Refine the exposure assessment using suitable models for specific conditions of use, populations and activities. If additional exposure information is needed:
Identify dominant exposure pathways through databases (Chemical and Product Categories Database https://actor.epa.gov/cpcat/faces/home.xhtml; [ 55]), targeted sampling of plausible environmental media and household products, and structure-based predictions of chemical function [ 56] Add chemical structure to suspect screening libraries for environmental and biological monitoring [ 57]
Evaluate existing chemical-specific toxicity data, determine sufficiency of the information for a chemical-specific screening level risk assessment for endpoints of potential concern (systemic toxicity or cholinesterase inhibition or genotoxicity). If additional hazard information is needed for potential concerns related to systemic toxicity:
Consider using read across. If chemical specific data are still needed, then consider a tiered approach utilizing HTS (e.g., ToxCast/Tox21, or whole genome transcriptomics). In a case where traditional in vivo toxicity testing is determined to be warranted, then a tiered approach should be contemplated.
If additional information is needed for potential concerns related to genotoxicity:
Consider conducting genotoxicity screening tests of the chemical (e.g., Ames assay, gene mutation assay in mammalian cells, in vitro micronucleus, in vivo mammalian genetox) and design a tiered testing strategy. Evaluate potential modes of action using HTS (ToxCast/Tox21) screening assays to identify potential molecular initiating events associated with existing AOPs for cancer.
4. If additional information is needed for potential concerns related to cholinesterase inhibition, review principles and procedures for selecting appropriate endpoints for assessing potential hazards to humans exposed to anticholinesterase pesticides and design a tiered testing strategy. |
