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Inflammaging

Id Subject Object Predicate Lexical cue
T1 0-66 Sentence denotes NTP Toxicology and Carcinogenesis Studies of Theophylline (CAS No.
T2 67-133 Sentence denotes 58-55-9) in F344/N Rats and B6C3F1 Mice (Feed and Gavage Studies).
T3 134-261 Sentence denotes Theophylline is an alkaloid found in tea (Thea sinensis) and chocolate and is structurally related to caffeine and theobromine.
T4 262-309 Sentence denotes Theophylline is used as a pharmaceutical agent.
T5 310-443 Sentence denotes It stimulates the heart and central nervous system, relaxes the smooth muscles of the bronchi and blood vessels, and causes diuresis.
T6 444-577 Sentence denotes The drug is used mainly as a bronchodilator in obstructive airway diseases, such as bronchial asthma, and for myocardial stimulation.
T7 578-903 Sentence denotes Theophylline was nominated for toxicologic and carcinogenicity testing as a representative of the purine structural subclass, particularly because of its relationship to purines such as caffeine, 1-methyl-3-hydroxyguanine, and 3-hydroxy-1-methylxanthine, the latter two compounds having been shown to induce sarcomas in rats.
T8 904-1165 Sentence denotes Additional reasons for testing theophylline included its widespread use in humans as a pharmaceutical agent, its possible genotoxicity in vitro, and the lack of information on its potential toxicity and/or carcinogenicity under conditions of chronic oral usage.
T9 1166-1320 Sentence denotes Based on reported teratogenicity and testicular toxicity, it was also recommended that reproductive studies be included in the evaluation of theophylline.
T10 1321-1519 Sentence denotes The oral route of administration was selected because it is the primary route of human exposure, and the gavage route was selected because it mimics the pharmaceutical use of theophylline in humans.
T11 1520-1706 Sentence denotes Male and female F344/N rats and B6C3F1 mice were given theophylline (greater than 99% pure) in feed or in corn oil by gavage for 16 days or 14 weeks or in corn oil by gavage for 2 years.
T12 1707-1860 Sentence denotes Genetic toxicology studies were conducted in Salmonella typhimurium, cultured Chinese hamster ovary cells, mouse bone marrow, and mouse peripheral blood.
T13 1861-1887 Sentence denotes 16-DAY FEED STUDY IN RATS:
T14 1888-2185 Sentence denotes Groups of five male and five female F344/N rats were given 0, 500, 1,000, 2,000, 4,000, or 8,000 ppm theophylline in feed for 16 days, which resulted in approximate daily doses of 50, 100, 250, 450, or 1,000 mg theophylline/kg body weight to males and 75, 150, 250, 450, or 1,100 mg/kg to females.
T15 2186-2231 Sentence denotes All rats survived until the end of the study.
T16 2232-2364 Sentence denotes The final mean body weights and body weight gains of 8,000 ppm males and females were significantly less than those of the controls.
T17 2365-2479 Sentence denotes The absolute and relative testis weights of 4,000 ppm males were significantly greater than those of the controls.
T18 2480-2582 Sentence denotes Increased incidences of uterine hypoplasia were observed microscopically in exposed groups of females.
T19 2583-2611 Sentence denotes 16-DAY GAVAGE STUDY IN RATS:
T20 2612-2874 Sentence denotes Groups of five male and five female F344/N rats were given 0, 12.5 (twice daily), 25 (once daily), 50 (once daily), 50 (twice daily), 100 (once daily), 200 (once daily), 200 (twice daily), or 400 (once daily) mg theophylline/kg body weight in corn oil by gavage.
T21 2875-2992 Sentence denotes All rats receiving 400 mg/kg once daily and all but one female receiving 200 mg/kg twice daily died during the study.
T22 2993-3206 Sentence denotes In groups dosed once daily, final mean body weights and body weight gains of males receiving 100 or 200 mg/kg and mean body weight gains of females receiving 50, 100, or 200 mg/kg were less than those of controls.
T23 3207-3388 Sentence denotes The final mean body weights and body weight gains of groups receiving theophylline twice daily were generally similar to those of groups receiving the same daily dosages once daily.
T24 3389-3477 Sentence denotes Clinical findings included rapid or labored respiration, hunched posture, and squinting.
T25 3478-3808 Sentence denotes In groups dosed once daily, absolute and relative uterus weights of females receiving 100 or 200 mg/kg once daily were significantly less than those of the controls, and the absolute and relative uterus weights of females receiving 100 mg/kg once daily were significantly less than those of females receiving 50 mg/kg twice daily.
T26 3809-3887 Sentence denotes Uterine atrophy was observed in three females receiving 200 mg/kg twice daily.
T27 3888-4002 Sentence denotes Periarteritis of the mesenteric arteries was observed in two males and two females receiving 400 mg/kg once daily.
T28 4003-4029 Sentence denotes 16-DAY FEED STUDY IN MICE:
T29 4030-4337 Sentence denotes Groups of five male and five female B6C3F1 mice were given 0, 500, 1,000, 2,000, 4,000, or 8,000 ppm theophylline in feed for 16 days, resulting in approximate daily doses of 250, 475, 950, 1,800, or800, or 2,000 mg theophylline/kg body weight to males and 300, 450, 1,225, 2,000, or 4,375 mg/kg to females.
T30 4338-4383 Sentence denotes All mice survived until the end of the study.
T31 4384-4559 Sentence denotes Final mean body weights of 4,000 and 8,000 ppm females and mean body weight gains of 2,000, 4,000, and 8,000 ppm females were significantly greater than those of the controls.
T32 4560-4752 Sentence denotes Feed consumption by exposed groups was similar to that by the controls, except that by the 8,000 ppm males, which was approximately 40% the amount of feed consumed by the control group.
T33 4753-4874 Sentence denotes Histopathologic examinations were not performed due to the absence of mortality and significant exposure-related lesions.
T34 4875-4903 Sentence denotes 16-DAY GAVAGE STUDY IN MICE:
T35 4904-5166 Sentence denotes Groups of five male and five female B6C3F1 mice were given 0, 12.5 (twice daily), 25 (once daily), 50 (once daily), 50 (twice daily), 100 (once daily), 200 (once daily), 200 (twice daily), or 400 (once daily) mg theophylline/kg body weight in corn oil by gavage.
T36 5167-5240 Sentence denotes Three males and all females receiving 400 mg/kg once daily died on day 1.
T37 5241-5327 Sentence denotes There were no significant differences in final mean body weights or body weight gains.
T38 5328-5403 Sentence denotes There were no histopathologic findings attributed directly to theophylline.
T39 5404-5431 Sentence denotes 14-WEEK FEED STUDY IN RATS:
T40 5432-5690 Sentence denotes Groups of 10 male and 10 female F344/N rats were given 0, 1,000, 2,000, or 4,000 ppm theophylline in feed for 14 weeks, which resulted in approximate daily doses of 75, 125, or 250 mg theophylline/kg body weight to males and 75, 125, or 275 mg/kg to females.
T41 5691-5796 Sentence denotes The final mean body weight of 1,000 ppm females was significantly greater than that of the control group.
T42 5797-5868 Sentence denotes Feed consumption by exposed groups was similar to that by the controls.
T43 5869-6009 Sentence denotes Mean cell volume and mean cell hemoglobin were significantly greater in males exposed to 2,000 or 4,000 ppm than those in the control group.
T44 6010-6129 Sentence denotes Segmented neutrophil counts of all groups of exposed females were significantly greater than that of the control group.
T45 6130-6328 Sentence denotes The absolute and relative kidney weights of 4,000 ppm males were significantly greater than those of the controls, and there was an exposure-related increase in the severity of nephropathy in males.
T46 6329-6455 Sentence denotes Exposure-related increases in the incidences of mesenteric and/or pancreatic periarteritis were observed in males and females.
T47 6456-6485 Sentence denotes 14-WEEK GAVAGE STUDY IN RATS:
T48 6486-6627 Sentence denotes Groups of 10 male and 10 female F344/N rats were given 0, 37.5, 75, or 150 mg theophylline/kg body weight in corn oil by gavage for 14 weeks.
T49 6628-6705 Sentence denotes One male and one female receiving 150 mg/kg died before the end of the study.
T50 6706-6805 Sentence denotes The mean body weight gain of 150 mg/kg females was significantly greater than that of the controls.
T51 6806-6955 Sentence denotes Mean cell volume of 150 mg/kg males and mean cell hemoglobin of all groups of dosed males were significantly greater than those of the control group.
T52 6956-7072 Sentence denotes There were slight dose-dependent increases in the incidences of mesenteric periarteritis in dosed males and females.
T53 7073-7100 Sentence denotes 14-WEEK FEED STUDY IN MICE:
T54 7101-7356 Sentence denotes Groups of 10 male and 10 female B6C3F1 mice were given 0, 1,000, 2,000, or 4,000 ppm theophylline in feed for 14 weeks, resulting in approximate daily doses of 175, 400, or 800 mg theophylline/kg body weight to males and 225, 425, or 850 mg/kg to females.
T55 7357-7402 Sentence denotes All mice survived until the end of the study.
T56 7403-7547 Sentence denotes The final mean body weights and body weight gains of all exposed groups of males and females were significantly less than those of the controls.
T57 7548-7619 Sentence denotes Feed consumption by exposed groups was similar to that by the controls.
T58 7620-7748 Sentence denotes Leukocyte, segmented neutrophil, and lymphocyte counts of 4,000 ppm males were significantly greater than those of the controls.
T59 7749-7875 Sentence denotes Leukocyte and segmented neutrophil counts of 2,000 or 4,000 ppm females were significantly greater than those of the controls.
T60 7876-7960 Sentence denotes There were no histopathologic findings attributed directly to theophylline exposure.
T61 7961-7990 Sentence denotes 14-WEEK GAVAGE STUDY IN MICE:
T62 7991-8131 Sentence denotes Groups of 10 male and 10 female B6C3F1 mice were given 0, 75, 150, or 300 mg theophylline/kg body weight in corn oil by gavage for 14 weeks.
T63 8132-8256 Sentence denotes Three males and all females receiving 300 mg/kg, one 75 mg/kg male, and one control female died before the end of the study.
T64 8257-8381 Sentence denotes Final mean body weights and body weight gains of 150 and 300 mg/kg males were significantly less than those of the controls.
T65 8382-8497 Sentence denotes Mean cell volume and mean cell hemoglobin of 300 mg/kg males were significantly greater than those of the controls.
T66 8498-8583 Sentence denotes There were no histopathologic findings attributed directly to theophylline treatment.
T67 8584-8612 Sentence denotes 2-YEAR GAVAGE STUDY IN RATS:
T68 8613-8741 Sentence denotes Groups of 50 male and 50 female rats were given 7.5, 25, or 75 mg theophylline/kg body weight in corn oil by gavage for 2 years.
T69 8742-8768 Sentence denotes Survival and Body Weights:
T70 8769-8852 Sentence denotes There were no significant differences in survival between dosed and control groups.
T71 8853-8969 Sentence denotes Final mean body weights of all groups of dosed males and females were significantly less than those of the controls.
T72 8970-8989 Sentence denotes Pathology Findings:
T73 8990-9066 Sentence denotes There were no significantly increased incidences of neoplasms in dosed rats.
T74 9067-9213 Sentence denotes The incidence of chronic inflammation of the mesenteric arteries was significantly increased in males receiving 75 mg/kg compared to the controls.
T75 9214-9411 Sentence denotes There were doserelated negative trends in the incidences of mammary gland fibroadenoma and fibroadenoma or carcinoma (combined) in females; these differences correlated with decreased body weights.
T76 9412-9440 Sentence denotes 2-YEAR GAVAGE STUDY IN MICE:
T77 9441-9636 Sentence denotes Groups of 50 male B6C3F1 mice were given 0, 15, 50, or 150 mg theophylline/kg body weight and groups of 50 female B6C3F1 mice were given 0, 7.5, 25, or 75 mg/kg in corn oil by gavage for 2 years.
T78 9637-9663 Sentence denotes Survival and Body Weights:
T79 9664-9741 Sentence denotes Survival of 150 mg/kg males was significantly less than that of the controls.
T80 9742-9886 Sentence denotes The final mean body weights of 150 mg/kg males, 25 mg/kg females, and 75 mg/kg females were significantly less than those of the control groups.
T81 9887-9906 Sentence denotes Pathology Findings:
T82 9907-10001 Sentence denotes There were no treatment-related increases in incidences of nonneoplastic lesions or neoplasms.
T83 10002-10177 Sentence denotes In males and females, there were decreased incidences of hepatocellular adenoma and of the combined incidences of hepatocellular adenoma or carcinoma compared to the controls.
T84 10178-10340 Sentence denotes Male mice had a pattern of nonneoplastic liver lesions along with silver-staining helical organisms in the liver consistent with Helicobacter hepaticus infection.
T85 10341-10451 Sentence denotes The incidences of these liver lesions in 150 mg/kg males were significantly lower than those in control males.
T86 10452-10613 Sentence denotes Increases in the incidences of hepatocellular neoplasms in male mice have been shown to be associated with H. hepaticus infection when hepatitis is also present.
T87 10614-10736 Sentence denotes Because of this association, interpretation of the decreased incidence of liver neoplasms in male mice was more difficult.
T88 10737-10898 Sentence denotes Incidences of lesions at other sites in this study were not considered to have been significantly impacted by H. hepaticus infection or its associated hepatitis.
T89 10899-10918 Sentence denotes GENETIC TOXICOLOGY:
T90 10919-11019 Sentence denotes Theophylline was not mutagenic in Salmonella typhimurium, with or without metabolic activation (S9).
T91 11020-11130 Sentence denotes It induced sister chromatid exchanges but not chromosomal aberrations in cultured Chinese hamster ovary cells.
T92 11131-11215 Sentence denotes The positive sister chromatid exchange response was noted only in the absence of S9.
T93 11216-11404 Sentence denotes In vivo, a mouse bone marrow sister chromatid exchange test showed positive results at a standard 23-hour harvest time; however, this test was not repeated and the response is unconfirmed.
T94 11405-11547 Sentence denotes An in vivo mouse bone marrow chromosomal aberrations test, that employed both standard and extended exposure protocols, gave negative results.
T95 11548-11728 Sentence denotes The frequency of micronucleated erythrocytes was determined in peripheral blood of male and female mice exposed to theophylline in dosed feed or in corn oil by gavage for 14 weeks.
T96 11729-11855 Sentence denotes No significant increases in the frequencies of micronucleated cells were seen in male or female mice in either of the studies.
T97 11856-11868 Sentence denotes CONCLUSIONS:
T98 11869-12049 Sentence denotes Under the conditions of these 2-year gavage studies, there was no evidence of carcinogenic activity of theophylline in male or female F344/N rats administered 7.5, 25, or 75 mg/kg.
T99 12050-12223 Sentence denotes There was no evidence of carcinogenic activity of theophylline in male B6C3F1 mice administered 15, 50, or 150 mg/kg or female B6C3F1 mice administered 7.5, 25, or 75 mg/kg.
T100 12224-12336 Sentence denotes Gavage administration of theophylline caused chronic inflammation of the mesenteric arteries in dosed male rats.
T101 12337-12441 Sentence denotes Decreased incidences of mammary neoplasms in female rats were likely associated with lower body weights.
T102 12442-12573 Sentence denotes There were dose-related decreases in the incidences of hepatocellular adenoma and hepatocellular carcinoma in male and female mice.
T103 12574-12583 Sentence denotes Synonyms:
T104 12584-12762 Sentence denotes 3,7-dihydro-1,3-dimethyl-1H-purine-2,6-dione; 1,3-dimethylxanthine; 1H-purine-2,6-dione; NSC 2066; pseusdotheophylline; theocin; theophyllin; theophylline, anhydrous Trade names:
T105 12763-13543 Sentence denotes Accurbron; Aerobin; Aerolate III; Afonilum; Aminophylline; Aquaphyllin; Armophylline; Asmalix; Bilordyl; Bronchoretard; Bronkodyl; Cetraphylline; Constant-T; Diffumal; Duraphyl; Duraphyllin; Elixicon; Elixophyllin; Euphylline L.A.; Euphylong; LaBID; Labophylline; Lanophyllin; Lasma; Liquophylline; Optiphyllin; Parkophyllin; Phylocontin; Physpan; Pro-Vent; PulmiDur; Pulmo-Timelets; Quibron; Respbid; Rona-Phyllin; Sabidal; Slo-bid; Slo-Phyllin; Solosin; Sustaire; Tefamin; Teobid; Teofyllamin; Tesona; Theal tablets; Theo-24; Theobid; Theocap; Theochron; Theoclear; Theocontin; Theo-Dur; Theofol; Theograd; Theolair; Theolan; Theolix; Theophyl; Theoplus; Theo-Sav; Theosol; Theospan; Theostat; Theovent; TheoX; T-Phyl; Truphylline; Uni-Dur; Unifyl; Uniphyl; Uniphyllin; Xanthium
T1 0-66 Sentence denotes NTP Toxicology and Carcinogenesis Studies of Theophylline (CAS No.
T2 67-133 Sentence denotes 58-55-9) in F344/N Rats and B6C3F1 Mice (Feed and Gavage Studies).
T3 134-261 Sentence denotes Theophylline is an alkaloid found in tea (Thea sinensis) and chocolate and is structurally related to caffeine and theobromine.
T4 262-309 Sentence denotes Theophylline is used as a pharmaceutical agent.
T5 310-443 Sentence denotes It stimulates the heart and central nervous system, relaxes the smooth muscles of the bronchi and blood vessels, and causes diuresis.
T6 444-577 Sentence denotes The drug is used mainly as a bronchodilator in obstructive airway diseases, such as bronchial asthma, and for myocardial stimulation.
T7 578-903 Sentence denotes Theophylline was nominated for toxicologic and carcinogenicity testing as a representative of the purine structural subclass, particularly because of its relationship to purines such as caffeine, 1-methyl-3-hydroxyguanine, and 3-hydroxy-1-methylxanthine, the latter two compounds having been shown to induce sarcomas in rats.
T8 904-1165 Sentence denotes Additional reasons for testing theophylline included its widespread use in humans as a pharmaceutical agent, its possible genotoxicity in vitro, and the lack of information on its potential toxicity and/or carcinogenicity under conditions of chronic oral usage.
T9 1166-1320 Sentence denotes Based on reported teratogenicity and testicular toxicity, it was also recommended that reproductive studies be included in the evaluation of theophylline.
T10 1321-1519 Sentence denotes The oral route of administration was selected because it is the primary route of human exposure, and the gavage route was selected because it mimics the pharmaceutical use of theophylline in humans.
T11 1520-1706 Sentence denotes Male and female F344/N rats and B6C3F1 mice were given theophylline (greater than 99% pure) in feed or in corn oil by gavage for 16 days or 14 weeks or in corn oil by gavage for 2 years.
T12 1707-1860 Sentence denotes Genetic toxicology studies were conducted in Salmonella typhimurium, cultured Chinese hamster ovary cells, mouse bone marrow, and mouse peripheral blood.
T13 1861-1887 Sentence denotes 16-DAY FEED STUDY IN RATS:
T14 1888-2185 Sentence denotes Groups of five male and five female F344/N rats were given 0, 500, 1,000, 2,000, 4,000, or 8,000 ppm theophylline in feed for 16 days, which resulted in approximate daily doses of 50, 100, 250, 450, or 1,000 mg theophylline/kg body weight to males and 75, 150, 250, 450, or 1,100 mg/kg to females.
T15 2186-2231 Sentence denotes All rats survived until the end of the study.
T16 2232-2364 Sentence denotes The final mean body weights and body weight gains of 8,000 ppm males and females were significantly less than those of the controls.
T17 2365-2479 Sentence denotes The absolute and relative testis weights of 4,000 ppm males were significantly greater than those of the controls.
T18 2480-2582 Sentence denotes Increased incidences of uterine hypoplasia were observed microscopically in exposed groups of females.
T19 2583-2611 Sentence denotes 16-DAY GAVAGE STUDY IN RATS:
T20 2612-2874 Sentence denotes Groups of five male and five female F344/N rats were given 0, 12.5 (twice daily), 25 (once daily), 50 (once daily), 50 (twice daily), 100 (once daily), 200 (once daily), 200 (twice daily), or 400 (once daily) mg theophylline/kg body weight in corn oil by gavage.
T21 2875-2992 Sentence denotes All rats receiving 400 mg/kg once daily and all but one female receiving 200 mg/kg twice daily died during the study.
T22 2993-3206 Sentence denotes In groups dosed once daily, final mean body weights and body weight gains of males receiving 100 or 200 mg/kg and mean body weight gains of females receiving 50, 100, or 200 mg/kg were less than those of controls.
T23 3207-3388 Sentence denotes The final mean body weights and body weight gains of groups receiving theophylline twice daily were generally similar to those of groups receiving the same daily dosages once daily.
T24 3389-3477 Sentence denotes Clinical findings included rapid or labored respiration, hunched posture, and squinting.
T25 3478-3808 Sentence denotes In groups dosed once daily, absolute and relative uterus weights of females receiving 100 or 200 mg/kg once daily were significantly less than those of the controls, and the absolute and relative uterus weights of females receiving 100 mg/kg once daily were significantly less than those of females receiving 50 mg/kg twice daily.
T26 3809-3887 Sentence denotes Uterine atrophy was observed in three females receiving 200 mg/kg twice daily.
T27 3888-4002 Sentence denotes Periarteritis of the mesenteric arteries was observed in two males and two females receiving 400 mg/kg once daily.
T28 4003-4029 Sentence denotes 16-DAY FEED STUDY IN MICE:
T29 4030-4337 Sentence denotes Groups of five male and five female B6C3F1 mice were given 0, 500, 1,000, 2,000, 4,000, or 8,000 ppm theophylline in feed for 16 days, resulting in approximate daily doses of 250, 475, 950, 1,800, or800, or 2,000 mg theophylline/kg body weight to males and 300, 450, 1,225, 2,000, or 4,375 mg/kg to females.
T30 4338-4383 Sentence denotes All mice survived until the end of the study.
T31 4384-4559 Sentence denotes Final mean body weights of 4,000 and 8,000 ppm females and mean body weight gains of 2,000, 4,000, and 8,000 ppm females were significantly greater than those of the controls.
T32 4560-4752 Sentence denotes Feed consumption by exposed groups was similar to that by the controls, except that by the 8,000 ppm males, which was approximately 40% the amount of feed consumed by the control group.
T33 4753-4874 Sentence denotes Histopathologic examinations were not performed due to the absence of mortality and significant exposure-related lesions.
T34 4875-4903 Sentence denotes 16-DAY GAVAGE STUDY IN MICE:
T35 4904-5166 Sentence denotes Groups of five male and five female B6C3F1 mice were given 0, 12.5 (twice daily), 25 (once daily), 50 (once daily), 50 (twice daily), 100 (once daily), 200 (once daily), 200 (twice daily), or 400 (once daily) mg theophylline/kg body weight in corn oil by gavage.
T36 5167-5240 Sentence denotes Three males and all females receiving 400 mg/kg once daily died on day 1.
T37 5241-5327 Sentence denotes There were no significant differences in final mean body weights or body weight gains.
T38 5328-5403 Sentence denotes There were no histopathologic findings attributed directly to theophylline.
T39 5404-5431 Sentence denotes 14-WEEK FEED STUDY IN RATS:
T40 5432-5690 Sentence denotes Groups of 10 male and 10 female F344/N rats were given 0, 1,000, 2,000, or 4,000 ppm theophylline in feed for 14 weeks, which resulted in approximate daily doses of 75, 125, or 250 mg theophylline/kg body weight to males and 75, 125, or 275 mg/kg to females.
T41 5691-5796 Sentence denotes The final mean body weight of 1,000 ppm females was significantly greater than that of the control group.
T42 5797-5868 Sentence denotes Feed consumption by exposed groups was similar to that by the controls.
T43 5869-6009 Sentence denotes Mean cell volume and mean cell hemoglobin were significantly greater in males exposed to 2,000 or 4,000 ppm than those in the control group.
T44 6010-6129 Sentence denotes Segmented neutrophil counts of all groups of exposed females were significantly greater than that of the control group.
T45 6130-6328 Sentence denotes The absolute and relative kidney weights of 4,000 ppm males were significantly greater than those of the controls, and there was an exposure-related increase in the severity of nephropathy in males.
T46 6329-6455 Sentence denotes Exposure-related increases in the incidences of mesenteric and/or pancreatic periarteritis were observed in males and females.
T47 6456-6485 Sentence denotes 14-WEEK GAVAGE STUDY IN RATS:
T48 6486-6627 Sentence denotes Groups of 10 male and 10 female F344/N rats were given 0, 37.5, 75, or 150 mg theophylline/kg body weight in corn oil by gavage for 14 weeks.
T49 6628-6705 Sentence denotes One male and one female receiving 150 mg/kg died before the end of the study.
T50 6706-6805 Sentence denotes The mean body weight gain of 150 mg/kg females was significantly greater than that of the controls.
T51 6806-6955 Sentence denotes Mean cell volume of 150 mg/kg males and mean cell hemoglobin of all groups of dosed males were significantly greater than those of the control group.
T52 6956-7072 Sentence denotes There were slight dose-dependent increases in the incidences of mesenteric periarteritis in dosed males and females.
T53 7073-7100 Sentence denotes 14-WEEK FEED STUDY IN MICE:
T54 7101-7356 Sentence denotes Groups of 10 male and 10 female B6C3F1 mice were given 0, 1,000, 2,000, or 4,000 ppm theophylline in feed for 14 weeks, resulting in approximate daily doses of 175, 400, or 800 mg theophylline/kg body weight to males and 225, 425, or 850 mg/kg to females.
T55 7357-7402 Sentence denotes All mice survived until the end of the study.
T56 7403-7547 Sentence denotes The final mean body weights and body weight gains of all exposed groups of males and females were significantly less than those of the controls.
T57 7548-7619 Sentence denotes Feed consumption by exposed groups was similar to that by the controls.
T58 7620-7748 Sentence denotes Leukocyte, segmented neutrophil, and lymphocyte counts of 4,000 ppm males were significantly greater than those of the controls.
T59 7749-7875 Sentence denotes Leukocyte and segmented neutrophil counts of 2,000 or 4,000 ppm females were significantly greater than those of the controls.
T60 7876-7960 Sentence denotes There were no histopathologic findings attributed directly to theophylline exposure.
T61 7961-7990 Sentence denotes 14-WEEK GAVAGE STUDY IN MICE:
T62 7991-8131 Sentence denotes Groups of 10 male and 10 female B6C3F1 mice were given 0, 75, 150, or 300 mg theophylline/kg body weight in corn oil by gavage for 14 weeks.
T63 8132-8256 Sentence denotes Three males and all females receiving 300 mg/kg, one 75 mg/kg male, and one control female died before the end of the study.
T64 8257-8381 Sentence denotes Final mean body weights and body weight gains of 150 and 300 mg/kg males were significantly less than those of the controls.
T65 8382-8497 Sentence denotes Mean cell volume and mean cell hemoglobin of 300 mg/kg males were significantly greater than those of the controls.
T66 8498-8583 Sentence denotes There were no histopathologic findings attributed directly to theophylline treatment.
T67 8584-8612 Sentence denotes 2-YEAR GAVAGE STUDY IN RATS:
T68 8613-8741 Sentence denotes Groups of 50 male and 50 female rats were given 7.5, 25, or 75 mg theophylline/kg body weight in corn oil by gavage for 2 years.
T69 8742-8768 Sentence denotes Survival and Body Weights:
T70 8769-8852 Sentence denotes There were no significant differences in survival between dosed and control groups.
T71 8853-8969 Sentence denotes Final mean body weights of all groups of dosed males and females were significantly less than those of the controls.
T72 8970-8989 Sentence denotes Pathology Findings:
T73 8990-9066 Sentence denotes There were no significantly increased incidences of neoplasms in dosed rats.
T74 9067-9213 Sentence denotes The incidence of chronic inflammation of the mesenteric arteries was significantly increased in males receiving 75 mg/kg compared to the controls.
T75 9214-9411 Sentence denotes There were doserelated negative trends in the incidences of mammary gland fibroadenoma and fibroadenoma or carcinoma (combined) in females; these differences correlated with decreased body weights.
T76 9412-9440 Sentence denotes 2-YEAR GAVAGE STUDY IN MICE:
T77 9441-9636 Sentence denotes Groups of 50 male B6C3F1 mice were given 0, 15, 50, or 150 mg theophylline/kg body weight and groups of 50 female B6C3F1 mice were given 0, 7.5, 25, or 75 mg/kg in corn oil by gavage for 2 years.
T78 9637-9663 Sentence denotes Survival and Body Weights:
T79 9664-9741 Sentence denotes Survival of 150 mg/kg males was significantly less than that of the controls.
T80 9742-9886 Sentence denotes The final mean body weights of 150 mg/kg males, 25 mg/kg females, and 75 mg/kg females were significantly less than those of the control groups.
T81 9887-9906 Sentence denotes Pathology Findings:
T82 9907-10001 Sentence denotes There were no treatment-related increases in incidences of nonneoplastic lesions or neoplasms.
T83 10002-10177 Sentence denotes In males and females, there were decreased incidences of hepatocellular adenoma and of the combined incidences of hepatocellular adenoma or carcinoma compared to the controls.
T84 10178-10340 Sentence denotes Male mice had a pattern of nonneoplastic liver lesions along with silver-staining helical organisms in the liver consistent with Helicobacter hepaticus infection.
T85 10341-10451 Sentence denotes The incidences of these liver lesions in 150 mg/kg males were significantly lower than those in control males.
T86 10452-10613 Sentence denotes Increases in the incidences of hepatocellular neoplasms in male mice have been shown to be associated with H. hepaticus infection when hepatitis is also present.
T87 10614-10736 Sentence denotes Because of this association, interpretation of the decreased incidence of liver neoplasms in male mice was more difficult.
T88 10737-10898 Sentence denotes Incidences of lesions at other sites in this study were not considered to have been significantly impacted by H. hepaticus infection or its associated hepatitis.
T89 10899-10918 Sentence denotes GENETIC TOXICOLOGY:
T90 10919-11019 Sentence denotes Theophylline was not mutagenic in Salmonella typhimurium, with or without metabolic activation (S9).
T91 11020-11130 Sentence denotes It induced sister chromatid exchanges but not chromosomal aberrations in cultured Chinese hamster ovary cells.
T92 11131-11215 Sentence denotes The positive sister chromatid exchange response was noted only in the absence of S9.
T93 11216-11404 Sentence denotes In vivo, a mouse bone marrow sister chromatid exchange test showed positive results at a standard 23-hour harvest time; however, this test was not repeated and the response is unconfirmed.
T94 11405-11547 Sentence denotes An in vivo mouse bone marrow chromosomal aberrations test, that employed both standard and extended exposure protocols, gave negative results.
T95 11548-11728 Sentence denotes The frequency of micronucleated erythrocytes was determined in peripheral blood of male and female mice exposed to theophylline in dosed feed or in corn oil by gavage for 14 weeks.
T96 11729-11855 Sentence denotes No significant increases in the frequencies of micronucleated cells were seen in male or female mice in either of the studies.
T97 11856-11868 Sentence denotes CONCLUSIONS:
T98 11869-12049 Sentence denotes Under the conditions of these 2-year gavage studies, there was no evidence of carcinogenic activity of theophylline in male or female F344/N rats administered 7.5, 25, or 75 mg/kg.
T99 12050-12223 Sentence denotes There was no evidence of carcinogenic activity of theophylline in male B6C3F1 mice administered 15, 50, or 150 mg/kg or female B6C3F1 mice administered 7.5, 25, or 75 mg/kg.
T100 12224-12336 Sentence denotes Gavage administration of theophylline caused chronic inflammation of the mesenteric arteries in dosed male rats.
T101 12337-12441 Sentence denotes Decreased incidences of mammary neoplasms in female rats were likely associated with lower body weights.
T102 12442-12573 Sentence denotes There were dose-related decreases in the incidences of hepatocellular adenoma and hepatocellular carcinoma in male and female mice.
T103 12574-12583 Sentence denotes Synonyms:
T104 12584-12762 Sentence denotes 3,7-dihydro-1,3-dimethyl-1H-purine-2,6-dione; 1,3-dimethylxanthine; 1H-purine-2,6-dione; NSC 2066; pseusdotheophylline; theocin; theophyllin; theophylline, anhydrous Trade names:
T105 12763-13543 Sentence denotes Accurbron; Aerobin; Aerolate III; Afonilum; Aminophylline; Aquaphyllin; Armophylline; Asmalix; Bilordyl; Bronchoretard; Bronkodyl; Cetraphylline; Constant-T; Diffumal; Duraphyl; Duraphyllin; Elixicon; Elixophyllin; Euphylline L.A.; Euphylong; LaBID; Labophylline; Lanophyllin; Lasma; Liquophylline; Optiphyllin; Parkophyllin; Phylocontin; Physpan; Pro-Vent; PulmiDur; Pulmo-Timelets; Quibron; Respbid; Rona-Phyllin; Sabidal; Slo-bid; Slo-Phyllin; Solosin; Sustaire; Tefamin; Teobid; Teofyllamin; Tesona; Theal tablets; Theo-24; Theobid; Theocap; Theochron; Theoclear; Theocontin; Theo-Dur; Theofol; Theograd; Theolair; Theolan; Theolix; Theophyl; Theoplus; Theo-Sav; Theosol; Theospan; Theostat; Theovent; TheoX; T-Phyl; Truphylline; Uni-Dur; Unifyl; Uniphyl; Uniphyllin; Xanthium