Assessing the Effects of Endocrine Disruptors in the National Children's Study

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Children are uniquely vulnerable to toxic chemicals in the environment. Among the environmental toxicants to which children are at risk of exposure are endocrine disruptors (EDs)--chemicals that have the capacity to interfere with hormonal signaling systems. EDs may alter feedback loops in the brain, pituitary, gonads, thyroid, and other components of the endocrine system. They can affect development. Effects of EDs have been described in wildlife populations, in animals exposed experimentally, and to a more limited extent in humans. Mechanisms of action of EDs are increasingly being elucidated, and genetic polymorphisms that convey differential susceptibility to EDs are beginning to be explored. It is hypothesized that in utero and early childhood exposures to EDs may be responsible, at least in part, for decreases in semen quality; increasing incidence of congenital malformations of the reproductive organs, such as hypospadias; increasing incidence of testicular cancer; and acceleration of onset of puberty in females. The National Children's Study (NCS) will provide a unique opportunity to test the validity of these hypotheses in the context of a large prospective multiyear epidemiologic investigation. It will be essential in the NCS to assess exposures to a range of putative natural and synthetic EDs, to assess outcomes possibly due to ED exposure, to examine the potential interplay between EDs and genetic polymorphisms, and to seek links between ED exposures in early life and endocrine, reproductive, neurobehavioral, and other outcomes throughout the life span. Key words: endocrine disruptors, environmental epidemiology, exposure assessment, National Children's Study. Environ Health Perspect 111:1678-1682 (2003). doi:10.1289/ehp.5799 available via http://dx.doi.org/[Online 18 March 2003]

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The National Children's Study (NCS) is a very large prospective epidemiologic study being developed by the National Institute of Child Health and Human Development, in collaboration with the National Institute of Environmental Health Sciences, the U.S. Environmental Protection Agency (EPA), and the Centers for Disease Control and Prevention. The goal of the NCS is to examine the influences of early exposures--environmental, behavioral, lifestyle, and socioeconomic--on human development and on child and adult health. The NCS will follow as many as 100,000 children in all regions of the United States, from early pregnancy to 21 years of age (Berkowitz et al. 2001). The NCS offers a unique opportunity to examine critically the possible etiologic contribution of early exposures to the genesis of developmental disabilities, asthma, reproductive problems, and possibly cancer. Critically important to the success of this complex study will be the careful choice of which hypotheses to test, which exposures to measure, which outcomes to assess, what data infrastructure to build, what specimens to store, and what sorts of ethical safeguards to impose.

To provide guidance to the NCS in assessing exposures to endocrine disruptors (EDs) and their effects on children's health and development, the Center for Children's Health and the Environment of the Mount Sinai School of Medicine convened a workshop titled "Endocrine Disruptors and Children's Health: A Workshop to Examine the Effects of Endocrine Disruptors on Child Development for a National Longitudinal Study" on 16-17 March 2000 (New York, NY). The goals were to review evidence of the impact of EDs on health and to provide evidence-based guidance on how to measure exposures to EDs and on how to assess the possible impacts of EDs on child health and development in the NCS.

The workshop was divided into three sessions: "Exposure Assessment," which identified chemical exposures suspected of causing endocrine disruption and discussed routes of exposure, timing of exposure, and approaches to quantification of these exposures; "Cellular and Molecular Mechanisms of Endocrine Disruption"; and "Epidemiology and Assessment of Outcomes," which offered recommendations on how to incorporate recent research on EDs into the NCS. In this article we introduce the series of reports that derived from this workshop and present an overall rationale for incorporating assessment of EDs into the NCS.

Why Study Children?

Children are uniquely vulnerable to toxic chemicals in the environment. They are at risk of exposure to more than 85,000 synthetic chemical compounds, most of which have been developed since World War II (U.S. EPA 1998a). They are at especially high risk of exposure to the approximately 3,000 high-production-volume (HPV) chemicals that are produced or imported in the United States in quantities [greater than equal to] one million lb/year. HPV chemicals have the potential to be widely dispersed in foods, household products, air, water, and waste sites. Many hundreds of HPV chemicals have not been tested for their potential human toxicity, and less than 20% have been studied for their possible developmental or pediatric toxicity (National Academy of Sciences 1984; U.S. EPA 1998b).

Children's heightened susceptibility to chemical toxins stems from several sources (Landrigan et al. 1999; National Research Council 1993): a) Children have disproportionately heavy exposures to environmental toxicants, b) Children's metabolic pathways, especially in the first months after birth, are immature. Children's ability to metabolize, detoxify, and excrete many toxicants is different from that of adults. In some instances, children are actually better able than adults to deal with environmental toxicants. Often, however, they are less well able to metabolize and excrete toxic chemicals and thus are more vulnerable to them. c) Children are undergoing rapid growth and development, and their developmental processes are easily disrupted by exposures to xenobiotics. d) Because children have more future years of life than most adults, they have more time to develop chronic diseases that may be triggered by early exposures. Many diseases that are caused by toxicants in the environment require decades to develop. Many of those diseases, including …