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Päivi Jokiniemi and Paul Trouth
Article related to: REACH
Making non-animal test methods the default
A lot of research is being done to develop test methods and strategies to assess the potential effects of chemicals on humans and the environment that can refine, reduce or replace the use of animals. These approaches are called ‘alternative methods’ to the traditional testing on animals that have been in place for decades. There are now legally recognised alternative methods to test for skin corrosion/irritation, serious eye damage/eye irritation, skin sensitisation and acute toxicity.
Legal changes to the REACH Regulation came into force on 20 June 2016 which set out the conditions under which animal testing is no longer required. This means that alternatives replacing some of the most frequently conducted animal studies are now the default requirement within Europe.
Skin irritation and corrosion are effects that can occur both in the workplace and at home. They are categorised as local effects, which means that they occur at the point of contact between the skin and substance.
A step-wise approach to testing is required when assessing irritation and corrosion. If you get a negative result from a validated in vitro skin corrosion study, you will then need to perform a validated in vitro skin irritation test to further assess skin irritation.
If you then obtain a negative result from a validated in vitro skin irritation study, you will not need to do further tests, as it can be concluded that the substance does not need to be classified for corrosion or irritation.
Serious eye damage/eye irritation
Serious eye damage and eye irritation are effects that can occur both in the workplace and at home and they are also categorised as local effects. The front parts of the eye, i.e. the conjunctiva, iris and cornea, are usually assessed for irritation and corrosive effects as a result of direct contact with a substance.
The current validated in vitro studies can only detect substances which cause serious eye damage (CLP/GHS category 1) or which do not need to be classified for eye irritation (no category CLP/GHS). However, they cannot detect chemicals which are classified as eye irritants category 2 under CLP/GHS.
Here also a step-wise approach is recommended: for serious eye damage/eye irritation effects, the first study you should conduct is a validated in vitro study that can detect substances causing serious eye damage but can also indicate substances that do not irritate the eyes. If a conclusion on classification cannot be made, additional in vitro studies should be considered.
However, if the conclusion is neither “no classification” or “serious eye damage”, then you will need to use in vivo models to further assess the potential to irritate the eye and to conclude on classification and risk assessment.
Acute dermal and oral toxicity
Acute toxicity means adverse effects which may occur within 24 hours of exposure to large amounts of a substance, either through skin contact, ingestion or inhalation. For example, an accidental spillage in the workplace could cause acute toxicity. The symptoms are generally rapid in their onset and affect various organs.
The test for contact with the skin can now be omitted if you can show that the substance does not need to be classified after the test related to oral toxicity. In addition, a validated in vitro test is available and can be used in combination with other information to show a lack of oral toxicity.
Skin sensitisation is an allergic reaction on the skin when it is exposed to a chemical for a second or more times. It is an immunological response.
From autumn 2016, alternatives (in vitro and in chemico methods) to animal testing are the default as a first step for generating new information to assess skin sensitisation potential as described in the REACH Regulation.
You can only test on animals if the alternatives for this endpoint are not suitable for your substance or if the results of the alternative tests do not provide the information required for classification and risk assessment.
How are registrants affected?
You must take these changed requirements into account when you submit information to ECHA.
If you have already registered your substance and submitted studies based on the previous requirements, you do not need to modify your registration dossier immediately. However, when updating your dossier, you will need to follow the new requirements, for example, registrants who met the previous requirements with an in vivo study do not need to carry out additional in vitro studies. However, when you update your dossier, you will need to explain why you did not submit an in vitro study.
To help you, ECHA is currently updating its guidance on information requirements. Advice on the use of OECD test guidelines related to skin and eye irritation have already been updated and published on ECHA’s website.
Irritants - cause a localised, reversible inflammatory reaction.
Corrosives - cause burns at the point of contact.
Sensitisers - give rise to an allergic reaction.
Acute toxicity - lead to various symptoms, ranging from discomfort to death, and arising from a short duration of exposure to a relatively large amount of a chemical.
Toxic(ological) endpoints - endpoints that are used to define the properties of a substance, which may result in adverse effects in humans.
Acute vs chronic endpoints - acute studies generally last no longer than a week and examine endpoints such as mortality and behaviour. With acute studies, a common endpoint is the dose of a compound required to kill half of the organisms in the study. Chronic studies are longer in duration (more than a week) and include endpoints such as reproduction, long-term survival and growth.
In vitro vs in vivo - in vitro studies are conducted in test tubes, i.e. outside the living organism, using cell or tissue cultures. In vivo studies are conducted within the living organisms as surrogates for humans, for example, rats and mice.
Ex vivo - studies where living cells/tissues or even organs are removed from a living organism and then used in a toxicity study to determine the effects of chemical exposure.
In chemico - the use of non-animal or in vitro measurement of the reactivity or other physicochemical properties of compounds.
REACH annexes amended – registrants to use alternative test methods, News alert 6 June 2016
Advice on skin and eye irritation testing helps reduce animal tests, News alert 5 July 2016
Registrants to use alternative test methods for skin sensitisation, News item 5 July 2016
OECD and EU test guidelines
Practical Guide for SME managers and REACH coordinators - How to fulfil your information requirements at tonnages 1-10 and 10-100 tonnes per year
How to use alternatives to animal testing to fulfil your information requirements for REACH registration
Manuals on preparing REACH dossiers
Multilingual explanations of terms
Text by Nedyu Yasenov
Top image: Fotolia
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