PBPK Modeling: Predicting disposition of a compound in humans
We are exposed to a wide range of chemicals from multiple sources including food, textiles, household cleaning products, cosmetics, fragrances, and medicines. Whether animal or cell-based studies are conducted to determine the dosage at which toxicity starts to occur, PBPK models can then be used to predict the equivalent doses for humans that would cause similar effect. The traditional and most common use for PBPK models in risk assessment is to understand how the compound is absorbed, distributed, metabolized and excreted (ADME). Beyond the traditional ADME, using PBPK models, we assist clients in:
- In vitro to in vivo extrapolation (IVIVE) or interspecies extrapolation: One of the more common uses of PBPK modeling is to translate data from in vitro or animal studies to human equivalent exposures.
- Intra-species extrapolation: Predicting exposure for vulnerable populations such as children, the elderly or occupational exposure. We submitted data from a PBPK model to the Environmental Protection Agency (EPA) that they used to determine children and adults were not different in how they were affected by a class of pesticides called pyrethroids (See case study for more details).
- Route-to-route extrapolation: Predicting concentration in blood or tissue from dermal exposure using oral exposure data.
- High-to-low dose extrapolation: Using high dosage exposure to predict concentration in blood and tissue for exposure at a lower dose.
- Population variability assessment: using PBPK modeling and statistical analysis such as Monte Carlo simulations to estimate variability in internal target doses across a population.
- Human biomonitoring data and epidemiological data: Estimating population daily exposure intakes that are consistent with blood or urine measures found in biomonitoring surveys.