title: Building scientific confidence in the development and evaluation of read-across.
abstract: 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.
authors: DuPont Haskell Global Centers, 1090 Elkton Road, Newark, DE 19711, USA. Electronic address: patlewig@hotmail.com.
authors: G
authors: G
authors: Patlewicz
authors: Toxicology & Environmental Research and Consulting (TERC), The Dow Chemical Company, Midland, MI 48674, USA.
authors: N
authors: N
authors: Ball
authors: Shell Health, Shell International b.v., PO Box 162, 2501 AN The Hague, The Netherlands.
authors: P J
authors: PJ
authors: Boogaard
authors: Regulatory and Technical Affairs Department, American Chemistry Council (ACC), Washington, DC 20002, USA.
authors: R A
authors: RA
authors: Becker
authors: CEFIC - The European Chemical Industry Council, 4 Avenue E. Van Nieuwenhuyse, B-1160 Brussels, Belgium; Hubesch Consult BVBA, Madeliefjeslaan 10, B-1600 Sint-Pieters-Leeuw, Belgium.
authors: B
authors: B
authors: Hubesch
mesh_terms: D000818:Animals; D062067:Chemical Safety / Q000379:methods*; D005062:European Union; D015386:Hazardous Substances / Q000633:toxicity; D006801:Humans; D018570:Risk Assessment / Q000379:methods*; D017751:Safety Management / Q000379:methods; D012586:Science / Q000379:methods*; D014116:Toxicology / Q000379:methods; D035501:Uncertainty
chemical_list: D015386:Hazardous Substances
keywords: (Quantitative) Structure Activity Relationship (Q)SAR; Adverse Outcome Pathway (AOP); Analogue approach; Chemical categories; Quantitative Mechanistic Models (QMM); Read-across; Scientific confidence