期刊
JOURNAL OF TOXICOLOGY AND ENVIRONMENTAL HEALTH-PART A-CURRENT ISSUES
卷 70, 期 20, 页码 1745-1751出版社
TAYLOR & FRANCIS INC
DOI: 10.1080/15287390701458991
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The absorption, distribution, metabolism, and excretion of volatile organic compounds (VOCs) are critically determined by a few chemical-specific factors, notably their blood and tissue partition coefficients (PC) and metabolism. Age-specific values for PCs in rats have rarely been reported or utilized in pharmacokinetic modeling for predicting dosimetry in toxicity studies with rats progressing through their lifestages. A mixture of six VOCs (benzene, chloroform, methyl ethyl ketone, methylene chloride, trichloroethylene, and perchloroethylene) was used to determine blood: air and tissue: air PCs in rats at three different ages (postnatal d 10, 60 d, and 2 yr) and blood: air PCs in pediatric and adult human blood. No differences with age in human blood: air PCs for the six compounds were observed. Rat blood: air PCs increased with age varying with compound. Tissue: air PCs showed tissue-specific changes with age. Water-soluble methyl ethyl ketone showed no age-dependent differences. Partition coefficients, particularly the blood: air PC, are key determinants of the rodent and human blood concentrations; age-appropriate values improve the accuracy of pharmacokinetic model predictions of population variability and age-specific exposures.
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