Evaluation of Serum Lipid, Thyroid, and Hepatic Clinical Chemistries in Association With Serum Perfluorooctanesulfonate (PFOS) in Cynomolgus Monkeys After Oral Dosing With Potassium PFOS

Toxicol Sci. 2017 Apr 1;156(2):387-401. doi: 10.1093/toxsci/kfw267.

Abstract

An oral dose study with perfluorooctanesulfonate (PFOS) was undertaken to identify potential associations between serum PFOS and changes in serum clinical chemistry parameters in purpose-bred young adult cynomolgus monkeys (Macaca fascicularis). In this study, control group (n = 6/sex) was sham-dosed with vehicle (0.5% Tween 20 and 5% ethanol in water), low-dose group (n = 6/sex) received 1 single K+PFOS dose (9 mg/kg), and high-dose group (n = 4-6/sex) received 3 separate K+ PFOS doses (11-17.2 mg/kg). Monkeys were given routine checkups and observed carefully for health problems on a daily basis. Scheduled blood samples were drawn from all monkeys prior to, during, and after K+PFOS administration for up to 1 year and they were analyzed for PFOS concentrations and clinical chemistry markers for coagulation, lipids, hepatic, renal, electrolytes, and thyroid-related hormones. No mortality occurred during the study. All the monkeys were healthy, gained weight, and were released back to the colony at the end of the study. The highest serum PFOS achieved was approximately 165 μg/ml. When compared with time-matched controls, administration of K+PFOS to monkeys did not result in any toxicologically meaningful or clinically relevant changes in serum clinical measurements for coagulation, lipids, hepatic, renal, electrolytes, and thyroid-related hormones. A slight reduction in serum cholesterol (primarily the high-density lipoprotein fraction), although not toxicologically significant, was observed. The corresponding lower-bound fifth percentile benchmark concentrations (BMCL1sd) were 74 and 76 μg/ml for male and female monkeys, respectively. Compared to the 2013-2014 geometric mean serum PFOS level of 4.99 ng/ml (0.00499 μg/ml) in US general population reported by CDC NHANES, this represents 4 orders of magnitude for margin of exposure.

Keywords: HDL; PFOS; cholesterol; monkeys; perfluorooctanesulfonate; thyroid..

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkanesulfonic Acids / blood*
  • Alkanesulfonic Acids / toxicity*
  • Animals
  • Blood Coagulation / drug effects
  • Body Weight / drug effects
  • Cholesterol, HDL / blood
  • Dose-Response Relationship, Drug
  • Female
  • Fluorocarbons / blood*
  • Fluorocarbons / toxicity*
  • Lipids / blood*
  • Liver / drug effects*
  • Liver / metabolism
  • Macaca fascicularis
  • Male
  • Thyroid Hormones / blood*

Substances

  • Alkanesulfonic Acids
  • Cholesterol, HDL
  • Fluorocarbons
  • Lipids
  • Thyroid Hormones
  • perfluorooctane sulfonic acid