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For additional assistance or questions about IRIS, contact the IRIS Hotline at (202) 566-1676 (phone), (202) 566-1749 (FAX) or hotline.iris@epa.gov (email).
Frequent Questions
- 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?
The Integrated Risk Information System (IRIS) is an electronic database 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.
What substances are in IRIS?
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 as available as well. You can also search multiple substances at once using Compare IRIS Values.
What is an RfD and RfC?
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 EPA 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 annual queries to EPA Program Offices and Regions for nominations for new substance assessments or updates of assessments currently on IRIS. Since the early 2000s, the IRIS Program has also sought nominations for new and updated assessments from the public. Substances are selected based on one or more of the following factors: (1) EPA statutory, regulatory, or program implementation need; (2) the availability of new scientific information or methodology that might significantly change current IRIS information; (3) interest to other levels of government or the public; and (4) the availability of a scientific assessment completed while meeting other EPA requirements, and for which only modest additional effort is needed to complete the review and documentation for IRIS. Because of limited Agency resources, not all nominated substances are selected for EPA assessment.
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) an annual 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 literature, (3) development of a draft Toxicological Review (other support document) and IRIS Summary, (4) internal peer consultation, (5) Agency Review, (6) Interagency Review, (7) external peer review and public comment, (8) final Agency Review, Interagency Review 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?
Contact the IRIS Hotline via the Contact us page or at (202) 566-1676 (phone), (202) 566-1749 (fax), or hotline.iris@epa.gov (email).
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 gathering and evaluating data on the types of health injury or disease that may be produced by a substance and on the conditions of exposure under which injury or disease is produced. In hazard identification, we attempt to determine whether it is scientifically correct to infer that toxic effects observed in one setting will occur in other settings (e.g., whether substances found to be carcinogenic or teratogenic in experimental animals are likely to have the same results in humans).
Dose-response assessment involves describing the quantitative relationship between the amount of exposure to a substance and the extent of toxic injury or disease. Data are derived from animal studies or, less frequently, from studies in exposed human populations. There may be many different dose-response relationships for a substance if it produces different toxic effects under different conditions of exposure. Even if the substance is known to be toxic, the risks of a substance cannot be ascertained with any degree of confidence unless dose-response relationships are quantified.
As IRIS assessment consists of hazard identification and dose-response assessment.
Exposure assessment involves describing the nature and size of the population exposed to a substance and the magnitude and duration of the exposure. The evaluation could concern past or current exposures, or exposures anticipated in the future.
Risk characterization integrates the data and analysis of the first three steps of the risk assessment process (hazard identification, dose-response assessment, and exposure assessment) to determine the likelihood that humans will experience any of the various forms of toxicity associated with a substance. Risk characterization must address the uncertainty, assumptions, and scientific judgements of the previous three steps to eventually formulate the most accurate estimate of risk to human health possible.
Risk assessment information is then used in the risk management process to decide how best to protect public health. 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.
Essentially, risk assessment provides INFORMATION on the health risk, and risk management is the ACTION taken based on that information.
References:
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.
U.S. EPA. (1985) Principles of Risk Assessment: A nontechnical review. Prepared for a risk assessment workshop. Easton, MD, March 17-18.
U.S. EPA. (1994) Peer Review and Peer Involvement at the US Environmental Protection Agency.
Presidential/Congressional Commission on Risk Assessment and Risk Management. (1997) Framework for Environmental Health Risk Management. Final Report. Volume 1. Available at: http://www.riskworld.com/Nreports/nr7me001.htm 
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The Presidential/Congressional Commission on Risk Assessment and Risk Management. (1997) Risk Assessment and Risk Management in Regulatory Decision-Making. Final Report. Volume 2. Available at: http://www.riskworld.com/Nreports/nr7me001.htm .