Evaluating hexabromocyclododecane (HBCD) toxicokinetics in humans and rodents by physiologically based pharmacokinetic modeling

Abstract Hexabromocyclododecane (HBCD) is a flame retardant largely found in textiles, electrical equipment and building materials. The potential exposure associated with adverse effects described in animals make HBCD a substance of interest. To better characterize the risk in humans, it is important to understand the dose-response relationship using available data concerning the exposure and toxicity of environmental contaminants such as HBCD. For this reason, a physiologically-based pharmacokinetic (PBPK) model was developed to describe the disposition of α-HBCD after a single oral administration. The results showed that the model can appropriately predict blood and tissue concentration in rodents. The model described that lipoproteins play a key role in the distribution of α-HBCD in the body even though its lipophilic nature would suggest preferential storage in adipose tissue. The model was also adapted to humans to predict plasma exposure to α-HBCD and showed reasonable estimates when compared against estimated diet levels and biomonitoring measures. As part of a larger study on integrating new toxicity data for human health risk assessment, the present PBPK model will serve as a supporting tool to help extrapolate and interpret in vitro and in vivo kinetics of flame retardants such as HBCD.