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Sources of Chronic Dose-Response Information

Hazard identification and dose-response assessment information for chronic exposure was obtained from various sources and prioritized according to (1) conceptual consistency with EPA risk assessment guidelines and (2) level of review received. EPA revises this information regularly to keep it as current as possible, but risk assessors are encouraged to consult the original sources to verify any values important to their assessments. The prioritization process was aimed at incorporating into our assessments the best available science with respect to dose-response information. The following sources were used:

US Environmental Protection Agency (EPA). EPA has developed dose-response assessments for chronic exposure to many of the pollutants in this study. These assessments typically specify anRfC (to protect against effects other than cancer) and/or URE (to estimate the probability of contracting cancer).

EPA disseminates dose-response assessment information in several forms, based on the level of review. Dose-response assessments that have achieved full intra-agency consensus are incorporated in the Integrated Risk Information System (IRIS), which is regularly updated and available on-line. All IRIS assessments since 1996 have also undergone independent external peer review. Dose-response assessments for some substances were prepared by the EPA Office of Research and Development, but never submitted for EPA consensus. EPA has assembled the results of many such assessments in the Health Effects Assessment Summary Tables (HEAST), which Table 1 uses as a source.

US Agency for Toxic Substances and Disease Registry (ATSDR). ATSDR, which is part of the US Department of Health and Human Services, develops and publishes Minimum Risk Levels (MRLs) for many toxic substances. The MRL is defined as an estimate of daily human exposure to a substance that is likely to be without an appreciable risk of adverse effects (other than cancer) over a specified duration of exposure. MRLs can be derived for chronic exposures by the inhalation and oral routes. ATSDR describes MRLs as substance-specific estimates to be used by health assessors to select environmental contaminants for further evaluation. MRLs are considered to be levels below which contaminants are unlikely to pose a health threat. Exposures above an MRL do not necessarily represent a threat, and MRLs are therefore not intended for use as predictors of adverse health effects or for setting cleanup levels.

Table 1 shows the ATSDR chronic MRL where no IRIS RfC or RfD is available, because the MRL's concept, definition, and derivation are philosophically consistent (though not identical) with EPA's guidelines for assessing noncancer effects. ATSDR publishes MRLs as part of pollutant-specific toxicological profile documents, and also in a regularly-updated on-line table. Table 1 also includes ATSDR draft MRLs, labeled "D-ATSDR."

California Environmental Protection Agency (CalEPA). The CalEPA Office of Environmental Health Hazard Assessment has developed dose-response assessments for many substances, based both on carcinogenicity and health effects other than cancer. The process for developing these assessments is similar to that used by EPA to develop IRIS values and incorporates significant external scientific peer review. The non-cancer information includes available inhalation health risk guidance values expressed as chronic inhalation and oral reference exposure levels (RELs). CalEPA defines the REL as a concentration level at (or below) which no health effects are anticipated, a concept that is substantially similar to EPA's non-cancer dose-response assessment perspective. Table 1 shows the chronic REL (including both final and proposed values) where no IRIS RfC/RfD or ATSDR MRL exists.

CalEPA's quantitative dose-response information on carcinogenicity by inhalation exposure is expressed in terms of the URE, defined similarly to EPA's URE. Table 1 shows specific CalEPA UREs where no IRIS values exist. CalEPA's dose response assessments for carcinogens and noncarcinogens are available on-line.

International Agency for Research on Cancer (IARC). The IARC, a branch of the World Health Organization, coordinates and conducts research on the causes of human cancer and develops scientific strategies for cancer control. The IARC sponsors both epidemiological and laboratory research, and disseminates scientific information through meetings, publications, courses and fellowships.

As part of its mission, the IARC assembles evidence that substances cause cancer in humans and issues judgments on the strength of evidence. IARC's "degrees of evidence" categories are Group 1 (carcinogenic in humans), Group 2A (probably carcinogenic), Group 2B (possibly carcinogenic), Group 3 (not classifiable), and Group 4 (probably not carcinogenic). The categorization scheme may be applied to either single chemicals or mixtures. The IARC does not develop quantitative dose-response metrics such as UREs, however.

IARC's WOE determinations for substances are included as supporting information for this assessment as a backup to EPA's WOE determinations, which do not cover all substances and in some cases may be out-of-date. The list of IARC evaluations to date is available on-line.

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