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ARR26 _ 3235 a7 | 512045a1G6ovSaugbeehSrronyi iTnoRxaitcith OneGenrnion Repro Evalions AR22DR6euvr-iosnetd35P3a28g6e35 `TRADE SECRET Study Tide H-24516: Subchronic Toxicity with One.9G0e-nDearaytGioanvaRgeepSrtoudduyetinonRaEtvsalustions Revision No. 1 Volume 2 of TEST GUIDELINES: U.S. EPA Health Effects Test Guidelines `OPPTS 870.3100 (1998) _ AUTHOR: Gregory S. Ladics, Ph.D., DAB.T. `ORIGINAL COMPLETED ON: December 3, 2001 REVISION NO. 1 COMPLETED ON: April 5, 2002 PERFORMING LABORATORY: EL du Pont de Nemours and Company Haskell Laboratory for Toxicology and Industrial Medicine NEelkwtaornk,RoDaed,fwPa.rO.e B1o9x71540-0050 WORK REQUEST NUMBE(R a swavice Cone None (ST) Seonson Srupy a] Ee Company Sanitized. 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BESoeoszi ii! $13345g 8 gS3z5 3E!| J|: 1ii355es2 EREEEN i Eg i2s23 }i ia iifgyi _ g SZz i ii: SC = i } iE Jee 3d| zgEz zzEz Esi ]i ii4s3]f ' | a 4h 1 55 | : ir 5: egT #< i ifnotg Pe LE {; zgg | 1 P {oEg Eog if PGE Bin HIE ths 1k Wi: o:go,tiEg en k gi o: |idig a ET EZ i 1.3 i i E&e 8% 2f%e 1l7g% ~ : i 3f8 te 5 i ese | i g B f | gila E i] IBii T ma:| : Eo 2 g dgiti l Fniie EcEEcEEEa! i EOEiE iEEgs! z Et TTIH : ;i$ ZZ3z j1184g g1{F3yE% | i223 zi :2 | : iLEy 2i _ gS5ei8gt! i :i: i1pi33af Zg B2L35E82R: |ii iP154a8% ~ |Z z2%2z} |: 1i3f2 of 5 22% : 153 2: os } i 2 gi%i:dz: |i 13338 3 FER i 7c ii E[5F2 ;g zgE d E~o i |i ff i: iiq gq g |%8g $ zg PBB Eis oF c |! POE IE EE ied Eis EiE: 82 ii . E iw HBOE5 oesJE IiEyC i 4 g| zd i 2 88 BF (4 iz 2 5% ud i%% _ ii:f 2: |i iiBEEgRae72 8gER7e EfRe 8% lie14g98 8 -B ii F Eoqglem BEE sng : , S iig gghigT t il L d Ei I gsiizeEEaasEiEgeigy) :i!3 E dL eL= TTErErTSieaaaREnEeE | 3 : " Bigoevesv: i : I i BE -g : r i*e | IH 1i ia24 ] _ 221 558%| | | R cE i _ lEgeZg z i iE] |g Za S- j i5i1f}s I1h1 137 iHi sd Ps d] F Zi g5a%z| i |:| ig- | ii 4ig; l g: | i || : i. Bhi ig 8 8 8 lfiaegidr aBr [oiI oln 3a 8 1i52 i1s 53 BLE i 1i%: -i3wt o: i0 EmREEeNCpEeei iiEi4# 38BB3 - i#i&}3 jBi= oTeLaBlT ii1] 8. E PEEIR[IJCS | Eopliem CBECE ! g 2& Lii F8 Tiio Fi i Eiis 3i Fig iad if [Epi iigz ! :: {3 TE i ii2 _gzBt24o28! }ii 1iiiE5i%; 52g g9g5z823si|| ||i iEfoEan _ 2 257%8!i1 |i} 11E3%E3: f 7gSC 2gp2zo8:i| ii! HiiHh 3 3i g= ESzREeEEzR!| i|i 1ir2red " iF Ez i it 25Z53%Z% | | !i| 111552 2 g 22d 8! ]| u14dg i2 322! |igOB oBg LEgp (iEGaHE Rky &E pBofE oAE3Ea E 23 g2 i . iiw g5p o3r 83 liifss 2223] 2% ~ 3238 g&: i gEE 5ii8gE 3P4i8 dzz iE 9% | ig ET 8% 23 gd I -.1iEg B5Z% 55%2 8i%s i7g%s 5 ~3 35] J -- 2e if Tu i i 3 HEE | g22 E gPiotelwli | o EaE8 2 gig ie Hd g g Zig E les i iy if i i E Zz E4 (iEER |13 i =g=E i| id]i {1{535g88 & Boo! ] ig2 ER i P22 225 | i 5s Z z28% 2|5i :| 1i52312 ~ g 2332:Z%1i S 383! |:|: 1ii1g84fs%3 5z 3fgl o8g5 oZa2gz2zz5 :ii fj15g:8 o3l 2= 23582; :i jr3k% Zz2% | 3 22% | :: {5i2a | 2| | I] 3 | tH g gz I ; g iHai% 3<2 go g i i;i EBE iiiigft 2% 5 Ep ifs 33 gz | ., 1B 5 ifs b2E3 ggE iz : ggE iiispF E fiii %esd H24E :fibOIE 8gf iings ~ iF EH Eos { - ; i H3H { Eep al p | . gigs 5 | i : 2 Eli ; 2888 0 oz gr Eoin: E! ri i iboaiy i i 2 iz= . Fi|| {a38 5B2E!E || id1 a 2i5 8 z8zi _ g eCEEdExt | 1H }]i 7i5i: | (5 f1z8 2g5z0f1 i 8 Zo || EH i | EH ; 1: | Hi g3 z2z5:5!| }i i1e : g=z= e!| i| iiggs os 5 5y : gFgI iisE 3 EE 0ied Ec 2 Bi2 ogZ g |i bo BE LiHdpsgx 1H5ie dg i 05 j 8g ief i 3 ig i: fis &*_i2fgd ~8 iI , TE{E 57.8hriR25%S50ioae | |: an ARE pri i ag iE aE l E} eT | I oh i PoP SHE BI n ozi: ii (E! S : Sms 188 id ! : = HH | 153 5: 2H3l 51 i{FEe | 1 EN -- |gZZz 7z e 2i 8%x%!| | |:g 222 283: bi8 i azz |sHi 5Z22532%.| 4 gc d i| i 58 Bl EE ::i| 4 I 13 333 || i; 2: 11i&82i3% ]i| : H : iBE ;E | Dogsi i: IE Lo digi IEEE 5i z8 EE iE :2 TE -- i i {oT 4 go asses | i 3 (EIR EDC ogggan g. [(JUEi -- EEE E Eg B {p wiT g gii ,ZE5ag 8m3eFn | 3: fg7ioggi i{RIBR aaERil --Coa23Ei5%idi1% 2 Z FH {5 33383 la 3 2 ji- Bi "$33 14 i 0: hE BS= egg!Pi2 (gEgf: 22i5e3 sRE1 18%! VED a 331 FE (88 8 252 i ing 2 G32 g Jg%: i] i7d: - J = 22228:1 i} ii) z 3gl I3 oEsgzgz!i :i ili]g is| 2 2z5g%d :| 1E5H7 1 558 | gE | i iis: 4 ET ] (33 i &i ig 0+ 2 gd i8 Pan E [I BI] iE GEE igs HH2 ~ <i74:8 g= I80% IiEs 3a3B3% IEied i } iih E8R22T iid122 9H-02-4D5a1y6:GaSvuabgeehrSotnudiyc iTnoxRiactistywith One-Generation Reproduction Evaluations ReDvuiPsoendtP5a3g6e8 TABLE 46 MEAN BODY WEIGHTS AND MEAN BODY WEIGHT GAINS OF P; MALE RATS Group (mgD/kogs/eday) w TEST DAY 8758 92 99 106 0 mr-0 25 v-o 100 20 20 20 555659.56((66321.36))8 559853..74((6634..24)) 607.6(64.7) MEAN BODY WEIGHT (grams) 554535..93((5524..97)) 558628..28((5586..05)) 590.5(62.5) 555497..35((3396..03)) 557699..15((4450..67)) 574.2(52.3) vi1-o 250 9 541965..10((4478..01))%% 553391..01((5591..87))*% 547.2(65.3)* -- Group 1-0 Dose 11-0 v=o 25 100 vi1-o 250 (mg/kgN/day) 20 20 20 1 TEST DAYS MEAN BODY WEIGHT GAIN (grams) 78-85 85-92 11330.99066.07)a 31.15.04500885)) 1102..27((31..03)) 12a1..92(181..43)) 92-99 99-106 1122..030055.50)) 183..a0076..50)) -59..70((:201..37))% 78..930(185..92))% 78-106 52.007.1) 46.7065) 26.6(30.1) a Standard deviation is reported in parentheses. 52.2327) * Sttesattis(tpi<cal0.l0y5)significant difference from control by Jonckheere-Terpstra `Company Sanitized. Does not contain TSCA CBI [0 -- 91.02D4a5y16G:avSaugbeehSvtoundiyc iTnoxRiactistywith One.Generation Reproduction Evaluations DReuvpiosnetd 5P3a6g5e TABLE 47 MEAN BODY WEIGHTS AND MEAN BODY WEIGHT GAINS OF Py FEMALE RATS DURING GESTATION pGroosvee (na kg!day) GEoSTaATION " 1 2 11o-0 FS 3330350.9730311.38))8 367.0035.) 453.209.00 192-0 1v0i0o vi2r5z0-o 1 1 1 HERN BODY WEIGHT (grams) 331a5a.l2a2238.l3)) 3330320.410087.05)) 3320900.230(2228.60)) 370.0(22.4) 366.0019.2) 367.202.000 454.9(58.008 432.7(30.000__84.5(35.5)d -- Gproossv.e 110 20s-0 1v0i0o vi2t50ro (mg/kgx/day) 16 1 1 GaDsaTvasTION HEAN BODY WEIGHT GAIN (grams) 70--174 2p.26.00a 2928.8) 3306.9) BG se 2.56.0 28.923.0) ns@nb 4-21 86.5(16.10 82.4048.504 71.928.3)d 82.0033.5)0 0-21 166.1019.91 135.805.7d_135.1029.11d_ ba rStoansdard deviation is reported in parentheses acwn-n10 146.2034.6d TherJeoncwkehreaernao-Tsetraptsitsrtaicatlelsty s(ipg<nif0i.c05a)n.t differences from control by `Company Sanitized. Doos not contain TSCA CBI --- = -- H9-02-4D5a1y6G:avSaugbeehSrtoundiyc iTnoxRiactistywith OnGeeneration Reproduction Evaluations Revised Page DuPon-5368 TABLE 48 MEAN BODY WEIGHTS AND MEAN BODY WEIGHT GAINS OF Py FEMALE RATS DURING LACTATION Group (mgD/OkSgE/.day) N LaCTATION DAY o 7 1 2 2-0 1-0 vi-o 25 100 3 " 1 5.536.208 346193100) 336501..62((3330..46)) MEAN BODY WEIGHT (grams) 3I5S1L.63((2390..87)) 336850..99((1188..49)) 3353070.02203121.09)) 337601..44((1148..81)) viri-o 250 1B 334491..37((2251..32)) 334612..17((4218..29)) Group 11-0 w-0 vi-o viri-o - (ng/Dkogs/eday) 25 100 250 ~ 13 1 u 3 LACTATION DAYS MEAN 30DY WEIGHT GAIN (grams) 0-7 7-14 Laa.aja B70) 0.322.612.8277) 29.6(19.7) 21.4112) 7.6(:7.0) 13.3(29.9) 14-21 -9.4(10.9) -15.0(14.2) -1LI(13.1) -21.5(43.5) 0-21 5.70208) 14.2021.3) 23.1028.5) a Standard deviation is reported in parentheses. -0.6(38.4) Sttesattis(tpi<cal0l.0y5)s.ignificant differences from control by Jonckheere-Terpstra `Company Sanitized. Does not contain TSCA CBI [3 91204D5a1y6:GaSvuabgcehrSotnuidcy iTnoxRiactistywith One.Generation Reproduction Evaluations RDeuvPiosnetd-5P3a6g8e TABLE 49 MEAN DAILY FOOD CONSUMPTION AND MEAN FOOD EFFICIENCY OF P, FEMALE RATS DURING GESTATION Group. (mgD/kogs/eday) GESTATION DAYS 11-0 w-0 vi-o viri-o 25 100 250 3 16 15 1 MEAN DAILY FOOD CONSUMPTION (grams) 70--714 22005800330.79)0a 26215.52(23..928)) 282.5.48(0120.91)) 2296..82(023.15)) 1-21 26.1(5.7) 2720.0) 27.003.3) 26.5(4.5)5 0-21 26.803.6) 26.42.) 27.101.8) ba oStwa-n1da3rd deviation is reported in parentheses. 27.62.50 TherJeonwceirheeernao-Tsetraptsitsrtaicatlelsyt s(ipgn<if0i.0c5a)nt differences from control by Grove 1-0 w-0 vi-o virz-o (rg/DkOgS/Eday) 25 100 250 N 1 16 15 1 GESTATION DAYS (grams weiEgAhtN gFaOiOnD/gErFaFnIsCIfEoNoCdY consumed) 0-7 7-14 0.167.046) 0.163(.039) 01162(.028) 0.141(.072) 0.172(.031) 0.163(.022) 0.134(.172) 0.165(.032) 14-21 0.553(.312) 0.365(.238) 0.395(.178) 0.4a0(.206)b 0-21 0.268(.053) 0.224(.088) 0.241(.050) ba oStna-nadasrd deviation is reported in parentheses 0.254(.056)5 TherAenalwyesriesnoofsVtaartiiasntciecal(lpy<si0.g0n5i)f.icant differences from control by One-Way Company Sanilized. Doesnot containTSCACBI 7 0HD--2Da4a5yy16GG:aavSvaugbeeehSSrttouunddiyycITinnoRxRaiatctisstwywiitthhOOnneeGGeenneerraattiioonnRReepprroodduuccttiioonnEEvvaalluuaattiioonnss DDRueuPvPoiosnnetdt55P33a66g88e TABLE 50 SUMMARY OF CLINICAL OBSERVATIONS IN P, RATS , uALE RATS GROUP NIu-m00berofRFIaIt-0s with V-O0bservaVtiIoOn DOSE (ng/kg/day)N20 2250 10200 21590 OBSERVATIONS ACloolpoerceida Discharge Eve(s) Colored Discharge Nose o1 o 02 21 o 0 1 TTeeeetthh CCrloiopkpeedd o 0 o0 150 Total No. of Rats with Masses o o Statistically significant trend by Cochran-Armitage test; p < 0.05) `Company Sanitized. Does not contain TSCA CBI ox - 0H--2D4a5y16G:avSaugbcehrSotnuidcyTionxiRcaittsywith OneGeneration Reproduction Evaluations ReDvuiPsonetdP5a3g6e8 TABLE 50 (CONTINUED) SUMMARY OF CLINICAL OBSERVATIONS IN P, RATS Py FEMALE RATS DURING OBSERVATIONS DAilaorprehceiaa soStraeined Abdomen SSttaaiinneedd PFaecreineun wTeeaekth Clipped WWeett UPenrdienrebuondy GESTATION DOSE GROUP NTuEm-b0er (mg/kg/day)N18 o1 10 00 o 0 of TR9a-t0s 2i5 1 0 00 o withVIO-b0 servaVtIiLoIn-0 11900 2750 2 21 o1 0 1 11 o0 11 0 11 Total Note: No. of Rats This table with Masses includes clinical [3 observations from o pregnant 0 animals o only. - P, FEMALE RATS DURING LACTATION GROUP NTuIm-0ber of TRVa-t0s withVIO-b0servaVtIiIoEn-0 DOSE (mg/kg/day)Nou 275 11040 2j5y0 OBSERVATIONS AAblnoopremcaila Gait or Mobility 1 o5 I1 o1 DCoilsocrheadrgeDiVsacghianragle ONpoesneing 00 1 11 00 THuenecthhedClOivpepre,d 00 1 i Total No. of Rats with Masses o o There<we0.r0e5.no statistically significant trends by Cochran-Armitage esi Company Sanltized. Does not contain TSCA CBI I-- -- 910.2-4D5a1y6:GavSaugbeehSrtoundiyc iTnoxRiactistywithOne-Generation Reproduction Evaluations ReDvuiPsoendtP5a3g68e TABLE 51 MEAN ESTROUS CYCLE PARAMETERS AND PRECOITAL INTERVAL. INP; FEMALE RATS oPfercDeanyts oPfercDeanyts PofercDeanyts Mean Cycle Group (mgD/kogs/eday) N Eistnrus Diiesntrus Proeisntrus Le(ndagyts)h 0 0 29 0 1 gansnab w-0 25 v2 os 13 as081) vi-o 100 0 2s 12 e09nb vi-o 250 1m 20 6 12 4.90.35 ba nSet1a9ndard deviation is presented in parentheses. P ENEelYs There were no significant trends (Jonckheere's test): p < 0.05. PrMeecoaintal Inttdeayrsv)al 3.se.a6c 3302.86) 2.501.300 3.602.004 Company Sanitized. Does not contain TSCA CBI 0 9204-5D1a6y:GavSaugbcehSrtoundiyc iTnoxRiactistywithOGneeneration Reproduction Evaluations DReuvPiosnetd-5P3a6g8e TABLE 52 SUMMARY OF SPERM PARAMETERS IN P; MALE RATS Dose (ng/kg!Gdraoyu)p 0 m2-5 0 1v0=0o vi2i50-o worsIppLe.IrcTeYnt Motile 933.360a 925..2800) 931.230110) 906.1300) "MORPPeHrOcLeOnGtY Normal sp. 950.88120) SPIPDeIrDYMCaAuLdaSPERM (Millions)298.7 s.0. 321300) 991..0100 27395..88(10) 99.2 0.700) 27a8l.s0110) 98.9 1.1010) 29696..25010) v5e.r0.gran Cauda 10m30i.l9e0) TESTPIeCrULTAeRstiSsPERMATIDS (Milli1o3n0s.)1 su. 100) 199484.3300) 12113.6800) 1791890.48010) 15190.39+00) 914550..57010) 11467.350410) - svepr. gram Testis 8182.35300 8142.0500) 1019.l110%10) 935.520010) a Number in group is in parentheses. * Statistically significant trend by Jonckheere-Terpstra test; p < 0.05 `Company Sanitized. Doesnotcontain TSCA CBI wa 9H-02-4D5a1y6G:avSaugbcehSrtoundiyc TinoxRiactistywithOGneeneration Reproduction Evaluations DReuvPiosnetd5P3a6g8e TABLE 53 SUMMARY OF REPRODUCTIVE INDICES: M(ATcINoGpulIaNtDeEdX/c(o3h)oused) DOMSAETE(RnNgA/Lkg/GdRaOyU)P II0-0 (1980/.200) F(4ERGTIeLlIiTvYereIdN/DcEoXpu(l8a)ted) @37/2l.2B) GESTATION LENGTH (days) 23 Number of per pIrmepglnaannttatifoenralSeites 16.0 (4.534 Implantation Efficiency (3) 39.63.36) P; GENERATION I2V5-0 10VI0-0 (12000/3.00) (1995/.200) (1875/200) (1747719) 22 2.4 13.4 139 (3.58) (2.95) (390..45m 1s6.i1d6) V2I5II0-0 (2984/.179) (1714.8/18) 2.4 1a (2.93) 1s9.a1s0) ba NSutmabnedrarodfdepuvpisatiboonrn/insumrbeeprortofediminplpaanrteanttihoensessi.tes X 100. -- bTyherCeochwreraen-Anromisttaagteistteiscta:llpy <sig0n.0i5f.icant trends in mating or fertility indices Tlheenrgethwabsy Onone-sttaaytiAsntailcyaslilsy osfignViarfiiacnacnet;dipff<er0e.0n5c.e from control in gestation * Statistically significant trend by Jonckheere's test; p < 0.05. ompany Sanitized. Does not contain TSCA CBI ) 9102-4D5a1y6G:avSaugbcehSrtoundiyc TinoxRiacthstywith One-Generation Reproduction Evaluations DuRePvoisnetd $P3a6g8e TABLE 54 MEAN PUP NUMBERS AND SURVIVAL: F; GENERATION D0MSAETE(RnMaAfLka/GdRaOyU)P 110-0 2Iv5-0 V1I00O vI2i5I0-O von n 1 7 BBoorrnn Alive Dbaayy 4 pPorsotceuulllliinngg DDaayy 174 Day 21 HN ERN UMOFBPUPE S/LwTIerTR TER wnaz awleo 1s6 8800 7766 80 76 onuas nniss w3e I7ise 66.33 7744 63 74 BBoorrnn Alive DDaayy 44 pPorsotceuulllliinngg DDaayy 714 Day 21 HEAN NUMBER OF MALE pup5s/LITIER 7.2 5.9 7.1 8sss 7711 i54 s8ls 7 aa22 3al6s 3333 35%9 aa22 3366 3333 3sie 6 Born MEAN vUMBER OF FEMALE pU6P.S0/LITIER 6.1 5s 5.5 --- DBaoyrn4AlPirvoeculling ssoo s1is 3sls 3 3p3 n DDaayy 47 posteulling 33sk alaloo 3slo iis DDaayy 2114 3iss aploes 3300 3siss Sex Ratio (males) sumvivaL (u) 0.55 oso HG3oe5as4ntantaiyoBnVoiranIbniAdlleiixtvtye w19o09'o0s 19s009r02e0 Lactation Index? 0000 0000 Litter survivale a Porcon: litters delivered having at 0.0 least one live pup 100.0 bePaerncenptorcleinttterssurvbiovranlwiftrhomatdayleastposotneeulpluipngalitvoedaoyn d2a1.y 21 050 06 as32ml0ds9 1990270.304 000 92 92.3 32.3 + statistically significant trend by Jonckheero-Torpstra test: p < 0.05 Statbirsotsiecnstawderfeorpeirnffoorrnmeadtioonn coonmlbyined pups por litter only. Yale and female data are ~ompany Sanitized. Does not contain TSCA CBY ww H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations Revised Page DuPont:5368 TABLE 55 MEAN PUP WEIGHTS: F) GENERATION DOSMEATE(RmNgA/LkgG/dRaOyU)P n IL-0 w2-50 1v0I0-0 13 17 13 MEAN PUP WEIGHTS (grams) oar poy & Preculling pay 4 Fosteulling fil urd Pred 6900.78 LIES) AGE W309) 906.0 60.306.) 670.6) Ae) AGT 18.022 3.06.0 60.3(5.5) 6.80.17 L308 sae 1B3G4 3610.2 58.343) vi2r5r0-o Fe) 6.40.6) 10.10.00 03am 15.5@D0 29.56.00 45.41.70 MEAN MALE PUP WEIGHTS (grams) ay 0 Day 4 eiecutl ng Day 4 Bogtenining - ov 7 Byiie Bye 7.0.0.1 HES) GS 10.82.00 IEE 6250.4) 690.0 LS) SG) 1820.3) ITED 61706.) 6.90.05 6.70.5 1230.9) 1070.8) 1230.0 10.807) 180.902.315.023) IAG 9.60.8 60.2(4.3) 45.71.71) MEAN FEMALE PUP WEIGHTS (grams) bay 0 6.60.7) 650.605 pay & preculling 10.505 118 ey 4 Sesteutitng OEE 1208 2p 7 es EE Day id 3.03.20 3650.0 fl 59.1063) 59.0(5.5) ba uS-ta1ndzard deviation is reported in parentheses. cna 650.05 LSD 4G) se 35.00.60 6.04.7) 6.20.6 9.8 23 1532.0 29.3.1) 45.0(8.0) + pSt<a0t.is0t5ically significant trends by linear contrast of least square means: NoteF:emalsetadtaitsatiacrael parneasleynsteesd wfeorre icnofnodrumcatteidononontlyh.e combined pup weights. Hale and *:mpany Sanitized. Doesnot contain TSCA CBI wa -- 20H9--02D-4aD5ya1y6G:GaaSvvuaabggceehSrStotunudidyyciTinnoRxRaiacttisstwywiitthhOOnnee-GGeenneerraattiioonnRReepprroodduuccttiioonnEEvvaalluuaattiioonnss RDDeuuvPPioosnnettdP55a33g668e8 TABLE 56 SUMMARY OF PUP CLINICAL OBSERVATIONS: F) GENERATION OBSERVATIONS DOMSEATE(RmNgA/Lkg/GdRaOyU)P 110-0 I2V5-0 10VI0-0 V2I5II0-0 WDeiaskcharge Nose o oo 0 a2q(una TNOUTMABLERNOUFMBELRITTOFERSOBSAEFRFVEACTTIEODNS OTAL NUNBER OF LITTERS 00 0 51 1 fa) 13 13 a Nnuumnbbeerrss oinutspiadreentthheesepsaraernethetsheesnuarmebertheofnulmibteterrsofafpfuepcsteadf.fected; the Therbe<we0r.0e5.no statistically significant trends by Cochran-Armitage test: Company Sanitizad. Does rt contain TSCA CBI ----------------a-- s -------------- 9H0--24D5a1y6:GavSaubgeehrSotniyTionxRicaistwyithOne Generation Reproduction Bvlustions DRuervons $P3a6g8e TABLE57 MEAN BODY WEIGHTS AND MEAN BODY WEIGHT GAINS OF F; MALE RATS (naacrogosvcemp) rmo 2rms v10s0 v2i50s 3 1 1 12 2 oaptslox MEAN BODY WEIGHT (grams) 1ss1 2 me63.73l(07.n53)0 236301) 1160920.0550(0750.300))) 2400609) 01560855.3600(1.53.9.6)0)) 223.0038) 1s447a5.o00l(0s5..a3))-% 206.001.40+ 32 39363710401305)) T3uea@Geu)ae 3219050008105.) 32106.200400..) Gbroosvee Po= maaan) 2Ese vfooto v2i50r n 1 12 12 --- ornasneox WER sopY wezGHT GAT (grams) aiss 1522 SS5e6a8h | s45o6o.o0)0 S10.00 sass 0t8i5.e2n) e190 5o6m5a6 ess 22925.3269 BSBOAUG5U.6S) sSeTsUg6oSn)e 536L.3r(015s.a6 5d5s.i0(2s55s)) 136 2100000 eeqge.sc 251.903.) 363.229) 5E = SDatE yandofarWdeadneivniagti+onTesits DTaeypor1.ied in parentheses. + Statistically significant trend by Jonckhoers-Terpscra test p < 0.05 CompanySaniized. DossnotcontainTSCACBI --- Tw 91.02-4D5a1y6:GaSgubechSruodnyc iTnoxRiactistywith One-Generaton Reproduction Evaluations RDeuvPiosned-5P3a6g8e TABL5E8 MEAN BODY WEIGHTS AND MEAN BODY WEIGHT GAINS OF F; FEMALE RATS aproosuep mo1 2w5-1 1v0i0i vi2r50r1 (mg/kgx/day) 3 ww 12 12 oAsYStaon MEAN BODY WEIGHT (grams) 81 9547..03(76..83)0 9584..65(6..33)) 905.6.47((73..09)) 8404..07((98..61))*+ 212s 116375..580039.60)) 113793.067(01231.69)) 116373..56(030..38)) 116214..780(99.81))% 3269 210960..40((1167..35)) 129150..68((2340..27)) 129112..46((1(51.78.)7) _ 201867..37((1133..94)) Gproosuep 1-o 1 251 v1i00t v2i50r - (mg/kg~/day) 13 ft) 2 2 DAeYsStaON MEAN BODY WEIGHT GAIN (grams) 1-8 Sesh 36.20.98) 53.705.) 35.2064) 158--2125 3a1s.7i0c8..4)) 434..7200.911)) 333.29(05.m4) .368.096(5..26)) 2292--3269 1262,.450(76..010) 22129.06.07.)00 223..91(46.29)) 1268.0050081.33.)0) 1-36 169.107.7) 160.326.7)__155.9016.3) _ 161.5018.7) ba SDatyandofardWedaenviinagti=onTesits rbaeypor1.ted in parentheses c nie + statistically significant trend by Jonckheere-Terpstra test: p < 0.05 Company Sanitized. Does no contain TSCA CBI. aw 0H--2D4a5y16G:avSaugbcehSrtoundiyc TinonRiactistywith OneGeneration Reproduction Evaluations RDeuvPiosnetd-5P3a6g8e TABLE 59 SUMMARY OF CLINICAL OBSERVATIONS IN F, RATS F, WALE RATS Number of Rats with Given Observation DOSE (mg/kg/GdRaOyU)P 1-1 2II5I-l 1v0e0l V2I5L0L No 16 12 12 ossERVATIONS There were no abnormal clinical observations observed in the F, Male Rats. Total No. of Rats with Masses 0 o o F, FEMALE RATS Number OofbseRravtastiwointh Given - DOSE (ng/ka/GdRaoyv)P II 2w5el 1V0I0 v2i50a N13 17 12 12 OBSERVATIONS Alopecia 1 Total No. of Rats with Masses o o o There<we0r.0e5.no statistically significant trends by Cochran-Armitage test: Company Sanitized. Does not contain TSCA CBI -- Ww 9H-02D4a51y6:GaSvuabgeehvSotnuidcy TinoxRiactistywith One-Generaton Reproduction Evaluations DReuvPiosnetd-P5a3g6e8 TABLE 60 SUMMARY OF DEVELOPMENTAL LANDMARKS IN F; RATS PREPUTIAL SEPARATION - F, MALE RATS DOSE (ng/kalGdoayp) 11 2I5l vTaol v2ii%l x on 16 12 12 AGE (Days) 39.9 als a2 a2 Gan _@.sv 0.6 2.10) VAGINAL OPENING - F, FEMALE RATS Dose (ng/kgGlaRaoyu)r I -1215 on Ig V1I0 v2i0a 12 1 - AGE (Daysa) G52a.0 Gwuaan awoan (nzss) Data summarized au: HSotaanndard Deviation a AAgpepenwadsixcaLLl:culaTetsetd dasayf+ol2l0owsdayussin=gAgdeata(dparyse)s.ented in Tcohnetrreaswtereofnoleassttatissqtuiacraellmyeanssign(icfoivcaarnitatter:ebnoddsy bwyeiglhitn)e.ar many Saniized. Does not contain TSCA CBI -- = "os 35 3 2gE -- < -- | c, 2aE ho 88 5 88 3 5% Ss i4g $9 = =z -~ =~ - =S2 gf-2 3-3 28-3 _ Zg 3g 3UdE g2d% d8d8 i) a = ts 3 g . 35 g2 Hg 53 =gf Sd saitvc g2 zz - ooo E$gie a 8 3 of 558 | :2d z lo 8S ges sg oo] EEN EERE 2 g g eg i2: = 2 :5 [88i4k 2 5] : g 3 iz 2i4d2 gzps f5 O82E i "3 [fF[fi3sd 2g3d 888EE2 EEsJF &3S3 g 2 5 2 s i $ iE 8 * - 8 * 3 g : = i 2 ] Eg EI, 8% 1 i ER oo wn se 2 Sl 2g ~~ 4 Z 8s 3g Z2Z o8o3.8. 83325388gg%i sg8a83 ~ aeLs E]&E : . - = Az -% 2igzfzZ2z ooog 855 338s%g8os3x iiss &1 <2 ER So ig=a eocs EErSeV H3 2z ooo ol 3g53% Z:| x2 _ 9%2 95a esal 432856 i7 83 Ife s3o37g%i S88d B4E.E8 - $31 i222:g 2 2 e ~ i2z3 5g i ::5 [8 i 58i g |g 52 : | 2% Eg gs y 2 2 | 3% (3 i3 88gPE 2 E8 R|s .3% ig 3 , 2 , $.3 ,83 8. 3.8.% 38 = he 28 83 28 35 5% 83 22 5% 3 2 PN 15 66 mo no oo oo mo et gd <32 FE , z g33338383 =Zz 7s C8E% a22% o8F% wErR 3E% w3T% a3m% Q3F% m9F3 o2S P" lc 66 mo ro oo oo mo srd a Bgwd 52 2 2 2% 28 8 8 5 2 3% dd 8 = I 3% 3% 3% 28 3% 58 33 2% 2% |Z3 & ggZ i3 FR 3353 35 33 38 33 i% E iE E 32 22 g FsE ozoz3zo3a3o3oa, <|: EgzY, $356 EGES BWRS 8ds5Gg6idaeimaeymaer3ma 2 Zz 9 - | Zg a 5: El g 3 23 gq $3& a3h8 5 g i 5 2 f -y 22 - Hgl 3 1| 32 i : 2: 3 Si. 5gg 5 42z Z "eo Tggzz& % LI &g =& -i, = Ee &2 E2l 8 I8 e 33 Sg9 =3 af gh oof ozs Se co es se o- o- =- o- =s2= 8% SZ 83 58 G6 oo oo oo FE 8%2 332 332 8%z 88 38 22 A3 2- 82JI3E L+I8E3 05. 8o& g 3oo.t 2 GR8E3 BEoAhE = g 8oxo:8 E88 EE 5 = 13 oar sh ss So So eo - - - 2o 2a 2o 88 338 a8 oo oo oo 8%2 8%= 3o 33 33 33 3=&3 8= =2R3I%E 4E8R3 eR2e2 7 3Bozo8 2 5 EE a 2 = 8 i i i i . 2 oy I3 ,- 2 3 <I.Bf 833 2 gs $s B2E 385% g8 LL) 8 8s 8 3 2825 o33f 8233 o2f gf 8&4 #4 gd 2 g2q a2 Ez ~iga 28&32 HR Tes 33 a3 835 83 3= e1g8 83a% A8n% R2e8 8383 a3n% * gf gr & gn gs gE 7 ge gE a gf IE - S z g= 8 52 - = ss. - 2 e 3. e 2 -= 2 32 fi, 35 Fg, 88 RE 23 8 33 ig 7 a 23 ~ 4 ma aa 7Z 2 22 82 3 Z| 53g 3% 3g 83 88 358 33% &% g 2 4 7 ges gl " 4d Fd gw Eas ga i 2d 1 4d Ff fF 2% 3 FR 2 8 FE 0% 08 i 58B 3 3 5 js 3 3 22 | Ee BoE Eg2 zgll 5388 Zi 3g88 ~5 is i2 E5 o.3 a 3.2 5 2 32 23 aoz _ 2Z 83% =gms 3 2 ne eo - $E3E.oe gd =a a2 38= gg= = il 2 2 =2 28 I5 22 5 a Sgii:e t = 2 Zl 5%, A EZ og gaa $8: g5 : Fa+ <4 8134%% s 8 | fd ~ ij i HEL 2i i 3 ei 3 z 2. | ~3 iz . E33 ~Soa saaaos oa J.J JS J. .2<3 FREREE ERR 88% 5z SS oa aoL a oa. E: 7c 25 83= 3%8 8%2 35dd2% E BRILL E - aTE8 Tz zr z= 25 2% 12 20 2b do J1El F2 oz5Edg i, e %% 8d % 28 EY 3% 2% i i g J gj iS 66 68 de ad EE 2. 5 g Zz 3 22 EE " 235 4 y % . 3f8F 8 2 8 4 3% 2 g 8 E # 3 % EYi]z zlg 5888 ; 2& 3g 8: i . E B 5 8 - EB 5 iz z gz FOES ox BOE BE : TL o5 sos -- 2 i < w 2 2 2 < -Z T -Z @= B8g 533% 33%3 8382 33% 8i B5g8 338% i z:2 FFoo ooF oye ~58 g ve 28 SF S58 RA =% To OB - E E= SoofoLo: Z 5 4 =: =2 i, 2388 3e2p8 35%s 32%5 &2%8 J oI, 83% * il 2 z Fe 36 de dS G4 +e 4 UN Jg HI i Ei a 1 = 39 3308 3 3495 3 i Dog. a al oi ou oll EL 2 4 Ez 8&4 38 _23 238 85 2% 5 L288 | 3 gos 85 FSS Ss gis 4 Reel : 2 <4 7 LL Tq 7 i Eg 31 8 8 5 g I. Z # 3 8&8 EE EE 3 & i 32 = 3 ft 5 5 EE 4 i 2 2 =2 2 8 I] & gd - = 2 gl Eg 2 gg ~ LH4 ER 2 g5 eBy 5 TE i i E 2 sa a 5 < w -s 2 Z| g hl CA 3 Soa a = -s = 2 szg 2ie IIF E22 E29 - EE ood . i 3z E5 39 885 838 , og gy 3i. g il 322z .Ii sdin ee ame EaSg E5l a] i 3 23 35 3 GsitT:av Ji gdhi, 3 si 8se o2go Bs1i3i: dg =F 8 00 Aid i8 El p 8d fg fF OF og |fu: z8 g g i 3a i: 4 gs 8 5 [3 4 24 gg ~ Iizg i| i8fa i 1&58 i3:d | : ii]: ii 7: ia i i Bai. i 18s] 2i i a i i gg i 3 Feri oo :2 iy . _ o z2& S5a8i} syfd zs 2 ios 8 2B Bz a 2 Lg EA2E04CH] ; &g: H uSlEiER| s|B &yzg i1k gi zg iPoE 2: i a i2t ALHER _ gi en g I ii i{ 25 i .| : gi 4 2 $a} eo o o oo ao 3 "I fg eiem. 2 i = . oo ee ee | 228raa]l =3 5 5 5 ae offi - 5eSE ]i 55 < 3iCcE EfEatR E: d] g:g dgfi :i :g R2 iCotH u5 2 o it a g! 8 i z ; gEA8 |g5 147 4PogfF B2L8E oz if 2|? ~ M2E4 EH 4gi: Es8 5gB5 "3F5 8p553 G8R0E gHhEB i% 8 8 8 E |. 58 ~ 3i3g ii :: 55 23 J : 3 EBSL 1 LT adda : i s I 3 z2 fJsaeid - - - i[HiE i 3 gob ess g j= = i[Hui 8 Z2hae! TzCzC: iz22 1%y 3 z i i 72 8 is 1 [Ff 5 _ 2 3.2 Eoo Eoo oo |ss 3 g 2 2:48 1 2g ERdE ki S 58} i5 $| Cgaaill iz 98 ERE:; EL I~ J 3 i i54 Pi E5 ELs E8 ~ 3 EH Gi 52 55 gE ELE EOF H3y aif 3ig 533 2g8s 22%8 an one 25 33 g [88 p/8d & 2h i aac OBE: 28 "x y ; i% NE H 5 5i Lb - i z EEN BE | i 3 3 codii 7= 7= E[3EEy Seni ~~ 3 2i5 2 585 1 oli gf i ii 3m Ee3l0f 0TTCooliSyriBsa g PL. BE zg, i 5 at _ CES CCE q2f%.:| i S EE: g S Aga Z g gS tB.aa :3 Z8 ARs:i iig i5 22 i; [2% 3% 3t%iiks oioin i2: i23 _ 22d2 23 { f8 eleee 4i fF gFaElyl 9 FBBEiiI FE5%OF g2 2q2e)I | ig g BE: & 2i P i LEi I gaea5aC22 ellfisi !: e 1s |i ; 35 8831i J .o|33ty &. FE e eogd of s 2 s i |iHg i5% Zz 3 of - gt -- - 2 Hodth ool 8 ih f 8= :so. i EE f8ip5 3i BRT ); z HE ii Zi| gS gHoagdi IE 2gE tEsE I| gai fz3 52%2 Z3ia3 $8 fg H2 E i | igs #s4l 88128k% BHfR | iF BBE 8 ai3: ;| 3 $58 Lo i 5 Bai ; g i 23 gg.aii oo &g i i 8 2 Geol 2| 4 i _ o :z 7 Teroif 5uff8|8 dIE=R: 5 3 33 F< B2 ZE-ss li= 2 Zz 38st |& 2 iE 1a 2 g ugh i i 5 SAE 5 9 | i & 8J 3 21 zi 5 i i% 4 ge BOT ZF ar oR la 58 CE i 2 2i4z PE i iz Io : Ein}i 2 : | i ZZo.$8} 3g o i : | : 1 zg z..li 3 Fed az: ]ii 8. i ~ = 2Z ; HoRi aPI4 2 ii 33 E FoE zE REiEgsi =2i 8 g L5dg9Ef8i: | % Saf. s gE i 2 ig 9 H 4 & i: 5 i8 3 ni ol 24 Eig BE gk 8 -5 ; i iidi i !i gg i] 3 & : i i a H! &E 35 1f8aaif ET 3 3 Hest a i 3] z |g 2 Joni uf - Ea8E25 ibE7I] $ 1886 |; 4|0 cgaie 3 1 g5 l55i8i 22 5 oS ERED Is z g iol $ Zg z E i g % z HEF % = os i a i 8 HE 9 ~ AE g3igfa"d 3 3 bE] i 5 12: adi Eg fed 8a a i 3 3227 .is.8saai0l 2i & 2 fai gq i zg ii zz 8 2 Hold <4 - d SRE9.2 i1 8B *5 2 i F2 E> is. e i< 4 8 258i QB BEai 3 3 o HE" El { Z ER q g iE < gz ii oe& bE2y2z "gd4 x5 g Lb fEls ii 8d gSii b5n7 ai 2 le - ; . i8 & i : , of 5 32 . ii +: gf: i EEgEaRtE wom mow: wom oof Pgaog z i fg i : FE : 2i EH 8: EH =B of8eli mw wmom mao Egelo2 gE gg24e ii EFegldptMf8O : S3T FiA.R ww ww on wo 1B48e2 fE 2, i gs i : Ef og :: gig= 2 - BH R85F8.ToRi| wm womeni momo BGa2l8e 2 2 | 23a58 i [Bd5e8s 1% : zz i | sogdy 1| F2E3R 38 bi< =2z3 gBail #i3i5f7 of% g[iRgaEs 4 g& is :g HgiEidHiy 2 b2E2 i3%: 5EH: ~ 24 5 3a] Bg | sgg.lf aE i5 2B S h8e3 | |g8a50ahtE ails HiIER B4EE03R% 8INE |EEEcp) BE Hgf EBR B EE EELE EBER BEEDUcoSo is i | . d ELi ii 5 i iz z| fg.i EK A 32 ERA wow won i 8 9 Pi od: Ei 584 ET id 5 2i =| | Es s gE B<X=z.lfoeonl|i woni=$ wen gf get HEH wsa8 2ge W| weHES i fe jie ; a 3 Hog - ew nf pi 2 i Ea ph 34i 212 2 73f5a5pi &gfS # Ei 0 53 aT 2 o8if E8reggin HFi ine 8| g3zif 24 a 8 5 58 * iz LH `H9-02-4D5a1y6:GavSaugbcehSrtoundiyc iTnoxRiactistywith One-Generation Reproduction Evaluations Revised Page DuPont5386 FIGURES Company Sanitized. Does not contain TSCATS 0 -- 9H0.2-4D5a1y6:GavSaugbcehSrtoundiyc iTnosRiacsitywithOneGeneration Reproduction Evaluations DReuvPiosnedt5P3aKg6e FIGURES EXPLANATORY NOTES Critical Dates Day 74 cMoallleecatendddfuermianlgetrhaetcodheasbiigtnaattieodnfarndrpeoprsotdmuacttiinogn epvearliuoadtsioanrse wreeproertceod-hioustehde.RepBrooddyucwteiivgehis Toxicology section Diy 90 Recovery period begins for rai designated for one-month and 3-month recovery periods. Day 91 Male rat designated or the 90-day exposure period were saciid. Day 52 9La0s-tdadyayeoxfpotseutresupbersitoadn.ce administrationfo ema rts designated for the Day 53 Female ats designatedfo 90-day exposure period were sacrificed. Day 119. Last dayofnon period. fusted body weight data collection fo as designated for the one-man recovery Duy 125 Male and ema as designated for theonemoth recovery period were sacrificed Day 175. Last dayofnon-asted body weight data collectionfo rats designated forthe 3-month recovery period - Day 181 Male and femalerasdesignated for 3-month recovery period were saceifced. Company Sanitized. Doos notcontain TSCA CBI -- EE _ 88g 2 iz 8 i , 332N83Yd2 oee 011E A)XWN tE[neHgtEg 58 IE = _ | 5 _852 siz fii5 Jd 2 2 3: =: 1ig 0E=:I : 3 i i& &k dx 31 oo TSOhn N"% \ }. I CI |5 ET=ii a ig Ii z gi g8-s g iEEiEisO a 8% It SrEE = EF si:i te i4f; le [7 EE a 54 EE 5 83 538 7 8 2 @) whtom Apog weap 23 - 2 5i%s 8 TR FeY: E ii5t3d3 8x Foss o0 22% 52 Xd\y & ! 8FE = PNRWY < Ng fd 55 E3E ii: HgEgg Iz 3 Z2z 33 H i : >k g g H :7 ~ id =3 aEWS 4%1 Tava Be 5 & &% a Re NA . uo fpog wow CisB 3 5 i$ 2 =z: 3E j= 4 8 [= 3% 5 3a3 5 is = 53 7a =%. 3iB%sF |e [F883 e iF Fis sf [D5 [ifis iF I. +- = sy =a wn z o= 2= 2 Eg & i] 28 2E ij]] =2g2 i% 22 i2 z2 g g< g = & ESEEES 82 Eisg Goam --I -- =B8 8 = g: 5 3 3 || < | = 2 "3 | 3 a3332 3 ZZ I3 2 & 3 24 ~ iMzi 2 88 8 88 8 8 8 8 (8%) yuangduquipasog --_ FH 3%4 8 223 Iz 558 : FEE & Ei i Soom 8 t :8 -- I g 7 z= -_ |g5 Z=2 f 22 --& - 5 z g 2 3 22 :i : z2gz = i 3% : Zz 22: 1 2 2 --~ 57i4 ff3 88 88 82 8gz 88 38 8= (8) ungdug quipsioy ~ 4s i iiz 2 3 34 z: g g Z gz 5 2 5 % g55| gzz = & 3 8 Zy g 583 25v5z%E5 $8 [2522 g 2Bi3s%se@2 iaSs comm i -- |lS] --1] g 3 o % 3 < 3 3& 8 = s st (3%) wiuon duo quipuy - a: 2| - :vg3 w3 = z = ~ 7E3 J] &22 2=E 3 =z 4g2 2 z |I az 53 zz gB8 8 3= 12N8Y32 g |FgEsS2ec g3 S5EF 8 ooam i 8 B 3 3 --7] _-35 & 33 E3l23 Z 33 ed -~ & 28 = 2 25 3 32% 8 % (3) widduupqauignpuigly aH ~ us 3 22 a2 =3 =E 2g& 2Zz 3 28z --_ 5~ 2= g2 iq = FI z 17 $123E52533f2523f898 55 3 cs&o8 mEmd J -- i [ii --7] 2g 3 2 n a8 g = |4 3 & | Z3z: PE3 24 ~ Z2 z5 2 2 4 8g%< 2= 288= g= gsgg zg (09%) swawasop Jo vonmng - 3: 2 g3 a: Zg g2 z g=s Szg - *= Jgl 2Ew gE zo25 3i EZg <5 = zg Z : 3 2 s88 5 3 EEYEY! $e2e2r4 -- -- S=EoRfo2sm%s 58 3 a= 35g 5 |3g 23 2= {5o332&E8 2g i Hoos S >E Z3| 5Z % 2 52 8 2 = 7 ~ 4 8 :2 & 2 | g 88 g&gs88zs8- (599 mmo Jo uoneing "3HH 5 23 z2g & 2 z 8 "Z gz 2Z --~ .5 J g=zz iI 2 3 2 == g = E= 2% = ig3 e2S 22 = ~ 5$52333334 EPsEesEg Gham -- -- SSJOoO q 3 2 3 5 22 a 38 &: -g oa 3 2 g <4 23< 4 3i Z gz g32 z2 = 23 ffJl oe=EZ% I= 3| z Eg25E5E%5E%] |22f2EgZdgE ooo ms zz8 5 i i : 7] FE o8 332E 73 2 : g 5: 32 2 e3 ~ #4 zz . < = g 2 2 82 28 28 38 28 B5 2 8s = SO 10 qn H9-02-4D5a1y6:GavSaugbeehSrtoundiyc TinoxRiactistywith One Generation Reproduction Evaluations DuPont5386 APPENDICES "JompanySanitized. Dossnot containTSCA CBI = --- H9-02-4D5a1y6:GavSaugbcehSrtoundiyc iTnoxRiactistywith One-Generation Reproduction Evaluations DuPont 5386 APPENDIX A ANALYTICAL DATA Company Saniized. Doss not contain TSCACBI -_-- 9H0-2-4D5a1y6:GavSaugbeehSrtoundiyc TinoxRiacsitywith OnGeeneration Reproduction Evaluations DuPont5386 abl I. Initial Homogeneity and StabilityofH-24316 in Dosing Suspensions. TTSew womlHs1 Faw6 em Type Nomml Mewwed Nominal wee HCoomxotgehnoeLity 000 NDA) - MoTboir 2255 230 247 920 988 Boron 25 240 Mean(); 2395008 96.0 5.6% ran Morovre BoTrow() 1100 897 102 o Mean); 140 11.1526 cv 2% 807 1020 1400 ano MoTnoir 225s 2240%8 190272 - Boron 25 ns Meant); 25.0816 940 ano) crn Stil 25 206 24 2s0 248810 89.94 Test Day 6 Contror 0m NDIA) -- MiTooorLe BoTrow 1100 99.2568 992565 10 Meant);992.363:0.19 923 26% cron SubiliyTM W Deere In) 903 903 _ (B) () TcDouhcpllaiivcceiranattgoeefmaevnaarlsiyuasriiseodnafcoorooingpcin,naamtliisdoadnml,pelveaensrdugpbpeorrpitesrotchaerntoorbfiagsmienidalnoaannlmae(lisyuprnaedrcswoielnscn,nottbstetoarnnedpfaoorrtdetdeadechvicnl, and ~ ) Subiity samples hed hos3 room temperre - Tw CompanySanitized.Does not contain TSCA CBI H-24516:Subehronic Toxicity 90-Day Gavage Study in Rats with Ore-Generation Reproduction Evaluations DuPont-5386 "Table 1. Mixing and Stability Study of H-24516 in Dosing Suspensions SempleTy__pe wgmlWaeste Pecan Dose Volume. Nominal Measured Nominal `Homogeneity 7C5omnTrgoL 000 NDA) - Tor Mine Borrow SOmUKg Conor 33 33 288 254 865 763 in 261 802 Mean(); 2.70502 11% von 000 NDA) - Tor Mio 50 50 453 42s 906 850 Bottom 50 439 75 Mean(); 4350.14 78%) avin Tor Mine 0 20 199 95 1 ) - Borrow 20 186 93.0 Mean(); 18.7211 03.5% Creu Tor Mibu: 00 500 534 526 1068 1052 Borin 500 540 1080 Mean(); 53.420.7 (106.3%) cris stability 0-DAY R1OO5MmTUEMKPgERATURE 333 270 S11 SHOU ROOM TEMPERATURE 333 266 9 4-DAY REFRIGERATED. 333 204 883 33 288 86.5 Meanl); 2915004 7.4%) 4-DAY REFRIGERATEDSS HOUR RT 33 a 2m 823 (8) TDheenoawveersapgoerdmseeanseudr,ed concentration, average percentofnomina(iln parentheses)standarddeviation, nd () Tchoecafviecriantgeomfveasrsiuatrieodnocofntceon,trmaitdidolne,,vaenrdgbeopoemersobfasneodmionnalme(ainsupraerdrtchoenscee)n.trsattainodnafrodrdceavcihstIivoen,, and coefficient of variationofduplicate samplesar based on mesarcd concenitaionfor ach evel Company Sanilized. Does not contain TSCA CBI ws 9H0-2-4D5a1y6:GavSaugbcehSrtoundiyc TinoxRiactistywith One-Generation Reproduction Evaluations DuPont5386 - "Table 11. Mixing and Stability Studyof H-2451i6n Dosing Suspensions (continued) TT SumieTye Dose Volume. Nominmalgm F-245M1e6asured TT Pewen Nominal SSOtambiUliKtye 0-DAY ROOM TEMPERATURE. 50 439 78 5-HOUR Roow TEMPERATURE 50 460 920 2DAY REFRIGERATED. 5500 4a7n6 954 052 Mearl:4.772001 95.4%) 3-DAY REFRIGERATED. 50 cava.02% 948 50 ad Mean(); 4.61202 80.6 2.2% 4-DAY REFRIGERATED. 50 cavx. 96.1 4-DAY REFRIGERATED! HOUR RT 50 a8 7.1 0-DAY ROOM TEMPERATURE 00 187 95 5HOUR ROOM TEMPERATURE 200 172 560 2.DAY REFRIGERATED. 20000 118807 9s 90.0 -- MeanlC); 18.3:0.5 15%) cv 3-DAY REFRIGERATED. 20 200 393 196 196.4 978 MeanlC:D); 29.4214 147.0% 4-DAY REFRIGERATED. 20 c1r96am 078 4-DAY REFRIGERATEDSS HOUR RT 20 176 882 0-DAY ROOM TEMPERATURE 500 534 1068 S-HOUR ROOM TEMPERATURE 500 83 9656 2DAY REFRIGERATED. 500 500 a3 94.7 84 96.5 Meani); 47.9208 5.8%) 3-DAY REFRIGERATED. 500 cv on 65 93.0 500 469 93.8 Mean(); 46.7503 3.4% ADAY REFRIGERATED. 500 car9 n 97.8 W4-DDeAoYwRsEoFrRdIGeEtRcAeTeErDI,S HOUR RT 500 419 957 (8) () TcTohheeefaaivvceeerrnaatggeeof vmmaeeraaissauutrrieeoddn ccoooftnncspec,nntrrmtaitioionln,,easavenerrdsagbgeeoppoeermrcceeannrttoobuffsnneoodmmiionnnaalls((uiin rpprreeensttchhoenssccses)n).t,rassttuianondndsa[rr0dd dceavcihateinone, deviton, and asd - (0) cRaoneedsfiwucilliletnnhtoetobfemvreaerapioatroitfoetndh.eofddupplliicaattecasnaamlpylessisaroefbtahsedoroinginmaelssasmeplde.coOnrcgeinnraalioannfaoer scadchiIcvee.d liot ror - ww Company Sanitized. Does not contain TSCA CBI 219002-.4DD5aa1yy6G:GaaSvvuaabggceehSrStouunddiyyciTinnoRrRaiattcsswwiitthhOOnneeGGeenneerraattiioonnReRepprroodduuccttiioonnEEvvaalluuaattioornss DDuuPboonn:t55338866 "Table, TT FSienaeHomogeneity Concentration VewrifeiclatiAonzofeH-e24516 in Dosing Suspensionsem Tone Tew a CHoovmotgreonerity 000 oA) i. joTor iimm 227019 I5n Borrow im Mean; 12002420.4 011032% MTooori 11333 c10sri 810 127 953 Borrow 1533 Mean; 1122%11.1 009683%) MoToors n3s scoron 529 24 07.1 Borrow nn Meant): 323451.2 0160503% cra Test Day 01 Control 000 NDA) -- `HMomTioogoreneity Borrow 3wm3 33000 9a01.6 3 Mean), s30o23003 057031) chin Concentration Verification I1333 Meal) 2122285304 crm 39o86i%.s0) n0n3 233 998616 Mean); 125203 cr wns ((8))DTTShoeovrcraiuogeommfdeevsasudtrieonccooofnnpccer.eanimton,,,a5av0rrseDgstppesrrceena ntooff eomb miionnnll(a(d ni sppodchorescne-- scdnsbaontseeciho)nno-- ,,n,ardd ~ Cofino arianof upc Fpl af Aeonmaar] cnet or co ll --_-- (CompanTy STanilized.BDeoteasntotacointanin TSCA CBI 1502-4D5a1y6:GeSvugeehrSotniye iToaveywithOneGenera Reproduction vations - Figure 1 Representative Analytical Calibration Curve of mmm ID fo Duponess6 (a) ' `Equation for the ied ine: ~~ 1i. -- i. (b) i Pp i TT Figure 1: Cmaelaisburraetmioenntusrv(sequsahroews)infgorlcianleiabrfatti(olninae)loirenploicfatHe2p45k16hedigihet dtioover a concenration ange o 0.0302 0.0.1511 mil. (4) Retention ime 35 - `minutes, (b) Retention = 4.17 minutes, (c) Retention time = 4.77 minutes.) --ComeSid commtcomainTscac 012-4D5a1y6:GavSaugbecrSotnuidcy iTnoxRiaciistywith One-Generaton Reproduction Evaluations Dupons36 - Figur2e Representative High Performance Liquid Chromatography Chromatograms ------ a | ||| s : | Ce -- mree rem -- T= Pett) Figure 2a: Representative GC chromatog of0mg/mL (control) sample with internal standard] H-24516 is approxima3.t5e,4l.1y,4.minutes. added. Retention time for Retention time for internal standard is approximately 3.9 minutes. I --_ | | [I i gE, I i i: I Figure 2b: Representative GC chromatogram of2.5 mg/mL H-24516 dosing solution diluted to a nominal concentration of 0.06 mg/mL. The measured concentration of the representative solution is 2.51 mg/mL Company Sanlized. Doss not contain TSCACB s tees te eeeeeeeyge seem r eee 9102-4D5a1y6:GovSaugbcehSrtoundiyc iTnoxRiactistywith OneGeneration Reproduction Ealutions Duponts386 - Figure2 (continued) Representative High Performance Liguid Chromatography Chromatograms [pe em-------- -- [ | [= lu | | "i - || BoiA] -- ALdiga i. Figure 2c:reRfeerpernceesseonltutaitoinGvCe chromatogramof 0.0756 mg/mL H-24516 analytical -- `Company Santized.DoesnotcontainTSCA CBI ww 9102-4D5a1y6:GavSaugbcehrSotnuidcy TinoxRiactistywithOneGeneration Reproduction Evaluations DuPont 5386 APPENDIX B INDIVIDUAL DOSE VOLUMES (ML) Company Sanilized. Doesnotcontain TSCACB --- 910.2-4D5a1y6:GavSaugbeehSrtoundiyc TinoxRiacistywith OneGeneration Reproduction Evaluations - INDIVIDUAL DOSE VOLUMES (ML) EXPLANATORY NOTES DuPont 5386 Critical Dates Day 74 Mhoaulseeda.ndDfoesmealveolruatmsedseasdigmniantiesdtefroerdrdeuprriondguctthieoncoehvaabliutaattiioonnsawnedrpeocsot--mating periods are documented in the study records. Day 89 Last day of test substance administration for male and female rats designated for one-month and 3-month recovery periods. Day 90 Last day of test substance administration for mal rats designated for the 90day exposure period. Day 92 Last dayoftest substance administration for female ras designated for the 90-day exposure period. Footnotes a. Due to error, data are missing. _ b. Animal may not have received total dose. c. Due to error, rat was dosed with vehicle only. d. On test day 18, all male rats and the first 11 female rats in the 25 mg/kg/day group received 37-39 mghkg/day. Abbreviations AK Accidentally Killed FD Found Dead SE Sacrificed in extremis `Company Sanitized. Does not contain TSCA CBI = -_-- ~3 2 8 3 2 i R pny vt ans peta nay ]|B 5 Mmmm 3 : Lun 1 :: RIT REBL IID - gl Bg8 og. STII a g igs ABE E. III g Hi L ImImImIILNSNIRNIUNIIILIEIG dL gz 32 . rmmIamIIIIInITIIIINRGIL RmMmmIImISISmmIsEa mmL Se iy iz2 3 eI n nm A IA IA GANR | it ie 9 - 8 33333I7 TEI3 TEI3 TT T9 TTI3 ERIE3II8 IRI7 ERE 3 2 - i, smemmmmTRET : i ; I Jr IN =a af. osm J$iF. BHF mI 8. mI g 23 semiarntioviazaczessansieyieaengeastreeses 3 o RNNERIINIIIRIINIINRIINIIIRINIIINNGINGID FE i1].isomes { ~ 3 3 |. cummins i PEERS i PR 7 FIININRINNNNINEI "2 Fa amaInsaaiiaiaiIIIIIIInIIsIIg - Eh 1 EE - I 5 INI i alr} . 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REIT |EL IRIAN gi 53 - Dep il i | BF emmeosemmmmmananmnaanma | iH a | i 2 : A ARR As 3 : NARARRRRNET REIEIRAARNRRTRARy TAAISNRANNINAART ii : A33EARANERAEAANENNNAIANSINGINANNRNNN I Tn g sg nn ae Aang va Ta 32 A & aaa | ~ i|Z:2 RA aan I, 2 8 ER ssa * 2 FE 1: : <[IE]= a aaa aA a aes asa NO HO rR mG wR A BN BEAR Am TA EN 2 i: 8 -~ 3g| i3 3 . 3 5 ARRANGES i a i : na Rae i | PRESS FE | 8 ARNIRIIRRRIIIMRARIRRARANNIANNN | Pa 2x | 4 gl 8 2 IENIIEINAGIIMINAMINIMNNIIMRNGAEAAR | 3 : A RAR ARABIAN | i ARITA } i: a hams fil RERRRImRRIERNINEEn 24 &z i 2: AAA 3 i --_ g z 3 ) IEEE :1 : 8 : ae Re AE I EEE PE EEREREE ER a OH 5 8& 5 3 2 GEE SENANNIIIANNANINNNAANIIANINNNNGG 5 FEELERS Es WITNESSING &Z 2 i: | 3 2 @ RIINIIIIIIEINIIININIIIEIINNIGIG | I 3]. noevessnasssesieanemasosanennonatosssesanasan | g ~ 3 i i i i a 2 I19533009SaNEASAAANIIAT AMINNIIE/MANIIR 3 ; : | g a ZamssasEIsIsfInmnamaaInIIaTIaEIngI i 3 8 Jagaesra AANA IAA | i3 i,i I Asn ANAIINIIIIIMNIIIRNARNIANALININNNGG & z 8 poy IIIIISINIIIIIIAINANIAINIIANIIIINALNL ziiz 7 nddandadsaanaaasasmannane 4% ig i EZ Ea AAR NANIANIAAIIARIAANINNINANARAANNGAGAS 8 z i 3 oo mommIaIEaETII Mmmm OF i i ~ Li I. 8 MENGE HME MA ONON TONEY NN NNONSMH ADN RA MANS 8 % MRA NANA NARA AN ANNAN NE NAN ANAS SER dra aden | RII RRA RR NR J ERRO RRR 2 damanmeimneninnienasuenas maanossniasnaatnane To { ITI ii SEITE ~$ 5 A ARSTEM ISCMAMCEA RANAMTMAAN GORNEGRENO NYSOANEGSTY H AA REN NR AN BEA OO RAMN N ANS EE FZ. fF oomaeiansoioanaIIINID SAMNINIIIIIIIIONN | iy ig | 20 nsessesnscnssnssesnnie | i FRE EERE EE EEEE EE RE HE EEE | - i 8, avomvenas sanee z g2 2| i vagrants il { lzx AFIRNFIT ATLANTIS i] || & id | oe 33233007 J2RREAIIINLAT FnRsIIn | a Hm ANE SY BNGAGS ANAS EN S0aS aNeS | 8 NRACARANN CaNANAANNA AAA ANN NAAA NNNNN NN --- 2 le a Ji 3a 2 8. 3 : ; 3 AARIAMIILIAAIIIIAIIT ammsIiInIIIININ - IANIILIREAREANAN mSIITIIIIIIGEE: gi PH i NEAR NANA ANNNA NNN AN NA ANNNN NNA aS | 2 & 1 2 =ERT2 FRTRINAITIE303 EAI - 2 REPU EP : oR ~ bJEo: sommmaronm fs mm sam 1 FE. sme ann 1. mmo omm s3y fi ame h.am if a: 8 :i NenAAaNNS 8 saw TEE L woman | wammEm | sxnsinana saeTIen a i -- Ed f ; i 8 I JERR ERE EEN _ Bi f Ic: Bl 8, io amma erating eanss " geting gi g 2 2 > NuNiNdNNN NaN ANANNNNANS $Fs op Sm eSRNm EESE EaEnEnNeE nSRiANnNEaRE:IN 5 i: { 5 3 %onamns auw STEN | z Ia | @ B 9 i SRYRITENILARIELESaTnse EINenTsIntS an ARTELE 9H0-2-4D5a1y6:GavSaugbcehSrtoundiyc TinoxRiactistywith OneGeneration Reproduction Evaluations DuPont-5386 APPENDIX C INDIVIDUAL BODY WEIGHTS ".ompany Sanitized. Doesnot contain TSCA CBI pee 9204-5D1a6y:GavSaugbeehSrtoundiyc iTnosRiatcstywithOneGeneration Reproducion Evalatons INDIVIDUAL BODY WEIGHTS EXPLANATORY NOTES Dupon5386 "ritical Dates Day 74 TcMooaxlliecctouolndodgdfyuersmiacnligeohrnaetscdoensaigbntattoedn fsonrdrepporsotd-umcattiionng epvearliuoadtsiaones wreerpeaciod-hionusteed.ReBprooddyucwteiivgehts Day 91 Male ris designate forthe 90-day exposure period were sified Day 93 Femaleras designated or 90-day exposure period were src. Day 119. Lpeartiodd.oyof no fstd body weight dts cllcio for ts designted fr the one-month recovery Day 125 Mal and female rats designated forthe one-month econry period were sacrificed Day 175 Last day ofno fasted by weight data collction for rs designatedfo the month recovery period. Day 181 Mia and mse rts designated for 3-month recovery period wee safc. Abbreviations AK Accdenaly Kiled Found Dead SE Sacrifind in cxtrmis `Company Sanitized. 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SAT aRsnnanoersey 28 $SEEEEETI ITITE ITE ITI ITE ITsIEESII : 2 S4r 1; nEnY ii ioc: an $ gs oH i 3 REAR :8 3 i 3i :| | : 3 3 |i 1 g - J2 18 5 $:: <2 25 % i5 ac3 re z i& i i E{ ro | B -~ 73 8 33 : [I g 3 GRUNERRIANIRIRIECASAARSIGAASAINRRD i 3 $EIINRALAILRILBURATAANICATAIRCIAS i ; SEIsERNIRIIIISIIVERSRRSIRdeRIEa gE: FETERRRSLERLRTAnLsR satay g = i :Lr7 S RAISISTISt RIRGIRSUn RRGESTIIs IREIANIR 2 i amananoayynaaesnnyanLaagnenny JBl EI iijssisrsssniisnissasscsrasiissaiss | < TT TT1 3 ARRECEINNIRIRRNARRTANTIRSIONIRARIRY 3 5 I : SRREEANERININTRARINRARANRERIRANRANE bE i | 2 2 2 ianiannRe enamine ead A dar Rand | ~ &32 +ESR ESE RIE REESE IEAEE TEAEE ERREIE REAERARE LREAIAETE REIRAEREE IRARLS ` ~ i i 3 dase 3 5 2 3 83523 i| | 3 $5885 2n3t7aenaeee | : 3 ARARTEURGEITRIZN | 8 TE Segsigeesadnein | 38 IE. assenasasasien: i fl 8; sasmesEsnaIesss iio:: Ec EREITFn IARINCn AREERS 9 gl. samaznmnnssaiemenennsescesananescen iy3 7y SaEREBERIIIORRBIIBTIRERNUIILANINNE 4 2 3 3 ; oo TiSnGndRsMiiGiIsaEeHniRdUaiSiRsiIaNiiTn $9 # ~ =5 333337327323335333333333333533528E3 | a8 | 3 3 geass i . enn 8 i 22888 i gf sid g Bos saan 5 33 FI 7Hi. i | $ g" em. 2EI 7; ges: | 2% i | 2 oo 25333 2g i 28583 e i .. ; - 3 8 # i i a 8 i i | 4 | RE: Hi 22 HfHII e 2 Z 3 8 5 LEE i558 29 i 8 g -1 i i 5 2 i senmivssiRResaninaNAanaiE i | B | peasneaensniannaenienenesnseemnean x B3EIIIEISIOTSASAIISIERNIANIINNN0NCE HE [EE gc EEI 33 or2 i oe meI neueR nnanI ceneE ennN munaE nmesE anasG van 9) ETI LAAT EATERIES iz 33339933955 95E00RRRREARERRERRE0EE : ; i z B 5: 8588 : a 2 > 35888 i 3 FRED BRRERALES | iE al| ngsmdesadssazagndasncnggsnsnd H5I RRRELng 2 g2| l. isenesnsersscasccsaeeainniasnies fs 7, 2% g 123 oorf IsernaEuEneCncIiEaeInIasNanNnCacNnaSiSenRyNenScaIsEanEe - i2 8 5So oSEmEIsRRIRRREIAAAERAAISRESEAAAESSIANRARASINIRAERIEISAAAERRESER 33333527333333333333I33ITTIITIIFRLEE g ~x 2i ; i tg; Faia | hi 2 & a ddgis 4 S8 2 I. 3 g [ 2 2 LE2 de] ARETR -- siagi = iisg = SAE BEERiEEIReMEEsEaRIiRREAnEARTIAAg F B3TIIIITIITITITTIIISITILILLITILIIIIIL ~ 8 2 3| I i | - |: 8 | | HE 5 a | i IIIS Ha H 3 ~ : : ssssiassdagdrsssadinndinindsesginrantdannag i |g - 58%8 gasIgdIeIsagsd ddszassce snisisisa iisissnan iT dsansiI in 2* ig :i |: 8. EERE FRRRRARSARRARIRRRRSfInnmmmnanfniammataancsmne semsgainzanssssnsesnaecsascesssanevessesvens i: LF apmeesessnenesn eas 23 7 AIAREREIREARNIRRRINRIRATRARACARIARARINRAARR _i 2 3 fae: |g | Hi diigsiigds i - B= aiainaiEsiiig diddeddnia # i : . amennfnnmennananns - % 8. nimmmIAEIILNG | 2 Ps B33EEEREANEAREE0 CIRCERANEHAINRUNERIRERNST 3 y 3 8 n2LEmEREiRNmEREnARmRRAmTAnAIAEILIITANRIICRAITInCIAEC LnIAENEE: Iz i i ofZ} i35z 3 $3883 : fasss i ed a Id 3 REIL 2 i: 3 8383 i& i [REINT 1: wu L5 I. bi3naosst no : i | mn EH 33ERERRERERENITIISiiiuissauiiiEIaEEmEmEERE 8 i Cf i 3 : i ~ I| o fl 2 i 3 bi i | g HEH ne ~ 3] 2ii : 3 I DunIRSEEaaaER | 3 (HRAARREANARAESRURAIRARREIENS $ I3 : sSHEEnRREoRIRmRRAmANAsRINuARANmARInNEAmRNAERAREARRERAREARR ~ 3 5 > a 3 "eine #8883 gE3%3 ig ] : 8B sa2unanias EERRERZLEE : i ERBERAREEE I agf] mHiEmmHEGEH Bfahfaan - 5. mmmnnun ol B 3 EARRERERARERNRD 3:24 18: EnnasEE i & Sina ZhoERARANR Hainan gx i i | SRE SRSERARNRXARALIIAINES 0 | 2% 5 AENRERRESENRNLRSERREIIRIRBRAINIANENIEZIRERRAR | L2E. n2mmmnnsnsnuunEana es SU iieeexsmurseonssasassgitiieassssnesiiesis | TORY mmmmsnnnanEs | 8 ~ i 5 el i 2 8 5 :oz 8n2i238 $ 5g i, gsiaggxess SE 2 2 3 :: : RSRiARZ . % BSeEaadRcIeasEhEans 8 i ~ 53 3: 3i i i8 | | _ 5 & 35 EE] i5d= :& | g| g! || | l Ho | 53 ` | 7HERaEr FiRiRis | 88 ~3 i2 : i s ICING deiddiiidiiisiiidiedas d g8 8 --~ i ~ vo =e - HI g BH rI GRAN ZARXAREASRS A ARANRRARTIARH NANAUNINRAISS ARR . FEI : | gil A, TRERERE & i B3 oF oimmssmmemanasiensasssaninascoases 2% RRIERZRNNLZCRENRIRINNINNENARRANLNER - 5; : i i 7 37m 2 3 338 i . ae 82 7 435 f : 3 42 py EEE AEE _ : Sal hE 5 5% zmides dag ded 3 | Ft IERINN 3iEF denseavaidssidsiiidded 2 53 :3 | HIER pagers te 2g Ce | ig Sasiaieassaiaaisaaaiadnasany -i 5 3 Iie 8 233 |f || 3 18 3 3 E32 JE --_ fed HER | EEgis Ei HE iim 9 EI 23 a 3g 3 enn 838 LEE iE :25 5 E i i i &1. -4 : ! 8 g I J B 2 | :!& | g :23 > Hor Ca : : : 3 SREZERZRARAHRARRACARARRARANARERGANE i i REZERSARIIRATASNLRNNALAIRARSIRRANAR i' | :fl 8%i SapAidiaiaiiidaRiiiEEdiiiEad 28 or I enamnen seeteneoTenatyaen & So nnalinamnnim | PH 3 FRRERANERARRENNRRANNREIRARIZARMANR 2 13 T vrenanaunnnegeanasnaeyeiennnnes iy 30. sEefdiserdEsiedirdasanisaiuiagaidis -- 24 G HEEEREIACACERRRRECIInCacRIniiaaiat - 8 2 5 i: soadend iE | } --_ g le if 5= Sadan iadiagg i: | 5 i sysannamanaansaeanaegaesreasg nog | : i8 3# -~ 3 2 2 z 8 5, J 3 A83E3 fi3 fangs ; i | 3% iFEE,E pAeEnRa i| 3: a 2 i: i x: Ee iy i. or 3 4 330859355RTEEEEEET0AEANEISNARRRIST |8 ~ {<| i If | L gh 33 gl a2 | 2 iiy gi: S33e8s5e2s | E ~3 3 eh 3 spp | EA 4 Nime enn EEE EAE SEAS ESE Een En i i: Rr g ! ENING | ~ 3 852 3 i i| z& - Be mnmom 533 : : ; TAGRERNER REM 28 Sinsim ESRESRAaNE | 3 : asnsarcanfnanrasnesnanan asanarsansnsaotasas 2 g 2 $1 Eh of 5p preeminence FPARRRRASANSRRALSRARHRENS sms SASLEASAUSSRRSRSESS 5 seyssmEsseEiRNgsInanESIISANIIINSINEAILE i iBg - i 3. oo i 3 338% g ARBAT | g : :3 38389 ZB gl 2s :a seans i oa S03 gl i32 iy EG fy ov iy 3i FJ ee tomy E2383 Sen SRRRRLARAA - 24 FE TREAESET aEREI IEE RI EES E E EE EER E TRE g3 -% 5 : i i 38 |8 - 5 2 ol 2 1: i i2 273 5:3 g iy i i none | 9H0-2-4D5a1y6:GaSvuabgcehrSotnuidcy TinoxRicaittsywith One-Generation Reproduction Evaluations DuPont-5386 APPENDIX D INDIVIDUAL FOOD CONSUMPTION -- company Sanitized. Does notcontainTSCA CBY H9-02-4D5a1y6G:avSaugbeehSrtoundiyc iTnoxRiactistwyith One-Generation Reproduction Evaluations INDIVIDUAL FOOD CONSUMPTION EXPLANATORY NOTES DuPont-5386 Critical Dates Day74 + Male and femaleratsdesignated for reproduction evaluations were co-housed. Last dayof food consumption data collection for rts designated for reproduction evaluation. Day $3-89 Ruraitnsedaensdigfneacteesdcfoollretchteio3n.-moFnotohdrceocnovseurmyppieornioddatwaerweastenmoporcaorllielcytheodufsoerdthiensmeeatnaibmoallissdmucraignegsthfiosr period. Day 91 Male rats designated forthe 90-day exposure period were sacrificed. Day 93 Female ras designated for 90-day exposure period were sacrificed. Day 119. Lpearsitodd.ayoffood consumption data collection fo animals designatedfo the one-month recovery Duy 125 Male and female rats designated for the one-month recovery period were sacrificed Duy 175. Last dayoffood consumption data collectionfo animals designatedfo the 3-month recovery period. - Day 181 Male and female rats designated for 3-month recovery period were sacrificed Abbreviations AK Accidentally Killed FD Found Dead SE Sacrificed in extremis Sompany Sanitized. 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