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Chemical-Specific Information
Chemicals with a Mutagenic Mode of Action (MOA) for Carcinogenesis
The Supplemental Guidance identifies 12 chemicals that have a mutagenic mode of action (MOA) for carcinogenesis. In addition, EPA determined that coke oven emissions have a mutagenic MOA for carcinogenesis (see 70 Federal Register 19992) and the Superfund Technical Support Center (SFTSC) at EPA's National Center for Environmental Assessment (NCEA)-Cincinnati has determined that 4,4'-methylenebis(2-chloroaniline) (MOCA) and 1,2-dibromo-3-chloropropane have a mutagenic MOA for carcinogenesis. All 15 of these chemicals/compounds are listed below:
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| CHEMICAL/COMPOUND | CASRN |
|---|---|
| Benzidine | 92-87-5 |
| Benzo[a]pyrene (BaP) | 50-32-8 |
| Dibenz[a,h]anthracene (DBA) | 53-70-3 |
| Diethylnitrosamine (DEN) (aka Diethylnitrosamine (DENA), N-nitrosodiethylamine (NDEA), N-ethyl-n-nitrosoethanamine) |
55-18-5 |
| Dimethylbenz[a]anthracene (DMBA) | 57-97-6 |
| Dimethylnitrosamine (DMN) (aka Dimethylnitrosoamine (DMNA), Nitrosodimethylamine (NDMA), N-methyl-n-nitrosomethanamine) |
62-75-9 |
| Ethylnitrosourea (ENU) (aka N-nitroso-ethylurea) |
759-73-9 |
| 3-methylcholanthrene (3-MC) | 56-49-5 |
| Methylnitrosourea (NMU or MNU) (aka N-nitroso-n-methylurea (NMU)) |
684-93-5 |
| Safrole | 94-59-7 |
| Urethane (aka Ethyl carbamate) |
51-79-6 |
| Vinyl chloride | 75-01-4 |
| Coke oven emissions | 8007-45-2 |
| * Provisional Peer Reviewed Toxicity Values for 4,4'-Methylenebis (2-chloroaniline) (CASRN 101-14-4)(PDF) (32 pp, 240K) | 101-14-4 |
| * Provisional Peer Reviewed Toxicity Values for 1,2-Dibromo-3-Chloropropane(CASRN 96-12-8) (PDF) (51 pp, 545K) | 96-12-8 |
*The determination that these contaminants are carcinogenic by a mutagenic mode of action was made in a Provisional Peer Reviewed Toxicity Value (PPRTV) assessment done by STSC for the EPA Superfund Program. The PPRTV database is currently not on the internet, and is accessible only to EPA computers. Other parties needing a PPRTV assessment for use on a potential Superfund or hazardous waste site can obtain PPRTV assessments by being placed on the PPRTV Registered User List and then requesting assessments from STSC. Please contact a risk assessor or toxicologist in the Superfund Program of the EPA Regional Office for your site(s) if you would like to be included on the PPRTV Registered User list to receive these assessments. If you do not know who to contact in a Regional Office, contact Dave Crawford in EPA/OSRTI at Crawford.Dave@epa.gov.
This list may change as new data become available, including:
- recently completed Integrated Risk Information System (IRIS) assessments or reassessments;
- and recently completed STSC assessments.
These assessments will include a mode of action determination for carcinogenesis. Thus, always check IRIS and the STSC for the latest information.
Potency Adjustments for Early-Life Exposure
For chemicals that have been determined to have a mutagenic MOA for carcinogenesis, chemical-specific information should be used to develop cancer slope factors that address any potential for differential potency in early life stages, if appropriate data are available. If appropriate chemical-specific data are not available, then the default age-dependent adjustment factors (ADAFs) should be applied to the cancer slope factor:
- a 10-fold adjustment for ages 0 - <2 years;
- a 3-fold adjustment for ages 2 - <16 years;
- no adjustment for ages 16 years and older.
These default ADAFs address the potential for differential potency associated with exposure during early life (less than 16 years of age).
Of the 15 chemicals determined to have a mutagenic MOA for carcinogenesis, 7 of these chemicals have oral slope factors and 6 of these chemicals have inhalation unit risks (see IRIS, accessed June 12, 2006, and SFTSC). Note that the availability of toxicity values are subject to revision, and IRIS and the SFTSC should always be checked for the most current information.
Currently, vinyl chloride is the only chemical with appropriate dose-response data for evaluating the differential susceptibility from early life exposure. To assess cancer risks from this chemical, see the chemical-specific analysis available in the IRIS Toxicological Review of Vinyl Chloride (PDF) (197 pp, 4.5MB) (EPA/635R-00/004, May 2000; see Section 5.3.5.1 - Basis for Recommending Adjustment in Cancer Risk Estimates to Account for Early-Life Sensitivity). For all other chemicals, the default ADAFs specified in the Supplemental Guidance are applied in estimating cancer risks (see the example calculations provided in the Cancer Risk Calculations section of this Handbook).
Potency Adjustments for Early-Life Exposure to Other Carcinogenic Polycyclic Aromatic Hydrocarbons (PAHs)
Benzo[a]pyrene (BaP) is often used as an index chemical to assess cancer risks from other carcinogenic PAHs (PDF) (1 pg, 24K). This is described in the Provisional Guidance for Quantitative Risk Assessment of Polycyclic Aromatic Hydrocarbons (EPA/600/R-93/089, 1993). When assessing early-life exposure for PAHs using such an approach, EPA recommends applying the default ADAF(s) to the BaP slope factor before using relative potency factors (PDF) (1 pg, 19K) to estimate risk from exposure to other PAHs (see the Science Policy Council's June 2006 memo on performing risk assessments that include carcinogens described in the Supplemental Guidance as having a mutagenic MOA (Communication II) (PDF) (4 pp, 235K)) and the example calculations provided in the Cancer Risk Calculations section of this Handbook).
Additional Information
For more information on how to apply the Supplemental Guidance to carcinogens that are described as having a mutagenic MOA, see the Science Policy Council's June 2006 memo on performing risk assessments that include carcinogens described in the Supplemental Guidance as having a mutagenic MOA (Communication II) (PDF) (4 pp, 235K).