PROMOTING REGULATORY ACCEPTANCE

Promoting Regulatory Acceptance

Chemical Read-across is a non-testing approach for safety assessment, widely used for regulatory purposes and a well-established alternative to animal testing.

Societal concerns on the impact of chemicals in human health and the environment are increasing, with the need to characterize potential hazards arising from the exposure to thousands of substances. Adding to this, concerns about animal welfare are embed in many chemical management frameworks, with some authorities already announcing plans to end the use of animal testing.

Read-across has been used for many years under the High Production Volume (HPV) program under the Organization for Economic Co-operation and Development (OECD) or the United States Environmental Protection Agency (US EPA). Under this program, read-across has been used mainly for prioritization purposes, allowing to identify chemicals of concern. Traditional approaches to generate toxicity information are resource intensive and time consuming, making chemical read-across an accessible and faster tool in assessing and identifying chemicals for potential hazard characterization and further testing.

The impetus for read-across has been largely driven in the European Union (EU) by the Cosmetics regulatory framework, but also notably the EU’s Registration, Evaluation, Authorization and Restriction of Chemicals regulation (EU REACH). EU REACH in particular encourages the use of (Q)SARs and read-across as a means of addressing endpoint information requirements, provided a number of conditions are met. For cosmetic manufacturers, it’s an important tool that allows to innovate in an era of sectoral animal testing restrictions.

To be accepted for regulatory purposes, a read-across proposal needs to meet strict requirements. In this approach there are many variables and areas of uncertainty that have to be considered with expert judgement, which can make it challenging to demonstrate that the proposed hypothesis is valid. Though there are different purposes for which read-across can be used (prioritization vs. filling data gaps), the underpinning pillars of a robust hypothesis are similar.

Despite the wealth of existing guidance, support tools and related work over many years, read-across proposals often face resistance to their acceptance.

On their third report on the use of alternatives to testing on animals for the REACH Regulation (ECHA, 2017), the European Chemicals Agency (ECHA) reported quality deficiencies in the read-across proposals such as:

  • Poor documentation
  • Insufficient substance identification
  • Significant deficiencies in the quality of the source studies
  • Lack of or low quality of supporting data,
  • Lack of qualitative and quantitative data to support predictions based on toxicokinetics
  • Shortcomings in the toxicological hypothesis

In this AFSA workstream our aim is to examine barriers to regulatory acceptance of scientifically robust read-across proposals and develop novel strategies to overcoming these.

Our strategy is to:

  • Provide a space for companies to share their experiences regarding well-constructed read-across proposals and build case studies
  • Foster dialogue with regulators
  • Support brainstorming & collaborative strategies to overcome barriers to regulatory acceptance
  • Potentially engage with appeal channels, to raise awareness and knowledge around the topic

References

The use of alternatives to testing on animals for the REACH Regulation, Third report under Article 117(3) of the REACH Regulation. European Chemicals Agency (2017). DOI 10.2823/023078 https://echa.europa.eu/documents/10162/13639/alternatives_test_animals_2017_en.pdf

Grace Patlewicz, Mark T.D. Cronin, George Helman, Jason C. Lambert, Lucina E. Lizarraga, Imran Shah. Navigating through the minefield of read-across frameworks: A commentary perspective. Computational Toxicology, Volume 6, Pages 39-54 (2018) ISSN 2468-1113 https://doi.org/10.1016/j.comtox.2018.04.002.

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