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Human metabolism and metabolic interactions of deployment-related chemicals.

Authors
Hodgson-E; Rose-RL
Source
Drug Metab Rev 2005 Jan; 37(1):1-39
NIOSHTIC No.
20036973
Abstract
It has been suggested that chemicals and, more specifically, chemical interactions, are involved as causative agents in deployment-related illnesses. Unfortunately, this hypothesis has proven difficult to test, because toxicological investigations of deployment-related chemicals are usually carried out on surrogate animals and are difficult to extrapolate to humans. Other parts of the problem, such as the definition of variation within human populations and the development of methods for designating groups or individuals at significantly greater risk, cannot be carried out on surrogate animals, and the data must be derived from humans. The relatively recent availability of human cell.fractions, such as microsomes, cytosol, etc., human cells such as primary hepatocytes, recombinant human enzymes, and their isoforms and polymorphic variants has enabled a significant start to be made in developing the human data needed. These initial studies have examined the human metabolism by cytochrome P450, other phase I enzymes, and their isoforms and, in some cases, their polymorphic variants of compounds such as chlorpyrifos, carbaryl, DEET, permethrin, and pyridostigmine bromide, and, to a lesser extent, other chemicals from the same chemical and use classes, including solvents, jet fuel components, and sulfur mustard metabolites. A number of interactions at the metabolic level have been described both with respect to other xenobiotics and to endogenous metabolites. Probably the most dramatic have been seen in the ability of chlorpyrifos to inhibit not only the metabolism of other xenobiotics such as carbaryl and DEET but also to inhibit the metabolism of steroid hormones.
Keywords
Chemical-agent-detectors; Chemical-analysis; Chemical-composition; Chemical-extraction; Chemical-hypersensitivity; Alcohols; Aldehydes; Chemical-agent-detectors; Chemical-properties; Chemical-reactions; Chemical-structure; Chemical-synthesis; Chemical-warfare-agents; Metabolism; Enzymatic-disorders; Enzymatic-effects; Enzyme-activity; Enzyme-complexes; Enzyme-inhibitors; Enzymes; Author Keywords: Alcohol dehydrogenase; Aldehyde dehydrogenase; Carbamates; Chemical warfare agents; Cytochrome P450; Deployment-related chemicals; Jet fuel components; Metabolic interactions; Metabolism; Organophosphorus compounds; Pyrethroids; Repellents; Xenobiotic-metabolizing enzymes
Contact
Ernest Hodgson, Department of Environmental and Molecular Toxicology, Box 7633, North Carolina State University, Raleigh, NC 27695
CODEN
DMTRAR
Publication Date
20050101
Document Type
Journal Article
Email Address
ernest_hodgson@ncsu.edu
Funding Type
Cooperative Agreement
Fiscal Year
2005
NTIS Accession No.
NTIS Price
Identifying No.
Cooperative-Agreement-Number-U50-OH-007551
Issue of Publication
1
ISSN
0360-2532
Source Name
Drug Metabolism Reviews
State
NC
Performing Organization
East Carolina University
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