Journal Article

Prenatal Perfluorooctanoic Acid Exposure in CD-1 Mice: Low-Dose Developmental Effects and Internal Dosimetry

Madisa B. Macon, LaTonya R. Villanueva, Katoria Tatum-Gibbs, Robert D. Zehr, Mark J. Strynar, Jason P. Stanko, Sally S. White, Laurence Helfant and Suzanne E. Fenton

in Toxicological Sciences

Volume 122, issue 1, pages 134-145
Published in print July 2011 | ISSN: 1096-6080
Published online April 2011 | e-ISSN: 1096-0929 | DOI: http://dx.doi.org/10.1093/toxsci/kfr076
Prenatal Perfluorooctanoic Acid Exposure in CD-1 Mice: Low-Dose Developmental Effects and Internal Dosimetry

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Perfluorooctanoic acid (PFOA) is an environmental contaminant that causes adverse developmental effects in laboratory animals. To investigate the low-dose effects of PFOA on offspring, timed-pregnant CD-1 mice were gavage dosed with PFOA for all or half of gestation. In the full-gestation study, mice were administered 0, 0.3, 1.0, and 3.0 mg PFOA/kg body weight (BW)/day from gestation days (GD) 1–17. In the late-gestation study, mice were administered 0, 0.01, 0.1, and 1.0 mg PFOA/kg BW/day from GD 10–17. Exposure to PFOA significantly (p < 0.05) increased offspring relative liver weights in all treatment groups in the full-gestation study and in the 1.0 mg PFOA/kg group in the late-gestation study. In both studies, the offspring of all PFOA-treated dams exhibited significantly stunted mammary epithelial growth as assessed by developmental scoring. At postnatal day 21, mammary glands from the 1.0 mg/kg GD 10–17 group had significantly less longitudinal epithelial growth and fewer terminal end buds compared with controls (p < 0.05). Evaluation of internal dosimetry in offspring revealed that PFOA concentrations remained elevated in liver and serum for up to 6 weeks and that brain concentrations were low and undetectable after 4 weeks. These data indicate that PFOA-induced effects on mammary tissue (1) occur at lower doses than effects on liver weight in CD-1 mice, an observation that may be strain specific, and (2) persist until 12 weeks of age following full-gestational exposure. Due to the low-dose sensitivity of mammary glands to PFOA in CD-1 mice, a no observable adverse effect level for mammary developmental delays was not identified in these studies.

Keywords: perfluorooctanoic acid; mammary gland; development; prenatal; dosimetry

Journal Article.  8601 words.  Illustrated.

Subjects: Medical Toxicology ; Toxicology (Non-medical)

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