Details

Autor(en) / Beteiligte

• Patlewicz, G.
• Ball, N.
• Boogaard, P.J.
• Becker, R.A.
• Hubesch, B.

Titel

Building scientific confidence in the development and evaluation of read-across

Ist Teil von

• Regulatory toxicology and pharmacology, 2015-06, Vol.72 (1), p.117-133

Ort / Verlag

Netherlands: Elsevier Inc

Erscheinungsjahr

2015

Quelle

Elsevier ScienceDirect Journals

Beschreibungen/Notizen

• •Guiding principles are outlined for the development of read-across justifications.•Scientific confidence considerations are discussed for read-across evaluation.•Aspects of these considerations are highlighted using 2 case studies.•These complement other frameworks in progress. Read-across is an alternative approach exploited to address information requirements for risk assessment and for regulatory programmes such as the European Union’s REACH regulation. Whilst read-across approaches are accepted in principle, difficulties still remain in applying them consistently in practice. Recent work within Cefic LRI and ECETOC attempted to summarize the state-of-the-art and identify some of the barriers to broader acceptance of read-across approaches to overcome these. Acceptance is undoubtedly thwarted partly by the lack of a systematic framework to characterize the read-across justification and identify the uncertainties particularly for complex regulatory endpoints such as repeated-dose toxicity or prenatal developmental toxicity. Efforts are underway by the European Chemical’s Agency (ECHA) to develop a Read-Across Assessment Framework (RAAF) and private sector experts have also considered the development of a similar framework. At the same time, mechanistic chemical categories are being proposed which are underpinned by Adverse Outcome Pathways (AOPs). Currently such frameworks are only focusing on discrete organic substances, though the AOP approach could conceivably be applied to evaluate more complex substances such as mixtures. Here we summarize the deliberations of the Cefic LRI read-across team in characterizing scientific confidence in the development and evaluation of read-across.