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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 4–7. 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. 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. Many 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.
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Abbreviations
ARE: antioxidant response element
ATSDR: Agency for Toxic Substances Disease Registry
BAL: British anti-Lewisite (dimercaprol)
BLL: blood lead level
CaNa2EDTA: calcium disodium ethylenediaminetetraacetic acid
CDC: Centers for Disease Control and Prevention
COX-2: cyclooxygenase 2; prostaglandin H synthase II
CV: cardiovascular
DMPS: sodium 2,3-dimercatopropane sulfonate
EEG: electroencephalogram
EPA: United States Environmental Protection Agency
ER: estrogen receptor
GI: gastrointestinal
GSH: reduced glutathione
GST: glutathione S-transferase
IARC: International Agency for Research on Cancer
IM: intramuscular
IV: intravenous
LOAEL: lowest adverse effect level
MCL: maximum contaminant level
MeHg+: methyl mercury
MMA: monomethylarsenic
NOAEL: no adverse effect level
NOx: nitrogen oxides
NQO1: quinone reductase
NTP: National Toxicology Program
PG: prostaglandin
RfD: reference dose
ROS: reactive oxygen species
SC: subcutaneous
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ASSESSMENT AND MANAGEMENT OF ENVIRONMENTAL RISK
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Environmental exposures to xenobiotics involve large populations exposed to many toxicants at low doses over long periods of time, which poses challenges for assessing the risks from those exposures. Thus, the focus of environmental risk assessment is on 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 are usually 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 provide complimentary approaches 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 examine potential toxic mechanisms of a chemical and 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 ...