Toxicological risk assessment of leachables from container closure system

Challenge

A pharmaceutical company needed to understand whether substances that may leach (i.e. leachables) from a container closure system of one of their medicinal products could present a risk of harm to persons using the topical medicine.

Solution

SLR was asked to undertake a toxicological risk assessment of the leachables identified in a laboratory extractable-leachable correlation study. Potential exposures to volatile and non-volatile leachables were conservatively estimated.

Toxicological information for each leachable was interrogated in order to derive safe permissible daily exposure levels by applying appropriate uncertainty factors to No Observed Adverse Effect Levels from experimental animal studies or relevant human information. Where insufficient toxicological information was found in the scientific literature, chemical grouping strategies and structure activity relationships were used to fill data gaps.

Impact

The assessment determined the likelihood of harm to human health as a result of exposure to potential leachables. The information was used by the client to determine whether method development or validation for determination of leachables in the product was considered to be required.