Risk assessment mixed-model mixture

On July 18, 2000, the Agency released HWIR-waste exemption levels for 36 chemicals that were developed using a risk model known as the Multimedia, Multi-pathway and Multi-receptor Risk Assessment (3MRA) Model.17 The May 16, 2001, HWIR-waste rule revised and retained the hazardous waste mixture and derived-from rules as previously discussed in this module. In addition, the rule finalized provisions that conditionally exempt mixed waste (waste that is both radioactive and hazardous), if the mixed waste meets certain conditions in the rule.5... 

FIGURE 5.1 Mixed-model mixture risk assessment approach. Note This illustrates the calculation of steps for combined effects of mixtures with similarly (e.g., Substances 1 to 3) and dissimilarly (e.g., Substances 1 to 3 versus Substances 6 to 8) acting components. 

In our opinion, the data are sufficiently clear to suggest that when it is not feasible to test the mixture in question, mixture extrapolation is the preferred option compared to no extrapolation. Indeed, all literature observations suggest that applying mixture extrapolation is to be preferred over not applying mixture extrapolation. Technical options for extrapolation are concentration addition, response addition, and the mixed-model approach, of which concentration addition is most often applied. Exceptions may apply in cases that are more specific. For example, when it is clear that 2 compounds precipitate (a situation of no exposure due to chemical interactions in the environment), one should acknowledge this prior to assessing mixture risks by mixture extrapolation approaches. When the data of a study allow, refined conclusions are possible. For example, when the study design is appropriate and the mathematical models are appropriate, researchers are able to discriminate between concentration addition and response addition, and (with sufficient experiment efforts) between these models and the mixed-model approach. 

Tier 3 involves the use of both CA and R A models together (mixed-model approaches). This approach differs from the previous tiers by using detailed information on the modes of action for the different mixture components as well as full-curve-based modeling approaches. Mixed models are used in human as well as ecological assessment. An example of mixed-model approaches in ecological risk assessments is the approach proposed for assemblages (De Zwart and Posthuma 2005) a similar approach has been proposed by Ra et al. (2006) see Chapter 4 and Figure 4.2. 

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