Biomedical subjects

National Toxicology Program

Publications and source records attributed to National Toxicology Program.

At least 577 records · Page 32Linked to original sources

PubMed1979

Bioassay of 2-nitro-p-phenylenediamine for possible carcinogenicity.

A bioassay for the possible carcinogenicity of 2-nitro-p-phenylenediamine was conducted using Fischer 344 rats and B6C3F1 mice. 2-Nitro-p-phenylenediamine 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-nitro-p-phenylenediamine were, respectively, 1,100 and 550 ppm for male rats, 2,200 and 1,100 ppm for female rats, and 4,400 and 2,200 ppm for mice of both sexes. The compound was administered in the diet for 78 weeks, followed by an observation period of 27 weeks for rats and 12 to 13 weeks for mice. There were no significant positive associations between the dietary concentrations of 2-nitro-p-phenylenediamine administered and mortality in rats and mice of either sex. 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 dosed rats and mice of both sexes, indicating that the concentrations administered to these animals may have approximated the maximum tolerated dosages. When the female mice in each group, having hepatocellular carcinoma or hepatocellular adenoma, were combined and the resulting incidences statistically analyzed, there was a significant positive association between concentration administered and the incidence of these tumors. This finding was supported by a significant high dose to control Fisher exact comparison. No tumors occurred in statistically significant increased incidences when dosed male or female rats or male mice were compared to their respective controls. Under the conditions of this bioassay, dietary administration of 2-nitro-p-phenylenediamine was carcinogenic to female B6C3F1 mice, causing an increased incidence of hepatocellular neoplasms, primarily hepatocellular adenomas. There was no convincing evidence for the carcinogenicity of the compound in Fischer 344 rats or in male B6C3F1 mice.

Journal Article↗

PubMed1979

Bioassay of N-(1-naphthyl)ethylenediamine dihydrochloride for possible carcinogenicity.

A bioassay for the possible carcinogenicity of N-(1-naphthyl)ethylenediamine dihydrochloride was conducted using Fischer 344 rats and B6C3F1 mice. N-(1-Naphthyl)ethylenediamine dihydrochloride was administered in the feed, at either of two concentrations, to groups of 50 male and 50 female animals of each species. Twenty-five rats of each sex and 50 mice of each sex were placed on test as controls. The high and low dietary concentrations of N-(1-naphthyl)ethylenediamine dihydrochloride administered to rats and male mice were 0.1 and 0.05 percent, respectively. The high and low time-weighted average concentrations administered to female mice were, respectively, 0.3 and 0.2 percent. The compound was administered in the diet for 104 weeks, followed by an observation period of 4 weeks for high dose rats, 3 weeks for low dose rats, low dose female mice, and high dose female mice, and 1 week for high dose male mice. There were no significant positive associations between the concentrations of N-(1-naphthyl)ethylenediamine dihydrochloride administered and mortality in rats of either sex or in male mice. There was a significant positive association between concentration and mortality in female mice. In all groups, except for high dose females, adequate numbers of animals survived sufficiently long to be at risk from late-developing tumors. Mean body weight depression, in relation to controls, was apparent for both sexes of rats and mice, indicating that higher concentrations of the test chemical would not have been tolerated by these animals. In rats or mice of either sex, there were no statistically significant positive associations between the concentration of N-(1-naphthyl)ethylenediamine dihydrochloride and tumor incidence. Under the conditions of this bioassay, dietary administration of N-(1-naphthyl)ethylenediamine dihydrochloride was not carcinogenic in Fischer 344 rats or B6C3F1 mice.

Journal Article↗

PubMed1979

Bioassay of tetraethylthiuram disulfide for possible carcinogenicity.

A bioassay of technical-grade tetraethylthiuram disulfide 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 tetraethylthiuram disulfide in the diet at one of two doses, either 300 or 600 ppm, for 107 weeks. Groups of 50 mice of each sex were administered the test chemical at one of two doses, either 500 or 2,000 ppm for the males and either 100 or 500 ppm for the females, for 108 weeks. Matched controls consisted of 20 untreated rats and 20 untreated mice of each sex. All surviving animals were killed at the ends of the periods of administration of the test chemical. Mean body weights of the dosed rats and mice of each sex were lower than those of corresponding controls and were dose related throughout most of the bioassay. Mortality was not significantly affected by administration of the test chemical to either the rats of the mice, except for the female rats, in which the mortality was higher in the control group than in the dosed groups; however, the survival at the end of the bioassay was 65% or greater in all dosed and control groups of rats and mice of either sex, and sufficient numbers of animals were at risk in each group 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 dosed groups than in corresponding control groups. It is concluded that under the conditions of this bioassay, tetraethylthiuram disulfide was not carcinogenic for F344 rats or B6C3F1 mice of either sex.

Journal Article↗

PubMed1979

Bioassay of 4-chloro-o-toluidine hydrochloride for possible carcinogenicity.

A bioassay of 4-chloro-o-toluidine hydrochloride 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 4-chloro-o-toluidine in the diet at one of two doses, either 1,250 or 5,000 ppm, for 107 weeks. Groups of 50 mice of each sex were administered the test chemical in the diet at one of two doses, either 3,750 or 15,000 ppm for the males and either 1,250 or 5,000 ppm for females, for 99 weeks, except for the high dose females (92 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 high-dose rats and the low- and high-dose mice of each sex were lower than those of corresponding controls, and those of the mice were dose related. Mortality was not significantly affected by administration of the test chemical to rats of either sex and survival was 75% or greater at the end of the study in dosed and control groups. Sufficient numbers of rats were at risk for the development of late-appearing tumors. In mice, mortality was dose related for each sex. In rats no tumors occurred at incidences which could clearly be related to administration of the test chemical. In both male and female mice, hemangiosarcomas occurred at incidences that were dose related (P</= 0.001), and in direct comparisons the incidences in the high-dose males and the low-and high-dose females were significantly higher (P<0.001) than those in the corresponding controls (males: controls 0/20; low-dose 3/50; high-dose 37/50; females: controls 0/18; low-dose 40/49, high-dose 39/50). The combined incidences of hemangiosarcomas and hemangiomas also were dose related and were significantly higher in the dosed groups of male and female mice than in the corresponding controls. There was a high incidence of hemosiderin deposit in the renal tubular epithelium, particularly in mice with hemangiosarcomas. It is concluded that under the conditions of this bioassay, 4-chloro-o-toluidine hydrochloride was not carcinogenic for F344 rats but was carcinogenic for B6C3F1 mice, including hemangiosarcomas and hemangiomas in both males and females. Levels of Evidence of Carcinogenicity: Male Rats: Negative Female Rats: Negative Male Mice: Positive Female Mice: Positive Synonym: 2-amino-4-chlorotoluene hydrochloride

Journal Article↗

PubMed1979

Bioassay of N-nitrosodiphenylamine for possible carcinogenicity.

A bioassay of N-nitrosodiphenylamine 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 N-nitrosodiphenylamine at one of two doses, either 1,000 or 4,000 ppm, for 100 weeks. Matched controls consisted of 20 untreated rats of each sex. All surviving rats were killed at the end of administration of the test chemical. Groups of 50 male mice were administered N-nitrosodiphenylamine at one of two doses, either 10,000 or 20,000 ppm, for 101 weeks. Groups of 50 female mice were administered the test chemical at one of two doses, initially 5,000 or 10,000 ppm, for 38 weeks. Because of excessive depression in the amount of mean body weight gained in the dosed groups, the doses for the females were then reduced to 1,000 and 4,000 ppm, respectively, and administration at the lowered doses was continued for 60 weeks. The time-weighted average doses for the female mice were either 2,315 or 5,741 ppm. Matched controls consisted of 20 untreated mice of each sex. All surviving mice were killed at the end of administration of the test chemical. Mean body weights of dosed rats and mice of each sex were lower than those of corresponding controls, and were dose related throughout the bioassay, except for those of female rats during the first part of the bioassay. Mortality was dose related in the female rats, but was not affected when the test chemical was administered to the male rats or the male or female mice. Survival at the end of the bioassay was 64% or greater in the dosed and control groups of rats and mice of each sex, and sufficient numbers of animals were at risk in all groups for the development of late-appearing tumors. Transitional-cell carcinomas of the urinary bladder occurred at incidences that were dose related (P</= 0.001) in both male and female rats, and in direct comparisons the incidences of these tumors in the high-dose groups of each sex were significantly higher (P</= 0.001) than those in the corresponding controls (males: controls 0/19; low-dose 0/46; high-dose 16/45; females: controls 0/18; low-dose 0/48; high-dose 40/49). The possible mechanism by which these tumors were induced, such as calculi formation in the bladder or nitrosation of amines present in feed to a carcinogenic nitrosoamine, is unknown. Fibromas of the integumentary system occurred in male rats at incidences that were dose related (P=0.003), although in direct comparisons the incidences of these tumors in the individual dosed groups were not significantly higher than those in the control group (controls 1/20, or 5%; low-dose 1/50, or 2%; high-dose 10/50, or 20%). The incidence of fibromas of the integumentary system in historical-control male F344 rats at this laboratory is 6/285, or 2%. These results suggest an association of the fibromas in the male rats with the administration of the test chemical. No tumors occurred in the mice of either sex at incidences that were significantly higher in the dosed groups than in the corresponding control groups. The only changes related to compound administration were chronic inflammatory lesions in the urinary bladders of dosed mice. It is concluded that under the conditions of this bioassay, N-nitrosodiphenylamine was carcinogenic for both sexes of F344 rats, including transitional-cell carcinomas of the urinary bladder, but was not carcinogenic for B6C3F1 mice of either sex.

Journal Article↗

PubMed1979

Bioassay of calcium cyanamide for possible carcinogenicity.

A bioassay of formulated calcium cyanamide 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 a commercial formulation containing 63% calcium cyanamide in the diet at one of two doses, either 100 or 200 ppm for the males and either 100 or 400 ppm for the females, for 107 weeks. Groups of 50 mice of each sex were administered the test chemical at one of two doses, either 500 or 2,000 ppm, for 100 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 only slightly lower than those of corresponding controls, except for the low-dose female mice, whose mean body weights were unaffected by the test chemical. Mortality was dose related only in male mice. Survival was 70% or greater in all dosed and control groups of each species and sex at the end of the bioassay, and sufficient numbers of animals were at risk in all groups for the development of late-appearing tumors. Both rats and mice may have been able to tolerate higher doses. No tumors occurred in the dosed rats of either sex at incidences that could clearly be related to administration of the calcium cyanamide. However, in the subchronic studies performed with the rats, calcium cyanamide was found to cause diffuse follicular hyperplasia of the thyroid, with periglandular fibrosis and prominent periglandular vascularity. In male mice, hemangiosarcomas were dose related in the males (P=0.006); however, in direct comparisons, incidences in the individual dosed groups were not significantly higher than those in the control group (controls 1/20 (5%); low-dose 2/50 (4%); high-dose 10/50 (20%)). The incidence of these tumors in historical-control male B6C3F1 mice was (13/323 (4%)), and the highest incidence observed was 2/19 (10%). In female mice, lymphomas or leukemias were dose related (P=0.009), and in a direct comparison the incidence of these tumors in the high-dose group was significantly higher (P=0.006) than that in the control group (controls 1/20 (5%); low-dose 11/46 (24%); high-dose 18/50 (36%)); however, the incidence of the lymphomas or leukemias in historical-control female B6C3F1 mice was 67/324 (21%), suggesting that the incidence of these tumors in the matched-control group of the present bioassay may have been abnormally low. Thus, neither the incidences of hemangiosarcomas of the circulatory system in male mice nor of lymphomas or leukemias in the female mice can clearly be related to administration of the test chemical. It is concluded that under the conditions of this bioassay, the test formulation of calcium cyanamide was not carcinogenic for F344 rats or B6C3F1 mice of either sex.

Journal Article↗

PubMed1979

Bioassay of 2,4-diaminotoluene for possible carcinogenicity.

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</= 0.020) than in the control group (controls 0/20, low-dose 15/30, high-dose 19/50). In the mice, hepatocellular carcinomas occurred in the females at incidences that were dose related (P=0.002) and in direct comparisons were higher in dosed groups (P</= 0.007) than in the control group (controls 0/19, low-dose 13/47, high-dose 18/46). In addition, lymphomas occurred at a significant incidence (P<0.001) in the low-dose female mice (controls 2/19, low-dose 29/47, high-dose 11/46). No tumors occurred at significantly increased incidences in the dosed male mice. Under the conditions of this bioassay, 2,4-diaminotoluene was carcinogenic for F344 rats, inducing hepatocellular carcinomas or neoplastic nodules in both males and females and carcinomas or adenomas of the mammary gland in females. The test chemical was also carcinogenic for female B6C3F1 mice, inducing hepatocellular carcinomas. The incidence of lymphomas in the female mice suggested that these tumors may also have been related to administration of the test chemical.

Journal Article↗

PubMed1979

Bioassay of phthalamide for possible carcinogenicity.

A bioassay of phthalamide 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 phthalamide at one of two doses, either 15,000 or 30,000 ppm for the males and either 5,000 or 10,000 ppm for the females, for 106 weeks. Groups of 50 mice of each sex were administered the test chemical at one of two doses, 25,000 or 50,000 ppm for the males, and at one of three doses, 6,200, 12,500, or 25,000 ppm, for the females, for 103 or 105 weeks. Matched controls consisted of 20 untreated rats of each sex, 20 untreated male mice, and two groups of 20 untreated female mice. All surviving rats and mice were killed at the end of administration of the test chemical. Mean body weights of the dosed groups of rats and mice were either slightly lower than those of corresponding control groups or essentially unaffected by administration of the test chemical. Also, survival was unaffected in the rats and mice except for early deaths in the high- and mid-dose groups of female mice. Survival was 66% or greater at the end of the bioassay in all dosed groups and control groups of each species and sex except for the high-dose group of female mice (36%). With the exception of the high-dose female mice, sufficient numbers of animals were at risk in all groups 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 corresponding control groups. However, phthalamide produced toxic lesions in the livers of male and female rats and the urinary systems of female rats and mice. The presence of nonneoplastic lesions suggests that the MTD may have been used or exceeded. It is concluded that under the conditions of this bioassay, phthalamide was not carcinogenic for F344 rats or B6C3F1 mice of either sex.

Journal Article↗

PubMed1979

Bioassay of 2,4,5-trimethylaniline for possible carcinogenicity.

A bioassay of 2,4,5-trimethylaniline 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 2,4,5-trimethylaniline at one of two doses, either 200 or 800 ppm for the rats and either 50 or 100 ppm for the mice, for 101 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 male and female rats were generally lower than those of corresponding controls; mean body weights of the dosed mice were only slightly lower in the males than in the corresponding controls and were unaffected or affected irregularly in the females. Survival was not affected significantly when the rats or mice were administered the test chemical and was 70% or greater in all dosed or control groups. Sufficient numbers of animals were at risk for late-appearing tumors. In the rats, hepatocellular carcinomas or neoplastic nodules occurred at incidences that were dose related in both males and females (P</= 0.001), and in direct comparisons the incidences were slightly higher in the high-dose males, high-dose females, and low-dose females (P</= 0.004) than in corresponding controls (males: controls 1/19; low-dose 6/50; high-dose 20/50; females: controls 0/20; low-dose 12/49, high-dose 27/50). In addition, alveolar/bronchiolar carcinomas or adenomas occurred in the female rats at incidences that were dose related (P=0.003), and in a direct comparison the incidence was significantly higher in the high-dose group (P=0.017) than in the corresponding control group (controls 0/20; low-dose 3/43; high-dose 11/50). In the female mice, hepatocellular carcinomas occurred at incidences that were dose related (P</= 0.001), and in direct comparisons the incidences were significantly higher (P</= 0.001) in the low- and high-dose animals than in the corresponding controls (controls 0/20, low-dose 18/49, high-dose 40/50). Because historical records of this laboratory for control B6C3F1 male mice show a relatively high incidence of hepatocellular carcinomas, an increased incidence of these tumors in 2,4,5-trimethylaniline dosed male mice as compared with matched controls could not be clearly associated with administration of the test compound. It is concluded that under the conditions of this bioassay, 2,4,5-trimethylaniline was carcinogenic for male and female F344 rats and female B6C3F1 mice, inducing hepatocellular carcinomas or neoplastic nodules in the rats of each sex, alveolar/bronchiolar carcinomas in the female rats, and hepatocellular carcinomas in female mice.

Journal Article↗

PubMed1979

Bioassay of phthalic anhydride for possible carcinogenicity.

A bioassay of phthalic anhydride 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 the test chemical at one of two doses, initially either 25,000 or 50,000 ppm, for 32 weeks. Because of excessive depressions in the amount of body weight gained in the dosed groups, the doses for the males were then reduced to 12,500 and 25,000 ppm, respectively, and the doses for the females were reduced to 6,250 and 12,500 ppm. Administration of the test chemical at the lowered doses was continued for 72 weeks. The time-weighted average doses for the males were either 16,346 or 32,692 ppm, and those for the females were either 12,019 or 24,038 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 the high-dose male rats and of the low- and high-dose mice of each sex were lower than those of the corresponding controls; mean body weights of the low-dose male rats and of both the low- and high-dose female rats were essentially unaffected by administration of the test chemical. Depressions in the amount of body weight gained in the male and female mice were dose related throughout the bioassay. Survivals of the rats and mice were not affected by administration of the test chemical. No tumors occurred in the rats or mice of either sex at incidences that could be clearly related to the administration of the test chemical. It is concluded that under the conditions of this bioassay, phthalic anhydride was not carcinogenic for F344 rats or B6C3F1 mice of either sex.

Journal Article↗

PubMed1979

Bioassay of (2-chloroethyl)trimethylammonium chloride (CCC) for possible carcinogenicity.

A bioassay of (2-chloroethyl)trimethylammonium chloride 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 either 1,500 or 3,000 ppm of the compound for 108 weeks, and 50 mice of each sex were administered 500 or 2,000 ppm for 102 weeks. Matched controls consisted of 20 untreated 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 dosed rats and mice were lower than those of corresponding controls for part or all of the bioassay, except for the dosed male mice, whose mean body weights were essentially the same as those of the corresponding controls. Survival was not affected significantly in any of the dosed groups of rats or mice and was at least 64% in every dosed or control group of each species at the end of the bioassay. Sufficient numbers of dosed and control rats and mice of each sex were at risk for the development of late-appearing tumors. Since there was virtually no decrease in mean body weight in dosed male mice and only a slight decrease in female mice, and since there were no other toxic signs and no dose-related mortality, the animals may have been able to tolerate higher doses. No tumors occurred in the rats or mice of either sex at incidences that could be associated with administration of the test chemical. It is concluded that under the conditions of this bioassay, (2-chloroethyl)trimethylammonium chloride was not carcinogenic for F344 rats or B6C3F1 mice of either sex.

Journal Article↗

PubMed1979

Bioassay of methyl parathion for possible carcinogenicity.

A bioassay of methyl parathion 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 methyl parathion at one of two doses, initially either 62.5 or 125 ppm. These doses were maintained for 102 weeks for the females; however, due to decreased mean body weight gain in the dosed males, the low and high doses for the males were reduced after 37 weeks to 20 and 50 ppm, respectively, and administration at the lowered doses was continued for 65 weeks. The time-weighted average doses for the male mice were 35 and 77 ppm, respectively, for the low- and high-dose groups. Matched controls consisted of 20 untreated mice of each sex. All surviving mice were killed at the end of administration of the test chemical. Mean body weights of the dosed male and female rats and mice were lower than those of the corresponding controls throughout the bioassay and were dose related. Survival was unaffected in both species except for an increase in mortality in the high-dose female rats, in which 46% of the animals were alive at the end of the study. No tumors occurred in any of the groups of 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, methyl parathion was not carcinogenic for F344 rats or B6C3F1 mice of either sex.

Journal Article↗

PubMed1979

Bioassay of p,p'-ethyl-DDD for possible carcinogenicity.

A bioassay of p,p'-ethyl-DDD 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 p,p'-ethyl-DDD at one of two doses, either 3,500 or 7,000 ppm, for 105 weeks. Matched controls consisted of 20 untreated rats of each sex. All surviving rats were killed at the end of administration of the test chemical. Groups of 50 male mice were administered p,p'-ethyl-DDD at one of two doses, either 2,500 or 5,000 ppm, for 105 weeks. Groups of 50 female mice were administered the test chemical at one of two doses, initially either 5,000 or 10,000 ppm. Because of excessive lowered body weights in the dosed groups of females, the doses for the females were reduced after 48 weeks to 1,000 and 3,000 ppm, respectively, and administration at the lowered doses was continued for 57 weeks. The time-weighted average doses for the female mice were 2,828 and 6,200 ppm. Matched controls consisted of 20 untreated mice of each sex. All surviving mice were killed at the end of administration of the test chemical. No tumors occurred in the male or female rats or in the male mice at incidences that could clearly be related to administration of the test chemical. In female mice, hepatocellular carcinomas or adenomas occurred at incidences that were dose related (P=0.011), but in direct comparisons the incidences in the individual dosed groups were not significantly higher than that in the corresponding control group. Although the occurrence of hepatocellular carcinomas or adenomas in the dosed female mice are not clearly related to the administration of the test chemical, the increased incidence of these tumors in the high-dose group suggests that the tumors may be related to the administration of p,p'-ethyl-DDD. It is concluded that under the conditions of this bioassay, p,p'-ethyl-DDD was not carcinogenic for male or female F344 rats or male B6C3F1 mice. However, the occurrence of hepatocellular carcinomas and adenomas in female mice was suggestive of a carcinogenic effect.

Journal Article↗

PubMed1979

Bioassay of 2,4,6-trichlorophenol for possible carcinogenicity.

A bioassay of 2,4,6-trichlorophenol 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 2,4,6-trichlorophenol at one of two doses, either 5,000 or 10,000 ppm, for 106 or 107 weeks. Matched controls consisted of 20 untreated rats of each sex. All surviving rats were killed at the end of administration of the test chemical. Groups of 50 male mice were administered 2,4,6-trichlorophenol at one of two doses, either 5,000 or 10,000 for 105 weeks. Groups of 50 female mice were administered the test chemical at one of two doses, initially either 10,000 or 20,000 ppm, for 38 weeks. Because of excessively lowered body weights in the dosed groups of the females, the doses for the females were then reduced to 2,500 and 5,000 ppm, respectively, and administration at the lower doses was continued for 67 weeks. The time-weighted average doses for the female mice were either 5,214 or 10,428 ppm. Matched controls consisted of 20 untreated mice of each sex. All surviving mice were killed at the end of administration of the test chemical. Mean body weights of dosed rats and mice of each sex were lower than those of corresponding controls and were dose related throughout the bioassay. Survivals to the end of the experiment were 68% or greater in all groups of rats and 80% or greater in all groups of mice. In the male rats, lymphomas or leukemias occurred at incidences that were dose related (P=0.006) and in direct comparisons were significantly higher in the low-dose(P=0.019) and high-dose (P=0.004) groups than in the corresponding control group (controls 4/20; low-dose 25/50; high-dose 29/50). Leukocytosis and monocytosis of the peripheral blood and hyperplasia of the bone marrow also occurred in some dosed male rats not having lymphoma or leukemia. In female rats, monocytic leukemia did not occur at incidences that were significant. However, as in the male rats, leukocytosis and monocytosis of the peripheral blood and hyperplasia of the bone marrow occurred in the dosed female rats but not in the controls (blood leukocytosis and monocytosis: controls 0/20, low-dose 6/50, high-dose 3/50; bone marrow hyperplasia: controls 0/20, low-dose 16/50, high-dose 2/50). In both the male and female mice, hepatocellular carcinomas or adenomas occurred at incidences that were dose related (P<0.001), and in direct comparisons were significantly higher in the low- and high-dose male groups and the high-dose female group (P</= 0.001) than in the corresponding control groups (males: controls 4/20, low-dose 32/49, high-dose 39/47; females: controls 1/20, low-dose 12/50, high-dose 24/48). It is concluded that under the conditions of this bioassay, 2,4,6-trichlorophenol was carcinogenic in male F344 rats, inducing lymphomas or leukemias. The test chemical was also carcinogenic in both sexes of B6C3F1 mice, inducing hepatocellular carcinomas or adenomas.

Journal Article↗

PubMed1979

Bioassay of azobenzene for possible carcinogenicity.

A bioassay of azobenzene 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 azobenzene at one of two doses, either 200 or 400 ppm, for 105 or 106 weeks. Matched controls consisted of 20 untreated rats of each sex. All surviving rats were killed at the end of administration of the test chemical. Groups of 50 male mice were administered azobenzene at one of two doses, either 200 or 400 ppm, for 105 weeks. Groups of 50 female mice were administered the test chemical at one of two doses, initially 400 or 800 ppm, for 38 weeks. Because of excessively lowered body weights in the dosed groups of the females, doses for the females were then reduced to 100 and 400 ppm, respectively, and administration at the lowered doses was continued for 67 or 68 weeks. The time-weighted average doses for the female mice were either 208 or 545 ppm. Matched controls consisted of 20 untreated mice of each sex. All surviving mice were killed at the end of administration of the test chemical. Mean body weights of dosed rats and mice of each sex were lower than those of corresponding controls, and were generally dose related throughout the bioassay. Mortality was dose related in the male rats and the female mice, but was not significantly affected in either the female rats or the male mice. Survival was 70% or greater at week 90 on study in all dosed and control groups of each species and sex; thus, sufficient numbers of animals were at risk in all groups for the development of late-appearing tumors. In rats, a large number of sarcomas, including fibrosarcomas, hemangiosarcomas, and osteosarcomas in both males and females and malignant hemangiopericytomas in females, occurred in the spleen and other abdominal organs at incidences that were dose related in each sex (P<0.001) and that in direct comparisons were significantly higher (P<0.001) in the high-dose groups of each sex than in the corresponding control groups (males: controls, 0/20, low-dose 6/49, high-dose 31/49; females: controls 0/20, low-dose 5/50, high-dose 21/50). In mice, no tumors occurred in either males or females 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, azobenzene was carcinogenic (sarcomagenic) for F344 rats, inducing various types of sarcomas in the spleen and other abdominal organs of both males and females. The test chemical was not carcinogenic for B6C3F1 mice of either sex.

Journal Article↗

PubMed1979

Bioassay of o-toluidine hydrochloride for possible carcinogenicity.

A bioassay of o-toluidine hydrochloride 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 o-toluidine hydrochloride at one of several doses, either 3,000 or 6,000 ppm for rats and either 1,000 or 3,000 ppm for the mice, for 101 to 104 weeks. Matched controls consisted of 20 untreated rats of each sex 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 dosed male and female rats and mice were lower than those of corresponding matched controls and were dose related. Mortalities of the male and female rats were dose related and were relatively high at the end of the bioassay. Mortalities of the male and female mice were not, however, significantly affected by administration of the test chemical. In rats, the administration of the test chemical induced several types of sarcomas of the spleen and other organs in both males and females, mesotheliomas of the abdominal cavity or scrotum in males, and transitional-cell carcinomas of the urinary bladder in females. Administration of the o-toluidine hydrochloride also resulted in increased incidences of fibromas of the subcutaneous tissue in the males and fibroadenomas or adenomas of the mammary gland in females. In mice, hemangiosarcomas were induced at various sites in males, and hepatocellular carcinomas or adenomas were induced in females. Under the conditions of this bioassay, o-toluidine hydrochloride was carcinogenic in both male and female F344 rats and B6C3F1 mice, producing a significant increased incidence of one or more types of neoplasms.

Journal Article↗

PubMed1979

Bioassay of ethyl tellurac for possible carcinogenicity.

A bioassay of technical-grade ethyl tellurac for possible carcinogenicity was conducted by administering the preparation in feed to F344 rats and B6C3F1 mice. Groups of 50 rats of each sex were administered ethyl tellurac at one of two doses, either 300 or 600 ppm for the males and either 150 or 300 ppm for the females, for 105 weeks. Matched controls consisted of 20 untreated rats of each sex. All surviving rats were killed at 105 weeks. Groups of 50 mice of each sex were administered ethyl tellurac at one of two doses, initially either 2,500 or 5,000 ppm. Due to signs of toxicity in the dosed animals, these doses were reduced to 500 and 2,000 ppm, respectively, starting at week 41 for the males and at week 38 for the females. The reduced doses were maintained for 66 weeks for the males; for the females, the reduced doses were raised after 3 weeks to 2,000 and 5,000 ppm, respectively, and maintained at these levels for 66 weeks. The time-weighted average doses for the males were either 1,255 or 3,132 ppm; for the females, either 2,132 or 4,915 ppm. Matched controls consisted of 20 untreated mice of each sex. All surviving mice were killed at 106 weeks. Mean body weights of the dosed groups of rats or mice were lower than those of corresponding controls throughout most or all of the bioassay. No other clinical signs in the rats or mice were clearly related to administration of the test chemical. Survival of the rats and the mice was not affected by the chemical, and sufficient numbers of all groups were at risk for the development of late-appearing tumors. In the male rats, mesotheliomas occurred at incidences that were dose related (P=0.012); in direct comparisons, the incidences of the tumors in the individual dosed groups were not significantly higher than that in the control group (controls 0/20, low-dose 2/49, high-dose 8/50). However, the historical-control data at this laboratory indicate an incidence of 12/416 (2.9%) in male F344 rats compared with 8/50 (16%) in the male high-dose group in this study. In the female rats, no tumors occurred at incidences that were related to administration of the test chemical. In both male and female mice, adenomas of the lacrimal (harderian) gland of the eye occurred in the dosed groups, but not in the corresponding controls (males: controls 0/17; low-dose 16/46, high-dose 10/49; females: controls 0/20, low-dose 6/50, high-dose 5/49). The incidences in the dosed groups were not high enough to show statistically significant dose-related trends. However, in direct comparisons of dosed and control groups of male mice, the incidence was statistically significant in the low-dose males (P=0.003). In female mice, direct comparisons of dosed and control groups indicated that the incidence of this tumor was not statistically significant. It is concluded that under the conditions of this bioassay, ethyl tellurac was not carcinogenic for F344 rats or B6C3F1 mice of either sex. The incidence of mesotheliomas in dosed male rats and the incidence of adenomas of the lacrimal (harderian) gland of the eye in dosed mice of either sex provided evidence which was suggestive but under the conditions of the bioassay insufficient to establish the carcinogenicity of ethyl tellurac in these animals.

Journal Article↗

PubMed1979

Bioassay of lead dimethyldithiocarbamate for possible carcinogenicity.

A bioassay of technical-grade lead dimethyldithiocarbamate for possible carcinogenicity was conducted by administering the test chemical in feed to F344 (Fischer) rats and B6C3F1 mice. Groups of 50 rats of each sex and 50 mice of each sex were administered lead dimethyldithiocarbamate at one of two doses, either 25 or 50 ppm, for 104 or 105 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 male rats and female mice were slightly lower than those of the corresponding controls; mean body weights of the dosed female rats and male mice were essentially the same as those of the corresponding controls. Survival rats in both species were unaffected by administration of the test chemical. The lack of toxicity in both species suggests that a maximum tolerated dose level may not have been used. Therefore, the studies may not have been conducted using maximum sensitivity for the assessment of the possible carcinogenicity of lead dimethyldithiocarbamate. 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, lead dimethyldithiocarbamate was not carcinogenic for F344 rats or B6C3F1 mice of either sex.

Journal Article↗