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Perluorooctanpsulfonate: PK During Pregnancy and Lactation + Analytical Protocol M. ." PROTOCOI, 418-008. COMBINED ORAL (GAVAGE) FERTII,11'Y, DEVELOPMENTAL PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9) AND PERINATAI,/POSTNATAL REPRODUCTION TOXI TABLE E20 (PAGE 1): I,ITTER OBSERVATIONS (NATURAI.1,Y DELIVERED PUPS) - SI)MMARY - F2 GENERATION LlrrERS ----------------- - --- ------- ----------- - -----------------I- - -------------------------------- MATERNAL DOSAGE GROUP 1 11 111 HATERNAI, DOSAGE (MG/KG/I)AY) 0 (VEHICI,E) 0.1 0.4 ----------------------- ---------------------- ----------------------- --------------------------------- DELIVERED LITTERS WITH ONE OR MORE LIVEBORN PUPS N 22 21 24 PUPS DELIVERED ITOTAL) N MEAN+S.D. 316 14.4 + 3.5 325 15.5 4 2.5 357 14.9 + 2.6 LIVEBORM MEAN+S.D. N(i) 14.1 + 3.5 310( 9-8.1) 15.1 + 2.4 318( 97.8) 14.3 + 2.5 344( 9i.4) STILLBORN MEAN+S.D. N(i) 0.3 4 0.6 6( 1.9) 0.3 + 1.1 7( 2.2) 0.5 + 0.9 13( i.6) PUPS FOUND DEAD OR PRESUMED CANNIBALIZED DAY I DAYS 2- 4 DAYS 5- 7 DAYS B-14 DAYS 15-21 VIABILITY INDEX b NIN(%) HIN(%) NIN(%) HIN(%) NIN(%) % NIN 2/310( 7/308( 0/171( 0/171( 0/171( 0.6) 2.3) 0.0) 0.0) 0.0) 97.1 301/310 2/318( 2/326( 2/167( 1/165( 0/164( 0.6) 0.6) 1.2) 0.6) 0.0) 98.7 314/318 2/344( 21/342( 5/291( 1/178( 0/177( 0.6) 3.2) 2.6) 0.6)a 0.0)a 96.2 331/344 LACTATION INDEX c % 100.0 98.2 96.7 NIN 171/171 164/167 177/183 ------------------------------------------------------------------------------------------------------------- DAY(S) - DAY(S) POSTPARTUM a. Excludes values for litter 13257; the dam was found dead on day 10 of lactation; eight pups were sacrifi b. Number of live pups on day 4 (preculling) postpartum/number of liveborn pups on day I postpartum. c. Number of live pups on day 21 (weaning) postpartum/number of live pups on day 4 (poetculling) postpartum PROTOCOL 418-008: COMBINED ORI@L (GA"GE) FERTILITY, DEVEI,OPMENTAL PFOS IN RAT!; (SPONSOR'S STUDY NUMBER: 629S.9) AND PERINATAL/POSTNATAL REPRODUCTION TOXI TABLE E20 (PAGE 1); LITTER OliSERVATIONS (NATURALLY DELIVERED PUPS) - SUMMARY - F2 GENERATION LITTERS -- ------------------------- ...........- --------- -- MA'I'ERNAL DOSAGE GROUP I MATERNAL DOSAGE (MG/KG/DAY) 0 (VEHICLE) .. ................................................ DELIVERED LITTERS WITH ONE OR MORE LIVEBORN PUPS N 22 ------------- ------- - ------------------------ ii III 0.1 0.4 .............................................. 21 24 SURVIVING PUPS/LITTER a DAY I b DAY 4 PRECULLING DAY,.4 POSTCULLING DAY 7 DAY 14 DAY 21 PERCENT MALE PUPS PER NUMBER OF PUPS SEXED MEAN*S.D. MEAN+S.D. MEAN+S.D. MEAN+S.D. MEAN+S.D. MEAN+S.D. 14.1 + 3.5 13.7 + 3.3 7.8 + 0.8 7.8 + 0.8 7.8 + 0.8 7.8 + 0.8 15.1 + 2.4 15.0 + 2.8 8.0 + 0.2 7.8 + 0.5 7.8 + 0.7 7.8 + 0.7 14.3 + 2.5 13.8 + 2.4 8.0 + 0.2 7.6 + 0.7 7.7 + 0.8 I 2i] C 7.7 + 0.0 24)c DAY I b MEAN+S.D. 47.9 + IS.2 S2.1 + 10.9 47.0 + 13.3 DAY 4 PRECULLING MEAN+S.D. 47.9 + 15.1 51.5 + 11.1 46.6 + 13.4 DAY 4 POSTCULLING MEAN+S.D. 47.0 + 10.0 49.6 + 1.6 49.1 + 5.7 DAY 7 MEAN*S.D. 47.0 + 10.0 48.9 + 3.9 48.7 + 6.4 DAY 14 MEAN+S.D. 47.0 + 10.0 49.2 + 2.6 48.3 + 6.2 DAY 21 MEAN+S.D. 47.0 + 10.0 49.2 + 2.6 ( 24)c 48.3 + 6.2 [ 24)c ------------------------------------------------------------------------------------------------------------- DAY - DAY POSTPARTUM - NUMBER OF VALUES AVERAGED a. Average number of live pups per litter, including litters with no surviving pups. b. Includes pups born alive, found dead day 1 postpartum. c. Excludes values for litter 13257; the dam was found dead on day 10 of lactation; eight pups were eacrifi PROTOCOL, 418-008: COMBINED ORA[, (GAVAGE) FERTILITY. DEVELOPMENTAL PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9) AND PERINATAL/POSTNATAL REPRODUCTION TOXIC TABI,E E20 (PAGE 3): Lil'TER OBSERVATIONS (NATURALLY R)EI,IVERED PUPS) - SUMMARY F2 GENERATION LITTERS ...... ....... -------------------- --- - MA*I'L'RNAI,DOSAGE (JROUII 1 11 111 MATERNAL DOSAGE (MG/KG/I)AY) 0 IVEIIICLE) 0.1 0.4 ... ............................................. ......................................................... DELIVERED LITTERS WITH ONE OR MORE LIVEHORN PUPS N 22 21 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 1S.0 + 2.8 13.8 + 2.4 DAY 4 POSTCULLING MEAN+S.D. 7.8 + 0.8 8.0 + 0.2 7.9 + 0.3 DAY 7 MEAN+S.D. 7.8 + 0.8 7.8 + 0.5 7.8 + 0.7 DAY 14 DAY 21 PUP WEIGHT/LITTER MEAN+S.D. MEAN+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 1 HEAN+S.D. 6.3 + 0.8 6.1 + 0.5 6.2 + 0.5 DAY 4 PRECULLING MEAN+S.D. 8.7 + 1.6 8.2 + 1.0 8.0 + 1.3 DAY 4 POSTCULLING MEAN+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 231a DAY 21 MEAN+S.D. 50.1 + 5.1 49.2 + 5.0 46.5 + 6.3 ( 231a -------------------------------------------------------------------------------------------------------------- DAY - DAY POSTPARTUM I ) - NUMBER OF VALUES AVERAGED a. Excludes values for litter 13257; the dam was found dead on day 10 of lactation; Significantly different from the vehicle control group value (p5O.OS). Significantly different from the vehicle control group value (plo.01). eight pups were socrific