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Id Subject Object Predicate Lexical cue
T1 0-62 Sentence denotes NTP Toxicology and Carcinogenesis Studies of Coumarin (CAS No.
T1 0-62 Sentence denotes NTP Toxicology and Carcinogenesis Studies of Coumarin (CAS No.
T2 63-120 Sentence denotes 91-64-5) in F344/N Rats and B6C3F1 Mice (Gavage Studies).
T2 63-120 Sentence denotes 91-64-5) in F344/N Rats and B6C3F1 Mice (Gavage Studies).
T3 121-247 Sentence denotes Coumarin is the basic structure of numerous naturally occurring compounds with important and diverse physiological activities.
T3 121-247 Sentence denotes Coumarin is the basic structure of numerous naturally occurring compounds with important and diverse physiological activities.
T4 248-476 Sentence denotes More than a thousand coumarin derivatives have been described, varying from simple coumarins containing alkyl and hydroxyl side chains to complex coumarins with benzoyl, furanoyl, pyranoyl, or alkylphosphorothionyl substituents.
T4 248-476 Sentence denotes More than a thousand coumarin derivatives have been described, varying from simple coumarins containing alkyl and hydroxyl side chains to complex coumarins with benzoyl, furanoyl, pyranoyl, or alkylphosphorothionyl substituents.
T5 477-875 Sentence denotes Coumarin and 3,4-dihydrocoumarin were nominated by the Food and Drug Administration and the National Cancer Institute for study because of the widespread use of coumarin in perfumes, cosmetics, and other products as a fragrance, continued interest in coumarin compounds as flavor-enhancing agents for foods, and the interest in structure-activity relationships of this important group of compounds.
T5 477-875 Sentence denotes Coumarin and 3,4-dihydrocoumarin were nominated by the Food and Drug Administration and the National Cancer Institute for study because of the widespread use of coumarin in perfumes, cosmetics, and other products as a fragrance, continued interest in coumarin compounds as flavor-enhancing agents for foods, and the interest in structure-activity relationships of this important group of compounds.
T6 876-1111 Sentence denotes Coumarin is believed to be metabolized to a 3,4-epoxide intermediate, which may be responsible for its toxic effects, while 3,4-dihydrocoumarin, which lacks the 3,4-double bond, is not considered likely to form an epoxide intermediate.
T6 876-1111 Sentence denotes Coumarin is believed to be metabolized to a 3,4-epoxide intermediate, which may be responsible for its toxic effects, while 3,4-dihydrocoumarin, which lacks the 3,4-double bond, is not considered likely to form an epoxide intermediate.
T7 1112-1315 Sentence denotes Toxicity and carcinogenicity studies were conducted by administering coumarin (97% pure) in corn oil by gavage to groups of male and female F344/N rats and B6C3F1 mice for 16 days, 13 weeks, and 2 years.
T7 1112-1315 Sentence denotes Toxicity and carcinogenicity studies were conducted by administering coumarin (97% pure) in corn oil by gavage to groups of male and female F344/N rats and B6C3F1 mice for 16 days, 13 weeks, and 2 years.
T8 1316-1464 Sentence denotes Genetic toxicology studies were conducted in Salmonella typhimurium, cultured Chinese hamster ovary cells, Drosophila melanogaster, and B6C3F1 mice.
T8 1316-1464 Sentence denotes Genetic toxicology studies were conducted in Salmonella typhimurium, cultured Chinese hamster ovary cells, Drosophila melanogaster, and B6C3F1 mice.
T9 1465-1486 Sentence denotes 16-DAY STUDY IN RATS:
T9 1465-1486 Sentence denotes 16-DAY STUDY IN RATS:
T10 1487-1688 Sentence denotes Groups of five male and five female rats received coumarin in corn oil by gavage at doses of 0, 25, 50, 100, 200, or 400 mg per kg body weight, 5 days a week for a total of 12 doses in a 16-day period.
T10 1487-1688 Sentence denotes Groups of five male and five female rats received coumarin in corn oil by gavage at doses of 0, 25, 50, 100, 200, or 400 mg per kg body weight, 5 days a week for a total of 12 doses in a 16-day period.
T11 1689-1749 Sentence denotes All female rats and four male rats receiving 400 mg/kg died.
T11 1689-1749 Sentence denotes All female rats and four male rats receiving 400 mg/kg died.
T12 1750-1883 Sentence denotes The mean body weight gains and final mean body weights of surviving dosed male and female rats were similar to those of the controls.
T12 1750-1883 Sentence denotes The mean body weight gains and final mean body weights of surviving dosed male and female rats were similar to those of the controls.
T13 1884-2099 Sentence denotes There were no clinical signs of organ-specific toxicity, and there was no evidence of impaired blood coagulation from measurements of capillary clotting time or prothrombin and activated partial thromboplastin time.
T13 1884-2099 Sentence denotes There were no clinical signs of organ-specific toxicity, and there was no evidence of impaired blood coagulation from measurements of capillary clotting time or prothrombin and activated partial thromboplastin time.
T14 2100-2121 Sentence denotes 16-DAY STUDY IN MICE:
T14 2100-2121 Sentence denotes 16-DAY STUDY IN MICE:
T15 2122-2323 Sentence denotes Groups of five male and five female mice received coumarin in corn oil by gavage at doses of 0, 40, 75, 150, 300, or 600 mg per kg body weight, 5 days a week for a total of 12 doses in a 16-day period.
T15 2122-2323 Sentence denotes Groups of five male and five female mice received coumarin in corn oil by gavage at doses of 0, 40, 75, 150, 300, or 600 mg per kg body weight, 5 days a week for a total of 12 doses in a 16-day period.
T16 2324-2432 Sentence denotes All mice receiving 600 mg/kg, two male mice receiving 300 mg/kg, and one male mouse receiving 75 mg/kg died.
T16 2324-2432 Sentence denotes All mice receiving 600 mg/kg, two male mice receiving 300 mg/kg, and one male mouse receiving 75 mg/kg died.
T17 2433-2566 Sentence denotes The mean body weight gains and final mean body weights of surviving dosed male and female mice were similar to those of the controls.
T17 2433-2566 Sentence denotes The mean body weight gains and final mean body weights of surviving dosed male and female mice were similar to those of the controls.
T18 2567-2771 Sentence denotes Clinical findings of inactivity, excessive lacrimation, piloerection, bradypnea, ptosis, or ataxia were observed in some mice from the 300 and 600 mg/kg groups within the first several hours after dosing.
T18 2567-2771 Sentence denotes Clinical findings of inactivity, excessive lacrimation, piloerection, bradypnea, ptosis, or ataxia were observed in some mice from the 300 and 600 mg/kg groups within the first several hours after dosing.
T19 2772-2864 Sentence denotes Capillary clotting time and platelet counts of dosed mice were similar to those of controls.
T19 2772-2864 Sentence denotes Capillary clotting time and platelet counts of dosed mice were similar to those of controls.
T20 2865-2887 Sentence denotes 13-WEEK STUDY IN RATS:
T20 2865-2887 Sentence denotes 13-WEEK STUDY IN RATS:
T21 2888-3024 Sentence denotes Groups of 10 male and 10 female rats received coumarin in corn oil by gavage at doses of 0,19, 38, 75,150, or 300 mg per kg body weight.
T21 2888-3024 Sentence denotes Groups of 10 male and 10 female rats received coumarin in corn oil by gavage at doses of 0,19, 38, 75,150, or 300 mg per kg body weight.
T22 3025-3083 Sentence denotes Three male and three female rats receiving 300 mg/kg died.
T22 3025-3083 Sentence denotes Three male and three female rats receiving 300 mg/kg died.
T23 3084-3236 Sentence denotes The mean body weight gains and final mean body weights of male rats that received 150 and 300 mg/kg were significantly lower than those of the controls.
T23 3084-3236 Sentence denotes The mean body weight gains and final mean body weights of male rats that received 150 and 300 mg/kg were significantly lower than those of the controls.
T24 3237-3301 Sentence denotes There were no clinical signs related to specific organ toxicity.
T24 3237-3301 Sentence denotes There were no clinical signs related to specific organ toxicity.
T25 3302-3484 Sentence denotes Male and female rats receiving coumarin exhibited dose-related decreases in mean erythrocyte volume and mean erythrocyte hemoglobin, and dose-related increases in erythrocyte counts.
T25 3302-3484 Sentence denotes Male and female rats receiving coumarin exhibited dose-related decreases in mean erythrocyte volume and mean erythrocyte hemoglobin, and dose-related increases in erythrocyte counts.
T26 3485-3755 Sentence denotes Serum levels of total bilirubin and one or more cytoplasmic enzymes including alanine aminotransferase, aspartate aminotransferase, ornithine carbamoyltransferase, and/or sorbitol dehydrogenase in males and females receiving 300 mg/kg were higher than those of controls.
T26 3485-3755 Sentence denotes Serum levels of total bilirubin and one or more cytoplasmic enzymes including alanine aminotransferase, aspartate aminotransferase, ornithine carbamoyltransferase, and/or sorbitol dehydrogenase in males and females receiving 300 mg/kg were higher than those of controls.
T27 3756-3906 Sentence denotes The absolute and relative liver weights of male and female rats that received 150 and 300 mg/kg were significantly greater than those of the controls.
T27 3756-3906 Sentence denotes The absolute and relative liver weights of male and female rats that received 150 and 300 mg/kg were significantly greater than those of the controls.
T28 3907-4080 Sentence denotes Centrilobular hepatocellular degeneration and necrosis, chronic active inflammation, and bile duct hyperplasia were observed in the liver of rats receiving 150 or 300 mg/kg.
T28 3907-4080 Sentence denotes Centrilobular hepatocellular degeneration and necrosis, chronic active inflammation, and bile duct hyperplasia were observed in the liver of rats receiving 150 or 300 mg/kg.
T29 4081-4300 Sentence denotes The high dose selected for the 2-year study was 100 mg/kg, which was just below the level at which mortality, lower final mean body weiody weights, and treatment-related liver lesions were observed in the 13-week study.
T29 4081-4300 Sentence denotes The high dose selected for the 2-year study was 100 mg/kg, which was just below the level at which mortality, lower final mean body weiody weights, and treatment-related liver lesions were observed in the 13-week study.
T30 4301-4323 Sentence denotes 13-WEEK STUDY IN MICE:
T30 4301-4323 Sentence denotes 13-WEEK STUDY IN MICE:
T31 4324-4462 Sentence denotes Groups of 10 male and 10 female mice received coumarin in corn oil by gavage at doses of 0, 19, 38, 75, 150, or 300 mg per kg body weight.
T31 4324-4462 Sentence denotes Groups of 10 male and 10 female mice received coumarin in corn oil by gavage at doses of 0, 19, 38, 75, 150, or 300 mg per kg body weight.
T32 4463-4502 Sentence denotes Two male mice receiving 300 mg/kg died.
T32 4463-4502 Sentence denotes Two male mice receiving 300 mg/kg died.
T33 4503-4655 Sentence denotes The mean body weight gain and final mean body weight of surviving male mice that received 300 mg/kg were significantly lower than those of the controls.
T33 4503-4655 Sentence denotes The mean body weight gain and final mean body weight of surviving male mice that received 300 mg/kg were significantly lower than those of the controls.
T34 4656-4700 Sentence denotes No clinical signs of toxicity were observed.
T34 4656-4700 Sentence denotes No clinical signs of toxicity were observed.
T35 4701-4833 Sentence denotes Male and female mice receiving coumarin exhibited dose-related decreases in mean erythrocyte volume and mean erythrocyte hemoglobin.
T35 4701-4833 Sentence denotes Male and female mice receiving coumarin exhibited dose-related decreases in mean erythrocyte volume and mean erythrocyte hemoglobin.
T36 4834-4981 Sentence denotes The absolute and relative liver weights of males and females that received 150 and 300 mg/kg were significantly greater than those of the controls.
T36 4834-4981 Sentence denotes The absolute and relative liver weights of males and females that received 150 and 300 mg/kg were significantly greater than those of the controls.
T37 4982-5080 Sentence denotes Centrilobular hepatocellular hypertrophy was observed in male and female mice receiving 300 mg/kg.
T37 4982-5080 Sentence denotes Centrilobular hepatocellular hypertrophy was observed in male and female mice receiving 300 mg/kg.
T38 5081-5243 Sentence denotes The high dose selected for the 2-year study was 200 mg/kg, which was just below the level at which mortality and liver lesions were observed in the 13-week study.
T38 5081-5243 Sentence denotes The high dose selected for the 2-year study was 200 mg/kg, which was just below the level at which mortality and liver lesions were observed in the 13-week study.
T39 5244-5265 Sentence denotes 2-YEAR STUDY IN RATS:
T39 5244-5265 Sentence denotes 2-YEAR STUDY IN RATS:
T40 5266-5404 Sentence denotes Groups of 60 male and 60 female rats were administered coumarin in corn oil by gavage at doses of 0, 25, 50, or 100 mg per kg body weight.
T40 5266-5404 Sentence denotes Groups of 60 male and 60 female rats were administered coumarin in corn oil by gavage at doses of 0, 25, 50, or 100 mg per kg body weight.
T41 5405-5464 Sentence denotes After 15 months, 10 animals from each group were evaluated.
T41 5405-5464 Sentence denotes After 15 months, 10 animals from each group were evaluated.
T42 5465-5511 Sentence denotes Survival, Body Weights, and Clinical Findings:
T42 5465-5511 Sentence denotes Survival, Body Weights, and Clinical Findings:
T43 5512-5702 Sentence denotes None of the male rats receiving 100 mg/kg and only two males receiving 50 mg/kg survived until the end of the study (vehicle control, 28/50; 25 mg/kg, 9/50; 50 mg/kg, 2/51; 100 mg/kg, 0/50).
T43 5512-5702 Sentence denotes None of the male rats receiving 100 mg/kg and only two males receiving 50 mg/kg survived until the end of the study (vehicle control, 28/50; 25 mg/kg, 9/50; 50 mg/kg, 2/51; 100 mg/kg, 0/50).
T44 5703-5798 Sentence denotes Survival of dosed female rats was similar to that of the controls (29/50, 38/50, 36/50, 30/50).
T44 5703-5798 Sentence denotes Survival of dosed female rats was similar to that of the controls (29/50, 38/50, 36/50, 30/50).
T45 5799-5938 Sentence denotes The reduced survival in dosed male rats was primarily attributed to chemical-related exacerbation of spontaneously occurring renal disease.
T45 5799-5938 Sentence denotes The reduced survival in dosed male rats was primarily attributed to chemical-related exacerbation of spontaneously occurring renal disease.
T46 5939-6074 Sentence denotes Final mean body weights of female rats that received 100 mg/kg and all dosed groups of male rats were lower than those of the controls.
T46 5939-6074 Sentence denotes Final mean body weights of female rats that received 100 mg/kg and all dosed groups of male rats were lower than those of the controls.
T47 6075-6229 Sentence denotes There were no clinical signs of toxicity in rats, other than nonspecific signs relating to debilitation as a result of renal or other spontaneous disease.
T47 6075-6229 Sentence denotes There were no clinical signs of toxicity in rats, other than nonspecific signs relating to debilitation as a result of renal or other spontaneous disease.
T48 6230-6264 Sentence denotes Hematology and Clinical Chemistry:
T48 6230-6264 Sentence denotes Hematology and Clinical Chemistry:
T49 6265-6535 Sentence denotes At the 15-month interim evaluation, the values for one or more hematologic parameters including mean erythrocyte volume, mean erythrocyte hemoglobin in 50 and 100 mg/kg rats, and hematocrit or hemoglobin in 100 mg/kg rats were significantly lower than those of controls.
T49 6265-6535 Sentence denotes At the 15-month interim evaluation, the values for one or more hematologic parameters including mean erythrocyte volume, mean erythrocyte hemoglobin in 50 and 100 mg/kg rats, and hematocrit or hemoglobin in 100 mg/kg rats were significantly lower than those of controls.
T50 6536-6680 Sentence denotes Activated partial thromboplastin times were also significantly lower in 50 and 100 mg/kg males, while platelet counts were significantly higher.
T50 6536-6680 Sentence denotes Activated partial thromboplastin times were also significantly lower in 50 and 100 mg/kg males, while platelet counts were significantly higher.
T51 6681-6909 Sentence denotes Activities of alanine aminotransferase, sorbitol dehydrogenase, or g-glutamyltransferase in 50 and 100 mg/kg male and 100 mg/kg female rats were significantly higher than those of the controls at the 15-month interim evaluation.
T51 6681-6909 Sentence denotes Activities of alanine aminotransferase, sorbitol dehydrogenase, or g-glutamyltransferase in 50 and 100 mg/kg male and 100 mg/kg female rats were significantly higher than those of the controls at the 15-month interim evaluation.
T52 6910-6929 Sentence denotes Pathology Findings:
T52 6910-6929 Sentence denotes Pathology Findings:
T53 6930-7072 Sentence denotes The principal lesions associated with the administration of coumarin to rats for up to 2 years occurred in the liver, kidney, and forestomach.
T53 6930-7072 Sentence denotes The principal lesions associated with the administration of coumarin to rats for up to 2 years occurred in the liver, kidney, and forestomach.
T54 7073-7184 Sentence denotes While the hepatic lesions were seen in all groups of males, they occurred only in the 50 and 100 mg/kg females.
T54 7073-7184 Sentence denotes While the hepatic lesions were seen in all groups of males, they occurred only in the 50 and 100 mg/kg females.
T55 7185-7347 Sentence denotes The lesions consisted of a spectrum of changes including hepatocellular necrosis, fibrosis, cytologic alteration, and increased severity of bile duct hyperplasia.
T55 7185-7347 Sentence denotes The lesions consisted of a spectrum of changes including hepatocellular necrosis, fibrosis, cytologic alteration, and increased severity of bile duct hyperplasia.
T56 7348-7424 Sentence denotes The incidences of hepatocellular neoplasms were not increased in dosed rats.
T56 7348-7424 Sentence denotes The incidences of hepatocellular neoplasms were not increased in dosed rats.
T57 7425-7546 Sentence denotes There was a chemical-related increase in the average severity of nephropathy in all groups of dosed male and female rats.
T57 7425-7546 Sentence denotes There was a chemical-related increase in the average severity of nephropathy in all groups of dosed male and female rats.
T58 7547-7707 Sentence denotes There were corresponding increased incidences of parathyroid gland hyperplasia in all groups of dosed males, probably as a result of compromised renal function.
T58 7547-7707 Sentence denotes There were corresponding increased incidences of parathyroid gland hyperplasia in all groups of dosed males, probably as a result of compromised renal function.
T59 7708-7941 Sentence denotes In the standard evaluation of single kidney sections, a low incidence of renal adenomas was seen in all groups of males and in 100 mg/kg females (males: vehicle control, 1/49; 25 mg/kg, 2/50; 50 mg/kg, 2/51; 100 mg/kg, 1/50; females:
T59 7708-7941 Sentence denotes In the standard evaluation of single kidney sections, a low incidence of renal adenomas was seen in all groups of males and in 100 mg/kg females (males: vehicle control, 1/49; 25 mg/kg, 2/50; 50 mg/kg, 2/51; 100 mg/kg, 1/50; females:
T60 7942-7966 Sentence denotes 0/49, 0/50, 0/50, 2/49).
T60 7942-7966 Sentence denotes 0/49, 0/50, 0/50, 2/49).
T61 7967-8075 Sentence denotes An evaluation of step sections identified additional individuals with renal tubule focal hyperplasia (males:
T61 7967-8075 Sentence denotes An evaluation of step sections identified additional individuals with renal tubule focal hyperplasia (males:
T62 8076-8110 Sentence denotes 2/49, 12/50, 10/51, 6/50; females:
T62 8076-8110 Sentence denotes 2/49, 12/50, 10/51, 6/50; females:
T63 8111-8154 Sentence denotes 1/49, 0/50, 4/50, 2/49) and adenoma (males:
T63 8111-8154 Sentence denotes 1/49, 0/50, 4/50, 2/49) and adenoma (males:
T64 8155-8187 Sentence denotes 0/49, 4/50, 5/51, 4/50; females:
T64 8155-8187 Sentence denotes 0/49, 4/50, 5/51, 4/50; females:
T65 8188-8231 Sentence denotes 0/49, 0/50, 1/50,1/49) in the dosed groups.
T65 8188-8231 Sentence denotes 0/49, 0/50, 1/50,1/49) in the dosed groups.
T66 8232-8392 Sentence denotes The incidences of forestomach ulcers in all groups of dosed male rats and in 100 mg/kg female rats were significantly greater than those of the controls (males:
T66 8232-8392 Sentence denotes The incidences of forestomach ulcers in all groups of dosed male rats and in 100 mg/kg female rats were significantly greater than those of the controls (males:
T67 8393-8428 Sentence denotes 7/48, 24/50, 35/51, 34/50; females:
T67 8393-8428 Sentence denotes 7/48, 24/50, 35/51, 34/50; females:
T68 8429-8453 Sentence denotes 1/48, 1/49, 6/50, 9/48).
T68 8429-8453 Sentence denotes 1/48, 1/49, 6/50, 9/48).
T69 8454-8479 Sentence denotes STOP-EXPOSURE EVALUATION:
T69 8454-8479 Sentence denotes STOP-EXPOSURE EVALUATION:
T70 8480-8621 Sentence denotes A group of 40 male rats received 100 mg/kg coumarin in corn oil by gavage for 9 months, when 20 of the animals were necropsied and evaluated.
T70 8480-8621 Sentence denotes A group of 40 male rats received 100 mg/kg coumarin in corn oil by gavage for 9 months, when 20 of the animals were necropsied and evaluated.
T71 8622-8724 Sentence denotes The remainder of the male rats received only the corn oil vehicle during the 15-month recovery period.
T71 8622-8724 Sentence denotes The remainder of the male rats received only the corn oil vehicle during the 15-month recovery period.
T72 8725-8875 Sentence denotes Similarly, a group of 30 male rats received 100 mg/kg coumarin in corn oil by gavage for 15 months, when 10 of the rats were necropsied and evaluated.
T72 8725-8875 Sentence denotes Similarly, a group of 30 male rats received 100 mg/kg coumarin in corn oil by gavage for 15 months, when 10 of the rats were necropsied and evaluated.
T73 8876-8956 Sentence denotes The remaining 20 rats received only corn oil during the 9-month recovery period.
T73 8876-8956 Sentence denotes The remaining 20 rats received only corn oil during the 9-month recovery period.
T74 8957-9096 Sentence denotes A group of 20 vehicle control male rats were necropsied at 9 months, and another 10 vehicle control male rats were necropsied at 15 months.
T74 8957-9096 Sentence denotes A group of 20 vehicle control male rats were necropsied at 9 months, and another 10 vehicle control male rats were necropsied at 15 months.
T75 9097-9307 Sentence denotes While chemical-related hepatic lesions were seen at both the 9- and 15-month interim evaluations, the incidences and severities of these lesions following the recovery period were generally similar to controls.
T75 9097-9307 Sentence denotes While chemical-related hepatic lesions were seen at both the 9- and 15-month interim evaluations, the incidences and severities of these lesions following the recovery period were generally similar to controls.
T76 9308-9389 Sentence denotes Thus, the hepatic lesions produced by 9 or 15 months of exposure were reversible.
T76 9308-9389 Sentence denotes Thus, the hepatic lesions produced by 9 or 15 months of exposure were reversible.
T77 9390-9592 Sentence denotes In contrast to the liver lesions, the severity of nephropathy in male rats following the recovery period was significantly greater than that of males examined at the 9- and 15-month interim evaluations.
T77 9390-9592 Sentence denotes In contrast to the liver lesions, the severity of nephropathy in male rats following the recovery period was significantly greater than that of males examined at the 9- and 15-month interim evaluations.
T78 9593-9719 Sentence denotes This is not unexpected, since nephropathy is a progressive degenerative disease that naturally increases in severity with age.
T78 9593-9719 Sentence denotes This is not unexpected, since nephropathy is a progressive degenerative disease that naturally increases in severity with age.
T79 9720-9988 Sentence denotes The incidence of renal tubule hyperplasia in the 15-month stop-exposure group (dosed for 15 months followed by the recovery period) and the incidence of renal tubule adenoma in the 9-month stop-exposure group were significantly greater than those of the control group.
T79 9720-9988 Sentence denotes The incidence of renal tubule hyperplasia in the 15-month stop-exposure group (dosed for 15 months followed by the recovery period) and the incidence of renal tubule adenoma in the 9-month stop-exposure group were significantly greater than those of the control group.
T80 9989-10010 Sentence denotes 2-YEAR STUDY IN MICE:
T80 9989-10010 Sentence denotes 2-YEAR STUDY IN MICE:
T81 10011-10168 Sentence denotes Groups of 70 male and 70 female mice were administered coumarin in corn oil by gavage at doses of 0, 50, 100, or 200 mg per kg body weight for up to 2 years.
T81 10011-10168 Sentence denotes Groups of 70 male and 70 female mice were administered coumarin in corn oil by gavage at doses of 0, 50, 100, or 200 mg per kg body weight for up to 2 years.
T82 10169-10231 Sentence denotes After 15 months, 19 or 20 mice from each group were evaluated.
T82 10169-10231 Sentence denotes After 15 months, 19 or 20 mice from each group were evaluated.
T83 10232-10278 Sentence denotes Survival, Body Weights, and Clinical Findings:
T83 10232-10278 Sentence denotes Survival, Body Weights, and Clinical Findings:
T84 10279-10447 Sentence denotes Survival of dosed male and female mice was similar to that of the controls (males: vehicle control, 43/50; 50 mg/kg, 47/50; 100 mg/kg, 42/50; 200 mg/kg, 37/51; females:
T84 10279-10447 Sentence denotes Survival of dosed male and female mice was similar to that of the controls (males: vehicle control, 43/50; 50 mg/kg, 47/50; 100 mg/kg, 42/50; 200 mg/kg, 37/51; females:
T85 10448-10476 Sentence denotes 33/50, 40/50, 42/51, 28/51).
T85 10448-10476 Sentence denotes 33/50, 40/50, 42/51, 28/51).
T86 10477-10596 Sentence denotes The mean body weights of 200 mg/kg male and female mice were lower than those of controls throughout much of the study.
T86 10477-10596 Sentence denotes The mean body weights of 200 mg/kg male and female mice were lower than those of controls throughout much of the study.
T87 10597-10664 Sentence denotes There were no clinical findings related to chemical administration.
T87 10597-10664 Sentence denotes There were no clinical findings related to chemical administration.
T88 10665-10699 Sentence denotes Hematology and Clinical Chemistry:
T88 10665-10699 Sentence denotes Hematology and Clinical Chemistry:
T89 10700-10889 Sentence denotes Mean erythrocyte volume, mean erythrocyte hemoglobin, and hematocrit of 200 mg/kg males and mean erythrocyte volume of 200 mg/kg females were significantly lower than those of the controls.
T89 10700-10889 Sentence denotes Mean erythrocyte volume, mean erythrocyte hemoglobin, and hematocrit of 200 mg/kg males and mean erythrocyte volume of 200 mg/kg females were significantly lower than those of the controls.
T90 10890-10992 Sentence denotes Blood platelet counts of 200 mg/kg males and females were significantly higher than those of controls.
T90 10890-10992 Sentence denotes Blood platelet counts of 200 mg/kg males and females were significantly higher than those of controls.
T91 10993-11096 Sentence denotes There were no biologically significant differences in enzyme activities between dosed and control mice.
T91 10993-11096 Sentence denotes There were no biologically significant differences in enzyme activities between dosed and control mice.
T92 11097-11116 Sentence denotes Pathology Findings:
T92 11097-11116 Sentence denotes Pathology Findings:
T93 11117-11222 Sentence denotes The principal toxic lesions associated with the administration of coumarin to mice occurred in the liver.
T93 11117-11222 Sentence denotes The principal toxic lesions associated with the administration of coumarin to mice occurred in the liver.
T94 11223-11366 Sentence denotes The incidences of centrilobular hypertrophy in 100 and 200 mg/kg males and 200 mg/kg females were significantly greater than those of controls.
T94 11223-11366 Sentence denotes The incidences of centrilobular hypertrophy in 100 and 200 mg/kg males and 200 mg/kg females were significantly greater than those of controls.
T95 11367-11501 Sentence denotes The incidences of syncytial alteration in all male dose groups and in 200 mg/kg females were also significantly greater than controls.
T95 11367-11501 Sentence denotes The incidences of syncytial alteration in all male dose groups and in 200 mg/kg females were also significantly greater than controls.
T96 11502-11661 Sentence denotes The incidences of eosinophilic foci, a putative preneoplastic lesion, and of hepatocellular adenoma were significantly greater in the 50 and 100 mg/kg females.
T96 11502-11661 Sentence denotes The incidences of eosinophilic foci, a putative preneoplastic lesion, and of hepatocellular adenoma were significantly greater in the 50 and 100 mg/kg females.
T97 11662-11773 Sentence denotes Hepatocellular carcinomas occurred with low incidences in the dosed females, but none occurred in the controls.
T97 11662-11773 Sentence denotes Hepatocellular carcinomas occurred with low incidences in the dosed females, but none occurred in the controls.
T98 11774-12074 Sentence denotes The overall incidence of hepatocellular neoplasms (benign and malignant combined) in the 50 and 100 mg/kg females (control, 8/50; 50 mg/kg, 27/49; 100 mg/kg, 31/51; 200 mg/kg, 13/50) exceeds the range in historical controls (range 2%-34%; 129/898, 14.4%) from recent NTP studies.
T98 11774-12074 Sentence denotes The overall incidence of hepatocellular neoplasms (benign and malignant combined) in the 50 and 100 mg/kg females (control, 8/50; 50 mg/kg, 27/49; 100 mg/kg, 31/51; 200 mg/kg, 13/50) exceeds the range in historical controls (range 2%-34%; 129/898, 14.4%) from recent NTP studies.
T99 12075-12208 Sentence denotes The reason for a lack of liver response in 200 mg/kg female mice is not known, but may be due in part to the decrease in body weight.
T99 12075-12208 Sentence denotes The reason for a lack of liver response in 200 mg/kg female mice is not known, but may be due in part to the decrease in body weight.
T100 12209-12386 Sentence denotes While the incidences of eosinophilic foci were marginally greater in dosed male mice, the incidences of hepatocellular neoplasms were similar among the dosed and control groups.
T100 12209-12386 Sentence denotes While the incidences of eosinophilic foci were marginally greater in dosed male mice, the incidences of hepatocellular neoplasms were similar among the dosed and control groups.
T101 12387-12517 Sentence denotes The incidences of alveolar/bronchiolar adenomas were significantly greater in 200 mg/kg male and female mice than in the controls.
T101 12387-12517 Sentence denotes The incidences of alveolar/bronchiolar adenomas were significantly greater in 200 mg/kg male and female mice than in the controls.
T102 12518-12644 Sentence denotes Further, the incidence of alveolar/bronchiolar carcinoma in 200 mg/kg females was also significantly greater than in controls.
T102 12518-12644 Sentence denotes Further, the incidence of alveolar/bronchiolar carcinoma in 200 mg/kg females was also significantly greater than in controls.
T103 12645-12753 Sentence denotes The overall incidence of pulmonary neoplasms (benign and malignant combined) in the 200 mg/kg groups (males:
T103 12645-12753 Sentence denotes The overall incidence of pulmonary neoplasms (benign and malignant combined) in the 200 mg/kg groups (males:
T104 12754-12788 Sentence denotes 14/50, 9/50,15/50, 25/51; females:
T104 12754-12788 Sentence denotes 14/50, 9/50,15/50, 25/51; females:
T105 12789-12996 Sentence denotes 2/51, 5/49, 7/49, 27/51) exceeds the range in historical controls (males: range 6%-28%; 166/900, 18.4%; females: range 0%-14%; 58/899, 6.5%) from recent NTP studies.
T105 12789-12996 Sentence denotes 2/51, 5/49, 7/49, 27/51) exceeds the range in historical controls (males: range 6%-28%; 166/900, 18.4%; females: range 0%-14%; 58/899, 6.5%) from recent NTP studies.
T106 12997-13277 Sentence denotes The incidence of squamous cell papilloma of the forestomach in 50 mg/kg males was greater than that of the controls (2/50, 8/50, 2/50, 0/51) and also exceeds the range of this neoplasm in control male mice from recent NTP studies (range 0%-14%; 27/902, 3.0%).
T106 12997-13277 Sentence denotes The incidence of squamous cell papilloma of the forestomach in 50 mg/kg males was greater than that of the controls (2/50, 8/50, 2/50, 0/51) and also exceeds the range of this neoplasm in control male mice from recent NTP studies (range 0%-14%; 27/902, 3.0%).
T107 13278-13528 Sentence denotes The incidence of squamous cell papilloma of the forestomach in 50 mg/kg female mice was also slightly increased (1/52, 5/50, 2/51, 2/51); however, the incidence did not exceed the NTP historical range (27/901, 3%; range, 0%-10%).
T107 13278-13528 Sentence denotes The incidence of squamous cell papilloma of the forestomach in 50 mg/kg female mice was also slightly increased (1/52, 5/50, 2/51, 2/51); however, the incidence did not exceed the NTP historical range (27/901, 3%; range, 0%-10%).
T108 13529-13548 Sentence denotes GENETIC TOXICOLOGY:
T108 13529-13548 Sentence denotes GENETIC TOXICOLOGY:
T109 13549-13782 Sentence denotes Coumarin induced gene mutations in Salmonella typhimurium strain TA100 in the presence, but not in the absence, of exogenous metabolic activation (S9); no mutations were induced in strains TA98, TA1535, or TA1537, with or without S9.
T109 13549-13782 Sentence denotes Coumarin induced gene mutations in Salmonella typhimurium strain TA100 in the presence, but not in the absence, of exogenous metabolic activation (S9); no mutations were induced in strains TA98, TA1535, or TA1537, with or without S9.
T110 13783-13931 Sentence denotes In Chinese hamster ovary cells, coumarin induced sister chromatid exchanges in the absence of S9, and chromosomal aberrations in the presence of S9.
T110 13783-13931 Sentence denotes In Chinese hamster ovary cells, coumarin induced sister chromatid exchanges in the absence of S9, and chromosomal aberrations in the presence of S9.
T111 13932-14114 Sentence denotes Coumarin did not induce sex-linked recessive lethal mutations in germ cells of male Drosophila melanogaster treated either as adults by feeding or injection, or as larvae by feeding.
T111 13932-14114 Sentence denotes Coumarin did not induce sex-linked recessive lethal mutations in germ cells of male Drosophila melanogaster treated either as adults by feeding or injection, or as larvae by feeding.
T112 14115-14284 Sentence denotes No increase in the frequency of micronucleated erythrocytes was observed in peripheral blood of male and female B6C3F1 mice administered coumarin by gavage for 13 weeks.
T112 14115-14284 Sentence denotes No increase in the frequency of micronucleated erythrocytes was observed in peripheral blood of male and female B6C3F1 mice administered coumarin by gavage for 13 weeks.
T113 14285-14297 Sentence denotes CONCLUSIONS:
T113 14285-14297 Sentence denotes CONCLUSIONS:
T114 14298-14486 Sentence denotes Under the conditions of these 2-year gavage studies there was some evidence of carcinogenic activity of coumarin in male F344/N rats based on increased incidences of renal tubule adenomas.
T114 14298-14486 Sentence denotes Under the conditions of these 2-year gavage studies there was some evidence of carcinogenic activity of coumarin in male F344/N rats based on increased incidences of renal tubule adenomas.
T115 14487-14642 Sentence denotes There was equivocal evidence of carcinogenic activity of coumarin in female F344/N rats based on a marginally increased incidence of renal tubule adenomas.
T115 14487-14642 Sentence denotes There was equivocal evidence of carcinogenic activity of coumarin in female F344/N rats based on a marginally increased incidence of renal tubule adenomas.
T116 14643-14790 Sentence denotes There was some evidence of carcinogenic activity of coumarin in male B6C3F1 mice based on the increased incidence of alveolar/bronchiolar adenomas.
T116 14643-14790 Sentence denotes There was some evidence of carcinogenic activity of coumarin in male B6C3F1 mice based on the increased incidence of alveolar/bronchiolar adenomas.
T117 14791-15000 Sentence denotes There was clear evidence of carcinogenic activity of coumarin in female B6C3F1 mice based on increased incidences of alveolar/bronchiolar adenomas, alveolar/bronchiolar carcinomas, and hepatocellular adenomas.
T117 14791-15000 Sentence denotes There was clear evidence of carcinogenic activity of coumarin in female B6C3F1 mice based on increased incidences of alveolar/bronchiolar adenomas, alveolar/bronchiolar carcinomas, and hepatocellular adenomas.
T118 15001-15176 Sentence denotes The marginally increased incidences of squamous cell papillomas of the forestomach in male and female mice receiving 50 mg/kg may have been related to coumarin administration.
T118 15001-15176 Sentence denotes The marginally increased incidences of squamous cell papillomas of the forestomach in male and female mice receiving 50 mg/kg may have been related to coumarin administration.
T119 15177-15448 Sentence denotes The administration of coumarin to rats was also associated with an increased severity of nephropathy in the kidney and of bile duct hyperplasia in the liver, increased incidences of ulcers of the forestomach, and necrosis, fibrosis, and cytologic alteration of the liver.
T119 15177-15448 Sentence denotes The administration of coumarin to rats was also associated with an increased severity of nephropathy in the kidney and of bile duct hyperplasia in the liver, increased incidences of ulcers of the forestomach, and necrosis, fibrosis, and cytologic alteration of the liver.
T120 15449-15594 Sentence denotes Administration of coumarin to mice was also associated with centrilobular hypertrophy, syncytial alteration, and eosinophilic focus in the liver.
T120 15449-15594 Sentence denotes Administration of coumarin to mice was also associated with centrilobular hypertrophy, syncytial alteration, and eosinophilic focus in the liver.
T121 15595-15604 Sentence denotes Synonyms:
T121 15595-15604 Sentence denotes Synonyms:
T122 15605-15902 Sentence denotes 5,6-benzo-alpha-pyrone, 2H-1-benzopyran-2-one, 2H-benzolblpyran-2-one, 1,2-oxo-1,2-benzopyran, 1,2-benzopyrone, cis-o-coumarinic acid lactone, coumarinic anhydride, cumarin, o-hydroxycinnamic acid lactone, kumarin, [2-propenoic acid, 3-(-2-hydroxyphenyl)-delta-lactone], Rattex, tonka bean camphor
T122 15605-15902 Sentence denotes 5,6-benzo-alpha-pyrone, 2H-1-benzopyran-2-one, 2H-benzolblpyran-2-one, 1,2-oxo-1,2-benzopyran, 1,2-benzopyrone, cis-o-coumarinic acid lactone, coumarinic anhydride, cumarin, o-hydroxycinnamic acid lactone, kumarin, [2-propenoic acid, 3-(-2-hydroxyphenyl)-delta-lactone], Rattex, tonka bean camphor