Site Help & Tools
- What is IRIS?
- What substances are in IRIS?
- What is an RfD and RfC?
- What is a cancer weight-of-evidence descriptor?
- What is a cancer slope factor and unit risk?
- How does EPA decide which substances to add or update?
- How do I generate a Multiple Substances Report?
- I am interested in Inhalation Toxicology values….should I search using the term “air” or “inhalation”?
- What is the process for developing IRIS assessments?
- How are IRIS toxicity values used?
- How do I contact the IRIS Hotline?
- What is the role of IRIS assessments in risk assessment and risk management?
What is IRIS?
EPA's Integrated Risk Information System (IRIS) is a human health assessment program that evaluates risk information on effects that may result from exposure to environmental contaminants. Through the IRIS Program, EPA provides the highest quality science-based human health assessments to support the Agency's regulatory activities. The IRIS database contains information for more than 540 chemical substances containing information on human health effects that may result from exposure to various substances in the environment. IRIS is prepared and maintained by the EPA’s National Center for Environmental Assessment (NCEA) within the Office of Research and Development (ORD).
The heart of the IRIS system is its collection of searchable documents that describe the health effects of individual substances and that contain descriptive and quantitative information in the following categories:
- Noncancer effects: Oral reference doses and inhalation reference concentrations (RfDs and RfCs, respectively) for effects known or assumed to be produced through a nonlinear (possibly threshold) mode of action. In most instances, RfDs and RfCs are developed for the noncarcinogenic effects of substances.
- Cancer effects: Descriptors that characterize the weight of evidence for human carcinogenicity, oral slope factors, and oral and inhalation unit risks for carcinogenic effects. Where a nonlinear mode of action is established, RfD and RfC values may be used.
A complete alphabetical list of the substances in IRIS is available at the A to Z List of IRIS Substances on the left navigation bar. Use Search the IRIS Database by substance name or CASRN to search for IRIS assessments for a specific substance. Other specific search criteria are available as well. You can also search multiple substances at once using Compare IRIS Values.
What is an RfD and RfC?
EPA’s IRIS is a human health assessment program that evaluates quantitative and qualitative risk information on effects that may result from exposure to specific chemical substances found in the environment. The IRIS database contains information that can be used to support the first two steps (hazard identification and dose-response evaluation) of the risk assessment process. When supported by available data, IRIS provides oral reference doses (RfDs) and inhalation reference concentrations (RfCs) for chronic non-cancer health effects, and oral slope factors and inhalation unit risks for carcinogenic effects. Combined with specific exposure information, government and private entities use IRIS to help characterize public health risks of chemical substances in a site-specific situation and thereby support risk management decisions designed to protect public health.
More specifically, the reference dose (RfD) and reference concentration (RfC) provide quantitative information for use in risk assessments for health effects known or assumed to be produced through a nonlinear (possibly threshold) mode of action. The RfD (expressed in units of mg of substance/kg body weight-day) is defined as an estimate (with uncertainty spanning perhaps an order of magnitude) of a daily exposure to the human population (including sensitive subgroups) that is likely to be without an appreciable risk of deleterious effects during a lifetime. An RfD can be derived from a no-observed-adverse-effect level (NOAEL), lowest-observed-adverse-effect level (LOAEL), or benchmark dose, with uncertainty factors generally applied to reflect limitations of the data used. The inhalation RfC (expressed in units of mg of substance/m3 air) is analogous to the oral RfD but provides a continuous inhalation exposure estimate. The inhalation RfC considers toxic effects for both the respiratory system (portal of entry) and effects peripheral to the respiratory system (extrarespiratory or systemic effects). Reference values may also be derived for acute (≤24 hours), short-term (>24 hours, up to 30 days), and subchronic (>30 days, up to approximately 10% of the life span) exposure durations, all of which are derived based on an assumption of continuous exposure throughout the duration specified. RfDs and RfCs are generally used in noncancer health assessments.
What is a cancer weight-of-evidence descriptor?
A cancer weight-of-evidence (WOE) descriptor is used by IRIS to describe a substance’s potential to cause cancer in humans and the conditions under which the carcinogenic effects may be expressed. This judgment is independent of consideration of the agent’s carcinogenic potency. Under EPA’s 1986 guidelines for carcinogen risk assessment, the WOE was described by categories “A through E”—Group A for known human carcinogens through Group E for agents with evidence of noncarcinogenicity. Under the EPA’s 2005 guidelines for carcinogen risk assessment, a narrative approach, rather than categories, is used to characterize carcinogenicity. Five standard weight-of-evidence descriptors (Carcinogenic to Humans, Likely to Be Carcinogenic to Humans, Suggestive Evidence of Carcinogenic Potential, Inadequate Information to Assess Carcinogenic Potential, and Not Likely to Be Carcinogenic to Humans) are used as part of the narrative.
What is a cancer slope factor and unit risk?
Cancer slope factors and unit risks are used to estimate the risk of cancer associated with exposure to a carcinogenic or potentially carcinogenic substance. A slope factor is an upper bound, approximating a 95% confidence limit, on the increased cancer risk from a lifetime exposure to an agent by ingestion. This estimate, usually expressed in units of proportion (of a population) affected per mg of substance/kg body weight-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. A unit risk is an 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 for a substance in drinking water would be as follows: if unit risk = 2 x 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 substance in 1 liter of drinking water.
How does EPA decide which substances to add or update?
EPA develops a list of substances for IRIS assessment development on an annual basis. The IRIS program submits queries to EPA Program Offices and Regions and the public for nominations for new assessments or updates of assessments currently on IRIS. Substances are selected based on one or more of the following factors: (1) potential public health impact; (2) EPA statutory, regulatory, or program-specific implementation needs; (3) availability of new scientific information or methodology that might significantly change the current IRIS information; (4) interest to other governmental agencies or the public; and (5) availability of other scientific assessment documents that could serve as a basis for an IRIS assessment. The decision to assess any given chemical substance depends on available Agency resources. Availability of risk assessment guidance, guidelines, and science policy decisions may also have an impact on the timing of EPA's decision to assess a chemical substance.
The list of new or updated assessments is published in the Federal Register (FR) as part of the IRIS annual agenda.
How do I generate a Multiple Substances Report?
To compare toxicity values for multiple substances, click on Compare IRIS Values on the left navigation bar. This link allows you to generate summary reports of the toxicity values for multiple substances.
I am interested in Inhalation Toxicology values….should I search using the term “air” or “inhalation”?
Either search term is helpful. Older IRIS assessments generally use the term “air”. This terminology has been updated and changed to “inhalation”. We recommend that you search using both terms, perhaps individually.
What is the process for developing IRIS assessments?
EPA's process for developing IRIS assessments consists of: (1) a Federal Register announcement of EPA's IRIS agenda and call for scientific information from the public on the selected substances, (2) a search of the current scientific literature, a Federal Register announcement that the literature search is available on the IRIS internet site, and a call to submit additional scientific information on the substance, (3) development of a draft Toxicological Review or other assessment document , (4) internal peer consultation, (5) internal Agency Review, (6) Science Consultation with other Federal agencies and White House offices, (7) external peer review and public comment, (8) final internal Agency Review, Interagency Science Discussion and ORD management approval, and (9) posting on the IRIS database.
This process is described more fully via the IRIS Process page.
How are IRIS toxicity values used?
IRIS provides hazard identification and dose-response assessment information. The information in IRIS can be used in combination with exposure information to characterize the public health risks of a given substance in a given situation. These risk characterizations can form the basis for risk-based decision-making, regulatory activities, and other risk management decisions designed to characterize and protect public health.
How do I contact the IRIS Hotline?
What is the role of IRIS assessments in risk assessment and risk management?
Risk assessment is a process that has been defined as "the characterization of the potential adverse health effects of human exposures to environmental hazards" (NRC, 1983). Estimates of environmental exposure are combined with the known adverse effects of exposure to determine an overall estimate of the potential public health risk.
A complete risk assessment consists of the following four steps:
- Hazard identification;
- Dose-response assessment;
- Exposure assessment; and
- Risk characterization.
Hazard identification involves the determination of whether exposure to an agent can cause an increased incidence of an adverse health effect, such as cancer or birth defects, and characterization of the nature and strength of the evidence of causation (NRC, 1994).
Dose-response assessment is the characterization of the relationship between exposure or dose and the incidence and severity of the adverse health effect. It includes consideration of factors that influence dose-response relationships such as intensity and patterns of exposure and age and lifestyle variables that could affect susceptibility. It can involve extrapolation of high-dose responses to low-dose responses and from animal responses to human responses (NRC, 1994).
Exposure assessment is the determination of the intensity, frequency, and duration of actual or hypothetical exposure of humans to the agent in question (NRC, 1994).
The risk characterization integrates information from the preceding components of the risk assessment and synthesizes an overall conclusion about risk that is complete, informative, and useful for decision makers (U.S. EPA, 2000). The risk characterization also addresses the uncertainty, assumptions, and scientific judgments of the previous three steps.
An IRIS health assessment consists of the hazard identification and dose-response assessment steps. The information in the IRIS assessment is combined with site- or problem-specific exposure assessments to provide the scientific support for EPA risk management decisions.
EPA considers risk assessment information along with social and economic factors, public health impacts, and statutes and regulations, in deciding how best to protect public health and the environment. Examples of risk management actions include deciding how much of a substance a company may discharge into a river; deciding which substances may be stored at a hazardous waste disposal facility; deciding to what extent a hazardous waste site must be cleaned up; setting permit levels for discharge, storage, or transport; establishing levels for air emissions; and determining allowable levels of contamination in drinking water.
References and further reading:
NRC (National Research Council). 1983. Risk Assessment in the Federal Government: Managing the Process. National Academy Press, Washington, DC.
NRC. (1994) Science and Judgment in Risk Assessment. Committee on Risk Assessment of Hazardous Air Pollutants, Board on Environmental Studies and Toxicology, Commission on Life Sciences. Washington, DC: National Academy Press.
NRC (2009) Science and Decisions: Advancing Risk Assessments. Committee on Improving Risk Analysis Approaches Used by the U.S. EPA, Board on Environmental Studies and Toxicology, Division on Earth and Life Studies. Washington, DC: the National Academies Press.
US EPA. (2000) Science Policy Council Handbook: Risk Characterization. Washington, DC: Office of Research and Development. EPA 100-B-00-002.