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Building scientific confidence in the development and evaluation of read-across
G Patlewicz1, N Ball2, P J Boogaard3
1DuPont Haskell Global Centers, 1090 Elkton Road, Newark, DE 19711, USA.
Regulatory Toxicology and Pharmacology : RTP
|April 11, 2015
Summary
Read-across, a method for chemical risk assessment, faces practical challenges. This study summarizes efforts to build confidence in read-across justifications, crucial for regulatory acceptance.
Area of Science:
- Toxicology and Chemical Risk Assessment
- Regulatory Science
- Computational Chemistry
Background:
- Read-across is a key alternative method for chemical safety assessments, particularly under regulations like REACH.
- Consistent practical application of read-across remains challenging, hindering broader regulatory acceptance.
- Existing frameworks lack systematic approaches for justifying read-across and quantifying uncertainties for complex toxicological endpoints.
Purpose of the Study:
- To summarize expert deliberations on characterizing scientific confidence in read-across approaches.
- To identify barriers to the acceptance and consistent application of read-across in regulatory risk assessment.
- To inform the development of systematic frameworks for read-across justification and uncertainty evaluation.
Main Methods:
- Review of recent work by Cefic LRI and ECETOC summarizing the state-of-the-art in read-across.
- Analysis of efforts by the European Chemicals Agency (ECHA) to develop a Read-Across Assessment Framework (RAAF).
- Discussion of proposed mechanistic chemical categories underpinned by Adverse Outcome Pathways (AOPs).
Main Results:
- Lack of systematic frameworks for justification and uncertainty assessment is a major barrier to read-across acceptance.
- Ongoing efforts by ECHA and private experts aim to develop standardized read-across assessment frameworks.
- Adverse Outcome Pathways (AOPs) offer a potential approach for evaluating complex substances, including mixtures, beyond discrete organic compounds.
Conclusions:
- Developing robust, systematic frameworks is essential for increasing scientific confidence and regulatory acceptance of read-across.
- The integration of mechanistic approaches like AOPs holds promise for advancing read-across capabilities.
- Continued collaboration between industry and regulatory bodies is vital for overcoming practical challenges in read-across application.
Keywords:
(Quantitative) Structure Activity Relationship (Q)SARAdverse Outcome Pathway (AOP)Analogue approachChemical categoriesQuantitative Mechanistic Models (QMM)Read-acrossScientific confidenceMore Related Videos
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