On November 9, 2020, EPA’s Office of Research and Development (ORD) released its long-awaited draft handbook that details the office’s process for developing chemical hazard assessments for its Integrated Risk Information System (IRIS) Program. The ORD Staff Handbook for Developing IRIS Assessments (IRIS Handbook) gives useful insight into ORD’s process to develop its IRIS assessments, which provide important toxicological information that federal and state environmental agencies consider when making regulatory and cleanup decisions under multiple statutory programs. EPA will accept comments on the draft handbook and charge questions until March 1, 2021.

Background

EPA established the IRIS Program in 1985, with the goal of creating a database of human health assessments for chemicals found in the environment to ensure that evaluation of chemical toxicity was consistent across the Agency. Today, EPA’s public IRIS website provides more than 560 assessments on a range of chemicals. Specifically, IRIS assessments identify credible health hazards associated with exposures to a chemical and characterize the quantitative relationship between chemical exposure and each credible health hazard. EPA uses these quantitative relationships to derive toxicity values (e.g., reference concentration, reference does, cancer descriptors, oral slope factor, inhalation unit risk). In many cases, IRIS assessments serve an important role in EPA’s risk management decisions when establishing protective air and water quality standards, and in the Superfund risk assessment and remedy selection process. IRIS toxicity values are not, however, legally binding or enforceable standards.

Development of the IRIS Handbook initially began nearly a decade ago, in response to recommendations EPA received from the National Research Council (NRC) after conducting a peer review of a formaldehyde assessment. In 2011, NRC released a series of recommendations on the overall IRIS assessment process, specifically that EPA make the assessment process more transparent, leading EPA to develop the handbook.

IRIS Assessment Process

The IRIS Handbook states that the overall process for developing assessments has not changed, but has been supplemented to improve systematic review approaches. The handbook lays out in detail the multi-step process that ORD follows when preparing IRIS assessments. This 13-step process is depicted in section 2, page 30 of the IRIS Handbook. See here.

ORD begins the process by defining the scope of the assessment through consultation with other EPA programs and regions and identifying potential health effects, types of studies, questions, and issues to be considered (i.e., problem formulation). Based on this information, IRIS Program staff will develop a draft assessment plan that outlines what the IRIS assessment will cover. Once the assessment plan is finalized, ORD develops a “systematic review protocol” that governs how the assessment will be conducted. The draft assessment plan and systematic review protocol are subject to public comment periods.

Next, IRIS Program staff will conduct a broad literature study to review and compile an inventory of studies that will be included in the assessment. ORD will classify its confidence in each study through a ranking system and provide documentation explaining its decision in the evaluation process.

Once the set of studies and outcomes is known, and conclusions about confidence in the studies have been made, ORD extracts relevant data to synthesize the results of human and animal-based studies. Evidence integration culminates in a final judgment about the extent to which the available evidence supports that the assessed chemical poses or is unlikely to pose risks in humans.

If the totality of the available evidence indicates that exposure to a chemical causes human health effects, toxicity values will be developed. In order to develop toxicity values for a given chemical, ORD will select the most informative studies and outcomes for dose-response analysis to develop a quantitative estimate for each hazard of concern and describe the level of uncertainty or confidence in its estimates.

TSCA Chemical Risk Evaluations

The other EPA office that performs chemical risk assessments is the Office of Chemical Safety and Pollution Prevention (OCSPP) under the 2016 amendments to the Toxic Substances Control Act (TSCA). TSCA risk evaluations go beyond general toxicity assessments performed under IRIS and determine whether the chemical presents an unreasonable risk to health or the environment under the chemical’s “conditions of use.” “Conditions of use” are the “circumstances, as determined by the Administrator,” under which a chemical substance is intended, known, or reasonably foreseen to be manufactured, processed, distributed in commerce, used or disposed of. As a result, OCSPP generally does not rely on IRIS toxicity values for purposes of TSCA risk evaluations. In some cases, this has led to issues when both offices have conducted assessments for the same chemical substance.

Future of IRIS and TSCA

Since 2016, efforts to reform the IRIS program and complete the handbook had slowed in part due to the OCSPP’s new duty to conduct chemical risk evaluations. But the incoming administration will likely reprioritize IRIS risk assessments over TSCA and keep ORD playing a pivotal role in conducting hazard assessments. The key questions will be whether the IRIS methodology will predominate over the TSCA program and what happens if the processes differ as to the same chemical substance, given TSCA’s new, more muscular approach. Another key issue will be whether ORD or EPA program offices are responsible for initiating new IRIS assessments. The draft handbook notes that the development of IRIS assessments requires consultation and close coordination with EPA programs, which could suggest that EPA programs may have more input in directing IRIS assessments in the future.

Additionally, efforts to bolster the IRIS process could also directly impact evaluations under the TSCA program. Currently, an ad hoc committee of the National Academies of Sciences, Engineering and Medicine is reviewing EPA’s TSCA Systematic Review Guidance Document as the toxics office has come under criticism for its systematic review approach. Ultimately, the IRIS Handbook may influence potential changes to the TSCA program as well. At the very least, the IRIS Handbook’s release fosters needed transparency and signals efforts by EPA to promote efficiency within the IRIS program

The 90-day public comment period for the draft handbook and charge questions began on November 30, and will end on March 1, 2021.