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Home » Study Results & Research Projects » NTP Study Reports » All Long-Term Reports » Abstract for TR-72 - Phenoxybenzamine Hydrochloride
Chemical Formula: | C18H22ClNO - ClH | - | 3D Structure* |
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Phenoxybenzamine hydrochloride is an antihypertensive agent that is used in controlling specific hypertensive crises such as those that result from high blood levels of sympathomimetic amines.
A bioassay of phenoxybenzamine hydrochloride for possible carcinogenicity was conducted by administering the test chemical by intraperitoneal injection to Sprague-Dawley rats and B6C3F1 mice.
Groups of 35 rats of each sex were administered phenoxybenzamine hydrochloride at one of two doses, either 5 or 10 mg/kg body weight, three times per week for 52 weeks, then observed for an additional 31 or 32 weeks. The vehicle used for most of the period of the bioassay was 6% propylene glycol in saline, although other vehicles, including 0.05% polysorbate 80 in saline, were used at the beginning. Controls consisted of groups of 10 vehicle controls and 10 untreated controls of each sex. All surviving rats were killed at 83-85 weeks.
Groups of 35 mice of each sex were administered phenoxybenzamine hydrochloride at one of two doses, either 12.5 or 25 mg/kg body weight, three times per week for 50 or 52 weeks, then observed for an additional 31-33 weeks. Controls consisted of groups of 15 males and 15 females which were administered the vehicle (vehicle controls), and groups of 14 males and 16 females which were untreated (untreated controls). All surviving mice were killed at 83-85 weeks.
Mean body weights of the low-dose male rats, low- and high-dose female rats, and low-dose male and female mice were comparable to those of the untreated and vehicle controls. The mean body weights of the high-dose male rats and the high-dose male and female mice, which died early, were lower than those of the controls.
Sarcoma of the abdominal cavity (peritoneum) was found in dosed animals of both species, but did not occur in either the untreated or vehicle controls. In male rats, this lesion occurred with a significant dose-related trend (P>0.001), using a vehicle controls, and also at significant incidences in direct comparisons of the dosed groups with the vehicle controls (controls 0/10, low-dose 11/31, P=0.027; high-dose 16/20, P<0.001). In female rats, the lesion occurred at a significant incidence in the high-dose group compared with the vehicle controls (controls 0/9, high-dose 16/30, P=0.004). None were observed among low-dose females.
In the mice, sarcoma of the abdominal cavity (peritoneum) occurred at a high and statistically significant incidence in the high-dose groups of each sex compared with vehicle controls (males: controls 0/15, high-dose 17/21, P<0.001; females: controls 0/13, high-dose 16/20, P<0.001). None were observed among low-dose groups. The morphology of the sarcoma was similar in the rats and the mice.
It is concluded that under the conditions of this bioassay, phenoxybenzamine hydrochloride was carcinogenic (sarcomagenic) for the peritoneum of both sexes of Sprague-Dawley rats and B6C3F1 mice.
Levels of Evidence of Carcinogenicity: | ||
Male Rats: | Positive | |
Female Rats: | Positive | |
Male Mice: | Positive | |
Female Mice: | Positive |
Synonym: N-(2-chloroethyl)-N-(1-methyl-2-phenoxyethyl)benzylamine hydrochloride
Target Organs from 2-year Studies
Report Date: 1978
Web page last updated on October 15, 2007
The National Institute of Environmental Health Sciences is one of the National Institutes of Health within the U.S. Department of Health and Human Services. The National Toxicology Program is headquartered on the NIEHS campus in Research Triangle Park, NC.