OEL considerations on an API and an intermediate

Client

A pharmaceutical developer.

Background

Bibra was asked to consider whether an occupational exposure limit (OEL) for workers exposed to an active pharmaceutical ingredient (API) should be revised, and to derive a new OEL for a structurally-related chemical intermediate.

Project goals

To identify and review toxicity data on both the API and its intermediate, and (if data gaps were identified) to evaluate the suitability of using read-across from one compound to the other. These data were then used in conjunction with current European guidance to inform on OELs for both the API and its intermediate.

Approach

Bibra was provided with a number of primary study reports on both the API and the intermediate. Comprehensive literature searches identified further laboratory data on the API. A comparison of the chemical structures of both compounds (including a consideration of structure-activity relationships (SARs)) indicated that toxicity data on the API should also be relevant to the intermediate for data-gap filling.

Project outcome

Bibra was able to revise the current systemic OEL for the API, and to use this value to derive a systemic OEL for the structurally-related intermediate.

Bibra project team

Beth O’Connell

Anne Edwards

James Hopkins

• Safe oral intakes for pharmaceutical excipients
• All
• Biocompatibility skin irritation sensitisation two medical devices