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Adjustments and Special Cases for Chronic Inhalation Risk Assessment
1. All inhalation dose-response assessment numbers have been converted to EPA's standard units of mg/m3 for RfCs or similar values, and (µg/m3)-1 for UREs. The URE for asbestos was not included in Table 1 because of its unique units, which cannot be directly converted to (µg/m3)-1. Asbestos is a group A (known human) carcinogen that causes lung cancer and mesothelioma, with a URE of 0.23 (fiber/ml)-1.
2. Benzene. The IRIS assessment contains a range of UREs for inhalation and oral exposure. The values that bracket this range are based on different interpretations of the human exposure information. Table 1 includes only the upper (i.e., more protective) end of the range. For more refined assessments it may be appropriate to develop a second risk estimate based on other UREs within this range.
3. Cadmium. Table 1 contains an RfD from IRIS that is intended for ingestion of drinking water. IRIS provides a different RfD (0.001 mg/kg/d) for food ingestion.
4. Chloroform. The narrative WOE in new IRIS assessment states that chloroform is likely to be carcinogenic by all routes of exposure under conditions that lead to cytotoxicity and regenerative hyperplasia in susceptible tissues, via a nonlinear mode of action. For this reason, the newly revised IRIS oral assessment lacks a carcinogenic potency slope because EPA has judged that the RfD should protect against cytotoxicity and therefore against cancer. EPA is currently developing an inhalation assessment, but the IRIS file still contains the old inhalation URE. However, we expect the next inhalation assessment to conform to a nonlinear mode-of-action, and we have accordingly removed the chloroform URE from Table 1.
5. 1,4-Dioxane. The CalEPA inhalation URE that would ordinarily have appeared in Table 1 was omitted. We did this because this URE was based on a different interpretation of the same study used to develop the IRIS oral CPS. Therefore, we judged that it would be more consistent to extrapolate the URE from that CPS.
6. Formaldehyde. A new EPA IRIS assessment is underway in light of a CIIT analysis that supports a URE on the order of 5.5E-9 per ug/m3. This value is substantially lower than the current IRIS URE of 1.3E-5 per ug/m3. (Chemical Industry Institute of Toxicology, 1999. Formaldehyde: Hazard characterization and dose-response assessment for carcinogenicity by the route of inhalation. Revised edition. Research Triangle Park, North Carolina.)
7. Lead. For lead and compounds, Table 1 shows the EPA national ambient air quality standard in lieu of an RfC for non-cancer effects. The CalEPA URE and CPS have been omitted because the IRIS assessment for lead concludes that data are not sufficient to quantify cancer risks (due to uncertainties in the exposure estimate and insufficient knowledge of lead pharmacokinetics).
8. 2-Nitropropane. Table 1 presents an inhalation URE derived by the Health Council of the Netherlands in preference to the value in HEAST, which does not reflect the most recent studies and analysis methods.
9. Polychlorinated biphenyls. The IRIS assessment for PCBs includes several oral cancer slope factors. Table 1 presents the upper-bound slope factor recommended for food chain exposure to high-risk and persistent PCBs.
10. Vinyl chloride. The IRIS assessment contains two UREs for both inhalation and oral exposure, one for exposure from birth and the other for exposure during adulthood. Table 1 includes only the UREs intended for exposure from birth. For more refined assessments it may be appropriate to use the IRIS values for adult exposure.