Application of the concept for the evaluation of a compound
Case 1: Risk assessment of dermal exposure with substance X for which no toxicological data are
available besides genotoxicity data and skin irritation/corrosion data
Step 1: Determine external exposure
Result: External exposure is 10 µg/kg bw/day
Step 2: Determine dermal absorption by appropriate method (e.g. OECD test No. 428)
Result: Dermal absorption is 50%
Step 3: Calculate internal exposure.
Result: Internal exposure is 5 µg/kg bw/day.
Step 4: Apply decision tree to allocate Cramer class
Result: Substance X is Cramer class I.
Step 5: Compare internal exposure with substance X to the internal TTC value of Cramer class I
Result: The internal exposure of 5 µg/kg bw/day is below the internal TTC value for Cramer class I
substances of 6.9 µg/kg bw/day.
Conclusion: The dermal exposure with substance X is of no immediate concern.
Case 2: In the context of REACH legislation, the need has to be assessed for further data on
reprotoxicity of the substance Y which has a consumer exposure on oral route.
Step 1: Determine external exposure
Result: External exposure is below 1 µg/kg bw/day
Step 2: Determine oral absorption by appropriate method (as described in OECD test No. 417).
Result: Oral absorption is 2%.
Step 3: Calculate internal exposure.
Result: Internal exposure is 0.02 µg/kg bw/day.
Step 4: Apply decision tree to allocate Cramer class
Result: Substance Y is Cramer class II/III
Step 5: Compare internal exposure with substance Y to the internal TTC value of Cramer class II/III.
Result: The internal exposure of 0.02 µg/kg bw/day is below the internal TTC value for Cramer class I
substances of 0.1 µg/kg bw/day.
Conclusion: The oral exposure with substance Y would qualify as ‘no relevant human exposure’ or ‘no
significant exposure’.