TOXICOLOGY AND THE LAW
4.34 Many toxicological tests are required by
In the UK, the Medicines Control Agency demands proof of safety
before it will license a new drug. Similarly, the Health and Safety
Executive demands the toxicological assessment of industrial chemicals
and various other products, which requires information "some
of which can only be obtained from animal testing".
4.35 Regulations on toxicity testing for new
compounds have now largely been harmonised internationally. This
is clearly beneficial in terms of animal use. For example, instead
of three very similar sets of tests being carried out for a new
drug to be licensed in the European Union, the United States and
Japan, only one set of tests needs to be carried out which is
accepted by the regulatory authorities in all three jurisdictions.
4.36 For new drugs and medicines, the harmonisation
body is the ICH the International Conference on Harmonisation.
There are four members regulators from the US, from Japan,
and from the European Union, and representatives from the global
pharmaceutical industry. Better harmonisation has already led
to a reduction in animal use (Q. 892), and the ICH plays "an
important quasi-legal role in drug development".
4.37 For new chemical compounds, the harmonisation
body is the OECD the Organisation for Economic Co-operation
and Development. There are 39 member states. Adoption of non-animal
toxicological tests is slow, as the OECD requires consensus from
all member states before new test guidelines are adopted.
4.38 It is important for regulatory authorities
to keep abreast of technological developments, and to be aware
of new non-animal testing methods which these may allow. We recognise
that decisions on whether individual animal tests can be replaced
or refined cannot be taken unilaterally by the UK Government,
but there appears to be no reason why the UK Government should
not take the initiative for moving the agenda forward.
4.39 One area where the Government could take
the initiative is in welfare standards in toxicological testing.
Currently, rats involved in many toxicological experiments are
kept in wire-bottomed cages. These are easier to clean than solid-bottomed
cages, and the lack of nesting material means that no extraneous
substances can interfere with the test. Such cages potentially
have a welfare cost, as rats not only have no nesting material,
but the wire floor can cause prolonged physical discomfort. It
is possible that these wire-bottomed cages seriously compromise
the welfare of hundreds of thousands of animals each year. We
learnt from the Organisation for Economic Co-operation and Development
that no government had yet even asked the OECD to consider including
in OECD Test Guidelines the recommendation to use solid-bottomed
cages, nesting materials, and other relatively uncontroversial
4.40 We recommend that the Government should
take greater steps to promote the adoption of replacements and
the incorporation of refinements into animal test guidelines issued
by the International Conference on Harmonisation and the Organisation
for Economic Cooperation and Development.
4.41 A number of witnesses have highlighted the
importance of the need for co-ordinated international action has
been highlighted by the recent European Commission White Paper,
Strategy for a future Chemicals Policy.
This proposes carrying out toxicity tests on thousands of chemicals
which have been in use for some time. The Institute for Environment
and Health, in a report prepared for the DTI in April 2001, estimated
that at least 12 million vertebrates would be required for the
4.42 The White Paper on Chemicals has already
been the subject of an Inquiry by the House of Lords European
Union Select Committee.
We note and endorse their conclusion relating to animal testing
that "the very success of any chemicals strategy depends
on the public being reassured that a serious effort is being made
to develop alternatives to animal testing" (para. 191).
4.43 We also consider that there is very little
political will to reduce the need for animals in toxicology. At
the European level, the funding for ECVAM is under constant pressure.
In the United Kingdom, our questioning of different Government
departments has revealed that no department is prepared to take
responsibility for the issue of animals in science in general,
and for the need for animals in toxicology in particular. We therefore
note and endorse the further observation of the House of Lords
European Union Select Committee that "there is a lack of
resources and of political will in the EU to bring non-animal
tests into use" (para. 197).
4.44 The Government and the scientific community
should engage in a systematic and visible search for methods involving
the Three Rs in toxicology. The Government should nominate one
department to take the lead on this.
4.45 The UK Government should use their influence
to urge the EU to make the development and validation of replacements
for animal experiments a priority, particularly in toxicology.
POTENTIAL OF DEVELOPING TECHNOLOGIES
4.46 There is considerable potential for companies
specialising in the Three Rs. We have taken evidence from Dr Robert
Coleman, the Director of Pharmagene in the UK, and have met Dr
Paul Silber, the Director of In Vitro Technologies in the US.
Both companies illustrate the commercial potential for non-animal
technologies, particularly in screening compounds in the relatively
early stages of drug development.
4.47 Dr Coleman said that there were problems
with the availability of human tissue for use in in vitro studies.
It is important that the events at Bristol Royal Infirmary and
Alder Hey do not provoke a reaction which prevents the provision
of human tissues to appropriate companies.
4.48 We also note that recent developments in
computer modelling in the UK have potential for use in toxicology.
The Food and Drug Administration in the United States is in discussions
about how a particular computer model can be incorporated into
Such replacement technologies are likely to be increasingly important
in the future. In parts of Europe, there is a move away from animal-based
research, particularly in toxicology. The UK should act now to
be in the forefront of new developments.
4.49 The promotion of the commercial advantages
of the Three Rs needs a clear lead from a nominated department
67 The point that animals are different from humans
and that the results of the research on animals are therefore
not applicable to humans is made by almost every opponent of vivisection,
including the BUAV, the NAVS, PETA, Professor Vernon Coleman,
Doctors and Lawyers for Responsible Medicine and many members
of the public who submitted written evidence. Back
Professor Vernon Coleman (Q. 1276) and Doctors and Lawyers for
Responsible Medicine (Qs 1721-24). See also paragraph 4.17. Back
BUAV (p. 89). The MRC disagree (p. 221), as do the Parkinson's
Disease Society of the UK (p. 251). Back
FRAME and Dr Hadwen Trust (Q. 462). Professor Rothwell said that
a treatment for stroke had been developed (Q. 651), but this statement
was criticised by Dr Pandora Pound (p. 317). Back
The BUAV cite the development of sucralose (p. 98). Back
BUAV (p. 81). Back
PETA (p. 255). Back
DoH (p. 163). Back
See in particular Dr Michael Festing, 'The Use of Animals as Models
of Humans in Biomedical Research', (p. 140). Back
Mr Smith, Royal Veterinary College (Q. 1752). Back
Goodman, S. & Check, E. 'The great primate debate', Nature,
vol. 417 (2002), 684-87; see also the Society for the Study of
Fertility (p. 321). Back
New Scientist, 8th June 2002, p. 53. Back
Dr Langley from the Dr Hadwen Trust acknowledged that this is
a "problem area", but pointed out that the rabies vaccine,
for example, became purer and safer once it was tested in vitro
(Q. 418). Back
See Types of animal experiments in Chapter 3. Back
United States Public Health Service, quoted by the Royal Society
(p. 286). The Royal Society also gives specific examples of the
"Contribution of Animal Research to Medical Advances"
(pp. 286-93). This paper was also submitted by Professor Colin
For example, the use of animal models for stroke and the use of
genetically modified mice as models for cystic fibrosis (see Qs
462 and 463); and research into xenotransplantation, BUAV (p.
The figures are - 1987: 3,631,400 procedures; 2000: 2,714,700
(Statistics, table 20). Back
Dr James Anderson, introductory session, House of Lords conference
(Appendix 4). Back
Statistics, p. 19. Back
MOD (p. 126). Back
See footnote 19. Back
Dr Michael Festing, giving evidence with the Royal Society (Q.
This point was made to us by Dr Langley from the Dr Hadwen Trust
(Q. 477) and Professor Balls from ECVAM (Q. 1466), although
other witnesses, such as Professor Goldberg from Johns Hopkins
University (Q. 1518) and the Royal Society (Q. 1051), disagreed
with this view. Back
See the report of the Working Group on Toxicology (House of Lords
conference, 21st May 2002), printed as part of Annex 4 to this
For a discussion of this process, see Christopher Atterwill and
Mark Wing, 'In Vitro Preclinical Lead Optimisation Technologies
(PLOTs) in Pharmaceutical Development', Alternatives to Laboratory
Animals, 28 (2000), 857-67. Back
A teratogen is any substance or factor which can cause malformation
of the embryo or foetus. Back
BUAV (p. 104). Back
Report by the Audit Commission, A spoonful of sugar: medicines
management in NHS hospitals (2001), cited by the BUAV (p. 104).
See also paragraph 4.4. Back
Professor Vernon Coleman (Q. 1235). This question is answered,
at least in part, in the memorandum by the Parliamentary Under-Secretary
of State, Lord Hunt of Kings Heath, printed with his oral evidence. Back
Dr Gill Langley, "Animal and non-animal tests-an uneven playing
field for validation", BUAV (p. 100). Back
Dr Smith (Q. 1003). Back
At present, once they are removed from the body, liver cells last
for no more than a few hours, which limits their usefulness for
in vitro studies. Back
Department of Health, "Assessment of Reproductive Toxicity"
(p. 173). Back
See Professor Iain Purchase, "Prospects for Reduction and
Replacement Alternatives in Regulatory Toxicology", Toxicology
in Vitro, 11 (1997), 313-19; for developments in in vitro
tissue culture methodology see FRAME (p. 149). Back
See memorandum by Professor Denis Noble (p. 250). Back
Professor Balls (Q. 1465). Back
Paragraph 9 of "The value of animal toxicity results for
predicting human health effects", Professor Iain Purchase
(printed with his oral evidence). Back
Dr Robert Coleman (Q. 1574). Back
Olson, H. et al., 'Concordance of the Toxicity of Pharmaceuticals
in Humans and Animals', Regulatory Toxicology and Pharmacology
32 (2000), 56-67. This paper is mentioned by the Department of
Health (p. 174). The DoH also submitted this paper, and nearly
50 other scientific papers, in support of their written evidence. Back
DoH (p. 171). Back
Paragraph 11 of "The value of animal toxicity results for
predicting human health effects", Professor Iain Purchase. Back
Dr Gill Langley, "The efficacy of animal tests in toxicology",
BUAV (p. 99). Back
Worth, A. P. & Balls, M., eds. (2002). Alternative (non-animal)
methods for chemicals testing: current status and future prospects.
A report prepared by ECVAM and the ECVAM Working Group on Chemicals.
ATLA 30, Supplement 1, 1-125. Back
This point was also made by Professor Purchase (Q. 646). Back
This meeting took place during our visit to Paris (see Appendix
See Report of the conference of 21st May, 2002 (Appendix 4), and
Professor Balls (Q. 1457). Back
84% of UK toxicological tests were required by law or regulation
in 2000 (Statistics, p. 19). Back
Health & Safety Executive (p. 162). Back
DoH (p. 164). Back
See note of the meeting with Herman Koeter from the OECD in Appendix
3, and also Lord Sainsbury (Q. 1696). Back
Presented by the Commission in February 2001 (COM(2001)88 final).
See also para. 4.18. Back
Testing Requirements for Proposals under the EC White Paper, "Strategy
for a future Chemicals Policy", MRC Institute for Environment
and Health, University of Leicester, 2001. Back
13th Report, Session 2001-02, "Reducing the Risk: Regulating
Industrial Chemicals" (HL Paper 81). Back
Professor Balls (Q. 1442). Back
See memorandum by Dr Robert Coleman (printed with his oral evidence). Back
Professor Denis Noble (p. 250). Back