[Federal Register Volume 59, Number 178 (Thursday, September 15, 1994)]
[Unknown Section]
[Page 0]
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