By JANNY SCOTT
Lee Angele Tnewi
A growing body of evidence is raising
doubts among some scientists about the
ability of animal experiments to predict
whether certain chemicals such as drugs,
food additives and pesticides will cause
cancer in humans.
The controversy centers on a critical
test used by regulatory agencies in deciding
whether chemicals are carcinogenic. Critics
say there is increasing evidence that the
test is overpriced, inefficient and unrelia-
The test in which rodents are ex-
posed to high doses of chemicals, then
dissected and examined for tumors has
helped identify hundreds of suspected car-
cinogens. As a result, many substances
have been banned from use or permitted
only under strict controls.
But critics say there is reason to doubt
that some of those chemicals actually cause
"This is a controversial
area because it
involves not just
Raymond W. Tennant,
cancer in people, even if they do cause
tumors in rodents. Some say the tests,
which can cost $1-million per.chemical and
take years to complete, may be misleading
in a third of all cases.
Those critics want broader use of alter-
native tests that simply examine the effects
of chemicals on individual cells in the labo-
ratory. Those, too, are fallible. But propo-
nents say they would make it possible to
screen more chemicals, and at a lower cost.
"Everybody was hoping that there
would be some way of testing that you could
say, 'positive' or 'negative' and that's it,"
said Dr. Gary Williams of the American
Health Foundation in New York. "Well,
nature just isn't that simple."
The debate comes at a time when the
Environmental Protection Agency (EPA) is
updating its guidelines for the assessment
of environmental health hazards in light of
The testing isue affects products used
in daily life, such as artificial sweeteners,
pharmaceuticals and pesticides. Carcinoge-
nicity testing also has significant financial
Please see CANCER 5-A
implications for individual firms
and society at large.
"This is a controversial area
because it involves not just science
but economics," said Raymond W.
Tennant, a federal carcinogenicity
researcher. "There are gaps in
scientific knowledge; and when
you have those sorts of gaps,
they're often filled by opinions."
t At least 50,000 chemicals are
how manufactured or processed in
the United States. Some *1,000
hew ones are produced in commer-
tial quantities each year. In addi-
tion, there are 600 active ingredi-
ents registered as pesticides with
the federal government, and thou-
sands of drugs.
i Many countries now regulate
chemical production and use,
largely in response to concern over
the health effects of toxic expo-
sures. In the United States, most
drugs, food additives and pesti-
cides, and some new chemicals,
must be tested for carcinogenicity.
i However, officials estimate
that less than 10 percent of the
chemicals available have been sub-
, 1 jected to adequate testing a
figure they say underlines the
pressing need for a quick, reliable
and affordable method of screen-
The lifetime rodent test is now
considered by regulators the "gold
standard" of carcinogenicity tests.
Although short-term laboratory
tests are used widely in industry
and even in regulation, regulators
require rodent studies as the final
"The rodent bioassays (are)
probably the most reliable indica-
tor, short of human data, for identi-
fying chemicals that may pose a.
cancer risk for man, and for trying
to express (their) potency," said
Jack Moore, acting deputy admin-
istrator of the EPA.
The tests entail exposing two
species, usually rats and mice, to
high doses of the chemical in ques-
tion. Animals of both sexes must
be studied. For purposes of com-
parison, control animals must also
be kept, under identical conditions
but without the exposure.
After about two years the
bulk of a rodent's lifetime the
animals are killed. Their tissue is
then scrutinized for tumors. If
there are significantly more tu-
mors in the exposed animals than
in the control group, the chemical
is often suspected to be the cause.
Because many carcinogens
produce cancer by altering genetic
material in cells, and because the
mammalian system is similar from
one species to another, scientists
think that substances that cause
tumors in rodents may well cause
cancer in people.
"With very, very few excep-
i tions, if a substance causes tumors
In a human being, it will cause
tumors not necessarily of the
same kind or in the same place -
in another species," said Jerry M.
Rice, a top biochemist at the Na-
tional Cancer Institute.
But does it work the other way?
Do chemicals that cause tumors in
animals at high doses necessarily
produce cancer in humans? Critics
of the federal reliance on rodent
tests say there is increasing evi-
dence that, in some cases, the
answer may be no.
"There are two big questions,"
said Lester B. Lave, co-author of a
paper on rodent tests published
this month in the British scientific
journal Nature. "How do you go
from rats to people? And how do
you go from extremely high doses
to low doses?"
Lave and his co-authors noted
in the paper that half the chemicals
tested by the U.S. National Toxi-
-cology Program have produced tu-
mors in rats or jce.0In 70percent
of the cases, the remts were the
same in both species. But in 30
:percent, they .Wre .ot.. : o.
Since mice a rats are more
similar to each other tan they are
to people, Lave suggeststhat ex-
trapolating to humans is. fraught
with uncertainty." At best, iodent
experiments might predict human
experience accrate*O terc
of the time, the autho L t
As an example, Jave cites the
,1969 ban on the seeter cycla-
-:mate because of lks t bbldder
,tumors in rats. Iowrdetmth ay
Scydamite is ulikey tp ca can-
cer by itself; hrtead,t may be a
Promoter that enham the effects
of true carcinogeas.