Human Metabolism and Interactions of Deployment-Related Chemicals
Abstract
Methods were developed for the investigation of the in vitro metabolism of deployment-related chemicals in humans. These studies utilized recombinant human enzymes, human liver cell fractions and isolated human hepatocytes. The metabolism of chlorpyrifos, DEET, permethrin, pyridostigmine bromide, sulfur mustard, naphthalene and nonane as well as a number of their metabolites and related chemicals was investigated. For the most part these were the first investigations of the metabolism of these chemicals in humans. Metabolic interactions, including inhibition of the metabolism of xenobiotics and endogenous metabolites such as testosterone and estradio were also examined. The potency of organophosphorus chemicals such as chlorpyrifos in the inhibition CYP-dependent monooxygenase reactions was, in many cases, dramatic and a cause for concern as was the ability of chlorpyrifos oxon to inhibit permethrin metabolism. The potential for interactions based on induction and on a combination of induction and cytotoxicity were demonstrated in the case of pyrethroids, DEET and chlorpyrifos in experiments utilizing human hepatocytes. Interactions involving JP-8 jet fuel components such as nonane and naphthalene were of interest because of the expected exposure scenarios and since the fuel itself appeared to function both as an inhibitor and as an inducer in human in vitro experiments. Preliminary genotyping experiments were conducted on two small sample sets of DNA from veterans of the first Gulf War. All of the above permitted a number of conclusions concerning human health risk analysis and possible populations and individuals at increased risk from chemical exposure. A number of recommendations were made concerning risk analysis specific to military needs and to research activities that should have a high priority in that regard.
Document Details
- Document Type
- Technical Report
- Publication Date
- Aug 01, 2008
- Accession Number
- ADA489766
Entities
People
- Alan A. Brimfield
- Andrew D. Wallace
- Ernest Hodgson
- Joyce E. Goldstein
- Randy L. Rose
Organizations
- North Carolina State University