168 • Alternatives to Animal Use in Research, Testing, and Education 
juries its product may cause after marketing (13). 
Similarly, if a new test becomes available, the man- 
ufacturer may be required to use it (14,29,47). 
Methods of Testing Required 
A manufacturer must normally use the safest 
and most effective testing method available. Thus, 
when monkeys provided the only reliable means 
for testing polio vaccine, they had to be used to 
test individual batches of drugs, despite the diffi- 
culty and expense of obtaining them (20). Although 
no cases could be found pertaining to drugs, this 
standard might not apply when testing is imprac- 
tical in relation to the risk of harm (30,48). 
Testing must reflect conditions of actual use as 
closely as possible. Thus, where the drug DES was 
to be used on pregnant women, the manufacturer 
should have tested pregnant animals and was held 
liable for cancer in offspring (3). Several smokers 
have tried to recover from cigarette manufactur- 
ers. They have been denied recovery to date be- 
cause when they started smoking, the risk of can- 
cer had not been demonstrated (28,40,43). 
A judge or jury would normally decide whether 
testing was adequate, but if there was a failure 
to comply with regulatory requirements, this would 
normally prove insufficient testing (16,33,39). How- 
ever, compliance with such requirements would 
not prove that testing was adequate (14). 
In addition to examining what tests were done, 
the judge or jury might look at the adequacy of 
the test protocols themselves. For example, the in- 
jured plaintiff might argue that the number of test 
animals was not large enough to determine if a 
risk was presented (11) or that the conditions un- 
der which the drug was tested did not represent 
actual use conditions (49,51). 
SUMMARY AND CONCLUSIONS 
The most widespread kind of testing with ani- 
mals is conducted for the elucidation of toxicity 
from drugs, chemicals, and so forth. Toxicology 
has advanced with the growth of the synthetic 
chemical industries and the use of chemicals in 
consumer products. Toxicological testing is used 
in the assessment of hazards and the management 
of health risks to humans. The use of animals for 
such testing did not become common until a few 
decades ago; it now accounts for several million 
animals per year. 
Many toxicological tests are standardized to aid 
in the comparison of results and because they have 
been shown to be acceptable tools for measuring 
certain phenomena. Most of the standard tests are 
descriptive in that they indicate an end result but 
do not necessarily elucidate the processes leading 
to it. Knowledge of the mechanisms by which a 
toxic effect occurs allows much greater reliabil- 
ity in extrapolation to humans. 
The design of a test involves many trade-offs. 
The choice of species is affected by its physiologi- 
cal similarity to humans, its cost and availability, 
and the amount of data for other substances avail- 
able for comparison. The route of exposure, dura- 
tion of exposure, and size of doses are affected 
by the possible nature and extent of exposure in 
humans, by the dose needed to produce a meas- 
urable toxic effect, and by convenience. Expected 
variability in the toxic response governs the num- 
bers of animals used. 
Commonly used tests include the following: 
• acute toxicity— -a single dose at high enough 
concentrations to produce toxic effects or 
death, often used to screen substances for rela- 
tive toxicity; 
• eye and skin irritation— usually a single ex- 
posure, generally used to develop warnings 
for handling and predict accidental exposure 
toxicity; 
• repeated-dose chronic toxicity— repeated 
exposure for periods ranging from 2 weeks 
to more than a year, used to determine the 
possible effects of long-term human exposure; 
• carcinogenicity— repeated exposure for 
most of lifespan, used to detect possible hu- 
man carcinogens; 
• developmental and reproductive toxicity— 
