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Factsheet

ECHA-12-FS-08-EN

Role of animal testing in ensuring
the safe use of chemical substances
It is the goal of the REACH Regulation
to ensure a high level of protection ofhuman health and the environment
from hazardous effects of chemicals.
The REACH Regulation represents
the balance established in thelegislative process between the needfor generating new information on
hazardous properties using animal tests
and the aim of avoiding unnecessary
animal testing. It therefore establishes
the principle that testing on vertebrate
animals shall be a last resort.
Companies producing or importing chemical
substances have to ensure that they can be usedsafely. This is achieved by using – and where necessary
generating – information on the intrinsic properties
of substances to assess their hazards both forclassification and risk assessment, and hence todevelop appropriate risk management measures toprotect human health and the environment.
A key motivation for developing REACH was to fill
information gaps for the large number of substances
already in use in the EU, as for many such substances
there was inadequate information on their hazardous
properties and the risks their use may pose.

Without a comprehensive set of information on theessential hazardous properties of higher volume
chemical substances, registrants cannot undertakea chemical safety assessment that will recommend
appropriate risk management measures to avoid orlimit exposure. In particular, information on properties
such as organ toxicity after long term exposure, thepotential to induce cancer, toxicity to the developing
foetus, toxicity to the reproductive functions, or longterm aquatic toxicity are often not available for suchsubstances.
Standard Information Requirements
REACH registrants have to provide all relevant andavailable information on the intrinsic properties of thesubstance in their registration dossier.
The information which must be provided in acompany’s registration dossier depends on thetonnage level at which a substance is imported
or produced. Higher tonnages of a substance areregarded as an indicator of a higher potential to cause
damage to human health and the environment andneed to be investigated more thoroughly than at lower
tonnages.
Annexes VII, VIII, IX and X of the Regulation specify
what information is required at levels of 1, 10, 100,or 1000 or more tonnes per year per registrant,respectively. These are called the ‘standard

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information requirements’ and are highest for
substances at or above 1000 tonnes per year.

No 440/2008) is the vehicle for the Commission to lay
down test methods to be used under REACH.

Where data for a basic (“core”) set of information
which addresses a number of intrinsic properties of a
substance (as specified in Annexes VII and VIII) is notavailable, registrants are responsible for generating
this data and providing it in their registration dossier.
Depending on the property concerned, the standard
information requirements may specify information
which can be obtained from standard tests. Dependingon the test specified either bacteria, cultured cells or
animals are normally used.

There are a number of options to use information
derived from other ‘non-standard’ methods or other
non-testing approaches, which are described below in
the following sections.

The core information is intended to show, for example,
if a single exposure, or one lasting a few hours or days,
has the potential to cause serious harm to humanhealth or the environment. Information from othertests, in bacterial cells for example, may be able togive an indication as to the potential of a substance tocause cancer.
At higher tonnage levels, there are additional
information requirements (as specified in Annexes IXand X). At these levels, more detailed and extensive
information is required and can be obtained using what
are called higher-tier studies. If data gaps have been
identified and cannot be filled otherwise, registrants
will have to conduct higher-tier studies to fulfil therequirements of Annexes IX and X. However, before
such testing can start, they have to submit testing
proposals and receive prior approval from ECHA.
Some of the studies to assess the properties ofsubstances, specifically for high tonnage registrations,are conducted on experimental animals. For most of
the hazardous properties studied in experimental
animals, the species used are rat and mouse, butrabbit, guinea pig, fish, and in rare cases bird, may also
be used (specifically bred strains).
REACH however requires that tests entailing the useof live animals shall be carried out in compliance withlegislation enacted under Directive 2010/63/EU on
the protection of animals used for scientific purposes.
This Directive covers a number of requirements on
the care for laboratory animals and requires thatscientifically satisfactory methods or strategies
using live animals should not be performed if theresults can be obtained by another scientificallysatisfactory method. The test method regulation (ECAvoiding Unnecessary Testing on Animals
There are several different mechanisms in REACH
to avoid unnecessary animal tests, in particular, data
sharing and the use of alternative test methods
and other approaches to predict the properties ofsubstances. However, the filling of data gaps meansthat some new animal testing will be necessary.
Registrants are obliged by REACH to limit new studies
using vertebrate animals for REACH registration
as they are to be conducted only as a last resort.
Registrants must first collect and assess all existing
data. They then have to identify data gaps andconsider whether these can be filled by using either invitro/ex vivo studies or other alternative approaches
including prediction methods before any new animal
tests are conducted.
This means that all available information is collected:
information from in vivo (using live animals), ex vivo
(for example, using tissues from animals) and in vitro
studies (for example, using bacteria or cultured cells),
information from human exposure, predictions on
the basis of information available from structurallyrelated substances (i.e. by ‘read-across’ and ‘chemicalcategories’) and predictions from valid computational
prediction methods, for example, (quantitative)
structure activity relationships ((Q)SAR).
To justify the use of non-standard tests or other nonanimal testing approaches, registrants may ‘adapt’ thestandard information requirements by complying witha number of preconditions (as specified in Annexes VIIto X, column 2 or Annex XI of the Regulation). Annex
XI enables the use of any information, even that notgenerated by recognised test methods, which avoids
or reduces the need for animal testing, it must also
be suitable for the purposes of classification, risk
assessment, and hazard communication.
In addition, there are data sharing obligations forregistrants of the same substance to avoid duplicate
testing using experimental animals.

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Registrants remain responsible for assessing theintrinsic properties of their substances for hazard
and/or risk assessment and classification; they areresponsible for making the respective technical andscientific judgments. However, ECHA can require missing information to be provided, including animal tests,
if the adaptation justification or non-standard data do
not meet the information needed according to REACH,
as an outcome of the dossier evaluation processes.

may choose to do this. Industry has to obtain all
the available relevant information and evaluate
it using the CLP classification criteria, in order toappropriately classify their chemical substancesand mixtures for hazard communication by means oflabelling, providing Safety Data Sheets (SDSs) andusing suitable packaging. In practice, this means thatmany substances can be (re)classified on the basis of
the REACH registration data.

The objectives in defining ECHA's role in evaluation
under REACH is to keep the responsibility forsafety of chemicals on industry whilst avoiding
unneccessary testing. ECHA performs compliancechecks of registration dossiers to verify whether theinformation requirements of the REACH Annexes aremet. ECHA´s role in evaluating testing proposals is toensure that if a test is performed the results will be
acceptable for REACH purposes. In this process, ECHA
is not expected to do any work that should normally bedone by the registrant. In both cases, the result may
be a draft decision requesting further information
including results from tests on animals.

Current Status of Alternative Approaches

On its website, ECHA publishes all testing proposals
involving vertebrate animals which are put forward
by registrants with a view to fulfilling the standard
information requirements specified in Annexes IX andX of REACH. These concern the higher-tier studies forcomplex endpoints which require most animals. Thirdparties, such as non-governmental organisations andcompanies, then have 45 days to submit scientificallyvalid information or studies that address the relevant
substance and hazard end-point specified in theTesting Proposal.
The companies that are addressed by ECHA’s draftdecisions, have the right to comment in the decision
making process. The Member States Competent
Authorities review all draft decisions and may proposeamendments. If so, the case is referred to the Member
State Committee, which has to reach a unanimous
agreement on the draft decision. If this is not reached,
ECHA refers the case to the Commission for decision.
This procedure was established to ensure that thebest possible use is made of existing information,and that animal testing is required only when thenecessary information is unavailable.
The Classification, Labelling and Packaging (CLP)
Regulation does not require new studies to beconducted, although some suppliers of substances

Over the past few years a number of in vitro test
methods that are suitable for REACH purposes havebeen adopted and incorporated in the Test Methods
Regulation. However, there are currently no in vitro/
ex vivo tests or test batteries that can act as a
like-for-like replacement of higher-tier toxicology
studies, such as those investigating carcinogenicity,
mutagenicity or reproductive toxicity (CMR), forREACH. However, they may be useful as part of aweight of evidence (WoE) approach or as a basis forclassification under CLP and can thus, depending on
the case, render testing on animals unnecessary.
Animal tests can be avoided if the hazardous
properties of a substance can be predicted using
computer models, sometimes referred to as in silico
methods, i.e. using QSARs or the SAR approach. At
present, such in silico predictions cannot be used alone
to predict a number of the toxicological properties(long-term toxicity, carcinogenicity, mutagenicity,and reproductive toxicity) of substances for REACH,
although they may be useful as part of a WoE approachor as a basis for classification under CLP.
Properties of substances can be predicted using
information from tests on analogues by the ‘readacross’ approach, or for a group of substances using
the ‘category’ approach. The registrant is responsible
for making the scientific arguments that these predicted properties are adequate for REACH, in terms
of providing comparable information to the animalstudies on the registered substance. Read-across andcategories are the most promising approaches to predict the long-term toxicological and CMR properties
of substances for REACH (and CLP). However, it should
be noted that sufficient information must be available
to support these predictions.
Registrants should be careful in using tools developed
in research and development projects and otherannankatu 18 , p.o. box 400, fi - 00121 helsinki, finland | echa.europa.eu

4innovative techniques for predicting properties anddata waiving as these are not necessarily suitable asregulatory tools for REACH and CLP. Registrants areadvised to be mindful of the limitations from suchpredictions, which will depend on the particular model
used and may be case-specific. Nevertheless, it may
be that non-standard and innovative predictions canserve to build up a fuller picture of the substanceproperty as part of a WoE approach or as part of an
Integrated Testing Strategy (ITS), even if the property
cannot be predicted adequately for REACH and CLP
using the technique alone.
Furthermore, newly-developed alternative in vitro
test methods undergo validation in order to assess
their relevance and reliability. The European Centre
for the Validation of Alternative Methods (ECVAM)
validates alternative methods that replace, reduceand refine the use of animals in scientific procedures.
Regulatory acceptance of validated alternativemethods will be facilitated and streamlined by thenew mechanism of “preliminary analysis of regulatory
relevance” (PARERE). These consultation networks ofthe European Commission involve EU Member State
contact points and relevant agencies and committees,such as ECHA.
Promoting Alternative Methods for
Animal Testing
Besides its role in the compliance check and thetesting proposal examination, ECHA has a role to playin helping registrants to implement REACH and byfacilitating the duties of the various actors in meetingthe legislative requirements, which balance the needto assess the risks of substances to human healthand the environment and to avoid unnecessary animaltesting. ECHA also promotes alternatives to testing on
animals that meet the regulatory needs, by providing
information on the opportunities and limitations ofalternative test methods and other approaches.
This is part of the day-to-day activities of the Agency:• ECHA facilitates and promotes the formationof Substance Information Exchange Fora (SIEFs)
where companies share existing data, for example
available data from animal tests.
• ECHA has developed a practical guide “Howto avoid animal testing” and a series of guidance
documents to support registrants in data sharing,chemical safety assessment and other REACH

related tasks that can help to avoid unnecessary
animal tests.
• ECHA Annual Progress Reports on Evaluation
provides recommendations for improving thequality of registrations. to help ensure chemical
substances can be used safely and that unecessary
animal testing is avoided.
• A specific report on the “Use of Alternatives toTesting on Animals for the REACH Regulation” ispublished by ECHA every three years.
• The unique set of information collected
through registration and published on the ECHA
dissemination website can help future registrants
to identify existing data, could encourage data
sharing and may facilitate further developments ofprediction methods.
• ECHA hosts the eChemPortal, which provides
free public access to information on propertiesof chemicals and direct links to collections of
information prepared for government chemical
review programmes at national, regional, andinternational levels. ECHA uses this information
to verify if information on animal tests are alreadyavailable from other authorities.
• The OECD QSAR Toolbox is an important tool for
supporting and enabling category building. ECHA
contributes actively to the further development ofthe Toolbox.
• The ECHA Helpdesk deals with enquiries on
information requirements, computer modelling(Q)SARs, read-across, adaptation rules and testing
proposals.
• ECHA is listening to the concerns of animal
welfare organisations and engaging stakeholders in
its work. The Agency organises targeted awarenessraising and stakeholder support activities, including
workshops, Stakeholder Days, webinars and otherweb-based information and tools.
• The development of internationally-agreed
alternative test methods is especially important
for avoiding unnecessary animal testing, since
they standardises the study protocols. ECHA
contributes to such developments by participatingin EU and OECD working groups, and maintaining
links with other important actors, such as theMember States, the Joint Research Centre of theEuropean Commission and other EU agencies
involved in risk assessment of chemicals.
Animal testing under REACH:
http://echa.europa.eu/web/guest/chemicals-in-ourlife/animal-testing-under-reachannankatu 18 , p.o. box 400, fi - 00121 helsinki, finland | echa.europa.eu