Smart studies: Examine how in vivo studies could provide more information encompassing novel studies (and endpoints)

Background:

Extended or “smart” studies can be defined as in vivo studies that employ additional or different endpoints from conventional studies.

They fall into 2 categories:
• those that follow up on activity from in silico/in vitro lines of evidence to explore potential severity and potency
• those that follow up on lack of activity in silico/in vitro lines of evidence to provide assurance on lack of toxicity.

They are routinely used in agrochemical R&D to select candidates for development including conventional studies.
Could studies be designed (“smart studies”) which could provide a higher level of evidence, especially when considered along with lines evidence from in silico and in vitro studies, to allow classification and the derivation of Health‐Based Guidance Values (HBGVs)? Could these studies be based on screening studies already included in REACH guidelines? Could the screening studies be enhanced to be more definitive?
This would lead to more information from the same number or fewer experimental animals using modern techniques to improve level of knowledge and confidence. This should increase the level of knowledge for lower tonnage chemicals and reduce the need for high animal usage studies e.g. carcinogenicity and multi- or extended-1-generation and developmental toxicity studies at higher tonnages.

This Task Force is part of the ECETOC Transformational Programme No. 2 ‘Development of an Integrated Approach for Chemicals Assessment’, in which a staged assessment concept has been developed.

Objectives:

• Improve the quality and regulatory value of animal testing, increase human relevance of such testing, meeting knowledge/information needs in a targeted way
• Determine how these studies fit into a tiered approach with other information e.g in vitro.
• Describe how these studies fit into an overall weight of evidence approach, integration with other lines of evidence and information
• Define when these studies should be used. E.g explore indications from in vitro, provide assurance on apparent lack of activity.
• Explore the global impact
• Translation guidance to regulators who have to assess data

Deliverables:

• Peer reviewed paper for discussion with relevant stakeholders (e.g. regulators, industry/ EPAA, NC3Rs)
• Presentation at major toxicological meetings (SOT/Eurotox)