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Background on Risk Characterization
Note: EPA no longer updates this information, but it may be useful as a reference or resource.- What health effects are caused by exposure to air toxics?
- How did EPA characterize risk from the modeled 2002 exposure estimates?
- How does EPA estimate cancer risk?
- How were the cancer risk estimates affected by EPA's recently revised Guidelines for Carcinogen
Risk Assessment (EPA/630/P-03/001F) and new Supplemental Guidance for Assessing Susceptibility from
Early-Life Exposure to Carcinogens (EPA/630/R-03/003F)?
- How accurate are these risk estimates?
- Does EPA distinguish among chemicals based on the type of data that supports its carcinogenic potential?
- Can cancer risk estimates for different substances be combined?
- How does EPA estimate risks for health effects other than cancer?
- Can noncancer hazard estimates for different substances be combined?
- How are diesel PM health effects considered?
1. What health effects are caused by exposure to air toxics?
Section 112 of the Clean Air Act identifies 187 compounds emitted from stationary, area, and mobile sources as hazardous air pollutants (also known as "air toxics"). The EPA has classified many of these substances as "known," "probable," or "possible" human carcinogens. Air toxics are associated with a wide variety of noncancer adverse health effects that include neurological, cardiovascular, liver, kidney, and respiratory effects as well as effects on the immune and reproductive systems. The seriousness of the harm can range from headaches and nausea to respiratory arrest and death. Severity varies with the amount and length of exposure, the nature of the chemical itself (e.g., how it interacts with various organs and organ systems), and the unique behaviors and sensitivities of individual people. Some chemicals pose particular hazards to people of certain ages or genetic backgrounds.
2. How did EPA characterize risk from the modeled 2002 exposure estimates?
To evaluate a chemical's potential to cause cancer and other adverse health effects, EPA examines which adverse effects a particular substance causes (in a "hazard identification"), determines the exposure to the population (in an "exposure assessment"), and evaluates the specific exposures at which these effects might occur (in a "dose-response assessment"). The evaluation is based on studies of humans, animals, and microorganisms, usually published in peer-reviewed scientific journals. In this national-scale assessment, EPA combined information from dose-response assessments with modeled exposure estimates in a "risk characterization" to describe the potential that real-world exposure to air toxics compounds might cause harm. The EPA also examined the uncertainties surrounding the characterization of risk.
3. How does EPA estimate cancer risk?
At present, EPA typically assumes a linear relationship between the level of exposure and the lifetime probability of cancer from an air toxics compound. It expresses this dose-response relationship for cancer in terms of a unit risk estimate. The unit risk estimate (URE) is an upper bound estimate of an individual's probability of contracting cancer over a lifetime of exposure to a concentration of one microgram of the pollutant per cubic meter of air. Risks from exposures to concentrations other than one microgram per cubic meter are usually calculated by multiplying the actual concentration to which someone is exposed by the URE. For example, the EPA may determine the URE of a particular air toxics compound to be one in ten thousand per microgram per cubic meter. This means that a person who inhales air containing an average of one microgram per cubic meter for 70 years would have (as an upper bound) one chance in ten thousand (or 0.01%) of contracting cancer as a result. The EPA has developed UREs for many substances, and continues to re-examine and update them as knowledge improves. More information on UREs can be found in the EPA's Integrated Risk Information System. The UREs used in this assessment, are included in the Health Effects Criteria (PDF) discussion.
4. How were the cancer risk estimates affected by EPA's recently revised Guidelines for Carcinogen Risk Assessment (EPA/630/P-03/001F) and new Supplemental Guidance for Assessing Susceptibility from Early-Life Exposure to Carcinogens (EPA/630/R-03/003F)?
This assessment is consistent with the revised cancer guidelines and the new Supplemental Guidance that makes recommendations with regard to estimating cancer risks to children. The recommendations concerning children's risk have been implemented for the following HAPs: benzidine, ethyl carbamate, and PAHs by applying a risk factor of 1.6 to account for the increase in risk due to childhood exposures. This was done because these HAPs have been shown to have a mutagenic mode of action and because there is no chemical-specific data to show that there are differences between children and adults in the way they respond to exposure to these agents.
In contrast, vinyl chloride does have chemical-specific data available. These data were used in the derivation of the unit risk estimate (URE) (see the IRIS website for a more thorough explanation). Therefore, the URE that is presented in the toxicity tables on the OAQPS website (PDF) (8pp, 108k), already reflects the risk due to childhood exposures, and no further adjustment (as was done for the other 3 HAPs) is necessary. A brief explanation of the adjustments to risk follows. The Supplemental Guidance recommends that risks to children be adjusted for carcinogenic chemicals acting through a mutagenic and linear mode of action,(i.e., chemicals that cause cancer by damaging genes). Where available data for the chemical are adequate, they should be used to develop age-specific potency values. Where available data do not support a chemical-specific evaluation of differences between adults and children, the Supplemental Guidance recommends the use of the following default adjustment factors for early-life exposures: increase the carcinogenic potency by 10-fold for children up to 2 years old, and 3-fold for children from 2 to 15 years old. These adjustments have the aggregate effect of increasing by about 60% (a 1.6 factor increase) the estimated risk for a 70-year (lifetime) constant inhalation exposure.
It is important to keep in mind that EPA recommends that the default adjustments be made only for carcinogens (1) acting through a mutagenic mode of action, (2) for which a linear dose response has been assigned, and (3) for which data to evaluate adult and juvenile differences are not available. The default adjustments are not recommended for carcinogens whose mode of action is unknown. EPA will determine as part of the IRIS assessment process which substances meet these criteria, and future national-scale assessments will reflect adjustments for those substances.
5. How accurate are these risk estimates?
The process of developing the unit risk estimate (URE) includes several important sources of uncertainty.
- Many of the air toxics compounds in this assessment were classified as probable carcinogens which means that data were not sufficient to prove these substances definitely cause cancer in humans. It is possible that some are not human carcinogens at environmentally relevant doses, and that the true cancer risk associated with these air toxics is zero.
- All UREs used in this assessment were based on linear extrapolation from high to low exposures. To the extent that true dose-response relationships for some air toxics compounds are less than linear, this assumption may result in overestimates of cancer risk.
- UREs for most of these substances were developed from animal data using heath protective methods to extrapolate between species. Actual human responses may differ from the predicted ones.
- Most UREs used in this assessment (benzene is a notable exception to this) were based on statistical procedures that give the upper bound on the URE, which will likely result in an overstatement of risk.
On balance, we believe that true cancer risk from the assessed air toxics would probably be less than that estimated in this assessment, although the possibility remains that it could be greater. It should be noted that there are air toxics for which no cancer dose-response information currently exist, i.e., only 80 of air toxics assessed have UREs), but there may be some qualitative evidence to suggest that a particular air toxic is a carcinogen, e.g., diesel PM. In this case, it is very likely that NATA is underestimating the true cancer risk.
6. Does EPA distinguish among chemicals based on the type of data that supports its carcinogenic potential?
The EPA uses a system called the weight-of-evidence for carcinogenicity for characterizing the extent to which the available data support the hypothesis that an agent causes 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 risk assessment guidelines, the WOE was described by categories "A through E", Group A for known human carcinogens through Group E for agents with evidence of noncarcinogenicity. The approach outlined in EPA's 2005 guidelines for carcinogen risk assessment considers all scientific information in determining whether and under what conditions an agent may cause cancer in humans, and provides a narrative approach to characterize carcinogenicity rather than categories. 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
7. Can cancer risk estimates for different substances be combined?
Because risk estimates are probabilities, cancer risks associated with different substances can be added together as long as the substances cause cancer by (1) similar mechanisms, or (2) completely independent mechanisms. Addition of cancer risk estimates is inappropriate only where substances interact in ways that either enhance or inhibit each other's carcinogenic potency. Had it been available, information on non-additive interactions would have been considered (as recommended in the EPA's 1986 Guidelines for the Health Risk Assessment of Chemical Mixtures. Because no such information was identified, the EPA used the guidelines' default assumption that cancer risks from different air toxics compounds may be added.
8. How does EPA estimate risks for health effects other than cancer?
The EPA typically expresses dose-response relationships for effects other than cancer in terms of the inhalation reference concentration (RfC). The RfC is a concentration of the compound in air thought to be without adverse effects even if a person is exposed continuously. In other words, exposures at or below the RfC are not likely to cause adverse noncancer health effects.
To express noncancer hazards the EPA uses the RfC as part of a calculation called the hazard quotient (HQ), which is the ratio between the concentration to which a person is exposed and the RfC. A value of the HQ at or below one indicates that the exposure is not likely to result in adverse health effects. A value of the HQ greater than one indicates that the exposure is higher than the RfC. However, because many RfCs incorporate protective assumptions in the face of uncertainty, an HQ greater than one does not necessarily suggest a likelihood of adverse effects. Furthermore, the HQ cannot be translated to a probability that adverse effects will occur and is not likely to be proportional to risk. An HQ greater than one can best be described as indicating that a potential exists for adverse health effects.
The EPA has developed RfCs for many substances, and continues to re-examine and update them as knowledge improves. More information on RfCs can be found in the EPA's Integrated Risk Information System. The RfCs (and equivalent values) used in this assessment, along with associated uncertainties and a summary of the EPA's risk assessment guidelines for effects other than cancer, may be found in the document, A Review of the Reference Dose and Reference Concentration Processes (PDF) (192pp, 2.8 MB) and are included on the Health Effects Criteria (PDF) (12pp, 82k) page.
9. Can noncancer hazard estimates for different substances be combined?
Because different pollutants may cause similar adverse health effects, it is often appropriate to combine hazard quotients associated with different substances. In 2000, EPA drafted supplementary guidance to their national guidelines on mixtures (PDF) (209pp, 1.1 MB) that support combining the effects of different substances in specific and limited ways. Ideally, hazard quotients should be combined for pollutants that cause adverse effects by the same toxic mechanism. However, because detailed information on toxic mechanisms were not available for most of the substances in this assessment, the EPA used a simpler and more health protective method. The combined noncancer hazards associated with respiratory irritation or neurological effects were calculated using the hazard index (HI), defined as the sum of hazard quotients for individual air toxics compounds that affect the same organ or organ system. The HI is only an approximation of the combined effect because some of the substances may affect the target organs in different, (i.e., non-additive) ways. As with the HQ, a value of the HI at or below 1.0 will likely not result in adverse effects over a lifetime of exposure. However, a value of the HI greater than 1.0 does not necessarily suggest a likelihood of adverse effects. Furthermore, the HI cannot be translated to a probability that adverse effects will occur and is not likely to be proportional to risk. An HI greater than one can be best described as indicating that a potential may exist for adverse effects to respiratory or nervous system.
10. How are diesel PM health effects considered?
In this assessment, the potential risk from diesel exhaust emissions is not addressed in the same fashion that other pollutants are. This is because data are not sufficient to develop a quantitative estimate of carcinogenic potency for this pollutant. However, EPA has concluded that diesel exhaust is among the substances that the national-scale assessment suggests pose the greatest relative risk. First, several human epidemiology studies link increased lung cancer associated with diesel exhaust. Furthermore, exposures in several of these epidemiology studies are in the same range as ambient exposures throughout the United States.
In addition to the potential for lung cancer risk, there is a significant potential for noncancer health effects as well, based on the contribution of diesel particulate matter to ambient levels of fine particles. Exposure to fine particles has been linked to significant public health impacts, including respiratory and cardiovascular effects, as well as premature mortality. These effects are not specifically presented in the national-scale assessment analysis but are considered in setting and implementing EPA's National Ambient Air Quality Standards for PM-2.5.
In addition, EPA has designated a chronic Reference Concentration (RfC) for diesel particulate of 5 ug/m3 based on specific noncancer effects found in several animal studies which showed adverse changes in lungs such as inflammation and lesions. The 2002 national-scale assessment results use this dose-response value in estimating the diesel PM HQ seen in the results. More information on health effects associated with diesel exhaust can be found in the Health Assessment Document for Diesel Exhaust.