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New study looks at hormones and endocrine-disrupting chemicals

By Sandra Madray

To some people, the mention of endocrine disrupting chemicals (EDCs) brings to mind BPA (bisphenol A) because it has had significant media coverage. And also, the Canadian government has banned its use in baby bottles. BPA is an example of an endocrine disrupting chemical. At low doses, these EDCs can adversely affect the hormonal system in humans as well as in wildlife.

EDCs are present everywhere. They can be found in products such as cosmetics, plastics, thermal receipt paper, lining of food and beverage containers and pesticides. They are also present in some recycled products.

Traditionally in toxicology, the greater the dose of a chemical, the more pronounced the resulting health effect. But with EDCs, this is not the case – adverse health effects are being observed at surprisingly low concentrations. This has become a very contentious issue within the scientific community and as a result, there is tremendous skepticism that such effects at low doses are meaningful or relevant to human health.

The recent paper “Hormones and Endocrine-Disrupting Chemicals: Low-Dose Effects and Nonmonotonic Responses(Vandenberg LN, et al. Endocrine Reviews, 2012, March 14) by 12 authors, reviewed 845 scientific papers citing evidence of EDCs having adverse health impacts at very low doses in animals and humans.

This extensive review did not ignore that the fact that there can be very detrimental human health effects from EDCs as a result of occupational and accidental exposures which are generally at higher concentrations. Occupational exposure is more likely to be ongoing, and effects are not necessarily the same as those observed for the same chemical at a very low dose. The effects produced at low doses can have far reaching consequences in our lives as they are thought to impact such health outcomes such as thyroid dysfunction, fertility, obesity, immune system problems, cancer and neurobehaviour.

The authors made reference to those EDCs having biological activity regardless of the dose. Such an example would be insecticides that are designed to mimic molting hormones. While there should be no argument that EDCs are present in many of our consumer products, the question remains as to what other effects could possibly result from these biologically active ingredients – effects that have not been investigated.

As previously pointed out, it is expected in traditional toxicology that a dose increase results in an increased intensity of response or effect. The resulting curve showing dose-response data is referred to as a monotonic dose-response curve. However, for EDCs, effects can be increased or decreased as the dose is increased. And even at very low doses, significant effects can be observed. This is referred to as a non-monotonic dose response (NMDR).

Therefore, when the data from a high dose of a chemical is used to determine the safety of that chemical at a lower dose, there is predictability for those chemicals that have a monotonic dose-response curve. However, this is not the case with EDCs, as their curves are generally non-monotonic dose response curves (NMDRCs). Thus, predicting the behavior of a chemical with a NMDRC based on the effects at a higher dose would be grossly inaccurate.

This has been rather controversial. There is skepticism as whether NMDRCs exist at all, and if they do, what is the relevance to determining a safe dose – if there is one at all.

The paper provides evidence that makes it very difficult to dispute the existence of NMDRCs. It tabulated and referenced chemicals that are considered examples of NMDRCs. They were categorized by chemical class and were identified in cell culture experiments, animal studies and epidemiological studies. Similarly, natural hormones with NMDRCs were also identified in epidemiological studies. It was noted that the reports of NMDRCs in the human population are relatively new.

Although there are some proposed mechanisms to explain the dose-response relationship from NMDRCs, issues such as a higher dose potentially having a smaller impact on human health as compared to that of a lower dose, still needs a more definite explanation. The study re-iterated the need for a more critical review of the literature on lo-doses because of recent epidemiological findings that link EDC exposures and disease.

One area that is crucial is neonatal exposure to EDCs and the resulting health outcomes both early and later on in life. With available biomonitoring data from large reference populations, the lower levels of manmade EDCs present in humans have sparked some interest in the scientific community.

It is important to note that the study recognized that we are not only exposed to one chemical at a time, but dozens or possibly hundreds. There is very little information as to the effects of combinations of chemicals though there are several studies indicating that when EDCs are in combination, there can be unexpected or unpredictable effects on human and animal health.

The authors duly note that human health would benefit from the reduction of use of EDCs.

In summary, it was stressed that for chemicals with NMDRCs, the effects of low loses cannot be predicted from the effects observed at higher doses and also, when there are observed adverse effects on animals and humans within the range of environmental exposures, low doses definitely cannot be ignored.

In conclusion, the authors recommended the following:

  • Scientists and journal editors should publish data demonstrating NMDRCs and low-dose effects even if the pathway cannot be explained;
  • A significant expansion of generalized safety testing and surveillance should be initiated in order to detect potential adverse effects of EDCs;
  • As new chemicals are developed, a wider range of doses including a low-dose range, should be fully developed to assess dose response.
  • With such an extensive review on low-dose effects and nonmonotonic dose responses with respect to EDCs, it is hoped that this will encourage more collaboration between research scientists in academia, industry and government which would eventually result in improved study designs, as the authors noted. The authors feel thata collaborative approach to information should result in the discontinuing use of EDCs which will ultimately eliminate their health impacts on humans and on wildlife.

Sandra Madray is a Memeber of the PCN Board and is also co-founder of the non-profit, volunteer organization, Chemical Sensitivities Manitoba which focuses on the awareness and acceptance of chemical sensitivities, chemical usage and safe chemical substitution. Sandra is actively involved in pesticides and other environmental issues and is a member of the Steering Committee of the Manitoba Eco-Network.

Also in the Spring 2012 Issue of An Ounce

Published: May 14th, 2012