Physiological changes associated with aging result in lower internal doses of toluene and perchloroethylene in simulations using pharmacokinetic modeling

Abstract

Physiologically based pharmacokinetic (PBPK) models were developed in order to translate external concentrations into internal dose estimates, but most PBPK models were developed for younger adults. A set of physiological parameters for ages 65, 75, and 85 of both genders were developed and were used with previously established human PBPK models of exposure to toluene and perchloroethylene (PERC) in order to investigate internal dose changes with increasing age. The predicted compartmental concentrations of toluene and PERC for aged adults were lower than predicted concentrations for younger adults, and this suggests that body composition changes with aging do not increase internal doses of inhaled toxicants alone after acute exposure. Hence, susceptibility to either toxicant was not expected to increase solely based on the physiological changes associated with aging. Predictions for a metabolite of PERC, however, were similar in magnitude across ages, which may lead to enhanced susceptibility if metabolic capacity changes with aging.

Keywords:

• PBPK modeling
• aging
• toluene
• perchloroethylene

Acknowledgments

This manuscript has been reviewed by the National Health and Environmental Effects Research Laboratory, U.S.E.P.A., and approved for publication. Mention of trade names and commercial products does not constitute endorsement or recommendation for use.

The authors would like to thank Dr Hisham El-Masri, Dr Rogelio Tornero-Velez, Dr Jane Ellen Simmons, Dr Mike DeVito, and Dr Linda Birnbaum for helpful comments during the preparation of this manuscript. Research support for Karen Yokley was provided by EPA CT833237.