Oxazepam and related benzodiazepines are used in the treatment of anxi
ety, Carcinogenicity studies of oxazepam were performed with the F344
rat because of marked differences in tumor responses observed in NTP s
tudies with B6C3F1 and Swiss-Webster mice compared to the results of S
prague-Dawley rat studies submitted to the FDA by a manufacturer to su
pport registration of the drug. Groups of 50 male and 50 female F344/N
rats were fed diets containing 0, 625, 2500, or 5000 ppm oxazepam for
up to 105 weeks. A stop-exposure group of 50 males and 50 females rec
eived 10,000 ppm oxazepam in diet for 26 weeks, after which animals re
ceived control diet. All 5000- and 10,000-ppm stop-exposure males died
before the end of the study. Survival of 2500-ppm males and females w
as lower than that of controls. Body weight gains of 2500- and 5000-pp
m males and females were less than those of controls, Male rats expose
d to 2500 ppm had an increased incidence of renal tubule adenoma and h
yperplasia. In addition, the incidences of renal tubule adenoma and hy
perplasia were increased in the 10,000-ppm stop-exposure group. The in
cidences of nephropathy in exposed females were greater than those in
controls, and the severity of nephropathy increased in exposed males.
Epithelial hyperplasia and chronic inflammation of the nonglandular st
omach were increased in males given 2500 and 5000 ppm and the incidenc
e of ulcers of the nonglandular stomach in 2500-ppm males was also gre
ater than that in controls. In males exposed to 5000 ppm, mineralizati
on of the glandular stomach and erosion of the duodenum were observed.
In females exposed to 2500 ppm, the incidences of epithelial hyperpla
sia, chronic inflammation, and ulcers of the nonglandular stomach and
the incidence of erosion in the glandular stomach were increased. The
incidences of centrilobular hepatocyte hypertrophy in males and female
s given 2500 and 5000 ppm were greater than those in controls. In summ
ary, there was equivocal evidence of carcinogenicity in males based on
increased renal tubule adenomas in groups which also had significantl
y enhanced nephropathy. There was no evidence of carcinogenicity of ox
azepam in females given a diet containing 625, 2500, or 5000 ppm for 2
years or 10,000 ppm for 6 months, (C) 1998 Society of Toxicology.