44
R. Williams et al.
Table 3.2 Summary of exclusion criteria for the defined approach
Exclusion criteria used in the defined approach
Information source applicable for
defined approach?
Derek
MIE/KE1KE2
KE3
Derek likelihood
Certain, probable,
plausible, doubted,
improbable
✓
Equivocal
✗
Derek negative prediction Non-sensitiser
✓
Non-sensitiser containing
misclassified feature(s)
✗
Non-sensitiser containing
unclassified feature(s)
✗
Metabolic activation
Prohapten
✓
✗
✓
✓
Lipophilicity
>3.5
✓
✓
✓
✗
>5
✓
✓
✗
✗
Lysine-reactivity
Exclusive
✓
✓
✗
✓
MIE/KE1 = molecular initiating event/key event 1 (hapten binding). KE2 = key event 2 (keratinocytes activation). KE3 = key event 3 (activation of dendritic cells). ✓ = information source is
prioritised in defined approach. ✗ = information source is de-prioritised in defined approach
Fig. 3.2 Defined approach decision tree uses exclusion criteria to de-prioritise in chemico/in vitro
assays and then uses the Derek outcome to determine which branch of the tree to follow. Between
1 and 3 in chemico/in vitro assays are then run in order of the AOP (MIE → KE2 → KE3)
unless de-prioritised in the previous step and the outcome(s) used to assign a hazard classification
(sensitiser/non-sensitiser) and predict the potency category (Basketter 1-4, 5/6) and GHS classification
to prioritise the information sources that are believed to be most informative for the
chemical in question (Table 3.2).
After a chemical has been assessed and any relevant exclusion criteria considered,
the results from prioritised assays were used in a 2 out of 3 approach (run in order of