Chapter 67

### INTRODUCTION

Humans are exposed to chemicals from their environment daily. Fortunately, mammals have evolved mechanisms to protect themselves from toxic effects of many exogenous chemicals, including the xenobiotic transport and metabolic mechanisms described in Chapters 4,5,6,7. While the human body is relatively well adapted to deal with xenobiotics, there are situations in which such environmental agents may cause significant toxicity. The industrial revolution and the development of chemical industries have increased human exposures to chemicals that were previously infrequent or absent. Occupational exposures to xenobiotics are of particular concern because workers often will be exposed to specific chemicals at concentrations that are orders of magnitude higher than those to which the general population is exposed. Increasing concern about environmental toxicants has stimulated interest and research in environmental toxicology, the study of how chemicals in our environment adversely affect human health, and in occupational toxicology, the study of how chemicals in the workplace affect human health. Myriad authoritative textbooks are available in these areas. 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.

### ENVIRONMENTAL RISK ASSESSMENT AND RISK MANAGEMENT

When assessing the risks of environmental exposures to xenobiotics, many of the same principles discussed in Chapter 4 for drug toxicity apply; there are, however, significant differences. With environmental exposures, one has to consider population exposures to low-dose toxicants over long periods of time. Thus, one must give more attention to the low end of the dose-response curve, using experiments based on chronic exposures. Particular attention is given to the potential for individuals with higher susceptibility. Unlike drugs, which are given to treat a specific disease and will 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.

Two complimentary approaches are used to predict the toxic effects of environmental exposures: epidemiology and toxicology. 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. Each of these approaches has strengths and weaknesses, and information from both is integrated into environmental risk assessment. Risk assessment is used to develop management approaches, such as laws and regulations, to limit exposures to environmental toxicants to a level that is considered safe.

Epidemiological Approaches to Risk Assessment

Epidemiologists use multiple approaches to assess the risks of human environmental exposures (Gordis, 2008). The disadvantage of these approaches is the variability between people in their exposures and genetics, ...

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