Dear Laxit, knowledge on systemic exposure is an integral part of a systemic tolerance study regardless of the route of administration. After dermal application, the systemic exposure at the systemic NOAEL will be compared to the (expected or measured) human exposure after maximum clinical use to obtain the safety margin for systemic effects. To maximize systemic exposure In dermal toxicity studies in minipigs, the maximum technical feasible area dose is usually applied onto 10% body surface area (if toxicity allows). Best regards, Clemens

Dear Laxit

The answer coild be short: yes, absolutely.

The reason is that toxicokinetics may give an answer to the justified question as to whether systemic uptake will take place and if so, in what quantities to estimate systemic toxicity.

I agree with Dr Clemens Guenther’s comments.

Wishing you success, best regards,

Frederik

Thank you to all three of you.

I have now more clearly understood the conceptof TK and its practical implication in toxicity studies.

Dear Laxit,

Irrespective of route of administration, any general toxicity study of NCE for regulatory purpose would be requiring TK estimation.