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Cited by 549Per- and polyfluoroalkyl substances researchToxic Organic Pollutants ImpactPharmacological Effects and Toxicity Studies

Exposure to Perfluorooctane Sulfonate during Pregnancy in Rat and Mouse. II: Postnatal Evaluation

Lau, C., Thibodeaux, J. R., Hanson, R. G., Rogers, J. M., Grey, B. E., Stanton, M. E., Butenhoff, J. L., Stevenson, L. A.·2003·Toxicological Sciences
DOI 10.1093/toxsci/kfg122
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Abstract

The postnatal effects of in utero exposure to perfluorooctane sulfonate (PFOS, C8F17SO3-) were evaluated in the rat and mouse. Pregnant Sprague-Dawley rats were given 1, 2, 3, 5, or 10 mg/kg PFOS daily by gavage from gestation day (GD) 2 to GD 21; pregnant CD-1 mice were treated with 1, 5, 10, 15, and 20 mg/kg PFOS from GD 1 to GD 18. Controls received 0.5% Tween-20 vehicle (1 ml/kg for rats and 10 ml/kg for mice). At parturition, newborns were observed for clinical signs and survival. All animals were born alive and initially appeared to be active. In the highest dosage groups (10 mg/kg for rat and 20 mg/kg for mouse), the neonates became pale, inactive, and moribund within 30-60 min, and all died soon afterward. In the 5 mg/kg (rat) and 15 mg/kg (mouse) dosage groups, the neonates also became moribund but survived for a longer period of time (8-12 h). Over 95% of these animals died within 24 h. Approximately 50% of offspring died at 3 mg/kg for rat and 10 mg/kg for mouse. Cross-fostering the PFOS-exposed rat neonates (5 mg/kg) to control nursing dams failed to improve survival. Serum concentrations of PFOS in newborn rats mirrored the maternal administered dosage and were similar to those in the maternal circulation at GD 21; PFOS levels in the surviving neonates declined in the ensuing days. Small but significant and persistent growth lags were detected in surviving rat and mouse pups exposed to PFOS prenatally, and slight delays in eye opening were noted. Significant increases in liver weight were observed in the PFOS-exposed mouse pups. Serum thyroxine levels were suppressed in the PFOS-treated rat pups, although triiodothyronine and thyroid-stimulating hormone [TSH] levels were not altered. Choline acetyltransferase activity (an enzyme that is sensitive to thyroid status) in the prefrontal cortex of rat pups exposed to PFOS prenatally was slightly reduced, but activity in the hippocampus was not affected. Development of learning, determined by T-maze delayed alternation in weanling rats, was not affected by PFOS exposure. These results indicate that in utero exposure to PFOS severely compromised postnatal survival of neonatal rats and mice, and caused delays in growth and development that were accompanied by hypothyroxinemia in the surviving rat pups.

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  • In Lau et al. (2003), only two male and female pups in each treatment group were assessed in the delayed alternation task, so caution is warranted due to insufficient statistical power, which may contribute to inconsistent findings across studies.

    “It is important to note that in this study, only two male and female pups in each treatment group were assessed in the delayed alternation task. Therefore, caution is warranted due to insufficient statistical power, which may contribute to inconsistent findings across studies.”

    From A Critical Review and Meta-Analysis of Impacts of Per- and Polyfluorinated Substances on the Brain and Behavior (2022) · cites this paper as Lau et al., 2003

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  • No significant changes in learning and memory in a T maze delayed alternation task were reported in male and female SD rats at PND 22 after in utero exposure to PFOS.

    “In contrast, no significant changes in learning and memory in a T maze delayed alternation task were reported in male and female SD rats at PND 22 after in utero exposure to PFOS (Lau et al., 2003).”

    From A Critical Review and Meta-Analysis of Impacts of Per- and Polyfluorinated Substances on the Brain and Behavior (2022) · cites this paper as Lau et al., 2003

    The Rat results report no overall significant difference in T-maze learning and memory between prenatally PFOS-exposed pups and controls; the T-Maze section says male and female results were pooled. However, the T-Maze methods place acclimation on PD 22 and delayed-alternation testing on PD 23, not PND 22. The supplied passages do not give page numbers. (LLM, conf=0.91)

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Research works printed but not linked: 3

  1. Cooper, R. L., and Goldman, J. M. (1999). Vaginal cytology. In An Evaluation and Interpretation of Reproductive Endpoints for Human Health Risk As- sessment (G. Daston and C. Kimmel, Eds.). pp. 42-56, ILSI Press: Wash- ington.
  2. Lau, C., and Kavlock, R. J. (1994). Functional toxicity in the developing heart, lung, and kidney. In Developmental Toxicology, 2nd ed. (C. A. Kimmel, and J. Buelke-Sam, Eds.), pp. 119 -188. Raven Press, New York.
  3. Legrand, J. (1986). Thyroid hormone effects on growth and development. In Thyroid Hormone Metabolism (G. Hennemann, Ed.), pp. 503-534.

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Authors
Lau, C., Thibodeaux, J. R., Hanson, R. G., Rogers, J. M., Grey, B. E., Stanton, M. E., Butenhoff, J. L., & Stevenson, L. A.
Affiliations
  • Environmental Protection Agency (US)
  • University of Delaware (US)
ORCID
Venue
Toxicological Sciences
Publisher
Oxford University Press (OUP)
Published
2003-05-28
Volume
74
Issue
2
Pages
382-392
ISSN
  • 1096-0929 (ISSN-L)
  • 1096-6080
DOI
10.1093/toxsci/kfg122
OpenAlex
W2100493261
Cited by
549
References
46
Citations by year
2026: 12 · 2025: 18 · 2024: 14 · 2023: 26 · 2022: 22 · 2021: 20 · 2020: 34 · 2019: 23 · 2018: 21 · 2017: 16 · 2016: 25 · 2015: 18 · 2014: 35 · 2013: 28 · 2012: 28
FWCI
13.36
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 exposure, postnatal effects, neonatal lethality, growth retardation, thyroid function, thyroxine, choline acetyltransferase, learning and memory, liver weight, developmental neurotoxicity, perfluorinated compounds, developmental toxicity, rats, mice, cross-fostering
MeSH terms
Administration, Oral, Animals, Animals, Newborn, Body Weight, Choline O-Acetyltransferase, Dose-Response Relationship, Drug, Female, Fluorocarbons, Liver, Longevity, Mice, Inbred Strains, Organ Size, Pregnancy, Prenatal Exposure Delayed Effects, Teratogens, Thyroxine, Rats, Sprague-Dawley, Prefrontal Cortex, Alkanesulfonic Acids, Maternal Exposure, Mice, Rats

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