Fundamental Toxicological Sciences

Paper Details

Fundamental Toxicological Sciences
Vol. 2 No. 4 September 28, 2015 p.177-190
Original Article
Repeated dose and reproductive/developmental toxicity of long-chain perfluoroalkyl carboxylic acids in rats: perfluorohexadecanoic acid and perfluorotetradecanoic acid
  • Akihiko Hirose (Division of Risk Assessment, Biological Safety Research Center, National Institute of Health Sciences /
Mutsuko Hirata-Koizumi 1) , Sakiko Fujii 2) , Kato Hina 1) , Mariko Matsumoto 1) , Mika Takahashi 1) , Atsushi Ono 1) , Akihiko Hirose 1)
1) Division of Risk Assessment, Biological Safety Research Center, National Institute of Health Sciences , 2) Safety Research Institute for Chemical Compounds Co., Ltd.
Keywords: Perfluoroalkyl carboxylic acids, Perfluorotetradecanoic acid, Perfluorohexadecanoic acid, Repeated dose toxicity, Reproductive and developmental toxicity, Rat

Perfluoroalkyl carboxylic acids (PFCAs) are global environmental contaminants that are the cause of concern due to their possible effects on wildlife and human health. Since few studies have investigated the toxicity of long-chain PFCAs, we have performed combined repeated dose toxicity studies with the reproduction/developmental toxicity screening tests. We previously examined perfluoroundecanoic acid (C11), perfluorododecanoic acid (C12), and perfluorooctadecanoic acid (C18). We herein reported our results for perfluorotetradecanoic acid (PFTeDA; C14) and perfluorohexadecanoic acid (PFHxDA: C16). Male and female rats were administered PFTeDA at 1, 3 or 10 mg/kg/day or PFHxDA at 4, 20 or 100 mg/kg/day by gavage, and each female was then mated with a male in the same dose group after 14 days. Males were dosed for a total of 42 days and females were dosed throughout the gestation period until day 5 after parturition. PFTeDA and PFHxDA caused hepatocyte hypertrophy and/or fatty changes in the liver at the middle and high doses. PFTeDA also induced follicular cell hypertrophy in the thyroid at the middle and high doses. The only reproductive/developmental effect observed was an inhibited postnatal body weight gain in pups in the 10 mg/kg/day PFTeDA group. Based on these results, the NOAELs for the repeated dose and reproductive/developmental toxicity were concluded to be 1 and 3 mg/kg/day for PFTeDA and 4 and 100 mg/kg/day for PFHxDA, respectively. Our current and previous results indicate that the toxicity of PFCAs decreases with increases in the carbon chain length from 12 to 18.