the tank mixture is calculated on the basis of the dilution to which the formulation is subjected, and the environmental concentration would be determined from modeling using, for example, PRZM2/EXAMS II.

Column 5 of Table 4-1 presents the final environmental exposure chemical concentrations, which are the sums of the concentrations of the individual chemicals in Column 4 (environmental exposure concentration). Most of the values are the same as presented in the previous column unless the chemical appears twice. For example, cypermethrin was present in the formulation to be applied with a residual amount (0.005 ppb) already present in the environment; thus, the final concentration of cypermethrin in the exposure environment is the sum of the two concentrations. The exposure analysis concerning the mixture of chemicals present in the environment is arguably the most challenging aspect of the mixture risk assessment owing to the high degree of uncertainty about the identity of chemicals and their environmental concentrations. Column 6 of Table 4-1 identifies chemicals expected to elicit toxicity by the same mechanism of action: chemicals that act similarly are assigned the same letter. Thus, cypermethrin and deltamethrin are both expected to elicit toxicity through the disruption of axonal sodium channels and are both assigned the letter a. Nonylphenol and polysorbate 20 have the ability to mobilize the pesticide and are identified with the letter b. Nonylphenol and ethinyl estradiol elicit estrogenic activity and are therefore identified with the letter c.

It is necessary at this stage to identify the adverse response of the listed species that is deemed most relevant to the pesticide of concern. In this exercise, disruption of axonal sodium channels is assumed to be the mechanism of action, and immobilization and loss of equilibrium are identified as the relevant responses because these sublethal responses are considered indicative of impending lethality or reproductive impairment. The other eight chemicals are considered only in their potential capacity to modify that response to cypermethrin. Thus, reproductive impairment associated with the combined estrogenicity of nonylphenol and ethinyl estradiol would not be considered relevant to the assessment of cypermethrin and would not be integrated into the toxicity assessment. If one or more components of the environmental mixture were predicted to elicit toxicity independently of cypermethrin, risk assessments of those components might be warranted.

Column 7 (K values) of Table 4-1 identifies chemicals that have the potential to enhance the toxicity of cypermethrin and the similarly acting chemical deltamethrin in a nonadditive manner. That would include synergists, PBO in this exercise. The modifying effect of the synergist PBO on the response to cypermethrin and deltamethrin is defined by a coefficient of interaction (K) (Mu and LeBlanc 2004; Rider and LeBlanc 2005; TenBrook et al. 2010), which can be viewed as a special case of the coefficient of synergism (ê) as described by Finney (1942). K values are typically determined experimentally by assessing the effect of increasing concentrations of a synergist on a specific response to a pesticide—such as an estimate of the effective concentration at which 50% of

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