National Cancer Institute carcinogenesis technical report series最新文献

A bioassay of p-cresidine for possible carcinogenicity was conducted using Fischer 344 rats and B6C3F1 mice. p-Cresidine was administered in the feed, at either of two concentrations, to groups of 50 male and 50 female animals of each species. The dietary concentrations used in the chronic bioassay for low and high dose rats were 0.5 and 1.0 percent, respectively. The time-weighted average concentrations fed to low dose male, low dose female, high dose male and high dose female mice were 0.22, 0.22. 0.46, and 0.44 percent, respectively. All dosed animals, except for high dose male mice, were administered p-cresidine in the diet for 104 weeks and observed for an additional period of up to 2 weeks. All high dose male mice were dead by the end of week 92. For each species, 50 animals of each sex were placed on test as controls and fed only the basal laboratory diet. Mortality rates were dose-related for both sexes of both species. That incidences of certain tumors were higher in low dose than in high dose groups was probably due to accelerated mortality in the high dose group. In dosed rats of both sexes, statistically significant incidences of bladder carcinomas (combined incidences of papillary carcinomas, squamous-cell carcinomas, transitional-cell papillomas, transitional-cell carcinomas, and undifferentiated carcinomas) and olfactory neuroblastomas were observed. The combined incidence of neoplastic nodules of the liver, hepatocelular carcinomas, or mixed hepato/cholangio carcinomas was also significant in low dose male rats. In both male and female dosed mice, the incidence of bladder carcinomas (combined incidence of carcinomas NOS, squamous-cell carcinomas, and transitional carcinomas) was significant. The incidence of hepatocellular carcinomas was also significant in dosed female mice. Under the conditions of this bioassay, p-cresidine was carcinogenic to Fischer 344 rats, causing increased incidences of carcinomas and of papillomas of the urinary bladder in both sexes, increased incidences of olfactory neuroblastomas in both sexes, and of liver tumors in males. p-Cresidine was also carcinogenic in B6C3F1 mice, causing carcinomas of the urinary bladders in both sexes and hepatocellular carcinomas in females.

A bioassay for possible carcinogenicity of 6-nitrobenzimidazole was conducted using Fischer 344 rats and B6C3F1 mice. 6-Nitrobenzimidazole was administered in the feed, at either of two concentrations, to groups of 50 male and 50 female animals of each species. The dietary concentrations used in the chronic bioassay were 0.5 and 0.12 percent for the high and low dose rats, respectively, and 0.24 and 0.12 percent for the high and low dose mice, respectively. After a 78-week period of compound administration, observation of the rats continued for up to an additional 29 weeks and observation of the mice continued for an additional 18 weeks. For each species and each dosed group, 49 or 50 animals of each sex were placed on test as controls. There were no significant positive associations between the administered dietary concentrations of 6-nitrobenzimidazole and mortality in either sex of rats or mice. In all groups adequate numbers of animals survived sufficiently long to be at risk from late-developing tumors. Among both male and female mice, the incidences of hepatocellular carcinomas in high dose groups were statistically significant relative to controls. Among rats of both sexes, nonneoplastic lesions of the eyes and of the Harderian glands appeared to be associated with administration of 6-nitrobenzimidazole. No neoplasms, however, were attributed to compound administration. Under the conditions of this bioassay, dietary administration of 6-nitrobenzimidazole was not carcinogenic to Fischer 344 rats; however, the compound was carcinogenic to B6C3F1 mice, causing hepatocellular carcinomas in both sexes.

A bioassay of aldicarb for possible carcinogenicity was conducted by administering the test chemical in feed to F344 rats and B6C3F1 mice. Groups of 50 rats and 50 mice of each sex were administered aldicarb at one of two doses, either 2 or 6 ppm, for 103 weeks and then observed for an additional 0 to 2 weeks. Matched controls consisted of 25 untreated rats and 25 untreated mice of each sex. All surviving animals were killed at weeks 103 to 105. Mean body weights of the dosed male and female rats were essentially the same as those of the corresponding controls. Mean body weights of the dosed male and female mice also were essentially the same as those of corresponding controls. Hyperactivity was noted in the dosed groups of mice. Survival was not affected significantly in dosed groups of either the rats or the mice and was 72% or greater in all dosed or control groups at week 90. Sufficient numbers of animals were at risk for the development of late-appearing tumors. No tumors occurred in either the rats or mice at incidences that could clearly be related to administration of the test chemical. In both rats and mice, however, there was no indication either through weight depression or early mortality that maximum tolerated dose levels were used. Therefore, the studies may not have been conducted using maximum sensitivity for the assessment of the possible carcinogenicity of aldicarb. It is concluded that under the conditions of this bioassay, technical-grade aldicarb was not carcinogenic for F344 rats or B6C3F1 mice of either sex.

A bioassay of BHT for possible carcinogenicity was conducted by administering the test chemical in feed to F344 rats and B6C3F1 mice. Groups of 50 rats and 50 mice of each sex were administered BHT at one of two doses, either 3,000 or 6,000 ppm; the rats for 105 weeks and the mice for 107 or 108 weeks. Matched controls consisted of 20 untreated rats and 20 untreated mice of each sex. All surviving animals were killed at the end of administration of the test chemical. Mean body weights of the dosed rats and mice were lower than those of the corresponding controls and were dose related throughout most of the bioassay. Survival was not affected significantly in the dosed groups of rats or mice, and the survival was 60% or greater in all dosed or control groups of rats and mice of each sex at the end of the bioassay. Sufficient number of animals were at risk for the development of late-appearing tumors. Alveolar/bronchiolar carcinomas or adenomas occurred in the female mice at a significant incidence in the low-dose group (P=0.009) but not in the high dose group, and the incidences were not significantly dose related (control 1/20, low-dose 16/46, high-dose 7/50). Thus, these lung tumors in the female cannot clearly be related to the administration of the BHT. No tumors occurred in either male or female rats at incidences that were significantly higher in dosed groups than in corresponding control groups. Nonneoplastic lesions that may have been related to the administration of the test chemical included focal alveolar histiocytosis at increased incidences in the dosed female rats and various lesions of the liver at increased incidences in the dosed male mice. It is concluded that under the conditions of this bioassay, BHT was not carcinogenic for F344 rats or B6C3F1 mice.

A bioassay for the possible carcinogenicity of N,N'-diethylthiourea was conducted using Fischer 344 rats and B6C3F1 mice. N,N'-Diethylthiourea was administered in the feed, at either of two concentrations, to groups of 50 males and 50 females of each species. Twenty animals of each sex and species, except for 19 male mice, were placed on test as controls. The high and low dietary concentrations of N,N'-diethylthiourea were, respectively, 250 and 125 ppm for rats and 500 and 250 ppm for mice. The compound was administered in the diet for 103 weeks, followed by an observation period of 1 week for all dosed groups. There were no significant positive associations between the dosages of N,N'-diethylthiourea administered and mortality in rats or mice of either sex. Adequate numbers of animals in all dose groups survived sufficiently long to be at risk from late-developing tumors. Compound-related mean body weight depression was apparent among dosed male and female mice when compared to their respective controls,indicating that the concentrations of N,N'-diethylthiourea administered to mice may have approximated the maximum tolerated dosages. There were statistically significant elevated incidences of follicular-cell carcinomas of the thyroid in high dose male rats. In addition, there were statistically significant elevated incidences of a combination of thyroid follicular-cell carcinomas and follicular-cell adenomas in high dose male and female rats. Under the conditions of this bioassay, N,N'-diethylthiourea was carcinogenic to Fischer 344 rats, causing follicular-cell carcinomas of the thyroid in males and follicular-cell neoplasms of the thyroid in females. There was no evidence for the carcinogenicity of the compound in B6C3F1 mice.

A bioassay of 2,4-diaminotoluene for possible carcinogenicity was conducted by administering the test chemical in feed to F344 rats and B6C3F1 mice. Groups of 50 rats of each sex were administered 2,4-diaminotoluene at one of two doses, initially either 125 or 250 ppm, for 40 weeks. Because of excessive depression in the amount of mean body weight gained in both low- and high-dose groups, doses were then reduced to 50 and 100 ppm, respectively. Administration of 50 ppm to the low-dose groups was continued for 63 weeks, and surviving animals in these groups were then killed. Surviving animals in the high-dose males and females administered 100 ppm were killed at the end of 39 and 44 weeks, respectively, due to morbidity. The time-weighted average dose was 79 ppm for the low-dose male and females for 103 weeks, 176 ppm for the high-dose males for 79 weeks, and 171 ppm for the high-dose females for 84 weeks. Matched controls consisted of 20 untreated rats of each sex. Groups of 50 mice of each sex were administered 2,4-diaminotoluene at one of two doses, either 100 or 200 ppm, for 101 weeks. Matched controls consisted of 20 untreated mice of each sex. Surviving mice were killed at the end of administration of the test chemical. Mean body weights of dosed male and female rats and mice were lower than those of corresponding controls and were dose related except for the low-dose male mice, for which mean body weights were only slightly lower than those of controls. Mortality was not dose related in either the male or female mice, but was dose related in both the male and female rats. Survival was decreased and lesions of hepatonephrotoxicity were observed in the animals administered the 2,4-diaminotoluene. In the rats, hepatocellular carcinomas or neoplastic nodules occurred at incidences that were dose related in both the males (P=0.014) and the females (P=0.008). In direct comparisons of incidences of the tumors in control and dosed groups, the incidence in the high-dose male group had a P value of 0.026 (males: controls 0/20, low-dose 5/49, high-dose 10/50; females: controls 0/20; low-dose 0/50, high-dose 6/49). The significance of the occurrence of these tumors in both the male and female rats was supported by the high incidences of associated nonneoplastic lesions of the liver in the dosed groups and by low incidences of liver tumors in historical-control male or female F344 rats at the same laboratory. In addition, carcinomas or adenomas of the mammary gland occurred in the female rats at incidences that were dose related (P=0.002) and in direct comparisons were higher in the dosed groups (P<0.001) than in the control group (control 1/20; low-dose 38/50, high-dose 41/50). In male rats, fibromas of the subcutaneous tissue occurred at incidences that were dose related (P=0.004) and in direct comparisons were higher in the dosed groups (P