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Humans are exposed to chemicals from their environment on a daily basis. 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 to 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, discusses carcinogens and chemoprevention and heavy metal intoxication and chelation therapy, and provides an overview of endocrine disruptors and immunotoxicants. The chapter concludes with emerging data on how microbiome-mediated metabolism contributes to xenobiotic biotransformation and toxicity.
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Abbreviations
AhR: aryl hydrocarbon receptor
AR: androgen receptor
ARE: antioxidant response element
ATSDR: Agency for Toxic Substances Disease Registry
BAL: British anti-Lewisite (dimercaprol)
BLL: blood lead level
BPA: bisphenol A
CaNa2EDTA: calcium disodium ethylenediaminetetraacetic acid
CDC: U.S. Centers for Disease Control and Prevention
COX-2: cyclooxygenase 2
DDE: dichlorodiphenyldichloroethylene
DDT: dichlorodiphenyltrichloroethane
DEHP: di-2-ethylhexyl phthalate
DMPS: sodium 2,3-dimercatopropane sulfonate, dimercaprol
EDC: endocrine-disrupting chemical
EDTA: ethylenediaminetetraacetic acid
EPA: U.S. Environmental Protection Agency
ER: estrogen receptor
FSHR: follicle-stimulating hormone receptor
GI: gastrointestinal
GSH: reduced glutathione
Hg0: elemental mercury
IARC: International Agency for Research on Cancer
LHR: luteinizing hormone receptor
LOAEL: lowest adverse effect level
MCL: maximum contaminant level
MeHg+: methyl mercury
MMA: monomethylarsenic
NF-κB: nuclear factor-κB
NO: nitric oxide
NOAEL: no adverse effect level
NR: nuclear receptor
PAH: polycyclic aromatic hydrocarbon
PCB: polychlorinated biphenyls
PFAS: per- and poly-fluoroalkyl substances
PFOA: perfluorooctanoic acid
PFOS: perfluorooctane sulfonate
PKC: protein kinase C
PM: particulate matter
PPAR: peroxisome proliferator-activated receptor
RfD: reference dose
ROS: reactive oxygen species
TCDD: 2,3,7,8-tetrachlorodibenzo-p-dioxin
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ASSESSMENT AND MANAGEMENT OF ENVIRONMENTAL RISK
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People are exposed to many environmental xenobiotics 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 ...