Background

The toxicity of constituents is not always independent when they are present in mixtures. The scientific literature has an increasing assortment of research articles concerning the interactive toxicological effects of chemicals. Increasingly, agencies such as the EPA and ATSDR are formulating guidance on how to assess mixtures. In human health risk assessment, we routinely consider mixtures of polycyclic aromatic hydrocarbons (PAHs), polychlorinated biphenyls (PCBs), and dioxins and dioxin-like compounds – all families of compounds with similar chemical structure and toxicity and for which international concensus has been reached on a means of mixture risk assessment. . However, it is becoming increasingly apparent that mixtures of substances with dissimilar chemical structure may have similar modes of action, similar target organs, and similar toxic effects. As such, these mixtures warrant an effective evaluation of interactions.

Recently, it was shown that elemental mercury, methyl mercury, and lead should be evaluated as a mixture with toxicological interactions, when co-exposure is confirmed or assumed (SNC-Lavalin Inc 2010). That report can be downloaded from the US FDA at: http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMateria...

Objective for a Work Group

The objectives of this Work Group will be established once the working group initiates its activities. However, likely issues of focus will include new topics and ideas related to evaluating dissimilar mixtures when conducting human health risk assessments, and to promote SETAC sponsorship of research and analyses that will advance the human health risk assessment of dissimilar mixtures.

Technical Approach

Initially, the working group will work to identify methods for grouping dissimilar metals into relevant categories for evaluation of toxicological interactions (perhaps based on target organ, mechanism of action, frequency of co-occurrence in the environment, etc), and then begin the process of identifying and compiling data and published studies relevant to preparing interaction profiles.