S 140 Managing Biotransformation: The Metabolic, Genomic, and Detoxification Balance Points

13th International Symposium of The Institute for Functional Medicine

INTRODUCTION
Over the past forty years, concern has grown that some of the 80,000 chemicals used commercially could be exerting adverse effects on children's health. Many of these chemicals were synthesized for the first time within recent decades, suggesting that the body's detoxification mechanisms, the results of thousands of years of evolution, might not be effective in limiting their impact. The potential for exposure is substantial, as the US Environmental Protection Agency (US EPA) estimates that 2.5 billion pounds of chemicals are emitted yearly by large industrial facilities. At the same time, it is remarkable how limited are the data on the toxicities associated with most of these chemicals. The US EPA maintains the Integrated Risk Information System (IRIS), which serves as the repository of the consensus scientific opinions on chemical toxicity. Yet IRIS lists only 550 chemicals, indicating significant lacunae in the knowledge needed to estimate and manage the risks associated with current exposures. For many chemicals, most of the available data pertains to occupational exposures. The amount of data available regarding the potential effects of chemicals on children's brain development is much more limited. It was not until the 1990s that the US EPA published guidelines for registrants with regard to testing in animal models of the developmental neurotoxicity of certain chemicals, primarily organophosphate pesticides, for application in human risk assessments (US EPA OPPTS Health Effects Test Guideline 870.6300;
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At present, for many of the chemical exposures of current concern
with regard to children, little or no data are available on either the extent of or the neurological effects. This is true for exposures associated with living in proximity to hazardous waste sites, emissions from municipal waste incinerators, solvents, groundwater pollutants such as arsenic and manganese, and widely used materials such as phthalates (plasticizers) and polybrominated
diphenyl ethers (flame retardants). More information is available about population exposures to potential neurotoxicants such as pesticides, dioxins, elemental mercury, and fluoride, but detailed data are lacking on potential effects of such exposures. The data available can be characterized as "considerable" only for the so-called "big three": inorganic lead, methylmercury, and polychlorinated biphenyls. Fortunately, recent initiatives undertaken by the US Centers for Disease Control (US CDC) are addressing these issues, issuing a periodic National Report on Human Exposure to Environmental Chemicals, based on the National Health and Nutrition Examination Survey (NHANES). The Second Report, issued in 2003, provided data on 116 chemicals, 89 of which had never before been measured in a nationally representative sample of the US population, including many that would be expected to affect brain function. In the Third Report, issued in July 2005, data were provided on 148 chemicals. This effort, while important, represents only half of the challenge. The other half involves the difficult task of determining the dose-response relationships associated with these chemicals, since the mere presence of a chemical in blood or urine does not mean that it is affecting health.