Cited by 564Per- and polyfluoroalkyl substances researchToxic Organic Pollutants ImpactImmunotoxicology and immune responses

Subchronic Toxicity Studies on Perfluorooctanesulfonate Potassium Salt in Cynomolgus Monkeys

Seacat, A. M.·2002·Toxicological Sciences

Abstract

This study was conducted to determine the earliest measurable response of primates to low-level perfluorooctanesulfonate (PFOS) exposure and to provide information to reduce uncertainty in human health risk assessment. Groups of male and female monkeys received 0, 0.03, 0.15, or 0.75 mg/kg/day potassium PFOS orally for 182 days. Recovery animals from each group, except the 0.03 mg/kg/day dose group, were monitored for one year after treatment. Significant adverse effects occurred only in the 0.75 mg/kg/day dose group and included compound-related mortality in 2 of 6 male monkeys, decreased body weights, increased liver weights, lowered serum total cholesterol, lowered triiodothyronine concentrations (without evidence of hypothyroidism), and lowered estradiol levels. Decreased serum total cholesterol occurred in the 0.75 mg/kg/day dose group at serum PFOS levels > 100 ppm. Hepatocellular hypertrophy and lipid vacuolation were present at term in the 0.75 mg/kg/day dose group. No peroxisomal (palmitoyl CoA oxidase) or cell proliferation (proliferating cell nuclear antigen immunohistochemistry) was detected. Complete reversal of clinical and hepatic effects and significant decreases in serum and liver PFOS occurred within 211 days posttreatment. Liver-to-serum PFOS ratios were comparable in all dose groups, with a range of 1:1 to 2:1. Serum concentrations associated with no adverse effects (0.15 mg/kg/day) were 82.6 +/- 25.2 ppm for males and 66.8 +/- 10.8 ppm for females. Comparison of serum PFOS concentrations associated with no adverse effect in this study to those reported in human blood samples (0.028 +/- 0.014 ppm) indicated an adequate margin of safety.

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Crossref · 10.1093/toxsci/68.1.249

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Authors
Seacat, A. M.
Affiliations
3M (United States) (US)
Corresponding author
Seacat, A. M.
Venue
Toxicological Sciences
Published
2002-07-01
Volume
68
Issue
1
Pages
249-264
ISSN
1096-0929 (ISSN-L)
OpenAlex
W2127286660
Cited by
564
References
36
Citations by year
2026: 6 · 2025: 25 · 2024: 16 · 2023: 18 · 2022: 12 · 2021: 25 · 2020: 27 · 2019: 23 · 2018: 31 · 2017: 17 · 2016: 25 · 2015: 31 · 2014: 24 · 2013: 24 · 2012: 35
FWCI
12.64
Type
journal article
Language
en
Open access
closed
Locations
  • Toxicological Sciences (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Physical Sciences › Environmental Science › Environmental Chemistry › Per- and polyfluoroalkyl substances research
  • Physical Sciences › Environmental Science › Health, Toxicology and Mutagenesis › Toxic Organic Pollutants Impact
  • Life Sciences › Immunology and Microbiology › Immunology › Immunotoxicology and immune responses
Keywords
PFOS, subchronic toxicity, Macaca fascicularis, hepatocyte hypertrophy, total cholesterol, triiodothyronine, estradiol, recovery after treatment, safety margin, human health risk assessment, peroxisomal function, cell proliferation
MeSH terms
Administration, Oral, Animals, Body Weight, Cell Division, Dose-Response Relationship, Drug, Female, Fluorocarbons, Immunohistochemistry, Liver, Longevity, Macaca fascicularis, Male, Organ Size, Remission Induction, Alkanesulfonic Acids, Toxicity Tests, Proliferating Cell Nuclear Antigen, Peroxisomes

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