The endocrine system in humans and other animals has an important job. It produces the hormones that regulate the body’s various processes, such as metabolism and reproduction, which are vital to the chemistry of life. One example of a hormone is insulin, which controls the level of sugar in our blood. Another is adrenalin, which helps us deal with stress or danger. Reproductive hormones impart sexual characteristics. Estrogens are hormones that impart female characteristics; androgens are hormones that impart male characteristics.
What Is Endocrine Disruption?
According to the Environmental Protection Agency (EPA), disruption of the endocrine system can occur when some chemicals “mimic a natural hormone, fooling the body into over responding to the stimulus (e.g., a growth hormone that results in increased muscle mass), or responding at inappropriate times (e.g., producing insulin when it is not needed).” Others “directly stimulate or inhibit the endocrine system and cause overproduction or underproduction of hormones (e.g., an over or underactive thyroid).” How exposure to endocrine disruptors is linked to human diseases remains “poorly understood and scientifically controversial,” according to EPA scientists (Kavlock et al., 1996, EPA, 1997).
What the Science Says
A few chemicals and some natural substances (e.g., soybeans are weakly estrogenic), can impact the endocrine system to some degree. However, there is no scientific agreement on how to define or test for an endocrine-active effect. Nor is there a consensus on whether human reproductive capacity in the general population has changed in recent years, let alone what may be responsible. Nevertheless, lists of alleged human endocrine disruptors continue to circulate. Given the lack of consensus on the definition and consequence of an endocrine-active effect, the relevance of these lists of alleged endocrine disruptors is in serious doubt.
The World Health Organization International Programme on Chemical Safety (WHO IPCS) conducted a global assessment of the state of the science relative to endocrine disruption. In its August 2002 report, the WHO IPCS stated that, “Analysis of the human data by itself, while generating concerns, has so far failed to provide firm evidence of direct causal associations between low-level (i.e., levels measured in the general population) exposure to chemicals with [endocrine disrupting effects] and adverse health outcomes.” The report concludes: “studies examining [endocrine disrupting chemical]-induced effects in humans have yielded inconsistent and inconclusive results, which is responsible for the overall data being classified as weak.” The report does point out, however, this classification “is not meant to downplay the potential effects of [endocrine disrupting chemicals]” and instead “highlights the need for more rigorous studies.”
Phthalates are frequently referred to as endocrine disruptors, or endocrine mimics, by some environmental organizations; but those characterizations are misleading. The major phthalates in commerce today do not interfere with or mimic either the estrogen or androgen receptors when tested in laboratory animals. That is, they neither activate the male or female hormone receptors, nor prevent activation by natural hormones.
High doses of some phthalates can interfere with normal sexual development in male rats, but this is not true in mice or monkeys and, therefore, is unlikely in humans given that there are significant differences in the male reproductive tracts of rodents vs. primates. Studies suggest that reactions to phthalates exposure vary from species to species because primates simply do not absorb phthalates as efficiently as rodents do.
Rodents vs. Primates
In a significant study first presented at the Society of Toxicology and published in 2006,1 researchers found that very high doses of DEHP administered to juvenile marmoset monkeys (which are much closer to humans in both physiology and development than are rodents) from weaning to sexual maturity had no negative effects on the development of the male reproductive tract. As marmosets are primates, the research indicates that the reproductive effects observed in rodents may not be relevant to humans.
A study published in 2004 may help explain the different reactions from species to species. In the study by Kessler, et al.,2 female rats and marmosets were fed equivalent doses of DEHP, and then tested for levels of MEHP, which is a major metabolite of DEHP. Blood levels of MEHP were as much as 7.5 times lower in the marmosets, and the total internal dose of MEHP was as much as 16 times lower. In other words, one reason primates appear to be less vulnerable to DEHP is that they experience lower internal doses at equivalent external exposures. They simply do not adsorb the DEHP as efficiently as rodents, nor do they convert it as efficiently to MEHP.
For More Information
Visit EPA's website to learn more about the human endocrine system and endocrine disruptors.
1 Tomonari Y., Kurata Y., Kawasuso T., David R., Gans G., Tsuchitani M., Katoh M. Effect of di(2-ethylhexyl) phthalate (DEHP) from juvenile common marmosets. Journal of Toxicology and Environmental Health, Part A, 69:1651-1672, 2006.
2 Kessler, W., Numtip, W., Grote, K., Csanady, G., Chahoud, I., and Filser, J. (2004). Blood burden of di(2-ethylhexyl) phthalate and its primary metabolite mono(2-ethylhexyl) phthalate in pregnant and nonpregnant rats and marmosets. Toxicology and Applied Pharmacology, 195:142-153.
