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Application of Physiologically Based Pharmacokinetic/Pharmacodynamic Modeling in Cumulative Risk Assessment for N-Methyl Carbamate Insecticides
Citation:
Zhang, X., J. B. KNAAK, R. TORNERO-VELEZ, J. N. BLANCATO, AND C. C. DARY. Application of Physiologically Based Pharmacokinetic/Pharmacodynamic Modeling in Cumulative Risk Assessment for N-Methyl Carbamate Insecticides. Third, Chapter 73, Robert Krieger (ed.), Handbook of Pesticide Toxicology. Elsevier Ltd, Oxford, Uk, 2:1591-1605, (2010).
Impact/Purpose:
The National Exposure Research Laboratory′s (NERL) Human Exposure and Atmospheric Sciences Division (HEASD) conducts research in support of EPA′s mission to protect human health and the environment. HEASD′s research program supports Goal 1 (Clean Air) and Goal 4 (Healthy People) of EPA′s strategic plan. More specifically, our division conducts research to characterize the movement of pollutants from the source to contact with humans. Our multidisciplinary research program produces Methods, Measurements, and Models to identify relationships between and characterize processes that link source emissions, environmental concentrations, human exposures, and target-tissue dose. The impact of these tools is improved regulatory programs and policies for EPA.
Description:
Human exposure to xenobiotics may occur through multiple pathways and routes of entry punctuated by exposure intervals throughout a work or leisure day. Exposure to a single environmental chemical along multiple pathways and routes (aggregate exposure) may have an influence on an organism if the exposure dose is absorbed and distributed to target tissues. Exposure to multiple chemicals belonging to a class of similar compounds having a common mechanism of action may have a cumulative effect on target tissues (cumulative toxicity). Under this situation, the evaluation of the toxic effect from one chemical is obviously not enough. Instead, the net effect from all chemicals should be considered. Whenever such scenarios are encountered, cumulative risk assessment (CRA) is needed in order to evaluate the net cumulative toxicity caused by the aggregate exposure from all routes of entry for a single chemical or a group of chemicals that have a common mechanism of toxicity (U.S. EPA, 2002a). The applications of pesticides for the purpose of insect pest control creates such possible scenarios, not only in occupational settings but also in the general population. Organophosphorus compounds, N-methyl carbamates (NMCs), and pyrethroids are three popular classes of insecticides widely used in the United States and worldwide. For the general population, these pesticide residues may enter exposure pathways in food, drinking water, breathable air, and on residential surfaces where exposure may occur by ingestion, inhalation, and dermal contact. Recognizing the risk imposed by exposure to multiple chemicals, the Food Quality Protection Act (FQPA) of 1966 in the United States and Regulation (EC) No. 396/2005 in the European Union both mandate CRAs on human health resulting from exposure to multiple chemicals that exert their toxicity by a common mechanism of action. The FQPA requires that the U.S. Environmental Protection Agency (EPA) consider the cumulative effects to human health that can result from pesticides and other substances with the same mechanism of toxicity. To know the background and history of regulations regarding CRA, readers are directed to the U.S. EPA (2002b) for the available papers.