Cancer Risk Calculations
Risk calculations for chemicals that act with a mutagenic mode of action for carcinogenesis are quantified using one of two possible approaches:
- For chemicals with chemical-specific data on susceptibility from early-life exposure, if data are available for deriving age-specific cancer slope factors, then these slope factors are used in the risk calculations.
- For chemicals without chemical-specific data on early life exposures, Age-Dependent Adjustment Factors (ADAFs) are applied in the risk calculations.
Each risk calculation approach is discussed below and example risk calculations are provided.
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Note: The case studies utilize the exposure factors and age intervals for a resident under current Superfund Guidance (EPA 1989, 1991, 2004). In applying the Supplemental Guidance to risk assessments, risk assessors should decide if a more refined, age-specific exposure assessment is warranted and use the exposure parameters/age grouping bins that make the most sense for their site. To assist with the computation of age-specific values in exposure estimates, exposure parameters from current EPA guidance (including EPA's Exposure Factors Handbook, Child-Specific Exposure Factors Handbook, Age-Grouping Guidance) were compiled. These values can be downloaded from the Exposure Assessment page of this Handbook.References
EPA. 1989. Risk Assessment Guidance for Superfund (RAGS). Volume I. Human Health Evaluation Manual (Part A). EPA/540/1-89/002, December.
EPA. 1991. Human Health Evaluation Manual, Supplemental Guidance: Standard Default Exposure Factors (PDF) (28 pp, 203K) OSWER 9285.6-03, March.
EPA. 2004. Risk Assessment Guidance for Superfund Volume I: Human Health Evaluation Manual (Part E, Supplemental Guidance for Dermal Risk Assessment). OSWER 9285.7-02EP, July.
Risk Estimates for Chemicals or Compounds with Chemical-Specific Data
The new Supplemental Guidance indicates that, for chemicals or compounds that act with a mutagenic mode of action for carcinogenesis, if chemical-specific data on susceptibility from early-life exposures are available, then these data are used to develop cancer slope factors that specifically address any potential for differential potency in early life stages.
An example of this is the Integrated Risk Information System (IRIS) assessment of vinyl chloride. Two slope factors are available for this chemical, one that accounts for exposure occurring during early life and one that accounts for exposure occurring later in life. Chemical-specific considerations for quantifying cancer risks from this chemical that account for early-life sensitivity are provided in Section 126.96.36.199 of the Toxicological Review of Vinyl Chloride (PDF) (197 pp, 4.5MB) (EPA/635R-00/004, May 2000) .
Risk Estimates for Chemicals without Chemical-Specific Data
The new Supplemental Guidance indicates that, for chemicals or compounds with a mutagenic mode of action for carcinogenesis, in the absence of chemical-specific data, the risk for exposures that occur at early life stages should be calculated by applying the following default age-dependent adjustment factors (ADAFs) to the non-age-specific slope factor:
|0 - <2||10|
|2 - <16||3|
[See also the Exposure Assessment section of this Handbook.]
The Supplemental Guidance further indicates that any grouping of ages in the exposure assessment will need to be integrated with the ADAF age groupings to derive age group-specific risk estimates.
For example, under current Superfund guidance, exposure factors for humans are divided into two age intervals:
Child = age 1 - 6
Adult = age 7 - 30
Thus, risks to an individual may be assessed by dividing the total exposure into four intervals:
|0 - <2||Child||2||10|
|2 - <6||Child||4||3|
|6 - <16||Adult||10||3|
|16 - <30||Adult||14||1|
|Note: Alternate age bins may be considered to address site-specific scenarios.|
Calculation of Cancer Risk
For each age interval "i", the cancer risk for exposure by a specified pathway [1,2] is computed as:
C = Concentration of the chemical in the contaminated environmental medium (soil or water) to which the person is exposed. The units are mg/kg for soil and mg/L for water. IRi = Intake rate of the contaminated environmental medium for age bin "i". The units are mg/day for soil and L/day for water. BWi = Body weight of the exposed person for age bin "i" (kg). EFi = Exposure frequency for age bin "i" (days/year). This describes how often a person is likely to be exposed to the contaminated medium over the course of a typical year. EDi = Exposure duration for age bin "i" (years). This describes how long a person is likely to be exposed to the contaminated medium during their lifetime. AT = Averaging time (days). This term specifies the length of time over which the average dose is calculated. For quantifying cancer risk, "lifetime" exposure employs an averaging time of 70 years (i.e., 70 years × 365 days/year). SF = Cancer slope factor (mg/kg-day)-1 ADAFi = Age-dependent adjustment factor for age bin "i" (unitless)
Total risk to the individual is the sum of the risks across all four age intervals. If exposure occurs across two pathways (e.g., ingestion and inhalation of volatiles in water), risks are also summed across pathways.
Based on this, the cancer risk to an individual exposed for 30 years starting at birth (the standard scenario for a Reasonable Maximum Exposure (RME) resident) is calculated for ingestion as follows:
See the following file for an example of this calculation for exposure to benzo[a]pyrene from the ingestion of soil and ingestion of water exposure pathways:
- Benzo[a]pyrene Risk Calculation (PDF) (2 pp, 111K) (Revision 1.0, 9/7/2006)
For an example of this calculation that sums cancer risks across exposure pathways, see the following file that presents risks from exposure to benzidine from the ingestion and dermal exposure pathways:
- Benzidine Risk Calculation (PDF) (4 pp, 105K) (Revision 2.0, 11/28/2007)
 Inhalation risk is calculated differently. For more information see Methods for Derivation of Inhalation Reference Concentrations and Application of Inhalation Dosimetry (EPA/600/8-90/066F, October 1994).
 Dermal risk is calculated differently. For more information see Risk Assessment Guidance for Superfund Volume I: Human Health Evaluation Manual Part E, Supplemental Guidance for Dermal Risk Assessment (OSWER 9285.7-02EP, July 2004).
Other Carcinogenic Polycyclic Aromatic Hydrocarbons (PAHs)
Benzo[a]pyrene (BaP) is often used as an index chemical when assessing other carcinogenic PAHs (PDF) (1 pg, 15K). Such a use 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, the ADAF(s) should be applied to the BaP slope factor before using relative potency factors (PDF) (1 pg, 11K) to estimate risk from exposure to other PAHs.
See the following file for an example of this calculation for chrysene:
- Chrysene Risk Calculation (PDF) (2 pp, 113K) (Revision 2.0, 10/23/2006)
See Section 6 of the Supplemental Guidance for additional risk calculation examples that adjust for early-life exposure to chemicals or compounds with a mutagenic mode of action (MOA) for carcinogenesis.