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Cited by 445Per- and polyfluoroalkyl substances researchToxic Organic Pollutants ImpactPharmacological Effects and Toxicity Studies

Exposure to Perfluorooctane Sulfonate during Pregnancy in Rat and Mouse. I: Maternal and Prenatal Evaluations

Thibodeaux, J. R., Hanson, R. G., Rogers, J. M., Grey, B. E., Barbee, B. D., Richards, J. H., Butenhoff, J. L., Stevenson, L. A. +1 more·2003·Toxicological Sciences
DOI 10.1093/toxsci/kfg121
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Abstract

The maternal and developmental toxicities of perfluorooctane sulfonate (PFOS, C8F17SO3-) were evaluated in the rat and mouse. PFOS is an environmentally persistent compound used as a surfactant and occurs as a degradation product of both perfluorooctane sulfonyl fluoride and substituted perfluorooctane sulfonamido components found in many commercial and consumer applications. Pregnant Sprague-Dawley rats were given 1, 2, 3, 5, or 10 mg/kg PFOS daily by gavage from gestational day (GD) 2 to GD 20; CD-1 mice were similarly treated with 1, 5, 10, 15, and 20 mg/kg PFOS from GD 1 to GD 17. Controls received 0.5% Tween-20 vehicle (1 ml/kg for rats and 10 ml/kg for mice). Maternal weight gain, food and water consumption, and serum chemistry were monitored. Rats were euthanized on GD 21 and mice on GD 18. PFOS levels in maternal serum and in maternal and fetal livers were determined. Maternal weight gains in both species were suppressed by PFOS in a dose-dependent manner, likely attributed to reduced food and water intake. Serum PFOS levels increased with dosage, and liver levels were approximately fourfold higher than serum. Serum thyroxine (T4) and triiodothyronine (T3) in the PFOS-treated rat dams were significantly reduced as early as one week after chemical exposure, although no feedback response of thyroid-stimulating hormone (TSH) was observed. A similar pattern of reduction in T4 was also seen in the pregnant mice. Maternal serum triglycerides were significantly reduced, particularly in the high-dose groups, although cholesterol levels were not affected. In the mouse dams, PFOS produced a marked enlargement of the liver at 10 mg/kg and higher dosages. In the rat fetuses, PFOS was detected in the liver but at levels nearly half of those in the maternal counterparts, regardless of administered doses. In both rodent species, PFOS did not alter the numbers of implantations or live fetuses at term, although small deficits in fetal weight were noted in the rat. A host of birth defects, including cleft palate, anasarca, ventricular septal defect, and enlargement of the right atrium, were seen in both rats and mice, primarily in the 10 and 20 mg/kg dosage groups, respectively. Our results demonstrate both maternal and developmental toxicity of PFOS in the rat and mouse.

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Authors
Thibodeaux, J. R., Hanson, R. G., Rogers, J. M., Grey, B. E., Barbee, B. D., Richards, J. H., Butenhoff, J. L., Stevenson, L. A., & Lau, C.
Affiliations
Environmental Protection Agency (US)
ORCID
Rogers, J. M.
Venue
Toxicological Sciences
Publisher
Oxford University Press (OUP)
Published
2003-05-28
Volume
74
Issue
2
Pages
369-381
ISSN
  • 1096-0929 (ISSN-L)
  • 1096-6080
DOI
10.1093/toxsci/kfg121
OpenAlex
W2098379965
Cited by
445
References
49
Citations by year
2026: 8 · 2025: 13 · 2024: 14 · 2023: 15 · 2022: 19 · 2021: 16 · 2020: 26 · 2019: 26 · 2018: 15 · 2017: 14 · 2016: 21 · 2015: 16 · 2014: 17 · 2013: 17 · 2012: 17
FWCI
16.18
Type
journal article
Language
en
Open access
closed
Locations
  • Toxicological Sciences (publishedVersion)
  • PubMed (publishedVersion)
Funders
U.S. Environmental Protection Agency
Topics
  • Physical Sciences › Environmental Science › Environmental Chemistry › Per- and polyfluoroalkyl substances research
  • Physical Sciences › Environmental Science › Health, Toxicology and Mutagenesis › Toxic Organic Pollutants Impact
  • Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Pharmacological Effects and Toxicity Studies
Keywords
PFOS, prenatal toxicity, developmental toxicity, maternal toxicity, thyroid function, thyroxine, serum triglycerides, liver hypertrophy, fetal weight, congenital malformations, cleft palate, ventricular septal defect, anasarca, atrial enlargement, perfluorinated compounds, prenatal exposure, tissue distribution, mice
MeSH terms
Abnormalities, Drug-Induced, Administration, Oral, Animals, Body Weight, Dose-Response Relationship, Drug, Drinking, Eating, Female, Fetus, Fluorocarbons, Liver, Mice, Inbred Strains, Organ Size, Pregnancy, Reproduction, Teratogens, Thyroxine, Triglycerides, Triiodothyronine, Rats, Sprague-Dawley, Alkanesulfonic Acids, Maternal Exposure, Fetal Weight, Mice, Rats

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