Figure 15.

Flowchart of the scheme for the assessment whether a substance exhibits time‐reinforced toxicity

• 1: Lifespan dose–response is calculated using the selected GUTS model, for both the active period and winter scenario.
2: This part has to be duplicated for the active period and the winter (inactive) period.
3: When an effect > 10% is predicted, either higher tier studies can be performed, or a specific TRT laboratory study can be executed. This second option is only applicable when this conclusion of > 10% effect is reached on the basis of the worst‐case assumption that Haber's exponent = −2.