Ch. 8— Alternative to Animal Use in Testing • 191 
factors. Another drawback is that human exposure 
can be great if there are long delays between ex- 
posure and observable effects. 
The LD 50 , probably the most common and most 
criticized toxicity test, is well suited to the limited 
use for which it was first developed. The biggest 
obstacle to limiting or eliminating use of the LD S0 
is institutional: Many regulatory schemes rely on 
it for classifying substances. The most promising 
alternatives in the short term are testing sequences 
that require fewer animals . Cell culture techniques 
and computer modeling show some promise, but 
they have limited value at this time. 
Another common and widely criticized test is 
the Draize eye irritation test. Several promising 
in vitro alternatives have been developed with cell 
cultures. Another technique uses the outer (chorio- 
allantoic) membrane of a 14-day -old chicken em- 
bryo. This technique, although it uses a whole ani- 
mal embryo, is thought to involve no pain because 
the membrane has no nerves. These alternatives 
may also apply to skin irritation. 
Alternatives to carcinogenicity testing and re- 
peated-dose toxicity testing are of special interest, 
in part because the potential savings in testing costs 
and time are quite large, and in part because these 
tests require large numbers of animals. The most 
promising replacements are batteries of tests in- 
volving cell cultures and living, nonanimal organ- 
isms. Mutagenicity testing uses many in vitro or 
nonanimal protocols. Mutagenicity is of particu- 
lar interest because mutation can be the first event 
in other kinds of toxicity, including carcinogenic- 
ity, and because it can permanently affect the hu- 
man gene pool. The most well known nonanimal 
mutagenicity assay is the Ames test. When it is com- 
bined with other tests, the Ames shows promise 
as an alternative to carcinogenicity testing, but it 
is not yet validated for this use. 
In general, the development of alternatives is 
being facilitated by the rapid development of bio- 
logical techniques, which are being applied to the 
search for alternatives in many different labora- 
tories. Major contributions to the coordination of 
these developments in the United States are being 
made by Rockefeller University and The Johns 
Hopkins Center for Alternatives to Animal Testing. 
The implementation of alternatives is hindered 
by various forms of institutional inertia, such as 
regulatory schemes (see ch. 7), product liability 
law (see ch. 7), and general resistance to change. 
Important impediments are the large body of ex- 
isting information— derived from animals— that is 
relied on for the interpretation of new data and 
the lack of sufficient information to support the 
use of alternatives. 
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