Determination of Partition coefficients for a Mixture of Volatile Organic Compounds in Rats and Humans at Different Life Stages

摘要

Pharmacokinetic differences in child, adult and elderly populations remain ill defined. Partition coefficients (PCs) are an integral component of pharmacokinetic models and determining differences in tissue partitioning of volatile organic chemicals across life stages can help reduce the uncertainty in risk assessment. PCs for methylene chloride 1 methyl ethyl ketone, chloroform, benzene, trichloroethylene and perchloroethylene were determined in blood, liver, kidney, fat, muscle and brain of male adult (60 days) and aged (22 months) Sprague-Dawley (S-D) rats (n = 10) and male and female S-D pups (n = 10 litters) at postnatal day 10, and in human blood from male and female pediatric and adult donors. Human adult and pediatric blood:air PCs were similar regardless of sex; values for the solvents ranged from 8.3 +/- 2.3 (adult female, benzenc) to 191.3 +/- 5.7 (pediatric male, methyl ethyl ketone). Liver:air methylene chloride PCs for adult male rats averaged 20.4 +/- 4.8 compared to 12.7 +/- 1.0 for male rat pups.