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

2. Assumption of Dose Additivity: Carcinogens 1. Multiple chemicals: Risk T =  Risk i 2. Multiple exposure pathways: Total Exposure Cancer Risk = Risk pathway1 + Risk pathway2 + … + Risk pathwayi 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 = EC 1 /RS 1 + EC 2 /RS 2 + … + EC i /Rs i X TR

4. Assumption of Dose Additivity: Noncarcinogens 1. Multiple chemicals: Hazard Index = E 1 /RfD 1 + E 2 /RfD 2 + … + E i /RfD i 2. Multiple exposure pathways: Total Hazard Index = HI pathway1 + HI pathway2 + … + HI pathwayi 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 = EC 1 /RS 1 + EC 2 /RS 2 + … + EC i /RS i

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 »Soil ni, Soil i, Soil es »GW 1, GW 2, GW es Not applicable to Soil GW, Soil sat, GW 3, Water sol, 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 Additivity Example ChemicalTarget OrganRSAdjusted RS Akidney24 8 Bkidney, liver15 5 C CNS10 Dkidney60 20 èDivide 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 nIf 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 COC Target THQ  RS THQ  RS THQ  RS A kidney 1.0 20.33 0.67 0.8 1.6 B kidney 1.0 900.33 30 0.1 9 C kidney 1.0 1200.33 40 0.1 12 Total HI 3.01.0 1.0

15. MO-2 Additivity Example: Calculation of a THI for Each Target Organ THI kidney = EC A /RS A + EC B /RS B + EC c /RS c where: EC = exposure concentration RS = RECAP Standard THI kidney = 1/1.6 + 0.5/9 + 3/12 = 0.93 P 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 (GW 1 or GW 2 ) and soil

18. Additivity: TPH Fractions nAliphatics C >6 -C 8 nAliphatics C >8 -C 16 (C >8 -C 10, C >10 -C 12, C >12 -C 16 ) nAliphatics C >16 -C 35 nAromatics C >8 -C 16 (C >8 -C 10, C >10 -C 12, C >12 -C 16 ) nAromatics C >16 -C 35

19. Additivity: TPH nAdditivity - 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 Fractions Example nSoil: ethylbenzene, aliphatics C >8 -C 10, C >10 -C 12, C >12 -C 16 nId of targets: ethylbenzene: liver, kidney, developmental aliphatics C >8 -C 10 : liver, hematological system aliphatics C >10 -C 12 : liver, hematological system aliphatics C >12 -C 16 : liver, hematological system nAdditivity - Liver: ethylbenzene and aliphatics C >8 -C 16 nAdjustment factor: 2 NOT 4 C >8 -C 16

21. Additivity: TPH Fractions Example (cont’d) nAdjustment of MO-1 Soil ni : ethylbenzene: 1500/2 = 750 mg/kg aliphatics C >8 -C 10 : 1100/2 = 550 mg/kg aliphatics C >10 -C 12 : 2100/2 = 1050 mg/kg aliphatics C >12 -C 16 : 3100/2 = 1550 mg/kg

22. MO-1 Additivity Example for Soil Table 2 - Gasoline release COC MO-1 Soil ni Target Organ/Effect benzene --- --- ethylbenzene1500 liver, kidney, develop. toluene690 liver, kid., CNS, nas.epi. xylene12,000  activity,  bw,  mort. aliphatics C6-8 --- kidney aliphatics C8-101100 liver, hematol. sys. aliphatics C10-122100 liver, hematol. sys. aromatics C8-10610  bw aromatics C10-121000  bw

23. MO-1 Additivity Example for Soil Table 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 Soil Table 2 - Gasoline release COC Adjusted MO-1 Soil ni 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 Soil Table 2 - Gasoline release Identification of the limiting soil RS: COC Soil ni Soil GWDW * Soil sat benzene1.54.8900 ethylbenzene500 29,040230 toluene230 52,800 520 xylene6000 79,200150 aliphatics C6-810,00010,000NA aliphatics C8-1036710,000 NA aliphatics C10-12700 10,000 NA aromatics C8-10305 10,000 NA aromatics C10-12500 10,000NA *based on a DF3 of 440

26. MO-1 Additivity Example for GW Table 3 - Gasoline release COC MO-1 GW 1 Target Organ/Effect benzene --- --- ethylbenzene --- liver, kidney, develop. toluene --- liver, kid., CNS, nas.epi. xylene ---  activity,  bw,  mortality aliphatics C6-832 kidney aliphatics C8-101.3 liver, hematol. sys. aliphatics C10-121.4 liver, hematol. sys. aromatics C8-100.34  bw aromatics C10-120.34  bw

27. MO-1 Additivity Example for GW Table 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 GW Table 3 - Gasoline release COC Adjusted MO-1 GW 1 benzene --- ethylbenzene --- toluene --- xylene--- aliphatics C6-832  3 = 11 (kidney) aliphatics C8-101.3  3 = 0.43 (liver) aliphatics C10-121.4  3 = 0.47 (liver) aromatics C8-100.34  2 = 0.17 (  bw) aromatics C10-120.34  2 = 0.17 (  bw)

29. MO-1 Additivity Example for GW Table 3 - Gasoline release Identification of the limiting GW RS: COC GW 1 Water sol benzene 0.0051800 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: GW 1 and GW 2 nInclude all NC COC when identifying targets nIf no current exposure:  Adjust GW 1 or GW 2 RS based on NC effects  Do not adjust GW 1 or GW 2 RS based on MCL

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