Perinatally Administered Bisphenol A as a Potential Mammary Gland Carcinogen in Rats

Abstract

Background: Environmental exposure to bisphenol A (BPA) affects mammary gland development in rodents and primates. Prenatal exposure to environmentally relevant doses of BPA increased the number of intraductal hyperplasias and ductal carcinomas in situ by 50 days of age in Wistar-Furth rats.Objective: We aimed to determine whether BPA exposure of dams during gestation only or throughout lactation affects the incidence of mammary gland neoplasia in female offspring.Methods: We treated pregnant Sprague-Dawley rats with BPA at 0, 0.25, 2.5, 25, or 250 μg BPA/kg BW/day from gestational day (GD) 9 to birth and from GD9 to postnatal day (PND) 21. Mammary glands from BPA-exposed offspring were examined at four time points for preneoplastic and neoplastic lesions. To assess circulating BPA levels, we exposed pregnant rats to vehicle or 250 μg BPA/kg BW/day during gestation only or during gestation/lactation and analyzed sera from dams, fetuses, and nursing pups for total and unconjugated BPA.Results: Total and unconjugated BPA were detected in sera from 100% of dams and fetuses and 33% of pups exposed to 250 μg BPA/kg BW/day. Unconjugated BPA levels in exposed dams and fetuses (gestational) and in exposed dams and pups (gestational/lactational) were within levels found in humans. Preneoplastic lesions developed in BPA-exposed female offspring across all doses as early as PND50. Unexpectedly, mammary gland adenocarcinomas developed in BPA-exposed offspring by PND90.Conclusions: Our findings suggest that developmental exposure to environmentally relevant levels of BPA during gestation and lactation induces mammary gland neoplasms in the absence of any additional carcinogenic treatment. Thus, BPA may act as a complete mammary gland carcinogen.Citation: Acevedo N, Davis B, Schaeberle CM, Sonnenschein C, Soto AM. 2013. Perinatally administered bisphenol A acts as a mammary gland carcinogen in rats. Environ Health Perspect 121:1040–1046; http://dx.doi.org/10.1289/ehp.1306734

Low dose effects of bisphenol A

“…[137][138][139] Another recent study revealed the presence of carcinomas in the mammary glands of rats exposed to low doses of BPA only during early development in the absence of any additional carcinogen treatment, providing further evidence that the mammary gland is affected by BPA. 140 A recent weight-ofevidence analysis found strong support for low dose effects and high levels of consistency between studies for both endpoints; 5 low doses were found to alter mammary gland morphology at many life stages, and numerous studies reported that low doses increase the incidence of preneoplastic and neoplastic lesions, as well as increase the response to chemical carcinogens. Some of these studies are discussed in more detail below.…”

Low‐Dose Bisphenol A Exposure: A Seemingly Instigating Carcinogenic Effect on Breast Cancer

“…Thus, these preliminary studies suggest that low‐dose BPA has the potential to pose health hazards. Recent studies have also aimed to evaluate the role of BPA in carcinogenesis,7, 22, 23 and have indicated that exposure to BPA may account, at least partially, for the increased incidence of multiple cancers, including breast cancer,24, 25, 26, 27 ovarian cancer,28, 29 uterine cancer,30 prostate cancer,31, 32 testicular cancer,33 and liver cancer 34. The carcinogenic effects of BPA are summarized in Table 1 .…”

A novel biotemplated synthesis of TiO2/wood charcoal composites for synergistic removal of bisphenol A by adsorption and photocatalytic degradation

“…However, even in ϯ low concentration (ng/L), BPA has been reported to cause adverse environmental and health effects because it can pose potential estrogenic and toxicological risk [9,10]. It was also reported that BPA has been associated with metabolic disorders including obesity and diabetes [11], and an increasing risk of miscarriages and cardiovascular disease in humans, and potential mammary gland carcinogen in mice [12]. Therefore, it is urgent to develop an efficient method to remove BPA in low concentration from aquatic environment.…”