The issue of environmental endocrine-active chemicals has received enormous attention during the past decade, and all manner of claims made that such compounds can affect human health, particularly male reproductive health. The primary focus has been on environmental estrogens, but it is unlikely that the compounds so far identified are potent enough to affect male reproductive development because of any intrinsic estrogenicity (5,8). Whether combinations of such chemicals could affect male reproductive development is less certain and is difficult to evaluate meaningfully. However, the focus of attention has now switched to environmental chemicals that can alter endogenous hormones and, as any clinical endocrinologist will know, when endogenous hormone levels/action are disturbed, disorders invariably result. The example most relevant to male reproductive development is exposure to certain phthalate esters (104). These compounds have numerous uses and are the most ubiquitous of all envi ronmental chemicals, so human exposure is quite high (109). When rats are treated with certain phthalates during the last week of pregnancy, which encompasses the period of sexual differentiation of the fetuses, the male offspring show a high incidence of cryptorchidism and hypospadias at birth and have reduced testis size in adulthood, which result in reduced sperm production (104,110,111). Although the cascade of events that leads to these disorders is not fully established, one important change is suppression of testosterone production by the fetal testis (104,111). Indeed, the spectrum of changes in male offspring that is induced by phthalate treatment in pregnancy is remarkably similar to testicular dysgenesis syndrome in humans (see Fig. 3) and may provide a model system through which to study this hypothesized human syndrome (104). Whether human exposure to phthalates causes this syndrome remains to be explored. The doses of phthalates used to induce a high prevalence of male reproductive disorders in rats certainly exceeds known human exposure levels (104), but a recent study has identified a subset of humans who have considerably higher exposure to relevant phthalates, and these were predominantly women of reproductive age (109). The suspicion is that the high exposure results from use of phthalates in cosmetics, shampoos, and other beauty aids. Until there are data to indicate whether humans are susceptible to similar effects of phthalates as are rats, and, our relative sensitivity to them, it is not possible to determine the risk to human health from these compounds.
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