Liver-Based Probabilistic Risk Assessment of Exposure to Organophosphate Esters via Dust Ingestion Using a Physiologically Based Toxicokinetic (PBTK) Model

Organophosphate esters (OPEs) are widely used and harmful to organisms and human health. Dust ingestion is an important exposure route for OPEs to humans. In this study, by integrating ToxCast high-throughput in vitro assays with in vitro to in vivo extrapolation (IVIVE) via physiologically based Toxicokinetic (PBTK) modeling, we assessed the hepatocyte-based health risk for humans around the world due to exposure to two typical OPEs (TPHP and TDCPP) through the dust ingestion exposure route. Results showed that the health guidance value of TPHP and TCDPP obtained in this study was lower than the value obtained through animal experiments. In addition, probabilistic risk assessment results indicate that populations worldwide are at low risk of exposure to TPHP and TDCPP through dust ingestion due to low estimated daily intakes (EDIs) which are much lower than the reference dose (RfDs) published by the US EPA, except in some regional cases. Most margin of exposure (MOE) ranges of TDCPP for children are less than 100, which indicates a moderately high risk. Researchers should be concerned about exposure to TDCPP in this area. The method proposed in this study is expected to be applied to the health risk assessment of other chemicals.