An oral two-generation reproductive toxicity study of S-111-S-WB in rats.
S-111-S-WB (CAS No. 72968-38-8), a mixture of perfluoro fatty acid ammonium salts, was administered daily via oral gavage to 30 Crl:CD(SD) rats/sex/group at 0.025, 0.125 and 0.6mg/(kgday) over two generations to assess potential reproductive toxicity. Reproductive performance, mean litter size, pup survival and pup weights were unaffected. Lower mean body weights were observed in 0.6mg/(kgday) group F(0) and F(1) males. Higher liver weights, correlating to hepatocellular hypertrophy in the 0.6mg/kg group, were noted for parental males in the 0.125 and 0.6mg/(kgday) groups, parental females in the 0.6mg/(kgday) group and F(1) pups in the 0.125 and 0.6mg/(kgday) groups. Higher kidney weights, correlating to renal tubule hypertrophy in the 0.6mg/kg group, were observed for parental males and females in the 0.125 and 0.6mg/(kgday) groups. Systemic exposure (measured only in females) to total S-111-S-WB was proportional to dose following 9 weeks of daily administration on the gestation day 19. Total S-111-S-WB concentration in the serum of male and female pups was 1.2-1.4-fold higher than in the dams 2h following administration to the dams on lactation day 13. A dosage level of 0.6mg/(kgday) was considered to be the no-observed-adverse-effect level (NOAEL) for reproductive function. A dosage level of less than 0.025mg/(kgday) was considered to be the NOAEL for F(0) and F(1) parental systemic toxicity based on microscopic hepatic findings in the males of all test article groups, and a dosage level of 0.025mg/(kgday) was considered to be the NOAEL for neonatal toxicity based on higher liver weights in the F(1) and F(2) pups at 0.125mg/(kgday) and higher.
Stump
Donald G
DG
WIL Research Laboratories, LLC, 1407 George Road, Ashland, OH 44805, USA. dstump@wilresearch.com
Holson
Joseph F
JF
Murphy
Sandra R
SR
Farr
Craig H
CH
Schmit
Bruno
B
Shinohara
Motoki
M
D000284:Administration, Oral; D000818:Animals; D000831:Animals, Newborn; D001724:Birth Weight / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D001947:Breeding; D004305:Dose-Response Relationship, Drug; D004435:Eating / Q000187:drug effects; D005227:Fatty Acids / Q000008:administration & dosage / Q000378:metabolism / Q000633:toxicity*; D005260:Female; D048788:Growth and Development / Q000187:drug effects; D006845:Hydrocarbons, Fluorinated / Q000008:administration & dosage / Q000378:metabolism / Q000633:toxicity*; D007668:Kidney / Q000187:drug effects / Q000473:pathology; D007774:Lactation; D008098:Litter Size / Q000187:drug effects; D008099:Liver / Q000187:drug effects / Q000473:pathology; D008297:Male; D019055:No-Observed-Adverse-Effect Level; D009929:Organ Size; D051381:Rats; D017207:Rats, Sprague-Dawley; D012098:Reproduction / Q000187:drug effects*; D013091:Spermatogenesis / Q000187:drug effects; D013501:Surface-Active Agents / Q000008:administration & dosage / Q000378:metabolism / Q000633:toxicity*; D013997:Time Factors; D036401:Toxicity Tests, Chronic
D005227:Fatty Acids; D006845:Hydrocarbons, Fluorinated; C528636:S-111-S-WB; D013501:Surface-Active Agents