Methods for evaluating variability in human health dose-response characterization.

Area of Science:

• Environmental Health Risk Assessment
• Toxicology
• Human Health Risk Evaluation

Background:

• Reference Dose (RfD) and Reference Concentration (RfC) are human health reference values (RfVs) for low-risk exposure levels.
• The 2009 NRC report recommended redefining RfVs as risk-specific doses.
• Current variability distributions rely heavily on pharmaceutical studies.

Purpose of the Study:

• To explore new data and methods for improving quantitative variability estimation in human response to environmental chemicals.
• To identify research categories that can inform updated human variability distributions for risk assessment.

Main Methods:

• Review of existing methods and identification of new research avenues.
• Consideration of controlled human experiments, epidemiology, animal models, and in vitro studies.
• Focus on in vitro toxicokinetic and toxicodynamic variability estimation.

Main Results:

• New data and methods are available to enhance human variability estimations.
• Several research categories can contribute to improved variability distributions.
• In vitro approaches offer significant near-term potential for advances.

Conclusions:

• Updated human variability distributions are crucial for refining risk-specific doses.
• In vitro methods, with further development, are most promising for near-term improvements.
• Integrating diverse data sources will enhance the accuracy of environmental health risk assessments.