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

• Published in: Reproductive toxicology (Elmsford, N.Y.) Vol. 25; no. 1; pp. 7 - 20
• Main Authors: Stump, Donald G., Holson, Joseph F., Murphy, Sandra R., Farr, Craig H., Schmit, Bruno, Shinohara, Motoki
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 2008; Elsevier
• Subjects: Administration, Oral; Animals; Animals, Newborn; Biological and medical sciences; Birth Weight - drug effects; Body Weight - drug effects; Breeding; Dose-Response Relationship, Drug; Eating - drug effects; Embryology: invertebrates and vertebrates. Teratology; Fatty Acids - administration & dosage; Fatty Acids - metabolism; Fatty Acids - toxicity; Female; Fundamental and applied biological sciences. Psychology; 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; Medical sciences; Multi-generation; No-Observed-Adverse-Effect Level; Organ Size; Perfluoroalkyl acid; Perfluoronanoate; Rat; Rats; Rats, Sprague-Dawley; Reproduction; Reproduction - drug effects; S-111-S-WB; Spermatogenesis - drug effects; Surface-Active Agents - administration & dosage; Surface-Active Agents - metabolism; Surface-Active Agents - toxicity; Teratology. Teratogens; Time Factors; Toxicity Tests, Chronic; Toxicology; Reproduction; S-111-S-WB; Perfluoronanoate; Rat; Multi-generation; Perfluoroalkyl acid; Reproduction diseases; Organic perhalocompound; Toxicity; Rodentia; Vertebrata; Mammalia; Animal; Fluorine Organic compounds
• ISSN: 0890-6238; 1873-1708
• DOI: 10.1016/j.reprotox.2007.10.002

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 F
0 and F
1 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 F
1 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 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 0.025
mg/(kg
day) was considered to be the NOAEL for neonatal toxicity based on higher liver weights in the F
1 and F
2 pups at 0.125
mg/(kg
day) and higher.