Ethics of Research involving animals
The potential for Replacement of animals in different areas of research
Toxicity testing required by regulation as a special case
11.15 There is a tendency for discussion on the potential for replacing animals to focus solely on toxicity testing required by regulation and efficacy testing (which comprises around 16 percent of all animal use in science). Tests for regulatory purposes have received the most obvious and specific attention with respect to the development of Replacements.10 Two factors have been influential in this respect: first, over the past 30 years public concern about the types of substances tested, such as cosmetics, household products and chemicals, and the type of tests carried out has increased (for example, the LD50 and Draize tests; see paragraph 9.14 and Box 11.2)11. Secondly, the nature of these tests suggests that it is easier to make progress in this field, as toxicity testing required by regulation asks defined questions and tends to involve a limited number of standardised tests, which are repeated (on different chemicals) many times. There is also an established institutional structure for the validation of alternatives (see paragraph 11.32).
11.16 Most toxicity testing required by regulation is carried out by industry which has devoted considerable resources and managed effort to the development and implementation of Replacements. These developments have occurred partly in response to activities by animal protection organisations, and partly because many alternative approaches are developed as ‘advanced methods’ to solve specific problems (paragraph 8.42). Added impetus has recently been given by the amendment of the EU Cosmetics Directive12 to impose a marketing ban on cosmetics that have been tested or have had any of their ingredients newly tested on animals.
11.17 Standard test methods are also used in the safety and efficacy assessment of biologicals, including vaccines. The technical problems in replacing these tests are quite different from those encountered in the testing of chemicals. Further efforts are required to develop and validate methods that allow replacement of the use of animals, particularly in highly distressful challenge tests (see paragraph 8.24 and Box 8.5).13
Biomedical research
11.18 In contrast to tests for safety and efficacy, the development of Replacements to current uses of animals in biomedical research is generally perceived as more difficult. The scientific questions that are addressed in biomedical research are more diverse and open-ended, with less-predictable outcomes. Moreover, the animal model itself is often the focus of the research (see Chapters 6 and 7). The objectives and designs of biomedical research projects are extremely diverse. It may sometimes be possible to identify certain basic, widely used techniques that would be amenable to replacement of animals. The replacement of the ascites method of production of monoclonal antibodies is one such example (see paragraph 5.26). In general, however, opportunities for replacement or avoidance of animal use in every project need to be explored on a case by case basis, with due regard to the specific objectives and the scientific barriers to the use of non-animal methods.
Footnotes9 ‘Nude mice’ are mice born without any T lymphocytes, which means that they effectively have no immune responses.
10 The British Toxicology Society (BTS) produced a report on the use of in vitro methods for toxicity testing in 1997, see Fielder R,
Atterwill CK, Anderson D et al. (1997) British Toxicology Society (BTS) Working Party Report on in vitro toxicology Hum Exp
Toxicol 16: S1–40. The Third FRAME Toxicity Committee has also published a comprehensive discussion on the development of
replacement methods for toxicity testing over the last decade, see Combes R, Schechtman L, Stokes WS and Blakey D (2002)
The international symposium on regulatory testing and animal welfare: recommendations on best scientific practices for
subchronic/chronic toxicity and carcinogenicity testing ILAR J 43, Supplement: S112–17; see also Salem H and Katz SA (1999)
Toxicity Assessment Alternatives – Methods, issues, opportunities (Totowa, NJ: Humana Press); Castell JV and Gómez-Lechón MJ
(Editors) (1997) In vitro Methods in Pharmaceutical Research (London: Academic Press); Knight DJ and Breheny D (2002)
Alternatives to animal testing in the safety evaluation of products Alternat Lab Anim 30: 7–22; Combes RD (2002) The ECVAM
workshops: a critical assessment of their impact on the development, validation and acceptance of alternative methods ATLA
30, Supplement 2: 151–65.
11 See The Boyd Group (1998) The use of animals for testing cosmetics: A discussion paper from the Boyd Group, available at:
http://www.boyd-group.demon.co.uk/cosmetics.htm. Accessed on: 29 Apr 2005; The Boyd Group (2002) The use of animals in
testing household products: A discussion paper and statement of principle, available at http://www.boydgroup.
demon.co.uk/householdproducts.pdf. Accessed on: 29 Apr 2005.
12 European Commission (2003) Directive 2003/15/EC of the European Parliament and the Council Official Journal of the European
Union 11 March 2003.
13 See Hendriksen CFM, Spires J-M, Akkermans A et al. (1998) Validation of Alternative Methods for the Potency Testing of
Vaccines: ECVAM Workshop Report 31, ATLA 26: 747–61, and Weissler K and Hechler U (1997) Animal Welfare Aspects in the
Quality Control of Immunobiologicals: A critical evaluation of the animal tests in Pharmacopoeial Monographs (London:
FRAME).
14 European Commission (2004) Opinion of the Scientific Committee on Toxicity, Ecotoxicity and the Environment on The BUAVEuropean
Coalition to End Animal Experiments Report: The Way Forward – Action to End Animal Toxicity Testing, available at:
http://europa.eu.int/comm/health/ph_risk/committees/sct/documents/out217_en.pdf. Accessed: 26 Apr 2005.