Journal
TOXICOLOGY LETTERS
Volume 134, Issue 1-3, Pages 9-16Publisher
ELSEVIER SCI IRELAND LTD
DOI: 10.1016/S0378-4274(02)00158-3
Keywords
mixtures; biological monitoring; toxicokinetic interaction; PBPK modelling; 1-hydroxypyrene; PAH1
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This short review is aimed at establishing general principles of biological monitoring for chemical mixtures. When interactions occur, they appear to be toxicokinetic in nature, often resulting from competition between two or more substances for the same biotransformation enzymes. A threshold is frequently observed for such an interaction, so that it might not influence the relationship between the absorbed dose and the value of the relevant biomarker. The extent of the interaction between pairs of chemicals also depends on the extent of biotransformation of each compound. As a result, the measurement of the parent compound or its metabolite will be differentially influenced by the presence of an interfering chemical. Biological limit values (BLV) are often established from the correlation between the bioindicator concentration in a given biological medium and the airborne concentration of the parent compound. When this relationship is derived from exposure to pure chemicals, it might not always yield an appropriate BLV for monitoring exposure to a mixture that includes this particular chemical. Under certain conditions such as the stability of mixture composition, a single biomarker such as 1-hydroxypyrene in PAH exposure can be used to reflect the overall exposure to a mixture. Finally, there is clearly a need for a greater research effort on the toxicology of mixtures to make biological monitoring a useful tool in occupational health. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved.
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