[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: 94-17453]


[[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 promethazine Hydrochloride

    The HHS' National Toxicology Program announces the availability of 
the NTP Technical Report on the toxicology and carcinogenesis studies 
of promethazine hydrochloride, a drug used for the management of 
allergic conditions, motion sickness and nausea, and as a sedative to 
treat psychiatric disorders.
    Toxicology and carcinogenicity studies were conducted by 
administering promethazine hydrochloride (>99% pure) in distilled water 
by gavage to groups of 60 male and 60 female F344/N rats and 
B6C3F1 mice once daily, 5 days per week for up to 103 weeks. Rats 
received doses of 0, 8.3, 16.6, and 33.3 mg/kg; male mice received 
doses of 0, 11.25, 22.5, and 45 mg/kg and female mice received 0, 3.75, 
7.5, and 15 mg/kg.
    Under the conditions of these 2-year gavage studies, there was no 
evidence of carcinogenic activity* of promethazine hydrochloride in 
male or female F344/N rates receiving 8.3, 16.6, or 33.3 mg/kg. There 
was no evidence of carcinogenic activity of promethazine hydrochloride 
in male B6C3F1 mice receiving 11.25, 22.5 or 45 mg/kg. There was 
no evidence of carcinogenic activity of promethazine hydrochloride in 
female B6C3F1 mice receiving 3.75, 7.5, or 15 mg/kg.
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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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    The decrease in the incidences of adrenal medullary 
pheochromocytoma in male rates was considered to be related to 
promethazine hydrochloride administration. The decrease in the 
incidences of pituitary gland adenoma in male rates and uterine stromal 
polyp in female rates may have been related to promethazine 
administration.
    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 Promethazine 
Hydrochloride (CAS No. 58-33-3) in F344/N Rates and B6C3F1 Mice 
(Gavage Studies) (TR-425) 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. 94-17453 Filed 7-18-94; 8:45 am]
BILLING CODE 4140-01-M