EPA Background Briefing: EPA Multi-path Particle Dosimetry (MPPD) Model 2021 (v. 1.01) Technical Support Documentation & User’s Guide
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The U.S. Environmental Protection Agency (EPA) introduced formal dosimetry modeling into its derivation procedures for risk assessment of inhaled materials with “Methods for Derivation of Inhalation Reference Concentrations and Application of Inhalation Dosimetry” (US EPA, 1994). To implement those methods for particle exposures, the EPA developed the Regional Deposited Dose Ratio (RDDR) model and software. The RDDR model was an empirical model fit to a unique set of experimental data from inhalation studies across several species. The dosimetry methods in that 1994 document were subsequently adopted by the U.S. EPA’s cancer guidelines in 2005.
Because mechanistic modeling of inhalation dosimetry for particles has matured significantly since 1994, EPA has developed a version of the multi-path particle dosimetry (MPPD) model (MPPD EPA 2020 v. 1.01) and software as a potential alternative to the RDDR model. The proposed MPPD model includes many modernized features, such as use of mechanistic descriptions instead of empirical fitting as the basis, the ability to predict retained dose by incorporating clearance processes, addressing a wider range of particle sizes, providing for simulation of multi-modal exposures, and inclusion of some different test species. The external peer review panel will evaluate the advantages or disadvantages of moving to deploy the MPPD model (and its software) and its software in Agency assessment applications, as well as the utility of the EPA Technical Support Documentation and User’s Guide. Specific applications may include evaluation of intra-human variability, interspecies extrapolation, informing experimental design, and in vitro to in vivo (IVIVE) extrapolation.