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 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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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PMID:Bioassay of Dibutyltin Diacetate for Possible Carcinogenicity (CAS No. 1067-33-0). 1277 95

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
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PMID:Bioassay of Michler's Ketone for Possible Carcinogenicity (CAS No. 90-94-8). 1277 96

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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PMID:Bioassay of 4-Nitro-o-phenylenediamine for Possible Carcinogenicity (CAS No. 99-56-9). 1277 97

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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PMID:Bioassay of p-Quinone Dioxime for Possible Carcinogenicity (CAS No. 105-11-3). 1277 98

A carcinogenesis bioassay of zearalenone, an estrogenic mycotoxin, was conducted by feeding diets containing 25 or 50 ppm zearalenone to groups of 50 F344/N rats of each sex and 50 or 100 ppm to groups of 50 B6C3F1 mice of each sex for 103 weeks. Groups of 50 rats and 50 mice of each sex served as controls. Estimates based on food consumption data indicate that the low-and high-dose rats received daily doses of about 1 and 2 mg, respectively, of zearalenone per kg of body weight. Low-dose and high-dose mice received estimated daily doses of about 7-10 and 14-20 mg, respectively, of zearalenone per kg of body weight. Survival of dosed and control rats of each sex was comparable. Mean body weight gains of dosed rats of each sex were lower than those of the corresponding controls; depression in mean body weight gain was dose related. Final body weights of dosed rats were <9% lower than those of control rats. The average daily feed consumption of dosed rats of each sex was 91%-102% that of controls. Inflammation of the prostate, testicular atrophy, and hepatocellular cytoplasmic vacuolization (male rats), and nephrosis (male and female rats) were compound-related. Retinopathy and cataracts occurred in low-and high-dose male rats and in low-dose female rats, and were associated with the closeness to fluorescent light. No compound-related, increased tumor incidences were observed in rats in the chronic study. Survival of dosed and control mice of each sex was comparable. Mean body weight gains of high-dose male and low-dose female mice were lower than those of the controls. Terminal body weights of dosed mice were <8% below those of control mice. The average daily feed consumption by dosed mice of each sex was 97-99% that of the controls. Myelofibrosis in the bone marrow, uterine fibrosis, and cystic ducts in the mammary gland were related to the administration of zearalenone in female mice. The incidence of hepatocellular adenomas in female mice was dose related (P</=0.003), and the incidence of these tumors in high-dose female mice was significantly higher (P</=0.006) than those in the controls (control, 0/50; low-dose, 2/49; high-dose, 7/49). Pituitary adenomas occurred with statistically significant positive trends (P</=0.022 for males and P</=0.001 for females). The incidences of these tumors in high-dose mice were significantly increased relative to controls (P</=0.032 for males: 0/40, 4/45, 6/44; and P</=0.003 for females: 3/46, 2/43, 13/42). Under the conditions of this bioassay, zearalenone was not carcinogenic for F344/N rats of either sex. Zearalenone should be considered carcinogenic in B6C3F1 mice, as evidenced by the increased proportion of male and female mice with pituitary adenomas and by the increased proportion of female mice with hepatocellular adenomas. Levels of Evidence of Carcinogenicity: Male Rats: Negative Female Rats: Negative Male Mice: Positive Female Mice: Positive Synonym: trans-zearalenone
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PMID:Carcinogenesis Bioassay of Zearalenone (CAS No. 17924-92-4) in F344/N Rats and B6C3F1 Mice (Feed Study). 1277 1

2-Biphenylamine (2-aminobiphenyl) is a chemical intermediate used in the manufacture of C.I. Acid Red 15. It is present as a contaminant in 4-biphenylamine (a rubber antioxidant) and in diphenylamine (a dye intermediate, stabilizer for nitrocellulose explosives, and a topical agent for prevention of screwworm infestation in animals). Single-dose, 14-day, and 13-week studies were conducted using technical-grade 2-biphenylamine (2-aminobiphenyl) containing up to 2.5% of the carcinogenic contaminant, 4-biphenylamine. When the contamination was recognized, analytical development was begun to purify the material. The salt, 2-biphenylamine hydrochloride, was prepared to obtain a more pure test product, which contained 0.006%-0.049% 4-biphenylamine. The prechronic tests were completed by the time purification was accomplished, so data from a second 14-day study with 2-biphenylamine hydrochloride were used to help set dose levels for the chronic study. The results of the comparative 14-day studies showed that technical-grade 2-biphenylamine was more toxic to mice than rats than 2-biphenylamine hydrochloride as evidenced by greater incidence of splenomegaly and greater weight gain depression. The technical-grade 2-biphenylamine caused a dose-related decrease in hemoglobin concentration and a dose-related increase in leukocyte count in male and female mice in the 13-week study. Hemosiderosis, congestion, and extramedullary hematopoiesis were present in the spleens of nearly all rats receiving 3,000 ppm or more of the chemical, and in nearly all mice with 1,000 ppm or more 2-biphenylamine in their diets. The chronic study was conducted with the purified 2-biphenylamine hydrochloride by feeding diets containing 1,000 or 3,000 ppm 2-biphenylamine hydrochloride to groups of 49 or 50 F344/N rats and 50 B6C3F1 mice of each sex for 103 weeks. Groups of 50 rats and 50 mice of each sex served as controls. Survival of dosed male and female rats and dosed female mice was comparable with that of the corresponding controls. Survival of high-dose male mice was significantly (P<0.010) less than that of low-dose and control male mice. There were little or no differences in body weight changes for rats or mice between dosed and control groups, although there was a slight decrease in body weight gain at the end of the study for high-dose male (-11%) and female (-8%) rats. Inflammatory cells and interstitial fibrosis were found in increased incidence in the kidneys of dosed male rats as compared with controls and were considered to be compound related. In addition to the increase in renal inflammation and fibrosis, dosed male rats had more focal cellular changes of the liver than did the controls. There were no increased or decreased incidences of tumors in rats that could be associated with chemical administration. Myelomonocytic leukemia in male rats (control, 14/50; low-dose, 1/50; high-dose, 4/50) and fibroadenomas of the mammary gland in female rats (22/50, 10/49, 9/50) occurred with significantly (P<0.03) decreasing trends and the incidences in the dosed groups were significantly (P<0.02) lower than that in the controls. There were no increased or decreased incidences of tumors in rats that could be associated with chemical administration. Hemangiosarcomas from all sites occurred in female mice with a statistically significant (P</=0.002) positive trend. The observed incidence of hemangiosarcomas was 0/49, 1/50, and 7/50 in the control, low-dose, and high-dose groups, respectively. The incidence in the high-dose group was significantly (P<0.01) higher than that in controls. The conclusion that this was due to 2-biphenylamine rather than the contaminant, 4-biphenylamine, is supported by the absence of urinary bladder tumors, which are common to 4-biphenylamine. Hemangiosarcomas also occurred in male mice with a statistically significant positive trend (P=0.040 by a life table test), with incidences of 0/50, 2/50, and 3/50. None of the pairwise comparisons were statistically different. The development of hemangiosarcomas may have been curtailedment of hemangiosarcomas may have been curtailed in the high-dose group of male mice, since only 21/50 survived until the termination of the study. The hemangiosarcomas found in female mice are uncommon with only 6/816 (0.7&percnt;) previously seen in controls at the same laboratory. The rate for control male mice is equally low: 7/803 (0.9&percnt;). Alveolar/bronchiolar adenomas of the lung occurred at a significantly (P&lt;0.01) decreased rate in male mice with an incidence in dose groups lower (P&lt;0.05) than that in controls. Under the conditions of the bioassay, 2-biphenylamine hydrochloride was not carcinogenic for F344/N rats of either sex. 2-Biphenylamine hydrochloride was carcinogenic for B6C3F1 female mice, inducing hemangiosarcomas at various sites. The evidence for an association between the administration of 2-biphenylamine hydrochloride and the increased incidence of hemangiosarcomas in male mice was equivocal. Levels of Evidence of Carcinogenicity: Male Rats: Negative Female Rats: Negative Male Mice: Equivocal Female Mice: Positive
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PMID:Carcinogenesis Bioassay of 2-Biphenylamine Hydrochloride (CAS No. 2185-92-4) in F344/N Rats and B6C3F1 Mice (Feed Study). 1277 3

A carcinogenesis bioassay of textile grade C.I. Acid Red 14 (67%-71% purity) was conducted by feeding diets containing 6,000 or 12,500 ppm of this dye for 103-104 weeks to groups of 50 male F344 rats, 12,500 or 25,000 ppm to groups of 50 female F344 rats, and 3,000 or 6,000 ppm to groups of 50 B6C3F1 mice of either sex. Groups of 90 untreated rats of either sex and 50 untreated mice of either sex served as controls. Throughout the study, mean body weights of dosed rats of either sex and dosed female mice were comparable with those of the controls, while the mean body weight of high-dose male mice was slightly lower than that of the controls. Fourteen male rats in the low-dose group and 2 in the high-dose group accidentally drowned between weeks 84 and 103; 56% and 60% of these groups survived to terminal kill compared with 78% of the controls. These losses may have reduced the sensitivity of the assay in male rats. Rats and mice may have tolerated higher doses, but the slight depression of mean body weight in high-dose male mice and the non-neoplastic lesions observed in dosed female mice and in rats of both sexes suggest that doses administered in this study could be considered maximum tolerated doses. Endometrial stromal polyps of the uterus were observed in high-dose female rats at an incidence significantly higher (P=0.008) than that seen in the controls (controls: 9/87, 10%; low-dose: 11/50, 22%; high-dose: 14/50, 28%). However, the observed incidence of this tumor in the dosed groups was similar to the historical rate in untreated female F344 rats at this laboratory (65/286, 23%; range 10%-37%). Hence, the increased incidence of this lesion is not regarded as being associated with the administration of C.I. Acid Red 14. Administration of C.I. Acid Red 14 to mice was not associated with an increased incidence of any tumor type. Under the conditions of this bioassay, C.I. Acid Red 14 was not carcinogenic for F344 rats or B6C3F1 mice of either sex. Levels of Evidence of Carcinogenicity: Male Rats: Negative Female Rats: Negative Male Mice: Negative Female Mice: Negative Synonym: 4-hydroxy-3-(4-Sulfo-1-naphthalenyl)azo-1-naphthalenesulfonic acid, disodium
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PMID:Carcinogenesis Bioassay of C.I. Acid Red 14 (CAS No. 3567-69-9) in F344/N Rats and B6C3F1 Mice (Feed Study). 1277 16

A carcinogenesis bioassay of 2,6-dichloro-p-phenylenediamine, a chemical intermediate, was conducted in groups of 50 F344 rats and B6C3F1 mice of either sex. Male rats were fed diets containing 1,000 or 2,000 ppm 2,6-dichloro-p-phenylenediamine and female rats were fed 2,000 or 6,000 ppm for 103 weeks. Mice were fed 1,000 or 3,000 ppm of the test chemical for 103 weeks and observed for an additional 8 weeks. Controls consisted of 50 untreated rats and 50 untreated mice of each sex. Throughout the study, mean body weights of dosed rats and mice of either sex were lower than those of the corresponding controls. A dose-related weight gain depression was particularly pronounced for rats. Ectopic hepatocytes were observed at an increased incidence in the pancreas and nephrosis was observed in increased severity in dosed rats of either sex when compared with the corresponding controls. No increase in any tumor type was observed in treated male or female rats when compared to controls. Increased incidences of liver tumors were observed in mice of both sexes. In male mice, the incidence of hepatocellular adenomas exhibited a significant positive dose-related trend (P=0.002), and the increased incidence of hepatocellular adenomas was statistically significant in the high-dose group(4/50, 7/50, 15/50: P=0.005). The combined incidence of hepatocellular adenomas and carcinomas showed a significant positive dose-related trend (P=0.004) and was statistically significant in the high-dose group (16/50, 19/50, 29/50: P=0.008). In female mice, hepatocellular carcinomas exhibited a significant positive dose-related trend (P=0.025), but no single dose group had a statistically significant increased incidence of either adenomas (4/50, 4/50, 9/50; high-dose effect: P=0.12) or carcinomas (2/50, 2/50, 7/50; high-dose effect: P=0.08) alone. When the incidences of hepatocellular adenomas and carcinomas were combined (6/50, 6/50, 16/50), these data gave a positive dose-related trend (P=0.004) and were statistically significant in the high-dose group (P=0.014). Under the conditions of this bioassay, 2,6-dichloro-p-phenylenediamine was carcinogenic for male and female B6C3F1 mice, causing increased incidences of combined hepatocellular adenomas and carcinomas, and for male B6C3F1 mice, causing an increased incidence of hepatocellular adenomas alone. 2,6-Dichloro-p-phenylenediamine was not carcinogenic for male or female F344 rats. Levels of Evidence of Carcinogenicity: Male Rats: Negative Female Rats: Negative Male Mice: Positive Female Mice: Positive
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PMID:Carcinogenesis Bioassay of 2,6-Dichloro-p-Phenylenediamine (CAS No. 609-20-1) in F344 Rats and B6C3F1 Mice (Feed Study). 1277 17

A carcinogenesis bioassay of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), a contaminant in several phenoxy herbicides, was conducted by administering TCDD by gavage to Osborne-Mendel rats and B6C3F1 mice for 104 weeks. Fifty rats and mice of each sex were given TCDD suspended in a vehicle of 9:1 corn oil-acetone 2 days per week for 104 weeks at doses of 0.01, 0.05, or 0.5 &mgr;g/kg/wk for rats and male mice and 0.04, 0.2, or 2.0 &mgr;g/kg/wk for female mice. Seventy-five rats and 75 mice of each sex served as vehicle controls. One untreated control group containing 25 rats and 25 mice of each sex was present in the TCDD treatment room, and one untreated control group containing 25 rats and 25 mice of each sex was present in the vehicle-control room. All surviving animals were killed at 105 to 108 weeks. In rats, a dose-related depression in mean body weight gain was observed in the males after week 55 of the bioassay and in the females after week 45. In mice, the mean body weight gain in the dosed groups was comparable to that of the vehicle-control groups. In male rats, increased incidences of follicular-cell adenomas in the thyroid were dose related and were significantly (P=0.001) higher in the high-dose group than in the vehicle controls (1/69, 1%; 5/48, 10%; 6/50, 12%; 10/50, 20%). Similarly in the female rats, an increase (though not statistically significant) was seen in the high-dose group (3/73, 4%; 2/45, 4%; 1/49, 2%; 6/47, 13%). In female rats, the incidence of neoplastic nodules of the liver in the high-dose group was significantly (P=0.006) higher than that in the vehicle control group (5/75, 7%; 1/49, 2%; 3/50, 6%; 12/49, 24%). In male and female mice, incidences of hepatocellular carcinomas were dose related and the incidences in the high-dose groups were significantly (P=0.002 and 0.014, respectively) higher than those in the corresponding vehicle control groups (males: 8/73, 11%; 9/49, 18%; 9/49, 16%; 17/50, 34%; females: 1/73, 1%; 2/50, 4%; 2/48, 4%; 6/47, 13%). In female mice, follicular-cell adenomas in the thyroid occurred at dose-related incidences, and were significantly (P=0.009) higher in the high-dose groups than those in the vehicle controls (0/69, 0%; 3/50, 6%; 1/47, 2%; 5/46, 11%). Increased incidences of toxic hepatitis related to the administration of the test chemical were detected among high-dose rats and high-dose mice of each sex. Under the conditions of this bioassay, 2,3,7,8-tetrachlorodibenzo-p-dioxin was carcinogenic for Osborne-Mendel rats, including follicular-cell thyroid adenomas in males and neoplastic nodules of the liver in females. TCDD was also carcinogenic for B6C3F1 mice, including hepatocellular carcinomas in male and females and follicular-cell thyroid adenomas in females. Levels of Evidence of Carcinogenicity: Male Rats: Positive Female Rats: Positive Male Mice: Positive Female Mice: Positive Synonyms: 2,3,7,8-TCDD; TCDD
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PMID:Carcinogenesis Bioassay of 2,3,7,8-Tetrachlorodibenzo-p-dioxin (CAS No. 1746-01-6) in Osborne-Mendel Rats and B6C3F1 Mice (Gavage Study). 1277 26

2,4-Dimethoxyaniline hydrochloride, the hydrochloride salt of the dye intermediate 2,4-dimethoxyaniline, was selected for bioassay by the National Cancer Institute because of the increased incidence of bladder cancer among dye manufacturing industry workers. Aromatic amines are one of several classes of chemicals thought to contribute to the increased cancer risk in this industry. A bioassay for the possible carcinogenicity of 2,4-dimethoxyaniline HCl was conducted using Fischer 344 rats and B6C3F1 mice. 2,4-Dimethoxyaniline HCl was administered in the feed, at either of two concentrations, to groups of 50 male and 50 female animals of each species. Twenty animals of each sex and species were placed on test as controls. The high and low dietary concentrations of 2,4-dimethoxyaniline HCl were, respectively, 3,000 and 1,500 ppm for rats and 5,000 and 2,500 ppm for mice. The compound was administered in the diet for 104 weeks to rats and 103 weeks to mice, followed by a 1-week observation period for both species. There were no significant positive associations between the concentrations of 2,4-dimethoxyaniline HCl administered and mortality in rats or mice of either sex. Adequate numbers of animals in all groups survived sufficiently long to be at risk from late-developing tumors. Dose-related mean body weight depression was observed for females of both species, indicating that the concentrations of 2,4-dimethoxyaniline HCl administered to these groups may have approximated the maximum tolerated concentrations. Compound-related mean body weight depression was only slight for male rats and was apparent in male mice only until week 50; however follicular-cell hyperplasias and cystic follicles of the thyroid were observed in dosed male mice, suggesting that the concentrations the male mice received may have approximated the maximum tolerated concentrations. Since no distinct mean body weight depression in relation to controls, no significant accelerated mortality, and no other signs of toxicity were associated with administration of 2,4-dimethoxyaniline HCl to male rats, it is possible that these animals may have been able to tolerate a higher dietary concentration. There was a significant positive trend between concentration of the test chemical and the incidence of a combination of hepatocellular carcinomas and adenomas in male mice and an increase in the combination of these lesions in female mice. However, no statistically significant differences in tumor incidence at any site were observed when dosed rats and mice were compared to their respective controls. Under the conditions of this bioassay there was no convincing evidence for the carcinogenicity of 2,4-dimethoxyaniline HCl in Fischer 344 rats or B6C3F1 mice. Levels of Evidence of Carcinogenicity: Male Rats: Negative Female Rats: Negative Male Mice: Negative Female Mice: Negative Synonyms: 2,4-dimethoxybenzenamine hydrochloride; 4-methoxy-o-anisidine hydrochloride; 2-methoxy-p-anisidine hydrochloride
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PMID:Bioassay of 2,4-dimethoxyaniline hydrochloride for possible carcinogenicity. 1279 92


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