Table 10. Matrix of BINWOE Determinations for Neurological, Developmental, Reproductive, Renal, and Carcinogenic Effects of Intermediate or Chronic Simultaneous Oral Exposure to Chemicals of Concern ON TOXICITY OF Uranium Uranium Radiation

Examination of the available joint toxic action data, presented in Section 2.2, reveals that no health effects data are available for the complete mixture, or for ternary submixtures. Because suitable toxicity data, joint action models, and PBPK models are lacking for the complete mixture, the recommended approach for the exposure-based assessment of joint toxic action of this mixture is to use a hazard index approach with a target-organ toxicity dose (TTD) modification and a qualitative WOE method. The hazard index, together with the WOE approach, assesses the potential consequences of additive and interactive joint action of the components of the mixture on noncarcinogenic endpoints of concern (ATSDR 2001b). Table 10 presents a matrix of the BINWOE values, where available, for each of the component pairs of the chemicals of concern as discussed in Chapter 2. Where appropriate, TTDs for oral exposure scenarios have been derived as described in the Appendices, using the methods recommended by ATSDR (2001b). However, in some cases, particularly for fluoride and cyanide, the effects on less-sensitive endpoints are not well studied, resulting in the application of very high uncertainty factors in calculation of TTD values. When the uncertainty associated with TTD calculation would result in numerical values lower than those of the MRL, which is based on the most sensitive observed effect identified and which is, in most cases, much better studied, the MRL value was recommended instead. Table 11 lists numerical values of these TTDs, and of the MRLs where available, for the shared endpoints of concern for chronic oral exposure to this mixture: renal, reproductive, and neurological effects. Additionally, for two components, fluoride and nitrate, the most sensitive endpoint is not a shared target of toxicity for the mixture. Therefore, the chronic MRL for fluoride is also presented. Since no toxicological profile or MRLs exist for nitrate, the RfD derived by U.S. EPA (IRIS 2002), is presented. Hazard indices for these unique sensitive endpoints can be calculated based on the MRL or RfD, respectively.