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Additional Information, Adjustments and Special Cases for Chronic Dose-Response Values in Table 1

1. All inhalation dose-response assessment numbers have been converted to EPA's standard units of mg/m3 for RfCs or similar values, and units of risk per ug/m3 for UREs. The URE for asbestos was not included in Table 1 because of its unique units, which cannot be directly converted to risk per ug/m3. Asbestos is a group A (known human) carcinogen that causes lung cancer and mesothelioma, with a URE of 0.23 risk per fiber/ml (IRIS).

2. For carcinogenic HAPs for which EPA data on early life susceptibility are not available and which EPA has concluded are carcinogenic by a mutagenic mode of action, EPA recommends that cancer risk assessments including ages younger than 16 years employ age-specific default adjustment factors (ADAFs) with the slope factor provided in Table 1 and age-specific exposure estimates as described in EPA’s Supplemental Guidance for Assessing Susceptibility from Early-Life Exposure to Carcinogens.1 The ADAFs are 10 for exposures prior to 2 years of age (i.e., spanning 2-year interval from birth until second birthday), and 3 from ages 2 through 16 (i.e., spanning a 14-year interval from second until sixteenth birthday). These HAPS are marked in Table 1 by “M*“ in the column labeled “MOA”.

In the case of trichloroethylene (TCE), however, the ADAFs only apply to the portion of slope factor reflecting risk of kidney cancer. For full lifetime exposure to a constant level of TCE exposure, the ADAF-adjusted unit risk estimate for TCE is 4.8 × 10-6 per mg/m3. For details on applying ADAFs in cases where exposure varies over the lifetime, see Section of Toxicological Review (and Excel spreadsheet available there).

3. 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 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.

4. 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.

5. 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.

6. Lead. For lead and compounds, Table 1 shows the level of the U.S. EPA national ambient air quality standard (NAAQS) in lieu of an RfC for non-cancer effects. The NAAQS is a not-to-be-exceeded 3-month average concentration of lead in total suspended particles (73 FR 66964). The CalEPA URE and CPS are not presented 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).

7. 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.

8. 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.

9. Vinyl chloride. The IRIS assessment contains separate UREs for exposure from birth and for continuous exposure during adulthood. Table 1 includes only the URE intended for continuous lifetime exposure from birth. For more refined assessments it may be appropriate to also use the IRIS value for adult exposure (4.4 x 10-6 risk per mg/m3).


1 For HAPs that are carcinogenic by an undetermined mode of action, the linear low-dose extrapolation approach is used to derive slope factors. As stated in the Supplemental Guidance, it is the Agency’s long-standing science policy position that use of the linear low-dose extrapolation approach (without further adjustment) provides adequate public health conservatism in the absence of chemical-specific data indicating differential early-life susceptibility or when the mode of action is not mutagenicity.

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