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PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTII,11'Y, DEVELOPMENTAL PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9) AND PF.RINATAt,/ POSTNATAL REPRODUCTION TOXICITY TABLE E20 (PAGE 1): I.ITTER OBSERVATIONS (NATURAI.1,Y DELIVERED PUPS) - ST)MMARY F2 GENERATION LITTERS ----------------- - --- ...................... ------------------- MATERNAL DOSAGE GROUP 1 11 HATERNAI, DOSAGE (MG/KG/I)AY) 0 (VEHICI,E) 0.1 ----------------------- ----------------------------------------------- DELIVERED LITTERS WITH ONE OR MORE LIVEHORN PUPS N 22 21 ......-----------------------------111 0.4 -------------------------------------- 24 PUPS DELIVERED ITOTAL) N MEAN+S.D. 316 14.4 + 3.5 325 15.5 + 2.5 357 14.9 + 2.6 LIVEBORN MEAN+S.D. N(i) 14.1 + 3.5 310( 98.1) 15.1 + 2.4 318( 97.8) 14.3 + 2.5 344( 96.4) STILLBORN MEAN+S.D. N(-t) 0.3 + 0.6 6( 1-.9) 0.3 + 1.1 7( i.2) 0.5 + 0.9 13( 3-.6) PUPS FOUND DEAD OR PRESUMED CANNIBALIZED DAY DAYS DAYS DAYS DAYS I 2- 4 S- 7 6-14 IS-21 N/N(t) NIN(lk) N/N(t) N/Nit) NIN(T) 2/310( 7/308( 0/171( 0/171( 0/1714 0.6) 2.3) 0.0) 0.0) 0.0) 2/318( 2/316( 2/167( 1/16S( 0/164( 0.6) 0.6) 1.2) 0.6) 0.0) 2/344( 11/342( 5/191( 1/178( 0/177( 0.6) 3.2) 2.6) 0.6)a 0.0)a VIABILITY INDEX b % NIN 97.1 301/310 98.7 314/318 96.2 331/344 LACTATION INDEX c t 100.0 98.2 96.7 NIN 171/171 164/167 277/183 ------------------------------------------------------------------------------------------------------------------ DAY(S) - DAY(S) POSTPARTUM a. Excludes values for litter b. Number of live pups on day c. Number of live pups on day 13257; the (lam was found dead on day 10 of lactation; eight pups were sacrificed. 4 (preculling) postpartum/number of liveborn pups on day 1 postpartum. 21 (weaning) postpartum/number of live pups on day 4 (postculling) postpartum. PROTOCOI, 418-008: COMBINED ORI,I. (GAVAGE) FERTILITY. DEVEI,OPMENTAB PPOS IN RAT!; ISPONSOR'S STUDY NUMSER; 6295.9) AND PER INATAI,/ POSTNATAL REPRODUCTION TOXICITY TABLE E20 (PAGE 2) 1 LITTER OIISERVATIONS (NATURALLY DEI,IVEIIED PUPS) - SUMMARY - F2 GENERATION LITTERS -- ------------------------ I ------------ --------- - MATERNAL, DOSAGE GROUP 1 MATERNAL DOSAGE (MG/KG/DAY) 0 (VEHICLE) .. .................................................... DELIVERED LITTERS WITH ONE OR MORE LIVEBORN PUPS N 22 ---------------------- ----------------------------- 11 111 0.1 0.4 ................................................... 21 24 SURVIVING PUPS/LITTER a DAY 1 b MEAN*S.D. 14.1 + 3.S 15.1 + 2.4 14.3 + 2.5 DAY 4 PRECULLING MF-kN+S.D. 13.7 + 3.3 15.0 + 2.8 13.8 + 2.4 DAY-.4 POSTCULLING MEAN+S.D. 7.8 + 0.8 8.0 + 0.2 8.0 + 0.2 DAY 7 HEAN+S.D. 7.8 + 0.8 7.8 + 0.5 7.8 + 0.7 DAY 14 DAY 21 PERCENT KALE PUPS PER NUMBER OF PUPS SEXED HEAN+S.D. MPM+S.D. 7.8 + 0.8 7.8 + 0.8 7.6 + 0.7 7.8 + 0.7 7.7 + 0.8 1 2ilc 7.7 + 0.8 2i)C DAY I b HEAN+S.D. 47.9 + 15.2 S2.1 + 10.9 47.0 + 13.3 DAY 4 PRECULLING MEAN+S.D. 47.9 + 15.1 Sl.5 + 11.1 46.6 + 13.4 DAY 4 POSTCULLING MEAN+S.D. 47.0 + 10.0 49.6 + 1.6 49.1 + S.7 DAY 7 MEAN*S.D. 47.0 + 10.0 40.9 + 3.9 48.7 + 6.4 DAY 14 MEAN+S.D. 47.0 + 10.0 49.2 + 2.6 48.3 + 6.2 1 24]C DAY 21 HEAN+S.D. 47.0 + 10.0 49.2 + 2.6 48.3 + 6.2 2ilc ----------------------------------------------------------------------------------------------------------------- DAY II a. b. c. - DAY POSTPARTUM - NUMBER OF VALUES AVERAGED Average number of live pups per litter, including litters with no surviving pups. Includes pups born alive, found dead day 1 postpartum. Excludes values for litter 13257; the dam was found dead on day 10 of lactation; eight pups were sacrificed. PROTOCOL 418-008: COMBINED ORAI, IGAVAGE) FERTILITY. DEVELOPMENTAL PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9) AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY TABLE E20 (PAGE 3): LTI'TER OBSERVATIONS (NATURALLY DELIVERED PUPS) - SUMMARY P2 GENERATION LITTERS ........ ....... MA'I*MRNAI, DOSAGE UROUIP MATERNAL DOSAGE (MG/KG/I)AY) ... ............................. DELIVERED LITTERS WITH ONE OR MORE LIVEBORM PUPS N . ...... ....... 1 11 0 IVElilCLE) 0.1 -----------------........................ 22 21 ---- ----------------- ----111 0.4 -------------------------------- 24 LIVE LITTER SIZE AT WEIGHING DAY I MEAN+S.D. 14.0 + 3.5 15.0 + 2.6 14.2 + 2.5 DAY 4 PRECULLING MEAN+S.D. 13.7 + 3.3 15.0 + 2.8 13.8 + 2.4 DAY 4 POSTCULLING DAY 7 MEAN+S.D. HEAN+S.D. 7.8 + 0.8 7.8 + 0.8 8.0 + 0.2 7.8 + 0.5 7.9 + 0.3 7.8 + 0.7 DAY 14 DAY 21 PUP WEIGHT/LITTER HEAN+S.D. HEAN+S.D. (GRAMS) 7.8 + 0.8 7.8 + 0.8 7.8 + 0.7 7.8 + 0.7 7.7 + 0.8 ( 23)a 7.7 + 0.8 23)a DAY I HEAN*S.D. 6.3 + 0.8 6.1 + 0.5 6.2 + 0.5 DAY 4 PRECULLING HEAN+S.D. 6.7 + 1.6 8.2 + 1.0 6.0 + 1.3 DAY 4 POSTCULLING HEAN+S.D. 8.8 + 1.6 8.3 + 1.0 8.0 + 1.3 DAY 7 MEAN+S.D. 14.7 + 2.4 13.9 + 2.2 12.8 + 2.6* DAY 14 MEAN+S.D. 32.0 + 3.5 31.8 + 3.1 28.9 + 4.7** 1 23)a DAY 21 MEAN+S.D. 50.1 + 5.1 49.2 + 5.0 46.5 + 6.3 [ 23)a -------------------------------------------------------------------------------------- -------------------------- DAY II a. - DAY POSTPARTUM - NUMBER OF VALUES AVERAGED Excludes values for litter 13257;- the dam was found dead on day 10 of lactation; Significantly different from the vehicle control group value (p!0.05). Significantly different from the vehicle control group value (plO.01). eight pups were sacrificed.