Endocrine disruptors and development of the reproductive system in the fetus and children: is there cause for concern?

Reports of decreased semen quality and increased rates of developmental abnormalities of the male reproductive tract along with increasing incidence of testicular cancer have focused attention on man-made chemicals as potential causative factors. A biologically plausible hypothesis has been advanced which suggests that man-made chemicals act as endocrine disruptors through interaction with the estrogen receptor resulting in altered development of the reproductive tract. Available evidence suggests that this mechanism may play only a minor role in the purported adverse effects described to date. Man-made chemicals, however, may induce adverse health effects through mechanisms independent of the estrogen receptor. Indeed, man-made chemicals have been shown to induce adverse effects on thyroid function and androgen-dependent processes in animal studies. Hence the focus on estrogenic mimics may be too simplistic and alternate mechanisms could be more relevant due to target gland exposure levels and potency of the toxicant. Before it can be concluded that man-made chemicals pose little or no risk to the development of the reproductive tract in the fetus and children it will be necessary to, at the very least, insure that: 1) exposure scenarios include the most sensitive developmental stage, 2) all endocrine targets have been evaluated for potential effects, and 3) the role of environmentally and biologically relevant levels of chemical mixtures in adverse health outcomes have been evaluated. Due to potential for exposure, sensitivity of the developing reproductive tract, suggestive evidence of a possible role of man-made chemicals in developmental abnormalities of the reproductive tract, and the many outstanding research questions, it is concluded that there is sufficient cause for concern.