Editorials

Potential Toxicity of Synthetic Chemicals: What You Should Know About Endocrine-Disrupting Chemicals



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Am Fam Physician. 2008 Sep 1;78(5):565-566.

A growing body of evidence suggests that many synthetic chemicals once considered safe can be harmful to the developing fetus, infant, and child. There is particular concern about the developmental effects of substances known as endocrine-disrupting chemicals (EDCs), which can mimic, block, or alter the synthesis, transport, binding, or metabolism of endogenous hormones.1

Just as the estrogenic effects of diethylstilbestrol affected the daughters and granddaughters of women exposed during pregnancy, exposure to EDCs during development has been found to interfere with physiologic signaling in experimental animals, permanently altering neurologic, reproductive, immune, and endocrine systems by disrupting thyroid hormones and sex steroid homeostasis.2 Human evidence is largely consistent with animal data, linking developmental EDC exposure to: (1) neurodevelopmental effects, including lowered IQ and attention deficits; (2) reproductive effects, such as hypospadias, cryptorchidism, decreased fertility, and accelerated puberty; (3) immune dysfunction linked to asthma and allergies; and (4) hormonally mediated cancers.3

Family physicians have the opportunity—during preconception counseling or in routine prenatal and well-child care—to educate patients and reduce exposure when possible to environmental contaminants, including EDCs.4

Human Exposure to EDCs

Humans encounter EDCs daily in many forms, including:

  • Polybrominated diphenyl ethers added as flame-retardants to computers, televisions, and furniture.

  • Phthalates added to soften plastics (e.g., toys) and vinyl products or to carry fragrances in cosmetics and household cleaners.

  • Bisphenol A, a component of hard plastics that leaches from some plastic containers and the linings of cans.

  • Perfluorooctanoic acid, which forms nonstick, stain repellant, or waterproof coatings on cookware, carpets, and clothing.

  • Organochlorines (e.g., polychlorinated diphenyl ethers), many of which are banned, but are still found in the environment.

All of these EDCs have been detected in the blood and urine of most U.S. children and adults in representative samples of the National Health and Nutrition Examination Survey cohort.5 They, along with more than 100 other environmental contaminants, have also been detected in breast milk6 and umbilical cord blood.7

Assessing Health Effects of Chemical Exposures

EDCs illustrate several concepts that physicians can use to evaluate emerging environmental health science.

Windows of vulnerability: In animal studies, even brief exposures to EDCs during critical developmental periods have produced direct health effects, as well as alteration in the response to future exposures. For example, although not a frank carcinogen, bisphenol A has been shown to increase animals' likelihood of developing breast cancer in response to subsequent estrogen exposure.8

Low-dose effects: Although classic toxicology asserts, “the dose makes the poison,” most hormonally active substances affect physiologic signaling mechanisms at extremely low doses, usually below those used in standard toxicology testing. Like their endogenous counterparts, many EDCs show nonlinear dose-response relationships, which make extrapolations from high-dose studies inaccurate.9

Multigenerational effects: Many EDCs alter gene expression, producing heritable effects known as epigenetic changes, which can affect animal offspring three generations after a single in utero exposure.10

Chronic, mixed exposures: Unlike experimental animals, humans are exposed to a mixture of chemicals, some of which produce additive or synergistic effects.11

These concepts illustrate that the traditional tools of toxicology and epidemiology are unable to accurately characterize human exposures to, or potential health effects of, synthetic chemicals and pollutants. In addition, it is difficult to capture health effects in case-control studies of universally exposed populations. Observational studies can only establish association, but not causality, and retrospective studies are often limited by lack of exposure data.

Financially vested industry groups have historically undermined scientific evidence when the findings could implicate their products.12 In the case of bisphenol A, 90 percent of government-funded studies found significant effects, whereas nearly all industry-funded studies produced negative findings, attributable to nonstandardized experimental conditions, methodologic errors, and failure to use positive controls.13

In November 2007, an expert panel on bisphenol A convened by The National Toxicology Program expressed “some concern” for neurologic and behavioral effects of in utero and childhood exposure, but only “minimal concern” for its potential reproductive effects.14 The panel's report was widely criticized for flaws and inconsistencies in its inclusion criteria and was investigated for its employment of consultants with ties to industry.15 A draft revised report released in April 2008 incorporated evidence from hundreds of studies not included in the first report, and raised the level of risk, expressing “some concern” for reproductive effects in addition to the neurologic and behavioral effects in fetuses, infants, and children exposed to bisphenol A.16

Recently, legislative bills and reports in the popular press have targeted EDCs, such as bisphenol A and phthalates. Now, the United States has banned phthlates in children's products, and some sources suggest alternatives to food products most likely to contain EDCs. Although the U.S. Food and Drug Administration does not currently recommend against these products, a task force is reassessing the safety of one EDC, bisphenol A.

Precautionary Action

As physicians, we will never have perfect information. However, widespread exposure to EDCs, at doses linked to chronic health effects in animals, combined with significant barriers to establishing definitive evidence of human harm, warrant that physicians and their patients be educated about developmental exposure to EDCs. Given the ubiquity of EDCs in the environment, true risk reduction will ultimately hinge on our ability as a society to reduce or eliminate the production and use of the most hazardous substances.

Address correspondence to Megan Schwarzman, MD, MPH, at mschwarzman@berkeley.edu. Reprints are not available from the author.

Resources

The Collaborative on Health and the Environment Searchable database of chemicals and diseases (http://database.healthandenvironment.org/index.cfm).

Center for Science in the Public Interest's Nutrition Action Health Letter List of resources about bisphenol A (http://www.cspinet.org/nah/bpa.html#reducing).

Greater Boston Physicians for Social Responsibility Fact sheets for patients and physicians, including the Pediatric Environmental Health Toolkit (http://psr.igc.org/hhep.htm).

Natural Resources Defense Council Consumer guides and summaries of the science (http://www.nrdc.org/health/).

Women's Health & the Environment Environmental health toolkit (http://www.womenshealthandenvironment.org/article.php?list=type&type=64).

REFERENCES

1. World Health Organization. Global assessment of the state-of-the-science of endocrine disruptors. http://www.who.int/ipcs/publications/new_issues/endocrine_disruptors/en/index.html. Accessed June 5, 2008.

2. Kavlock RJ, Daston GP, DeRosa C, et al. Research needs for the risk assessment of health and environmental effects of endocrine disruptors: a report of the U.S. EPA-sponsored workshop. Environ Health Perspect. 1996;104(suppl 4):715–740.

3. Grandjean P, Bellinger D, Bergman A, et al. The faroes statement: human health effects of developmental exposure to chemicals in our environment. Basic Clin Pharmacol Toxicol. 2008;102(2):73–75.

4. Genuis SJ. Health issues and the environment—an emerging paradigm for providers of obstetrical and gynaecological health care. Hum Reprod. 2006;21(9):2201–2208.

5. Centers for Disease Control and Prevention. Third National Report on Human Exposure to Environmental Chemicals. Atlanta, Ga.: CDC, 2005. http://www.cdc.gov/exposurereport/report.htm. Accessed June 5, 2008.

6. LaKind JS, Amina Wilkins A, Berlin CM Jr. Environmental chemicals in human milk: a review of levels, infant exposures and health, and guidance for future research. Toxicol Appl Pharmacol. 2004;198(2):184–208.

7. Houlihan J, Kropp T, Wiles R, Gray S, Campbell C, et al. Body burden: the pollution in newborns. Washington, DC: Environmental Working Group; July 14, 2005. http://archive.ewg.org/reports_content/bodyburden2/pdf/bodyburden2_final-r2.pdf. Accessed June 5, 2008.

8. Birnbaum LS, Fenton SE. Cancer and developmental exposure to endocrine disruptors. Environ Health Perspect. 2003;111(4):389–394.

9. National Toxicology Program's report of the endocrine disruptors low-dose peer review. August 2001. Department of Health and Human Services, Research Triangle Park, N.C. http://ntp.niehs.nih.gov/ntp/htdocs/liason/LowDosePeerFinalRpt.pdf. Accessed June 5, 2008.

10. Edwards TM, Myers JP. Environmental exposures and gene regulation in disease etiology. Environ Health Perspect. 2007;115(9):1264–1270.

11. Crofton KM, Craft ES, Hedge JM, et al. Thyroid-hormone-disrupting chemicals: evidence for dose-dependent additivity or synergism. Environ Health Perspect. 2005;113(11):1549–1554.

12. Huff J. Industry influence on occupational and environmental public health. Int J Occup Environ Health. 2007;13(1):107–117.

13. vom Saal FS, Welshons WV. Large effects from small exposures. II. The importance of positive controls in low-dose research on bisphenol A. Environ Res. 2006;100(1):50–76.

14. National Toxicology Program, U.S. Department of Health and Human Services. NTP-Center for the Evaluation of Risks to Human Reproduction (CERHR) Expert Panel report on the reproductive and developmental toxicity of bisphenol A. November 26, 2007. http://cerhr.niehs.nih.gov/chemicals/bisphenol/BPAFinalEPVF112607.pdf. Accessed June 5, 2008.

15. Environmental Working Group. Attachment 1: failure of CERHR assessment of BPA to meet basic scientific standards. August 6, 2007. http://www.ewg.org/files/BPAletter20080125.pdf. Accessed June 5, 2008.

16. National Toxicology Program, National Institutes of Health, U.S. Department of Health and Human Services. Draft NTP brief on bisphenol A. April 14, 2008. http://cerhr.niehs.nih.gov/chemicals/bisphenol/BPADraftBriefVF_04_14_08.pdf. Accessed June 5, 2008.


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