Biomedical subjects

National Toxicology Program

Publications and source records attributed to National Toxicology Program.

At least 559 records · Page 31Linked to original sources

PubMed1979

Bioassay of C.I. vat yellow 4 for possible carcinogenicity.

A bioassay of C.I. vat yellow 4, a commercial formulation containing dibenzo(b, def) chrysene-7,14-dione, 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 and 50 mice of each sex were administered C.I. vat yellow 4 in the diet at one of two doses, either 3,500 or 7,000 ppm for the rats, either 25,000 or 50,000 ppm for male mice, and either 12,500 or 25,000 ppm for the female mice. The rats were administered the test chemical for 104 weeks; the mice, for 106 weeks. Matched controls consisted of 20 untreated rats and 20 untreated mice of each sex. All surviving animals were killed at the end of the period of administration of the test chemical. Mean body weights of the dosed rats were lower than those of corresponding controls throughout the bioassay, but the differences in weights were slight for the males. Mean body weights of the dosed mice were not affected by the test chemical. Survival of the rats and mice were not affected adversely by the chemical, and sufficient numbers of dosed and control rats and mice of each sex were at risk for the development of late-appearing tumors. In the male and female rats and the female mice, no tumors occurred at incidences that were significantly higher in dosed groups than in control groups. In the male mice, lymphomas occurred at incidences that were dose related (P=0.002) and, in a direct comparison, the incidence of the tumor in the high-dose group was significantly higher (P=0.019) than that in the control group (controls 3/20, or 15%; low-dose 7/47, or 15%; high-dose 22/50, or 44%). The incidence of lymphomas and leukemias in historical-control male B6C3F1 mice, at this laboratory was 38/323 (12%). It is concluded that under the conditions of this bioassay, the formulated product containing C.I. vat yellow 4 was not carcinogenic for male or female Fischer 344 rats or for female B6C3F1 mice, but was carcinogenic for male B6C3F1 mice, causing an increased incidence of lymphomas.

Journal Article↗

PubMed1979

Bioassay of 3-nitro-p-acetophenetide for possible carcinogenicity.

A bioassay for possible carcinogenicity of 3-nitro-p-acetophenetide was conducted using Fischer 344 rats and B6C3F1 mice. 3-Nitro-p-acetophenetide was administered in the feed, at either of two concentrations, to groups of 50 male and 50 female animals of each species, with the exception of low dose male mice, of which there were 49. Fifty animals of each sex and species were placed on test as controls. The high and low time- weighted average dietary concentrations of 3-nitro-p-acetophenetide were, respectively, 0.36 and 0.18 percent for rats and 1.46 and 0.73 percent for mice. The compound was administered in the diet for 78 weeks, followed by an observation period of up to 30 weeks for rats and 20 weeks for mice. There were no significant positive associations between the concentrations of 3-nitro-p-acetophenetide administered and mortality in rats or mice of either sex. In addition, adequate numbers of animals in all groups survived sufficiently long to be at risk from late-developing tumors. There was a statistically significant increased incidence of a combination of hepatocellular carcinomas and adenomas when high dose male mice were compared to controls. No other neoplasm in any other dosed group occurred in significant positive increased incidences when compared to controls. Under the conditions of this bioassay, dietary administration of 3-nitro-p-acetophenetide was not carcinogenic in Fischer 344 rats of either sex or in female mice. The compound, however, was considered carcinogenic in male B6C3F1 mice based on a significant increase in the combined incidence of hepatocellular carcinomas and hepatocellular adenomas in these animals.

Journal Article↗

PubMed1979

Bioassay of 2,5-dithiobiurea for possible carcinogenicity.

A bioassay of 2,5-dithiobiurea for possible carcinogenicity was conducted using Fischer 344 rats and B6C3F1 mice. 2,5-Dithiobiurea was administered in the feed, at either of two concentrations, to groups of 50 male and 50 female animals of each species, with the exception of high dose male rats, of which there were only 49. The dietary concentrations used in the chronic bioassay were 0.6 percent for the low dose rats and 1.2 percent for the high dose rats. The dietary concentrations used for low and high dose mice were 1.0 and 2.0 percent, respectively. After a 78-week dosing period, observation of the mice continued for an additional 16 weeks. For each species, 50 animals of each sex were placed on test as controls. In both species, adequate numbers of animals in all groups survived sufficiently long to be at risk from late-developing tumors. Compound-related mean body weight depression was observed in mice but not in rats. No consistent pattern of clinical signs was observed in either species. No tumors occurred at a significantly higher incidence in dosed rats than in their controls. Among female mice, the Cochran-Armitage test indicated a significant positive association between the incidence of hepatocellular carcinoma and dietary concentrations of 2,5-dithiobiurea. According to results of the Fisher exact test, the incidence of hepatocellular carcinoma was significantly higher in the high dose female mouse group when compared to the corresponding control group but not when compared to the laboratory historical control data. No neoplasms occurred at a significantly higher incidence in dosed male mice than in their controls. Under the conditions of this bioassay, the evidence suggested, but was insufficient to establish the carcinogenicity of 2,5-dithiobiurea for female B6C3F1 mice. The compound was not carcinogenic to male B6C3F1 mice or to male or female Fischer 344 rats.

Journal Article↗

PubMed1979

Bioassay of trimethylthiourea for possible carcinogenicity.

A bioassay for the possible carcinogenicity of trimethylthiourea was conducted using Fischer 344 rats and B6C3F1 mice. A mixture containing 80 percent trimethylthiourea and 15 percent dimethylthiourea was administered in the feed, at either of two concentrations, to groups of 50 male and 50 female animals of each species. Twenty animals of each sex and species were placed on test as controls. The high and low dietary concentrations of trimethylthiourea were, respectively, 500 and 250 ppm for rats and 1,000 and 500 ppm for mice. The compound was administered in the diet for 77 weeks, followed by an observation period of 29 weeks for rats and 14 weeks for mice. There were no significant positive associations between the dosage of trimethylthiourea administered and mortality in rats or mice of either sex. Adequate numbers of animals in all groups survived sufficiently long to be at risk from late-developing tumors. For high dose female rats and for dosed mice of both sexes, compound-related mean body weight depression was observed, indicating that the dosages of trimethylthiourea administered to these animals may have approximated the maximum tolerated dosages. Since no mean body weight depression relative to controls, no significant accelerated mortality, and no other signs of toxicity were associated with administration of trimethylthiourea to male rats, it is possible that these animals may have been able to tolerate a higher dietary concentration. The incidences of follicular-cell carcinomas of the thyroid in female rats were dose-related, and there was a significant difference between the incidences in the high dose and control. This same relationship was established for the combination of follicular-cell carcinomas and follicular-cell adenomas in female rats. Under the conditions of this bioassay, dietary administration of trimethylthiourea was carcinogenic in female Fischer 344 rats, inducing follicular-cell carcinomas of the thyroid. There was not sufficient evidence for the carcinogenicity of the compound in male Fischer 344 rats or in B6C3F1 mice of either sex.

Journal Article↗

PubMed1979

Bioassay of 3,3'-dimethoxybenzidine-4,4'-diisocyanate for possible carcinogenicity.

A bioassay for the possible carcinogenicity of 3,3'-dimethoxybenzidine-4,4'-diisocyanate was conducted using Fischer 344 rats and B6C3F1 mice. 3,3'-Dimethoxybenzidine-4,4'-diisocyanate was administered, at either of two concentrations, to groups of 50 male and 50 female animals of each species, with the exception of 49 high dose female rats. The compound was administered in the feed with the exception of the first 22 weeks of the rat bioassay, when it was administered by gavage. Twenty animals of each sex and species were placed on test as controls. During intubation the high and low dosages were 3,000 and 1,500 mg/kg, respectively, while the high and low concentrations administered in the feed to both rats and mice were 44,000 and 22,000 ppm, respectively. The compound was administered for a period of 78 weeks, followed by an observation period of 26 weeks for rats and 25 weeks for mice. There was a significant positive association between the administration of 3,3'-dimethoxybenzidine- 4,4'-diisocyanate and mortality in male and female rats, but not in male or female mice. Adequate numbers of animals in all groups survived sufficiently long to be at risk from late-developing tumors. For both sexes of rats, there was a significant positive association between dosage and the incidence of leukemia and malignant lymphoma. There was a significantly higher incidence of neoplasms of the skin, excluding skin of the ear, when dosed male rats were compared to controls. There was a significant positive association between the dosages administered and the incidences of endometrial stromal polyps in female rats. None of the statistical tests for any site in male and female mice indicated a significant positive association between compound administration and tumor incidence. Under the conditions of this bioassay, administration of 3,3'-dimethoxybenzidine-4,4'-diisocyanate was carcinogenic to Fischer 344 rats, causing neoplasms of the skin (excluding skin of the ear) in males, endometrial stromal polyps in females, and leukemia and malignant lymphoma in both sexes. The compound was also associated with the development of a combination of squamous-cell carcinomas and sebaceous adenocarcinomas of the Zymbal's gland and skin of the ear in rats of both sexes. There was no evidence of the carcinogenicity of the compound in B6C3F1 mice.

Journal Article↗

PubMed1979

Bioassay of piperonyl sulfoxide for possible carcinogenicity (CAS No. 120-62-7).

A bioassay of technical-grade piperonyl sulfoxide 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 piperonyl sulfoxide in the diet at one of several doses, either 1,500 or 3,000 ppm for the males and either 3,000 or 6,000 ppm for the females, for 105 weeks. Matched controls consisted of 20 untreated rats of each sex. All surviving rats were killed at the end of the period of administration of the test chemical. Groups of 50 male mice were administered one of two doses, either 350 or 700 ppm, for 104 or 105 weeks. Groups of 50 female mice were initially administered one of two doses, either 700 or 1,400 ppm. Due to excessive weight depression in the dosed female mice, the doses for this sex were reduced after week 20 to 200 and 600 ppm, respectively, and administration of the test chemical at the lower doses was continued for 84 or 85 weeks. The time-weighted average doses for the females were 295 and 754 ppm. Matched controls consisted of 20 untreated mice of each sex. All surviving mice were killed at the end of the period of administration of the test chemical. Mean body weights of dosed groups of rats and mice of each sex were lower than those of corresponding control groups, and the depressions in the amount of mean body weight gained were dose related for most or all of the bioassay; the depression in the amount of mean body weight gained was slight, however, in the dosed male rats. Survival of the rats and mice was unaffected by the piperonyl sulfoxide and was 78% or higher in all groups at week 90 of the bioassay; thus sufficient numbers of dosed and control rats and mice of each sex were at risk for the development of late-appearing tumors. In the male and female rats and in the female mice, no tumors occurred at incidences that were significantly higher in dosed groups than in control groups. In the male mice, hepatocellular carcinomas occurred at incidences that were dose related (P<0.001); in direct comparisons, the incidence of these tumors in the high-dose group was significantly higher (P<0.001) than that in the control group (controls 6/18, low-dose 31/50, high-dose 46/50). It is concluded that under the conditions of this bioassay, technical-grade piperonyl sulfoxide was not carcinogenic for male or female Fischer 344 rats or for female B6C3F1 mice, but was carcinogenic for male B6C3F1 mice, producing an increased incidence of hepatocellular carcinomas.

Journal Article↗

PubMed1979

Bioassay of 2,7-dichlorodibenzo-p-dioxin (DCDD) for possible carcinogenicity.

A bioassay of 2,7-dichlorodibenzo-p-dioxin (DCDD) for possible carcinogenicity was conducted by administering the test chemical in feed to Osborne-Mendel rats and B6C3F1 mice. Groups of 35 rats of each sex were administered DCDD at one of two doses, either 5,000 or 10,000 ppm, for 110 weeks. Groups of 50 mice of each sex were administered these same doses for 90 weeks. Controls consisted of 35 untreated rats of each sex and 50 untreated mice of each sex. All surviving male rats were killed at 110 to 112 weeks, all surviving female rats at 110 to 117 weeks, all surviving male mice at 92 to 101 weeks, and all surviving female mice at 91 to 98 weeks. Mean body weights of most of the dosed groups of rats and mice were lower than those of corresponding controls both when placed on study and for much of the study period; however, survival of any group was not significantly affected by administration of the test chemical. Sufficient numbers of dosed and control rats and mice of each sex were at risk for the development of late-appearing tumors. No tumors were induced in male or female rats or female mice at incidences that were significantly higher in the dosed groups than in the corresponding control groups. Both low-and high-dose rats had toxic hepatic lesions characterized by centrilobular fatty metamorphosis and/or necrosis. In the male mice, hepatocellular adenomas or carcinomas occurred at incidences that were dose related (P=0.008), and, in direct comparisons, were higher in the low-dose group (P=0.008) and the high-dose group (P=0.010) than in the control group (controls 8/49, low-dose 20/50, high-dose 17/42). However, the historical incidence of this lesion in control male B6C3F1 mice at this laboratory does not permit a clear association of the lesion with the administration of the test compound. There were also significant increases in the incidence of combinations of leukemias and lymphomas and of hemangiosarcomas and hemangiomas in the low-dose male mice, but these findings were not supported by the high-dose animals. It is concluded that under the conditions of this bioassay, DCDD was not carcinogenic for Osborne-Mendel rats of either sex or for female B6C3F1 mice. The marginal increased incidences of combinations of leukemias and lymphomas, of hemangiosarcomas and hemangiomas, and of hepatocellular carcinomas and adenomas in male B6C3F1 mice are, however, considered as suggestive of a carcinogenic effect of 2,7-dichlorodibenzo-p-dioxin in these animals.

Journal Article↗

PubMed1979

Bioassay of dibenzo-p-dioxin for possible carcinogenicity.

A bioassay of dibenzo-p-dioxin (UDD) for possible carcinogenicity was conducted by administering the test chemical in feed to Osborne-Mendel rats and B6C3F1 mice. Groups of 35 rats of each sex were administered UDD at one of two doses, either 5,000 or 10,000 ppm, for 110 weeks. Groups of 50 mice of each sex were administered the same doses for 87 or 90 weeks. Controls consisted of groups of 35 untreated rats of each sex and 50 untreated mice of each sex. All surviving male rats were killed at 110 weeks, all surviving male mice at 92 to 97 weeks, and all surviving female mice at 91 to 93 weeks. Mean body weights of the dosed male and female rats and mice were lower than those of the corresponding controls; the depression in the amount of weight gained in the dosed male mice was, however, relatively slight. Except for the male rats, survival at the end of the bioassay was lower in the dosed groups of both rats or mice than in the corresponding control groups. At week 90, at least 57% of the rats and 54% of the mice were still alive. Because the mean body weights and survival rates of the dosed animals were lower than those of corresponding controls and because there was an increase in the incidence of hepatotoxic lesions, the 10,000-ppm concentration administered to the rats and mice is considered to be the maximum tolerated dose. No tumors were induced in rats or mice of either sex at incidences that were significantly higher in the dosed groups than in the corresponding control groups. It is concluded that under the conditions of this bioassay, UDD was not carcinogenic for Osborne-Mendel rats or B6C3F1 mice.

Journal Article↗

PubMed1979

Bioassay of dimethyl terephthalate for possible carcinogenicity.

A bioassay of dimethyl terephthalate 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 and 50 mice of each sex were administered dimethyl terephthalate at one of two doses, either 2,500 or 5,000 ppm, for 103 weeks, then observed for 2 additional weeks. Matched controls consisted of 50 untreated rats of each sex and 50 untreated mice of each sex. All surviving rats were killed at 105 or 106 weeks and all surviving mice at 104 or 105 weeks. Administration of dimethyl terephthalate had no appreciable effect on the mean body weights of the rats and mice of either sex. No clinical signs related to administration of the test chemical were noted in the rats. Survivals of the rats and mice at the end of the bioassay were not affected by the test chemical. Both species may have been able to tolerate higher doses. In rats and mice of each sex, no tumors occurred at incidences that clearly were related to administration of the test chemical. Although it is recognized that both rats and mice may not have received a dose of the test chemical sufficiently high to provide maximum test sensitivity, it is concluded that under the conditions of this bioassay, dimethyl terephthalate was not carcinogenic for F344 rats or B6C3F1 mice.

Journal Article↗

PubMed1979

Bioassay of piperonyl butoxide for possible carcinogenicity (CAS No. 51-03-6).

A bioassay of technical-grade piperonyl butoxide 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 piperonyl butoxide in the diet at one of two doses, either 5,000 or 10,000 ppm, for 107 weeks. Matched controls consisted of 20 untreated rats of each sex. All surviving rats were killed at the end of the period of administration of the test chemical. Groups of 50 mice of each sex were initially administered piperonyl butoxide at one of two doses, either 2,500 or 5,000 ppm. After week 30, the doses for the mice were reduced to 500 and 2,000 ppm, respectively, and administration of the test chemical at the lowered doses was continued for 82 weeks. The time-weighted average doses for the mice were either 1,036 or 2,804 ppm. Matched controls consisted of 20 untreated mice of each sex. All surviving mice were killed at the end of the period of administration of the test chemical. Mean body weights of dosed groups of rats and mice of each sex were lower than those of corresponding control groups, and the depressions in body weights were dose related. Survival of the rats and mice was unaffected by the piperonyl butoxide and was 80% or greater in all groups at week 90 of the bioassay; thus, sufficient numbers of dosed and control rats and mice of each sex were at risk for the development of late-appearing tumors. In female rats, lymphomas occurred at incidences that were dose related (P=0.007); in a direct comparison, the incidence of the tumor in the high-dose group was higher (P=0.020) than that in the control group (controls 1/20, low-dose 7/50, high-dose 15/50). However, the incidence of lymphomas, leukemias, and reticuloses in historical-control female Fischer 344 rats at the same laboratory was 19/191 (10%). These historical-control groups include one with an incidence of animals with lymphoma or leukemia of 7/20 (35%) and another with an incidence of 6/20 (30%). Thus, the incidence of lymphomas in the control female rats of the present bioassay may have been abnormally low, and the occurrence of the higher incidence in the dosed groups cannot be clearly related to administration of piperonyl butoxide. In the male mice, adenomas of the lacrimal gland occurred at incidences that were dose related (P=0.023), but in direct comparisons the incidences in the individual dosed groups were not significantly higher than that in the control group (controls 0/20, low-dose 0/49, high-dose 4/50); thus, the occurrence of this tumor in the male mice was not clearly related to administration of the test chemical. It is concluded that under the conditions of this bioassay, piperonyl butoxide was not carcinogenic for Fischer 344 rats or B6C3F1 mice.

Journal Article↗

PubMed1979

Bioassay of 6-nitrobenzimidazole for possible carcinogenicity (CAS No. 94-52-0).

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.

Journal Article↗

PubMed1979

Bioassay of 4'-(chloroacetyl)-acetanilide for possible carcinogenicity.

A bioassay for the possible carcinogenicity of 4'-(chloroacetyl)-acetanilide was conducted using Fischer 344 rats and B6C3F1 mice. 4'-(Chloroacetyl)-acetanilide was administered in the feed, at either of two concentrations, to groups of 50 male and 50 female animals of each species. Twenty animals of each sex and species were placed on test as controls. The high and low dietary concentrations of 4'-(chloroacetyl)-acetanilide were, respectively, 2,000 and 1,000 ppm for rats and 10,000 and 5,000 ppm for mice. The compound was administered for 87 weeks of a 102-week period in rats and for 90 weeks of a 105-week period in mice. Mice were killed at the end of the last week of compound administration, while rats were observed for 1 week after compound administration ceased. There were no significant positive associations between the concentration of 4'-(chloroacetyl)-acetanilide administered and mortality in rats or mice of either sex. Adequate numbers of animals in all groups survived sufficiently long to be at risk from late-developing tumors. Dose-related mean body weight depression was observed for males and females of both species, indicating that the concentrations of 4'-(chloroacetyl)-acetanilide administered to the animals in this bioassay may have approximated the maximum tolerated concentrations. None of the statistical tests for any site in rats of either sex or in male mice indicated a significant positive association between compound administration and tumor incidence. Although there was a significant positive association between the concentration of the compound administered and the incidences of hepatocellular adenomas in female mice, the Fischer exact comparisons were not significant. Under the conditions of this bioassay, 4'-(chloroacetyl)-acetanilide was not carcinogenic when administered in the diet to Fischer 344 rats or B6C3F1 mice of either sex.

Journal Article↗

PubMed1979

Bioassay of lithocholic acid for possible carcinogenicity.

A bioassay for the possible carcinogenicity of lithocholic acid was conducted using Fischer 344 rats and B6C3F1 mice. Lithocholic acid was administered by gavage, at either of two dosages, to groups of 50 male and 50 female animals of each species, except for 49 low dose female rats. Twenty animals of each sex and species were placed on test as controls. The high and low dosages of lithocholic acid administered were, respectively, 500 and 250 mg/kg for rats and 250 and 125 mg/kg for mice. The compound was administered to rats and mice for 103 weeks. The period of compound administration was followed by an observation period of 1 week for rats and 2 weeks for mice. There were no significant positive associations between the dosages of lithocholic acid administered and mortality in rats or mice of either sex. Adequate numbers of animals in all groups survived sufficiently long to be at risk from late-developing tumors. Slight dose-related mean body weight depression was observed in male rats and female mice and high incidences of chronic kidney inflammation were observed in female rats, indicating that the dosages of lithocholic acid administered to these animals in this bioassay may have approximated the maximum tolerated dosages. Since no mean body weight depression, relative to controls, no significant accelerated mortality, and no other signs of toxicity were associated with administration of lithocholic acid to male mice, it is possible that these animals may have been able to tolerate a higher dosage. However, in the subchronic study there were deaths among all dosed male mouse groups, even those receiving lithocholic acid at a level only twofold greater than the high dose utilized in the chronic study. None of the statistical tests for any site in rats or in mice of either sex indicated a significant positive association between compound administration and tumor incidence. Under the conditions of this bioassay, lithocholic acid was not carcinogenic when administered by gavage to Fischer 344 rats or B6C3F1 mice.

Journal Article↗

PubMed1979

Bioassay of p-phenylenediamine dihydrochloride for possible carcinogenicity.

A bioassay of p-phenylenediamine dihydrochloride for possible carcinogenicity was conducted using Fischer 344 rats and B6C3F1 mice. p-Phenylenediamine dihydrochloride was administered in the feed, at either of two concentrations, to groups of 50 male and 50 female animals of each species. The high and low concentrations of p-phenylenediamine dihydrochloride were, respectively, 1,250 and 625 ppm for both rats and mice. After a 103-week period of compound administration, there were additional observation periods of 2 weeks for rats and 1 week for mice. Twenty animals of each sex and species were placed on test as controls. There were no significant positive associations between the concentrations of p-phenylenediamine dihydrochloride administered and mortality in rats or mice of either sex. Adequate numbers of animals in all groups survived sufficiently long to be at risk from late developing tumors. Slight dose-related mean body weight depression was observed in female rats and the mean body weights among high dose male rats and dosed female mice were slightly depressed in relation to their respective controls, indicating that the concentrations of p-phenylenediamine dihydrochloride administered to these animals in this bioassay may have approximated the maximum tolerated concentrations. Since no distinct mean body weight depression relative to controls, no significant accelerated mortality, and no other signs of toxicity were associated with administration of p-phenylenediamine dihydrochloride to male mice, it is possible that these animals may have been able to tolerate a higher dietary concentration. None of the statistical tests for any site in rats or mice of either sex, including time to leukemia or malignant lymphoma analysis in female mice, indicated a significant positive association between compound administration and tumor incidence. Under the conditions of this bioassay, there was no convincing evidence that dietary administration of p-phenylenediamine dihydrochloride was carcinogenic in Fischer 344 rats or B6C3F1 mice.

Journal Article↗

PubMed1979

Bioassay of carbromal for possible carcinogenicity.

A bioassay for the possible carcinogenicity of carbromal was conducted using Fischer 344 rats and B6C3F1 mice. Carbromal was administered in the feed, at either of two concentrations, to groups of 50 male and 50 female animals of each species with the exception of 49 low dose male mice and high dose female mice. Twenty animals of each sex and species were placed on test as controls. The high and low dietary concentrations of carbromal were, respectively, 2,500 and 1,250 ppm for rats and 2,500 and 1,250 ppm for mice. The compound was administered for 103 weeks to rats and for 78 weeks to mice. The period of compound administration was followed by an observation period of 1 week for rats and 26 weeks for mice. There was no significant positive associations between the concentrations of carbromal administered and mortality in rats or mice of either sex. Adequate numbers of animals in all groups survived sufficiently long to be at risk from late-developing tumors. Slight dose-related mean body weight depression was observed for male rats and for females of both species and the mean body weight among dosed male mice was lower than that for controls, indicating that the concentrations of carbromal administered to the animals in this bioassay may have approximated the maximum tolerated concentrations. None of the statistical tests for any site in female rats or in mice of either sex indicated a significant positive association between compound administration and tumor incidence. There was a significant positive association between the concentrations administered and the incidences of adrenal pheochromocytomas in male rats; however, the Fisher exact comparisons were not significant. Under the conditions of this bioassay, dietary administration of carbromal was not carcinogenic in Fischer 344 rats or B6C3F1 mice.

Journal Article↗

PubMed1979

Bioassay of sodium diethyldithiocarbamate for possible carcinogenicity.

A bioassay of sodium diethyldithiocarbamate 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 sodium diethyldithiocarbamate at one of two doses, either 1,250 or 2,500 ppm, for 104 weeks. Groups of 50 mice of each sex were administered sodium diethyldithiocarbamate at one of two doses, either 500 or 4,000 ppm, for 108 or 109 weeks. Matched controls consisted of 16 untreated male rats, 20 untreated female rats and 20 untreated mice of each sex. All surviving rats and mice were killed at the end of administration of the test chemical. Mean body weights of all dosed groups of rats and mice were lower that those of corresponding controls and were dose related throughout the bioassay except those of the low-dose male rats, which were essentially unaffected by administration of the test chemical. Survivals of the rat and mice were unaffected, and no other clinical signs could be related to administration of the test chemical; thus, the animals may have been able to tolerate higher doses. Sufficient numbers of dosed and control animals of each species and sex were at risk for the development of late-appearing tumors. No tumors occurred in the rats or mice of either sex at incidences that were significantly higher in the dosed groups than in the control groups. It is concluded that under the conditions of this bioassay, sodium diethyldithiocarbamate was not carcinogenic for F344 rats or B6C3F1 mice of either sex.

Journal Article↗

PubMed1979

Bioassay of 2,4-dimethoxyaniline hydrochloride for possible carcinogenicity.

2,4-Dimethoxyaniline hydrochloride, the hydrochloride salt of the dye intermediate 2,4-dimethoxyaniline, was selected for bioassay by the National Cancer Institute because of the increased incidence of bladder cancer among dye manufacturing industry workers. Aromatic amines are one of several classes of chemicals thought to contribute to the increased cancer risk in this industry. A bioassay for the possible carcinogenicity of 2,4-dimethoxyaniline HCl was conducted using Fischer 344 rats and B6C3F1 mice. 2,4-Dimethoxyaniline HCl was administered in the feed, at either of two concentrations, to groups of 50 male and 50 female animals of each species. Twenty animals of each sex and species were placed on test as controls. The high and low dietary concentrations of 2,4-dimethoxyaniline HCl were, respectively, 3,000 and 1,500 ppm for rats and 5,000 and 2,500 ppm for mice. The compound was administered in the diet for 104 weeks to rats and 103 weeks to mice, followed by a 1-week observation period for both species. There were no significant positive associations between the concentrations of 2,4-dimethoxyaniline HCl administered and mortality in rats or mice of either sex. Adequate numbers of animals in all groups survived sufficiently long to be at risk from late-developing tumors. Dose-related mean body weight depression was observed for females of both species, indicating that the concentrations of 2,4-dimethoxyaniline HCl administered to these groups may have approximated the maximum tolerated concentrations. Compound-related mean body weight depression was only slight for male rats and was apparent in male mice only until week 50; however follicular-cell hyperplasias and cystic follicles of the thyroid were observed in dosed male mice, suggesting that the concentrations the male mice received may have approximated the maximum tolerated concentrations. Since no distinct mean body weight depression in relation to controls, no significant accelerated mortality, and no other signs of toxicity were associated with administration of 2,4-dimethoxyaniline HCl to male rats, it is possible that these animals may have been able to tolerate a higher dietary concentration. There was a significant positive trend between concentration of the test chemical and the incidence of a combination of hepatocellular carcinomas and adenomas in male mice and an increase in the combination of these lesions in female mice. However, no statistically significant differences in tumor incidence at any site were observed when dosed rats and mice were compared to their respective controls. Under the conditions of this bioassay there was no convincing evidence for the carcinogenicity of 2,4-dimethoxyaniline HCl in Fischer 344 rats or B6C3F1 mice. Levels of Evidence of Carcinogenicity: Male Rats: Negative Female Rats: Negative Male Mice: Negative Female Mice: Negative Synonyms: 2,4-dimethoxybenzenamine hydrochloride; 4-methoxy-o-anisidine hydrochloride; 2-methoxy-p-anisidine hydrochloride

Journal Article↗

PubMed1979

Bioassay of a solution of b-nitrostyrene and styrene for possible carcinogenicity.

A bioassay of a solution of 30 percent b-nitrostyrene and 70 percent styrene for possible carcinogenicity was conducted using Fischer 344 rats and B6C3F1 mice. The solution of the two test materials in corn oil was administered by gavage, at either of two dosages, to groups of 50 male and 50 female animals of each species. The high and low dosages utilized in the study were, respectively, 300 and 150 mg/kg for male rats; 150 and 75 mg/kg for female rats; and 175 and 87.5 mg/kg for mice of both sexes. These dosages are expressed in terms of the b-nitrostyrene contained in the styrene solution. Twenty animals of each species and sex were placed on test as controls, and were gavaged with corn oil on the same schedule as dosed animals. A 79-week period of chemical administration was followed by an additional observation period of 29 weeks for rats, and a 78-week period of chemical administration was followed by an additional 14-week observation period for mice. There was no significant difference between the survival of rats dosed with the test solution and that of their controls, and there was no significant association between dosage and mortality among female mice. There was a significant positive association between dosage and mortality among male mice; however, adequate numbers of animals in all groups survived sufficiently long to be at risk from late-developing tumors. There was distinct mean body weight depression when high dose female mice or male rats were compared to their controls, indicating that the dosage administered to these animals may have approximated the maximum tolerated dosage. Since no distinct mean body weight depression, no significantly accelerated mortality, and no other toxic effects were associated with the administration of b-nitrostyrene and styrene to female rats or male mice, it is possible that these animals may have been able to tolerate a higher dosage. There were no significant positive associations between administration of the solution and increased tumor incidence in rats of either sex. When those male mice having either alveolar/bronchiolar carcinomas or alveolar/bronchiolar adenoma were combined and the resulting tumor incidences for each group were statistically analyzed, the low dose to control Fisher exact comparison was significant. The Cochran-Armitage test and the high dose to control comparison, however, were not. No other tests for tumors of any site in either male or female mice were significant. Under the conditions of this bioassay, there was no convincing evidence for the carcinogenicity of a solution of b-nitrostyrene and styrene in Fischer 344 rats or in B6C3F1 mice.

Journal Article↗