Bioassay of 1H-Benzotriazole for Possible Carcinogenicity (CAS No. 95-14-7)
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Chemical Formula: C6H5N3
1H-Benzotriazole is an anticorrosive chemical used primarily on copper, but also on iron, steel, cadmium, chromium, zinc, and silver-nickel alloys.
A bioassay of 1H-benzotriazole for possible carcinogenicity was conducted by administering the test chemical in feed to Fischer 344 rats and B6C3F1 mice.
Groups of 50 rats of each sex were administered 1H-benzotriazole at one of two time-weighted average doses, either 6,700 or 12,100 ppm, for 78 weeks. Except for five control and five high-dose rats of each sex, which were killed at week 78, all animals surviving at that time were observed for 26-27 additional weeks. Controls consisted of groups of 50 untreated rats of each sex and were observed for 105-106 weeks. All rats surviving to weeks 104-106 were then killed.
Groups of 50 mice of each sex were administered 1H-benzotriazole at one of two time-weighted average doses, either 11,700 or 23,500 ppm, for 104 weeks, then observed for 2 additional weeks. Controls consisted of groups of 50 untreated mice of each sex and were observed for 109 weeks. All mice surviving to weeks 106-109 were then killed.
Mean body weights of the dosed male and female rats and mice were lower than those of the corresponding controls throughout most of the bioassay. Survival of animals in dosed and control groups of both rats and mice was at least 60%, and sufficient numbers of animals were at risk for development of late-appearing tumors.
In male rats, neoplastic nodules of the liver occurred at a statistically significant incidence (P=0.024) in the high-dose group when compared with the control group (controls 0/48, low-dose 0/46, high-dose 5/45 [11%]). The incidence of this tumor in control Fischer 344 rats used in similar bioassays of other test chemicals at the same laboratory has varied from 0 to 11%, with 2/13 historical-control groups having incidences of 10-11%. Since the incidence in the high-dose groups is no higher than has been observed in some control groups, these tumors cannot be clearly associated with administration of the test chemical.
Brain tumors occurred in three dosed male rats, in one dosed female rat, and in none of the controls. The occurrence of this rare tumor in dosed animals of each sex is suggestive of, but not considered as sufficient evidence of, carcinogenicity.
In female rats, the incidence of endometrial stromal polyps in the low-dose group was significantly higher (P=0.010) than that in the corresponding controls (controls 2/48, low-dose 10/45, high-dose 8/50). However, the incidence in the high-dose group was not significant, and when the incidences of endometrial stomal polyps and endometrial stromal sarcomas were combined, they were not significant in either the low- or high-dose groups. Thus, these tumors cannot be associated with administration of the chemical.
In male mice, no tumors occurred in dosed groups at incidences that were significantly higher than those in controls.
In female mice, alveolar/bronchiolar carcinomas occurred at a statistically significant incidence (P=0.001) only in the low-dose groups when compared with the control group (controls 0/49, low-dose 9/49 [18%], high-dose 3/59 [6%]). The incidence in the high-dose group was not significant, and the data did not show a dose-related trend. It should be noted that the incidence of these tumors in control B6C3F1 female mice from other bioassays at this laboratory has varied from 0 to 7%, with a mean of 4%. Therefore, the occurrence of this tumor in female mice cannot be clearly related to the administration of the test chemical.
In female B6C3F1 mice there was an increased incidence of alveolar/bronchiolar carcinomas, suggesting a possible carcinogenic effect of 1H-benzotriazole. In Fischer 344 rats there was an increased incidence of brain tumors, suggesting a possible carcinogenic effect. However, there was no convincing evidence that under the conditions of this bioassay 1H-benzotriazole was carcinogenic in B6C3F1 mice or Fischer 344 rats of either sex.
Report Date: 1978