4.1. FRACTION-BASED NONCANCER RISK ASSESSMENT

Noncancer health hazard assessment for the entire hydrocarbon mixture using the fraction approach is performed at a screening level using the HI approach. The quantitative exposure information for these individual chemicals or fractions is based on analytical data from the hazardous waste sites. Figure 4–Figure 7 provide graphic illustrations of how noncancer risk assessments are carried out using the toxicity values for the total petroleum hydrocarbon fractions under two scenarios: Option 1 (see Figures 4 and 5), where environmental media have been analyzed for the total fraction concentration only; and Option 2 (see Figures 6 and 7), where environmental media have been analyzed for the total fraction concentration as well as individual fraction components. For the sake of completeness, Figure 4–Figure 7 show summation across all six fractions, but, depending on the source of the mixture and weathering and transport, exposure may not include all fractions.

Figure 4

Fraction-Based Oral Noncancer Risk Assessment for Complex Mixtures of Aliphatic and Aromatic Hydrocarbons: Option 1.

Figure 7

Fraction-Based Inhalation Noncancer Risk Assessment for Complex Mixtures of Aliphatic and Aromatic Hydrocarbons: Option 2.

Figure 5

Fraction-Based Inhalation Noncancer Risk Assessment for Complex Mixtures of Aliphatic and Aromatic Hydrocarbons: Option 1.

Figure 6

Fraction-Based Oral Noncancer Risk Assessment for Complex Mixtures of Aliphatic and Aromatic Hydrocarbons: Option 2.

where:

The steps involved in noncancer risk assessment of the hydrocarbon mixture using Option 1 are as follows:

• Oral

  1)

  Aliphatic low, medium, and high carbon range fractions and aromatic medium and high carbon range fractions:

  1. Combine exposure estimate (mg/kg-day) for the fraction with the appropriate duration (subchronic or chronic) RfD from Table 18 to estimate HI for each fraction.

  2)

  Aromatic low carbon range fraction:

  1. Combine individual exposure estimates for components with their corresponding toxicity values in Table 18 to calculate HIs for each component; sum HIs across the components.

  3)

  Sum HIs across all fractions assessed at the site.

• Inhalation

  1)

  Aliphatic low and medium carbon range fractions and aromatic medium and high carbon range fractions:

  1. Combine exposure estimate (mg/m³) for the fraction with the appropriate duration (subchronic or chronic) RfC from Table 18 to estimate HI for each fraction.

  2)

  Aromatic low carbon range fraction:

  1. Combine individual exposure estimates for components with their corresponding toxicity values in Table 18 to calculate HIs for each component; sum HIs across the components.

  3)

  Sum HIs across all fractions assessed at the site. Note: data do not support inhalation noncancer assessment for the aliphatic high carbon range fraction.

Table 18

Fraction-Specific Noncancer Toxicity Values for Option 1: Exposure Media Analyzed for BTEX and Fractions.

The steps involved in noncancer risk assessment of the hydrocarbon mixture using Option 2 are as follows:

• Oral

  1)

  Aliphatic medium and high carbon range fractions:

  1. Combine exposure estimate (mg/kg-day) for the fraction with the appropriate duration (subchronic or chronic) RfD from Table 19 to estimate HI for each fraction.

  2)

  Aromatic low carbon range fraction:

  1. Combine individual exposure estimates for components with their corresponding toxicity values in Table 19 to calculate HIs for each component; sum HIs across the components.

  3)

  Aliphatic low and aromatic medium and high carbon range fractions:

  1. Combine individual exposure estimates for components with their corresponding toxicity values in Table 19 to calculate component-specific HIs.
  2. Subtract doses or concentrations (mg/kg-day) of all components assessed individually (by route and exposure duration) from the estimated dose or concentration of the total fraction to estimate the exposure concentration for the balance of the fraction.
  3. Combine the exposure estimate (mg/kg-day) for the balance of the fraction with the appropriate duration (subchronic or chronic) RfD fr the surrogate shown in Table 19.
  4. Sum the HIs for the components with the HI calculated for the remaining fraction mass to estimate the HI for the fraction.

  4)

  Sum HIs across all fractions assessed at the site.

• Inhalation

  1)

  Aliphatic medium range fraction:

  1. Combine exposure estimate (mg/m³) for the fraction with the appropriate duration (subchronic or chronic) RfC from Table 19 to estimate HI for each fraction.

  2)

  Aromatic low carbon range fraction:

  1. Combine individual exposure estimates for components with their corresponding toxicity values in Table 19 to calculate HIs for each component; sum HIs across the components.

  3)

  Aliphatic low and aromatic medium and high carbon range fractions:

  1. Combine individual exposure estimates for components with their corresponding toxicity values in Table 19 to calculate component-specific HIs.
  2. Subtract doses or concentrations (mg/m³) of all components assessed individually (by route and exposure duration) from the estimated dose or concentration of the total fraction to estimate the exposure concentration for the balance of the fraction.
  3. Combine the exposure estimate (mg/m³) for the balance of the fraction with the appropriate duration (subchronic or chronic) RfC for the surrogate shown in Table 19.
  4. Sum the HIs for the components with the HI calculated for the remaining fraction mass to estimate the HI for the fraction.

  4)

  Sum HIs across all fractions assessed at the site. Note: data do not support inhalation noncancer assessment for the aliphatic high carbon range fraction.

Table 19

Fraction-Specific Noncancer Toxicity Values for Option 2: Analytical Data Available for Individual Components and Fractions.

There may be circumstances in which a combination of Options 1 and 2 are used. For example, if there are analytical data for individual components of the aromatic medium carbon range fraction, but not the aromatic high carbon range fraction, Option 2 would be used for the medium fraction, while Option 1 would be used for the high fraction.

4.2. FRACTION-BASED CANCER RISK ASSESSMENT

Cancer health risk assessment for the entire hydrocarbon mixture using the fraction approach is performed using a combination of dose- and response-addition methods. Dose-addition methods are used in application of the RPFs to cancer risk assessment of PAHs that lack cancer risk values. Response addition is used for the components with corresponding OSFs or IURs. Figures 8 and 9 provide graphic illustrations of how oral and inhalation cancer risk assessments are carried out using the toxicity values for petroleum fractions. For the sake of completeness, Figures 8 and 9 show summation of all fractions, but exposure at some sites may be limited to fewer fractions. Figure 10 details three options for estimating oral cancer risk for exposure to the aromatic high carbon range fraction.

Figure 8

Fraction-Based Oral Cancer Risk Assessment for Complex Mixtures of Aliphatic and Aromatic Hydrocarbons.

Figure 9

Fraction-Based Inhalation Cancer Risk Assessment for Complex Mixtures of Aliphatic and Aromatic Hydrocarbons.

Figure 10

Options for Oral Cancer Risk Assessment for the Aromatic High Carbon Range Fraction.

where:

The steps involved in cancer risk assessment of the hydrocarbon mixture are shown below for oral and inhalation exposures.

• Oral:

  1)

  Aliphatic low, medium, and high carbon range fractions and aromatic medium carbon range fraction:

  1. Data do not currently support direct cancer assessment.

  2)

  Aromatic low carbon range fraction:

  1. Combine individual lifetime oral exposure estimate (mg/kg-day) for aromatic low carbon range fraction with the OSF for benzene in Table 20 to estimate risk for the fraction.

  3)

  Aromatic high carbon range fraction:

• Option 1:

  1. Combine oral exposure estimate (mg/kg-day) for fraction with the OSF for benzo[a]pyrene in Table 20 to estimate risk for the fraction.
• Option 2:

  1. For PAHs with RPFs, multiply each individual exposure estimate by its corresponding RPFs from Table 21 and the OSF for benzo[a]pyrene to estimate risks.
  2. Sum risks across the PAHs.
• Option 3:

  1. Combine individual exposure estimates (mg/kg-day) for components with OSFs in Table 20 to estimate risks.
  2. For PAHs⁹ with RPFs, multiply each individual exposure estimate by its corresponding RPF from Table 21 and the OSF for benzo[a]pyrene to estimate risks.
  3. Sum risks across the PAHs, subPAH, and other carcinogenic fraction member with OSFs.

  4)

  Sum risks across aromatic low and high carbon range fractions (if assessed at the site).

• Inhalation:

  1)

  Aliphatic low and medium carbon range fractions:

  1. Combine inhalation exposure estimate (mg/m³) for each fraction with its corresponding IUR from Table 20 to estimate risk for each fraction.

  2)

  Aromatic low carbon range fraction:

  1. Combine individual exposure estimate (mg/m³) for the aromatic low carbon range fraction with the IUR for benzene in Table 20 to estimate risk for the fraction.

  3)

  Aromatic high carbon range fraction:

• Option 1:

  1. Combine inhalation exposure estimate (mg/m³) for fraction with the IUR for benzo[a]pyrene in Table 20 to estimate risk for the fraction.
• Option 2:

  1. For PAHs with RPFs, multiply each individual exposure estimate by its corresponding RPFs from Table 21 and the IUR for benzo[a]pyrene to estimate risks.
  2. Sum risks across the PAHs.

  5)

  Sum risks across all fractions assessed at the site.

Table 20

Fraction-Specific Cancer Toxicity Values.

Table 21

RPFs for PAH Carcinogenicity.

4.3. UNCERTAINTY ASSESSMENT

Mixture risk assessment with dose- or response-addition is a default approach that is used to evaluate potential health risks when whole mixture toxicity data are not available. Application of the petroleum fraction method, using both dose- and response-addition approaches, involves assumptions that may be difficult to substantiate for complex mixtures of petroleum contaminants, including:

1)

The surrogate mixture or component(s) represents the toxicity of the entire fraction.

2)

Synergistic or potentiating toxicological interactions among chemicals are less likely to happen at low environmental contamination levels.

3)

Compounds act through independent modes of toxic action when compounds are evaluated using response addition, OR there is a common mode of toxic action for compounds evaluated using dose-addition.

Whenever possible, these assumptions should be evaluated and verified as part of the risk assessment process, and the results should be articulated as part of the final risk characterization. This PPRTV assessment, and the companion documents on individual compounds, mixtures, or fractions, can provide information pertaining to the first assumption. The second assumption can be evaluated through literature review. If two or more chemicals at a site are detected at high exposure concentrations, the toxicology literature should be consulted for information on toxicological interactions among these chemicals. If interactions are demonstrated, especially if synergism or potentiation is shown, this information should be described in the risk characterization along with the quantitative risk or hazard estimates. The assumptions regarding modes of toxic action may be informed by review of the toxicity assessments (IRIS toxicological reviews, PPRTV assessment documents, or ATSDR toxicological profiles) for the most important contaminants. For further guidance, details, and discussion, see U.S. EPA (2000) and the other references cited above.

An important source of uncertainty is the use of an indicator compound or surrogate mixture to represent the toxicity of an untested mixture or portion of a mixture. Therefore, the U.S. EPA suggests that risk assessors characterize the percentage of the estimated risk or of the HI that is calculated using an indicator chemical or surrogate mixture approach. To that end, the U.S. EPA suggests that when a hybrid approach (as described above) is used, risk assessors estimate the risk associated with the measured amount of the surrogate compound (e.g., TMBs for the aromatic medium carbon range or BaP for the aromatic high carbon range) separately from the balance of the fraction, as a means of explicitly characterizing the more uncertain portion associated with the balance of the fraction. For example, when a hybrid approach is used for the chronic inhalation toxicity of the aromatic medium carbon range fraction, risks or HIs would be calculated separately for isopropylbenzene, n-propylbenzene, and TMBs, before using the toxicity value of TMBs to estimate the risk or HI associated with the balance of the fraction.

The quality of the underlying toxicity data used to develop either a provisional or screening RfD, a provisional or screening RfC, or a provisional or screening OSF or IUR is an additional source of uncertainty. To convey the difference in quality in the mixture risk assessment, the U.S. EPA suggests that risk assessors identify the percentage of the estimated risk or of the HI that is associated with screening toxicity estimates (i.e., screening OSFs, screening p-RfDs, or screening p-RfCs) and the percentage based on provisional estimates (i.e., p-OSFs, p-IURs, or p-RfDs). Such examinations of mixture risk estimates are consistent with mixture risk assessment practices (Rice et al., 2005; U.S. EPA, 2000).