Systematic Review Protocol for the Hexavalent Chromium IRIS Assessment (Preliminary Assessment Materials)

       The Integrated Risk Information System (IRIS) Program is undertaking a reassessment of the health effects of hexavalent chromium (Cr[VI]). Significant new epidemiologic and experimental animal toxicity information for Cr(VI) has become available since EPA’s IRIS assessment for Cr(VI) was posted in 1998, including updates of occupational cohort studies (Proctor et al., 2016; Gibb et al., 2015) and a National Toxicology Program (NTP) bioassay that reported increased incidences of tumors in rats and mice exposed to Cr(VI) in drinking water (NTP, 2008). The dose-response information from epidemiologic and experimental animal studies published since 1998 could result in changes to current toxicity values. Cr(VI) was included on the December 2015 IRIS Program multiyear agenda (https://www.epa.gov/iris/iris-agenda) as a chemical having high priority for assessment development. It was also included in the December 2018 IRIS Program Outlook that provides an updated outlook of IRIS program activities (https://www.epa.gov/sites/production/files/2018-12/documents/iris_program_outlook_december_2018.pdf). Given the widespread exposure to Cr(VI) and the availability of studies that provide significant new health effects information, the IRIS Program is developing an updated assessment of Cr(VI).
       Preliminary materials for the Cr(VI) reassessment were released to the public in April and August 2014, and public meetings were held in June and October 2014 to seek input regarding the Cr(VI) assessment from the scientific community and interested parties (U.S. EPA, 2014b, c). The preliminary materials included a summary of the IRIS Program’s scoping and problem formulation conclusions, information on the approaches used to identify pertinent literature, results of the literature search, approaches for selection of studies for hazard identification, and presentation of studies eligible for study evaluation in evidence tables and exposure-response arrays. A preliminary summary of toxicokinetic and mechanistic studies pertinent to the assessment was also presented.
       The protocol is a new document adopted by the IRIS Program as part of its full implementation of systematic review [see presentation materials for the NAS Workshop “Review of Advances Made to the IRIS Process” (Bahadori and Thayer, 2018) and the NASEM (2018) report Progress Toward Transforming the Integrated Risk Information System]. The chemical-specific protocol describes how the assessment will be conducted, while the IRIS Assessment Plan (IAP), typically released early in the assessment process, describes what the assessment plans to cover based on scoping and problem formulation. As noted above, scoping and problem formulation documents were previously released for public comment; this protocol summarizes and updates those earlier materials (e.g., see Sections 1−4). Because development of the chromium assessment began before the introduction of these early stage documents to the IRIS process, EPA is retroactively releasing the protocol, which presents the methods for conducting the systematic review and dose-response analysis, to provide similar public engagement steps and documentation as other assessments that started more recently. This protocol also includes specific aims and populations, exposures, comparators, and outcomes (PECO) criteria that were not a part of the 2014 preliminary materials but are now a part of IRIS Systematic Review materials. The IRIS Program posts assessment protocols on its website and in the Zenodo repository (https://zenodo.org/). Public comments will be considered as part of developing the draft assessment. This protocol documents the studies identified during the initial literature searches (U.S. EPA, 2014b, c) and updates to those literature searches. Additional literature search updates will be posted to the IRIS website when they are available.

      This document is a public comment draft for review purposes only. This information is distributed solely for the purpose of public comment. It has not been formally disseminated by EPA. It does not represent and should not be construed to represent any Agency determination or policy. Mention of trade names or commercial products does not constitute endorsement or recommendation for use.