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Päivi Jokiniemi and Paul Trouth
Article related to: REACH
More progress needed to replace animal tests
ECHA’s report on how non-animal approaches can be applied sees promising development on alternatives to animal testing, but proposes a continuous and active dialogue between the research community and regulatory authorities to ensure further progress.
The report describes how non-animal approaches can be applied to REACH, CLP and the Biocidal Products regulations and reviews their current status as well as needs for future development. Overall, non-animal approaches are increasingly being developed and used.
Testing chemicals on animals should be carried out as the last resort, only after all other scientifically reliable methods have been explored.
To further develop non-animal approaches, dialogue between researchers and regulatory authorities is needed. “We must ensure that innovations can be considered for regulatory use without delay. We propose an inventory of non-animal approaches, covering different stages of development and regulatory applicability. This would help to identify current gaps and determine future steps to enhance their use,” says Dr Hannele Huuskonen, Senior Scientific Officer in the Evaluation Directorate at ECHA.
Significant scientific progress
|Hannele Huuskonen. |
Over the last 10 years, there has been significant progress in developing non-animal approaches.
“There are various methods and promising tools that have increased our understanding of biological and (eco)toxicological mechanisms. For example, advances in
‘-omics’ that reflect the activity of biological pathways and metabolism in cells and tissues have enabled us to get information on how substances can cause molecular and functional changes in cells,” Dr Huuskonen tells.
Technical developments now allow in vitro microsystems to be used – this is also known as organ-on-a-chip technology. “This method uses human cells that grow on a microchip. They can simulate human organs and even interactions between different organs. It is a promising approach for predicting toxicity in various organs.”
Concepts such as the integrated approach to testing and assessment (IATA) and the adverse outcome pathways (AOPs) enable data from non-animal approaches to be better used.
“This has already reduced the need for animal testing. These developments can also help regulators to take further steps towards replacing, reducing and refining animal testing,” Dr Huuskonen explains.
High-throughput and high-content techniques are used to screen substances for possible further analyses and also potentially for future identification of hazards and safety levels. They help to quickly analyse properties of many chemicals and therefore can provide more information on their toxicity.
“Overall, the new approaches will help to produce and analyse data on the toxicity of chemicals and improve their safety evaluation – hazard classification and risk assessment. This will reduce the need for animal-based data in regulatory work,” she states.
Combining new methods
Many of these new approaches are still under development and not yet accepted as a direct replacement for animal testing. They need further research and standardisation in order to find an agreement on how to interpret their results in a harmonised way. Only after this can the methods be validated for use under the EU chemicals legislation. This is especially the case for more complex endpoints, such as repeated dose toxicity or reproductive toxicity, where non-animal approaches are not yet available to be used as standalone methods.
However, many of these methods can be used as supporting evidence for other data – for example, as part of grouping and read-across or a weight-of-evidence approach. These are ways to use existing data to predict toxicity of new substances and they reduce the need to carry out new tests on animals. The non-animal approaches can also be very useful for screening substances for further regulatory action.
“To improve the interpretation of results of non-animal approaches, information from humans, animal studies and non-animal approaches need to be combined, so that we can produce reliable and consistent results that can be used for registration purposes or to classify the hazards of chemicals”, Dr Huuskonen says.
Some non-animal approaches, such as in vitro tests, using cells or tissue, and in chemico tests (using abiotic assays) are already the default method for companies who need to provide data on skin corrosion/irritation, serious eye damage/eye irritation, mutagenicity or skin sensitisation of their substance. These methods were included in the REACH Annexes in 2016.
“We expect registrants to use in vitro and in chemico methods wherever possible. Animal tests can only be used if the non-animal ones are not adequate for the substance or cannot be used for hazard classification and risk assessment. Companies are encouraged to read our guidance to help them get familiar with using non-animal approaches. We also provide tools and advice through updated guidance, practical guides, IT tools, case studies and webinars,” Dr Huuskonen reminds.
Adverse outcome pathway - sequence of events from the chemical structure of a target chemical or group of similar chemicals through the molecular initiating event to an in vivo outcome of interest.
High-throughput screening - method involving an automated operation platform, data processing and control software to quickly conduct many biochemical, genetic or pharmacological tests.
In chemico - abiotic assay measuring chemical reactivity or other physicochemical properties of substances.
In silico - information from computer software or simulation.
In vitro - Studies using cells, tissues or organs.
Omics - large-scale analytical techniques that can be used to support and understand biological and (eco)toxicological mechanisms.
Interview by Tiiu Brautigam
Published on: 15 February 2018
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Biocidal Products Committee:
26 February-1 March
Committee for Risk Assessment:
Committee for Socio-Economic
18-22 March (tentative)
Management Board meeting:
Member State Committee:
13-17 May (tentative)