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bisphenol a and endocrine disruption
Human Health & Safety >> Health Effects Research

Endocrine Activity Studies on Bisphenol A

Background on Endocrine Disruption
Endocrine Disruption and Bisphenol A
Estrogenic Activity of Bisphenol A
Low-Dose Endocrine Effects

Return to TopBackground on Endocrine Disruption

Our Stolen Future, a book published in 1996, popularized the theory that natural and man-made substances that exhibit hormone-like properties in the laboratory can affect wildlife populations, thus speculating that humans may be at risk of "hormone disruption." While this theory has been widely discussed in the open scientific literature, it caught the public's attention resulting in a U.S. Congressional mandate to test man-made chemicals for any hormonal properties.

Since that time there have been hundreds of published studies testing the hypothesis, including assays that show a positive response. These assays are often misused to label certain substances "endocrine disrupters," although a more accurate term, "hormonally active agents," was recently coined by the U.S. National Academy of Sciences.

To date, the mechanisms through which hormonally active agents act in a living organism have not been documented, although a number of theories have been proposed. The research community in cooperation with government agencies and industry are working to clarify and characterize any risks posed by hormonally active agents in the environment.

Return to TopEndocrine Disruption and Bisphenol A

There is no known risk from environmentally relevant exposures of bisphenol A to humans, wildlife or the environment.

Bisphenol A exhibits extremely weak hormonal activity in test tube assays, such as those utilizing yeast or human breast cancer cells. Effects have also been observed in compromised laboratory animals at high doses of bisphenol A. However, reproduction and development are not affected by relatively high levels of bisphenol A in multi-generational studies, which are designed to detect disruptions in normal hormone activity (doses are compared to the extremely low levels of possible consumer exposure).

Return to TopEstrogenic Activity of Bisphenol A

The estrogenic activity of bisphenol A (BPA) has been identified over the past several decades. The earliest reference noted for the estrogenic action of BPA was a report of a bioassay for a positive estrus response, as measured by cornification in vaginal smears, that occurred in ovariectomized rats dosed (route unspecified) twice daily with 100 mg BPA dissolved or suspended in sesame oil on three successive days (Dodds and Lawson, 1936). In this study, the effective estimated daily dose was 800 mg/kg/day (100 mg/250 grams body weight/twice daily).

A more comprehensive study was reported in 1970 (Bitman and Cecil, 1970) in which DDT and 52 structurally related compounds, including BPA, were injected subcutaneously into immature rats. Estrogenic activity was measured 18 hours following dosing by measuring uterine glycogen content. The minimally effective dose of BPA to produce an increase in uterine glycogen content was 0.25 mg/rat, or about 5 mg/kg/day.

A series of similar studies were undertaken in rats by the National Institute for Occupational Safety and Health (NIOSH) (Bond et al., 1980); also personal communication from NIOSH to Morrissey, et al. mentioned in Morrissey, et al., (1987). In these studies ovariectomized rats were administered BPA: intraperitoneally (50-130 mg/kg), orally (1250 mg/kg, dermally (8000 mg/kg), or via inhalation (156 mg/m3 for 6 hours), and, following various times, estrogenic activity was confirmed by measuring changes in percentage uterine water.

An example of a more recent reference demonstrating estrogenic activity of BPA is an in vitro study where levels of BPA were found to induce progesterone receptors in cultured human mammary cancer cells (MCF-7) at a potency of 5000 times less than estradiol. BPA also increased the rate of proliferation of MCF-7 cells, and competed with estradiol for estrogen receptor binding sites (Krishnan, et al., 1993).

These studies have shown that BPA possesses estrogenic activity in special experimental systems. However, it is not at all clear how these results can be related to specific toxicologic endpoints that are relevant to human health. For example, estrogenic activity was mainly identified in ovariectomozed rats or in even less relevant in vitro models. In addition, estrogenic activity was seen in animals administered large doses of BPA or animals exposed via only experimental routes of exposure, such as intraperitoneally or subcutaneously.

Return to Top Low-Dose Endocrine Effects

For a discussion of bisphenol A and low-dose endocrine effects research, click here.


   
 

Health Effects Research

General Toxicity

Carcinogenicity

Reproductive And
  Developmental Toxicity


Endocrine Activity

Low-Dose Endocrine Effects

Metabolism


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