The ethics of research involving animals - Nuffield Council on ...
The ethics of research involving animals - Nuffield Council on ...
The ethics of research involving animals - Nuffield Council on ...
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T h e e t h i c s o f r e s e a r c h i n v o l v i n g a n i m a l s<br />
ambiguities can act as potential sources <str<strong>on</strong>g>of</str<strong>on</strong>g> avoidable suffering for the <str<strong>on</strong>g>animals</str<strong>on</strong>g>.<br />
9.36 Other examples <str<strong>on</strong>g>of</str<strong>on</strong>g> toxicity endpoints that are likely to be painful and stressful include skin<br />
irritati<strong>on</strong> and corrosi<strong>on</strong> where single doses are applied to shaved areas <str<strong>on</strong>g>of</str<strong>on</strong>g> the backs <str<strong>on</strong>g>of</str<strong>on</strong>g><br />
rabbits. Exposure can extend over four hours, and the <str<strong>on</strong>g>animals</str<strong>on</strong>g> may experience ulcerati<strong>on</strong> <str<strong>on</strong>g>of</str<strong>on</strong>g><br />
the skin as well as swelling and itching. In sensitisati<strong>on</strong> testing, multiple dosing is practised,<br />
and in additi<strong>on</strong> to the above signs, the skin may crack and peel. Other signs that can be<br />
observed during acute, sub-acute and chr<strong>on</strong>ic toxicity testing include both external and<br />
internal bleeding, diarrhoea, loss <str<strong>on</strong>g>of</str<strong>on</strong>g> appetite, vomiting (in n<strong>on</strong>-rodents), aggressi<strong>on</strong>,<br />
salivati<strong>on</strong>, changes in blood pressure, coma, c<strong>on</strong>vulsi<strong>on</strong>s, lateral recumbency and tremors,<br />
loss <str<strong>on</strong>g>of</str<strong>on</strong>g> fur and hair, dehydrati<strong>on</strong>, or nasal discharge. Some <str<strong>on</strong>g>of</str<strong>on</strong>g> the less drastic effects <str<strong>on</strong>g>of</str<strong>on</strong>g><br />
toxicity can arise merely from the act <str<strong>on</strong>g>of</str<strong>on</strong>g> dosing.<br />
9.37 Very severe adverse effects can become manifest extremely rapidly as a result <str<strong>on</strong>g>of</str<strong>on</strong>g><br />
neurotoxicity following dosing. For example, during the mouse bioassay for diarrhoetic<br />
shellfish toxins, atypical results 21 can arise which cause rapid death, following signs <str<strong>on</strong>g>of</str<strong>on</strong>g><br />
substantial distress from shock and extensive trauma, accompanied by violent and rapid leg<br />
and body movements and ag<strong>on</strong>al breathing (abnormal and uncertain respirati<strong>on</strong> <str<strong>on</strong>g>of</str<strong>on</strong>g>ten<br />
characterised by gasping for breath), collapse and finally death from heart failure. 22<br />
General observati<strong>on</strong>s c<strong>on</strong>cerning the assessment <str<strong>on</strong>g>of</str<strong>on</strong>g> animal welfare in toxicity studies<br />
9.38 It is difficult to assess accurately either the individual or the collective burden <str<strong>on</strong>g>of</str<strong>on</strong>g> suffering<br />
that is sustained by <str<strong>on</strong>g>animals</str<strong>on</strong>g> used in toxicity testing. Many toxicity procedures do not usually<br />
result in more than some discomfort to most <str<strong>on</strong>g>of</str<strong>on</strong>g> the <str<strong>on</strong>g>animals</str<strong>on</strong>g> c<strong>on</strong>cerned, at least in the case<br />
<str<strong>on</strong>g>of</str<strong>on</strong>g> rodents. Moreover, <strong>on</strong>ly certain test groups <str<strong>on</strong>g>of</str<strong>on</strong>g> <str<strong>on</strong>g>animals</str<strong>on</strong>g> will be subjected to tests leading<br />
to overt signs <str<strong>on</strong>g>of</str<strong>on</strong>g> toxicity during an experiment. <str<strong>on</strong>g>The</str<strong>on</strong>g>se groups <str<strong>on</strong>g>of</str<strong>on</strong>g> <str<strong>on</strong>g>animals</str<strong>on</strong>g> comprise the<br />
c<strong>on</strong>current positive c<strong>on</strong>trols (<str<strong>on</strong>g>animals</str<strong>on</strong>g> treated with a chemical known to have adverse effects<br />
as a comparator <strong>on</strong> the sensitivity <str<strong>on</strong>g>of</str<strong>on</strong>g> the test substance) and those <str<strong>on</strong>g>animals</str<strong>on</strong>g> that receive high<br />
doses in dose-resp<strong>on</strong>se studies. However, in such cases it is likely that significant pain and<br />
distress could result, depending <strong>on</strong> the type <str<strong>on</strong>g>of</str<strong>on</strong>g> toxicity elicited. All <str<strong>on</strong>g>animals</str<strong>on</strong>g> used in toxicity<br />
testing are routinely killed immediately at the end <str<strong>on</strong>g>of</str<strong>on</strong>g> experiments for examinati<strong>on</strong> (see<br />
paragraphs 3.47–3.49).<br />
CHAPTER 9 ANIMAL USE IN TOXICITY STUDIES<br />
9.39 <str<strong>on</strong>g>The</str<strong>on</strong>g> fact that <str<strong>on</strong>g>animals</str<strong>on</strong>g> can suffer stress during toxicity testing has been investigated in studies<br />
in rats by assessing stress and discomfort from clinical and pathological observati<strong>on</strong>s. 23 A<br />
substantial proporti<strong>on</strong> <str<strong>on</strong>g>of</str<strong>on</strong>g> the <str<strong>on</strong>g>animals</str<strong>on</strong>g> suffered from serious discomfort, with some having<br />
obvious clinical signs, such as impaired locomoti<strong>on</strong> and anaemia. Most <str<strong>on</strong>g>of</str<strong>on</strong>g> these <str<strong>on</strong>g>animals</str<strong>on</strong>g> <strong>on</strong>ly<br />
displayed n<strong>on</strong>-specific clinical signs and the development <str<strong>on</strong>g>of</str<strong>on</strong>g> humane endpoints was<br />
c<strong>on</strong>founded. <str<strong>on</strong>g>The</str<strong>on</strong>g> difficulty <str<strong>on</strong>g>of</str<strong>on</strong>g> interpreting data where overt toxicity is induced can be<br />
exacerbated by the fact that dosing <str<strong>on</strong>g>of</str<strong>on</strong>g> very high levels <str<strong>on</strong>g>of</str<strong>on</strong>g> test material might be required,<br />
with accompanying adverse welfare c<strong>on</strong>sequences for <str<strong>on</strong>g>animals</str<strong>on</strong>g>, including death. Death as an<br />
endpoint in toxicity testing, particularly when caused by the above c<strong>on</strong>diti<strong>on</strong>s (the<br />
administrati<strong>on</strong> <str<strong>on</strong>g>of</str<strong>on</strong>g> ‘heroic’ doses), can be a misleading indicati<strong>on</strong> <str<strong>on</strong>g>of</str<strong>on</strong>g> hazard, since it might<br />
well not reflect any direct biological effects <str<strong>on</strong>g>of</str<strong>on</strong>g> the test material. Rather, death in such<br />
20 Combes RD, Gaunt I and Balls M (2004) A scientific and animal welfare assessment <str<strong>on</strong>g>of</str<strong>on</strong>g> the OECD health effects test guidelines<br />
for the safety testing <str<strong>on</strong>g>of</str<strong>on</strong>g> chemicals under the European Uni<strong>on</strong> REACH system. ATLA 32: 163-208.<br />
21 <str<strong>on</strong>g>The</str<strong>on</strong>g>se effects are ‘atypical’ in the sense that they arise very rapidly, usually within minutes <str<strong>on</strong>g>of</str<strong>on</strong>g> administrati<strong>on</strong> <str<strong>on</strong>g>of</str<strong>on</strong>g> the toxin (in<br />
most other cases effects more comm<strong>on</strong>ly occur within a timespan <str<strong>on</strong>g>of</str<strong>on</strong>g> several hours).<br />
22 Combes RD (2003) <str<strong>on</strong>g>The</str<strong>on</strong>g> mouse bioassay for diarrhetic shellfish pois<strong>on</strong>ing: a gross misuse <str<strong>on</strong>g>of</str<strong>on</strong>g> laboratory <str<strong>on</strong>g>animals</str<strong>on</strong>g> and <str<strong>on</strong>g>of</str<strong>on</strong>g><br />
scientific methodology Alternat Lab Anim 31: 595–610.<br />
23 Van Vlissingen JMF, Kuijpers MHM, van Oostrrum ECM et al. (1999) Retrospective evaluati<strong>on</strong> <str<strong>on</strong>g>of</str<strong>on</strong>g> clinical signs, pathology and<br />
related discomfort in chr<strong>on</strong>ic studies, in Humane Endpoints in Animal Experiments for Biomedical Research, Hendriksen CFM<br />
and Mort<strong>on</strong> DB (Editors), (L<strong>on</strong>d<strong>on</strong>: Royal Society <str<strong>on</strong>g>of</str<strong>on</strong>g> Medicine Press), pp89–94.<br />
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