Applying Chemical Engineering Concepts to Toxicology

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Octamethylcyclotetrasiloxane (D4) and decamethylcyclopentasiloxane (DS) are common additives in personal care products. Both D4 and D5 are volatile, lipophilic chemicals that can be absorbed through the skin and lungs. Exposure to D4 has resulted in enzyme induction in the liver similar to that resulting from exposure to phenobarbital. Exposure to D5 has resulted in toxicity in the lung of the rat. However, it is not clear if these compounds will have similar effects in humans. To determine if these health effects are likely to occur in humans as well as rats, the mode of action of the compounds and the relationship between dose at the target tissue and response must be determined. As a first step to determining the mode of action and dose-response relationship, the major goal of this research project is to use chemical engineering methodolgies to develop physiologically based pharmacokinetic (PBPK) models for estimating D4 and D5 concentrations at the target tissue in both rats and humans. To achieve this goal, existing pharmacokinetic data for D4 and D5 distribution in the rat from the literature will be used in combination with PBPK model parameters measured experimentally (i.e., tissue:air and blood:air partition coefficients and kinetic constants for biotransformation). The resulting PBPK models for D4 and D5 distribution in humans can be used to assess the risk these compounds pose to humans.