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INTRODUCTION

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Myriad authoritative textbooks are available in the area of environmental toxicology. This chapter does not attempt a thorough coverage; rather, it sets forth a few basic principles, briefly discusses carcinogens and chemoprevention, and then focuses on the pharmacotherapy of heavy metal intoxication.

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ASSESSMENT AND MANAGEMENT OF ENVIRONMENTAL RISK

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When assessing the risks of environmental exposures to xenobiotics, one must consider population exposures to low-dose toxicants over long periods of time. Thus, one must give careful attention to the low end of the dose-response curve, using experiments based on chronic exposures. Unlike drugs, which are given to treat a specific disease and should have benefits that outweigh the risks, environmental toxicants usually are only harmful. In addition, exposures to environmental toxicants usually are involuntary, there is uncertainty about the severity of their effects, and people are much less willing to accept their associated risks.

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Epidemiology and toxicology are 2 approaches used to predict the toxic effects of environmental exposures. Epidemiologists monitor health effects in humans and use statistics to associate those effects with exposure to an environmental stress, such as a toxicant. Toxicologists perform laboratory studies to try to understand the potential toxic mechanisms of a chemical to predict whether it is likely to be toxic to humans. Information from both approaches is integrated into environmental risk assessment. Risk assessment is used to develop laws and regulations to limit exposures to environmental toxicants to a level that is considered safe.

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EPIDEMIOLOGICAL APPROACHES TO RISK ASSESSMENT

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Assessing human exposures over long periods of time and drawing conclusions about the health effects of a single toxicant present great challenges. Epidemiologists usefully rely on biomarkers in assessing risk. There are 3 types of biomarkers:

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  • Biomarkers of exposure usually are measurements of toxicants or their metabolites in blood, urine, or hair. Blood and urine concentrations measure recent exposures, while hair levels measure exposure over a period of months. An example of an unusual exposure biomarker is X-ray fluorescent measurement of bone lead levels, which estimates lifetime exposure to lead.

  • Biomarkers of toxicity are used to measure toxic effects at a subclinical level and include measurement of liver enzymes in the serum, changes in the quantity or contents of urine, and performance on specialized exams for neurological or cognitive function.

  • Biomarkers of susceptibility are used to predict which individuals are likely to develop toxicity in response to a given chemical. Examples include single nucleotide polymorphisms in genes for metabolizing enzymes involved in the activation or detoxification of a toxicant. Some biomarkers simultaneously provide information on exposure, toxicity, and susceptibility. For example, the measurement in the urine of N7-guanine adducts from aflatoxin B1 provides evidence of both exposure and a toxic effect (in this case, DNA damage). Such biomarkers are valuable because they can support a proposed mechanism of toxicity.

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Several types of epidemiological studies are ...

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