ECHA

Everyone agrees that testing chemicals on animals should be avoided whenever possible. However, it is still happening because chemicals regulations require some of these tests. How far away are we from making testing on animals a thing of the past? Two experts shared their views with us.

The REACH Regulation says that testing on animals is the last resort. It encourages the use of alternative approaches, such as using existing data on similar chemicals or in vitro studies, as long as they give the same extent and quality of information as an animal study. In autumn 2016, REACH was amended in response to scientific developments to make certain in vitro methods the default for assessing skin irritation, eye irritation and skin sensitisation.

Whereas in the past, talk was about replacing, reducing and refining animal testing, we are now talking more and more about new approaches. “These new approaches are about describing the mechanisms of action of a substance when it comes into contact with humans and the environment. The idea is to do something better than animal testing,” explains Dr Costanza Rovida, Scientific Officer at the Centre for Alternatives to Animal Testing (CAAT-Europe) based at the University of Konstanz (Germany). She is also the Italian member of the European consensus platform for alternatives (ecopa).

Wera Teubner. Image: Wera Teubner.

“The interest to minimise animal testing is there. We are now doing all our modelling with animal data. In the future, we will be able to have a perfect prediction for the toxicity of a substance in rats – but what we want to have is a perfect prediction for humans,” says Dr Wera Teubner, Regulatory Toxicologist at BASF Schweiz AG.

Planning together with authorities could help

Although the good will is there, companies are still uncertain about whether the authorities will accept the alternative approaches or not.

According to Dr Teubner, companies only get feedback on their use of alternative approaches if they are not accepted. This is not helpful, because in many cases alternative methods require extensive scientific expertise and the costs are generally higher than using standard methods.

Therefore, the uncertainty can tip the balance in favour of sticking to the established methods. “It would make sense to have the chance to discuss the planned strategy with ECHA in advance,” Dr Teubner says and continues, “to get a pre-indication from the authorities if the chosen approach is likely to be accepted for registrations. That would be very useful and would encourage companies to put their efforts into alternative methods”.

According to Dr Rovida, it is also important to explain how to justify the use of alternative methods to avoid the misconception that alternative approaches are not going to be accepted by ECHA. “Many people think that regulatory authorities will not accept alternative methods but I know this is not true. The challenge is in presenting them well and having adequate documentation for the justification,” she explains.

Shortage of expertise

It requires specific scientific expertise to assess substances using alternative methods. Only very large companies have experts with specific knowledge and experience in-house to do the job. When it comes to the rest, they cannot do it without consultants or contract research organisations that carry out the tests. “Finding a contract research organisation can be difficult. Often they do not have the experience needed and they are not experts in in vitro methods. This is something that needs to be resolved,” Dr Rovida says.

Costanza Rovida. Image: Costanza Rovida.

To improve the situation, Dr Rovida calls for more education in the field, both at university level but also by expert training for those who already know the basics. “We are working hard to train more experts. There is a directive about the use of animals for scientific purposes and it includes a specific requirement for education on alternative methods. We hope that this will bring a change in the future,” she explains.

Dr Teubner agrees that specific expertise is needed. An example of assessing skin sensitisation shows the complexity of the work. “Skin sensitisation requires at least two in vitro studies, which must then be combined in a weight-of-evidence approach,” she explains. The OECD (Organisation for Economic Cooperation and Development) test guidelines for each of the in vitro studies support the scientist, but there are many different ways of evaluating the results and that requires expertise.

Read-across for similar substances

The read-across approach is one of the methods used to avoid animal testing. With some substances, it can be more useful than with others. “If you have a substance with a lot of close structural analogues, the chances are high that you can cover many endpoints by using modelling or read-across,” Dr Teubner says.

“However, it is not possible to use alternative methods for every substance. A read-across or QSAR assessment is only as good as the available experimental data on structural analogues and on the mechanistic understanding of the endpoint. Using an alternative method can only happen after a thorough analysis of the available information on the substance itself and on the structural analogues,” she adds.

If one test result cannot offer you enough justification for your data, the weight-of-evidence approach, that allows you to combine the results gathered with different methods, can offer a solution.

Where to start?

Your substance is always the starting point for planning what method to use to assess its properties. Even though it may sound obvious, the first thing is to make sure that you know the identity of your substance. Only after that can you start considering whether to use, for example, modelling or read-across.

According to Dr Teubner, there are several useful databases when looking for structural analogues, CAS numbers, literature and existing information on chemicals, such as:

eChemPortal;
ChemIDplus (advanced);
OECD QSAR Toolbox;
TOXNET;
PubMed.

“I find the free-text search of the eChemPortal very useful. The portal does not allow you to look for analogues by structure, but if you have the chemical name, you can use part of it in the free-text search with an asterisk at the end, and eChemPortal will give you a list of all other substances that have the fragment in the name,” Dr Teubner says. It contains direct links to chemical hazard and risk information prepared for chemical review programmes at national, regional and international levels.

Once you have decided which method works best with your substance, there is support material available. “The information is unfortunately in different places, so there is not just one reference point to go to. The OECD website contains the official guidelines for using alternative methods and ECHA has a web page for alternative methods as well as guidance with information requirements on specific endpoints,” Dr Rovida says.

Dr Teubner points out that a good way to keep yourself up-to-date on the different in vitro methods and their official acceptance is to check the Joint Research Centre’s website. They have a page that is dedicated to tracking the progress of alternative methods that are on their way towards regulatory acceptance.

So how close are we to ending animal tests?

Both Dr Rovida and Dr Teubner believe that stronger political demand and stricter requirements are needed to make the future animaltest free.

“People do what they have to do, it is only human. So if they have to use in vitro alternative methods, then they will do it. But if using alternatives is only voluntary, it will never happen,” Dr Rovida says and continues, “I would penalise companies who are doing in vivo studies when alternatives exist”. Stronger regulatory pressure would also help companies gain more experience in using alternative methods, which in turn could lead to reduced costs and further increase the pace of development.

But it is not only about the stick. According to Dr Rovida, there needs to be carrots for those willing to give it a try. The right incentives for companies who invest time and money on alternative methods could help. “We need to make it worth their effort. Maybe through economic support or for example by giving them a priority lane for assessment at ECHA,” she suggests.

Although Dr Teubner is more hesitant in her prediction for the future, she agrees that there are developments that can help to further minimise the use of animal testing. She also emphasises that it is extremely difficult to reflect the complex body functions in a limited number of non-animal tests. “REACH is generating a lot of new experimental data which should help with the model building and use of alternative methods," she says and continues, "however, the high demand for information is now, whereas it takes years to develop a new method and get it accepted by the authorities".

For Dr Rovida, it is only a matter of time until we have a world without animal testing. Science makes progress all the time and we can already build a tissue of human organs in 3D instead of using a traditional in vitro system in a petri dish. But we also need a change of attitude. “Companies must realise that animals are not objects or just lab material, and in vivo studies on mammals must only be done if no other possibilities exist,” she concludes.

Video interviews

At the Stakeholders' Day on 5 April 2017, we spoke with Mike Penman from Penman Consulting and Monica Locatelli from TEAM Mastery about using alternative methods. Watch the videos and hear their top tips.
 

Alternatives to testing on animals   There are different ways to avoid unnecessary testing on animals to fulfil your legal obligations for a REACH registration. 1. Share any reliable existing data. 2. Consider alternatives, such as: Weight of evidence – combining several independent sources of information, for example in vitro, read-across and QSAR results. QSAR models – computer models predicting properties based on structural similarity of substances. In vitro methods – tests with isolated tissues, organs or cells that are performed in a controlled environment. Grouping and read-across – using data from a similar substance to predict the property of the substance being registered. Remember that you always need to justify why you are not performing the ‘standard’ animal test and you need to provide scientific data to support your justification.

Organisations BASF Schweiz AG is the Swiss representative of the BASF group. BASF has been involved in developing and validating alternative testing methods for more than 20 years. They have two laboratories dedicated to alternative methods alone. About one third of all toxicological studies at BASF are performed using replacement and supplementary methods. www.alternative-methods.basf.com/group/corporate/ alternatives/en/microsites/alternatives/index Centre for Alternatives to Animal Testing Europe brings together industry and academics to develop alternative methods and promote human science. It is based at the University of Konstanz, Germany. cms.uni-konstanz.de/leist/caat-europe/ European consensus platform for alternatives aims to create a consensus between government and regulatory authorities, academia, industry and animal protection and welfare organisations. It aims to replace, reduce and refine use of animals in research, testing, education and training in Europe. www.ecopa.eu/

Further information:

European Union Reference Laboratory for Alternatives to Animal Testing (EURL ECVAM)

Joint Research Centre – Tracking system for alternative methods towards regulatory acceptance (TSAR)

OECD guidance on integrated approaches to testing and assessment (IATA)

How to avoid unnecessary testing on animals

Grouping of substances and read-across

Animals used for scientific purposes

Multilingual explanation of terms

Interview by Päivi Jokiniemi
Top image: Fotolia
 

If you liked this article, you may also like: Want to know about… read-across, Newsletter 1/2017 Making non-animal test methods the default, Newsletter 3/2016 Alternatives to animal testing – what’s new in 2016?, Newsletter 1/2016