External Peer Review of the Multiple-Path Particle Dosimetry (Mppd) Model and the EPA Mppd Technical Support Documentation and User's Guide (External Review Draft)

Abstract

EPA is announcing an external expert peer review and public comment for the EPA Multiple-Path Particle Dosimetry (MPPD) Model Software (MPPD EPA 2021 v. 1.01) and its associated “Technical Support Documentation and User's Guide (External Review Draft)” ([EPA/600/R-20/406]). The document was prepared by the Center for Public Health and Environmental Assessment (CPHEA) within EPA's Office of Research and Development (ORD), with contributions from Applied Research Associates, Inc., and Fred J. Miller, LLC. EPA is releasing this draft model software version and associated document to seek review by external experts and the public. This external review draft document and model software (MPPD EPA 2021 v. 1.01) are not final and do not represent, and should not be construed to represent, any final Agency policy or views. When revising the document and the model software, EPA will consider any peer or public comments submitted during the public comment period specified in this document.

Dates

Public Comment Period

The 30-day public comment period begins March 23, 2021 and ends April 22, 2021. Comments must be received on or before April 22, 2021.

Public Meetings

• Day 1: Tuesday, May 4: 4 ½ hours
  12:00 to 4:30 PM
• Day 2: Thursday, May 6: 5 ½ hours
  11:30 AM to 5:00 PM
• Day 3: Monday, May 10: 5 ½ hours
  11:30 AM to 5:00 PM

Registration Instructions

• Click to Register (EXIT EPA) to attend any of the MPPD Meeting Webinars listed above.

To obtain a copy of the external review draft or the associated MPPD software (EPA 2021 v. 1.01), contact ERG by email at peerreview@erg.com with the subject line: MPPD EPA 2021 Peer Review; or by phone at 781-674-7362.

Background

The EPA is undertaking an external peer review of an EPA version of the Multiple-Path Particle Dosimetry (MPPD) model (MPPD EPA 2021 v. 1.01) and its software, together with an EPA Technical Support Documentation and User's Guide. The EPA introduced formal dosimetry modeling into its derivation procedures for risk assessment of inhaled materials with its 1994 document entitled “Methods for Derivation of Inhalation Reference Concentrations (RfCs) and Application of Inhalation Dosimetry” (US EPA, 1994). These methods relied upon the Regional Deposited Dose Ratio (RDDR) model and underwent two expert technical panel and two expert Science Advisory Board (SAB) reviews prior to finalization. The dosimetry adjustments were also subsequently incorporated into the Agency's guidelines for carcinogen risk assessment (US EPA, 2005).

The EPA RDDR model was an empirical model fit to a unique set of experimental data from inhalation studies across five laboratory animal species commonly used in testing for regulatory risk assessment as well as for humans. The model provided predictions of inhaled deposited dose in various regions of the respiratory tract, including the extrathoracic (ET), tracheobronchial (TB), pulmonary (PU), thoracic (TB + PU) or total respiratory tract (TOTAL).

However, since 1994, mechanistic modeling of inhalation dosimetry for particles has matured. The MPPD model and its software include many modernized features, with some dose metric predictions now based on mechanistic descriptions instead of empirical fitting, the ability to address a wider range of particle size, providing prediction of retained mass for some species, and including some different test species.

The EPA is convening this external peer review to evaluate the MPPD model. The model results provide dosimetry adjustment of inhalation exposures for the following purposes: Interspecies extrapolation, evaluation of intra-human variability, informing experimental design, and in vitro to in vivo (IVIVE) extrapolation.

The EPA Multiple-Path Particle Dosimetry (MPPD) Model Software (MPPD EPA 2021 v. 1.01) and its associated “Technical Support Documentation and User's Guide (External Review Draft)” will be discussed at a virtual external expert peer review meeting, which will be open to the public. In addition to the opportunity to submit written comments during the public comment period announced in this notice, the public will have an opportunity to make brief oral comments during the virtual expert peer panel meeting. For more information about the peer review meeting, including information about how to register, please visit: https://projects.erg.com/​conferences/​peerreview/​register-mppd.html.

Peer Review Event Point of Contact (POC):

For information regarding the peer review contact: peerreview@erg.com. Please include the subject line "MPPD EPA 2021 Peer Review" with your comment or contact by phone at 781-674-7362.

• To request the MPPD user's guide and model, click to contact ERG via email.
• FR Notice: Mar 23, 2021