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Environment
and Disease
Laboratory Animal
Studies
 Use of laboratory animal studies as a
method to identify carcinogens is only 50 or 60 years old. These
studies have been much improved in the last few years and attempts
to examine their reliability and predictability have increased
over the last 5 or 10 years. During this time scientists have
refined the methodology of laboratory animal studies. Today
these studies are better constructed, performed, and evaluated
than they were 10 years ago. A good animal study is a very complex
study. It is not the simple observation of a dozen rats in a
shoebox.
 The critical question to ask about a laboratory
animal study is its predictability. Do results of laboratory
animal studies predict for those effects in a human population?
The International Agency for Research on Cancer, a part of the
World Health Organization, assembles expert groups of independent
scientists to determine if there is adequate evidence to indicate
a chemical is carcinogenic. This agency has published a list
of about 20 chemicals that are carcinogenic in man. Nearly all
of the chemicals on this list also are carcinogenic in laboratory
animals. Two exceptions are arsenic compounds and benzene. However,
there is new evidence that strongly suggests that benzene causes
leukemia in rats and mice in the same way it causes leukemia
in man. In addition, arsenic may well be a cocarcinogen, at
least qualitatively. This list strongly suggests that chemicals
that are carcinogenic in man will have been found to be carcinogenic
in animals.
Another important
issue focuses on the amount of a chemical needed to cause cancer.
Are the amounts or doses of chemicals that cause cancer in man
the same as those that cause cancer in the laboratory animals?
Several years ago,
a study committee of the National Academy of Sciences' National
Research Council carefully reviewed this problem. The committee
compared the available evidence for amounts of chemicals needed
to cause human cancer with laboratory data about cancer in the
animal species most sensitive to a particular chemical. Three out of the six situations studied
showed a direct relationship between the amount of chemical
exposure and cancer in animals and man. For both the dye benzidine
and chlornaphazine, a drug no longer in use, the amount of the
chemical causing cancer in occupationally exposed people was
the same as the amount that caused cancer in laboratory animals.
 Although it is very difficult to encourage
a mouse to smoke cigarettes and apparently not at all difficult
to persuade people to smoke, there seems to be a very close
relationship between the number of cigarettes smoked and the
production of cancer in both people and animals.
In three other test
situations, the relationship was not as direct. The most sensitive
laboratory species was ten times more susceptible than man to
cancer caused by a fungal toxin (aflatoxin) of peanuts, corn,
and other vegetables. Although animals appear to be more sensitive
to diethylstilbestrol (DES), the human population is still at
risk for this chemical. In fact, if in the future more diethylstilbestrol-caused
cancer is observed in people, carcinogenicity in animals and
man will be closely related. It is possible that the carcinogenicity
of diethylstilbestrol could have been predicted.  After the chemical was observed to be carcinogenic in young women whose
mothers took DES, animal studies clearly showed that DES produced
exactly the same cancer in the offspring of mice.  The same may be true for vinyl chloride. Again, the animals seem to
be more sensitive, but the worker population exposed to vinyl
chloride is still very much at risk.
These examples show
that animal studies predict carcinogenicity and that the predication
of disease is fairly accurate. Animal studies are not perfect
but they do have merit. l believe that with increasing frequency
we will encounter situations like DES in which animal studies
could have predicted carcinogenicity in man. Vinyl chloride
was discovered to cause cancer in animal studies before like
effects were observed in factory workers in Louisville. Aflatoxins
were observed to cause cancer first in trout, then in laboratory
animals, and finally in human populations by use of epidemiological
studies in Africa. Another example is bischloromethyl ether,
a chemical by-product of an open pot manufacturing process.
 Although an epidemic of lung cancer had been
noticed in a small factory, laboratory animal tests pinpointing
the single chemical bischloromethyl ether  as the cause of lung cancer were required
in order to close the manufacturing process and prevent further
worker exposure to the dangerous chemical. As a result of this
decreased exposure, the incidence of lung cancer decreased.
On to Criticism of Animal Tests
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