Endocrine modulators in the food chain and environment.

Recently, considerable attention has been focused on certain environmental contaminants--"endocrine disruptors"--of industrial origin that may mimic the action of sex hormones. Natural compounds and their effects on other types of hormonal activity (eg, on adrenal or thyroid function) have for some reason not provoked similar attention. As exemplified by tributyltin and certain bioaccumulating chlorinated compounds, available evidence indicates that "endocrine disruption" caused by xenobiotics is primarily an ecotoxicologic problem. In mammals, certain phenylmethyl-substituted siloxanes have been found to be by far the most potent endocrine disrupters among various synthetic xenobiotics. On the other hand, it has not been possible to scientifically substantiate either certain alarming reports of powerful synergistic effects between chlorinated pesticides or the alleged adverse effects on the male reproductive tract in rodents (induced by alkylphenols and plasticizers at extremely low exposures). Whereas there is compelling evidence that estrogens in certain foods and herbal medicines can induce hormonal changes in women as well as overt toxicity in men, existing data are insufficient to support a causal relationship between exposure of the general human population to nonpharmaceutical industrial chemicals and adverse effects operating via the endocrine system. Moreover, in terms of magnitude and extent, all such exposures to so-called endocrine disruptors are dwarfed by the extensive use of oral contraceptives and estrogens for treatment of menopausal and postmenopausal disorders. Also, the exposure to hormonally active xenobiotics is virtually insignificant when compared with the intake of the phytoestrogens that are present in food and beverages, and it is even more insignificant when compared with certain herbal potions used in "alternative medicine." Furthermore, while there has been much concern about negligible exposures to xenobiotics with weak hormonelike activities, the potent endocrine disruptor licorice is freely given to children. Long-term exposure to this substance induces severe toxic symptoms of mineral corticoid hormone imbalance. Although exposures to xenobiotics and many natural compounds occur by identical routes of administration and may contribute to the same toxicological end point, they are, regrettably, judged by completely different standards. As is the case with all other chemicals, rational risk assessment and risk management of man-made and natural endocrine modulators must be based on the mode of action and dose-response relationships. Such end points as the induction of reproductive developmental effects, cancer, etc, relating to actual exposures must also be taken into consideration.