[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