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J Toxicol Environ Health A

Title:		Age-dependent partition coefficients for a mixture of volatile organic solvents in Sprague-Dawley rats and humans
Author(s):		Mahle DA; Gearhart JM; Grigsby CC; Mattie DR; Barton HA; Lipscomb JC; Cook RS;
Address:		"AFRL/HEPB, Wright-Patterson Air Force Base, Ohio 45433, USA. deirdre.mahle@wpafb.af.mil"
Journal Title:		J Toxicol Environ Health A
Year:		2007
Volume:		70
Issue:		20
Page Number:		1745 - 1751
DOI:		10.1080/15287390701458991
ISSN/ISBN:		1528-7394 (Print) 0098-4108 (Linking)
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"
Keywords:		"Absorption Adult Aged Aged, 80 and over Aging/*metabolism Animals Child Child, Preschool Cholesterol/blood Female Humans Male Middle Aged Muscles/metabolism Rats Rats, Sprague-Dawley Solvents/metabolism/*pharmacokinetics Tissue Distribution Triglycerides/;"
Notes:		"MedlineMahle, Deirdre A Gearhart, Jeffery M Grigsby, Claude C Mattie, David R Barton, Hugh A Lipscomb, John C Cook, Robert S eng Research Support, U.S. Gov't, Non-P.H.S. England 2007/09/22 J Toxicol Environ Health A. 2007 Oct; 70(20):1745-51. doi: 10.1080/15287390701458991"