Dosimetric and Toxicokinetic Parameters for the Developing Organism
The purpose of this project is to develop approaches for the application of dosimetric and toxicokinetic adjustments for assessing human health risks from exposures to environmental agents from conception through adolescence.
*What is the appropriate metric in adjusting for size-dependent lifestage metabolic differences?
*When is adjustment based on body surface area preferable to body weight?
*How should physiological changes be reflected in adjustment of internal dose for different life stages?
*How do changes in toxicokinetics and toxicodynamics during development affect dose to target tissues, and can these changes be incorporated in life-stage-specific dosimetric adjustment factors?
*Recognizing the variability at a given life stage, how should this be reflected in dosimetric adjustments; can distributions be used in place of discrete adjustment factors?
These and other questions apply both to the human and to laboratory animals (rat, mouse) for cross-species extrapolation in risk assessments. A background document has been prepared addressing the questions referred to above. Using this document, EPA plans to summarize the available data and information on dose metrics at various early-life stages for humans and common laboratory animal species. The report will evaluate the current state of the science, address the critical questions, and make recommendations for application of dosimetric adjustments in specific risk assessment situations. Variability and uncertainty will be considered and addressed. The final report or parts of it will be submitted for publication in the peer-reviewed literature.
- Journal Publication: Scaling Factors and Interspecies Extrapolation for Conception Through Adolescence