AN UPDATED REVIEW OF ENVIRONMENTAL ESTROGEN AND ANDROGEN MIMICS AND ANTAGONISTS

For the last 40 y, substantial evidence has surfaced on the hormone-li ke effects of environmental chemicals such as pesticides and industria l chemicals in wildlife and humans. The endocrine and reproductive eff ects of these chemicals are believed to be due to their ability to: (1 ) mimic the effect of endogenous hormones, (2) antagonize the effect o f endogenous hormones, (3) disrupt the synthesis and metabolism of end ogenous hormones, and (4) disrupt the synthesis and metabolism of horm one receptors. The discovery of hormone-like activity of these chemica ls occurred long after they were released into the environment. Aviati on crop dusters handling DDT were found to have reduced sperm counts, and workers at a plant producing the insecticide kepone were reported to have lost their libido, became impotent and had low sperm counts. S ubsequently, experiments conducted in lab animals demonstrated unambig uously the estrogenic activity of these pesticides. Manmade compounds used in the manufacture of plastics were accidentally found to be estr ogenic because they fouled experiments conducted in laboratories study ing natural estrogens. For example, polystyrene tubes released nonylph enol, and polycarbonate flasks released bisphenol-A. Alkylphenols are used in the synthesis of detergents (alkylphenol polyethoxylates) and as antioxidants. These detergents are not estrogenic; however, upon de gradation during sewage treatment they may release estrogenic alkylphe nols. The surfactant nonoxynol is used as intravaginal spermicide and condom lubricant. When administered to lab animals it is metabolized t o free nonylphenol. Bisphenol-A was found to contaminate the contents of canned foods; these tin cans are lined with lacquers such as polyca rbonate. Bisphenol-A is also used in dental sealants and composites. W e found that this estrogen leaches from the treated teeth into saliva; up to 950 mu g of bisphenol-a were retrieved from saliva collected du ring the first hour after polymerization. Other xenoestrogens recently identified among chemicals used in large volumes are the plastizicers benzylbutylphthalate, dibutylphthalate, the antioxidant butylhydroxya nisole, the rubber additive p-phenylphenol and the disinfectant o-phen yl-phenol. These compounds act cumulatively. In fact, feminized male f ish were found near sewage outlets in several rivers in the U.K.; a mi xture of chemicals including alkyl phenols resulting from degradation of detergents during sewage treatment seemed to be the causal agent. E strogen mimics are just a class of endocrine disrupters. Recent studie s identified antiandrogenic activity in environmental chemicals such a s vinclozolin, a fungicide, and DDE, and insecticide. Moreover, a sing le chemical may produce neurotoxic, estrogenic and antiandrogenic effe cts. It has been hypothesized that endocrine disrupters may play a rol e in the decrease in the quantity and quality of human semen during th e last 50 y, as well as in the increased incidence of testicular cance r and cryptorchidism in males and breast cancer incidence in both fema les and males in the industrialized word. To explore this hypothesis i t is necessary to identify putative causal agents by the systematic sc reening of environmental chemicals and chemicals present in human food s to assess their ability to disrupt the endocrine system. In addition , it will be necessary to develop methods to measure cumulative exposu re to (a) estrogen mimics, (b) antiandrogens, and (c) other disrupters . (C) 1998 Elsevier Science Ltd. All rights reserved.