Limitations The information in the Integrated Risk Information System (IRIS) is most useful if applied in the larger context of risk assessment as outlined by the National Academy of Sciences. IRIS supports the first two steps of the risk assessment process; namely, the hazard identification and dose- response assessment steps. The primary qualitative and quantitative health hazard information in IRIS, the oral reference doses (RfDs), inhalation reference concentrations (RfCs), and carcinogenicity assessments, can serve as guides in evaluating potential health hazards and selecting a response to alleviate a potential risk to human health. The RfD and RfC can be used to estimate a level of environmental exposure at or below which no adverse effect is expected to occur. The RfD or RfC is 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 appreciable risk of deleterious effects during a lifetime. RfDs and RfCs are based on an assumption of lifetime exposure and may not be appropriately applied to less-than-lifetime exposure situations. RfDs and RfCs are also derived for the noncarcinogenic effects of chemicals that are carcinogenic. The carcinogenicity assessments in IRIS begin with a qualitative weight-of-evidence judgment as to the likelihood that a chemical may be a carcinogen for humans. This judgment is made independent of consideration of the agent's potency. A quantitative assessment, which may include an oral slope factor and oral and/or inhalation unit risks, is then presented. The oral slope factor is an upper-bound estimate of the human cancer risk per mg of agent/kg body weight/day. The unit risk, which is calculated from the slope factor, is an estimate in terms of either risk per ug/L drinking water, or risk per ug/cu.m air concentration. In general IRIS values cannot be validly used to accurately predict the incidence of human disease or the type of effects that chemical exposures have on humans. This is due to the numerous uncertainties involved in risk assessment, including those associated with extrapolations from animal data to humans and from high experimental doses to lower environmental exposures. The organs affected and the type of adverse effect resulting from chemical exposure may differ between study animals and humans. In addition, many factors besides exposure to a chemical influence the occurrence and extent of human disease. Any alteration to an RfD, RfC, slope factor or unit risk as they appear in IRIS (for example, the use of more or fewer uncertainty factors than were applied to arrive at an RfD) invalidates and distorts their application in estimating the potential health risk posed by chemical exposure. Each reference dose/concentration and carcinogenicity assessment has been reviewed by a group of EPA health scientists using consistent chemical hazard identification and dose-response assessment methods. These methods are discussed or referenced in the Background Documents. It is important to note that the information in IRIS may be revised by EPA, as appropriate, when additional health effects data become available and new developments in assessment methods are adopted. Last updated: February 4, 1998 URL: http:/www.epa.gov/iris/GLOSSARY.HTM