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Target Concepts:
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Query: UMLS:C0023418 (
leukemia
)
93,477
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Allyl isovalerate, a synthetic fragrance and flavoring ingredient in use since the 1950's, may be found in various products at the following concentrations: soap, 30 ppm; detergent, 3 ppm; creams, 15 ppm; perfume, 50 ppm; nonalcoholic beverages, 9 ppm; ice cream, 18 ppm; candy, 22 ppm; baked goods, 15-48 ppm; and gelatins and puddings, 1 ppm. A colorless liquid with an apple-like odor and taste, allyl isovalerate is approved by the U.S. Food and Drug Administration for use in foods. Specific production figures are not available, but U.S. production in 1980 exceeded 1,000 pounds. Carcinogenesis studies of allyl isovalerate (96% pure) were conducted by administering the test chemical in corn oil gavage to groups of 50 male and 50 female F344/N rats and to groups of 50 male and 50 female B6C3F1 mice at doses of 31 or 62 mg/kg. The doses selected were based on the chemically-induced toxic effects and depressed weight gains obtained from the 13-week studies. Doses were administered five times per week for 103 weeks. Groups of 50 rats and 50 mice of each sex received corn oil by gavage on the same dosing schedule and served as vehicle controls. Survival and mean body weight gain of rats of each sex and male mice were not adversely affected by the administration of allyl isovalerate. The significantly lower survival (P=0.001) and the lower mean body weight of low-dose female as compared with controls are likely consequences of the high incidence of a genital tract infection in the low-dose females. This infection was probably responsible for the deaths of 11/19 control, 22/33 low-dose, and 13/25 high-dose female mice that died before the end of the study. Squamous cell papillomas and epithelial hyperplasia of the nonglandular stomach were observed in dosed male mice in the 2-year studies (squamous cell papillomas: 0/50, 1/50, 2%, 3/48, 6%; epithelial hyperplasia: 1/50, 2%, 1/50, 2%, 7/48, 15%). The papillomas occurred with a significant positive trend (P<0.05). The incidence of high-dose male mice with squamous cell papillomas of the nonglandular stomach was also higher (P<0.01) than the historical rate for vehicle control male B6C3F1 mice in the Bioassay Program (5/881, 0.6%). Forestomach lesions were also observed in female mice: squamous cell papillomas (1/50, 0/50, 2/50) and epithelial hyperplasia of the nonglandular stomach (0/50, 2/50, 3/50). Pancreatic acinar-cell adenomas occurred at higher incidences in the dosed male rats than in the controls (control, 1/50, 2%; low-dose, 4/50, 8%; high-dose, 2/50, 4%). Pancreatic acinar-cell tumors were not observed in female rats. Preputial gland adenomas were observed in increased incidence in low-dose male rats (0/50, 4/50, 8%; P<0.05, 1/50, 2%). Mononuclear-cell leukemias in rats and lymphomas in mice occurred with increased incidences. This consistent dose-response increase among both rats and mice indicates that allyl isovalerate adversely affects the hematopoietic system. Cholangiofibrosis, nodular regeneration, cirrhosis, focal necrosis, fatty metamorphosis, and cytoplasmic vacuolization were observed at increased incidences in the livers of high-dose male and female rats in the 2-year study. No compound-related nonneoplastic lesions were observed in the mice of either sex. Liver neoplasms were not increased in either dosed rats or mice of either sex. Significant (P<0.05) decreases in tumor incidences were observed in male mice for hepatocellular carcinomas (18/50, 6/50, 9/50), for alveolar/bronchiolar adenomas or carcinomas (13/50, 6/50, 5/49), and for follicular-cell adenomas of the thyroid gland (5/47, 0/46, 1/49). Allyl isovalerate was not mutagenic for Salmonella typhimurium (tester strains TA 98, 100, 1535, and 1537) with or without metabolic activation. Under the conditions of these studies, allyl isovalerate was carcinogenic for F344/N rats and B6C3F1 mice, causing increased incidences of hematopoietic system neoplasms (mononuclear-cell
leukemia
in male rats and lymphoma in female mice). Levels of Evidence of
Carcinogenicity
: Male Rats: Positive Female Rats: Negativen female mice). Levels of Evidence of
Carcinogenicity
: Male Rats: Positive Female Rats: Negative Male Mice: Negative Female Mice: Positive
...
PMID:Carcinogenesis Studies of Allyl Isovalerate (CAS No. 2835-39-4) in F344/N Rats and B6C3F1 Mice (Gavage Studies). 1274 92
The term "asbestos" has a commercial/industrial derivation limited to naturally occurring fibrous minerals of the serpentine or amphibole series. Chrysotile is the only type of asbestos in the serpentine series, whereas the amphibole series is represented by actinolite, amosite, anthophyllite, crocidolite, and tremolite. The essential characteristic of asbestos minerals is their fibrous nature. Large portions of the population ingest asbestos through consumption of food and water. Asbestos or asbestos-like fibers may gain access to water supplies as a result of mining (Lake Superior), from the presence of natural serpentine or amphibole deposits in watersheds (Seattle, WA, and San Francisco, CA) or, under certain conditions, through the use of asbestos-cement pipes for municipal water supplies. For the latter, erosion of the pipe with release of fibers is associated with the "aggressiveness" of the water, a term representing a mathematical expression of pH, alkalinity, and calcium content. The EPA estimated that 68.5% of water systems in the United States utilize water that is potentially capable of eroding asbestos-cement pipe. Carcinogenesis studies of amosite asbestos alone or in combination with the intestinal carcinogen 1,2-dimethylhydrazine dihydrochloride (DMH) were conducted in male and female rats. Amosite asbestos was administered at a concentration of 1% in pelleted diet for the entire lifetime of the rats, starting with the dams of the study animals. One group of amosite asbestos-exposed rats (amosite preweaning gavage) also received chrysotile asbestos via gavage during lactation. Group sizes varied from 100 to 250. Litter size was the same, but the offspring from mothers exposed to amosite asbestos were smaller at weaning than those from nonexposed mothers and remained smaller throughout their life. The DMH was administered by gavage at a dose of 7.5 mg/kg for males and 15 mg/kg for females every 14 days, starting at 8 weeks of age, for a total of five doses. The administration of DMH did not affect body weight gain either in amosite-exposed or nonexposed animals. The amosite-exposed rats showed enhanced survival compared with that of the nonexposed rats. DMH exposure reduced survival by approximately 1 year, although the survival of the amosite plus DMH groups was slightly greater than that of the DMH group alone. Significant increases in the incidences of C-cell carcinomas of the thyroid gland (untreated control, 11/117; amosite, 50/246, P<0.05; amosite preweaning gavage, 14/100) and of
leukemia
(38/117; 106/249, P<0.05; 49/100, P<0.01) in male rats were observed in amosite-exposed groups. However, the biologic significance of the C-cell carcinomas in relation to amosite asbestos exposure is discounted because of a lack of significance when C-cell adenomas and carcinomas were combined and because the positive effect was not observed in the amosite preweaning gavage group. The biologic significance of an increased incidence of
leukemia
is questionable because of a lack of statistical significance in the amosite group when evaluated by life table analysis and because no toxic lesions were observed in the target organs, i.e., gastrointestinal tract and mesothelium. DMH caused a high incidence (62%-74%) of intestinal neoplasia in amosite-exposed and nonexposed groups. Neither an enhanced carcinogenic nor a protective effect was demonstrated by exposure to amosite asbestos. Conclusions: Under the conditions of these feed studies, amosite asbestos was not overtly toxic, did not affect survival, and was not carcinogenic when ingested at a concentration of 1% in the diet by male or female F344/N rats. The cocarcinogenic studies using DMH were considered inadequate because of the high incidence of DMH-induced intestinal neoplasia in both the amosite asbestos-exposed and nonexposed groups. Levels of Evidence of
Carcinogenicity
: Amosite Asbestos: Male Rats: Negative. Female Rats: Negative. Amosite Asbestos + DMH: Male Rats: Inadequate. Female Rats: Inadequate. Note: Amosite Asbestos was previously tested in Syrmosite Asbestos was previously tested in Syrian Golden Hamsters administered in feed (See TR-249, reported 1983).
...
PMID:NTP Toxicology and Carcinogenesis Studies of Amosite Asbestos (CAS No. 12172-73-5) in F344/N Rats (Feed Studies). 1274
4,4'-Methylenedianiline is used primarily as a chemical intermediate in the closed system production of isocyanates and polyisocyanates. These chemicals are used extensively in the manufacture of rigid polyurethane foams for thermal insulation and in the production of semiflexible polyurethane foams for automobile safety cushioning. The saturated isocyante of 4,4'-methylenedianiline [4,4'-methylene-bis(cyclohexylisocyanate)] is an intermediate in the production of light-stable, high-performance polyurethane coatings. 4,4'-Methylenedianiline is also a curing agent for epoxy resins and urethane elastomers, a dye intermediate, and a corrosion inhibitor. NTP Carcinogenesis studies of 4,4'-methylenedianiline dihydrochloride (98.6% pure) were conducted by administering this chemical in the drinking water of F344/N rats and B6C3F1 mice. Groups of 50 rats and 50 mice of each sex received drinking water containing 150 or 300 ppm 4,4'-methylenedianiline dihydrochloride (dosage expressed as the free base) for 103 weeks. Groups of 50 rats and 50 mice of each sex, given drinking water adjusted with 0.1N HCl to the pH (3.7) of the 300-ppm formulation, served as controls. Survival was comparable among groups except for male mice receiving the high dose of 4,4'-methylenedianiline dihydrochloride; survival in that group was lower (P=0.006) than that in controls. Mean body weight was reduced in high dose female rats and in high dose male and female mice. Water consumption was reduced in a dose-related manner in both sexes of rats. No compound-related clinical effects were observed. Compound-related nonneoplastic lesions of the thyroid in female rats included follicular cysts and hyperplasia. The incidence of thyroid follicular cell hyperplasia was elevated in high dose male and female mice. The incidences of thyroid neoplasms in the high dose groups were elevated compared with those of the control groups for both sexes of both species. Thyroid follicular cell carcinoma was increased in male rats (controls, 0/49; low dose, 0/47; high dose, 7/48, 15%: P</=0.012). Follicular cell adenoma was increased in high dose female rats (0/47; 2/47, 4%; 17/48, 35%: P<0.001), in high dose male mice (0/47; 3/49, 6%; 16/49, 33%: P<0.001), and in high dose female mice (0/50; 1/47, 2%; 13/50, 26%: P<0.001) as compared with controls. In female rats, thyroid C-cell adenoma was also elevated in a dose-related manner (0/47; 3/47, 6%; 6/48, 13%, P</=0.029). Dose-related increases in nonneoplastic lesions were observed for male rats (nonspecific liver dilatation) and for male and female rats (fatty metamorphosis and focal cellular change). Liver degeneration was present in 80% of the low dose and 60% of the high dose male mice but was not found in the controls. Neoplastic nodules of the liver were observed at greater incidences (P</=0.002) for low and high dose male rats as compared with controls (control, 1/50, 2%; low dose, 12/50, 24%, P</=0.002; high dose 25/50, 50%, P<0.001). Hepatocellular adenoma was increased in a dose-related manner in dosed female mice (3/50, 6%; 9/50, 18%; 12/50, 24%, P<0.011). Hepatocellular carcinoma was observed in greater incidence in dosed male mice (10/49, 20%; 33/50, 66%, P<0.001; 29/50, 58%, P<0.001) and in high dose female mice (1/50, 2%; 6/50, 12%; 11/50, 22%, P=0.002). Male rats had a dose related increase in kidney mineralization. Nephropathy was increased in dosed mice of both sexes; renal papillary mineralization was greater in high dose male mice and female mice than in the controls. Other tumors that were elevated in dosed animals included adrenal pheochromocytomas in male mice (control, 2/48, 4%; low dose, 12/49, 24%, P</=0.006; high dose, 14/49, 29%; P</=0.001), alveolar/bronchiolar adenoma in female mice (1/50, 2%; 2/50, 4%; 6/49, 12%, P</=0.05) and malignant lymphomas in female mice (13/50,26%; 28/50, 56%, P=0.002; 29/50, 58%; P=0.001). Uncommon tumors were observed in dosed animals at low incidences but may be important because the historical control incidences are very low; bile duct adenoma in 1/50 high dose male (13/50,26%; 28/50, 56%, P=0.002; 29/50, 58%; P=0.001). Uncommon tumors were observed in dosed animals at low incidences but may be important because the historical control incidences are very low; bile duct adenoma in 1/50 high dose male rats (historical control 3/3,663), transitional-cell papillomas of the urinary bladder in female rats (historical control, 3/3,664, 0.08%; low dose, 2/50, 4%; high dose, 1/50, 2%) and granulosa cell tumors of the ovary in female rats (historical control, 11/3,642, 0.3%; low dose, 3/50, 6%; high dose, 2/50, 4%). Decreases in tumor incidences were observed for
leukemia
in male rats (control, 12/50, 24%; low dose, 6/50, 12%; high dose, 5/50, 10%, P=0.048) and alveolar or bronchiolar adenomas (combined) in male mice (12/49, 24%; 9/49, 18%; 3/49, 6%, P≤0.011). Under the conditions of these studies, 4,4'-methylenedianiline dihydrochloride was carcinogenic for F344/N rats and B6C3F1 mice of each sex, causing significantly increased incidences of thyroid follicular cell carcinomas in male rats, thyroid follicular cell adenomas in female rats and in mice of each sex, C-cell adenomas of the thyroid gland in female rats, neoplastic nodules in the liver of male rats, hepatocellular carcinomas in mice of each sex, adenomas of the liver and malignant lymphomas in female mice, and adrenal pheochromocytomas in male mice. Levels of Evidence of
Carcinogenicity
: Male Rats: Positive Female Rats: Positive Male Mice: Positive Female Mice: Positive
...
PMID:NTP Carcinogenesis Studies of 4,4'-Methylenedianiline Dihydrochloride (CAS No. 13552-44-8) in F344/N Rats and B6C3F1 Mice (Drinking Water Studies). 1275 Jul 45
Diallyl phthalate is a widely used crosslinking agent for unsaturated polyesters. Diallyl phthalate or diallyl phthalate polyester blends are used primarily as plasticizers and carriers for adding catalysts and pigments to polyesters and in molding, electrical parts, laminating compounds, and impregnation of metal castings. Rubber compounds, epoxy formulations, and polyurethane foams may also contain diallyl phthalate. Annual production of diallyl phthalate in the United States exceeds 5,000 pounds; precise figures are not available. A NTP Carcinogenesis bioassay of diallyl phthalate (99% pure) was conducted by administering 0 (vehicle control), 150, or 300 mg/kg diallyl phthalate in corn oil by gavage, 5 days per week for 103 weeks, to groups of 50 male and 50 female B6C3F1 mice. Survival rates and mean body weights of dosed mice were not different from those of the controls, and pathological lesions unrelated to proliferative changes were not observed. Therefore, a maximally tolerated dose for the purposes of carcinogenicity testing may not have been achieved. The incidences of lymphoma and either lymphoma or
leukemia
in dosed male mice were no significantly greater than those in the controls according to pairwise comparisons (P=0.051 to P=0.096), but the trend tests were statistically significant by either life table or incidental tumor analysis (P=0.031 to P=0.045). The incidence of lymphomas in the high-dose male mice was 12/50 (24%) in comparison with 6/50 (12%) in the controls. Recent historical incidences at the performing laboratory and in the NTP Bioassay Program were 18/120 (15%) and 71/661 (11%), respectively. Since the incidence of high-dose male mice with
leukemia
was not significantly greater than that of concurrent or historical controls at the performing laboratory by pairwise comparisons, this marginal increase was considered only to be equivocally related to diallyl phthalate administration. Increased incidences of squamous cell papillomas, hyperplasia, and inflammatory lesions of the forestomach were observed in diallyl phthalate-dosed mice of both sexes in a dose-related manner. Papillomas of the forestomach were observed in 0%, 2%, and 4% of the control, low-dose, and high-dose mice of both sexes. The recent historical incidence of this tumor in gavage control mice from both the performing laboratory and other laboratories within the Bioassay Program was less than 1%. Forestomach hyperplasia was diagnosed in 0%, 15%, and 18%, and in 8%, 2%, and 29% of the control, low-dose, and high-dose male and female mice, respectively; chronic inflammation of the forestomach was diagnosed in 0%, 9%, and 16% and in 4%, 2%, and 18% of the control, low-dose, and high-dose male and female mice, respectively. Because of the numerical elevation of the forestomach papillomas in the high-dose mice of both sexes, the concomitant observation of dose related forestomach hyperplasia, and the rarity of this tumor in corn oil (gavage) control B6C3F1 mice, the development of squamous cell papillomas of the forestomach may have been related to diallyl phthalate administration. Under the conditions of this bioassay, the development of chronic inflammation and hyperplasia of the forestomach in both male and female B6C3F1 mice was considered to be related to the administration of diallyl phthalate. The development of squamous cell papillomas of the forestomach may also have been related to chemical administration, but the available data are insufficient to indicate a clear cause and effect relationship. An increase in the incidence of male mice with lymphomas was observed, but this increase was considered only to be equivocally related to diallyl phthalate administration. The results of this bioassay, therefore, do not indicate that diallyl phthalate is carcinogenic in B6C3F1 mice, although a maximum tolerated dose may not have been achieved. A carcinogenicity study by the National Toxicology Program of diallyl phthalate in male and female Fisher 344/N rats, employing daily gavage doses of 0 (vehicle control), 50, or 100 mg/kg boicology Program of diallyl phthalate in male and female Fisher 344/N rats, employing daily gavage doses of 0 (vehicle control), 50, or 100 mg/kg body weight is currently being evaluated. Levels of Evidence of
Carcinogenicity
: Male Mice: Equivocal Female Mice: Equivocal
...
PMID:NTP Carcinogenesis Bioassay of Diallyl Phthalate (CAS No. 131-17-9) in B6C3F1 Mice (Gavage Study). 1275 Jul 51
Propyl gallate is a white to nearly white odorless powder having a slightly bitter taste. Solutions of propyl gallate turn dark in the presence of iron or iron salts. Propyl gallate has been used since 1948 as an antioxidant to stabilize cosmetics, food packaging materials, and foods containing fats. As an additive, it may be found in edible fats, oils, mayonnaise, shortening, baked goods, candy, dried meat, fresh pork sausage, and dried milk, and it is used in hair grooming products, pressure-sensitive adhesives, lubricating oil additives, and transforming oils. A NTP Carcinogenesis bioassay of propyl gallate was conducted by feeding diets containing 6,000 or 12,000 ppm propyl gallate to groups of 50 F344/N rats and 50 B6C3F1 mice of each sex for 103 weeks. Groups of 50 untreated rats and 50 untreated mice of each sex served as controls. Survival of rats and mice was not adversely affected by propyl gallate, but mean body weights of dosed rats and mice of each sex were lower than those of the controls. At 104 weeks, mean body weights of low-and high-dose rats were 4% and 8% lower than those of the controls for males and 11% and 19% lower than those of the controls for females. Similarly, mean body weights of low-and high-dose mice were 5% and 8% lower than those of the controls for males and 11% (both dose groups) lower than those of the controls for females. Thyroid follicular-cell adenomas or carcinomas (combined) occurred in male rats with a statistically significant (P<0.05) positive trend, but the incidences in the dosed groups were not statistically significant in direct comparisons with the control groups. Moreover, the incidence of high-dose male rats with follicular-cell tumors (3/50, 6%) was not statistically different from the historical control rate (14/584, 2.4%) for the laboratory that conducted this bioassay. Rare tumors (an astrocytoma or a glioma) were found in the brains of two low-dose female rats. The incidence of all brain tumors in the Bioassay Program is only 0.86%. The absence of this tumor in the high-dose female rat group reduces the likelihood that this tumor is related to propyl gallate administration. Increased incidences of hepatic cytoplasmic vacuolization and suppurative inflammation of the prostate were observed in dosed male rats. These findings were considered to be related to administration of propyl gallate. Tumors (mostly benign) of the preputial gland, islet-cell tumors of the pancreas, and pheochromocytomas of the adrenal gland were observed with significantly (P<0.05) higher incidences in the low- dose male rats, but there was little evidence of an effect in the high-dose group. The incidences of male rats with tumors of the preputial gland were 1/50 (2%) for controls, 8/50 (16%) for the low-dose, and 0/50 (0%) for the high-dose group. Islet-cell tumors of the pancreas occurred in 2/50 (4%) control males, 9/50 (18%) low-dose males, and 4/50 (8%) for high-dose males. Pheochromocytomas of the adrenal gland were observed in 4/50 (8%) control males, 13/48 (25%) low-dose males, and 8/50 (16%) high-dose males. Negative trends (P<0.05) were observed for
leukemia
in male rats (16/50, 7/50, 6/50) and for fibroadenomas of the mammary gland in female rats (11/50, 2/50, 5/50). In male mice, malignant lymphoma was observed with a significantly (P</=0.014) positive trend (control, 1/50, 2%; low-dose, 3/49, 6%; high-dose, 8/50, 16%), and the incidence in the high-dose group was significantly (P</=0.028) higher than that observed in the concurrent controls. However, the high-dose incidence was not statistically different from the historical rate (60/640, 9.4%) for the laboratory that conducted this bioassay. Adenomas of the liver in female mice occurred with a statistically significant (P</=0.022) positive trend, and the incidence in the high-dose group was significantly (P</=0.039) higher than that of the controls (0/50, 0%; 2/50, 4%; 5/49, 10%). The incidences of hepatocellular adenomas or carcinomas (combined) were similar in control and dosed groups (3/50, 6%; 3/50, 6%; 5/49, 10%). Negative%; 2/50, 4%; 5/49, 10%). The incidences of hepatocellular adenomas or carcinomas (combined) were similar in control and dosed groups (3/50, 6%; 3/50, 6%; 5/49, 10%). Negative trends (P<0.05) were obtained for fibromas of the skin or subcutaneous tissue in male mice (5/50, 1/49, 0/50). Under the conditions of this bioassay, propyl gallate was not considered carcinogenic for F344/N rats, although there was evidence of an increased proportion of low-dose male rats with preputial gland tumors, islet-cell tumors of the pancreas, and pheochromocytomas of the adrenal glands; rare tumors of the brain occurred in two low-dose females. Propyl gallate was not considered to be carcinogenic for B6C3F1 mice of either sex, although the increased incidence of malignant lymphoma in male mice may have been related to the dietary administration of propyl gallate. Levels of Evidence of
Carcinogenicity
: Male Rats: Equivocal Female Rats: Negative Male Mice: Equivocal Female Mice: Negative Synonyms: 2,4,5 trihydroxybenzoic acid propyl ester; gallic acid propyl ester; Progallin P; Tennox PG
...
PMID:NTP Carcinogenesis Bioassay of Propyl Gallate (CAS No. 121-79-9) in F344/N Rats and B6C3F1 Mice (Feed Study). 1275 Jul 52
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
...
PMID:Bioassay of Phenol for Possible Carcinogenicity (CAS No.108-95-2). 1277 76
A subchronic and a chronic carcinogenesis study of vinylidene chloride (99% pure), a widely used chemical intermediate and monomer, were conducted in F344/N rats and B6C3F1/N mice. In subchronic studies, groups of 10 rats and 10 mice of either sex were administered vinylidene chloride in corn oil by gavage five times per week at 0, 5, 15, 50, 100, or 250 mg/kg body weight for 13 weeks. At the end of this study, representative tissues from these animals were subjected to histopathological examination. The liver was identified as a target organ for vinylidene chloride toxicity. In the 104-week chronic exposure study, conducted primarily to determine possible carcinogenic potential of vinylidene chloride by the oral route, 50 F344/N rats and 50 B6C3F1/N mice of either sex were gavaged with vinylidene chloride suspended in corn oil at dose levels of 1 or 5 mg/kg (rats) and 2 or 10 mg/kg (mice). Groups of 50 rats and 50 mice of either sex received corn oil alone and served as vehicle controls. Throughout most of the study, mean body weights of the dosed rats of either sex and high-dose female mice were slightly lower than those of the controls. The absence of compound-related effects on survival or clinical signs suggests that the rats and mice of either sex could have tolerated higher doses. While no significant differences in survival were observed for any group of rats, 12 control and 10 low-dose males were killed accidentally during week 82; this may have compromised the sensitivity of the male rats study. The results of histopathological examination indicated an increased incidence of necrosis of the liver in high-dose male and low-dose female mice and chronic renal inflammation in high-dose rats of either sex. The only observed significant (P>0.05) increase in tumor incidence occurred in low-dose female mice: lymphoma (2/48, 9/49, 6/50) and lymphoma or
leukemia
(7/48, 15/49, 7/50). These increases were not considered to be related to vinylidene chloride administration because similar effects were not found in the high-dose female mice or in male mice or rats. Under the conditions of this bioassay, vinylidene chloride administered by gavage was not carcinogenic for F344/N rats or B6C3F1/N mice of either sex. However, since the use of a maximum tolerated dose in this study has not been clearly demonstrated and since previously reported studies have shown that carcinogenicity is associated with inhalation exposure to vinylidene chloride, this study should not be taken as proof that the chemical is not a carcinogen. Levels of Evidence of
Carcinogenicity
: Male Rats: Negative Female Rats: Negative Male Mice: Negative Female Mice: Negative Synonyms: 1,1-dichloroethylene; VDC; 1,1-DCE
...
PMID:Carcinogenesis Bioassay of Vinylidene Chloride (CAS No. 75-35-4) in F344 Rats and B6C3F1 Mice (Gavage Study). 1277 8
A carcinogenesis bioassay of bisphenol A, an intermediate used in the manufacture of epoxy, polycarbonate, and polyester-styrene resins, was conducted by feeding diets containing 1,000 or 2,000 ppm of the test chemical to groups of 50 F344 rats of either sex, 1,000 or 5,000 ppm to groups of 50 male B6C3F1 mice, and 5,000 or 10,000 ppm to groups of 50 female B6C3F1 mice for 103 weeks. Groups of 50 rats and 50 mice of either sex served as controls. Mean body weights of rats of either sex and of high-and low-dose female mice and high-dose male mice were lower than those of the controls throughout the study. Since food consumption of dosed female rats was only 70% to 80% that of the controls throughout most of this study, reduced body weight gain was probably due to reduced food consumption. Food consumption by dosed male rats was 90% that of controls. Food consumption among all groups of mice appear to be similar.
Leukemias
occurred at increased incidences in dosed rats of both sexes. In male rats, the dose-related (13/50, 12/50, 23/50) trend was statistically significant (P=0.021) by a Cochran-Armitage test, but neither the trend nor the increase in the high-dose group was significant by life table analyses, which adjust for survival differences among groups. The increased incidences in dosed female rats were also not statistically significant (7/50, 13/50, 12/50). Interstitial-cell tumors of the testes occurred at statistically significant incidences in low- and high-dose male rats; however, since this lesion normally occurs at a high incidence in aging F344 male rats, the increased incidence observed in this study was not considered compound related (35/49, 48/50, 46/49). In male mice, there was an increased incidence of leukemias or lymphomas (2/49, 9/50, 5/50), but this increase was not statistically significant. A compound-related increased incidence of multinucleated giant hepatocytes was observed in male mice (1/49, 41/49, 41/50), but there was no increase of liver tumors in male mice. The marginally significant increase in leukemias in male rats, along with an increase (not statistically significant) in leukemias in female rats and a marginally significant increase in the combined incidence of lymphomas and leukemias in male mice, suggests that exposure to bisphenol A may be associated with increased cancers of the hematopoietic system. A statistically significant increase in interstitial-cell tumors of the testes in male rats was also suggestive of carcinogenesis, but was not considered to be convincing evidence of a compound-related effect because this lesion normally occurs at a high incidence in aging F344 rats. Under the conditions of this bioassay, there was no convincing evidence that bisphenol A was carcinogenic for F344 rats or B6C3F1 mice of either sex. Levels of Evidence of
Carcinogenicity
: Male Rats: Equivocal Female Rats: Equivocal Male Mice: Equivocal Female Mice: Negative Synonym: 4,4'-isopropylidenediphenol
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PMID:Carcinogenesis Bioassay of Bisphenol A (CAS No. 80-05-7) in F344 Rats and B6C3F1 Mice (Feed Study). 1277 20
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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PMID:Carcinogenesis Bioassay of Butyl Benzyl Phthalate (CAS No. 85-68-7) in F344/N Rats and B6C3F1 Mice (Feed Study). 1277 22
Carcinogenesis studies of 80% pure C.I. Acid Orange 10 (a monoazo textile dye) were conducted by feeding to groups of 50 male and 50 female F344/N rats diets containing 1,000 or 3,000 ppm C.I. Acid Orange 10 for 103 weeks. Groups of 50 male and 50 female B6C3F1 mice were fed diets containing 3,000 or 6,000 ppm for 103 weeks. Groups of 90 male and 90 female untreated rats and 50 male and 50 female untreated mice served as controls. Mean body weights and clinical signs of control and dosed rats and mice were comparable. Because no toxic effects or consistent weight differences were observed, the rats and mice may have been able to tolerate higher doses. In male rats with neoplastic nodules of the liver, the dose response trend was positive (P<0.05) and the incidence in the 3,000 ppm group was increased (P<0.05) compared to controls (control, 5/90, 6%; low dose, 3/50, 6%; high dose, 8/50, 16%). One male rat in the high dose group had both a neoplastic nodule and a carcinoma of the liver. This marginal increase in liver cell neoplasms may have been associated with the dietary administration of C.I. Acid Orange 10. For both dose groups of male and female rats,
leukemia
was significantly (P<0.05) decreased in a dose related (P<0.005) trend (male: 22/90, 24%; 4/50, 8%; 3/50, 6%; female: 16/88, 18%; 2/50, 4%; 0/50). No compound-related nonneoplastic or neoplastic lesions were observed in the female rats or in mice of either sex. For 103 weeks C.I. Acid Orange 10 was given in the diets of male and female F344/N rats (0, 0.1, or 0.3%) and of male and female B6C3F1 mice (0, 0.3%, or 0.6%). Under these conditions, there was no evidence of carcinogenicity for male and female F344/N 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 Synonym: 7-hydroxy-8-(phenylazo)-1,3-naphthalenedisulfonic acid, disodium salt
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PMID:Carcinogenesis Studies of C.I. Acid Orange 10 (CAS No. 1936-15-8) in F344 Rats and B6C3F1 Mice (Feed Studies). 1277 24
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