Modeling Approaches for Estimating the Dosimetry of Inhaled Toxicants in Children

Abstract

Risk assessment of inhaled toxicants has typically focused upon adults, with modeling used to extrapolate dosimetry and risks from lab animals to humans. However, behavioral factors such as time spent playing outdoors may lead to more exposure to inhaled toxicants in children. Depending on the inhaled agent and the age and size of the child, children may receive a greater internal dose than adults because of greater ventilation rate per body weight or lung surface area, or metabolic differences may result in different tissue burdens. Thus, modeling techniques need to be adapted to children in order to estimate inhaled dose and risk in this potentially susceptible life stage. This paper summarizes a series of inhalation dosimetry presentations from the U.S. EPA's Workshop on Inhalation Risk Assessment in Children held on June 8–9, 2006 in Washington, DC. These presentations demonstrate how existing default models for particles and gases may be adapted for children, and how more advanced modeling of toxicant deposition and interaction in respiratory airways takes into account children's anatomy and physiology. These modeling efforts identify child-adult dosimetry differences in respiratory tract regions that may have implications for children's vulnerability to inhaled toxicants. A decision framework is discussed that considers these different approaches and modeling structures including assessment of parameter values, supporting data, reliability, and selection of dose metrics.

ACKNOWLEDGMENTS

The preparation of this manuscript was supported by combined funding from USEPA Office of Children's Health Protection (OCHP) and USEPA, Office of Research and Development, National Center for Environmental Assessment, as part of the funding for the June 8–9, 2006 Children's Inhalation Workshop held in Washington, DC. In addition, research presented in Section (default modeling approaches) was supported by OCHP and the preparation of Section (CFD modeling) was supported by funds provided by the American Chemistry Council (ACC) to the Chemical Industry Institute of Toxicology. The development of age-specific CFD models by scaling an adult model by children's nasal volumes was supported by the ACC and the U.S. Environmental Protection Agency conducted in collaboration with Ms. Annie Jarabek. The authors also wish to thank the peer review and insightful comments provided by Drs. Melvin Andersen, Linda Birnbaum, Harvey Clewell, Lynn Flowers, Gary Hatch, Elaina Kenyon, and Deirdre Murphy.

Notes

¹ The U.S. EPA included in its definition of reactivity the ability of the inhaled gas to serve as a substrate for metabolism in respiratory tract tissues. For example, vinyl acetate, while not especially water soluble, is readily extracted in the URT via carboxylesterase metabolism and is considered a Category 1 gas.

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