Is the use of a LD50 an acceptable point of departure?

No. The use of an LD50 (lethal dose 50%) is not an acceptable point of departure for establishing health-based exposure limits (HBEL).

Source: Questions and answers on implementation of risk based prevention of cross contamination in production and ‘Guideline on setting health based exposure limits for use in risk identification in the manufacture of different medicinal products in shared facilities’ (EMA/CHMP/CVMP/SWP/169430/2012)  page 3. Q5.

In addition, as shown below, the Active Pharmaceutical Ingredients Committee (APIC) Guidance on Aspects of Cleaning Validation in Active Pharmaceutical Ingredient Plants (rev. April 2019 (updated in February 2021)) strongly advises against the use of the LD50 since these values are not reliable for predicting long-term health effects (p 9-10).

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