I. AW for ecotoxicity
Selection of primary group is based on the maximal number of analogues with experimental data. The following profilers was selected as appropriate for primary categorization:
- US-EPA New Chemical Categories;
- Acute aquatic toxicity classification by Verhaar (Modified);
- Acute aquatic toxicity MOA by OASIS;
- Aquatic toxicity classification by ECOSAR;
- Organic Functional groups;
- Organic functional groups (US EPA);
- Organic functional groups, Norbert Haider (checkmol).
The profiler providing the most populated category is selected to build the first category. This eliminates the possibility to miss some good analogues with observed data. If two or more profilers are providing equally populated categories, then AND mode is applied for category building.
II. AW for SS
There are three possible cases to form an analogues set when execute AW for SS:
1) if the target have an active alert as a parent (Protein binding alerts for skin sensitization by OASIS v.1.4. profiler is used);
2) if the target have an active alert as a result of autoxidation or skin metabolism activation (Protein binding alerts for skin sensitization by OASIS v.1.4. profiler is used in combination with Autoxidation simulator or Skin metabolism simulator);
3) if no alert is found in the target or its metabolites.
If a protein binding alert is identified in the target (case 1) or is produced as a result of autoxidation or skin metabolism (case 2) then primary grouping is based on this alert. In the last case (case 3) the primary group is defined using structurally based profiling schemes such as the Organic Functions Groups, US EPA New Chemical Categories or Acute aquatic toxicity classification by ECOSAR.
You can go through all executed steps during the workflow by click on the different levels of document tree (Figure 1). Furthermore, all used profilers used for the prediction are described in the final report.