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J Toxicol Environ Health A. 2007 Oct;70(20):1745-51.

Age-dependent partition coefficients for a mixture of volatile organic solvents in Sprague-Dawley rats and humans.

Author information

  • 1AFRL/HEPB, Wright-Patterson Air Force Base, Ohio 45433, USA. deirdre.mahle@wpafb.af.mil

Abstract

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.

PMID:
17885931
DOI:
10.1080/15287390701458991
[PubMed - indexed for MEDLINE]
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