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1 Animal use intoxicity studiesChapter 9155 The ethics of research involving animalsCHAPTER 9 ANIMAL USE IN toxicity STUDIESA nimal use in toxicity In this Chapter we describe the purpose and principal methods of toxicity studies. Most ofthese studies are conducted to assess the degree to which substances are toxic (poisonous)for humans, animals or the environment, to investigate the mechanism of toxic chemicals, orto develop new or improved tests for specific types of chemically induced effects. We beginby explaining the scientific rationale behind important types of studies. These include:examination of adverse effects that may occur on first exposure to a single dose of asubstance (acute toxicity studies), studies that seek to assess the potential of substances tointeract with genetic material (genotoxicity), tests that aim to identify whether toxicityoccurs after continuous exposure to a substance (repeated-dose toxicity studies), tests thatare undertaken to find out whether cancers may develop as a result of exposure to certainchemicals, and studies to ensure the safety of medicines.

2 In the second part of the Chapter we discuss a range of welfare implications that may arisefor animals involved in toxicity testing. We consider first effects that may result from thedosing and sampling methods that are commonly used, and then effects related directly tothe toxicity of the chemical that has been administered. toxicity studies are highly variable indesign, and where they involve the use ofanimals the implications for animal welfaremust be considered on a case by case concentrate here on the morestandardised animal methods that arewidely used to characterise the adverseeffects of chemicals on human and animalhealth, and on the environment.

3 Many ofthe tests described are also used in thetesting of medicines. For the most part wedo not differentiate in the descriptionbetween these different current The vast majority of toxicity testing is carried out in the context of regulatory requirementsgoverning particular types of chemical in different parts of the world (see ). Regulatory bodies often emphasise the necessity of toxicity tests to preservecurrent levels of human health and environmental of all newchemicals placed on the EU market for the first time must be given to the competentauthorities of the Member EU is currently considering a proposal for aRegulation concerning the Registration, Evaluation, Authorisation and Restriction ofChemicals (REACH) which would require large numbers of existing chemicals to be evaluatedfor safety.

4 Reach would be binding for all Member States (Box ). Separate EuropeanDirectives specify requirements for animal testing in the authorisation or licensing of plant-protection products, biocides and pharmaceuticals (see paragraphs ). In other1 European Commission (2004) Opinion of the Scientific Committee on toxicity , Ecotoxicity and the Environment on The BUAV-European Coalition to End Animal Experiments Report: The Way Forward - Action to End Animal toxicity Testing, available at: Accessed: 26 Apr information that must be supplied by a manufacturer is laid down in the Dangerous Substances Directive (67/548/EEC),implemented in the UK by the Notification of New Substances Regulations.

5 toxicity studies number ofanimals used Procedures for toxicological purposes accounted for16 percent of all animal procedures undertaken in2003 in Great Britain. Approximately ten percent of allanimal procedures were carried out forpharmacological safety and efficacy 13 percent of all animal procedures weretoxicological tests conducted to conform to legislativeor regulatory : Home Office (2004) Statistics of ScientificProcedures on Living Animals Great Britain 2003(London: HMSO).156 The ethics of research involving animalscases, for example for cosmetics and cosmetic ingredients, testing requirements are notspecified in regulations but there is a general requirement for safety, which could be met bythe use of animal or non-animal tests.

6 National authorities in the EU issue guidance on howthe provisions laid out in the Directives should be met, which, due to preferences ofregulators, usually means that data from established animal tests must be provided. So as tomaximise returns, many chemicals are marketed worldwide, and testing must then conformto the requirements of other regulatory bodies, particularly those of the USA and Current testing regimes have evolved significantly over the past three decades. Existingpractices have changed and new methods have been added. A major influence on thesedevelopments has been the Test Guidelines Programme of the Organisation for EconomicCooperation and Development (OECD), which has developed standardised methods oftesting that are accepted in principle by all 30 OECD Member Countries3through anagreement on the mutual acceptance of OECD approach has largely removed theneed for testing according to different protocols to satisfy regulatory authorities in differentcountries, and has thus substantially reduced the total number of animals used for certainstandard tests.

7 It also provides a focus for the introduction of new methods that replace,reduce or refine animal use. Change and revision have been slow but there are many currentinitiatives, within both the scientific and regulatory communities, that challenge presentpractice with the aim of providing the same or even better levels of human safety whileusing fewer animals (see Box and paragraph ). The International Conference onHarmonisation of Technical Requirements for Registration of Pharmaceuticals for HumanUse (ICH) also seeks to standardise the approach to testing of pharmaceuticals (seeparagraphs , and ).

8 Box : The EU REACH Initiative: Registration,Evaluation and Authorisation of ChemicalsRegistration, Evaluation and Authorisation of Chemicals(REACH) refers to the new EU regulatory framework forchemicals proposed by the EC in October 2003. At thetime of writing, the proposal is being considered by theEuropean Parliament and the Council of the EU. Thelegislation is intended to bring 30,000 chemicalsmanufactured within or imported into the EU under asingle regulatory regime. REACH aims to makemanufacturers responsible for the chemicals that theyproduce and to make it easier for highly toxic chemicalsto be removed from the market.

9 Under the new system,businesses that manufacture or import more than onetonne of a chemical substance each year would berequired to register it in a central database.* The European Commission has stated that newlegislation is necessary due to the inadequacy of thecurrent legislative framework for chemicals. A particularproblem concerns the arbitrary cut-off date in 1981,which provides the distinction between new and existing chemicals. At present, new chemicals thathave been placed on the market after 1981 must betested if their production exceeds 10 kg per year,whereas there are no such provisions for existing chemicals.

10 Therefore, it is argued, the currentlegislation encourages the continued use of untestedexisting chemicals because it is easier and cheaper. REACH has proved controversial, not least because itsrequirements will result in a substantial increase in thenumber of animal experiments. Many chemicals havebeen in use for decades and there is concern that sometests may duplicate those already performed by privatecompanies. The UK Government is advocating a policyof one substance-one Registration , as a means ofminimising animal testing and reducing costs andbureaucracy. This means that companies would berequired by law to share data on tested substances, inthe hope that universally available data will avoidduplicate testing of that substance.