IRIS Public Science Meeting (Nov 2021)

[UPDATE] The presentation and oral testimony were posted on the EPA website.

Meeting Details

The IRIS Program convene IRIS Public Science Meetings to encourage the scientific community and the public to participate in discussions on IRIS draft assessment materials.

At this meeting, the IRIS Program invited the public to the discussion on the key science issues identified in the following document:

• IRIS Assessment Plan (IAP) for Naphthalene.

During Fiscal Year 2018, EPA prioritized its IRIS assessments to meet the highest needs of EPA Programs and Regions (see IRIS Program Outlook (Apr 2019) (pdf) (124.05 KB) ). At that time, the IRIS Assessment of naphthalene was not identified as a priority and was suspended. The assessment was suspended after release of the IRIS Assessment Plan for public comment in July 2018, but before a public science meeting could be held to discuss the IRIS Assessment Plan

In Fiscal Year 2021, naphthalene was renominated as a priority for assessment, and has been unsuspended (see IRIS Program Outlook (Jun 2021) (pdf) (195.99 KB) ). EPA is resuming rescheduling this public meeting to discuss the key science issues identified in the IRIS Assessment Plan for Naphthalene (see 83 FR 31388). Comments previously submitted to EPA during the public comment period for this IAP document may be reviewed by visiting Regulations.Gov (Docket No. EPA-HQ-ORD-2014-0527).

Following the public meeting, a revised version of the IAP will be posted on the IRIS website as part of the IRIS systematic review protocol for naphthalene and released for public comment in Fiscal Year 2022.

Dates

• The meeting was held on Nov 9, 2021.

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Meeting Materials

• IRIS Webinar Meeting Agenda (Final) Nov 2021 (PDF) (1 pp, 195 KB)
• EPA Introductory Presentation for the November 2021 Public Science Meeting for Naphthalene (PDF) (35 pp, 1 MB)
• Testimony of Reviewers from the Naphthalene Public Science Meeting (Nov 2021) (PDF) (5 pp, 54 KB)

Naphthalene Key Science Topics and Materials

Naphthalene Assessment Managers: Erin Yost & Ingrid Druwe

• IRIS Assessment Plan (IAP) for Naphthalene
• Primary Literature Search References Sorted by Author (Naphthalene) (dynamic literature link - generated by HERO)

Key Science Topics

What is an IRIS Assessment Plan? An IRIS Assessment Plan (IAP) communicates to the public the plan for assessing each individual chemical and includes summary information on the IRIS Program’s scoping and initial problem formulation; objectives and specific aims for the assessment; the PECO (Populations, Exposures, Comparators, and Outcomes) criteria that outlines the evidence considered most pertinent to the assessment; and identification of key areas of scientific complexity.

The IRIS Program is seeking a discussion with the public aimed at improving or clarifying the IAP. Below are questions to facilitate the discussion of these science topic:

• Are the assessment objectives and specific aims articulated clearly?
• Does the background information and context that is provided support the objectives for the assessment presented in the plan?
• Does the proposed PECO (Populations, Exposures, Comparators, Outcomes) framework identify the most pertinent evidence to address the stated needs of the Agency programs and regions?

Science Topics

Topic 1. Species differences in toxicokinetics

The IRIS program is seeking discussion on species differences associated with exposure to naphthalene. Background information is provided below.

Differences in metabolism: Naphthalene is known to be converted to a reactive intermediate(s) through cytochrome P450 (CYP)-dependent metabolism, primarily the CYPF subfamily. While much progress has been made in the characterization of mouse CYP2F2, the CYP thought to be primarily involved in naphthalene metabolism in mice, characterizing the relative contribution of P450 oxidizing enzymes to naphthalene metabolism in rats and humans has been more difficult (Buckpitt et al., 2002; Shultz et al., 1999). The results available at present indicate that there are likely major interspecies catalytic differences between mouse, rat and human CYPF enzyme homologs.

Health effects:  The rate and extent of metabolism of naphthalene in various tissues and in different animal species along with anatomical differences in the nasal turbinates between species will be important considerations in evaluating region-specific differences in the production of reactive metabolites across species.

PBPK: Evaluation of the current and available naphthalene PBPK models for reliable route-to-route, interspecies, and/or intraspecies extrapolation is needed. If necessary, further development of PBPK models will also be considered.

Topic 2. Mode of action for carcinogenicity

The IRIS program is seeking discussion on possible modes of action associated with exposure to naphthalene. Background information is provided below.

Multiple animal and in vitro studies published since the 1998 IRIS Toxicological Review have provided mechanistic information and postulated the involvement of several biological processes in the development of naphthalene-induced tumor formation. These proposed processes include genotoxicity, cytotoxicity, and sustained regenerative cell proliferation. Among the key events identified by these studies are the depletion of glutathione and the formation of reactive naphthalene quinone metabolites via the cytochrome P450 pathway. The role and biological plausibility of each of these proposed mechanisms occurring in humans and their role in the formation of naphthalene-induced tumors will need to be evaluated. Differences in enzyme activities between human and rodent tissues exist; therefore, evaluation of the cancer MOA in the context of toxic metabolite formation and the relevance of these toxic metabolites to human cancer hazard will also need to be evaluated.