Can calculation of HBELs be based on clinical data only?

The aim of determining a health-based exposure limit is to ensure human safety, and consequently it is considered that good quality human clinical data is highly relevant. Unintended pharmacodynamic effects in patients caused by contaminating active substances may constitute a hazard thus clinical pharmacological data should be considered when identifying the critical effect. Consideration should be given to what extent the active substance in question has been associated with critical adverse effects in the clinical setting. If the most critical effect identified to determine a health-based exposure limit is based on pharmacological and/or toxicological effects observed in humans rather than animals, the use of the PDE formula may be inappropriate and a substance-specific assessment of the clinical data may be used for this purpose.