[Federal Register Volume 59, Number 137 (Tuesday, July 19, 1994)]
[Unknown Section]
[Page 0]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 94-17452]
[[Page Unknown]]
[Federal Register: July 19, 1994]
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DEPARTMENT OF HEALTH AND HUMAN SERVICES
National Toxicology Program; Availability of Technical Report on
Toxicology and Carcinogenesis Studies of Triamterene
The HHS' National Toxicology Program announces the availability of
the NTP Technical Report on the toxicology and carcinogenesis studies
of triamterene, a potassium-sparing diuretic used in the treatment of
edema associated with congestive heart failure, cirrhosis of the liver,
and other diseases in which edema may occur.
Toxicity and carcinogenicity studies were conducted by
administering triamterene (greater than 99% pure) in feed to groups of
50 male and female F344/N rats at doses of 0, 150, 300, or 600 ppm and
to 50 male and female B6C3F1 mice at doses of 0, 100, 200, or 400
ppm for 2 years. Because of a dosing error involving the high-dose mice
at week 40, a second study was conducted with groups of 50 male and
female mice fed diets containing 0 or 400 ppm triamterene. Additional
animals were included for interim evaluations at 3 and 15 months.
Under the conditions of these 2-year feed studies, there was
equivocal evidence of carcinogenic activity* of triamterene in male
F344/N rats based on a marginal increase in the incidence of
hepatocellular adenoma. There was no evidence of carcinogenic activity
of triamterene in female F344/N rats administered 150, 300, or 600 ppm.
There was some evidence of carcinogenic activity of triamterene in male
B6C3F1 mice based on a marginal increase in the incidence of
hepatocellular carcinoma in the first study and a significantly
increased incidence of hepatocellular adenoma in the second study.
There was some evidence of carcinogenic activity of triamterene in
female B6C3F1 mice based on significantly increased incidences of
hepatocellular adenoma and of adenoma and carcinoma (combined).
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*The NTP uses five categories of evidence of carcinogenic
activity observed in each animal study: two categories for positive
results (``clear evidence'' and ``some evidence''), one category for
uncertain findings (``equivocal evidence''), one category for no
observable effect (``no evidence''), and one category for studies
that cannot be evaluated because of major flaws (``inadequate
study'').
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Exposure to triamterene was associated with an increased incidence
of hepatocellular foci, primarily mixed cell type, and an increase in
the severity of nephropathy in female rats. In mice, exposure to
triamterene was associated with an increased incidence of
hepatocellular foci in females and an increased incidence of thyroid
gland follicular cell hyperplasia in males and females.
Questions or comments about the Technical Report should be directed
to Central Data Management at P.O. Box 12233, Research Triangle Park,
NC 27709 or telephone (919) 541-3419.
Copies of Toxicology and Carcinogenesis Studies of Triamterene (CAS
No. 396-01-0) in F344/N Rats and B6C3F1 Mice (Feed Studies) (TR-
420) are available without charge from Central Data Management, NIEHS,
MD A0-01, P.O. Box 12233, Research Triangle Park, NC 27709; telephone
(919) 541-3419.
Dated: July 13, 1994.
Kenneth Olden,
Director, National Toxicology Program.
[FR Doc. 94-17452 Filed 7-18-94; 8:45 am]
BILLING CODE 4140-01-M
