Biomedical subjects

National Toxicology Program

Publications and source records attributed to National Toxicology Program.

At least 523 records · Page 29Linked to original sources

PubMed1982

Carcinogenesis Bioassay of Caprolactam (CAS No. 105-60-2) in F344 Rats and B6C3F1 Mice (Feed Study).

A carcinogenesis bioassay of caprolactam, a chemical intermediate used in the production of nylon 6, was conducted by feeding diets containing 3,750 or 7,500 ppm caprolactam to groups of 50 male or female F344 rats and 7,500 or 15,000 ppm to groups of 50 male or female B6C3F1 mice for 103 weeks. Control groups consisted of 50 undosed rats and 50 undosed mice of each sex. Throughout the bioassay, mean body weight gains for dosed rats and mice of either sex were decreased when compared with those of the controls. No other compound-related effects were observed. Under the conditions of this bioassay, caprolactam 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 Synonyms: aminocaproic lactam; 2-oxohexamethylenimine

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PubMed1982

Carcinogenesis Bioassay of Butyl Benzyl Phthalate (CAS No. 85-68-7) in F344/N Rats and B6C3F1 Mice (Feed Study).

A carcinogenesis bioassay of butyl benzyl phthalate, a plasticizer for vinyl chloride plastics, was accomplished by feeding diets containing 6,000 or 12,000 ppm of the phthalate to groups of 50 F344/N rats and 50 B6C3F1 mice of each sex for 28 to 103 weeks. Mean body weights of dosed female rats and mice of each sex were lower than those of the control animals throughout most of the study. After week 14, an increasing number of dosed male rats died as a result of an unexplained internal hemorrhaging, and all surviving male rats were killed at week 29 to 30. Because of compound-related mortality, butyl benzyl phthalate was not adequately tested for carcinogenicity in male F344/N rats. Mononuclear cell leukemias occurred at a statistically significant (P=0.011) increased incidence in the high-dose group of female rats when compared with the control group and with a significantly (P=0.006) increasing trend (controls 7/49, 14%; low-dose 7/49, 14%; high-dose 18/50, 36%). The incidence in the high-dose group and the overall trend remained statistically significant (P=0.008 and P=0.019) when compared with the historical incidence for F344/N female rats with leukemia at this laboratory (77/ 399, 19%). Further, this leukoproliferation was generally characterized by splenomegaly and often by hepatomegaly. Administration of butyl benzyl phthalate was not associated with increased incidences of any type of tumor among male or female mice. Tumor rates were decreased in female rats for fibroadenomas of the mammary glands (20/49, 14/49, 9/50) and in male mice for lymphomas of the hematopoietic system (13/50, 11/49, 4/50) and for alveolar/bronchiolar adenomas or carcinomas (17/50, 11/49, 8/50). Under the conditions of this bioassay, butyl benzyl phthalate was probably carcinogenic for female F344/N rats, causing an increased incidence of mononuclear cell leukemias. The male F344/N rat study was considered inadequate for evaluation due to compound-related toxicity and early mortality. Butyl benzyl phthalate was not carcinogenic for B6C3F1 mice of either sex. Levels of Evidence of Carcinogenicity: Male Rats: Inadequate Study Female Rats: Positive Male Mice: Negative Female Mice: Negative Synonyms: BBP; benzyl butyl phthalate; phthalic acid; benzyl butyl ester; Santicizer 160

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PubMed1982

Carcinogenesis Bioassay of Di(2-ethylhexyl)adipate (CAS No. 103-23-1) in F344 Rats and B6C3F1 Mice (Feed Study).

Di(2-ethylhexyl)adipate is a plasticizer used to give flexibility to vinyl plastics. A carcinogenesis bioassay was conducted by feeding diets containing 12,000 or 25,000 ppm of di(2-ethylhexyl)adipate to groups of 50 male and 50 female F344 rats and 50 male and 50 female B6C3F1 mice for 103 weeks. Groups of 50 undosed rats and mice of each sex served as controls. All surviving animals were killed at 104 to 107 weeks. Mean body weights of high-dose rats and mice of either sex were lower than those of the controls throughout the study. Compound administration was not associated with tumor formation in F344 rats of either sex. Hepatocellular carcinomas or adenomas occurred in mice of both sexes in a dose-related fashion at incidences that were significantly higher for high-dose males and for low- and high-dose females than those in the controls. When compared with the incidence in historical laboratory control mice, however, the liver tumors in male mice could not be clearly related to compound administration. Under the conditions of this bioassay, di(2-ethylhexyl)adipate was not carcinogenic for F344 rats. Di(2-ethylhexyl)adipate was carcinogenic for female B6C3F1 mice, causing increased incidences of hepatocellular carcinomas, and was probably carcinogenic for male B6C3F1 mice, causing hepatocellular adenomas. Levels of Evidence of Carcinogenicity: Male Rats: Negative Female Rats: Negative Male Mice: Positive Female Mice: Positive Synonyms: bis(2-ethylhexyl)adipate; DEHA; octyl adipate; dioctyl adipate; DOA

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PubMed1982

Carcinogenesis Bioassay of 1,2-Dibromoethane (CAS No. 106-93-4) in F344 Rats and B6C3F1 Mice (Inhalation Study).

A carcinogenesis bioassay of 1,2-dibromoethane, a widely used nematocide and leaded gasoline additive, was conducted by exposing groups of 50 F344 rats and B6C3F1 mice of each sex by inhalation to concentrations of 10 or 40 ppm of the 1,2-dibromoethane for 78-103 weeks. Untreated controls consisted of 50 rats and 50 mice of each sex exposed in chambers to ambient air. Throughout the study, mean body weights of high-dose rats and high-dose mice of either sex were lower than those of the corresponding untreated controls. Survival of the high-dose rats of either sex and of the low- and high-dose female mice was significantly shorter than that in the corresponding controls. The principal cause of early death in control and dosed male mice was ascending, suppurative urinary tract infection that resulted in necrotic, ulcerative lesions around the urethral opening, chronic or suppurative cystitis (often with urinary tract obstruction), and ascending suppurative pyelonephritis. Carcinomas and adenocarcinomas of the nasal cavity were observed with significantly increased incidences (P<0.001) in high-dose rats of either sex relative to controls. The incidences of adenocarcinomas and adenomas of the nasal cavity were also significantly increased (P<0.001) in low-dose rats of either sex. Adenomatous polyps of the nasal cavity showed significantly increased incidence (P<0.001) in low-dose male rats. The combined incidence of alveolar/bronchiolar adenomas and carcinomas was statistically significant (P=0.024) for high-dose female rats. Hemangiosarcomas of the circulatory system (mainly spleen) and mesotheliomas of the tunica vaginalis occurred in high-dose male rats with significantly increased incidences (P<0.001) relative to controls. The incidence of fibroadenomas of the mammary gland was significantly elevated (P<0.001) in dosed female rats relative to controls. The incidences of alveolar/bronchiolar carcinoma and alveolar/bronchiolar adenoma were significantly increased(P<0.001) in high-dose male mice relative to controls. These tumors were also increased in high-dose female mice (P=0.007 for adenomas and P<0.001 for carcinomas). Hemangiosarcomas occurred in low- and high dose female mice at incidences significantly greater (P<0.001) than the incidence in the controls (0/50). High-dose female mice also had significantly increased incidences of subcutaneous fibrosarcomas (P<0.001) and of nasal cavity carcinomas (P=0.013). Low-dose female mice also showed a significantly increased incidence (P<0.001) of mammary gland adenocarcinomas. Exposure to 1,2-dibromoethane was also associated with hepatic necrosis and toxic nephropathy in rats of either sex, testicular degeneration in male rats, retinal degeneration in female rats, and epithelial hyperplasia of the respiratory system in mice. Under the conditions of this bioassay, 1,2-dibromoethane was carcinogenic for F344 rats, causing increased incidences of carcinomas, adenocarcinomas, adenomas of the nasal cavity, and hemangiosarcomas of the circulatory system in males and females; mesotheliomas of the tunica vaginalis and adenomatous polyps of the nasal cavity in males; and fibroadenomas of the mammary gland and alveolar/bronchiolar adenomas and carcinomas (combined) in females. 1,2-Dibromoethane was carcinogenic for B6C3F1 mice, causing alveolar/bronchiolar carcinomas and alveolar/bronchiolar adenomas in males and females; and hemangiosarcomas of the circulatory system, fibrosarcomas in the subcutaneous tissue, carcinomas of the nasal cavity, and adenocarcinomas of the mammary gland in females. Levels of Evidence of Carcinogenicity: Male Rats: Positive Female Rats: Positive Male Mice: Positive Female Mice: Positive Synonyms: ethylene dibromide; EDB; ethylene bromide

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PubMed1982

Carcinogenesis Bioassay of 2,3,7,8-Tetrachlorodibenzo-p-dioxin (CAS No. 1746-01-6) in Osborne-Mendel Rats and B6C3F1 Mice (Gavage Study).

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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PubMed1982

Carcinogenesis Bioassay of 1,2-Dibromo-3-chloropropane (CAS No. 96-12-8) in F344 Rats and B6C3F1 Mice (Inhalation Study).

1,2-Dibromo-3-chloropropane (DBCP), a contaminant (0.05%) of the flame retardant tris(2,3-dibromopropyl)phosphate, has been used primarily as a soil fumigant to control nematodes. Unlike other halogenated nematocides, DBCP can be applied to soil without damaging growing perennials. Since it is slightly soluble in water at the concentrations used (30 ppm), DBCP can be either injected directly into the soil or added to irrigation water. By 1972, an estimated 12.3 million pounds were being used annually; in 1977, a total of 832,000 pounds were used in California, mostly on grapes and tomatoes. A carcinogenesis bioassay of technical grade 1,2-dibromo-3-chloropropane (DBCP), which contained trace amounts of epichlorohydrin and 1,2-dibromoethane, was conducted by exposing groups of 50 F344 rats and B6C3F1 mice of each sex by inhalation to concentrations of 0.6 or 3.0 ppm DBCP for 6 hours per day, 5 days per week, for 76 to 103 weeks. Untreated chamber controls consisted of 50 rats and 50 mice of each sex. Surviving high-dose rats were killed at week 84. Surviving high-dose female mice and low-and high-dose male mice were killed at week 76. Low-dose rats and female mice were killed at week 104. Accelerated mortality occurred in the high-dose groups of both species. Early deaths of high-dose rats and mice were associated with respiratory tract tumors. Interference with breathing and metastasis to the brain were major contributing factors in these deaths. Among male mice, accelerated mortality occurred in low-dose and control groups as well as in the high-dose group. Urogenital infection appeared to be associated with these deaths. Carcinomas, squamous-cell carcinomas, and adenocarcinomas of the nasal cavity and squamous-cell papillomas of the tongue each occurred in high-dose male rats at incidences significantly higher than those in the corresponding controls. Adenocarcinomas, adenomas, adenomatous polyps, and squamous-cell papillomas of the nasal cavity and adenomatous polyps of the nasal turbinates occurred in low-dose male rats with significantly increased incidences relative to controls. Carcinomas and adenocarcinomas of the nasal cavity, squamous-cell papillomas of the tongue, squamous-cell papillomas and carcinomas (combined) of the pharynx, and adenomas of the adrenal cortex each occurred in high-dose female rats at incidences significantly higher than those in the corresponding controls. Also, adenomas and squamous-cell papillomas of the nasal cavity, adenomas of the adrenal cortex, and fibroadenomas of the mammary gland were increased significantly in low-dose female rats when compared with controls. Adenocarcinomas of the nasal cavity in high-dose female mice, papillary carcinomas in low-dose female mice, and carcinomas, squamous cell carcinomas of the nasal cavity, and alveolar/bronchiolar adenomas or carcinomas of the lung in high-dose male and female mice occurred at incidences significantly higher than those in the corresponding controls. Exposure to DBCP vapor was also associated with toxic tubular nephropathy in rats and mice of either sex and with proliferative changes in the nasal mucosa, lung, and forestomach in mice. Under the conditions of this bioassay, DBCP was carcinogenic for male and female F344/N rats, including increased incidences of nasal cavity tumors and tumors of the tongue in both sexes, and cortical adenomas in the adrenal glands of females. DBCP was carcinogenic in male and female B6C3F1 mice, including increased incidences of nasal cavity tumors and lung tumors. Levels of Evidence of Carcinogenicity: Male Rats: Positive Female Rats: Positive Male Mice: Positive Female Mice: Positive Synonyms: DBCP; dibromochloropropane; Nemagon; Fumazone

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PubMed1981

Carcinogenesis Bioassay of FD & C Yellow No. 6 (CAS No. 2783-94-0).

A carcinogenesis bioassay was conducted using groups of 50 male and 50 female F344 rats and B6C3F1 mice which were fed diets containing 12,500 or 25,000 ppm FD & C Yellow No. 6, a widely used food colorant, for 103 weeks. Groups of 90 male and 90 female rats and 50 male and 50 female mice served as undosed controls. Throughout the study, mean body weights of high-dose female rats and all low-dose groups were comparable with those of the controls, but mean body weights of high-dose male rats and high-dose male and female mice were slightly lower (10% or less) than those of the controls. No compound-related neoplastic or nonneoplastic lesions were observed in the rats. The incidence of hepatocellular carcinomas in low-dose male mice was significantly higher than that in the controls, but the lack of a significant increase in high-dose males and the variability of liver tumors in B6C3F1 male mice precluded clearly relating the occurrence of these tumors to the administration of FD & C Yellow No.< >6. Under the conditions of this bioassay, there was no clear evidence of the carcinogenicity of FD & C Yellow No. 6 in 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: Sunset Yellow FCF

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PubMed1981

Carcinogenesis Bioassay of Cytembena (CAS No. 21739-91-3).

A carcinogenesis bioassay of cytembena, a cytostatic agent, was conducted by injecting intraperitoneally 7 or 14 mg/kg into groups of 50 male and 50 female F344 rats and 12 or 24 mg/kg into groups of 50 male or 50 female B6C3F1 mice three times per week for 104 weeks. Groups of 50 rats and 50 mice of both sexes served as vehicle controls. Mean body weights of dosed and vehicle-control rats were comparable throughout the bioassay. Mean body weights of dosed and vehicle-control mice were comparable for the first 73 weeks of the bioassay; mean body weight of the high dose male mice was slightly lower than that of the vehicle controls after 73 weeks, and that of the high-dose female mice was lower after week 87. In dosed male rats, mesotheliomas in the tunica vaginalis and malignant mesotheliomas in multiple organs occurred with dose-related trends and at incidences in each of the dosed groups which were significantly higher than those in the vehicle control rats. In dosed female rats, fibroadenomas in the mammary gland occurred with a dose-related trend and at a significantly higher incidence in the high-dose group than in vehicle control rats. Under the conditions of this bioassay, cytembena was carcinogenic for male and female F344 rats, causing increased incidences of mesotheliomas in the tunica vaginalis and in multiple organs of males and fibroadenomas in the mammary gland of females. Cytembena was not carcinogenic for male or female B6C3F1 mice. Levels of Evidence of Carcinogenicity: Male Rats: Positive Female Rats: Positive Male Mice: Negative Female Mice: Negative Synonyms: cytembene; 2-butenoic acid; 3-bromo-4-(4-methoxyphenyl)-4-oxo-, sodium salt

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PubMed1980

Bioassay of Phenol for Possible Carcinogenicity (CAS No.108-95-2).

Phenol ranked 38th in production among U.S. chemicals in 1978 with annual production of 2.38 billion pounds. Approximately 90% of the phenol produced is used in the manufacture of phenolic (phenol formaldehyde) resins, caprolactam, bisphenol A, alkyl phenol, and adipic acid. The remainder of the phenol is used to produce an assortment of end products, including salicylic acid, phenacetin, dyes, metal cleaners, disinfectants, antiseptics, photographic chemicals, wood preservatives (pentachlorophenol), paints, paint and varnish removers, and agricultural chemicals (2,4-D and parathion). A bioassay of phenol to test for possible carcinogenicity was conducted by providing this substance in drinking water to F344 rats and B6C3F1 mice. Groups of 50 rats and 50 mice of each sex were given drinking water containing 2,500 or 5,000 ppm phenol for 103 weeks. As matched controls, groups of 50 rats and 50 mice of each sex received tap water. A dose-related depression in mean body weight gain occurred in rats and mice of each sex. Rats and mice given water containing phenol drank less than did the corresponding controls. A dose-related decrease in water consumption was observed for mice. An increased incidence of leukemia or lymphomas was detected in male rats and may have been associated with the administration of phenol. Although the incidence of these tumors in the low-dose group was significantly higher than that in controls, the incidence in the high-dose group was not. Thus an association with administration of phenol was not established. Under the conditions of this bioassay, phenol was not carcinogenic for either male or female F344 rats or male and female B6C3F1 mice. Levels of Evidence of Carcinogenicity: Male Rats: Negative Female Rats: Negative Male Mice: Negative Female Mice: Negative

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PubMed1980

Bioassay of a Mixture of 1,2,3,6,7,8-Hexachlorodibenzo-p-dioxin and 1,2,3,7,8,9-Hexachlorodibenzo-p-dioxin (Dermal Study) for Possible Carcinogenicity (CAS No. 57653-85-7; CAS No. 19408-74-3).

Hexachlorodibenzo-p-dioxin (HCDD) is formed as a byproduct during the manufacture of certain chlorophenols and has been found in trichlorophenol, tetrachlorophenol, pentachlorophenol and in the chlorophenol-derived herbicides 2,4-dichlorophenoxyacetic acid (2,4-D) and 2,4,5-trichlorophenoxyacetic acid (2,4,5-T). From 1967 to 1970, the concentration of HCDD in commercial pentachlorophenol ranged from 0.03 to 38 ppm. Since then, HCDD levels in pentachlorophenol have been reduced to less than 1 ppm. A bioassay of a mixture of 1,2,3,6,7,8-and 1,2,3,7,8,9-hexachlorodibenzo-p-dioxins (HCDD) for possible carcinogenicity was conducted by dermal application of a suspension of this substance to Swiss-Webster mice. HCDD (0.01 &mgr;g) suspended in 0.1 ml acetone was applied to the backs of 30 mice of each sex 3 days per week for 104 weeks. During the first 16 weeks, doses were 0.005 &mgr;g HCDD per application. An additional 30 mice of each sex were pretreated with one application of 50 &mgr;g DMBA in 0.1 ml acetone 1 week before the initiation of the HCDD applications. As vehicle controls, 45 mice of each sex received 0.1 ml of acetone three times per week. Thirty animals of each sex served as untreated controls. Mean body weights of all test and vehicle control mice were comparable throughout the bioassay; mean body weights of untreated controls were higher than those of the test and vehicle-control groups. In male mice, the incidence of alveolar/bronchiolar carcinomas in the group administered only HCDD was significantly higher (P=0.045) than that in the vehicle-control group; however, the incidence was not significantly higher when compared with untreated controls. In female mice, the incidences of fibrosarcomas of the skin were significantly higher (P=0.044) in animals administered HCDD (both with and without pretreatment with DBMA) than in the untreated-control group; however, when the incidences were compared with those of the vehicle controls (relative risk=3.037) the results were not significant. Under the conditions of this bioassay, HCDD was not carcinogenic for male or female Swiss-Webster mice. Levels of Evidence of Carcinogenicity: Male Mice: Negative Female Mice: Negative Synonym: HCDD

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PubMed1980

Bioassay of 2,6-Toluenediamine Dihydrochloride for Possible Carcinogenicity (CAS No. 15481-70-6).

2,6-Toluenediamine is used as an intermediate in the production of dyes for furs and textiles, and of flexible polyurethane foams and elastomers. A bioassay of 2,6-toluenediamine dihydrochloride for possible carcinogenicity was conducted by feeding diets containing the test chemical to F344 rats and B6C3F1 mice. Groups of 50 rats of each sex were fed the test chemical at two doses, 250 or 500 ppm, for 103 weeks and observed for 1 additional week. Groups of 50 mice of each sex were fed the test chemical at two doses, 50 or 100 ppm, for 103 weeks and then observed for 1 additional week. Groups of 50 untreated rats and 50 untreated mice of each sex were used as matched controls. All surviving animals were killed and necropsied at 104 weeks. Weight gain depression was less than 10% for dosed groups of male rats and male and female mice, when compared with controls. Mean body weight gain was depressed 17% in low-dose female rats and 27% in high-dose female rats. Mortality was not increased in rats or mice of either sex by the test chemical. No clinical evidence indicated that mice of either sex received a maximum tolerated dose of the compound. In male rats, islet-cell adenomas of the pancreas and neoplastic nodules or carcinomas of the liver occurred in dose-related trends that were significant using the Cochran-Armitage test (P=0.025 and P=0.037, respectively). The results of the Fisher exact test were not significant for either lesion. The occurrences of tumors in dosed female rats were not significantly different from those in control rats. Significant results in the negative direction were observed in the incidences of C-cell tumors of the thyroid in male rats and of fibroadenomas of the mammary gland in female rats. In male mice, in the low-dose group, lymphomas occurred at an incidence significantly higher (P=0.046) than that of the corresponding control group; however, the incidence was not significant when the Bonferroni criterion for multiple comparison was used. The occurrence of hepatocellular carcinomas in female mice was dose related, but the result of the Fisher exact test comparing the incidence in the high-dose group with that in the controls was not significant. It was concluded that, under the conditions of the bioassay, 2,6-toluenediamine dihydrochloride was not carcinogenic for male and female F344 rats or for male and female B6C3F1 mice. Levels of Evidence of Carcinogenicity: Male Rats: Negative Female Rats: Negative Male Mice: Negative Female Mice: Negative

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PubMed1980

Bioassay of Selsun(R) for Possible Carcinogenicity.

A bioassay of Selsun(R) for possible carcinogenicity was conducted by applying this substance dermally to ICR Swiss mice. Selsun(R), an antidandruff shampoo, contains 2.5% selenium sulfide. Groups of 50 mice of each sex were exposed to 0.05 ml of 25% or 50% Selsun(R) in distilled water three times a week on a 2-x 3-cm clipped dorsal surface. Vehicle controls consisted of 50 mice of each sex that were clipped and treated with distilled water. Untreated controls consisted of 50 mice of each sex that were only clipped. Surviving mice were killed and necropsied at week 88. Mean body weights of untreated control, vehicle control, low-dose, and high-dose groups were comparable throughout the bioassay. Amyloidosis was a factor in the deaths of most animals after 1 year. In male mice, alveolar/bronchiolar carcinomas or adenomas occurred witha dose-related trend that was significant (P=0.008). The result of the Fisher exact test comparing the incidence in the high-dose group with that in the vehicle controls is also significant, but the incidence of the high-dose group, when compared with that of the untreated controls, is not significant. Under the conditions of this bioassay, dermal application of Selsun(R) was not carcinogenic for ICR Swiss mice. The study was limited, however, by the relatively short lifespan of this strain of mouse. Levels of Evidence of Carcinogenicity: Male Mice: Negative Female Mice: Negative

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PubMed1980

Bioassay of a Mixture of 1,2,3,6,7,8-Hexachlorodibenzo-p-dioxin and 1,2,3,7,8,9-Hexachlorodibenzo-p-dioxin (Gavage) for Possible Carcinogenicity (CAS No. 57653-85-7,CAS No. 19408-74-3).

Hexachlorodibenzo-p-dioxins (HCDD) are formed during the manufacture of certain chlorophenols. They have been found in trichlorophenol, tetrachlorophenol, and pentachlorophenol and in the chlorophenol-derived herbicides, 2,4-dichlorophenoxyacetic acid (2,4-D) and 2,4,5-trichlorophenoxyacetic acid (2,4,5-T). From 1967 to 1970, the concentration of HCDD in commercial pentachlorophenol ranged from 0.03 to 38 ppm. Since then, HCDD levels in pentachlorophenol have been less than 1 ppm. A bioassay of a mixture of 1,2,3,6,7,8- and 1,2,3,7,8,9-hexachlorodibenzo-p-dioxin (HCDD) for possible carcinogenicity was conducted by administering the test material by gavage to Osborne-Mendel rats and B6C3F1 mice for 104 weeks. Fifty rats and 50 mice of each sex were administered HCDD suspended in a vehicle of 9:1 corn oil-acetate 2 days per week for 104 weeks at doses of 1.25, 2.5, or 5 &mgr;g/kg/wk for rats and male mice and 2.5, 5, or 10 &mgr;g/kg/wk for female mice. Seventy-five rats and 75 mice of each sex served as vehicle controls. In addition, one untreated control group containing 25 rats and 25 mice of each sex was present in the HCDD 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 became evident in the males after week 68 of the bioassay and in the females after week 33. In mice, the mean body weight gain in the dosed groups was comparable with that of the vehicle control groups. No other toxic clinical signs were reported in either the rats or the mice. Administration of HCDD had no adverse effect on the survival of either species. In male rats, hepatocellular carcinomas or neoplastic nodules occurred at low incidences that were dose related (P=0.003). In a direct comparison, the incidence of these tumors in the high-dose group was higher (P=0.022) than that in the corresponding vehicle-control groups, but the Bonferroni requirement of P=0.017 for the multiple comparison of three dosed groups with a control group was not met. In female rats, hepatocellular carcinomas, adenomas, or neoplastic nodules occurred at incidences that were dose related (P<0.001), and in direct comparisons the incidences of these tumors in the mid-and high-dosed groups were significantly higher (P=0.006 and P<0.001, respectively) than those in the corresponding vehicle-control group. In male mice, hepatocellular carcinomas or adenomas occurred at incidences that were dose related (P=0.001), and in a direct comparison the incidence of these tumors in the high-dose group was significantly higher (P=0.001) than that in the corresponding vehicle-control group. In female mice, hepatocellular carcinomas or adenomas occurred at incidences that were dose-related (P=0.002), and the incidence of these tumors in the high-dose group was significantly higher (P=0.004) than that in the corresponding vehicle-control group. Complex nonneoplastic toxic liver lesions were seen in all dosed groups of rats and mice. Compound-associated hyperplastic lesions of the lung were also found in both male and female rats. Under the conditions of this bioassay, HCDD administered by gavage was carcinogenic, causing increased incidences of hepatocellular carcinomas or neoplastic nodules in female Osborne-Mendel rats and inducing hepatocellular carcinomas and adenomas in male and female B6C3F1 mice. HCDD was not demonstrated to be carcinogenic for male rats. Levels of Evidence of Carcinogenicity: Male Rats: Equivocal Female Rats: Positive Male Mice: Positive Female Mice: Positive Synonym: HCDD

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PubMed1980

Bioassay of Selenium Sulfide (Dermal Study) for Possible Carcinogenicity (CAS No. 7446-34-6).

Selenium is an essential nutrient, and various selenium compounds have industrial and medical uses. The possible carcinogenicity of selenium sulfide (a component in shampoos) was investigated by applying a suspension of this substance to the skin of ICR Swiss mice. Groups of 50 mice of each sex were treated by applying 0.5 mg or 1.0 mg selenium sulfide three times a week for 86 weeks to a clipped 2-x 3-cm dorsal surface. The selenium sulfide was suspended in 0.05 ml saline solution containing 0.5% carboxymethylcellulose. Mean body weights of all dosed and control groups were comparable throughout the study. Amyloidosis, previously reported as a cause of death in Swiss mice, was a factor in the deaths of most treated and control mice after 1 year, andthe study was terminated after 88 weeks when the majority of animals in all dosed and control groups had died. Under the conditions of this bioassay, dermal application of selenium sulfide did not produce a carcinogenic effect in ICR Swiss mice, but the study was limited by the relatively short lifespan of this strain of mouse. Levels of Evidence of Carcinogenicity: Male Mice: Negative Female Mice: Negative

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PubMed1980

Bioassay of Cinnamyl Anthranilate for Possible Carcinogenicity (CAS No. 87-29-6).

A bioassay of cinnamyl anthranilate (a synthetic flavoring agent) 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 the test chemical in diets containing 15,000 or 30,000 ppm for 103 weeks and then observed for an additional 2 or 3 weeks. Controls consisted of groups of 50 untreated rats and 50 untreated mice of each sex. All surviving animals were killed and necropsied at 105 to 107 weeks. Mean body weights of the dosed male and female rats and mice were lower than those of the corresponding controls throughout the bioassay, and weight decrements were dose related. Mortality in rats and mice of either sex was not affected by administration of the test chemical. In male rats, adenocarcinomas or adenomas of the renal cortex and acinar-cell carcinomas or adenomas of the pancreas were found in low incidences in dosed rats but not in control rats. In direct comparisons with matched control groups, the incidences of these tumors were not significantly increased; however, because these tumors rarely occur spontaneously in aging F344 rats, they were considered to be related to compound administration. Similar pancreatic or renal tumors have not been detected among 634 historical-control male F344 rats at the same laboratory. In the female rats, no tumors occurred at incidences that could be clearly related to the administration of the test chemical. In both male and female mice, the incidences of hepatocellular carcinomas or adenomas were dose related (P<0.001) and significant (P</= 0.001) in direct comparisons of dosed and control groups. It was concluded that under the conditions of this bioassay cinnamyl anthranilate was carcinogenic for male and female B6C3F1 mice, inducing increased incidences of hepatocellular carcinomas or adenomas. The test chemical was also carcinogenic for male F344 rats, inducing low incidences of acinar-cell carcinomas or adenomas of the pancreas and adenocarcinomas or adenomas of the renal cortex. Cinnamyl anthranilate was not carcinogenic for female F344 rats. Levels of Evidence of Carcinogenicity: Male Rats: Positive Female Rats: Negative Male Mice: Positive Female Mice: Positive

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PubMed1980

Bioassay of Fluometuron for Possible Carcinogenicity (CAS No. 2164-17-2).

Fluometuron is a phenylurea herbicide used in agriculture to control broad- leaved and grass weeds in cotton and sugarcane fields. The area of heaviest use is the Mississippi delta. Applications of low concentrations selectively kill weeds. A bioassay of the phenylurea herbicide fluometuron 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 fed diets containing 125 or 250 ppm of fluometuron for 103 weeks, and groups of 50 mice of each sex were fed diets containing 500 or 1,000 ppm of fluometuron for 103 weeks. Matched controls consisted of groups of 50 untreated rats and 25 untreated mice of each sex. All surviving animals were killed at 103 to 105 weeks. Splenomegaly observed in rats in the subchronic studies influenced selection of the doses for the chronic study; however, no splenic effects were observed in the chronic study. Mean body weights of the dosed groups of male and female rats and mice were essentially the same as those of the corresponding control groups. Survival of dosed groups of rats and mice was similar to that of the corresponding control groups. Similarities between mean body weights and survival between dosed and control animals in thechronic study suggest that these animals could have tolerated higher doses. The only possible carcinogenic effects from compound administration were in male mice. Incidences of hepatocellular carcinomas or adenomas in male mice were dose related, and the incidence in the high-dose group was marginally higher than that in the corresponding matched controls or pooled controls from concurrent studies. Under the conditions of this bioassay, fluometuron was not carcinogenic for F344 rats or for female B6C3F1 mice. Equivocal results were obtained for male B6C3F1 mice which may have had an increased incidence of hepatocellular tumors. Because of the equivocal findings and because both rats and mice may have been able to tolerate higher doses, it is concluded that additional testing of fluometuron for carcinogenicity is warranted. Levels of Evidence of Carcinogenicity: Male Rats: Negative Female Rats: Negative Male Mice: Equivocal Female Mice: Negative Synonym: 1,1-dimethyl-3-(a,a,a-trifluoro-m-tolyl) urea

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PubMed1980

Bioassay of Selenium Sulfide (Gavage) for Possible Carcinogenicity (CAS No. 7446-34-6).

Selenium sulfide is an ingredient in dandruff shampoos used in concentrations of 1% in products sold over-the-counter and 2.5% in products which are available by prescription only. Prescription shampoos have been shown in clinical studies to be of therapeutic value against dandruff. An antimitotic mechanism of action is suggested by data showing that selenium sulfide decreases the rate of incorporation of radioactively labeled thymidine into the DNA of dermal epithelial cells. Approximately 200 kg of selenium sulfide is estimated to be used annually for this purpose. A bioassay of selenium sulfide for possible carcinogenicity was conducted by administering this substance by gavage to F344 rats and B6C3F1 mice. Groups of 50 rats and 50 mice of each sex were administered selenium sulfide suspended in 0.5% aqueous carboxymethylcellulose 7 days per week for 103 weeks at either 3 or 5 mg/kg/day for rats and 20 or 100 mg/kg/day for mice. As vehicle controls, groups of 50 rats and 50 mice of each sex were administered only the 0.5% aqueous carboxymethylcellulose. Similar groups of untreated controls also were used. All surviving rats and mice were killed and necropsied at week 104 or 105. The significant effects that could be related to administration of selenium sulfide at the doses used were decreased body weight and increased tumor formation in female mice and in rats of each sex. Dosed rats and female mice had an increased incidence of hepatocellular carcinomas and adenomas. Dosed female mice also had an increased incidence of alveolar/bronchiolar carcinomas and adenomas. Under the conditions of this bioassay, selenium sulfide was carcinogenic for F344 rats and female B6C3F1 mice, including hepatocellular carcinomas in male and female rats and female mice and alveolar/bronchiolar carcinomas and adenomas in female mice. Selenium sulfide was not carcinogenic for male mice; but they have been able to tolerate higher doses. Levels of Evidence of Carcinogenicity: Male Rats: Positive Female Rats: Positive Male Mice: Negative Female Mice: Positive

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PubMed1980

Bioassay of 4,4'-Oxydianiline for Possible Carcinogenicity (CAS No. 101-80-4).

4,4'-Oxydianiline is used in the manufacture of high temperature resistant metal adhesives, molding and machine parts, and insulators. A bioassay of this chemical for possible carcinogenicity was conducted by feeding diets containing 200, 400, or 500 ppm of the test chemical to groups of 50 male or female F344 rats and 150, 300, or 800 ppm to groups of 50 male or female B6C3F1 mice for 104 weeks. Matched controls consisted of 50 untreated rats and 50 untreated mice of each sex. All surviving animals were killed at 104 to 105 weeks. A dose-related decrement in mean body weight gain was observed for all groups of dosed rats and mice. Survival was significantly shortened in the high-dose female rats and in the low- and mid-dose female mice. In male and female rats, hepatocellular carcinomas or neoplastic nodules occurred at incidences that were dose-related, and the incidences in all dosed groups (except low-dose females) were higher than those in the controls. The occurrence of follicular-cell adenomas or carcinomas of the thyroid was dose-related. Among groups of male and female rats, the incidences in the mid- and high-dose groups of either sex were significantly higher than those of the corresponding controls. In male and female mice, adenomas in the harderian glands occurred in all dosed groups at incidences that were significantly higher than the incidence in the matched controls. In low-dose male mice and in high-dose female mice, hepatocellular adenomas or carcinomas occurred at incidences significantly higher than those in the matched controls. In female mice, follicular-cell adenomas in the thyroid occurred with a positive linear trend, and in a direct comparison the incidence in the high-dose group was also significantly higher than that in the controls. Tumors occurring among male mice at increased incidences which could not be statistically related to the chemical were adenomas in the pituitary and hemangiomas of the circulatory system. Under the conditions of this bioassay, 4,4'-oxydianiline was carcinogenic for male and female F344 rats, inducing hepatocellular carcinomas or neoplastic nodules and follicular-cell adenomas or carcinomas of the thyroid. 4,4'-Oxydianiline was also carcinogenic for male and female B6C3F1 mice, including adenomas in the harderian glands, hepatocellular adenomas or carcinomas in both sexes, and follicular-cell adenomas in the thyroid of females. Levels of Evidence of Carcinogenicity: Male Rats: Positive Female Rats: Positive Male Mice: Positive Female Mice: Positive

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