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 ...
Create successful ePaper yourself
Turn your PDF publications into a flip-book with our unique Google optimized e-Paper software.
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 />
9.5 Toxicity has two main comp<strong>on</strong>ents: the effect caused and the level <str<strong>on</strong>g>of</str<strong>on</strong>g> exposure (dose) at<br />
which the effect is observed. Some tests are designed specifically to detect a particular effect<br />
(such as skin and eye irritancy, skin sensitisati<strong>on</strong> and mutagenicity studies). Other tests (such<br />
as sub-chr<strong>on</strong>ic and chr<strong>on</strong>ic studies) are designed to detect a wider range <str<strong>on</strong>g>of</str<strong>on</strong>g> less-specific<br />
effects <strong>on</strong> organs or body systems and the dose range over which the effect develops.<br />
9.6 Informati<strong>on</strong> from toxicity tests is first used to provide a classificati<strong>on</strong> for a chemical, for<br />
example to assign appropriate warning labels for c<strong>on</strong>tainers, and, where necessary, for<br />
selecting measures, such as protective equipment, during manufacture, exposure and use.<br />
Data from tests that characterise the relati<strong>on</strong>ship between dose and toxicological resp<strong>on</strong>se<br />
are integrated with informati<strong>on</strong> <strong>on</strong> human exposure to produce a risk assessment, and to<br />
identify c<strong>on</strong>trol measures necessary to manage and reduce any identified risk. Tests <strong>on</strong><br />
species such as fish and amphibians are used in a similar way to assess the potential<br />
envir<strong>on</strong>mental effects <str<strong>on</strong>g>of</str<strong>on</strong>g> chemicals. For pharmaceuticals, results from animal tests are used<br />
in combinati<strong>on</strong> with data <strong>on</strong> the efficacy <str<strong>on</strong>g>of</str<strong>on</strong>g> a potential medicine to decide whether the<br />
beneficial effects <str<strong>on</strong>g>of</str<strong>on</strong>g> the treatment would outweigh the risks <str<strong>on</strong>g>of</str<strong>on</strong>g> adverse side effects, and to<br />
establish a safe dose for use in clinical trials (see paragraphs 8.26–8.28). <str<strong>on</strong>g>The</str<strong>on</strong>g>y may also<br />
indicate potential side effects that must be m<strong>on</strong>itored carefully.<br />
9.7 <str<strong>on</strong>g>The</str<strong>on</strong>g> predicti<strong>on</strong> <str<strong>on</strong>g>of</str<strong>on</strong>g> the likely effects <str<strong>on</strong>g>of</str<strong>on</strong>g> chemical exposure <strong>on</strong> human health is based primarily<br />
<strong>on</strong> the results <str<strong>on</strong>g>of</str<strong>on</strong>g> tests <str<strong>on</strong>g>involving</str<strong>on</strong>g> experimental <str<strong>on</strong>g>animals</str<strong>on</strong>g>. <str<strong>on</strong>g>The</str<strong>on</strong>g> number <str<strong>on</strong>g>of</str<strong>on</strong>g> <str<strong>on</strong>g>animals</str<strong>on</strong>g> involved in<br />
these tests varies. A full complement <str<strong>on</strong>g>of</str<strong>on</strong>g> toxicity tests for a successful pharmaceutical<br />
compound that proceeds to the market, <str<strong>on</strong>g>involving</str<strong>on</strong>g> single dosing, repeat sub-chr<strong>on</strong>ic and<br />
chr<strong>on</strong>ic dosing, reproductive testing, genotoxicity and carcinogenicity testing, can involve<br />
between 1,500 and 3,000 <str<strong>on</strong>g>animals</str<strong>on</strong>g>. <str<strong>on</strong>g>The</str<strong>on</strong>g> actual numbers required will depend <strong>on</strong> the need for<br />
further tests according to the nature <str<strong>on</strong>g>of</str<strong>on</strong>g> the test substance and also its toxic properties. <str<strong>on</strong>g>The</str<strong>on</strong>g><br />
numbers <str<strong>on</strong>g>of</str<strong>on</strong>g> <str<strong>on</strong>g>animals</str<strong>on</strong>g> used to test other types <str<strong>on</strong>g>of</str<strong>on</strong>g> chemical are generally lower, but in some<br />
cases, where there is particular c<strong>on</strong>troversy about the safety <str<strong>on</strong>g>of</str<strong>on</strong>g> a chemical, tests may be<br />
repeated, with modificati<strong>on</strong>s, resulting in the use <str<strong>on</strong>g>of</str<strong>on</strong>g> even more <str<strong>on</strong>g>animals</str<strong>on</strong>g>.<br />
CHAPTER 9 ANIMAL USE IN TOXICITY STUDIES<br />
9.8 Large numbers <str<strong>on</strong>g>of</str<strong>on</strong>g> <str<strong>on</strong>g>animals</str<strong>on</strong>g> are also used in several other tests. For example, a carcinogenicity<br />
bioassay generally involves 800 <str<strong>on</strong>g>animals</str<strong>on</strong>g> in total (400 <str<strong>on</strong>g>of</str<strong>on</strong>g> each sex) and may be c<strong>on</strong>ducted <strong>on</strong><br />
both rats and mice. Adult <str<strong>on</strong>g>animals</str<strong>on</strong>g> (typically at least 80 <str<strong>on</strong>g>animals</str<strong>on</strong>g> <str<strong>on</strong>g>of</str<strong>on</strong>g> each sex per study),<br />
<str<strong>on</strong>g>of</str<strong>on</strong>g>fspring and fetuses are used in reproductive and development studies. Rats and mice are<br />
most comm<strong>on</strong>ly used (74 percent), but in some cases testing is carried out <strong>on</strong> other <str<strong>on</strong>g>animals</str<strong>on</strong>g><br />
such as rabbits (four percent), guinea pigs (three percent), dogs (<strong>on</strong>e percent) or primates<br />
(less than <strong>on</strong>e percent). 5 <str<strong>on</strong>g>The</str<strong>on</strong>g> interpretati<strong>on</strong> <str<strong>on</strong>g>of</str<strong>on</strong>g> the results for assessing human safety<br />
depends <strong>on</strong> a number <str<strong>on</strong>g>of</str<strong>on</strong>g> assumpti<strong>on</strong>s. First, unless there is specific knowledge <str<strong>on</strong>g>of</str<strong>on</strong>g> species<br />
differences in the test resp<strong>on</strong>se, it is assumed that the effects detected in rodents or other<br />
species are the same as those that would be induced in humans. Sec<strong>on</strong>dly, it is assumed that<br />
the sensitivity <str<strong>on</strong>g>of</str<strong>on</strong>g> the test <str<strong>on</strong>g>animals</str<strong>on</strong>g> represents, at best, the average sensitivity <str<strong>on</strong>g>of</str<strong>on</strong>g> the highly<br />
heterogeneous human populati<strong>on</strong> and that for some members <str<strong>on</strong>g>of</str<strong>on</strong>g> the human populati<strong>on</strong><br />
the health risk could be much higher (see paragraph 8.39, Box 9.3 and paragraph 10.33).<br />
We c<strong>on</strong>sider next a range <str<strong>on</strong>g>of</str<strong>on</strong>g> examples to illustrate the different kinds <str<strong>on</strong>g>of</str<strong>on</strong>g> toxicity tests which<br />
are currently used.<br />
5 Figures refer to percentages <str<strong>on</strong>g>of</str<strong>on</strong>g> procedures started in 2003 and carried out for the purpose <str<strong>on</strong>g>of</str<strong>on</strong>g> toxicology or safety and efficacy<br />
evaluati<strong>on</strong>. See Home Office (2004) Statistics <str<strong>on</strong>g>of</str<strong>on</strong>g> Scientific Procedures <strong>on</strong> Living Animals Great Britain 2003 (Norwich: HMSO).<br />
157