Repeated dose and reproductive/developmental toxicity of perfluoroundecanoic acid in rats

Abstract

Perfluoroalkyl acids (PFAAs) are environmental contaminants that have received attention because of their possible effects on wildlife and human health. In order to obtain initial risk information on the toxicity of perfluoroundecanoic acid (PFUA), we conducted a combined repeated dose toxicity study with the reproduction/developmental toxicity screening test (OECD test guideline 422). PFUA was administered by gavage to rats at 0 (vehicle: corn oil), 0.1, 0.3 or 1.0 mg/kg/day. At 1.0 mg/kg/day, body weight gain was inhibited in both sexes, and there was a decrease in fibrinogen in both sexes and shortening of the activated partial thromboplastin time in males. An increase in blood urea nitrogen and a decrease in total protein in both sexes and increases in alkaline phosphatase and alanine transaminase and a decrease in albumin in males were observed at 1.0 mg/kg/day. Liver weight was increased in males at 0.3 mg/kg/day and above and in females at 1.0 mg/kg/day, and this change was observed after a recovery period. In both sexes, centrilobular hypertrophy of hepatocytes was observed at 0.3 mg/kg/day and above and focal necrosis was observed at 1.0 mg/kg/day. In reproductive/developmental toxicity, body weight of pups at birth was lowered and body weight gain at 4 days after birth was inhibited at 1.0 mg/kg/day, while no dose-related changes were found in the other parameters. Based on these findings, the no observed adverse effect levels (NOAELs) for the repeated dose and reproductive/developmental toxicity were considered to be 0.1 mg/kg/day and 0.3 mg/kg/day, respectively.