Biomedical subjects

National Toxicology Program

Publications and source records attributed to National Toxicology Program.

At least 613 records · Page 34Linked to original sources

PubMed1978

Bioassay of 2,5-toluenediamine sulfate for possible carcinogenicity.

A bioassay for possible carcinogenicity of 2,5-toluenediamine sulfate was conducted using Fischer 344 rats and B6C3F1 mice. 2,5-Toluenediamine sulfate was administered in the feed, at either of two concentrations, to groups of 50 males and 50 females of each species. The high and low time-weighted average concentrations of the compound were, respectively, 0.2 and 0.06 percent for rats and 0.1 and 0.6 percent for mice. Because compound administration to the high and low dose groups of each species was not begun simultaneously, each dosed group was assigned a control group. All control groups consisted of 50 animals, except for the high dose male and female rat control groups which were composed of 25 animals. The dosing period was for 78 weeks, followed by an additional 28 to 31 weeks of observation in rats and an additional 16 to 19 weeks in mice. There was no significant association between compound administration and accelerated mortality in either sex of either species. Adequate numbers of animals in all groups survived sufficiently long to be at risk from late-developing tumors. A statistically significant incidence of interstitial-cell neoplasms of the testis in dosed male rats was not considered attributable to administration of the compound since the spontaneous incidence of these neoplasms in male Fischer 344 rats is both high and variable. No neoplasms were observed in female rats at statistically significant incidences. A statistically significant increase in lung tumors in high dose female mice was not considered convincing evidence of a compound-related carcinogenic effect because high dose male mice were received in separate shipments from their controls and housed in separate rooms from their controls. Under the conditions of this bioassay, sufficient evidence was not obtained to demonstrate the carcinogenicity of 2,5-toluenediamine sulfate in either Fischer 344 rats or B6C3F1 mice.

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PubMed1978

Bioassay of dioxathion for possible carcinogenicity.

A bioassay for possible carcinogenicity of technical-grade dioxathion was conducted using Osborne-Mendel and B6C3F1 mice. Dioxathion 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 time-weighted average concentrations were, respectively, 180 and 90 ppm for male rats and 90 and 45 ppm for female rats. The high and low time-weighted average concentrations for male mice were 567 and 284 ppm, respectively, and for female mice were 935 and 467 ppm, respectively. After a 78-week period of chemical administration, observation of the rats continued for an additional 33 weeks and the mice were observed for an additional 12 to 13 weeks. For rats, 50 animals of each sex were placed on test as controls and fed only the basal diet, while for mice, 20 animals of each sex served as controls. In both species adequate numbers of animals survived long enough to be at risk from late-appearing tumors. A variety of neoplasms was observed in treated animals of both species; however, none of the neoplasms observed were either histopathologically unusual or in statistically significant incidences. Under the conditions of this bioassay, dietary administration of dioxathion was not carcinogenic in Osborne-Mendel rats or B6C3F1 mice.

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PubMed1978

Bioassay of 5-nitroacenaphthene for possible carcinogenicity (CAS No. 602-87-9).

A bioassay of 5-nitroacenaphthene for possible carcinogenicity was conducted using Fischer 344 rats and B6C3F1 mice. 5-Nitroacenaphthene was administered in the feed, at either of two concentrations, to groups of 50 male and 50 female animals of each species. For male and female rats, the high and low dietary concentrations of 5-nitroacenaphthene were 0.24 and 0.12 percent, respectively. The high and low time-weighted average concentrations for mice were 0.12 and 0.06 percent, respectively, for males and 0.12 and 0.05 percent, respectively, for females. After a 78-week dosing period, observation of surviving rats continued for up to 22 weeks and observation of the mice continued for 18 weeks. For the chronic rat bioassay, 49 male and 50 female rats were placed on test as high dose controls, and 50 rats of each sex served as low dose controls. For the mice, 50 males and 50 females were placed on test as controls. Accelerated mortality was observed in all dosed groups except the low dose female mice. There was a positive association between mortality and dietary concentration of 5-nitroacenaphthene for both sexes of both species. Early deaths were most apparent among high dose male mice; half of the animals in this group were dead by week 20 and insufficient male mice survived to be at risk from late-developing tumors. Among rats, the incidence of malignant tumors of the ear canal (incidences of ceruminous carcinomas and squamous-cell carcinomas were combined) was significant at each dose level in each sex. Among both dosed groups of female rats, the incidence of clitoral gland carcinoma and the incidence of mammary adenocarcinoma were significant. A significant incidence of alveolar/bronchiolar carcinoma was observed in low dose rat groups of each sex. Among female mice, the incidence of hepatocellular carcinoma was significant at each dose level. The combined incidence of granulosa-cell tumors, luteomas, and tubular-cell adenomas of the ovary was significant in the high dose female mouse group. Under the conditions of this bioassay, 5-nitroacenaphthene was carcinogenic to Fischer 344 rats, causing increased incidences of malignant tumors of the ear canal and lung in both sexes, and of the clitoral gland and mammary gland in females. 5-Nitroacenaphthene was also carcinogenic to female but not male B6C3F1, mice, causing carcinomas of the liver and ovarian tumors.

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PubMed1978

Bioassay of p-Anisidine Hydrochloride for Possible Carcinogenicity (CAS No. 20265-97-8).

A bioassay for possible carcinogenicity of p-anisidine hydrochloride was conducted using Fischer 344 rats and B6C3F1 mice. p-Anisidine hydrochloride was administered in the feed, at either of two concentrations, to groups of 55 male and 55 female animals of each species. Fifty-five animals of each sex and species were placed on test as controls. The high and low dietary concentrations of p-anisidine hydrochloride were, respectively, 0.6 and 0.3 percent for rats and 1.0 and 0.5 percent for mice. The compound was administered in the diet for 103 weeks, followed by an observation period of 2 to 3 weeks for rats and 2 weeks for mice. There were no significant positive associations for either species between the concentration of p-anisidine hydrochloride administered and mortality. In addition, adequate numbers of animals in all groups survived sufficiently long to be at risk from late-developing tumors. In male rats there were significant associations between compound administration and the incidences of both squamous-cell carcinomas of the skin and alveolar/bronchiolar adenomas. None of the Fischer exact comparisons, however, supported these findings. When those males having adenomas NOS or carcinomas NOS of the preputial gland were combined and the resulting incidences statistically analyzed, the only test providing a significant result was the Fisher exact comparison of the low dose to the control. There were no significant positive associations between the administration of p-anisidine hydrochloride and the incidence of any tumor in mice of either sex. Although, under the conditions of this bioassay, there appeared to be an association between chemical administration and the increased incidence of preputial gland tumors in low dose male rats, the evidence was insufficient to establish the carcinogenicity of p-anisidine hydrochloride in Fischer 344 rats. The compound was not carcinogenic in B6C3F1 mice.

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PubMed1978

Bioassay of sulfallate for possible carcinogenicity (CAS No. 95-06-7).

A bioassay for possible carcinogenicity of sulfallate was conducted using Osborne-Mendel rats and B6C3F1 mice. Sulfallate was administered in the feed, at either of two concentrations, to groups of 50 male and 50 female animals of each species. Twenty mice and 50 rats of each sex were placed on test as controls for the bioassay. The time-weighted average high and low dietary concentrations of sulfallate were, respectively, 410 and 250 ppm for male rats, 404 and 250 ppm for female rats, 1,897 and 949 ppm for male mice, and 1,815 and 908 ppm for female mice. After a 78-week period of chemical administration, there was an additional observation period of 25 to 26 weeks for dosed rats, 33 weeks for control rats, and 12 to 13 weeks for dosed and control mice. There were significant positive associations between increased sulfallate concentration and accelerated mortality in both sexes of rats and in female mice. However, adequate numbers of animals in all groups survived sufficiently long to be at risk from late-developing tumors. Statistical analyses of the incidences of mammary adenocarcinomas in female rats, stomach neoplasms (i.e.,combination of papillomas NOS, squamous-cell papillomas, and squamous-cell carcinomas) in male rats, combined alveolar/bronchiolar carcinomas and alveolar/bronchiolar adenomas in male mice, and adenocarcinomas of the mammary gland in female mice revealed a significant positive association between dosage and incidence. These associations were all supported by at least one significant Fisher exact comparison. The incidences of toxic tubular nephropathy observed in male rats and in mice of both sexes increased with the concentration of the compound administered. This nonneoplastic lesion was not observed in control animals. Under the conditions of this bioassay, dietary administration of sulfallate was carcinogenic to Osborne-Mendel rats and to B6C3F1 mice, inducing mammary gland tumors in females of both species, tumors of the forestomach in male rats, and lung tumors in male mice.

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PubMed1978

Bioassay of 2,3,5,6-tetrachloro-4-nitroanisole for possible carcinogenicity (CAS No. 2438-88-2).

A bioassay for possible carcinogenicity of 2,4,5,6-tetrachloro-4-nitroanisole was conducted using Fischer 344 rats and B6C3F1 mice. 2,3,5,6-Tetrachloro-4-nitroanisole was administered in the feed, at either of two concentrations, to groups of male and female animals of each species. The high and low dietary concentrations used in the chronic bioassay were 0.012 and 0.006 percent, respectively, for both species. After a 104-week period of chemical administration, observation of rats continued for up to 3 weeks and observation of mice continued for up to 1 week. For rats 50 animals of each sex were placed on test as controls, while for mice 55 animals of each sex were placed on test as controls. There were no significant positive associations between the dietary concentration of 2,3,5,6-tetrachloro-4-nitroanisole 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. No neoplasms, except for interstitial-cell testicular tumors in males, occurred at statistically significant incidences in dosed rats. Because of the high and variable spontaneous incidence of these lesions in Fischer 344 rats, these tumors were not considered to be associated with the administration of the test compound. Among dosed male mice the combined incidence of leukemia and malignant lymphoma was statistically significant. However, since these lesions were not spontaneously and with high variation in B6C3F1 mice, the lesions were not considered to be associated with the administration of the test compound. No neoplasms were of a statistically significant incidence in dosed female mice. Under the conditions of this bioassay, dietary administration of 2,3,5,6-tetrachloro-4-nitroanisole was not carcinogenic to male or female Fischer 344 rats or B6C3F1 mice of either sex.

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PubMed1978

Bioassay of 2-chloro-p-phenylenediamine sulfate for possible carcinogenicity (CAS No. 61702-44-1).

A bioassay for possible carcinogenicity of 2-chloro-p-phenylenediamine sulfate was conducted using Fischer 344 rats and B6C3F1 mice. 2-Chloro-p-phenylenediamine sulfate 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 0.3 and 0.15 percent for the high and low dose rats, respectively, and 0.6 and 0.3 percent for the high and low dose mice, respectively. Compound administration was for 105 to 107 weeks in rats, 87 weeks in high dose mice, and 104 to 105 weeks in low dose mice. The only groups observed during an untreated period after dosing were the high dose mice, observed for 18 weeks after compound administration ceased. For each species, 20 animals of each sex were placed on test as controls. There were no significant positive associations between the administered dietary concentrations of 2-chloro-p-phenylenediamine sulfate and mortality for rats of either sex or male mice. There was a significant positive association between dosage and mortality for female mice; however, adequate numbers of animals in all groups survived sufficiently long to be at risk from late-developing tumors. There were no statistically significant positive associations between dietary exposure to the compound and the incidences of any tumor in rats. There was an increased incidence of transitional-cell hyperplasia of the renal pelvic epithelium in both male and female rats, and transitional-cell tumors of the urinary bladder were present in three dosed rats. These lesions indicated a possible carcinogenic effect, but are not considered as sufficient evidence of carcinogenicity. In mice, no tumors occurred in statistically significantly higher incidences in the dosed mice than in controls. Under the conditions of this bioassay there was insufficient evidence that dietary administration of 2-chloro-p-phenylenediamine sulfate was carcinogenic to Fischer 344 rats and B6C3F1 mice.

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PubMed1978

Bioassay of 3-amino-4-ethoxyacetanilide for possible carcinogenicity (CAS No. 17026-81-2).

A bioassay of 3-amino-4-ethoxyacetanilide for possible carcinogenicity was conducted using Fischer 344 rats and B6C3F1 mice. 3-Amino-4-ethoxyacetanilide was administered in the feed, at either of two concentrations, to groups of approximately 50 male and 50 female animals of each species. The dietary concentrations used in the chronic bioassay for low and high dose rats were 0.4 and 1.5 percent, respectively. The dietary concentrations used for low and high dose mice were 0.4 and 0.8 percent, respectively. After a 78-week period of chemical administration, observation of rats continued for up to 18 weeks. For each species, 50 animals of each sex were placed on test as controls for low dose groups and approximately 50 animals of each sex were placed on test as controls for high dose groups. In both species, adequate numbers of animals in all groups survived sufficiently long enough to be at risk from late-developing tumors. Among rats the only clearly compound-related lesion was hemosiderosis of the thyroid gland. No neoplastic lesions were statistically significant in dosed rats. Among mice the incidence of follicular-cell carcinomas of the thyroid gland was significant for high dose males. An elevated incidence of thyroid hyperplasia was observed in each dosed group. Hemosiderosis of the thyroid cells were found in nearly all dosed mice, but not in any control mice. Under the conditions of this bioassay, 3-amino-4-ethoxyacetanilide was carcinogenic in male B6C3F1 mice, causing follicular-cell carcinomas of the thyroid gland. Evidence provided by this bioassay was insufficient to establish the carcinogenicity of 3-amino-4-ethoxyacetanilide in female mice or in Fischer 344 rats of either sex.

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PubMed1978

Bioassay of 1-amino-2-methylanthraquinone for possible carcinogenicity (CAS No. 82-28-0).

A bioassay for possible carcinogenicity of technical-grade 1-amino-2-methylanthraquinone was conducted using Fischer 344 rats and B6C3F1 mice. 1-Amino-2-methylanthraquinone was administered in the feed, at either of two concentrations, to groups of 45 to 50 males and females of each species. The high and low time-weighted average concentrations of 1-amino-2-methylanthraquinone were 0.20 and 0.10 percent, respectively, for male and female rats. For mice, two dosage regimens (designated A and B) were used, but the time-weighted average concentrations were the same, 0.06 percent. For each species, 50 animals of each sex were placed on test as controls. The period of compound administration was 78 weeks for rats followed by 26 to 28 additional weeks of observation, and 73 weeks for mice followed by 24 to 25 additional weeks of observation. A statistically significant positive association between compound administration and mortality was established for the male and female dose A mice. Dose A mice did not survive sufficiently long to be at risk from late-developing tumors. Survival in all other groups was adequate. The incidence of hepatocellular carcinomas was statistically significant among dosed rats of both sexes. Kidney neoplasms (the combined incidence of tubular-celladenomas, tubular-cell adenocarcinomas, and adenocarcinomas NOS) were significantly increased among dosed male rats. Administration of the compound was associated with a significant increase in the combined incidence of hepatocellular carcinomas and neoplastic liver nodules in female mice. No other neoplasms occurred in statistically significant positive incidences in male or female mice. 1-Amino-2-methylanthraquinone demonstrated nephrotoxic properties in mice of both sexes. Under the conditions of this bioassay, 1-amino-2-methylanthraquinone was carcinogenic in Fischer 344 rats, inducing hepatocellular carcinomas in rats of both sexes, and kidney tumors in male rats. The compound was carcinogenic in female B6C3F1 mice, producing an increased combined incidence of hepatocellular carcinomas and neoplastic nodules.

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PubMed1978

Bioassay of iodoform for possible carcinogenicity (CAS No. 75-47-8).

A bioassay for possible carcinogenicity of technical-grade iodoform was conducted using Osborne-Mendel rats and B6C3F1 mice. Iodoform in corn oil was administered by gavage, at either of two dosages, to groups of 50 male and 50 female animals of each species. Administration of the chemical occurred 5 days per week, for a period of 78 weeks, followed by an observation period of 34 weeks for rats and 13 or 14 weeks for mice. The high and low time-weighted average dosages of iodoform were, respectively, 142 and 71 mg/kg/day for male rats, 55 and 27 mg/kg/day for female rats, and 93 and 47 mg/kg/day for male and female mice. For each species, 20 animals of each sex were placed on test as vehicle controls. These animals were gavaged with pure corn oil at the same rate as the high dose group of the same sex. Twenty animals of each sex were placed on test as untreated controls for each species. These animals were not intubated. A significant positive association between dosage and mortality was observed in male rats but not in female rats or in mice of either sex. Adequate numbers of animals in all groups survived sufficiently long to be at risk from late-developing tumors. No statistical significance could be attributed to the incidences of any neoplasms in rats or mice of either sex when compared to their respective controls. Under the conditions of this bioassay, no convincing evidence was provided for the carcinogenicity of iodoform in Osborne-Mendel rats or B6C3F1 mice.

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PubMed1978

Bioassay of 4-nitroanthranilic acid for possible carcinogenicity (CAS No. 619-17-0).

A bioassay of 4-nitroanthranilic acid for possible carcinogenicity was conducted using Fischer 344 rats and B6C3F1 mice. 4-Nitroanthranilic acid 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 time-weighted average concentrations used for the chronic study were, respectively, 1.5 and 0.46 percent for rats and 1.0 and 0.46 percent for mice. After a 78-week period of chemical administration, the rats were observed for an additional period of up to 32 weeks and the mice for an additional period of up to 17 weeks. For rats 50 animals of each sex were placed on test as low dose controls and 25 animals of each sex were placed on test as high dose controls. For mice 50 animals of each sex were placed on test as controls for each dose group. No statistically significant increases in tumor incidence were observed among rats or mice receiving diets containing 4-nitroanthranilic acid. Under the conditions of this bioassay evidence was not provided for the carcinogenicity of 4-nitroanthranilic acid in Fischer 344 rats or B6C3F1 mice.

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PubMed1978

13-week subchronic toxicity studies of direct blue 6, direct black 38, and direct brown 95 dyes.

Thirteen-week subchronic toxicity studies of direct blue 6, direct black 38, and direct brown 95 dyes were conducted by administering the test chemicals in feed to Fischer 344 rats and B6C3F1 mice. Groups of 10 rats and 10 mice of each sex were administered one of the three dyes at one of five concentrations for 13 weeks and then necropsied, beginning the second day after the end of the dosing period. The concentrations used for the rats were 190, 375, 750, 1,500, and 3,000 ppm. The concentrations used for the mice were 750, 1,500, 3,000, 6,000, and 12,500 ppm, except for the female mice administered direct brown 95 dye, which were given concentrations of 375, 750, 1,500, 3,000, and 6,000 ppm. Matched controls consisted of groups of 10 untreated rats and 10 untreated mice of each sex. Mean body weights of the male and female rats administered the two or three highest doses of any one of the test dyes were lower than mean body weights of the corresponding controls, and the depressions in mean body weight were dose related. Mean body weights of the male and female mice administered the highest dose of any one of the test dyes were slightly lower than mean body weights of the corresponding controls; mean body weights of mice administered lower doses were generally unaffected. All male and female rats administered 3,000 ppm of any one of the dyes or 1,500 ppm of direct brown 95 dye died before the end of the studies. One male administered 1,500 ppm direct blue 6 dye, six males administered 1,500 ppm direct black 38 dye, and two males administered 750 ppm direct brown 95 dye also died by the end of the studies. No deaths occurred in any other dosed group or in any control group of rats. All male and female mice administered the test dyes survived to the end of the studies, except for one male whose death was attributed to bacterial infection. Benzidine and monoacetyl benzidine were detected in the urine of male and female rats and mice administered the test dyes, but neither compound was detected in the urine of control rats and mice. Determinations of methemoglobin in control and dosed rats showed no differences. In rats, neoplastic lesions occurred only in dosed groups and consisted of hepatocellular carcinomas and neoplastic nodules of the liver. The incidences of hepatocellular carcinomas in female rats administered 3,000 ppm direct blue 6 dye (4/9) and male rats administered 1,500 ppm direct black 38 dye (4/9) were significant (P=0.033) when related to the incidences of the tumors in the corresponding controls (0/10); hepatocellular carcinomas were also observed in two male rats administered 1,500 ppm direct blue 6 dye and in one female rat administered 1,500 ppm direct brown 95 dye. No control rats from any of the three studies developed hepatocellular carcinomas. When incidences of neoplastic nodules were combined with those of hepatocellular carcinomas, the significance increased to P<0.001 for male rats administered 1,500 ppm direct blue 6 dye, P=0.001 for females administered 3,000 ppm direct blue 6 dye, P<0. 001 for males administered 1, 500 ppm direct black 38 dye, and P=0.007 for females administered 1,500 ppm direct brown 95 dye. No controls developed neoplastic nodules. Female rats administered direct black 38 dye developed no hepatocellular carcinomas, but had an incidence of neoplastic nodules of 5/10, with a significance of P=0.016. Male rats administered direct brown 95 dye developed neither hepatocellular carcinomas nor neoplastic nodules, but as indicated below, had significant incidences of preneoplastic lesions. The failure of groups of rats administered 3,000 ppm dye to develop tumors when other groups administered 1,500 ppm did develop tumors may be due to earlier deaths at the higher dose. Preneoplastic hepatic lesions (basophilic foci) occurred only in dosed rats and did not occur in the controls. The incidences of the basophilic foci were significant (P<0.033) in male (4/9) and female (7/9) rats administered 3,000 ppm direct blue 6 dye and in male rats (7/8) administered 1, 500 ppm direct brown 95 dye. Basophilic foci also occurred, at lower incidences, in males (1/10) administered 1,500 ppm direct blue 6 dye, in males (3/9) administered 1,500 ppm direct black 38 dye, in females (1/8) administered 3,000 ppm direct black 38 dye, in males administered 750 ppm (3/10) or 3,000 ppm (2/9) direct brown 95 dye, and in females administered 1,500 ppm (3/8) or 3,000 ppm (3/8) direct brown 95 dye. When incidences of foci of cellular alteration, a possible preneoplastic lesion, were added to those of basophilic foci, significance occurred in additional dosed groups. In mice, no neoplastic lesions occurred in the liver or other tissues of groups administered the different dyes. However, three mice administered 12,500 ppm direct black 38 dye and one mouse administered 12,500 ppm direct brown 95 dye had foci of cellular alteration, in which the cells were basophilic when compared with surrounding normal cells. It is concluded that under the conditions of these 13-week subchronic toxicity studies, direct blue 6 and direct black 38 dyes were carcinogenic in male and female Fischer 344 rats and direct brown 95 was carcinogenic in female rats; all three dyes induced hepatocellular carcinomas and neoplastic nodules in the liver. The test dyes were not carcinogenic for B6C3F1 mice in the 13-week subchronic toxicity studies.

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PubMed1978

Bioassay of 5-nitro-o-toluidine for possible carcinogenicity (CAS No. 99-55-8).

A bioassay of 5-nitro-o-toluidine for possible carcinogenicity was conducted using Fischer 344 rats and B6C3F1 mice. 5-Nitro-o-toluidine was administered in the feed, at either of two concentrations, to groups of 50 male and 50 female animals of each species. The time-weighted average high and low dietary concentrations of 5-nitro-o-toluidine were, respectively, 0.01 and 0.005 percent for rats, and 0.23 and 0.12 percent for mice. After a 78-week period of compound administration, observation of the rats continued for an additional 30 to 31 weeks and observation of the mice continued for up to an additional 20 weeks. For each species, 50 animals of each sex were placed on test as controls and fed only the basal diet. There were no significant positive associations between the concentration of 5-nitro-o-toluidine administered and mortality in rats or mice of either sex, and adequate numbers of animals in all groups survived sufficiently long to be at risk from late-developing tumors. No unusual tumors were observed in rats of either sex and no convincing statistical evidence was provided for a significant positive association between compound administration and the incidence of any neoplasm in rats. Among mice there was a statistically significant positive association between administration of the chemical and the incidences of hepatocellular carcinomas in both males and females. The combined incidence of hemangiomas and hemangiosarcomas in male mice and the incidence of hemangiosarcomas in female mice were not statistically significant in relation to their respective control groups. However, they were considered to be associated with compound administration since they rarely occur in untreated B6C3F1 mice. Under the conditions of this bioassay 5-nitro-o-toluidine was carcinogenic in B6C3F1 mice, causing hepatocellular carcinomas in both sexes, an increase in the combined incidence of hemangiomas and hemangiosarcomas in male mice, and an increased incidence of hemangiosarcomas in female mice. The compound was not carcinogenic in Fischer 344 rats.

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PubMed1978

Bioassay of trichlorofluoromethane for possible carcinogenicity (CAS No. 75-69-4).

The bioassay of technical-grade trichlorofluoromethane for possible carcinogenicity was conducted using Osborne-Mendel rats and B6C3F1 mice. Trichlorofluoromethane in corn oil was administered by gavage, at either of two dosages, to groups of 50 male and 50 female animals of each species, 5 days per week, over a period of 78 weeks. The time-weighted average high and low dosages of trichlorofluoromethane in the chronic bioassay were, respectively, 977 and 488 mg/kg/day for male rats, 1,077 and 538 mg/kg/day for female rats, and 3,925 and 1,962 mg/kg/day for mice of both sexes. After a 78-week dosing period, rats were observed for an additional period of up to 33 weeks and mice were observed for an additional period of up to 13 weeks. For each species, 20 animals of each sex were placed on test as vehicle controls. These animals were gavaged with corn oil at the same time that dosed animals were gavaged with trichlorofluoromethane. Twenty animals of each sex were placed on test as untreated controls for each species. These animals were not gavaged. A high rate of early deaths occurred among male and female rats in this bioassay. An insufficient number of rats of either sex survived long enough to be at risk from late-developing tumors. Survival of mice was adequate for meaningful statistical analysis of late-developing tumors. Results of a time-adjusted statistical analysis of tumor incidence in rats indicated no significant positive associations between administration of trichlorofluoromethane and tumor incidence. No groups of male or female mice dosed with trichlorofluoromethane had significantly increased tumor incidences relative to their respective control groups. The results of the bioassay of trichlorofluoromethane in Osborne-Mendel rats for possible carcinogenicity are not conclusive because inadequate numbers of rats survived sufficiently long enough to be at risk from late-developing tumors. Under the conditions of this bioassay, trichlorofluoromethane was not carcinogenic to male or female B6C3F1 mice.

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PubMed1978

Bioassay of m-Cresidine for possible carcinogenicity (CAS No. 102-50-1).

A bioassay of technical-grade m-cresidine for possible carcinogenicity was conducted using Fischer 344 rats and B6C3F1 mice. m-Cresidine in corn oil was administered by gavage five days a weeks at either of two dosages, to groups of 50 male and 49 or 50 female animals of each species. The dosages used in the chronic bioassay for low and high dose rats were 0.08 and 0.16 gm/kg/day, respectively. The time-weighted average dosages used for low and high dose mice were 0.06 and 0.11 gm/kg/day, respectively. After a 77-week dosing period observation of rats continued for an additional 32 to 33 weeks. After a 53-week dosing period, observation of mice continued for an additional observation period of up to 41 weeks. For each species, 50 animals of each sex were placed on test as untreated controls and 25 animals of each sex were placed on test as vehicle controls. The urinary bladder and the kidney were the target organs of m-cresidine toxicity in male and female rats. Papillary transitional-cell carcinomas of the urinary bladder occurred in 0/45 low dose males, 5/44 (11 percent) high dose males, 1/46 (2 percent) low dose females, and 2/44 (5 percent) high dose females but did not occur in any untreated control or vehicle control rats. Although the incidences in each dosed rat group were not statistically significant when compared to vehicle controls, comparison with historical controls indicates that these bladder carcinomas are rare and are, therefore, considered to be compound-related in both sexes. Among mice, dose-related nonneoplastic lesions were observed at higher incidences for males than females in the kidneys, spleen and thymus. Dose-related toxic effects were also observed in testes of male mice. No neoplasms occurred in male mice at statistically significant incidences. Under the conditions of this bioassay, m-cresidine was carcinogenic to Fischer 344 rats, causing papillary transitional-cell carcinomas of the urinary bladder in both sexes. No convincing evidence was provided for carcinogenicity in female B6C3F1 mice. Poor survival of male B6C3F1 mice receiving m-cresidine precluded evaluation of the possible carcinogenicity of the compound in these animals.

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PubMed1978

Bioassay of 1-phenyl-2-thiourea for possible carcinogenicity.

A bioassay of 1-phenyl-2-thiourea for possible carcinogenicity was conducted using Fischer 344 rats and B6C3F1 mice. 1-Phenyl-2-thiourea 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 1-phenyl-2-thiourea utilized in the chronic bioassay were, respectively, 120 and 60 ppm for rats and 300 and 150 ppm for mice. Twenty animals of each species and sex were placed on test as controls. A 78-week period of chemical administration was followed by an additional observation period of 26 weeks for rats and 13 weeks for mice. Adequate numbers of animals in all groups survived sufficiently long to be at risk from late-developing tumors. Distinct dose-related depression of mean body weight gain was observed in male and female mice when compared with their controls, but growth retardation was not observed in any dosed rat group. In addition, since no significant accelerated mortality or other toxic effects were associated with the dietary administration of 1- phenyl-2-thiourea to rats, it is possible that the compound was not administered to these animals at the maximum tolerated concentrations. There were no tumors in either sex of rats or mice for which a significant positive association could be established between chemical administration and tumor incidence. Under the conditions of this bioassay, 1-phenyl-2-thiourea was not carcinogenic to Fischer 344 rats or B6C3F1 mice.

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PubMed1978

Bioassay of mexacarbate for possible carcinogenicity.

A bioassay of technical-grade mexacarbate for possible carcinogenicity was conducted using Osborne-Mendel rats and B6C3F1 mice. Mexacarbate was administered in the feed, at either of two concentrations, to groups of 50 male and 50 female animals of each species. The time-weighted average high and low dietary concentrations of mexacarbate were 418 and 209 ppm for male rats, 678 and 339 ppm for female rats, 654 and 327 ppm for male mice and 135 and 68 ppm for female mice. After a 78-week period of chemical administration, observation of rats continued for an additional 33 to 34 weeks and observation of mice continued for 14 to 15 additional weeks. For each species, 20 animals of each sex were placed on test as controls. All groups except the male control mice survived sufficiently long to be at risk from late-appearing tumors. Because of poor survival of the male control mice, a pooled control group was used for statistical analysis of tumor incidence in male mice. The possibility that female mice in this study did not receive maximum tolerated dosages of mexacarbate should be considered. Administration of mexacarbate had no significant effect on survival or body weights of female mice. No neoplasms occurred in statistically significant increased incidences when dosed rats were compared to controls. Among male mice surviving at least 56 weeks, significant associations with dietary concentrations were indicated by the Cochran-Armitage test for hepatocellular carcinomas, for subcutaneous fibrosarcomas and for fibromas of the skin. In none of these cases, however, were these results supported by significant Fisher exact tests. Under the conditions of this bioassay, sufficient evidence was not obtained for the carcinogenicity of mexacarbate for Osborne-Mendel rats or B6C3F1 mice.

Journal Article↗

PubMed1978

Bioassay of 3-chloro-p-toluidine for possible carcinogenicity.

A bioassay for the possible carcinogenicity of 3-chloro-p-toluidine was conducted using Fischer 344 rats and B6C3F1 mice. 3-Chloro-p-toluidine 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 time-weighted average dietary concentrations of 3-chloro-p-toluidine administered to rats of both sexes were 3,269 and 1,635 ppm for the high and low dose groups, respectively. The high and low dietary concentrations of 3-chloro-p-toluidine administered to mice were, respectively, 1,200 and 600 ppm for males and 600 and 300 ppm for females. The compound was administered in the diet for 78 weeks, followed by an observation period of 24 weeks for high dose male rats, 25 weeks for all other dosed rats, and 12 weeks for mice. There were no significant positive associations between the concentrations of 3-chloro-p-toluidine administered and mortality in either species. Adequate numbers of animals in all groups survived sufficiently long to be at risk from late-developing tumors. Mean body weight depression, relative to controls, was observed in high dose rats and mice of both sexes, indicating that the concentrations administered to these animals may have approximated the maximum tolerated dosages. The unusual incidences of nonneoplastic spleen and liver lesions in high dose rats supports this assumption. Under the conditions of this bioassay there was no convincing evidence for the carcinogenicity of 3-chloro-p-toluidine in Fischer 344 rats or B6C3F1 mice.

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