Cutting Edge PBPK Models and Analyses: Providing the Basis for Future Modeling Efforts and Bridges to Emerging Toxicology Paradigms.

Physiologically based Pharmacokinetic (PBPK) models are used for predictions of internal or target dose from environmental and pharmacologic chemical exposures. Their use in human risk assessment is dependent on the nature of databases (animal or human) used to develop and test them, and includes extrapolations across species, experimental paradigms, and determination of variability of response within human populations. Integration of state-of-the science PBPK modeling with emerging computational toxicology models is critical for extrapolation between in vitro exposures, in vivo physiologic exposure, whole organism responses, and long-term health outcomes.

The US EPA reference dose for methylmercury: sources of uncertainty.

The US Environmental Protection Agency (EPA) derived a reference dose for methylmercury in 2001, based on an extensive analysis by the National Research Council (NRC) of the National Academy of Sciences. The NRC performed benchmark dose analysis on a number of endpoints from three longitudinal prospective studies: the Seychelles Islands, the Faroe Islands, and the New Zealand studies. Adverse effects were reported in the latter two studies, but not in the Seychelles study.