Fifteen years after "Wingspread"--environmental endocrine disrupters and human and wildlife health: where we are today and where we need to go

Abstract

In 1991, a group of expert scientists at a Wingspread work session on endocrine-disrupting chemicals (EDCs) concluded that "Many compounds introduced into the environment by human activity are capable of disrupting the endocrine system of animals, including fish, wildlife, and humans. Endocrine disruption can be profound because of the crucial role hormones play in controlling development." Since that time, there have been numerous documented examples of adverse effects of EDCs in invertebrates, fish, wildlife, domestic animals, and humans. Hormonal systems can be disrupted by numerous different anthropogenic chemicals including antiandrogens, androgens, estrogens, AhR agonists, inhibitors of steroid hormone synthesis, antithyroid substances, and retinoid agonists. In addition, pathways and targets for endocrine disruption extend beyond the traditional estrogen/androgen/thyroid receptor-mediated reproductive and developmental systems. For example, scientists have expressed concern about the potential role of EDCs in increasing trends in early puberty in girls, obesity and type II diabetes in the United States and other populations. New concerns include complex endocrine alterations induced by mixtures of chemicals, an issue broadened due to the growing awareness that EDCs present in the environment include a variety of potent human and veterinary pharmaceutical products, personal care products, nutraceuticals and phytosterols. In this review we (1) address what have we learned about the effects of EDCs on fish, wildlife, and human health, (2) discuss representative animal studies on (anti)androgens, estrogens and 2,3,7,8-tetrachlorodibenzo-p-dioxin-like chemicals, and (3) evaluate regulatory proposals being considered for screening and testing these chemicals.

FIG. 1.

Schematic of a standard multigenerational test.

FIG. 2.

Power curves for reproductive organ weights, malformation rates, anogenital distance and age at preputial separation (puberty). The data from our transgenerational study with DEHP were analyzed using PROC MIXED available on SAS to obtain estimates of components of variation (for litters vs. pups within litters) that make up the overall variability of the means in order to assess the implications for statistical power of using data from multiple pups per litter. Following this analysis, we calculated power to detect the treatment effects as described by Raudenbush and Xiao-Feng (2001). The objective of this was to determine the proportion of the overall error variance due to litter-to-litter variability versus the proportion accounted for by the pups within litters. This retrospective analysis can be useful for designing optimal sampling strategies for future studies. It basically allows one to determine how much the statistical power of a study is enhanced by examining several pups from the same litter rather than using only one pup/per sex/litter. Because the pups in the DEHP treated litters do not respond identically, the more variable the pups are within the litter the more power is enhanced, and hence the standard error of the mean is reduced, by examining multiple pups from the same litter.