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Subchronic Toxicity Studies on Perfluorooctanesulfonate Potassium Salt in Cynomolgus Monkeys
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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“exposure to PFAS, primarily PFOS and PFOA, can lead to decreased food consumption and decreased weight gain in adult animals”
From A Critical Review and Meta-Analysis of Impacts of Per- and Polyfluorinated Substances on the Brain and Behavior (2022) · cites this paper as Seacat, 2002
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Perfluoroalkyl Acids: A Review of Monitoring and Toxicological Findings
Lau, C., Anitole, K., Hodes, C., Lai, D., Pfahles-Hutchens, A., & Seed, J. (2007) · Toxicological Sciences · doi:10.1093/toxsci/kfm128 · Cited by 2,620
Olsen, G. W., Burris, J. M., Ehresman, D. J., Froehlich, J. W., Seacat, A. M., Butenhoff, J. L., & Zobel, L. R. (2007) · Environmental Health Perspectives · doi:10.1289/ehp.10009 · Cited by 2,049
Self-citationThe Developmental Toxicity of Perfluoroalkyl Acids and Their Derivatives
Lau, C., Butenhoff, J. L., & Rogers, J. M. (2004) · Toxicology and Applied Pharmacology · doi:10.1016/j.taap.2003.11.031 · Cited by 867
Accumulation of perfluorinated alkyl substances (PFAS) in agricultural plants: A review
Ghisi, R., Vamerali, T., & Manzetti, S. (2019) · Environmental Research · doi:10.1016/j.envres.2018.10.023 · Cited by 705
Epidemiologic Evidence on the Health Effects of Perfluorooctanoic Acid (PFOA)
Steenland, K., Fletcher, T., & Savitz, D. A. (2010) · Environmental Health Perspectives · doi:10.1289/ehp.0901827 · Cited by 660
Metadata
- Authors
- Seacat, A. M.
- Affiliations
- 3M (United States) (US)
- Corresponding author
- Seacat, A. M.
- Venue
- Toxicological Sciences
- Publisher
- Oxford University Press (OUP)
- 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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