Bioavailability of octamethylcyclotetrasiloxane (D(4)) after exposure to silicones by inhalation and implantation.

We developed a physiologically based pharmacokinetic (PBPK) model to predict the target organ doses of octamethylcyclotetrasiloxane (D(4)) after intravenous (IV), inhalation, or implantation exposures. The model used (14)C-D(4) IV disposition data in rats to estimate tissue distribution coefficients, metabolism, and excretion parameters. We validated the model by comparing the predicted blood and tissues concentrations of D(4) after inhalation to experimental results in both rats and humans. We then used the model to simulate D(4) kinetics after single and/or repeated D(4) exposures in rats and humans. The model predicted bioaccumulation of D(4) in fatty tissues (e.g., breast), especially in women. Because of its high lipid solubility (Log P(oct/water) = 5.1), D(4) persisted in fat with a half life of 11.1 days after inhalation and 18.2 days after breast implant exposure. Metabolism and excretion remained constant with repeated exposures, larger doses, and/or different routes of exposure. The accumulation of D(4) in fatty tissues should play an important role in the risk assessment of D(4) especially in women exposed daily to multiple personal care products and silicone breast implants.