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 0.6 mg/(kg day) 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 0.6 mg/(kg day) group F0 and F1 males. Higher liver weights, correlating to hepatocellular hypertrophy in the 0.6 mg/kg group, were noted for parental males in the 0.125 and 0.6 mg/(kg day) groups, parental females in the 0.6 mg/(kg day) group and F1 pups in the 0.125 and 0.6 mg/(kg day) groups. Higher kidney weights, correlating to renal tubule hypertrophy in the 0.6 mg/kg group, were observed for parental males and females in the 0.125 and 0.6 mg/(kg day) 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 2 h following administration to the dams on lactation day 13. A dosage level of 0.6 mg/(kg day) was considered to be the no-observed-adverse-effect level (NOAEL) for reproductive function. A dosage level of less than 0.025 mg/(kg day) was considered to be the NOAEL for F0 and F1 parental systemic toxicity based on microscopic hepatic findings in the males of all test article groups, and a dosage level of 0.025 mg/(kg day) was considered to be the NOAEL for neonatal toxicity based on higher liver weights in the F1 and F2 pups at 0.125 mg/(kg day) and higher.