Neuroendocrine Effects of Perfluorooctane Sulfonate in Rats
Open accessAbstract
Perfluorooctane sulfonate (PFOS) is a degradation product of sulfonyl-based fluorochemicals that are used extensively in industrial and household applications. Humans and wildlife are exposed to this class of compounds from several sources. Toxicity tests in rodents have raised concerns about potential developmental, reproductive, and systemic effects of PFOS. However, the effect of PFOS on the neuroendocrine system has not been investigated thus far. In this study, adult female rats were injected intraperitoneally with 0, 1, or 10 mg PFOS/kg body weight (BW) for 2 weeks. Food and water intake, BW, and estrous cycles were monitored daily. At the end of treatment, PFOS levels in tissues were measured by high-performance liquid chromatography (HPLC) interfaced with electrospray mass spectrometry. Changes in brain monoamines were measured by HPLC with electrochemical detection, and serum corticosterone and leptin were monitored using radioimmunoassay. Treatment with PFOS produced a dose-dependent accumulation of this chemical in various body tissues, including the brain. PFOS exposure decreased food intake and BW in a dose-dependent manner. Treatment with PFOS affected estrous cyclicity and increased serum corticosterone levels while decreasing serum leptin concentrations. PFOS treatment also increased norepinephrine concentrations in the paraventricular nucleus of the hypothalamus. These results indicate that exposure to PFOS can affect the neuroendocrine system in rats.
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PFOS accumulation in the hypothalamus was associated with increased concentrations of serum leptin in Austin et al. (2003).
“Austin et al. (2003) found that PFOS accumulation in the hypothalamus was associated with increased concentrations of serum leptin”
From A Critical Review and Meta-Analysis of Impacts of Per- and Polyfluorinated Substances on the Brain and Behavior (2022) · cites this paper as Austin et al., 2003
The “Accumulation of PFOS in tissues” section reports greater hypothalamic accumulation in rats given the high dose. But the “Serum leptin” section reports that the high dose markedly decreased serum leptin, from 10.5 ± 1.5 ng/mL in controls to 1.5 ± 0.5 ng/mL—not increased it. (LLM, conf=0.95)
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Experimental — accuracy not yet measuredAustin et al. (2003) reported the highest PFOS concentration in the hypothalamus (15,706 ng/g) and the lowest in the cortex (4,487 ng/g) after exposing female rats to 10 mg/kg/day via intraperitoneal injection for 2 weeks.
“Austin et al. (2003) reported the highest concentration of PFOS in the hypothalamus (15,706 ng/g), and the lowest concentration in the cortex (4,487 ng/g), after exposing female rats to 10 mg/kg/day via intraperitoneal injection for 2 weeks.”
From A Critical Review and Meta-Analysis of Impacts of Per- and Polyfluorinated Substances on the Brain and Behavior (2022) · cites this paper as Austin et al., 2003
The Animals section reports daily intraperitoneal injections of 10 mg/kg PFOS in adult female rats for 14 days. The Accumulation of PFOS in tissues section says the hypothalamus had the greatest accumulation among brain regions at the higher dose, but our copy does not show the claimed 15,706 or 4,487 ng/g values or establish that the cortex was lowest; the extracted Table 1 contains only its header. (LLM, conf=0.86)
Experimental — accuracy not yet measuredStudies in a rodent model and human brain samples showed a similar pattern of brain distribution for PFOS, PFHxS, and PFHxA as was seen in polar bears.
“Studies in a rodent model and human brain samples showed a similar pattern of distribution in the brain for PFOS, perfluorohexanesulfonic acid (PFHxS), and perfluorohexanoic acid (PFHxA) as was seen in the polar bears.”
From A Critical Review and Meta-Analysis of Impacts of Per- and Polyfluorinated Substances on the Brain and Behavior (2022) · cites this paper as Austin et al., 2003
The ‘Accumulation of PFOS in tissues’ section (page unavailable) reports PFOS in several brain regions of exposed rats, with greater accumulation in the hypothalamus at the higher dose. The paper does not report brain distributions of PFHxS or PFHxA, examine human brain samples, or compare its findings with polar bears. (LLM, conf=0.88)
Experimental — accuracy not yet measuredBoth rodent and human brain studies reported brain-region-specific accumulation of PFAS, with increased exposure in the hypothalamus and decreased exposure in the cortex.
“both studies reported brain-region-specific accumulation, demonstrating increased exposure in the hypothalamus and decreased exposure in the cortex (Austin et al., 2003; Di Nisio et al., 2022).”
From A Critical Review and Meta-Analysis of Impacts of Per- and Polyfluorinated Substances on the Brain and Behavior (2022) · cites this paper as Austin et al., 2003
The 'Accumulation of PFOS in tissues' section reports brain-region-specific accumulation in rats: at the higher dose, hypothalamic PFOS was at least three times higher than in other brain areas. It does not specifically report decreased accumulation in the cortex; it also studies rats, not humans. This verdict addresses Austin et al. (2003) only, not the other citation. (LLM, conf=0.87)
Experimental — accuracy not yet measuredExposure to PFAS, primarily PFOS and PFOA, can lead to decreased food consumption and decreased weight gain in adult animals.
“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 Austin et al., 2003
The Abstract reports that PFOS exposure decreased food intake and body weight in adult female rats, and the Food intake section reports a significant decrease at the high dose. The paper did not test PFOA; it says only that PFOA is thought to have effects similar to PFOS. Thus it supports the claim for PFOS in adult rats, but not for PFOA. (LLM, conf=0.86)
Experimental — accuracy not yet measured
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References 24 · Cited by 347
Research works printed but not linked: 2
- Petrusz P, Merchenthaler I. 1992. The corticotropin-releasing factor system. In: Neuroendocrinology (Nemeroff CB, ed). Boca Raton, FL: CRC Press, 129-184.
- Ramirez VD, Feder HH, Sawyer CH. 1984. The role of brain cate- cholamines in the regulation of LH secretion: a critical inquiry. In: Frontiers in Neuroendocrinology, vol. 8 (Martini L, Ganong WF, eds). New York: Raven Press, 27-84.
- Authors
- Austin, M. E., Kasturi, B. S., Barber, M., Kannan, K., MohanKumar, P. S., & MohanKumar, S. M. J.
- Affiliations
- Michigan State University (US)
- Venue
- Environmental Health Perspectives
- Publisher
- American Chemical Society (ACS)
- Published
- 2003-09-01
- Volume
- 111
- Issue
- 12
- Pages
- 1485-1489
- ISSN
- 0091-6765 (ISSN-L)
- 1552-9924
- PMC
- PMC1241651
- OpenAlex
- W2022879961
- Cited by
- 347
- References
- 24
- Citations by year
- 2026: 8 · 2025: 19 · 2024: 20 · 2023: 7 · 2022: 17 · 2021: 11 · 2020: 15 · 2019: 11 · 2018: 17 · 2017: 13 · 2016: 14 · 2015: 24 · 2014: 17 · 2013: 7 · 2012: 17
- FWCI
- 7.25
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- public-domain
- creativecommons.org/licenses/by/4.0/ (vor, 5233 d)
- Locations
- Environmental Health Perspectives (publishedVersion, public-domain)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Michigan State University
- National Institutes of Health
- College of Engineering, Michigan State University
- National Institute on Aging (R01AG005980, AG05980)
- Topics
- Physical Sciences › Environmental Science › Environmental Chemistry › Per- and polyfluoroalkyl substances research
- Physical Sciences › Environmental Science › Health, Toxicology and Mutagenesis › Toxic Organic Pollutants Impact
- Physical Sciences › Environmental Science › Health, Toxicology and Mutagenesis › Effects and risks of endocrine disrupting chemicals
- Keywords
- PFOS, neuroendocrine toxicity, fluorochemicals, brain monoamines, norepinephrine, paraventricular nucleus, corticosterone, leptin, estrous cyclicity, dietary intake, tissue accumulation, dose-dependent effects
- MeSH terms
- Animals, Brain Chemistry, Corticosterone, Dose-Response Relationship, Drug, Environmental Pollutants, Feeding Behavior, Female, Fluorocarbons, Injections, Intraperitoneal, Neurosecretory Systems, Norepinephrine, Tissue Distribution, Biogenic Monoamines, Rats, Sprague-Dawley, Alkanesulfonic Acids, Leptin, Rats
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