Toxicological evaluation of ammonium perfluorobutyrate in rats: twenty-eight-day and ninety-day oral gavage studies

Reprod Toxicol. 2012 Jul;33(4):513-530. doi: 10.1016/j.reprotox.2011.08.004. Epub 2011 Aug 19.

Abstract

Sequential 28-day and 90-day oral toxicity studies were performed in male and female rats with ammonium perfluorobutyrate (NH(4)(+)PFBA) at doses up to 150 and 30mg/kg-d, respectively. Ammonium perfluorooctanoate was used as a comparator at a dose of 30mg/kg-d in the 28-day study. Female rats were unaffected by NH(4)(+)PFBA. Effects in males included: increased liver weight, slight to minimal hepatocellular hypertrophy; decreased serum total cholesterol; and reduced serum thyroxin with no change in serum thyrotropin. During recovery, liver weight, histological, and cholesterol effects were resolved. Results of RT-qPCR were consistent with increased transcriptional expression of the xenosensor nuclear receptors PPARα and CAR as well as the thyroid receptor, and decreased expression of Cyp1A1 (Ah receptor-regulated). No observable adverse effect levels (NOAELs) were 6 and >150mg/kg-d for male and female rats in the 28-day study and 6 and >30mg/kg-d in the 90-dat study, respectively.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Administration, Oral
  • Animals
  • Body Weight / drug effects
  • Cholesterol / blood
  • Dose-Response Relationship, Drug
  • Female
  • Fluorocarbons / blood
  • Fluorocarbons / pharmacokinetics
  • Fluorocarbons / toxicity*
  • Gene Expression / drug effects
  • Liver / drug effects
  • Liver / metabolism
  • Liver / pathology
  • Male
  • Organ Size / drug effects
  • RNA, Messenger / genetics
  • Rats
  • Rats, Sprague-Dawley
  • Thyroid Gland / drug effects
  • Thyroid Gland / metabolism
  • Thyroid Gland / pathology
  • Thyroid Hormones / blood
  • Toxicity Tests, Subchronic / methods*
  • Water Pollutants, Chemical / blood
  • Water Pollutants, Chemical / pharmacokinetics
  • Water Pollutants, Chemical / toxicity*

Substances

  • Fluorocarbons
  • RNA, Messenger
  • Thyroid Hormones
  • Water Pollutants, Chemical
  • perfluorobutyric acid
  • Cholesterol