Human Metabolism and Interactions of Deployment-Related Chemicals
Abstract
This study examines the metabolism and interactions of xenobiotic toxicants important in military deployments as inducers, substrates and/or inhibitors of human enzymes including the important isoforms of these enzymes HPLC analytical methods have been brought on line for chlorpyrifos, DEET, permethrin and methods for pyridostigmine bromide and sulfur mustard metabolites are being tested. Five human cytochrome P450 (P450) isoforms metabolizing chlorpyrifos have been identified. They include forms known to be inducible and forms known to be polymorphic. These forms vary through a 50-fold range in their ability to produce chlorpyrifos oxon, the active metabolite, as compared to the production of detoxication products. Both quantitative and qualitative variations between the ability of microsomes from individual human livers to metabolize chlorpyrifos were observed, suggesting that different sensitivities toward organophosphorus toxicants exist in the human population. DEET is shown to be metabolized by human P450 isoforms and, in mice, to be an inducer of P450. These and the remaining studies will permit more confident extrapolation of animal studies to humans and permit identification of interactions not apparent from animal studies. It may also permit identification of human subpopulations at greater risk from specific xenobiotic toxicants and will produce specific analytic methodologies for assessment of future exposures.
Document Details
- Document Type
- Technical Report
- Publication Date
- Feb 01, 2001
- Accession Number
- ADA388641
Entities
People
- Alan A. Brimfield
- Ernest Hodgson
- Joyce E. Goldstein
- Randy L. Rose
Organizations
- North Carolina State University