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PubMed_ArguminSci

Id Subject Object Predicate Lexical cue
T1 137-236 DRI_Background denotes Salicylazosulfapyridine is widely used for the treatment of ulcerative colitis and Crohn's disease.
T2 237-403 DRI_Background denotes It has been beneficial in the treatment of psoriasis and rheumatoid arthritis, and it has been used in veterinary medicine for the treatment of granulomatous colitis.
T3 404-639 DRI_Background denotes Salicylazosulfapyridine was nominated for toxicity and carcinogenicity testing by the National Cancer Institute on the basis of its widespread use in humans and because it is a representative chemical from a class of aryl sulfonamides.
T4 640-895 DRI_Background denotes Salicylazosulfapyridine is a suspect carcinogen because reductive cleavage of the azo linkage yields a p-amino aryl sulfonamide (sulfapyridine), and a related p-amino aryl sulfonamide (sulfamethoxazole) has been shown to produce thyroid neoplasms in rats.
T5 896-981 DRI_Background denotes Toxicology and carcinogenicity studies were conducted in F344/N rats and B6C3F1 mice.
T6 982-1112 DRI_Background denotes Rats and mice were administered salicylazosulfapyridine (96% to 98% pure) in corn oil by gavage for 16 days, 13 weeks, or 2 years.
T7 1113-1255 DRI_Background denotes The gavage route of administration was selected for these studies because it approximates the typical route of human exposure to the chemical.
T8 1256-1448 DRI_Background denotes Genetic toxicology studies were conducted in vitro in Salmonella typhimurium and cultured Chinese hamster ovary cells and in vivo in rat and mouse bone marrow and mouse peripheral blood cells.
T9 1449-1649 DRI_Background denotes 16-DAY STUDY IN RATS: Groups of five male and five female rats were administered 0, 675, 1,350, or 2,700 mg salicylazosulfapyridine/kg body weight in corn oil by gavage for 16 days excluding weekends.
T10 1650-1692 DRI_Approach denotes All rats survived to the end of the study.
T11 1693-1858 DRI_Outcome denotes With the exception of the 675 mg/kg male group, the final mean body weights of all dosed groups of males and females were significantly lower than those of controls.
T12 1859-1935 DRI_Approach denotes Mean body weight gains of all dosed groups were less than those of controls.
T13 1936-2044 DRI_Background denotes Clinical findings included ruffled fur and distended abdomens in male and female rats receiving 2,700 mg/kg.
T14 2045-2239 DRI_Background denotes Hypothyroidism, evidenced by decreased serum triiodothyronine and thyroxine concentrations and increased thyroid-stimulating hormone concentrations, occurred in 2,700 mg/kg male and female rats.
T15 2240-2409 DRI_Background denotes The absolute and relative thymus weights of male rats receiving,350 or 2,700 mg/kg and female rats receiving 2,700 mg/kg were significantly lower than those of controls.
T16 2410-2474 DRI_Outcome denotes At necropsy, all dosed rats had enlarged cecae/large intestines.
T17 2475-2587 DRI_Background denotes Male rats receiving 1,350 mg/kg and male and female rats receiving 2,700 mg/kg had red, enlarged thyroid glands.
T18 2588-2701 DRI_Background denotes Chemical-related microscopic lesions were present in the forestomach, thymus, thyroid gland, and pituitary gland.
T19 2702-2820 DRI_Background denotes Minimal to mild hyperplasia of the forestomach mucosa was present in the 1,350 and 2,700 mg/kg male and female groups.
T20 2821-2929 DRI_Background denotes Lymphoid depletion was observed in the thymus of three male and three female rats in the 2,700 mg/kg groups.
T21 2930-3136 DRI_Background denotes Male and female rats receiving 1,350 and 2,700 mg/kg had thyroid gland follicular cell hyperplasia and an increase in thyroid-stimulating hormone producing cells in the pars distalis of the pituitary gland.
T22 3137-3337 DRI_Background denotes 16-DAY STUDY IN MICE: Groups of five male and five female mice were administered 0, 675, 1,350, or 2,700 mg salicylazosulfapyridine/kg body weight in corn oil by gavage for 16 days excluding weekends.
T23 3338-3453 DRI_Background denotes There were no chemical-related deaths, and final mean body weights of dosed mice were similar to those of controls.
T24 3454-3527 DRI_Background denotes No chemical-related clinical findings were noted for male or female mice.
T25 3528-3663 DRI_Background denotes There were no differences in triiodothyronine, thyroxine, or thyroid-stimulating hormone concentrations between dosed and control mice.
T26 3664-3800 DRI_Background denotes There were no biologically significant differences in absolute or relative organ weights between dosed and control male and female mice.
T27 3801-3882 DRI_Background denotes At necropsy, male mice receiving 2,700 mg/kg had enlarged cecae/large intestines.
T28 3883-3999 DRI_Background denotes There were no biologically significant histopathologic lesions attributed to salicylazosulfapyridine administration.
T29 4000-4178 DRI_Background denotes 13-WEEK STUDY IN RATS: Groups of 10 male and 10 female rats were administered 0, 84, 168.8, or 337.5 mg salicylazosulfapyridine/kg body weight in corn oil by gavage for 13 weeks.
T30 4179-4221 DRI_Approach denotes All rats survived to the end of the study.
T31 4236-4433 DRI_Outcome denotes The final mean body weights of dosed male rats were similar to those of controls; the final mean body weights and body weight gains of dosed females were significantly lower than those of controls.
T32 4434-4537 DRI_Background denotes No chemical-related clinical findings were noted in dosed male or female rats during the 13-week study.
T33 4538-4649 DRI_Background denotes No significant differences in hematology or urinalysis parameters between control and dosed rats were observed.
T34 4650-4770 DRI_Background denotes The absolute and relative right kidney weights of 337.5 mg/kg females were significantly greater than those of controls.
T35 4771-4844 DRI_Background denotes At necropsy, some 337.5 mg/kg male rats had red, enlarged thyroid glands.
T36 4845-4978 DRI_Background denotes Histopathologic changes were noted primarily in the thyroid gland and pituitary gland of males and females in the 337.5 mg/kg groups.
T37 4979-5064 DRI_Background denotes The thyroid gland lesions observed were similar to those present in the 16-day study.
T38 5065-5224 DRI_Background denotes Nine male rats receiving 168.8 mg/kg and ten male and seven female rats receiving.5 mg/kg had minimal but consistent changes in thyroid gland follicular cells.
T39 5225-5412 DRI_Background denotes In the pituitary gland of 337.5 mg/kg males and females, the thyroid-stimulating hormone producing cells were enlarged and contained pale-staining cytoplasm and prominent Golgi complexes.
T40 5413-5684 DRI_Background denotes Decreased serum triiodothyronine and thyroxine concentrations and increased thyroid-stimulating hormone concentration, similar to differences observed in the 16-day study, occurred in 337.5 mg/kg male rats; thyroid hormone concentrations were not affected in female rats.
T41 5685-5775 DRI_Outcome denotes Sperm motility of all dosed groups of males was significantly lower than that of controls.
T42 5776-5865 DRI_Background denotes Vaginal cytology parameters of dosed groups of females were similar to those of controls.
T43 5866-6045 DRI_Background denotes 13-WEEK STUDY IN MICE: Groups of 10 male and 10 female mice were administered 0, 675, 1,350, or 2,700 mg salicylazosulfapyridine/kg body weight in corn oil by gavage for 13 weeks.
T44 6046-6088 DRI_Approach denotes All mice survived to the end of the study.
T45 6089-6181 DRI_Background denotes The final mean body weights of dosed male and female mice were similar to those of controls.
T46 6182-6276 DRI_Outcome denotes The mean body weight gains of 1,350 and 2,700 mg/kg male mice were less than that of controls.
T47 6277-6380 DRI_Background denotes No chemical-related clinical findings were noted in dosed male or female mice during the 13-week study.
T48 6381-6460 DRI_Background denotes There was minimal evidence of a responsive anemia in mice in the 13-week study.
T49 6461-6516 DRI_Background denotes The anemia was probably related to a methemoglobinemia.
T50 6517-6636 DRI_Background denotes There were minimal decreases in thyroxine concentration in all dosed groups of male and female mice in the -week study.
T51 6637-6774 DRI_Background denotes There were, however, no differences in triiodothyronine and thyroid-stimulating hormone concentrations between dosed and control animals.
T52 6775-6905 DRI_Background denotes Absolute and relative liver weights of all groups of dosed male and female mice were significantly greater than those of controls.
T53 6906-6951 DRI_Approach denotes There were no chemical-related gross lesions.
T54 6952-7073 DRI_Background denotes Microscopic evaluation of the liver revealed centrilobular hypertrophy in five 1,350 mg/kg and all 2,700 mg/kg male mice.
T55 7074-7222 DRI_Approach denotes The right cauda weight of the 1,350 mg/kg group and the right epididymis weights of all dose groups were significantly lower than those of controls.
T56 7223-7326 DRI_Background denotes There was no evidence of chemical-related alteration in the vaginal cytology parameters of female mice.
T57 7327-7506 DRI_Background denotes 2-YEAR STUDY IN RATS: Groups of 60 male and 60 female rats were administered 84, 168, or 337.5 mg salicylazosulfapyridine/kg body weight in corn oil by gavage for up to 105 weeks.
T58 7507-7613 DRI_Background denotes Groups of 70 male and 60 female rats were administered the corn oil vehicle by gavage for up to 105 weeks.
T59 7614-7839 DRI_Background denotes A stop-exposure group of 70 male rats was administered 337.5 mg/kg salicylazosulfapyridine in corn oil by gavage for 6 months, after which animals received the corn oil vehicle by gavage for the remainder of the 2-year study.
T60 7840-8035 DRI_Background denotes Ten animals from the vehicle control male group and 10 animals from the 337.5 mg/kg stop-exposure group were evaluated at 6 months; animals from each core-study group were evaluated at 15 months.
T61 8036-8309 DRI_Background denotes Survival, Body Weights, and Clinical Chemistry: Survival of 337.5 mg/kg male core-study rats was significantly lower than that of controls; survival of 84 and 168 mg/kg core-study males, all groups of dosed females, and the stop-exposure male group was similar to controls.
T62 8310-8418 DRI_Background denotes Mean body weights of core-study males and stop-exposure males were similar to controls throughout the study.
T63 8419-8551 DRI_Outcome denotes From week 45 to the end of the study, females in the 337.5 mg/kg group had mean body weights that were lower than those of controls.
T64 8552-8844 DRI_Background denotes The serum thyroxine concentration in 337.5 mg/kg core-study males at study termination was minimally lower than that of controls; the serum thyroid-stimulating hormone, triiodothyronine, and reverse triiodothyronine concentrations of dosed males and females were similar to those of controls.
T65 8845-9133 DRI_Background denotes Pathology Findings: Administration of salicylazosulfapyridine for 2 years was associated with transitional epithelial papilloma in the urinary bladder of male rats and may have been associated with transitional epithelial papilloma of the kidney and of the urinary bladder of female rats.
T66 9134-9264 DRI_Background denotes Nonneoplastic effects in the urinary bladder and kidney of male and female rats and in the spleen of male rats were also observed.
T67 9265-9601 DRI_Background denotes Dosed male and female rats had increased incidences of grossly and microscopically observed urinary bladder concretions (diagnosed grossly as calculi at necropsy); male and female rats that developed transitional epithelial papillomas of the urinary bladder had grossly observed concretions (calculi) in the urinary bladder at necropsy.
T68 9602-9883 DRI_Background denotes The microscopic neoplastic and nonneoplastic urinary bladder and kidney effects observed in dosed male rats during the 2-year continuous study did not occur in dosed rats during the 2-year stop-exposure study, nor were there gross observations of concretions (calculi) at necropsy.
T69 9884-9967 DRI_Background denotes The incidences of mononuclear cell leukemia in male and female rats were decreased.
T70 9968-10159 DRI_Background denotes The thyroid gland hyperplasia seen in the -week study was not observed in the 2-year study, and there was no evidence of chemical-related thyroid gland follicular cell adenomas or carcinomas.
T71 10160-10345 DRI_Background denotes 2-YEAR STUDY IN MICE: Groups of 60 male and 60 female mice were administered 0, 675, 1,350, or 2,700 mg salicylazosulfapyridine/kg body weight in corn oil by gavage for up to 104 weeks.
T72 10346-10402 DRI_Approach denotes Ten animals from each group were evaluated at 15 months.
T73 10403-10539 DRI_Background denotes Survival, Body Weights,and Clinical Chemistry: Survival of all the dosed groups of male and female mice was similar to that of controls.
T74 10540-10648 DRI_Background denotes Mean body weights of 675 and 1,350 mg/kg male and female mice were similar to controls throughout the study.
T75 10649-10770 DRI_Outcome denotes From week 12 to the end of the study, 2,700 mg/kg male mice had mean body weights that were lower than those of controls.
T76 10771-10898 DRI_Outcome denotes From week 14 to the end of the study, the 2,700 mg/kg female mice had mean body weights that were lower than those of controls.
T77 10899-11104 DRI_Background denotes There were no chemical-related differences in triiodothyronine, reverse triiodothyronine, thyroxine, or thyroid-stimulating hormone concentrations between dosed and control mice at the 15-month evaluation.
T78 11105-11293 DRI_Background denotes Pathology Findings: Exposure of mice to salicylazosulfapyridine in corn oil by gavage for 2 years was associated with increased incidences of hepatocellular neoplasms in males and females.
T79 11294-11383 DRI_Background denotes Nonneoplastic effects in the liver and spleen were also observed in male and female mice.
T80 11384-11513 DRI_Background denotes The incidences of forestomach squamous cell papilloma in females and forestomach hyperplasia in males and females were decreased.
T81 11514-11756 DRI_Background denotes GENETIC TOXICOLOGY: Salicylazosulfapyridine was not mutagenic in Salmonella typhimurium strains TA97, TA98, TA100, or TA1535, and it did not induce sister chromatid exchanges or chromosomal aberrations in cultured Chinese hamster ovary cells.
T82 11757-11843 DRI_Background denotes These in vitro assays were performed with and without S9 metabolic activation enzymes.
T83 11844-11882 DRI_Outcome denotes Results from in vivo mouse bone marrow
T84 11896-12098 DRI_Outcome denotes aberration tests were uniformly negative, while results of micronucleus assays performed on male or female mice exposed to salicylazosulfapyridine for periods ranging from 3 days to weeks were positive.
T85 12099-12221 DRI_Outcome denotes Micronucleus tests in male mice for shorter exposure times (1 to 2 days) yielded negative or very weakly positive results.
T86 12222-12331 DRI_Outcome denotes A three-treatment (72-hour exposure time) micronucleus test performed in male rats yielded equivocal results.
T87 12332-12549 DRI_Outcome denotes Overall, results of these in vivo assays indicate that salicylazosulfa pyridine is capable of inducing chromosomal damage, possibly in the form of aneuploidy, in mouse bone marrow cells after multiple administrations.
T88 12550-12787 DRI_Background denotes CONCLUSIONS: Under the conditions of these 2-year gavage studies, there was some evidence of carcinogenic activity of salicylazosulfapyridine in male and female F344/N rats based on increased incidences of neoplasms in the urinary tract.
T89 12788-13005 DRI_Background denotes There was an increased incidence of transitional epithelial papilloma of the urinary bladder in males and a low incidence of rare transitional epithelial papillomas of the kidney and of the urinary bladder in females.
T90 13006-13172 DRI_Background denotes There was clear evidence of carcinogenic activity of salicylazosulfapyridine in male and female B6C3F1 mice based on increased incidences of hepatocellular neoplasms.
T91 13173-13322 DRI_Background denotes Increased incidences of nonneoplastic lesions of the urinary bladder and kidney in male and female rats and of the spleen in male rats were observed.
T92 13323-13431 DRI_Background denotes Increased incidences of nonneoplastic lesions of the liver and spleen in male and female mice were observed.
T93 13432-13561 DRI_Background denotes Decreased incidences of mononuclear cell leukemia in male and female rats were related to salicylazosulfapyridine administration.
T94 13562-13744 DRI_Background denotes Decreased incidences of forestomach squamous cell papilloma in female mice and forestomach hyperplasia in male and female mice were related to salicylazosulfapyridine administration.
T95 13745-14127 DRI_Background denotes Synonyms: 2-Hydroxy-5-[[4-[2-(pyridinylamino)sulfonyl]phenyl]azo]benzoic acid; 5-[p- (2-pyridylsulfamoyl)phenylazo]salicylic acid; sulfasalazine; salazosulfapyridine; 5-[4-(2-pyridylsulfamoyl)phenylazo]-2-hydroxybenzoic acid; 4-(pyridyl-2-amidosulfonyl)-3'-carboxy-4'-hydroxyazobenzene; sulphasalazine Trade names: Azopyrin, Azulfidine, Benzosulfa, Colo-Pleon, Reupirin, Salazopyrin