[Federal Register Volume 59, Number 178 (Thursday, September 15, 1994)]
[Unknown Section]
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From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 94-22814]
[[Page Unknown]]
[Federal Register: September 15, 1994]
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DEPARTMENT OF HEALTH AND HUMAN SERVICES
Public Health Service National Toxicology Program; Availability
of Technical Report on Toxicology and Carcinogenesis Studies of
Coumarin
The HHS' National Toxicology Program announces the availability of
the NTP Technical Report on the toxicology and carcinogenesis studies
of coumarin, which is used in perfumes, cosmetics, and as a flavor-
enhancing agent for foods.
Toxicology and carcinogenicity studies were conducted by
administering coumarin (97% pure) in corn oil by gavage to groups of 60
male and female F344/N rats for up to 2 years at doses of 0, 25, 50, or
100 mg per kg body weight. Groups of 70 male and female B6C3F1
mice were administered courmarin in corn oil by gavage at doses of 0,
50, 100, or 200 mg per kg body weight for up to 2 years.
Under the conditions of these 2-year gavage studies there were some
evidence of carcinogenic activity\1\ of coumarin in male F344/N rats
based on increased incidences of renal tubule adenomas. There was
equivocal evidence of carcinogenic activity of coumarin in female F344/
N rats based on a marginally increased incidence of renal tubule
adenomas. There was some evidence of carcinogenic activity of coumarin
in male B6CF1 mice based on the increased incidence of alveolar/
bronchiolar adenomas. There was clear evidence of carcinogenic activity
of coumarin in female B6C3F1 mice based on increased incidences of
alveolar/bronchiolar adenomas, alveolar/bronchiolar carcinomas, and
hepatocellular adenomas. The marginally increased incidences of
squamous cell papillomas of the forestomach in male and female mice
receiving 50 mg/kg may have been related to courmarin administration.
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\1\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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The administration of coumarin to rats was also associated with an
increased severity of nephropathy in the kidney and of bile duct
hyperplasia in the liver, increased incidences of ulcers of the
forestomach, and necrosis, fibrosis, and cytologic alteration of the
liver. Administration of coumarin to mice was also associated with
centrilobular hypertrophy, syncytial alteration, and eosinophilic focus
in the liver.
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 Coumarin (CAS
No. 91-64-5) in F344/N Rats and B6C3F1 Mice (Gavage studies) (TR-
422) 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: September 8, 1994.
Kenneth Olden,
Director, National Toxicology Program.
[FR Doc. 94-22814 Filed 9-14-94; 8:45 am]
BILLING CODE 4140-01-M