This website uses non-intrusive cookies to improve your user experience. You can visit our cookie privacy page for more information.

Vertebrate Testing

In vivo vertebrate tests should not be conducted for the purposes of fulfilling the requirements of regulation (EC) No 1107/2009 (concerning the placing of plant protection products on the market) where accepted alternatives are available and could reasonably have been used.  HSE  will not accept  in vivo studies where an accepted alternative is available.

Contents of this guidance:

  1. Background
  2. Current Accepted Alternatives
  3. Dates of Application
  4. What this means for applicants
  5. New OECD Test Guidelines
  6. Regulatory Framework
  7. Adverse data
  8. Links to relevant documents and websites
  9. Footnotes

1. Background

Regulation (EC) No. 1107/2009 aims to minimise vertebrate testing.  When new, alternative OECD Test Guidelines become available that can fully or partially replace in vivo tests, any new studies submitted for the purposes of plant protection product regulation should be conducted using these alternatives.  This requirement is in addition to considerations under animal welfare legislation (Directive 2010/63/EU 1). 

The Regulation applies from 14 June 2011 and sets out  a number of requirements aimed at avoiding unnecessary testing on vertebrate animals, including the avoidance of duplicate testing, and for the sharing of tests and studies involving vertebrate animals.   In addition, The Regulation states in Article 62 (1) that:  

‘Testing on vertebrate animals for the purposes of this Regulation shall be undertaken only where no other methods are available’.

Currently validated in vitro alternatives are available that can replace in vivo skin and eye irritation studies.  For mixtures, the calculation method can be used to replace in vivo studies for acute toxicity, skin and eye irritation and skin sensitisation when a reliable classification can be determined by this method. 

In the UK, the Plant Protection Products Regulation 2011 (Statutory Instrument 2011 No. 2131) is the enforcing regulation for Regulation (EC) No 1107/2009, and provides under regulation 15(1) that:

1)  A person must not undertake tests on vertebrate animals in contravention of the first sentence of Article 62(1), or cause or permit another person to do so.

And under regulation 23 that:

A person who contravenes or fails to comply with –

Any paragraph of regulations 9 to 13, 15 to 19, or 22;…… is guilty of an offence

The fact that a test may also be carried out for the purposes of an application or authorisation in another Non-EU regulatory body/authority which may have less stringent rules regarding testing on vertebrate animals does not invalidate the provisions of Article 62.

HSE will contact applicants where there is a concern that a breach of Article 62 (1) of the Regulation has occurred. 

Biocides

Please note that this position applies only to pesticides.  When considering conducting vertebrate studies to support an application under Regulation (EU) No. 528/2012, please consult the HSE biocides website: Vertebrate testing in support of applications for active substance approval or product authorisation under the Biocidal Products Regulation (528/2012).

2. Current Accepted Alternatives

2.1 Calculation method

Before initiating any testing of plant protection products, consideration should be given to using calculation methods to determine the classification (under (EC) No. 1272/2008).  If a robust conclusion on classification can be reached using the information available on the components, this would remove the need for any testing (in vitro or in vivo), and associated expense.

2.2 In vitro studies

A. Skin irritation/corrosion studies

Guidance on an integrated approach on testing and assessment (IATA) for skin corrosion and irritation is available in OECD GD No. 203 (2014).

A validated in vitro test to determine skin irritation (OECD Test Guideline 439) has been available since July 2010.  A number of validated In vitro tests to determine skin corrosion have been available since 2004.  These tests are able to determine the classification of test substances to meet the requirements of Regulation (EC) No. 1272/2008 for skin irritation and corrosion.2 Therefore in vivo skin irritation/corrosion studies in the rabbit (OECD Test Guideline 404) should no longer be conducted.

B. Eye irritation/corrosion studies

Validated in vitro/ex vivo eye irritation/corrosion OECD Test Guidelines (OECD 437 and 438) have been available since September 2009 for the detection of Category 1 eye irritants, and were revised in July 2013 to take account of new data showing they could identify non-irritants too.  In addition any test substance that is classified as corrosive to the skin is automatically classified as a severe eye irritant and does not require further testing for eye irritation/corrosion. Therefore in vivo eye irritation/corrosion studies in the rabbit (OECD Test Guideline 405) should only be conducted as part of an integrated testing strategy. In all cases validated in vitro and ex vivo tests for eye irritation/corrosion should be conducted first, and may provide a definite classification for eye irritation/corrosion without the need for an in vivo test.  In the event that an in vivo test is considered necessary, agreement on the uncertainty should be sought from HSE before undertaking any study.

Details of any in vitro or ex vivo tests performed prior to an in vivo test should be provided either within the in vivo study report or as supporting documentation.

3. Dates of Application

The approach to in vivo testing/alternative methods is currently in operation within HSE, as the supporting legislation has been in place since the Regulation was adopted.

3.1 Skin irritation/corrosion 

Studies commissioned after 14 June 2011 can be completely replaced with in vitro methods.

3.2 Eye irritation/corrosion 

Studies commissioned after 14 June 2011 can be partially replaced with in vitro methods.

3.3 For mixtures 

The calculation method should be used to replace in vivo studies commissioned after 14 June 2011 where a reliable classification can be determined using this method.  This applies to acute oral toxicity, acute dermal toxicity, acute inhalation toxicity, skin irritation/corrosion, eye irritation/corrosion and skin sensitisation studies.

4. What this means for Applicants

HSE will contact applicants where there is a concern that a breach of Article 62 (1) of the Regulation has occurred.  This applies to vertebrate studies commissioned after 14 June 2011.

If any in vivo studies are submitted to HSE as part of an application for authorisation of a pesticide product or active substance, and the date of the study indicates it was commissioned after 14 June 2011 AND an acceptable alternative method (e.g. an adopted OECD Test Guideline for an in vitro alternative, or the calculation method) could reasonably have been used, then the application will be rejected.  HSE will also consider whether to conduct an investigation in relation to the potential breach of article 62(1) of the Regulation.

The applicant may resubmit the application using either the calculation method or acceptable in vitro studies. 

5. New OECD Test Guidelines

When new OECD Test Guidelines become available that can replace in vivo tests, any new studies submitted for the purposes of plant protection product authorisation should be conducted using these alternatives.  In vivo tests conducted before alternative Test Guidelines were adopted by the OECD may be submitted, subject to the requirements of Article 62 regarding data sharing, but no new vertebrate studies should be conducted for the purposes of fulfilling the requirements of the Regulation when there are alternative methods available.

6. Regulatory Framework

Article 62 (1) of the Regulation states that:

Testing on vertebrate animals for the purposes of this Regulation shall be undertaken only where no other methods are available’.

The Regulation states that dossiers submitted for the approval of active substances and authorisation of plant protection products should include ‘for each test or study involving vertebrate animals, a justification of the steps taken to avoid animal testing and duplication of tests and studies on vertebrate animals’ (Article 8(1)(d) and Article 33(3)(c) respectively).

Regulations (EU) No. 283/2013 and 284/2013 setting out data requirements for active substances and plant protection products respectively state that information shall be generated in accordance with Directive 2010/63/EU1 and that tests on vertebrate animals shall be undertaken only where no other validated methods are available. The interim data requirements under Regulations (EU) No. 544/2011 and 545/2011 also state that information shall have been generated in accordance with the requirements of Council Directive 86/609/EEC on the protection of animals used for experimental and other scientific purposes (Animal Welfare Directive).

7. Adverse data

Compliance with Article 62 (1) of the Regulation does not obviate the applicant’s obligation to submit adverse data.  Under Article 56 (1) of the Regulation an authorisation holder has an obligation to report all adverse data which may include in vivo studies which show adverse findings not identified in in vitro studies or from using the calculation method.  These in vivo studies would be accepted as adverse data but cannot be accepted for the purposes of obtaining an authorisation.

8. Links to Relevant Documents and Websites

OECD test guidelines on the OECD website

Regulation (EC) No.1107/2009

OECD GD No. 203 (2014) New Guidance on an integrated approach to testing and assessment for skin corrosion and irritation

Directive 2010/63/EU on the protection of animals used for scientific purposes

Directive 86/609/EEC regarding the protection of animals used for experimental and other scientific purposes

Regulation (EC) No. 1272/2008 on the classification, labelling and packaging of substances and mixtures

Legislation on plant protection products including the data requirements in Regulations (EC) No. 283/2013 and 284/2013

The Plant Protection Products Regulations 2011.  Statutory Instrument 2011 No. 2131

9. Footnotes

1. Directive 2010/63/EU on the protection of animals for scientific purposes which updates and replaces Directive 86/609/EEC. 

2. It is noted that there is currently no adopted OECD Test Guideline for an in vitro test that can detect UN GHS Category 3 Skin Irritants (mild irritants), however this category is not used in the EU under Regulation (EC) No.1272/2008 therefore it is not an adequate justification for performing an in vivo test for the purposes of the Regulation.

Updated 2017-02-09