3. Recommendation for Exposure-Based Assessment of Joint Toxic Action of the Mixture To conduct exposure-based assessments of possible noncancer or cancer health hazards from oral exposures to mixtures of 2,3,7,8-TCDD, hexachlorobenzene, p,p’-DDE, methylmercury, and PCBs, component-based approaches

To conduct exposure-based assessments of possible noncancer or cancer health hazards from oral exposures to mixtures of 2,3,7,8-TCDD, hexachlorobenzene, p,p’-DDE, methylmercury, and PCBs, component-based approaches are recommended, because there are no direct data available to characterize health hazards (and dose-response relationships) from exposure to the mixture. In addition, PBPK/PD models have not yet been developed that would predict appropriate target doses of the components. Recommendations focus on oral exposure scenarios (e.g., from breast milk intake or other food sources) because these are most pertinent to public health concerns from these biopersistent chemicals. As discussed by ATSDR (1992, 2001a), the exposure-based assessment of potential health hazard is a screening approach, to be used in conjunction with evaluation of community-specific health outcome data, consideration of community health concerns, and biomedical judgement, to assess the degree of public health hazard presented by mixtures of substances released into the environment. In a componentbased approach for noncancer health effects: (1) joint additive actions of the components on shared targets of toxicity are assumed; (2) oral intakes are calculated based on measured concentrations of the components in media of concern (e.g., breast milk); (3) intakes are divided by MRLs or target-organ toxicity doses (TTDs); and (4) the resulting hazard quotients are summed to arrive at a hazard index. For cancer, a similar approach is taken, but the last two steps involve multiplication of the intakes by EPA cancer slope factors and summation of the resultant risk estimates.