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RECAP

RECAP. Addressing Exposure to Multiple Constituents that Elicit Noncarcinogenic Effects on the Same Target Organ/System. Assumption of Dose Additivity: Carcinogens. 1. Multiple chemicals: Risk T =  Risk i 2. Multiple exposure pathways:

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RECAP

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  1. RECAP Addressing Exposure to MultipleConstituents that Elicit Noncarcinogenic Effects on the Same Target Organ/System

  2. Assumption of Dose Additivity: Carcinogens 1. Multiple chemicals: RiskT =  Riski 2. Multiple exposure pathways: Total Exposure Cancer Risk = Riskpathway1 + Riskpathway2 + … + Riskpathwayi RAGS-A EPA 1989

  3. Carcinogens and the RBCA Approach • A target risk level of 10-6 for individual chemicals and pathways generally will lead to a cumulative risk within the 10-6 to 10-4 range (SSG 1996) • Total Exposure Cancer Risk should be < 10-6 to 10-4 • Risk = EC1/RS1 + EC2/RS2 + … + ECi/Rsi X TR

  4. Assumption of Dose Additivity: Noncarcinogens 1. Multiple chemicals: Hazard Index = E1/RfD1 + E2/RfD2 + … + Ei/RfDi 2. Multiple exposure pathways: Total Hazard Index = HIpathway1 + HIpathway2 + … + HIpathwayi RAGS-A EPA 1989

  5. Assumption of Dose Additivity: Noncarcinogens • Simultaneous subthreshold exposures to multiple noncarcinogenic chemicals could result in an adverse health effect • Only applicable to noncarcinogenic chemicals that affect the same target organ/critical effect (RfD) RAGS-A EPA 1989

  6. Noncarcinogens and the RBCA Approach • No acceptable risk “range” • When multiple chemicals and/or pathways are present, target HQ should be adjusted so that the Total HI < 1.0 • Total HI = EC1/RS1 + EC2/RS2 + … + ECi/RSi

  7. MO-1 and MO-2 RS • Represent an acceptable exposure level for exposure to a single chemical via a single medium • Do not address additivity due to exposure to multiple chemicals or multiple exposure media • RS do address exposure via multiple pathways

  8. MO-1 and MO-2 RS • Risk-based RS must be adjusted to account for potential additive effects • Soilni, Soili, Soiles • GW1, GW2, GWes • Not applicable to SoilGW, Soilsat, GW3, Watersol, background levels, quantitation limits, MCLs, ceiling values

  9. MO-1: Accounting for Additivity • Modification of risk-based MO-1 RS: • group noncarcinogenic chemicals by target organ/critical effect

  10. MO-1: Accounting for Additivity 1. Identify the target organ/critical effect for each noncarcinogenic chemical (RfD) • http://www.epa.gov/iris/subst/index.html 2. Group the chemicals by target organ/critical effect 3. Divide the RS by the number of chemicals affecting the same target organ

  11. MO-1: Accounting for AdditivityExample Chemical Target Organ RS Adjusted RS A kidney 24 8 B kidney, liver 15 5 C CNS 10 D kidney 60 20 • Divide the RS for A, B, and D by 3 (kidney) (Same as calculating a RS using a THQ of 0.33)

  12. Additivity - MO-1 • If many noncarcinogenic COC are present: • Adjust NC RS to account for additivity • Compare adjusted NC RS to C RS and choose the lower of the two • NC RS presented in Appendix I Worksheets

  13. MO-2: Methods for Accounting for Additivity • Modification of risk-based MO-2 RS: • group by target organ/critical effect • site-specific apportionment of RS or THQ • calculation of a total HI for each target organ

  14. MO-2: Additivity Example:Site-specific apportionment COCTargetTHQRSTHQRSTHQRS A kidney 1.0 2 0.33 0.670.8 1.6 B kidney 1.0 90 0.33 300.1 9 C kidney 1.0 120 0.33 400.1 12 Total HI 3.0 1.0 1.0

  15. MO-2 Additivity Example:Calculation of a THI for Each Target Organ THIkidney = ECA/RSA + ECB/RSB + ECc/RSc where: EC = exposure concentration RS = RECAP Standard THIkidney = 1/1.6 + 0.5/9 + 3/12 = 0.93 • THI must be < 1.0

  16. MO-3B: Accounting for Additivity Modification of risk-based MO-3 RS: • site-specific apportionment of RS or THQ • calculation of a total HI for each target organ/effect • group by target organ/critical effect

  17. Additivity Exposure to Multiple Media • If there is exposure to chemicals via more than one medium, then RS must be modified to account for additivity • Applicable only to MO-2 and MO-3 • MO-2 Example: a receptor is being exposed to chemicals via drinking water (GW1 or GW2) and soil

  18. Additivity: TPH Fractions • Aliphatics C>6-C8 • Aliphatics C>8-C16 (C>8-C10, C>10-C12, C>12-C16) • Aliphatics C>16-C35 • Aromatics C>8-C16 (C>8-C10, C>10-C12, C>12-C16) • Aromatics C>16-C35

  19. Additivity: TPH • Additivity - TPH RS based on 10,000 cap • Do not adjust 10,000 cap • Identify risk-based value in Appendix I worksheets or calculate • Adjust risk-based RS to account for additive effects • If adjusted risk-based RS < 10,000, use risk-based RS • If adjusted risk-based RS > 10,000, use 10,000 cap

  20. Additivity: TPH FractionsExample • Soil: ethylbenzene, aliphatics C>8-C10, C>10-C12, C>12-C16 • Id of targets: ethylbenzene: liver, kidney, developmental aliphatics C>8-C10: liver, hematological system aliphatics C>10-C12: liver, hematological system aliphatics C>12-C16 : liver, hematological system • Additivity - Liver: ethylbenzene and aliphatics C>8-C16 • Adjustment factor: 2 NOT 4 C>8-C16

  21. Additivity: TPH FractionsExample (cont’d) • Adjustment of MO-1 Soilni: ethylbenzene: 1500/2 = 750 mg/kg aliphatics C>8-C10: 1100/2 = 550 mg/kg aliphatics C>10-C12: 2100/2 = 1050 mg/kg aliphatics C>12-C16 : 3100/2 = 1550 mg/kg

  22. MO-1 Additivity Example for SoilTable 2 - Gasoline release COCMO-1 SoilniTarget Organ/Effect benzene --- --- ethylbenzene 1500 liver, kidney, develop. toluene 690 liver, kid., CNS, nas.epi. xylene 12,000 activity, bw,mort. aliphatics C6-8 --- kidney aliphatics C8-10 1100 liver, hematol. sys. aliphatics C10-12 2100 liver, hematol. sys. aromatics C8-10 610 bw aromatics C10-12 1000 bw

  23. MO-1 Additivity Example for SoilTable 2 - Gasoline release Summarize by target organ: (3) liver: ethylbenzene, toluene, aliphatics C8-12 (3) kidney: ethylbenzene, toluene, aliphatics C6-8 (1) developmental: ethylbenzene (1) CNS: toluene (1) nasal epithelium: toluene (1) hyperactivity: xylene (2) bw: xylene, aromatics C8-12 (1) mortality: xylene (1) hematological system: aliphatics C8-12

  24. MO-1 Additivity Example for SoilTable 2 - Gasoline release COCAdjusted MO-1 Soilni benzene --- ethylbenzene 1500  3 = 500 (liver) toluene 690  3 = 230 (liver) xylene 12,000  2 = 6,000 (bw) aliphatics C6-8 --- aliphatics C8-10 1100  3 = 367 (liver) aliphatics C10-12 2100  3 = 700 (liver) aromatics C8-10 610 2 = 305 (bw) aromatics C10-12 1000  2 = 500 (bw)

  25. MO-1 Additivity Example for SoilTable 2 - Gasoline release Identification of the limiting soil RS: COCSoilniSoilGWDW*Soilsat benzene 1.5 4.8 900 ethylbenzene 500 29,040 230 toluene 230 52,800 520 xylene 6000 79,200 150 aliphatics C6-8 10,000 10,000 NA aliphatics C8-10 367 10,000 NA aliphatics C10-12 700 10,000 NA aromatics C8-10 305 10,000 NA aromatics C10-12 500 10,000 NA *based on a DF3 of 440

  26. MO-1 Additivity Example for GWTable 3 - Gasoline release COCMO-1 GW1Target Organ/Effect benzene --- --- ethylbenzene --- liver, kidney, develop. toluene --- liver, kid., CNS, nas.epi. xylene --- activity, bw, mortality aliphatics C6-8 32 kidney aliphatics C8-10 1.3 liver, hematol. sys. aliphatics C10-12 1.4 liver, hematol. sys. aromatics C8-10 0.34 bw aromatics C10-12 0.34 bw

  27. MO-1 Additivity Example for GWTable 3 - Gasoline release Summarize by target organ: (3) liver: ethylbenzene, toluene, aliphatics C8-12 (3) kidney: ethylbenzene, toluene, aliphatics C6-8 (1) developmental: ethylbenzene (1) CNS: toluene (1) nasal epithelium: toluene (1) hyperactivity: xylene (2) bw: xylene, aromatics C8-12 (1) mortality: xylene (1) hematological system: aliphatics C8-12

  28. MO-1 Additivity Example for GWTable 3 - Gasoline release COCAdjusted MO-1 GW1 benzene --- ethylbenzene --- toluene --- xylene --- aliphatics C6-8 32  3 = 11 (kidney) aliphatics C8-10 1.3  3 = 0.43 (liver) aliphatics C10-12 1.4  3 = 0.47 (liver) aromatics C8-10 0.34  2 = 0.17 (bw) aromatics C10-12 0.34  2 = 0.17 (bw)

  29. MO-1 Additivity Example for GWTable 3 - Gasoline release Identification of the limiting GW RS: COCGW1Watersol benzene 0.005 1800 ethylbenzene 0.7 170 toluene 1 530 xylene 10 160 aliphatics C6-8 11 NA aliphatics C8-10 0.43 NA aliphatics C10-12 0.47 NA aromatics C8-10 0.17 NA aromatics C10-12 0.17 NA

  30. Additivity: GW1 and GW2 • Include all NC COC when identifying targets • If no current exposure: • Adjust GW1 or GW2 RS based on NC effects • Do not adjust GW1 or GW2 RS based on MCL

  31. Additivity: GW1 and GW2 • If exposure is occurring: • Adjust GW1 or GW2 RS based on NC effects • For GW1 or GW2 RS based on MCL: 1. Calculate GW1 or GW2 RS for NC effects (Appendix I or J) 2. Adjust RS to account for additivity

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