[Federal Register Volume 59, Number 179 (Friday, September 16, 1994)]
[Unknown Section]
[Page 0]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 94-22815]


[[Page Unknown]]

[Federal Register: September 16, 1994]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES
 

National Toxicology Program; Availability of Technical Report on 
Toxicology and Carcinogenesis Studies of 3,4-Dihydrocoumarin

    The HHS' National Toxicology Program announces the availability of 
the NTP Technical Report on the toxicology and carcinogenesis studies 
of 3,4-dihydrocoumarin, which is used as a flavoring agent in 
beverages, gelatins, puddings, candy, and other food items and as a 
fragrance in perfumes, creams, and cosmetics.
    Toxicity and carcinogenicity studies were conducted by 
administering 3,4-dihydrocoumarin (99% pure) in corn oil by gavage to 
groups of 60 male and female F344/N rats at doses of 0, 150, 300, or 
600 mg/kg body weight for 2 years. Groups of 70 male and female B6C3F 
mice received 3,4-dihydrocoumarin in corn oil by gavage at doses of 0, 
200, 400, or 800 mg/kg body weight for 2 years.
    Under the conditions of these 2-year gavage studies, there was some 
evidence of carcinogenic activity\1\ of 3,4-dihydrocoumarin in male 
F344/N rats based on increased incidence of renal tubule adenomas and 
focal hyperplasia. The transitional cell carcinomas in two 600 mg/kg 
males may also have been chemical related. There was no evidence of 
carcinogenic activity of 3,4-dihydrocoumarin in female F344/N rats 
receiving 150, 300, or 600 mg/kg. There was no evidence of carcinogenic 
activity of 3,4-dihydrocoumarin in male B6C3F\1\ mice receiving 200, 
400, or 800 mg/kg. There was some evidence of carcinogenic activity in 
female B6C3F\1\ mice based on increased incidences of hepatocellular 
adenoma and hepatocellular adenoma or carcinoma (combined).
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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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    3,4-Dihydrocoumarin caused ulcers, hyperplasia, and inflammation of 
the forestomach, parathyroid gland hyperplasia, and increased severity 
of nephropathy in male rats.
    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 3,4-
Dihydrocoumarin (CAS No. 119-84-6) in F344/N Rats and B6C3F\1\ Mice 
(Gavage Studies) (TR-423) 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. 94-22815 Filed 9-15-94; 8:45 am]
BILLING CODE 4140-01-M