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National Toxicology Program

Publications and source records attributed to National Toxicology Program.

At least 541 records · Page 30Linked to original sources
PubMed1980

Bioassay of Benzoin for Possible Carcinogenicity (CAS No.119-53-9).

A bioassay of benzoin for possible carcinogenicity was conducted by incorporating the test chemical in diets of F344 rats and B6C3F1 mice. Benzoin is used as a photopolymerization catalyst, chemical intermediate, and flavor ingredient. Groups of 50 male rats were fed diets containing 125 or 250 ppm benzoin for 104 weeks, and similar groups of female rats received feed containing 250 or 500 ppm. Groups of 50 mice of each sex were fed diets containing 2,500 or 5,000 ppm, benzoin for 104 weeks. Groups of 50 untreated rats and mice of each sex were used as matched controls. Rats and mice of either sex probably could have tolerated higher doses. An increased incidence of lymphomas or leukemia occurred in dosed male rats, but the observed dose-related trend was not statistically significant. Mean body weights and clinical signs of low-dose, high-dose, and control male and female rats and male mice were comparable throughout the study. After week 44, mean body weights of dosed female mice were slightly lower (10% or less) than those of the controls. The incidences of lymphomas that occurred in male mice varied with each dose but were not statistically significant when compared with those of matched controls. Lymphomas or leukemias occurred in low-dose female mice at an incidence that was significant when compared with the matched controls. However, because the incidence of lymphomas or leukemias in the high-dose female mice was not significant, the occurrence of these tumors was not clearly related to administration of the test compounds. Under the conditions of this bioassay, benzoin was not carcinogenic for F344 rats or B6C3F1 mice. Levels of Evidence of Carcinogenicity: Male Rats: Negative Female Rats: Negative Male Mice: Negative Female Mice: Negative Synonym: 2-hydroxy-1,2-diphenylethanone

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PubMed1979

Bioassay of 2-(Chloromethyl)Pyridine Hydrochloride for Possible Carcinogenicity (CAS No. 6959-47-3).

2-(Chloromethyl)pyridine hydrochloride, an aromatic heterocycle used in a variety of syntheses, was selected for bioassay by the National Cancer Institute because of the structural similarity of this compound to 2-(a,b-dichloroethyl)-pyridine hydrochloride, a carcinogen in rats, mice, Syrian hamsters, and Mongolian gerbils. A bioassay for the possible carcinogenicity of 2-(chloromethyl)pyridine hydrochloride was conducted using Fischer 344 rats and B6C3F1 mice. 2-(Chloromethyl)pyridine hydrochloride was administered by gavage, at either of two dosages, to groups of 50 male and 50 female animals of each species, with the exception of 49 male rats in the high dose group. Twenty animals of each sex and species were placed on test as vehicle controls. The high and low dosages of 2-(chloromethyl)pyridine hydrochloride administered were, respectively, 150 and 75 mg/kg for rats and 250 and 125 mg/kg for mice. The compound was administered for 99 weeks to rats and mice. The period of compound administration was followed by an observation period of 6 weeks for rats and 5 weeks for mice. There were no significant positive associations between the dosages of 2-(chloromethyl)pyridine hydrochloride 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 mice of both sexes, indicating that the dosages of 2-(chloromethyl)pyridine hydrochloride administered tothese animals in this bioassay may have approximated the maximum tolerated concentrations. Since no distinct mean body weight depression relative to vehicle controls, no significant accelerated mortality, and no other signs of toxicity were associated with administration of 2-(chloromethyl)pyridine hydrochloride to rats, it is possible that these animals may have been able to tolerate a higher dosage. 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 trend between the dosages administered and the incidences of subcutaneous fibromas in male rats. The Fisher exact comparisons, however, were not significant. Under the conditions of this bioassay, administration of 2-(chloromethyl)pyridine hydrochloride was not carcinogenic to 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-(Cl-methyl)pyridineHCl; 2-pyridylmethyl chloride hydrochloride; 2-picolylchloride hydrochloride

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PubMed1979

Bioassay of Malathion for Possible Carcinogenicity (CAS No. 121-75-5).

Malathion is an organophosphate insecticide considered to be suitable as a substitute for certain uses of DDT. U.S. consumption in 1974 was 16 million pounds, surpassing that of all other organophosphate insecticides except methyl parathion. Household applications accounted for approximately 10% of that volume. A bioassay of malathion for possible carcinogenicity was conducted by administering the test chemical in feed to F344 rats. Groups of 49 or 50 rats of each sex were fed diets containing 2,000 or 4,000 ppm malathion for 103 weeks and were then observed for an additional 2 or 3 weeks. Matched controls consisted of 50 untreated rats of each sex. All surviving rats were killed at 105 or 106 weeks. No tumors occurred in the dosed groups of rats of either sex at incidences that could be related clearly to administration of the test chemical. Compound-related toxic effects were not observed in female rats at the doses used, but in males decreased mean body weights, increased mortality, gastritis, and gastric ulcers were dose related. It was concluded that under the conditions of this bioassay, malathion was not carcinogenic in male or female rats, but the females may not have received a maximum tolerated dose. Levels of Evidence of Carcinogenicity: Male Rats: Negative Female Rats: Negative Synonym: S-(1,2-bis(ethoxycarbonyl)-ethyl) O,O-dimethylphosphorodithioate

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PubMed1979

Bioassay of Technical Grade Bis(2-chloro-1-methylethyl) ether for Possible Carcinogenicity (CAS No. 108-60-1).

Bis(2-chloro-1-methylethyl) ether is a beta-haloether and a byproduct of propylene oxide and propylene glycol manufacture. A bioassay of technical grade bis(2-chloro-1-methylethyl) ether for possible carcinogenicity was conducted by administering the test chemical by gavage to F344 rats. Groups of 50 rats of each sex were administered a solution of bis(2-chloro-1-methylethyl) ether in corn oil 5 days per week at either 100 or 200 mg/kg/day for 103 weeks. Vehicle controls consisted of groups of 50 rats of each sex that were administered the corn oil alone. Untreated-control groups of the same size were also used. All surviving rats were killed at week 104 or 105. Mean body weights of the dosed groups of male and female rats were lower than those of the corresponding vehicle-control groups throughout most of the study and were dose related. Similarly, survivals of the high-dose males and of both the high- and low-dose females were lower than those of the corresponding vehicle controls and were dose related. Almost all animals in the high-dose groups died by the end of the bioassay. No tumors occurred in the dosed groups of rats of either sex at incidences that were significantly higher than those of the vehicle-control groups. It is concluded that under the conditions of this bioassay, the technical-grade test material, bis(2-chloro-1-methylethyl) ether, was not carcinogenic for F344 rats of either sex. Levels of Evidence of Carcinogenicity: Male Rats: Negative Female Rats: Negative Synonym: bis(2-chloro-isopropyl) ether Report Date: 1979

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PubMed1979

Bioassay of p-Nitrosodiphenylamine for Possible Carcinogenicity (CAS No. 156-10-5).

p-Nitrosodiphenylamine is used to accelerate the vulcanization of rubber. It is also used as an intermediate in the manufacture of dyes and pharmaceutical compounds and as an inhibitor of polymerization during the production of vinyl monomers such as styrene. A bioassay for the possible carcinogenicity of p-nitrosodiphenylamine was conducted using Fisher 344 rats and B6C3F1 mice. p-Nitrosodiphenylamine was administered in the feed, at either of two concentrations, to groups of 50 male and 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 p-nitrosodiphenylamine were, respectively, 5000 and 2500 ppm for rats. The high and low time-weighted average concentrations for mice were 9000 and 4254 ppm, respectively. The compound was administered for 78 weeks to rats, for 50 weeks to high dose mice and for 57 weeks to low dose mice. The period of compound administration was followed by an observation period of 27 weeks for rats and 35 weeks for mice. There were significant positive associations between the concentrations of p- nitrosodiphenylamine administered and mortality among male and female mice, but not for rats of either sex. Although 19/50 high dose male mice and 21/50 high dose female mice died before week 52, adequate numbers of mice and rats survived sufficiently long to be at risk from late-developing tumors. The toxicity observed in mice and the dose-related mean body weight depression apparent in male and female rats indicated that the concentrations of p-nitrosodiphenylamine administered to these animals in this bioassay may have approached or exceeded the maximum tolerated concentrations. In male rats, there was a significant positive association between concentration administered and the incidence of a combination of hepatocellular carcinomas and neoplastic nodules. In addition, both the high dose to control and thelow dose to control Fisher exact comparisons were significant. There was also a significant positive association between concentration administered and the incidence of alveolar/bronchiolar adenomas in male rats; however, neither of the Fisher exact comparisons were significant. There were no positive, significant statistical tests for tumor incidence at any site in female rats. Due to the large number of early deaths among high dose mice of both sexes, the statistical conclusion concerning carcinogenicity was based on comparisons between the low dose and control groups. The incidence of hepatocellular carcinomas was significantly higher among the low dose males than among their controls. Although hepatocellular neoplasms were observed in dosed females, there were no tumors occurring with a statistically increased incidence when low dose females were compared to their controls. Under the conditions of this bioassay, p-nitrosodiphenylamine was carcinogenic when administered in the diet to male B6C3F1 mice, causing hepatocellular carcinomas. The chemical was also carcinogenic in male Fisher 344 rats, causing liver neoplasms. No evidence was provided for the carcinogenicity of p-nitrosodiphenylamine in female B6C3F1 mice or in female Fisher 344 rats. Levels of Evidence of Carcinogenicity: Male Rats: Positive Female Rats: Negative Male Mice: Positive Female Mice: Negative Synonyms: 4-nitroso-N-phenylbenzeneamine; 4-nitrosodiphenylamine; p-nitroso-N-phenylaniline; TKB

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PubMed1979

Bioassay of p-Chloroaniline for Possible Carcinogenicity (CAS No. 106-47-8).

p-Chloroaniline, a dye and chemical intermediate, was selected for bioassay by the National Cancer Institute because of the high incidence of bladder cancer observed among dye manufacturing industry workers. A bioassay for the possible carcinogenicity of p-chloroaniline was conducted using Fisher 344 rats and B6C3F1 mice. p-Chloroaniline 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 p-chloroaniline were, respectively, 500 and 250 ppm for rats and 5000 and 2500 ppm for mice. The compound was administered in the diet for 78 weeks, followed by an observation period of 24 weeks for rats and 13 weeks for mice. There were no significant positive associations between the dietary concentrations of p-chloroaniline administered and mortality in female rats or in mice of either sex; however, there was a significantly positive association between concentration and mortality in male rats. Adequate numbers of animals in all groups survived sufficiently long to be at risk from late-developing tumors. Mean body weight depression, in relation to controls, was observed in high dose female rats and dosed mice of both sexes, indicating that the concentration of p-chloroaniline administered to these animals may have approximated the maximum tolerated concentrations. Although splenic lesions were observed in male rats, no mean body weight depression relative to controls was associated with administration of p-chloroaniline to these animals. Therefore, it is possible that these animals may have been able to tolerate a higher dietary concentration of the compound. The only neoplastic lesions found that might be related to administration of the compound were mesenchymal tumors in the spleens of male rats and hemangiomatous tumors in mice. In male rats, there was a significant positive association between compound administration and the incidences of fibroma or fibrosarcoma of the spleen. Theincidences of these tumors were not significantly elevated when compared to those in control rats, but the rarity of these tumors in male Fisher 344 rats (0/360 in historical male control rats in this laboratory) strongly suggests a chemically related effect. In addition, three sarcomas of other types were found in high dose male rats. In mice of both sexes, hemangiomas and hemangiosarcomas were found at elevated incidences, when compared to control mice, in the spleen, liver, kidney, and multiple body sites. The increased incidences in dosed mice were statistically related to dose but were not statistically significant when compared directly to matched control animals. In comparison to historical control data, the incidences of hemangiomatous tumors in the dosed mice were elevated, but not greatly. The evidence was considered insufficient to conclusively relate the hemangiomatous tumors in mice to compound administration. Nonneoplastic proliferative and chronic inflammatory lesions were also found in the spleens of dosed rats and mice. The findings of small numbers of fibromas and sarcomas in the spleens of male rats was considered strongly suggestive of carcinogenicity because of the rarity of these tumors in the spleens of control rats. Hemangiomatous tumors in dosed mice may also have been associated with administration of p-chloroaniline. However, it is concluded that, under the conditions of this bioassay, sufficient evidence was not found to establish the carcinogenicity of p-chloroaniline for Fisher 344 rats or B6C3F1 mice. Levels of Evidence of Carcinogenicity: Male Rats: Equivocal Female Rats: Negative Male Mice: Equivocal Female Mice: Equivocal Synonyms: 4-chlorobenzeneamine; 4-chlorophenylamine; 4-chloroaniline; 4-CA; 1-amino-4-chlorobenzene

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PubMed1979

Bioassay of 5-Chloro-o-toluidine for Possible Carcinogenicity (CAS No. 95-79-4).

5-Chloro-o-toluidine, an aromatic amine and dye intermediate, was selected for bioassay by the National Cancer Institute because of the high incidence of bladder cancer observed among dye manufacturing industry workers. A bioassay for the possible carcinogenicity of 5-chloro-o-toluidine was conducted using Fisher 344 rats and B6C3F1 mice. 5-Chloro-o-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 high and low dietary concentrations of 5-chloro-o-toluidine were 5,000 and 2,500 ppm for rats and 4,000 and 2,000 ppm for mice. The compound was administered in the diet for 78 weeks, followed by an observation period of 26 weeks for rats and 13 weeks for mice. There were significant positive associations between the concentrations of 5-chloro-o-toluidine administered and mortality among male and female mice, but not among rats of either sex. Adequate numbers of animals in all groups survived sufficiently long to be at risk from late-developing tumors. Distinct mean body weight depression was apparent when dosed female rats and dosed mice of both sexes were compared to their controls, indicating that the concentrations administered to these animals in this bioassay may have approximated the maximum tolerated concentrations. Since no mean body weight depression, relative to controls, no significantly accelerated mortality, and no signs of toxicity other than fatty metamorphosis of the liver were associated with administration of 5-chloro-o-toluidine to male rats, it is possible that these animals may have been able to tolerate a higher dietary concentration of the compound. There was a significant positive association between the concentration of 5-chloro-o-toluidine administered to male rats and the incidence of adrenal pheochromocytomas in these animals; however, neither of the Fisher comparisons was significant. None of the other statistical tests fortumors at any site in male and female rats indicated a significant positive association between dosage and incidence. In mice of both sexes there were significant positive associations between concentration administered and the incidence of hemangiosarcomas. In addition, the high dose to control Fisher exact comparisons for both sexes were significant. The Cochran-Armitage tests were also significant and positive for the incidences of hepatocellular carcinomas in both sexes of mice. For males and females the high dose to control Fisher exact comparisons were significant, and for females the low dose to control comparison was also significant. Under the conditions of this bioassay, 5-chloro-o-toluidine was carcinogenic to B6C3F1 mice, inducing hemangiosarcomas and hepatocellular carcinomas in both males and females. There was no conclusive evidence of the carcinogenicity of the compound in Fisher 344 rats. Levels of Evidence of Carcinogenicity: Male Rats: Negative Female Rats: Negative Male Mice: Positive Female Mice: Positive Synonyms: 5-chloro-2-methylbenzeneamine; p-chloro-o-aminotoluene; 4-chloro-2-aminotoluene; 2-amino-4-chlorotoluene; o-amino-p-chlorotoluene; 5-chloro-2-methylaniline; 2-methyl-5-chloroaniline; 1-amino-2-methyl-5-chlorobenzene; 1-amino-3-chloro-6-methylbenzene; Fast Red KB Base; Azogene Fast Red KB; Brentamine Fast Red KB Base; Naphthosol Fast Red Base; Naphthanil Red KB Base

Journal Article↗
PubMed1979

Bioassay of 4,4'-Methylenebis-(N,N-dimethyl)benzeneamine for Possible Carcinogenicity (CAS No. 101-61-1).

4,4'-Methylenebis(N,N-dimethyl)benzeneamine, a bicyclic aromatic amine and an intermediate in dye manufacture, was selected for bioassay by the National Cancer Institute because of a high incidence of bladder cancer observed among dye manufacturing industry workers. A bioassay for the possible carcinogenicity of 4,4'-methylenebis-(N,N-dimethyl)benzeneamine was conducted using Fisher 344 rats and B6C3F1 mice. 4,4'-Methylenebis-(N,N-dimethyl)benzeneamine 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 4,4'-methylenebis-(N,N-dimethyl)benzeneamine were, respectively, 750 and 375 ppm for rats and 2500 and 1250 ppm for mice. The compound was administered for 59 weeks to rats and for 78 weeks to mice. The period of compound administration was followed by an observation period of 45 weeks for rats and 13 weeks for mice. There were no significantly positive associations between the concentrations of 4,4'-methylenebis-(N,N-dimethyl)benzeneamine administered and mortality among rats or mice of either sex. Adequate numbers of animals survived sufficiently long to be at risk from late-developing tumors. There was slight dose-related mean body weight depression among female rats, the mean body weight of high dose male rats was slightly less than that for controls, and the mean body weights of dosed mice were significantly lower than their controls, indicating that the concentrations of 4,4'-methylenebis-(N,N-dimethyl)benzeneamine administered to these animals in this bioassay may have approximated the maximum tolerated concentrations. For both male and female rats, there was a significant positive association between the concentrations of 4,4'-methylenebis-(N,N-dimethyl)benzeneamine administered and the incidences of follicular-cell carcinomas of the thyroid (i.e., 1/18, 4/50, and 21/46 in the control, low dose, and high dose males, respectively; and 0/20, 3/46, and 23/45 in the control, low dose, and high dose females, respectively). The high dose to control Fisher exact comparisons were also significant for each sex. Liver neoplasms were observed among male and female mice. There were elevated incidences of hepatocellular adenomas in dosed mice when compared to controls (i.e., 2/20, 3/50, and 16/48 in control, low dose, and high dose males, respectively; and 1/19, 18/49, and 22/48 in control, low dose, and high dose females). The incidences of hepatocellular carcinomas in dosed mice did not differ greatly from those in controls (i.e., 3/20, 9/50, and 6/48 in control, low dose, and high dose males, respectively; and 0/19, 1/49, and 1/48 in control, low dose, and high dose females). Among both sexes of mice, there was a significant positive association between the concentrations of the chemical administered and the incidences of a combination of hepatocellular adenomas and hepatocellular carcinomas. For male mice, the Fisher exact comparisons were not significant; however, for females, both the high dose to control and the low dose to control comparisons were significant. In both sexes of both species nonneoplastic proliferative lesions of the thyroid occurred in dosed animals but not in any of the controls. Under the conditions of this bioassay, 4,4'-methylenebis-(N,N-dimethyl)benzeneamine was carcinogenic in Fisher 344 rats, inducing thyroid follicular-cell carcinomas in both males and females. Administration of the compound was carcinogenic in female B6C3F1 mice, inducing liver neoplasms. There was no conclusive evidence that 4,4'-methylenebis-(N,N-dimethyl)benzeneamine was carcinogenic in male B6C3F1 mice. Levels of Evidence of Carcinogenicity: Male Rats: Positive Female Rats: Positive Male Mice: Equivocal Female Mice: Positive Synonyms: 4,4'-methylenebis(N,N-dimethyl)aniline; tetramethyldiaminodiphenylmethane; 4,4'-bis(dimethylamino) diphenylmethane; Tetra base; Methane base; Michler's base; Michler's hydride; Michler's methane

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PubMed1979

Bioassay of Styrene for Possible Carcinogenicity (CAS No.100-42-5).

Styrene, a widely used intermediate in the manufacture of plastics, elastomers, and resins, was selected for bioassay by the National Cancer Institute because of the widespread use of this compound and a lack of adequate carcinogenicity data. A bioassay for the possible carcinogenicity of styrene was conducted using Fischer 344 rats and B6C3F1 mice. Styrene was administered by gavage to groups of 50 male and 50 female animals of each species. Forty rats of each sex and twenty mice of each sex were placed on test as vehicle controls. The high, medium, and low dosages of styrene administered to rats were, respectively, 2,000, 1,000, and 500 mg/kg. The high and low dosages administered to mice were 300 and 150 mg/kg, respectively. The compound was administered for 78 weeks to high and medium dose rats, for 103 weeks to low dose rats, and for 78 weeks to mice. The period of compound administration was followed by an observation period of 27 weeks for high and medium dose rats, 1 week for low dose rats, and 13 weeks for mice. Mortality among male and female high dose rats was significantly higher than that among their respective vehicle controls. In response to this elevated and early mortality, an additional dosed group of each sex was included in the chronic bioassay. No significant positive association was apparent between dosage and mortality among any other dosed rat groups. For mice, there was a significant positive association between mortality and the dosages of styrene administered to males, but not to females. Adequate numbers of animals in all groups, except for the high dose male and female rats, survived sufficiently long to be at risk from late-developing tumors. Slight dose-related mean body weight depression was apparent when male rats and female mice were compared to their respective vehicle controls, indicating that the dosages administered to these animals during the chronic bioassay may have approximated the maximum tolerated dosages. There was no distinct depression in mean body weight when dosed female rats anddosed male mice were compared to their respective vehicle controls. However, since there was significant accelerated mortality among high dose female rats, it is possible that the dosage administered to the medium dose female rats may have exceeded the maximum tolerated dosage. In male mice, there was a significant positive association between styrene dosage and the incidences of a combination of adenomas and carcinomas of the lung. This finding was supported by the high dose to control Fisher exact comparison. However, the variation of the incidence of these neoplasms in historical control male mice at this laboratory does not permit a firm conclusion of carcinogenicity. There was no significant difference between tumor incidence at any other site in male mice, or at any site in rats or female mice, when dosed groups were compared to vehicle controls. The findings of an increased incidence of a combination of adenomas and carcinomas of the lung provided suggestive evidence for the carcinogenicity of styrene in male B6C3F1 mice. However, it is concluded that, under the conditions of this bioassay, no convincing evidence for the carcinogenicity of the compound was obtained in Fischer 344 rats or B6C3F1 mice of either sex. Levels of Evidence of Carcinogenicity: Male Rats: Negative Female Rats: Negative Male Mice: Equivocal Female Mice: Negative Synonyms: ethenylbenzene; vinylbenzene; vinylbenzol; styrolene; styrol; styrole; styropol; styropor; styron; cinnamene; cinnamol; phenethylene; phenylethylene; phenylethene

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PubMed1979

Bioassay of Nitrofen for Possible Carcinogenicity (CAS No. 1836-75-5).

Nitrofen, a substituted diphenyl ether, is one of several agricultural pesticides selected for bioassay by the National Cancer Institute because of a lack of carcinogenicity data. A bioassay for the possible carcinogenicity of nitrofen was conducted using Fischer 344 rats and B6C3F1 mice. Nitrofen 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 nitrofen were 6000 and 3000 ppm for both species. The compound was administered to rats and mice for 78 weeks, followed by a period of no compound administration of 26 weeks for rats and 13 weeks for mice. There were no significant positive associations between the concentrations of nitrofen 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, relative to controls, was observed for males and females of both species, indicating that the concentrations of nitrofen 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 indicated a significant positive association between compound administration and tumor incidence. There was a significant positive association between the concentrationof nitrofen administered and the incidences of hepatocellular carcinomas in mice of both sexes. In another bioassay of nitrofen for possible carcinogenicity, the compound was found to induce hepatocellular carcinomas in B6C3F1 mice of both sexes and hemangiosarcomas of the liver in male B6C3F1 mice. In addition, adenocarcinomas of the pancreas were induced in female Osbourne-Mendel rats. Under the conditions of this bioassay, dietary administration of nitrofen was carcinogenic to B6C3F1 mice, causing hepatocellular carcinomas in both sexes. There was no evidence for carcinogenicity in Fischer 344 rats. Levels of Evidence of Carcinogenicity: Male Rats: Negative Female Rats: Negative Male Mice: Positive Female Mice: Positive Synonyms: 2,4-dichloro-1-(4-nitrophenoxy)-benzene, 2,4-dichlorophenyl-p-nitrophenyl ether, nitrophene, Tok E-25, Nip

Journal Article↗
PubMed1979

Bioassay of Dibutyltin Diacetate for Possible Carcinogenicity (CAS No. 1067-33-0).

Dibutyltin diacetate, a widely used catalyst for polymerization reactions, was selected for bioassay by the National Cancer Institute in an effort to screen a number of organo-metallic compounds for carcinogenicity. A bioassay for the possible carcinogenicity of dibutyltin diacetate was conducted using Fischer 344 rats and B6C3F1 mice. Dibutyltin diacetate was administered in the feed, at either of two concentrations, to groups of 50 male and female animals of each species. Twenty animals of each sex and species were placed on test as controls. The high and low time-weighted average dietary concentrations of dibutyltin diacetate were, respectively, 133 and 66.5 ppm for rats and 152 and 76 ppm for mice. The compound was administered for 78 weeks to rats and mice, followed by a period of no compound administration of 26 weeks for rats and 14 weeks for mice. There were significant positive associations between the concentrations of dibutyltin diacetate administered and mortality in male rats and female mice. There were no significant positive associations between the concentrations administered and mortality in female rats or male mice. 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 male mice and significantly accelerated mortality, relative to controls, was observed in male rats and female mice, indicating that the concentrations of dibutyltin diacetate administered to these animals may have approximated the maximum tolerated concentrations. Since no mean body weight depression, no significantly accelerated mortality, and no other signs of toxicity were associated with administration of dibutyltin acetate to femalerats, it is possible that these animals may have been able to tolerate a higher dietary concentration. There were no neoplasms occurring in statistically significant higher incidences in dosed rats or mice when compared to their respective controls. However, there was an accidental loss of tissues from high dose female rats which precluded an evaluation of carcinogenicity in this group of animals. There was a significant positive association between the concentrations administered and the incidences of hepatocellular adenomas in females mice; however, the Fisher exact comparisons were not significant using the Bonferroni criterion. Liver neoplasms (i.e., a combination of adenomas and carcinomas) were also observed in male mice; however, the occurrence was not statistically significant. Under the conditions of this bioassay, there was no conclusive evidence for the carcinogenicity of dibutyltin diacetate in male Fischer 344 rats or B6C3F1 mice of either sex. The loss of tissues taken from high dose female rats in this bioassay precluded an evaluation of the carcinogenicity of dibutyltin diacetate to female Fischer 344 rats. Levels of Evidence of Carcinogenicity: Male Rats: Negative Female Rats: Inadequate Study Male Mice: Negative Female Mice: Negative Synonyms: bis(acetyloxy)dibutylstannae; diacetoxydibutylstannae; diacetoxybutyltin; dibutyl tin diacetate

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PubMed1979

Bioassay of Michler's Ketone for Possible Carcinogenicity (CAS No. 90-94-8).

Michler's ketone, a dye intermediate and derivative of dimethylaniline, was selected for bioassay by the National Cancer Institute because of the elevated incidence of bladder cancer noted among dye manufacturing industry workers. A bioassay for the possible carcinogenicity of technical-grade Michler's ketone was conducted using Fischer 344 rats and B6C3F1 mice. Michler's ketone 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 Michler's ketone were respectively, 500 and 250 ppm for male rats, 1,000 and 500 ppm for female rats, and 2,500 and 1,250 ppm for mice of both sexes. The compound was administered to rats and mice for 78 weeks. The period of compound administration was followed by an observation period of 28 weeks for male and high dose female rats, 29 weeks for low dose female rats and 13 weeks for mice. There were significant positive associations between the concentrations of Michler's ketone administered and mortality in rats and mice of both sexes. Adequate numbers of animals in all groups survived sufficiently long to be at risk from late-developing tumors. There was distinct dose-related mean body weight depression in female rats and in mice of both sexes, and the mean body weight among dosed male rats was slightly lower than that in controls, indicating that the concentrations of Michler's ketone administered tothese animals in this bioassay may have approximated the maximum tolerated concentrations. There were significant positive associations between the concentrations of Michler's ketone administered and the incidences of hepatocellular carcinomas in both sexes of rats and in female mice and hemangiosarcomas in male mice. In all of these cases the high dose to control Fisher exact comparison was also significant. Under the conditions of this bioassay, dietary administration of Michler's ketone was carcinogenic to male and female Fischer 344 rats and female B6C3F1 mice, causing hepatocellular carcinomas, and to male B6C3F1 mice, causing hemangiosarcomas. Levels of Evidence of Carcinogenicity: Male Rats: Positive Female Rats: Positive Male Mice: Positive Female Mice: Positive Synonyms: bis[4-(dimethylamino)phenyl]methanone; 4,4'-bis(dimethylamino)benzophenone; p,p'-bis(dimethylamino)benzophenone; bis[p-(N,N'-dimethylamino)phenyl]ketone; tetramethyldiaminobenzophenone

Journal Article↗
PubMed1979

Bioassay of 4-Nitro-o-phenylenediamine for Possible Carcinogenicity (CAS No. 99-56-9).

4-Nitro-o-phenylenediamine, a component of both semipermanent and permanent hair dye formulations, was selected for bioassay by the National Cancer Institute because of the high incidence of bladder cancer reported among workers in the dye manufacturing industry. A bioassay for the possible carcinogenicity of 4-nitro-o-phenylenediamine was conducted using Fischer 344 rats and B6C3F1 mice. 4-Nitro-o-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 4-nitro-o-phenylenediamine were, respectively, 750 and 375 ppm for rats and 7500 and 3750 ppm for mice. The compound was administered for 103 weeks to rats and for 102 weeks to mice. The period of compound administration was followed by an observation period of 2 weeks for rats and mice. There were no significant positive associations between the concentrations of 4-nitro-o-phenylenediamine 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. Distinct dose-related mean body weight depression was observed in mice, indicating that the concentrations of 4-nitro-o-phenylenediamine administered to these animals in this bioassay may have approximated the maximum tolerated concentrations. Since no distinct mean body weightdepression relative to controls, no significantly accelerated mortality, and no other manifestations of chronic toxicity were associated with administration of 4-nitro-o-phenylenediamine to male or female rats, 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 in mice of either sex indicated a significant positive association between compound administration and tumor incidence. Under the conditions of this bioassay, dietary administration of 4-nitro-o-phenylenediamine was not carcinogenic 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: 4-nitro-1,2-benzenediamine; 4-nitro-phenylenediamine; 4-nitro-1,2-diaminobenzene; 1,2-diamino-4-nitrobenzene; 2-amino-4-nitroaniline; 4-NO; 4-NOP; 4-NOPD; 4-N-o-PDA; C.I. 76020

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PubMed1979

Bioassay of p-Quinone Dioxime for Possible Carcinogenicity (CAS No. 105-11-3).

p-Quinone dioxime, a rubber vulcanization accelerator, was selected for bioassay by the National Cancer Institute because of a lack of adequate carcinogenicity data. A bioassay for the possible carcinogenicity of p-quinone dioxime was conducted using Fischer 344 rats and B6C3F1 mice. p-Quinone dioxime 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, with the exception of 18 in the control male mouse group. The high and low concentrations of p-quinone dioxime were 750 and 375 ppm for rats and 1,500 and 750 ppm for mice. The compound was administered to rats and mice for 104 weeks. The period of compound administration was followed by an observation period of 1 week for both species. There were no significant positive associations between the concentrations of p-quinone dioxime 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. Distinct dose-related mean body weight depression was observed among rats and slight mean body weight depression, relative to controls, was observed among mice, indicating that the dosages of p-quinone dioxime administered to the animals in this bioassay may have approximated the maximum tolerated concentrations. Tumors of the urinary bladder were observed only in dosed rats. For female rats, there was a significant positive association between concentration administered and the incidences of a combination of urinary bladder neoplasms. The high dose to control Fisher exact comparison was also significant for these tumors in female rats. No compound-related neoplasms were observed in male rats or mice of either sex. Under the conditions of this bioassay, dietary administration of p-quinone dioxime was carcinogenic to female Fischer 344 rats, causing neoplasms of the urinary bladder. The compound was not carcinogenic to male Fischer 344 rats or B6C3F1 mice of either sex. Levels of Evidence of Carcinogenicity: Male Rats: Negative Female Rats: Positive Male Mice: Negative Female Mice: Negative Synonyms: 2,5-cyclohexadiene-1,4-dione; dioxime p-benzoquinone; p-quinonedioxime; dioxime 1,4-cyclohexadienedione

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PubMed1979

Bioassay of sulfisoxazole for possible carcinogenicity.

A bioassay of sulfisoxazole for possible carcinogenicity was conducted by administering the chemical by gavage to Fischer 344 rats and B6C3F1 mice. Groups of 50 rats of each sex and 50 mice of each sex were administered sulfisoxazole suspended in aqueous 0.5% carboxymethyl cellulose 7 days per week at one of two doses, either 100 or 400 mg/kg body weight for the rats and either 500 or 2,000 mg/kg for the mice. Vehicle controls consisted of groups of 50 rats of each sex and 50 mice of each sex that were administered only the aqueous 0.5% carboxymethyl cellulose. Untreated controls consisted of groups of 50 rats of each sex and 50 mice of each sex. The dosed groups of the rats and mice were administered the chemical by gavage for 103 weeks, then observed for 1 to 3 additional weeks; the vehicle-control groups were similarly administered 0.5% carboxymethyl cellulose alone. All surviving rats and mice were killed at weeks 104 to 106. Mean body weights of high-dose male rats and female mice were slightly lower than those of corresponding vehicle controls during the last 40 to 50 weeks of the bioassay; mean body weights of dosed female rats and male mice were unaffected. Survival rates were unaffected by the test chemical, and adequate numbers of animals were at risk for the development of late-appearing tumors. No tumors occurred in the dosed groups of rats or mice of either sex at incidences that were significantly higher than those of the vehicle-control groups. It is concluded that under the conditions of this bioassay, sulfisoxazole was not carcinogenic for either Fischer 344 rats or B6C3F1 mice

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PubMed1979

Bioassay of diazinon for possible carcinogenicity.

A bioassay of diazinon 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 diazinon at one of two doses, either 400 or 800 ppm for the rats and either 100 or 200 ppm for the mice, for 103 weeks and were then observed for an additional 1 or 2 weeks. Matched controls consisted of groups of 25 untreated rats and 25 untreated mice of each sex. All surviving animals were killed at the end of 104 or 105 weeks. There was no appreciable effect of administration of diazinon on mean body weights of rats or mice of either sex. Mortality was not increased in any of the dosed groups of rats or mice, when related to that in the corresponding controls, and survival was 84% or greater in all dosed and control groups of animals at week 78. Some hyperactivity was noted in the dosed groups of both species; however, both the rats and mice may have been able to tolerate higher doses. Sufficient numbers of animals were at risk in all groups for the development of late-appearing tumors. No tumors occurred in any of the dosed groups of rats or mice of either sex at incidences that could clearly be related to the administration of diazinon. It is concluded that under the conditions of this bioassay, diazinon was not carcinogenic for F344 rats or B6C3F1 mice of either sex

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PubMed1979

Bioassay of aldicarb for possible carcinogenicity.

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

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PubMed1979

Bioassay of malaoxon for possible carcinogenicity.

A bioassay of malaoxon, the oxygen analogue of malathion (an organophosphate insecticide), 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 fed diets containing 500 or 1,000-ppm malaoxon for 103 weeks and were then observed for up to an additional 2 weeks. Matched controls consisted of groups of 50 untreated rats and 50 untreated mice of each sex. All surviving animals were killed at 103 to 105 weeks. The only effects that could be related to administration of malaoxon at the doses used were increased mortality among male mice, decreased mean body weights of female mice, gastric ulcers in male and female rats, and possibly C-cell adenomas or carcinomas of the thyroid among treated female rats. The incidence of C-cell adenomas or carcinomas among historical controls, however, precluded relating the incidence of these tumors to administration of the chemical. It was concluded that under the conditions of this bioassay malaoxon was not carcinogenic for F344 rats or B6C3F1 mice.

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