Age-dependent partition coefficients for a mixture of volatile organic solvents in Sprague-Dawley rats and humans.
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.
Mahle
Deirdre A
DA
AFRL/HEPB, Wright-Patterson Air Force Base, Ohio 45433, USA. deirdre.mahle@wpafb.af.mil
Gearhart
Jeffery M
JM
Grigsby
Claude C
CC
Mattie
David R
DR
Barton
Hugh A
HA
Lipscomb
John C
JC
Cook
Robert S
RS
D000042:Absorption; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000378:metabolism*; D000818:Animals; D002648:Child; D002675:Child, Preschool; D002784:Cholesterol / Q000097:blood; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009132:Muscles / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012997:Solvents / Q000378:metabolism / Q000493:pharmacokinetics*; D014018:Tissue Distribution; D014280:Triglycerides / Q000097:blood
D012997:Solvents; D014280:Triglycerides; D002784:Cholesterol