This Article Full Text (PDF) References Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Saved Citations Download to citation manager Request Permissions Request Reprints Add to My Marked Citations Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Dennison, J. E Articles by Andersen, M. E Search for Related Content PubMed PubMed Citation Articles by Dennison, J. E Articles by Andersen, M. E Social Bookmarking                   What's this?

Occupational exposure limits in the context of solvent mixtures, consumption of ethanol, and target tissue dose

Center for Environmental Toxicology & Technology, Department of Environmental and Radiological Health Sciences, Colorado State University, CO, USA, dennison{at}colostate.edu

Philip L Bigelow

Workplace Studies, Institute for Work & Health, Toronto, Ontario, Canada

Melvin E Andersen

CIIT Centers for Health Research, Research Triangle Park, NC, USA

Individuals are exposed to mixtures, and never to single chemicals. Depending on the composition of the elements of mixtures, significant toxicological interactions between the components may occur. These interactions are complex and often difficult to predict, ranging from synergistic to additive and subadditive interactions. The nature of the interactions needs to be evaluated as the target tissue dose of the active form of each chemical. PBPK modeling is an effective tool for determining the target tissue dose and evaluating these interactions when data are available for model development. Some of the interactions are pharmacokinetic in nature, affecting the disposition of other chemicals in the body. Other interactions can be pharmacodynamic in nature, altering the effects that other chemicals have on the organism. For many organic solvents, these interactions occur principally at the level of the metabolizing enzyme, cytochrome P-450 2E1 (CYP2E1). Many solvents are known to induce or inhibit CYP2E1, or both. Mixtures may be comprised of concomitant exposures to chemicals or from components encountered separately on-the-job, off-the-job, through the diet, and otherwise. Examples of mixtures where the exposure to separate components occurs off the job will be discussed, with special emphasis on ethanol consumption as a modifier of solvent pharmacokinetics. The present practice of the linear extrapolation of the toxicity of individual mixture components in the interpretation of occupational exposure limits will also be critiqued.

Key Words: CYP2E1 • ethanol • induction • inhibition • mixtures • OELs • PBPK • TLVs

CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?