94-17448. National Toxicology Program; Availability of Technical Report on Toxicology and Carcinogenesis Studies of Oxazepam

[Federal Register Volume 59, Number 137 (Tuesday, July 19, 1994)]
[Unknown Section]
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From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 94-17448]


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[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 Oxazepam

    The HHS' National Toxicology Program announces the availability of 
the NTP Technical Report on the toxicology and carcinogenesis studies 
of oxazepam, which is one of a number of benzodiazepines used 
therapeutically as a sedative-hypnotic and antianxiety agent.
    Toxicology and carcinogenesis studies were performed by 
administering oxazepam (greater than 99% pure) to groups of 60 male and 
60 female Swiss-Webster and B6C3F1 mice in feed at concentrations 
of 0, 2,5000, or 5,000 ppm for 57 weeks (Swiss-Webster), or 2 years 
(B6C3F1 ). Additional groups of 60 male and 60 female B6C3F1 
mice received 125 ppm of oxazepam in feed to allow for concentrations 
similar to those achieved in humans taking a therapeutic dose.
    Under the conditions of these feed studies, there was clear 
evidence of carcinogenic activity* of oxazepam in male and female 
Swiss-Webster mice based on increased incidences of hepatocellular 
adenoma and carcinoma. There was clear evidence of carcinogenic 
activity of oxazepam in male and female B6C3F1 mice based on 
increased incidences of hepatoblastoma and hepatocellular adenoma and 
carcinoma. Increased incidences of hyperplasia of thyroid gland 
follicular cells in male and female B6C3F1 mice and of follicular 
cell adenomas in female B6C3F1 mice were also related to oxazepam 
exposure.
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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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    Administration of oxazepam to Swiss-Webster mice resulted in 
centrilobular hepatocellular hypertrophy and increased incidences and 
severity of systemic amyloidosis. Administration of oxyazepam to 
B6C3F1 mice also resulted in centrilobular hepatocellular 
hypertrophy.
    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 [phone].
    Copies of Toxicology and Carcinogenesis Studies of Oxazeham (CAS 
No. 604-75-1) in Swiss-Webster and B6C3F1 Mice (Feed Studies) (TR-
443) are available without charge from Central Data Management, NIEHS, 
MD A0-01, P.O. Box 12233, Research Triangle Park, NC 27709; telephone 
[phone].

    Dated: July 12, 1994.
Kenneth Olden,
Director, National Toxicology Program.
[FR Doc. 94-17448 Filed 7-18-94; 8:45 am]
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