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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. An additional assessment of 1,2,3-trichloropropane was added to IRIS in 2009. All 19 of these chemicals/compounds are listed below:

CHEMICAL/COMPOUND CASRN
Acrylamide 79-06-1
Benzidine 92-87-5
Benzo[a]pyrene (BaP) 50-32-8
Coke oven emissions 8007-45-2
Dibenz[a,h]anthracene (DBA) 53-70-3
Dichloromethane
EPA has concluded, by a weight of evidence evaluation, that dichloromethane is carcinogenic by a mutagenic mode of action.
75-09-2
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
*  Provisional Peer Reviewed Toxicity Values for 4,4'-Methylenebis (2-chloroaniline) (CASRN 101-14-4)(PDF) (32 pp, 240K,  About PDF) 101-14-4
*  Provisional Peer Reviewed Toxicity Values for 1,2-Dibromo-3-Chloropropane(CASRN 96-12-8) (PDF) (51 pp, 545K,  About PDF) 96-12-8
Safrole 94-59-7
Trichloroethylene
EPA has concluded, by a weight-of-evidence evaluation, that TCE is carcinogenic by a mutagenic mode of action for induction of kidney tumors.
79-01-6
1,2,3-Trichloropropane 96-18-4
Urethane
     (aka Ethyl carbamate)
51-79-6
Vinyl chloride 75-01-4

*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.

This list may change as new data become available, including:

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:

These default ADAFs address the potential for differential potency associated with exposure during early life (less than 16 years of age).

IRIS has recently released a Toxicity Assessment for TCE. IRIS suggests that the kidney risk be assessed using the mutagenic equations and the liver and non-Hodgkin lymphoma (NHL) be addressed using the standard cancer equations. For an example of how to calculate the TCE slope factor and inhalation unit risk using the ADAFs for the kidney endpoint can be found on the Trichloroethylene Quickview page.

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,  About PDF) (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,  About PDF).  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,  About PDF)) 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,  About PDF).

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