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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 47. 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.





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




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.


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 assessment is used ...

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