Editorial: Estrogens from Plastic-Are We Being Exposed?

The controversy over the potential negative impact on public health of environmental chemicals with estrogenic activity has spilled over from scientific journals (1, 2) into the public domain. News articles on the subject have appeared in multiple sources including Science (3), Journal of the American Medical Association (4), Chemical and Engineering News (5), Science News (6) and Newsweek (7), and in many newspapers, as well as on National Public Radio. The book Our Stolen Future (8) has emphasized the effects of environmental chemicals on wildlife and their long-term effects on the environment. Some stories have hyped the risk of environmental chemicals with provocative terms such as “Ecocancers” (6) and titles such as “Can environmental estrogens cause breast cancer? (9). Proponents of the position that environmental estrogens are hazardous raise concerns about birth defects due to fetal exposure (8, 10), the increased incidence of breast cancer (9, 11), falling sperm counts and decreased fertility (12), and numerous other conditions (3–12). However, in each case there is controversy over the findings with opponents making strong counter-arguments. In all of these conditions, the risk is hypothetical, with no data yet proving a causal relationship between environmental estrogens and illness or disease in people. The claim that environmental estrogens are causing a decline in sperm counts has been especially contentious. Investigators in this field have so far failed to agree on whether sperm counts are, in fact, falling. If sperm counts are in decline, they certainly cannot agree on whether environmental estrogens are even remotely involved (12, 13). Similarly, the proposal that environmental estrogens contributed to an increased incidence of breast cancer (11) was quickly refuted (14). Scientifically sound experiments have documented that various environmental chemicals are capable of acting as endocrine disrupters, either hormone agonists or antagonists, which can potentially alter the hormonal balance in animals and people. A number of studies, including our own (15), have clearly shown the estrogenic activity of some environmental chemicals. What remains controversial and open to serious debate is the level of exposure of the population to these agents and an ascertainment of whether these levels are sufficient to cause harmful effects. The critical question is whether the population is exposed to a high enough concentration of chemicals to cause, in the in vivo setting, the effects that these agents have been demonstrated to initiate in vitro. This question is not easily answered. Although the estrogenic activity of these substances is very much weaker than estradiol, as discussed below, new chemicals with endocrine disrupting potential continue to be discovered, unanticipated pathways of exposure continue to be found, and concern about the cumulative effects of these agents continues to grow. However, the level of exposure is difficult to quantify and the array of potential target organs in the body continues to rise. In this issue of the journal, Ben-Jonathan and her group extend the accumulated data on the estrogenic activity of Bisphenol-A (BPA), a compound used to manufacture the plastic called polycarbonate. In this article, Steinmetz et al. (16) argue that the pituitary cells that regulate PRL release are a new target for environmental estrogens in general and BPA in particular. Although there are many substances considered to be environmental estrogens, including pesticides, pollutants, and various chemicals, this paper deals with the estrogenicity of BPA, and I will therefore focus my discussion primarily on the estrogenic substances derived from plastics. BPA is the monomeric unit used to produce the ubiquitous plastic, polycarbonate. This plastic has excellent properties making it tremendously useful in many applications. In 1993, my group reported on the estrogenic activity of BPA that was released from polycarbonate flasks during the autoclaving of media (15). We showed that BPA could act on MCF-7 human breast cancer cells as an estrogen, stimulating cellular proliferation and inducing progesterone receptors. BPA could bind to estrogen receptors, and the estrogenic effects induced by BPA were blocked by the estrogen antagonist tamoxifen, thus supporting the notion that the estrogenic activity of BPA was mediated via the estrogen receptor. Although the chemical structure of BPA is quite similar to diethylstilbestrol (DES), a well known and very potent nonsteroidal estrogenic compound with a bis-phenolic structure, BPA was a much weaker estrogen, approximately 1000to 2000-fold less potent than estradiol (15). Our results were of interest for two reasons. First, we wanted to alert other investigators about the potential risk of estrogenic artifacts causing spurious effects in laboratory experiments. Second, we wanted to raise for scientific scrutiny the possibility that BPA was a risk to public health. Because polycarbonate is used in the packaging, storing, and preparation of a myriad of foods and beverages, including water jugs, bottled beverages, baby food, and juice containers, we wondered whether BPA might contaminate the food supply and potentially harm the public. However, because limited data were available upon which to draw a conclusion, we cautiously raised the question for study and made no claim that a public health risk existed (15). In addition to our work, Soto, Sonnenschein, and colleagues at Tufts University showed very similar results with another component of different plastics, p-nonyl-phenol (17). This alkylphenolic substance, used as plastic additive and Received February 24, 1997. Address all correspondence and requests for reprints to: David Feldman, M.D., Stanford University School of Medicine, Division of Endocrinology, Gerontology and Metabolism, Stanford, California 94305-5103. E-mail: feldman@CMGM.Stanford. edu. 0013-7227/97/$03.00/0 Vol. 138, No. 5 Endocrinology Printed in U.S.A. Copyright © 1997 by The Endocrine Society