An oral two-generation reproductive toxicity study of S-111-S-WB in rats

Reprod Toxicol. 2008 Jan;25(1):7-20. doi: 10.1016/j.reprotox.2007.10.002. Epub 2007 Oct 7.

Abstract

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.

MeSH terms

  • Administration, Oral
  • Animals
  • Animals, Newborn
  • Birth Weight / drug effects
  • Body Weight / drug effects
  • Breeding
  • Dose-Response Relationship, Drug
  • Eating / drug effects
  • Fatty Acids / administration & dosage
  • Fatty Acids / metabolism
  • Fatty Acids / toxicity*
  • Female
  • Growth and Development / drug effects
  • Hydrocarbons, Fluorinated / administration & dosage
  • Hydrocarbons, Fluorinated / metabolism
  • Hydrocarbons, Fluorinated / toxicity*
  • Kidney / drug effects
  • Kidney / pathology
  • Lactation
  • Litter Size / drug effects
  • Liver / drug effects
  • Liver / pathology
  • Male
  • No-Observed-Adverse-Effect Level
  • Organ Size
  • Rats
  • Rats, Sprague-Dawley
  • Reproduction / drug effects*
  • Spermatogenesis / drug effects
  • Surface-Active Agents / administration & dosage
  • Surface-Active Agents / metabolism
  • Surface-Active Agents / toxicity*
  • Time Factors
  • Toxicity Tests, Chronic

Substances

  • Fatty Acids
  • Hydrocarbons, Fluorinated
  • S-111-S-WB
  • Surface-Active Agents