IRIS

Basic Information about the Integrated Risk Information System

EPA’s mission is to protect human health and the environment. EPA’s IRIS Program supports this mission by identifying and characterizing the health hazards of chemicals found in the environment. Each IRIS assessment can cover a chemical, a group of related chemicals, or a complex mixture.

IRIS assessments:

  • Are the preferred source of toxicity information used by EPA
  • Are an important source of toxicity information used by state and local health agencies, other federal agencies, and international health organizations

The IRIS Program is located within EPA’s National Center for Environmental Assessment (NCEA) in the Office of Research and Development (ORD). The placement of the IRIS Program in ORD is intentional. It ensures that IRIS can develop impartial toxicity information independent of its use by EPA’s program and regional offices to set national standards and clean up hazardous sites.

IRIS Toxicity Values

IRIS assessments provide the following toxicity values for health effects resulting from chronic exposure to chemicals.

Reference Concentration (RfC): An estimate (with uncertainty spanning perhaps an order of magnitude) of a continuous inhalation exposure to the human population (including sensitive subgroups) that is likely to be without an appreciable risk of deleterious effects during a lifetime. It can be derived from a NOAEL, LOAEL, or benchmark concentration, with uncertainty factors generally applied to reflect limitations of the data used.

Reference Dose (RfD): An estimate (with uncertainty spanning perhaps an order of magnitude) of a daily oral exposure to the human population (including sensitive subgroups) that is likely to be without an appreciable risk of deleterious effects during a lifetime. It can be derived from a NOAEL, LOAEL, or benchmark dose, with uncertainty factors generally applied to reflect limitations of the data used. HelpRfCAn estimate (with uncertainty spanning perhaps an order of magnitude) of a continuous inhalation exposure to the human population (including sensitive subgroups) that is likely to be without an appreciable risk of deleterious effects during a lifetime. It can be derived from a NOAEL, LOAEL, or benchmark concentration, with uncertainty factors generally applied to reflect limitations of the data used. Generally used in EPA's noncancer health assessments. [Durations include acute, short-term, subchronic, and chronic and are defined individually in this glossary].

Cancer descriptors characterize the chemical as:

  • Carcinogenic to Humans
  • Likely to Be Carcinogenic to Humans
  • Suggestive Evidence of Carcinogenic Potential
  • Inadequate Information to Assess Carcinogenic Potential
  • Not Likely to Be Carcinogenic to Humans

Oral slope factorHelpOral slope factorAn upper bound, approximating a 95% confidence limit, on the increased cancer risk from a lifetime oral exposure to an agent. This estimate, usually expressed in units of proportion (of a population) affected per mg/kg-day, is generally reserved for use in the low-dose region of the dose-response relationship, that is, for exposures corresponding to risks less than 1 in 100. (OSF) is an estimate of the increased cancer risk from oral exposure to a dose of 1 mg/kg-day for a lifetime. The OSF can be multiplied by an estimate of lifetime exposure (in mg/kg-day) to estimate the lifetime cancer risk.

Inhalation unit riskHelpunit riskThe upper-bound excess lifetime cancer risk estimated to result from continuous exposure to an agent at a concentration of 1 µg/L in water, or 1 µg/m³ in air. The interpretation of unit risk would be as follows: if unit risk = 2 × 10⁻⁶ per µg/L, 2 excess cancer cases (upper bound estimate) are expected to develop per 1,000,000 people if exposed daily for a lifetime to 1 µg of the chemical per liter of drinking water. (IUR) is an estimate of the increased cancer risk from inhalation exposure to a concentration of 1 µg/m3 for a lifetime. The IUR can be multiplied by an estimate of lifetime exposure (in µg/m3) to estimate the lifetime cancer risk.

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What's the Role of IRIS Assessments in Risk Assessment?

Risk assessment is a four-step process described by the National Research Council (NRC) in 1983 as "the characterization of the potential adverse health effects of human exposures to environmental hazards." Characterizing risk involves integrating information on hazard, dose-response, and exposure.

An IRIS assessment includes the first two steps of the risk assessment process:

  • Hazard Identification, which identifies credible health hazards associated with exposure to a chemical, and
  • Dose-Response Assessment, which characterizes the quantitative relationship between chemical exposure and each credible health hazard. These quantitative relationships are then used to derive toxicity values.

EPA’s program and regional offices identify human exposure pathways and estimate the amount of human exposure under different exposure scenarios (Exposure Assessment). Then they combine their exposure assessment with the hazard information and toxicity values from IRIS to characterize potential public health risks (Risk Characterization).

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Guidance & Tools

EPA follows Agency guidance in developing IRIS assessments. Key guidelines, technical documents and a few popular tools used by the IRIS Program for developing assessments are listed below. Additional Agency guidance, models and tools are available at the EPA Risk Assessment website.

EPA Guidance Documents

Tools


EPA Guidance Documents

EPA Cancer Guidelines

EPA Risk Assessment Guidelines

EPA Science Policy Council Guidelines

Other Guidance Documents and Technical Panel Reports

References Cited in Older Assessment Documents but Superseded by More Recent Guidance

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Tools

Health and Environmental Research Online (HERO)

HERO is a searchable database of more than 1.6 million scientific studies and other references used to support the development of EPA assessments. Each HERO record provides detailed bibliographic information. Since 2010, all citations in new IRIS assessments are linked to entries in the HERO database.

Benchmark Dose Software (BMDS)

Benchmark dose (BMD) modeling is EPA’s preferred approach for deriving points of departure (PODs) used to develop toxicity values. Use of BMD modeling involves fitting a set of mathematical models to dose-response data from human and animal studies. EPA’s benchmark dose software (BMDS) was designed to facilitate the application of BMD methods in dose-response assessment.

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IRIS Process for Developing Human Health Assessments

IRIS Process Diagram Illustrates the 7-Step Process for Developing IRIS AssessmentClick to enlarge: IRIS Process Figure

Step 1. Draft Development

Before beginning to develop a draft assessment, the IRIS Program undertakes internal scoping to identify EPA program and regional office needs for an assessment. Scoping is followed by problem formulation. Problem formulation frames the scientific questions that will be the focus of systematic reviews conducted as part of assessment development. EPA releases these scoping and problem formulation materials; a public meeting is held to obtain input from the scientific community and the general public on these materials.

Draft development begins with a comprehensive search and systematic review of the scientific literature. During early stages of draft development, EPA provides preliminary assessment materials to the public and an opportunity for public input on these materials. Announcements of public meetings and other opportunities for public input are posted on the IRIS website.

Step 2. Agency Review

Scientists in EPA’s program offices and regions review the draft assessment. The draft assessment is revised based on the comments received.

Step 3. Interagency Science Consultation

Other federal agencies, including the Executive Office of the President, review the draft assessment. The draft assessment is revised based on the comments received.

Step 4. Public Comment and External Peer Review

The draft assessment is released for public review and comment. EPA announces the availability of the draft assessment and draft peer review charge questions for public review and comment on the IRIS website. A public meeting is held to discuss the draft assessment, draft peer review charge questions, and specific science questions raised by the assessment. The IRIS Program revises the draft assessment and peer review charge questions in response to the public’s comments. Additionally, EPA prepares a response to major public comments received during the public comment period.

Subsequently, the draft assessment and peer review charge questions are released for external peer review by the EPA’s Scientific Advisory Board (SAB) Chemical Assessment Advisory Committee (CAAC). During external peer review, a public external peer review meeting is held; the public is allowed to attend the peer reviewers’ discussion of the draft assessment and provide comments. The SAB announces the dates and location of the peer review meeting.

Step 5. Revise Assessment

The IRIS Program revises the assessment to address peer review comments. They also prepare a written response-to-comment document.

Step 6. Final Agency Review/Interagency Science Discussion

The revised assessment is reviewed by EPA’s program offices and regions, other federal agencies, and the Executive Office of the President.

Step 7. Final Assessment

The final IRIS assessment is posted to the IRIS website.

Note: To learn more about the historical development of the IRIS Process see the history of IRIS.

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