Quantitative Risk Analysis of Particulate Matter in the Air: Interspecies Extrapolation with Bioassay and Mathematical Models

We analyzed the health risk of particulate matters in the air to humans using bioassay data and a mathematical model. We designed an original dosimetry model to estimate the particle concentration in human respiratory organs, and the concentration of the inhaled particles at the target organ was used for interspecies extrapolation from rat to human. Our model is based on the conventional dosimetry model and deposition model in the previous literature, but clearance parameters have been newly introduced for the simulation of long-term exposure. Lung cancer was set as the risk endpoint in our risk study, and the dose-response relationship at the target organ (lung) was quantitatively analyzed by the benchmark dose (BMD) method. For interspecies extrapolation based on target organ concentration, we assumed benchmark concentration (BMC) related to 1% excess cancer in rats and humans, and the human equivalent concentration (HEC) was searched by back-estimation using our model. The obtained HEC was 948 to 1098 mg/m³, and the unit risk to humans was 9.11 to 10.5 × 10⁻⁹ per 1 μ g/m³ of particulate matter. The estimated cancer risk for Japanese people in general was estimated as approximately 9–10 persons per 100,000,000 when the particle concentration in the air is 10 μg/m³.