the foreign formulation will be difficult to assess. For example, EPA’s ecological risk assessment of glyphosate (EPA 2008) concludes that the probability that glyphosate will affect reproduction of mammals and birds is minimal, and similar conclusions have been drawn in several other risk assessments of glyphosate (WHO 1994; Giesy et al. 2000; Williams et al. 2000). One study in the South American literature, however, indicates that exposure to a South American formulation of Roundup, which contains glyphosate and proprietary surfactants, reduces testosterone concentrations in rats (Dallegrave et al. 2007). Similar reductions were observed in mallards after exposure to a South American formulation of Roundup (Oliveira et al. 2007). As part of the public comments on the registration review of glyphosate, it has been suggested that EPA use the data on the South American formulations to assess the risks to birds and mammals associated with exposures to US formulations (BeyondPesticides 2009); that is, the information on the foreign formulations should essentially be bridged to US formulations. Although pesticide manufacturers are required to disclose information on the composition of pesticide formulations registered in the United States to EPA, the requirement does not extend to pesticide formulations used only outside the United States. Therefore, EPA and the Services probably do not have access to information that would be useful in assessing the similarities or dissimilarities between US and foreign formulations. In the absence of that information, the merits of including data from studies of foreign formulations cannot be determined.
Magnitude of Interactions
EPA seldom addresses interactions quantitatively in ecological risk assessments of pesticides. In three BiOps, NMFS (2008, 2009, 2010) does address information on joint action and relies primarily on the publication by Laetz et al. (2009), which assayed acetylcholinesterase inhibition in Pacific salmon (Oncorhynchus kisutch) for all binary combinations of three organophosphates (diazinon, malathion, and chlorpyrifos) and two carbamates (carbaryl and carbofuran). The study by Laetz et al. (2009) notes interactions that range from additivity to synergism with an increasing prevalence of synergism as the exposures increased. The latter observation is consistent with the concept of interaction thresholds described above. The BiOps, however, do not attempt to use the information from Laetz et al. (2009) to adjust estimates of expected biological responses to mixtures quantitatively. NMFS (2009, p.266) noted that “we are unable to create a predictive model of synergistic toxicity as dose response relationships with multiple ratios of pesticides are not available and the mechanism remains to be determined.” Other BiOps contain similar language and express concerns about mixtures.
EPA’s agency-wide supplementary guidance for mixture risk assessment (EPA 2000) discusses methods for quantitatively addressing toxic interactions, but the methods are cumbersome to apply, and experiments that would be useful