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Advance Publication

Environ Health Perspect; DOI:10.1289/ehp.1307449

Dose-Dependent Incidence of Hepatic Tumors in Adult Mice following Perinatal Exposure to Bisphenol A

Caren Weinhouse,1* Olivia S. Anderson,1* Ingrid L. Bergin,2 David J. Vandenbergh,3,4 Joseph P. Gyekis,3 Marc A. Dingman,3,4 Jingyun Yang,5 and Dana C. Dolinoy
Author Affiliations close
1Department of Environmental Health Sciences and 2Unit for Laboratory Animal Medicine, University of Michigan, Ann Arbor, Michigan, USA; 3Department of Biobehavioral Health, 4Neuroscience Program, and 5Methodology Center, Pennsylvania State University, University Park, Pennsylvania, USA. *These authors contributed equally to this work.
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This EHP Advance Publication article has been peer-reviewed, revised, and accepted for publication. EHP Advance Publication articles are completely citable using the DOI number assigned to the article. This document will be replaced with the copyedited and formatted version as soon as it is available. Through the DOI number used in the citation, you will be able to access this document at each stage of the publication process.

Citation: Weinhouse C, Anderson OS, Bergin IL, Vandenbergh DJ, Gyekis JP, Dingman MA, Yang J, Dolinoy DC. Dose-Dependent Incidence of Hepatic Tumors in Adult Mice following Perinatal Exposure to Bisphenol A. Environ Health Perspect; http://dx.doi.org/10.1289/ehp.1307449.

Received: 31 July 2013
Accepted: 17 January 2014
Advance Publication: 3 February 2014

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Abstract

Background: Bisphenol A (BPA) is a high production-volume chemical with hormone-like properties that has been implicated as a potential carcinogen. Early life exposure has been linked to increased risk for precancerous lesions in mammary and prostate glands and the uterus, but no prior study has shown a significant association between BPA exposure and cancer development.

Objective: We explored the effects of exposure to BPA during gestation and lactation on adult incidence of hepatic tumors in mice.

Methods: Isogenic mice were perinatally exposed to BPA through maternal diets containing one of four environmentally relevant doses (0, 50 ng, 50 µg, or 50 mg of BPA per kg diet) and approximately one male and one female per litter were followed until 10 months of age. Animals were tested for known risk factors for hepatocellular carcinoma, including bacterial and viral infections.

Results: We report dose-dependent incidence of hepatic tumors in exposed 10-month mice. 23% of offspring presented with hepatic tumors or preneoplastic lesions. A statistically significant dose-response relationship was observed, with an odds ratio for neoplastic and preneoplastic lesions of 7.23 (95% CI: 3.23, 16.17) for mice exposed to 50 mg BPA per kg diet compared with unexposed controls. Observed early disease onset, absence of bacterial or viral infection, and lack of characteristic sexual dimorphism in tumor incidence support a non-classical etiology.

Conclusions: To our knowledge, this is the first report of a statistically significant association between BPA exposure and frank tumors in any organ. Our results link early life exposure to BPA with the development of hepatic tumors in rodents, with potential implications for human health and disease.


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