10 Bone Marrow I (A) (A) (2) CD (3) (0) (1) &m) Hypocellularlty, diffuse 00 1l 300 Thymus i (A) (5) ( 2) (0) (4) (1) (1) a Lymphocytic depletion, diffuse 0 0 o o Thymusltls, pyogranulomatous, 202 10 8 focal S3 O 00 00001 8SI09 * () " Number of tissues evaluated yj o .^y.A v. . t ..7., III 12 26 5 M M5 (5) (5) VI 12 26 55 MM (5) (5) 00 (4) (5) 00 (5) (5) 00 (5) (4) 00 (5) (5) 00 o0 0 'o - !1 (5) (5) i\*.''.tVk&^ (5) 00 00 (1) (2) (2) (3) 00 00 (5) (5) (5) (5) 00 00 00 00 H-14008 : J TABLE II (Continued! SUMMARY OP HISTOPATHOLOGY DATA Port 2 Group:____ I_ Days on Study: 12 26 No. of A n i m a l s 5 Tissue/Observation Sex: Lymph Node (Thymic) f/Vj jItr Lymphocytic hyperplasia, diffuse Trachea ... ~ ~ Tracheitis, lymphocytic, focal Lungs; k 00 (4) (4)' 00 (5) (5) J& Pneumonitis, interstitial,. 8 * a ;n i s i O B ia tC !u a ,, m u l t i f q a l |i{ Irsif ; . v;:.. . . '^ldnes 2 . ' S A - (5> j ' T39 3) C<O 3a s< N* k: a ; 'b' '\i D O(d f j <3/> O o o3** fi> 5' H co o > purulent, bilateral, multifocal Nephritis, lymphocytic, inter stitial, focal v Tubular epithelium, basophilia focal or multifocal Nephrosis, multifocal, unilateral Capsulitis, fibrlnopurlent, hemorrhagic, multifocal, uni lateral 0 1 2 0 <> a Number of tissues evaluated 0 1 2 0 II 8 10 10 I1DR 26 2 14 l 1 M M ___ M____ M_ M (2) ( l ) (4) (0) (1) 0 00 o0 (1) (.1) (4) CO) (1) 00 10 0 ;< # ' (1) (4) Cl) (1) U- 0 1 ; Q; ' 1 . (2) (1) CD CD vj v - 2141 0 00001 00 00 1 hi 12 26 55 MM (5) (5) 01 (4) (5) 20 (5) (5) , .5, . <5)t C5) 00 22 12 0 00 0 0 00 0 00 ... .. .... / v.;v ' it/....,_>/* - IV 12 s M 26 D M (4) (3) 00 (5) (4) 20 (5) (5) I4 (5) :(5) 00 11 03 10 10 H-14008 1 TABLE II (Continued) SUMMARY OP HISTOPATHOLOGY DATA Part 3 Group: r>Avn on Studvs Do, of Animal"* I 12 5 M 26 5 M Testis (es); Seminiferous tubular epithelium, atrophy, diffuse, bilateral Interstitial cell hyper plasia, diffuse, bilateral Epididymis (des): Epididymitis, intersitial, lymphocytic, focal, unilateral (5) (5) 00 00 10 11 8 10 12 15 26 2 1411 MM MM M (l) U ) (4) (1) (1) 0000 0 00000 00000 III 12 26 55 MM (5) (5) 10 10 00 IV 1 26 35 MM (5) (5) 00 00 00 Company Sanitized, Doss not contain TSOA CSS () => Number of tissues evaluated APPENDIX B E. I. d u P o n t d e N e m o u r s & C o m p a n y H a s k e u . La b o r a t o r y t o r T o x ic o l o g y and In d u s t r ia l M e d ic in e i El k t o n R o a d , N e w a r k , D e l a w a r e lj9711 I CENTRAL research and developm ent EPARtMENT *I Haskjell Laboratory No. 14008 I . .' ; June 29, X981 Blood 8ample^fM^tlygj^^roup^ofl0jnale rats intragastrically dosed: 10 levels of 0 mg/kg (controls), 10 mg/kg and rats dosed with 1000 mg/kg were examined. i ! . After the tenth dose, bjlood was taken from |he tails of these rats for the measurement of erythrocytes (BBC), hemoglobin (Hb), mean corpuscular volume (MCV), platelets, leukocytes (WBC) and relative number of neutrophils (Neut), lymphocytes (Lymph),| eosinophils (Spain), monocytes (Mono) and baso phils (Base) , The hematocrit (St), mean corpusphlar hemoglobin (MCH) and mean corpuscular hemoglobin concentration (MCHC) were calculated from these data. Alkaline phosphatase (AP), glutand'c^pyruyic transaminase (GPT), glu tamic-oxaloacetic transaminase (GOT), urea nitrogen (BUN), creatinine (CHEAT), and total protein (TPROT) ve|re also measured in the serum. Five rats from the 0 mg/kg, 10 mg/kg and 100 mg/kg groups and four, rats from the 1000 mg/kg group were then sacrificed for pathology.. After a 14-day recovery period, the measurements were repeated oh the surviving rats in each group. The data were analysed Statistically by a one-way apalys Leas^signifleant differences were calculated to compare 0 H l H B % r e a t e d rats with the controls when Che ratio 5f variances Lcaced a fforanos among tee groups. Significance was judged at the 0.05 probability level. The results of the clinical laboratory measurements, are summarized in Table I; statistical analysis in Table 11; Measurements on individual ani mals are listed in the computer printout attacfrbii to the report. chan nor to the the data showed that rats dosed 10 times with ,t levels of 100' hg/kg and 1000 mg/kg had higher tyuitoty tc Counts and hematocrits which appeared to be related These two >.rou^s also had a slightly lower MCH and MCHC when 20 Company Sanitised. Dees not contain TSCA CBI I ^ comoared to the control animals. Bats dosed with 1000 mg/kgl hlghet leukocyte counts almost twice "the normal the controls. These animals, also showed a three-- fold increase in serum BUN and increasedhemoglobin, ,<^T and creatinine. The 100 mg/kg treated rats showed a slight] increase in serum iotal protein. Examination of the differential smeara Showed an increase in the relative nunfcer of neutrophils in the 1000 *g/kg group and a light to moderate hypochromia in the 100 mg/kg and 1000 aagg//kkgg| gzroups. Fourteen da^ laterr,, only one rat remained in the 1000 mg/kg 1 treated g^oup. Statistical analysis at this time Included Jie control, 10 mg/kg and 100 mg/kg dose levels, Other than a slight increase in serum creatinine levels in the 100 mg/lcgHjreated r a t s ^ ^ ^ ^ ^ t e a H j ^ ^ ^ significant difference between the control rats J ted rats was found for the Other measurements made on the bloor Import hyjjOaH L l l L ad. Catherine C. Matarese Technician CCM:JBB:mjh Approved by: ( John R. Barnes Chief, Clinical Pathology Section -21Company SasSsted. Doss rsst contain TSCA CBi Company Sanitized. Does not contain TSCA CBI TABLE I AVERAGE CLINICAL LABORATORY VALUES ON bats INTUBATED ______ i i i w W B B I M -- RECOVERY Erythrocytes 10/mm^ Q jpb/Hs - 1 ffg/fcg . 100 ms/ks 6.64 6.64 7.21 "1000 me/ke I---0--mft/ke 10 me/ke 8.11 7.01 6.93 6.98 Hemoglobin gX 15.3 15.1 15.9 17.6 15.4 15.3 15.4 Hematocrit X 38 38 41 48 40 39 40 MCV y3 58 57 57 59 57 57 57 MOI pg 23 23 22 22 22 22 22 MCHC % 40 40 40 37 38 39 39 Platelet 103/inm3 I 1366 1069 1198 1028 1070 1075 1190 KM> Leukocytes 103/mm3 12.9 12.3 14.0 23.0 13.2 10.5 13.7 I Neutrophils 17 16 11 38 16 20 15 Lymphocytes 75 79 84 53 80 73 81 Eosinophils 0.5 0.3 0.3 0.9 0.6 1.0 0.2 Monocytes 5.3 5.2 4.4 8.6 3.8 6.4 3.6 Basophils AP IU 0.0 f 258 0.0 203 0.0 246 0.0 291 0.0 276 0.0 217 0.0 243 CPT IU 19 19 20 23 20 18 19 GOT IU 53 51 56 60 47 52 44 BUN mg/dl 20 21 21 78 20 18 19 CREAT mg/dl 0.6 0.6 0.6 1.0 0.6 0.6 0.7 TPROT g/dl 5.9 5.8 6.1 5.8 6.3 6.2 6.4 * - only one rat survived the recovery period 6.25 14.1 37 59 23 38 1214 12.6 22 67 1.0 10.0 0.0 245 14 25 29 0.6 6.4 Company Sanitized. Doss not i to ;oOs fj) S' hi cn o o co W F* RBC Hb Ht MCV MCH MCHC Platelet WBC Neut Lymph Eosin Mono AP GPT K GOT BUN CREAT TPROT 23. J 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 TABLE I I SUMMARY OF STATISTICAL ANALYSTS WIIHP " 10 m^/k| 0 0 0 0 0 0 0 0 0 0 0 0 10 DAY 100 1000 -- 4Rats intubatrh F# 10 RECOVERY 100 0 0 0 0 0 F* - Significant if T 2.89 " Significant i f '>'3.88 (0) - Not Significantly different than controls (+) - Significantly high, r than controls (") " Significantly lower than controls i/ r r if'; : to ^ .: jxrfcy*. ii- I-*'fr ' Si.-.. -: fr' I-..: n; GROUP: 1CH DOSE: SAMPLE DATE: 15 MAY-81 SEX: MALE . SPECIES: RAT BIRTH DAT?: 13-MAR-81 ANIMAL#: 301540 301541 301542 301543 301544 301545 301546 301547 301548 301549 RBC MM/cm 6 .9 1 6.67 6.41 6.64 6.77 6.35 6.47 6.87 6.86 6.46 Hb eS 15.2 15.2 14.6 15.9 15.1 14.1 15.3 15.8 16.0 15.4 AVG. S. D. S. B. 6.641 0.208 0.066 15.26 0.59 0 .19 Ji t Hey \% /erne 56.38. 55. 3 31] 58. 3i 58. 57. 57. 58. 41 59. 4<1 59. 37 57. 38 .2 15 0 .5 57.6 1.2 0.4 MCH /mag 22. 23. 23. 24. 22. 22. 24. 23. 23. 24. 23.0 0.8 0.3 MCHC PLAT % M/cmo 40. 1071. 39. 1058. 40. 1005. 41. 898. 39. 1180. 39. 1167. 4J. 972. 39. 1080. 40. 1061. 42. 1163. 40.0 1065.5 1.1 90.5 0.3 28.6 GROUP: 2M DOSE: 1000| MG/KG SAMPLE DATE: 15-MAY-81 j SEX: MALE SPECIES: RAT BIRTO DATE: 13-MAR-81 ANIMAL#: 301550 301551 301553 301554 301555 301557 301558 RBC MM/cm 7.57 7.21 8.53 8.29 7.66 9.29 8.25 Hb 89 16.5 15.4 18.3 17.8 16.8 20.5 18.1 AVG. S. D. S. E. 8.114 0.698 0.264 17.63 1.63 o ;61 H 45 43 50 49 45 55 1 47f 47 j7 40 15 MCV /cac 59. 59. 59. 59. 58 59. 57. MCH /mag 22. 21. 2 li. 22. 22. 22. 22. MCHC PLAT % M/cnm 37. 1351. 36. 797. 37. 822. 36. 1210. 38. 888. .37. 1329. : W . 802. 58.6 21.7 0.8 0.5 0.3 : 0.2 37.0 1028.4 0.8 256.4 0.3 96.9 i j 24 - Company Sanitized. Does not contain TSC CBI MR: CC PERIOD:1 TOXICOLOGIST: DASHIELL SKfeLL#: 14008 HASKELL CODE# DPRTMNT: PPDACP REPORT DATE: 9-Jun-8l CLINICAL LAB: KATARESE GROUP: 1CM DOSE; CONTROL SAMPLE DATE: 15-MAY-81 ; SEX: MALE SPECIES: RAT BIRTH DATE: 13-MAR-81 ANIMAL#: 301540 301541 301542 301543 301544 301545 301546 301547 301548 301549 AVG. S. D. S. E. NBC M/cm 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 Nut * 18. 19. 15. 19. 17. 17. 19. 19. 12. 12. 16.7 2.8 0.9 Lynpl1 % n 75 82, 73. 78, 48, 76, 77, 80. 80. 1 745 9J7 34 1 Eoaln % 0. 0. 0. 1. 0. 1. 1. 1. 1. 0. 0.5 0.5 0.2 Mono * 6. 6. 3. 7. 5. 4. 4. 3. 7. 8. 5.3 1.8 0.6 Bao % 0. 0. 0. 0. 0. 0. 0. 0. 0. 0. 0.0 0.0 0*0 I GROUP: 2M DOSE: 1000 MG/KG SAMPLE DATE: 15-MAY-81 ! . ' '' SEX: MALE SPECIES: RAT BIRTH DATE: 13-MAR-81 ANIMAL#: 301550 301551 301553 301554 301555 3ri557 38 A S. D. S. E. NBC M/cm 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 Lymph %; 56. 57J 714 61.! 63.; 2 2 .; 41.1 -1 j 5 3 .|o 16.14 6.2 Eoaln % 0. 0. 1. 0. 0. 3. 2. 0.9 1.2 0.5 Mono S 8. 9. 4. 10. 5. 12. 12. 8.6 3.2 1.2 Baso % 0. 0. 0. 0. 0. 0. 0. 0.0 0*0 0.0 - 25 - C om paq Sa???fesc?, Dee* '* * t SCA rR f MR: COMPNDd PERIOD:' DAI TOXICOLOGIST: DASHIELL HASKELL#: 14008 HASKELL CODE#: DPHTMNT: PPDACP REPORT DATE: 9-Jun-8l CLINICAL LAB: MATARESE GROUP: 3M DOSE: 100 Kp/XS SAMPLE DATE: 15-MAY-81 j SEX: HALE SPECIES: RAT BIRTH PATE: 13-MAR-81 , ANIMAL#: 301582 NBC M/cm 9.7 Neut Lymph Eoain f $!1 18. 74. ! 0. Mono $ 8. Baso % 0. 301583 14.3 14. 79. ! 0. 7. 0. 301584 13.8 13. 83. .1. 3. 0. 301585 9.0 10. 88. 0. 2. 0. 301586 14.6 5. 88. 1. 6. 0. 301587 10.7 11. 87. 0. 2. 0. 301588 19.7 1?. 84. 0. 4. 0. 301589 15.8 11. 84. 0. 5. 0. 301590 17.5 10. 85. 1. 4. 0. 301591 15.2 6. 91. 0. 3. 0. fri;! AVG. 14.03 11.0 84.3 0.3 4.4 0.0 S. D. 3.40 3.7 4.3 0.5 2.1 0. S. E. 1.08 1.2 r.? 0.2 0.7 0.0 GROUP: 4M DOSE: IO MG/KG SAMPLE DATE: 15-MAY-81 ! SEX: MALE SPECIES: RAT BIRTH DATE: 13-MAR-81 NBC Neut Lymphi Eosin Meno Baso it ANIMAL#: M/ca $ i i %i ; 301592 14.9 12. 85. ! 0. 3. 0. 301593 17.6 10. 86. : 0. 4. 0. - 301594 13.9 22. 69. i 0. 9. 0. 301595 10.4 16. 8i, ; ,0. 3. 0. 301596 10.5 22. 72. ; 2. 4. 0. i 301597 10.3 14. 82. i 0. 4. 0. 1 301598 9.5 9. 85. i 0. 6. 0. 301599 10.6 14. 80. 0. 6. 0. 301600 10.4 15. 76. 1. 8. 0. I 301601 14.6 25. 70.| 0. 5. 0. ` AVG. 12.27 15.9 78.6) 0.3 5.2 0.0 S. D. 2.75 5.4 6.4! 0.7 ; 2 .0 O'. S. E. 0.87 1.7 2.0 0.2 0.6 0.0 - 26 - Company Sanitized. Does no! contain TSCA CBi MRs ' C0MHID7] PERIOD:RECOVERY TOXICOLOGIST DASHIEL I KELL#: 14008 HASKELL CODE#: DPRTMNT: PPD&CP REPORT DATE: 1-Jun-81 CLINICAL LAB: MATARESE f| w GROUP: 1CM DOSE: CONTROL SAMPLE DATE: 29-MAY-&1 SEX: MALE SPECIES: RAT BIRTH DATE: 13-MAR-81 ANIMAL# : , 301540 . 301541 301542 301543 301544 301545 301546 301547 301548 301549 RBC MM/on 7.53 6.35 7.02 7.11 7.C2 Hb 15.9 14.2 16.2 15.6 15.2 Ht *' i MCV /case 42. 36. 3. fl. j<0. 55. 57. 61. 57. 57. M3J /rang 21. 22. 23. 22. 22. MCHC PLAT % M/cmm 38. 1220. 40. 1062, 38. 944. 38. 1142. 38. 980. AVG. S. D. S. E. 7.006 15.42 0.423 0.78 0.189 0*35 10.4 i2.7 j1.2 57.4 2.2 1.0 22*0 ,0*7' 0.3 38.4 1069.6 0.9 113.7 0.4 50.9 -1 GROUP: 2M DOSE: 10(10 MG/KG SAMPLE DATE : 29-MAY-81 SEX: MALE SPRPTRS BIRTH DATE: 13-MAR-81 ANIMAL#: 301550 301551 301553 301554 301555 301557 301558 RBC MM/cm 6.25 Hb g% 14.1 jHfc MCV % /cmc ':% 59. MCN MCHC PLAT /mug % M/cmm 23. 38. 1214. AVG. S. D. S. E. 6.250 14.10 " 37.0 | i- 59.0 23.0 '- 38.0 1214.0 . - - 27 - Dees not cornato TSCA TOXICOLOGIST: DASHIEL 14008 HASKELL CODE#: m 1 DPRTMNT: PPD&CP REPORT DATE: 18-May-81 CLINICAL LAB: MATARESE GROUP: 3M DOSE: 100 MS/KC SAMPLE DATE: 15-HAY-81 SEX:. MALE SPECIES : RAT BIRTH DATE: 13-MAR-81 ANIMAL#: 301582 301583 301584 301585 301586 301587 301588 301569 301590 301591 AVG. S. D. S. E. AP ID 225. 235. 180. 285. 220. 230. 330. 290. 240. 225. 246.0 43-3 13.7 GPT IU 23. 25. 14. 19. 21. 16. 19. 25. 19. 19. GO^ BUN ID Mg? 70. 25.0 75. 24.0 4P* 20.0 50.. 24.0 5 K* 19.0 6 r* ' 21.0 5 P* 21.0 6 20.0 5 P . 18.0 4 5# 20.0 GREAT ngi 0.6 0.3 0.6 0.6 0.6 0.5 9.6 0.6 0.5 0.6 TPSOT * 6.2 5.7 6.0 ' 5.7 6.2 6.1 6.4 6.3 6.3 6.3 20.0 3.6 1.1 5 5.5 21.20 11.4 2.35 3.8 0.74 0.56 6.12 0.10 0.25 0.03 . 0.08 GROUP: 4M DOSE: 10 kj/KG SAMPLE DATE: 15-HAT-81 | SEX: MALE SPECIES BIRTH DATE: 13-MAR-81 ANIMAL#: 301592 301593 301594 301595 301596 301597 301598 301599 301600 301601 AVG. S. D. S. E. AP IU 145. 280. 170. 195. 230. 170. 205. 185. 250. 200. G1P0T 17. 17. 19. 17. 21. 19. 21. 19. 21. 19. 3GC T 0 50. 50. 60. 55. t55. 5. 15. 1c0. 5. l 5. BUN mg? 20.0 19.0 25.0 21.0 2!2.0 20.0 18.0 21.0 17.0 22.0 CnHEs*AT 0.5 0.5 0.6 0.7 0.5 0.6 0.6 0.7 0.5 0.6 TPROT ef 6.1 5*8 5.8 5.8 5.7 5.9 5.5 5.7 5.6 203.0 40.6 12.8 19.0 1.6 0.5 1.0 20.50 5.2 2.27 1.6 0.72 0.59 0.06 0.02 '5.80 D.19 0.06 - 28 - Company Sanitized. Does not contain TSCA CSf MR: Xk A _ PERIOD:" O DAY TOXICOLOGIST: DASHIEL HASKELL# * ; i 14008 HASKELL CODE#: DPRTMNT: PPD4CP REPORT DATE: 18-May-81 CLINICAL LAB: MATARESE GROUP: 1CM DOSE: CONTROL SAMPLE DATE: 15-MAY-81 ANIMAL#: 301540 301541 301542 301543 301544 301545 301546 301547 301548 301549 AP IU 195. 255. 265. 265. 185. 265. 325. 280. 240. 300. GPT IU 16. 19. 19. 23. 19. 17. 19. 17. 19. 21. GOT sIoU; 65 ; 451 601 50 60; 50+ 45. 504 55j nBUgNl 22.0 22.0 18.0 21.0 19.0 20.0 21.0 19.0 20.0 21.0 SEE: MALE SPECIES: RAT BIRTH DATE.: 13-MAR-81 CREAT TPROT agl S% .7 5.8 0,5 5.8 0.7 5.7 0.6 5.9 0.6 5.5 0.7 5.9 0 . 6 ' 6.0 0.7 6.2 0.6 6.0 0.5 5.9 AVG. - 257.5 S. D. 42.8 S. E. 13.5 18.9 2.0 0.6 6153<j0 20*30 7 1.34 2n1 0.42 0.62 0.06 0.02 5.87 0.19 0.06 I GROUP: 2M DOSE: 1000 Im G/RG SAMPLE DATE: 15-MAY-81 * SEX: MALE SPECIES: RAT BIRTH DATE: 13-MAR-81 ANIMAL#: 301550 301551 301553 301554 301555 301557 301558 AVG. S. D. S. E. AP IU 290. 395. 305. 240. 315. 210. 285. OPT IU 19. 28. 19. 2258.. 25. 19. GOT IU 45. 65. 55. 60. 75. 70. 50. BUN ngjt 74,0 61.0 66.0 79.0 91.0 106.0 66.0 GREAT agl 1.1 1.0 0.9 1.2 1.3 0.9 0.8 s*TPROT : 5.8 5.5 5.8 6.2 5.5 5.8 291.4 58.9 22.2 23.3 4.2 1,6 60. 77.57 10,8 16.05 4,jl 6.07 1.02 0.18 0.7 5.76 0.24 0.09 - 29 Company ^Si2c! *-'Oes rsof c o n ia i r c A CBt I MR COI PERIOD:"TO DAY TOXICOLOGIST: DASHIEL W: 14008 HASKELL CODE#: DPRTMNT: PPD4CP REPORT DATE: l8-May-8l CLINICAL LAB: MATARESE GROUP: 3M DOSE: 100 MB/KC SAMPLE DATE: 15-MAY-81 SEX: MALE BIRTH DAIS: 13-MAR-81 RBC it MCV MCH MCHC PLAT ANIMALS: MM/cm 301582 7.49 % /one /mng 55. 22. 5 M/cnan 39. 1021. 301583 7.01 . 60. 23. 38. 1322. 30158 6.72 * 55. 22. 0. 1307. 301585 7.27 55. 21. 39. 1089. 301586 7.20 I 57. 22. 38. 1101 . 301587 6.65 1 57. 22. 38. 021. 301588 7.79 I* 55. 21. 39. 15C:. 301589 7.41 57. 23. 40. 1152. 301590 7.9 58. 23. 39. 1157. r 301591 7.10 57. 22. 39. 1217. AVG. 7.213 15.91 40.8 !.6 22.3 38.9 1198.0 S. D. 0.356 0.79 2.0 1.6 0.7 0.7 148.7 S. E. 0.113 0.25 0.6 0.5 0.2 ' 0.2 47.0 i 1' GROUP: 4M DOSE: 10 fjfG/ICG SAMPLE DATE: 15-MAY-81 SEX: MALE s BIRTH TATE: 13-MAR-81 ANIMAL#: 301592 301593 301594 301595 301596 301597 301598 301599 301600 301601 RBC MM/cn 6.78 6.84 6.21 6.89 6.64 6.76 7.10 6.12 6.63 6.41 Hb 8* 14.9 14.9 14.2 15.6 15.6 14.5 15.6 15.0 15.4 14.9 MCV [ t /erne 3t i. 56. 3 . 55. 3!i. 56. 3! . 57. 3 . ' 59. 3* . 56. 4C 56. 3i 59. A3S 58. 58. MCH /nog 22. 22. 23. 23. 24. 22. 22. 25. 23. 23. MCHC PLAT ;* % M/csim 39. 1226. 39. 1268. 41. 983. 40. 972. 40. 992. 39. 913. 39. 944. 42. 898. 40. 1262. Jp. 1231. AVG. S. D. S. E. 6.638 15.06 0.308 S. *9 0.098 0.15 bt|.9 i.5 ** 57.0 1.4 0.4 22.9 1.0 0.3 39.9 1068.9 1.0 156.2 0.3 49.4 - 30 Company Sanitised. Does not contain TSCA CB MR:| COMP}:] PERIOD: RECOVERY TOXICOLCr~*T: DASHIEL ^008 HASKELL CODE#: DPRTMNT:, PPD&CP REPORT DATE: 1-Jun-81 CLINICAL, LAB: MAtARESE GROOP: 3M DOSE: 100 MG/KO SAMPLE '/t e : 29-MAY-81 RBC ANIMAL#; MM/cm p. ! Hb MCV 83 /erne 301582 301583 1i 301584 1i 301585 301586 301587 4c|.301588 301589 301590 4.301591 6.90 7.18 6.80 6.69 7.31 15.4 15.1 15.4 15.3 16.0 t 39. 58. 54. 58. 59. r5. AVG. S. D. S. B. 6.976 0.261 0.117 15.44 0.34 O.15 39L6 01.9 0.4 56.S 2.2 1.0 SEX: MALE SPECIES: RAT BIRTH DATE: 13-MAR- MCH MCHC PLAT /rang M/enm ?2 . 21. 23. 23. 22. 39. 1142. 39. 1292. 39. 1260. 39. 1020. 39. 1238. 22.2 . 39.0 1190,4 0.8 0.0 110.5 0.4 0,0 49.4 GROOP: 4M DOSE: SAMPLE DATE: 29-MAY-8 ANIMAL#: 301592 301593 301594 301595 301:96 301597 301598 301599 301600 301601 RBC MM/em 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 15.34 0.382 0.65 0.171 0.29 1 39J 38J 39j 43< 37.] 2.3 1.D MCV /emc 55. 56. 57. 58. 57. 1.1 0.5 SEY MALE SPECIES: RAT BIRTH DATE: 13-MAR-81 MCH MCHC PLAT /nmg j K/cnm 22. 22. 22. 22. 23. 22.2 0.4 0.2 39. 39. 39. 38. 4 980. 986. 1066. 1204. 1138. o' ?90 1074.8 7 97.0 0 .3 43.4 - 31 Company S anili ra:n S C OBI C f l M P M p l _____ PERIOD :TECOYRY TOXICOLOGIST: DASHIELL L#: 14008 HASKELL CODE# DPR1WNT: PPD&CP REPORT DATE: 9-Jan-81 CLINICAL LAB: MATARESE I i GROUP: 1CM DOSE: CONTpOL SEX: MALE . SPECIES: RAT SAMPLE DATE: 29-MAY-81 ! BIRTH DATE: 13-KAR-81 ANIMAL#: 301540 301541 WBC M/cm Neut % Lyoptb Eoaln %I % i Mono > Baso * 301542 301543 301544 i1 301545 12.3 12. 84 j 0. 4, 0. 301546 15.4 29. 67. 1. 3. 0. 301547 10.3 13. 82 .i 0. 5. 0. 301548 14.9 20. 75.; i. 4. 0. 301549 13.2 6. 90.; 1. 3 * 0. f- . AYG. 13.22 16.0 79.6 0.6 3.8 0.0 S. D. 2.06 8*8 8.8 0.5 0.8 0.0 S. E. 0.92 3.9 4.6 0.2 0.4 0.0 i GROUP: 2M DOSE: 1000 MG/KC SAMPLE DATE: 29-MAY-81 | SEX: MALE SPECIES: RAT BIRTH DATE: 13-MAR-81 ANIMAL#: 301550 301551 301553 301554 30155 301557 301558 AYG. S. D. S. E. WBC M/em 12.6 12.60 Neut Lymph Eosin * * * 22. 67. 1. (j22.0 87. 1.0 ii Mono % 10. 10.0 Baso % 0. 0.0 Doesompany Saniiizsd no! contain TSCA CBI MR: I COMPNDll PERIOD:1 TOXICOLOGIST: DASHIELL 14008 HASKELL CODE# DPHTMNT: PPDACP REPORT DATE: 9-Jun-8l CLINICAL LAB: MATARESE GROUP: 3M DOSE: 100 wd/XG SAMPLE DATE; 29-MAY-81 j SEX: MALE SPECIES: RAT BIRTH DATE: 13-MAR-81 ANIMAL#: 301582 301583 301584 301585 301586 301587 301588 301589 301590 301591 NBC M/em 13.1 18.6 15.2 10.8 10.9 AVG. S. D. S. E. 13.72 3.27 1.46 SNeut i f fILymph jEoain Mono i i!' !_ 9. 87. 15. 81. 17. do. 19. 75. 14. 84. 1. 0. o. 0. 0. 14.8 3.8 1.7 81.4 0.2 4*5 I 0.4 2.0 0.2 3. 4. 3. 6. 2. 3.6 1.5 0.7 Baso % 0. 0. 0. 0. o. 0.0 Q. 0.0 GROUP: 4M DOSE: TO MG/KG SAMPLE DATE: 29-MAY-81 SEX: MALE SPECIES: RAT BIRTH DATE: 13-MAR-81 ? NBC Neut Lymph Eosin Mono Baso ANIMAL#: M/cm *301592 $ % *% 301593 301594 301595 301596 1.1 -1 . > 301597 10.4 23. 74. 1. 2. 0. 301598 10.4 14. 82. j 1. J. 0. 301599 9.3 15. 76. 1 1. 8. 0. 301600 12.0 27. 58. ! 2. 13. 0. } 301601 10.2 21. 73. j! 0. 6. 0. \t4 AVO. 10.46 20.0 72.6 ! 1.0 6.4 0.0 S. D. 0.97 5.5 8.9 : 0.7 4.4 0.0 Se Ea 0.44 2.4 4.0 ! 0.3 2.0 0.0 II I i Ij 33 - Company Sanlfesd Does r :CA CBS j <1 MR:| COMPNDii PERIOD:1 TOXICOLOGIST: DASHIEL ETELLS: 1*1008 HASKELL CODE#: F DPRTMNT: PPDACP l REPORT DATE: 29-May-8l CLINICAL LAB: MATARESE GROUP: 1CM DOSE: CONTROL SAMPLE DATE: 29-MAY-81 SEX: MALE SPECIES: PAT BIRTH DATE: 13-MAR-81 ANIMAL#: 301540 301541 301542 301543 301544 301545 301546 301547 301548 301549 AP ID 290. 300. 275. 225. 290. GPT IU 17. 19. 17. 21. 25. G BUN CREAT TpROT CO mg* sg? )5. 22.0 55. 18.0 55. 19.0 0. 18.0 'r0. 22.0 0.6 6.3 0.6 6.1 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 17.0 19.80 16.8 2.05 7.5 0.92 0.62 0.02 0.01 6.30 0.14 0.06 GROUP: 2M DOSE: 10)0 MG/KG SAMPLE DATE: 29-MAY-81 SEX: MAfeE SPECIES: RAT BIRTH DATE: 13-MAR-81 ANIMAL#: 301550 301551 301553 301554 301555 301557 301558 AVG D S. E AP IU 245. 245.0 GPT G IU fu ' i' 1 1 i j 14. 25. 1 ! i 14.0 >5.0 BON CHEAT 5TPR0T 45? 08$ * 29.0 0.6 6.4 29.00 0.64 6.40 'I t I- - 34 - _ Company Sanitized. Does not contain TSCA CBI ; ; I MRsl COMPND: PERIOD:1 TOXICOLOGIST: DASHIEL [SKELL#: 14008 HASKELL CODE# . DPRTMNT.: PPD4CP REPORT PATE: 29-May_gi CLINICAL LAB: MATARESE GROUP: 3M DOSE: 100 MG/KG ' SAMPLE DATE: 29-MAY-81 SEX: MALt SPECIES: RAT BIRTH DATE: 13-MAR-81 ANIMAL#: 301582 301583 301584 301585 301586 301587 301588 301589 301590 301591 AP 10 240. 275. 245. 240. 215. GPT JO 14. . 21. 25. 16. 17. COT BON CREAT T?ROT W 6*' 8* ' gl I I I BO. 15.0 0.8 6 .1 m - 20.0,, 0.7 4 y6.5 50. 19.0 0.8 ' 6.6 K 18.0 0.6 v-,6.4 35. 2 1 .0 6.5 AVG. S. D. S. E. 243.0 21.4 9.6 18.6 4.4 2.0 14.0 10.8 4.8 i 18.60 2.30 1.03 0.72 0 .0 0.02 6.42 0.19 0.09 'fi GROOP: 4M DOSE: 10 MG/KG SAMPLE DATE: 29-MAY-81 : SBK; MALE SPECIES: RAT BIRTH DATE: 13-MAR-81 ANIMAL#: 301592 301593 301594 301595 301596 301597 301598 301599 301600 301601 AP ID 180. 240. 210. 245. 210. AVG. S. D. S. E. 217.0 26.4 11.8 GPT 10 17. t9. 17. 21. 17. 18.2 01..88 GT BON CREAT.. tPROT CO 8 rag gl 1 60. 15.0 50. 19 .0 50. 18.0 60. 18.0 40. 2 1.0 52.0 18.20 8.4- 2 .1 7 3.7 0.97 0.6 6.1 0.6 6.0 0.6 . 1 0.5 6.5 0.7 6 .2 0.5Sf 6 .18 ,0.05 0.19 0.03 0.09 - 35 - Company Sanitized. Does not contain TSCA CBi September 16, 1981 HASKELL LAB AMD DEVELOPMENT F: DETERMINATION OF FLUORINE IN RAT BLOOD J. y'"-. (Job No. 812-668; PRAL Nos, 8l|2l6l-2U9.81r2419-?434,81-2611-2612; !K rt of s t u d l e s H H H H H H ( e x p o s u r e of rats to| _ _______ 37 n^olo^aemjplep*3bbmitted 5/20/81 - 6711/81 have been analyzed for fluorine by tfae wickbold Torch procedure. The analyses were done by Erik Kissa at Jackson Lab (After preliminary freeze-drying here), and results are given in the attached copy of his report,' S. S. Stafford Attachments Jah Key Words: Fluorine y L __________ ___ Blood Analysis Wickbold Torch 1 36 Company Sanitized. Does not contain TSCA CBI There'saw.1dofthingswe're doing something about C H .IM l R cy . I E. I. ou Pont os N emours & Company W i l m i n g t o n , D e l a w a r e 198981 JCAHCEKMSIOCNALLSAaBnOdRAPITGOMREYNTS DEPARTMENT :;i Ni \ Sally S. Stafford i : 'Polymers '& Plasties Department Experimental Station 2169/212 FLUORINE IN RAT BLOOD CONTAINING September 1, 1981 The fluorine eontent ot dried rat blood was determined by the I oxyhydrogen torch method calibrated with p-fluorobenzoic acid (corrected for a hi*nk[an# irdjiisted to 100% fluorine ref Th^esulte (see attached pages) suggest that jbhef---^ ^ ^ ^ " "ecovexy rate is similar to that oi -- i Average F ppm Dilate Sampled -- izu 197 25* 79 25 30 12 0*9 0.5 *0nly one rat survived Two fluorine values. Seemingly out of line, were _co_n_f_i_rm,,IeT.Ud tby dcuopnltiecnatteo f analyses. blood is The standard deviation larger than that Of the of the fluorine analytical method, indicating a large varfai op of f i l i n g in blood from rat to rat. We need only about -8-1 affi blo&for analyses, if a rat can donate this amount and recover*- it may be better to sample the same rat periodically to follow the decrease of fluorine in blood with!time. E. Rissa j Physical & Analytical ! |* EK:mml A ttach. : - 37 - mPan/ Sanitized. Does not contain TSCA CBI FLUORINE IN RAT BLOOD CONTAINING Sample Designation ( * ) usee received 81-2101 5/20/81 81-2102 81-2103 81-2104 ' 5/20/81 5/20/81 5/20/81 81-2105 5/20/81 Ri t . 3(1540 3 3,541 31:i542 3(11543 3( 1545 81-2106 81-2107 81-2108 81-2109 5/20/81 5/20/81 5/20/81 5/20/81 3( 1550 3C1551 3Q1553 3cjl55;4 81-2110 81-2111 81-2112 81-2113 81-2114 5/20/81 5/20/81 5/20/81 5/20/81 5/20/81 301582 3<j1583 * 3<(1584^ 301585 30 1586 81-2115 81-2116 5/20/81 5/20/81 30 1592 3Q|L593 Group. Tube # I Ti'Se ! I Tuue 2 I Tube 3 I Tube; 4 I Tube $ II Tube 6 II Tube 7 II Tube 8 II Tube 9 III Tube 10 III Tube 11 til Tube 12 H I Tube 13 H I Tube 14 W Tube^lS IV Tube 16 81-2117 81-2118 81-2119 81-2419 81-2420 81-2421 81-2422 81-2423 5/20/81 5/20/81 5/20/81 6/1/81 6/1/81 6/1/81 6/1/81 6/1/81 30 :L594 30pL595 303L596 ij' 303545 303546 30p1547 3Op 548 30(3S49 IV Tube 17 IV Tube 118 iv Tube 19 I Tubf X I Tube 2 I Tube 3 I Tube 4 I Tube 5 81-2424 6/1/81 301555 _t I II Tube 6 1.3 1.2 1.4 0.6 0.2 212 190 172 213 81 79 78 S3 76 25.6 31.3, 29.8 Avg. 30.6 16.7 22.8 21.7 (b) Group Average X - 0.94 a - 0.52 X - 197 a 19.6 X - 79.4 a - 2.7 i X - 23.5 CT * 5.1 0.1 1.0 0.5 0.5 0.3 X - 0.48 a - 0.34 23.1, 26.9 Avg. 25. to - 38 Company :0sse. :-S-ssniaSn TSC CBS FLUORINE IN RAT BLOOD CONTAINljNG -------- Sample Designation (a ) PRAT. Nn -nvet*. Ao _c_c_e_'iiv--e a 81-2425 31-2426 81-2427 81-2428 81-2429 6/1/81 ` 6/1/81 6/1/81 6/1/81 6/1/81 i ------R'a1t a#\-!-.--- Group. Tube # 30158J7 301588 301589 30159p 30159)L Ill Tube 7 III Tube 8 III Tube 9 III Tube 10 H I Tube 1 1 ' 81-2430 81-2431 81-2432 81-2433 81-2434 81-2611 81-2612 6/1/81 6/1/81 6/1/81 6/1/81 6/1/81 6/11/81 6/11/81 30159^ 30159 30159i 301604 301601 30427^ 30427 IV Tube I? IV Tube 13 IV Tube 14 IV Tube 1 % ; IV Tube 16 Fluorine Content, me/ke F Group Average 20.4 31.0 22.8 27.7 X - 25.1 a - 4.2 23.6 5.4 9.2 11.8 18.6 14.0 X 11.8 a 5.0 0.0 0.2 (a) Sample Designation for Group I - control Group II - high, 1000 ag/ks Group III - internediate,lQ0 mg/kg Group IV low, 10 mg/fcg j For samples 81-2101 through -2119, recovery time was 4 hours, after the final ose 5/15/81. For samples 81-J|419 through -2434, recovery time was 14 days. Samples 51-2611 and 81-2612 were ''blanks", blood from stock rats not part of the study but dried and analyzed along with th others. (b) Total fluorine content, not corrected for inorgattid fluorine values which are probably insignificant. 39 Company Sanitized. Does no! contain TSCA CBI