ExLax Ingrediant Cancerous to Rats

By PAUL RECER

ROCKVILLE, Md. (AP) An ingredient used for more than 90 years in a common
laxative causes cancer in laboratory rats at high doses, a new study by
federal scientists shows.

Rats fed high doses of a compound called phenolphthalein, one of the
ingredients in the popular laxative ExLax, developed lymphomas after six
months, according to researchers at the National Toxicology Program office in
Research Triangle Park, N.C.

The doses of phenolphthalein that caused cancer were 30 times higher than
humans would absorb from prescribed doses of the overthecounter laxative,
according to officials of the Food and Drug Administration.

The report was presented at a meeting of the Carcinogen Assessment Committee
of the FDA. The committee went into executive session, excluding the public,
without taking action.

The group will make a report to another FDA committee which, in turn, could
decide whether the agency will move to restrict or modify the use of
phenolphthalein in laxatives, said Joseph J. DeGeorge of the FDA, chairman of
the committee.

The manufacturer of ExLax said the product has been sold since 1905 and that
the company knows of no health risks from the product when consumers follow
the directions on the package.

``We believe that the dose levels used to test on the rats is very high,''
said Mark B. Gelbert, vice president of Novartis Consumer Health Inc. of
Summit, N.J., which makes ExLax. He said the rats used in the study may not
be a ``valid model for determining risks in humans.

``Based on over 90 years of human use, we still believe the drug is extremely
safe,'' he said.

June K. Dunnick of the Toxicology Program said tumors taken from the
laboratory rats were tested for the presence of a gene called p53 and that of
21 cancers tested, all lacked that gene. P53 is a cancer suppressor gene, and
it is missing or flawed in many human cancers.

``There was clear evidence of the loss of p53,'' said Dunnick.

The new study is the second to show that phenolphthalein may pose a cancer
risk. The National Toxicology Program scientists a year ago found that high
doses of the compound fed to rats for two years caused a variety of tumors
including lymphomas and cancers of the kidney, ovary and adrenal gland.

FDA officials at that time asked the toxicologists to conduct more studies,
using lower doses of the chemical.

In the new studies, phenolphthalein was fed to five groups of rats at doses
of 200, 375, 750, 3,000 and 12,000 parts per million for six months. For
comparison, another group of rats received none of the chemical.

``Thymic lymphoma was significantly increased in groups receiving'' the very
highest doses, the toxicologists reported. Changes in tissue, a condition
called hyperplasia that is often a precursor to cancer, were found in animals
getting the 750 ppm dose or higher. There were also changes found in blood
cells, the scientists reported.

Some of the types of cancers found in the first study were not reported in
the latest findings.

DeGeorge said the first effect in the rats was shown in doses that would be
equivalent to about 30 times the normal labeled dose of phenolphthalein in
laxatives.

The committee chairman said it may be several days before his group reports
to the Over The Counter committee of the FDA. It is not known when that
committee might start considering the issue.