3.4. Common mechanism of action
Human health risk assessments for pesticides, including OPs, have been routinely performed using the reference dose (RfD) or acceptable daily intake (ADI) approaches, which define an acceptable level of human exposure to compounds, that would be without appreciable risks of deleterious effects during a lifetime of exposure to the general population, including sensitive subgroups. No-observed-adverse-effect-levels (NOAELs) are derived from subchronic or chronic animal studies identifying the most sensitive adverse effect; division of the NOAEL by uncertainty factors (generally based on interspecies extrapolation and intraspecies variability) allow the determination of the RfD (or ADI). Even though an individual may be exposed to more than one OP at any given time (e.g., through consumption of multiple residues on foods), risk characterization has been based on toxicity of, and exposure to, individual chemicals [93]. With the enactment by the US Congress of the Food Quality Protection Act (FQPA) in 1996, the US Environmental Protection Agency (US EPA) is now required to conduct combined risk assessments for pesticides showing a “common mechanism of toxicity” [65]. In essence, if two or more pesticides are considered to act through a common mechanism, then cumulative effects of co-exposure would have to be considered in the evaluation and setting of tolerance levels.