Difficulties are compounded because species are usually chosen not on anticipated similarity to people but on non-scientific grounds such as cost.(12) The most commonly used animals in research are rodents which make up some 85% of the total.(13) One of the most important characteristics is size which largely determines both the cost of the animals and the space needed during the experimental period. Another key factor which can influence costs is the animals' productivity in terms of the number of babies they can produce. Rats and mice can produce far more offspring than cats, dogs and primates.
Species variation in toxicity tests can often be traced to differences in the way people and animals metabolize, or break down drugs in the body. In this respect rats and mice are known to be among the most unsuitable models for humans yet they still feature prominently in test procedures. A comparative study of 23 chemicals showed that in only four cases did rats and humans metabolize products along the same biochemical pathway.(14) So great are the differences that American pharmacologist Bernard Brodie argues that55 "it is often a matter of pure luck that animal experiments lead to clinically useful drugs."
Small rodents are the main species used in acute toxicity tests such as the LD50, so it is fortunate that few take the results seriously. According to their LD50s in rats, aspirin should be safer in overdose than another, similar painkiller, ibuprofen. Yet clinical experience does not tally with this and suggests that ibuprofen is the safer drug.15 On the basis of its LD50 in rats, the heart drug digitoxin would seem around 100 times safer than it actually is in human subjects.16 As Dr. G. N. Volans, Director of Britain's National Poisons Center at New Cross Hospital in London, has pointed out, acute toxicity data from animal tests contribute "very little of value" to the prevention and management of drug overdose.(15)
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