Endocrine disrupting chemicals mixtures

Mixtures of endocrine disrupting chemicals have been shown to produce additive, synergistic, and unexpected dose-response effects. The following studies are illustrative of the effects noted. 

In an in vitro study, mixtures of six synthetic endocrine disrupting chemicals and plant-derived phytoestrogens were evaluated for estrogenic activity The EDCs were... 

The allowable levels of air and water emissions of toxic chemicals should be reduced by at least one order of magnitude to account for the toxic effects of mixtures that remain largely unknown, but are increasingly being found to induce toxic effects at very low concentration levels. Endocrine disrupting chemicals and mixtures are examples of such compounds (Chapter 22). 

Human exposure to single endocrine-disrupting chemicals is generally considered to be low, and the compounds arc much less potent than the natural hormones. However, humans are expected to be exposed to a mixture of potential endocrine-disrupting chemicals. Hence, potential additive or synergistic effects have to be considered to assess the human risk. Furthermore, in vivo potency is often different from in vitro potency since the mcchani.sm.s of hormonal action of chemicals may not be adequately reflected by the in vitro assays. 

Fumes from welding mild steel can reasonably be expected to include vapors and particulates of the earlier list as well as carbon monoxide, carbon dioxide, fluorides, oxides of nitrogen, and ozone [78], Welders of mild steel, but not stainless steel, have been found to have reduced semen quality and decreased fecundity compared with non-welders [79], Welders are exposed to complex chemical mixtures that act via an unknown mechanism. It is interesting to note that one might have expected stainless steel welders to have a more adverse reaction due to the presence of chromium, which is an endocrine-disrupting chemical, but this is not the case. 

PCBs and phthalates are endocrine-disrupting chemicals that adversely impact male fertility, especially sperm motility. In a sperm motility study, exposure to a mixture of PCB-153 and monobenzyl phthalate or monobutyl phthalate produced greater than expected negative impacts. The authors of the study hypothesized that the mechanism is throngh interactions between PCB metabolites and enzymes responsible for phthalate metabolism [83]. PCBs accumulate in body adipose tissue and metabolize slowly. Phthalates metabolize rapidly and are not known to accumulate in body tissues. Accordingly, it is more than likely that exposures to phthalates long after exposures to PCBs can produce enhanced negative sperm motility effects in men and dramatically reduce their fertility. 

A proper assessment of the ability of chemicals, or mixtures of chemicals, to act as endocrine disrupters requires a multi-tiered approach which is able to identify mechanisms, give early warning of adverse effects and identify which of these effects is likely to be ecologically relevant. A strategy has been proposed by Depledge and Billinghurst " and is outlined below. 

HPV-lnerts data set — It contains 623 high production volume inerts (human papilloma virus-[HPV] Inerts), which is a subset of the Toxic Substances Control Act (TSCA) Inventory. The EPA is including HPV-lnerts in version 2 of the Endocrine Disruption Priority Setting Database (EDPSD2), and there was a need to prioritize HPV-lnerts for further experimental evaluation. Of 623 chemicals, 166 chemicals were either mixtures or their structures were not available, excluding them from prediction. The activities (or otherwise) of457 chemicals were predicted by this system. 

Amphibian endocrine disruption is of special interest to humans. The estrogen found in the painted turtle is identical to that found circulating in the human bloodstream and the endocrine disruptors that threaten wildlife populations have also been shown to be jeopardizing human reproductionAccordingly, animal studies on endocrine disrupting properties of toxic chemicals are relevant to understanding human responses to these chemicals. Pesticide mixtures have been shown to be powerful endocrine disruptors in numerous other animal studiesJ16 Illustrative examples follow. 

In keeping with the stated purpose of this book, the endocrine disrupting effects of single chemicals are discussed briefly and serve as an introduction to a discussion of the endocrine toxic effects of chemical mixtures. 

At low doses, additive effects were observed. At higher doses, however, the responses of mixtures of synthetic EDCs and phytoestrogens were greater than additive. In this study, mixtures of the synthetic chemicals alone interacted in a less than additive manner. These results illustrate the often unpredictable interaction of endocrine disrupting mixtures. 

Many single chemicals have been identified as endocrine disruptors, but little is known about the endocrine disrupting effects of chemical mixtures. What little is known suggests that the effects of mixtures are greater... 

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