Mixtures endocrine disruptors

Endocrine disruptor. An exogenous substance or mixture that alters function(s) of the endocrine system and consequently causes adverse health effects in an intact organism or its progeny or (sub)popu-lations. 

An overview of the literature shows that in the majority of cases, CA did yield accurate predictions of combination effects, even with mixtures composed of chemicals that operate by diverse modes of action. The studies available were dealing with mixtures of chemicals having an unspecific mode of action (membrane disturbance or narcosis) or with pesticides, mycotoxins, or endocrine disruptors. In ecotoxicol-ogy, CA usually produced more conservative predictions than IA. There are indications that this is true also for mammalian toxicology, but more data are needed to come to more definitive conclusions. The validity of CA or IA was confirmed for individual-based endpoints like growth or reproduction, but also for effects at the cellular or subcellular level and for community-based endpoints. 

As we have seen, there are many other chemicals capable of causing these effects, although they are generally very much less potent that the natural oestrogens and the synthetic oestrogens used in the contraceptive piU. Mixtures of these chemicals, which includes natural substances from plants, pesticides, and industrial chemicals, may be more potent than the individual components. This phenomenon is called synergy (see p. 35) and is currently an area of intense scientific interest, as is the subject of endocrine disruptors. 

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. 

Chen PJ, Rosenfeldt EJ, Kullman SW, et al. Biological assessments of a mixture of endocrine disruptors at environmentally relevant concentrations in... 

Sperm counts in men have declined by about 50% during the time period 1940-90, from an average of 113 million per milliliter of semen in 1940 to an average of 66 million in 1990. During the same time frame there has been a decrease in seminal volume from 3.40 to 2.75 ml. 51 The reasons for the observed decline in semen quality are exposures to pesticide mixtures 52 and other xenobiotic endocrine disruptors, 53 maternal consumption of beef-containing anabolic steroids 54 and other xenobiotics, and tobacco smoking. 55 ... 

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... 

One study that overcomes some of the shortcomings of those just cited reported adverse neurodevelopment outcomes following maternal exposures to 19 organic solvents and mixtures of these. 13 In this study, the women were occupationally exposed to the chemicals listed in Table 24.3. Also included in this table are the K, values and whether or not the specific chemical is a known teratogen or a known endocrine disruptor. 5 It is interesting to note that only three of the chemicals in the study—ethanol, trichloroethylene, and mineral spirits (a mixture of hydrocarbon solvents)—are endocrine disruptors. This shows that teratogenic effects can be induced by chemicals and mixtures that are independent of the endocrine system. 

A. Kortenkamp, Introduction endocrine-disruptors—exposure assessment, novel end points, and low-dose and mixture effects, Environ. Health Perspect. 115 (Suppl. 1) (2007) 7. 

The effect of these compounds on human health has been a major cause of concern. Toxicity to humans depends on exact structure, but exposure is ubiquitous and involves a mixture of compounds, from fossil fuel and natural and anthropogenic burning and from food, mainly grilled or barbecued meat. In the broader environment, PAHs are endocrine disruptors and bind to the aryl hydrocarbon receptor. They have been shown to depress immune function in some wildlife. They may be responsible for reproductive disorders in aquatic organisms, especially in shellfish and sediment dwellers. 

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