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Inflammaging

Id Subject Object Predicate Lexical cue
T1 0-89 Sentence denotes NTP Toxicology and Carcinogenesis Studies of Scopolamine Hydrobromide Trihydrate (CAS No.
T2 90-147 Sentence denotes 6533-68-2) in F344 Rats and B6C3F1 Mice (Gavage Studies).
T3 148-251 Sentence denotes Scopolamine hydrobromide trihydrate is used in ophthalmic preparations and as a preanesthetic sedative.
T4 252-329 Sentence denotes Its major use is in transdermal patches for the treatment of motion sickness.
T5 330-501 Sentence denotes Scopolamine hydrobromide trihydrate was selected for study because of considerable human exposure resulting from its use in prescription and over-the-counter preparations.
T6 502-634 Sentence denotes Scopolamine was a suspect carcinogen because it contains an aliphatic epoxide moiety which may act as a biological alkylating agent.
T7 635-798 Sentence denotes Male and female F344/N rats and B6C3F1 mice received scopolamine hydrobromide trihydrate (89% pure) in distilled water by gavage for 16 days, 14 weeks, or 2 years.
T8 799-946 Sentence denotes Genetic toxicology studies were conducted in Salmonella typhimurium, cultured Chinese hamster ovary cells, and mouse peripheral blood erythrocytes.
T9 947-968 Sentence denotes 16-DAY STUDY IN RATS:
T10 969-1154 Sentence denotes Groups of five male and five female rats were administered 0, 75, 150, 300, 600, or 1,200 mg scopolamine hydrobromide trihydrate/kg body weight in distilled water by gavage for 16 days.
T11 1155-1197 Sentence denotes All rats survived to the end of the study.
T12 1198-1403 Sentence denotes The final mean body weights and body weight gains of males receiving 600 and 1,200 mg/kg and the mean body weight gain of males receiving 300 mg/kg were significantly lower than those of the control group.
T13 1404-1540 Sentence denotes Clinical findings included bilateral pupillary dilation in all dosed animals and red eyelids in males and females receiving 1,200 mg/kg.
T14 1541-1614 Sentence denotes There were no significant treatment-related gross or microscopic lesions.
T15 1615-1636 Sentence denotes 16-DAY STUDY IN MICE:
T16 1637-1823 Sentence denotes Groups of five male and five female mice were administered 0, 150, 250, 450, 900, or 1,800 mg scopolamine hydrobromide trihydrate/kg body weight in distilled water by gavage for 16 days.
T17 1824-1928 Sentence denotes One male and two females receiving 1,800 mg/kg and one female receiving 150 mg/kg died during the study.
T18 1929-2037 Sentence denotes The final mean body weights and body weight gains of dosed mice were similar to those of the control groups.
T19 2038-2201 Sentence denotes Clinical findings related to scopolamine hydrobromide trihydrate administration included bilateral pupillary dilation and squinting in all dosed males and females.
T20 2202-2355 Sentence denotes The relative liver weights of males receiving 1,800 mg/kg and of females in all dosed groups were significantly greater than those of the control groups.
T21 2356-2429 Sentence denotes There were no significant treatment-related gross or microscopic lesions.
T22 2430-2452 Sentence denotes 14-WEEK STUDY IN RATS:
T23 2453-2634 Sentence denotes Groups of 10 male and 10 female rats were administered 0, 15, 45, 135, 400, or 1,200 mg scopolamine hydrobromide trihydrate/kg body weight in distilled water by gavage for 14 weeks.
T24 2635-2835 Sentence denotes One female receiving 45 mg/kg, one male and one female receiving 135 mg/kg, six males and one female receiving 400 mg/kg, and eight males and seven females receiving 1,200 mg/kg died during the study.
T25 2836-2980 Sentence denotes The final mean body weights and mean body weight gains of all dosed males and females were significantly lower than those of the control groups.
T26 2981-3160 Sentence denotes Clinical findings included bilateral pupillary dilation in all dosed males and females and reddening of the eyes in 15 mg/kg males and 135, 400, and 1,200 mg/kg males and females.
T27 3161-3332 Sentence denotes Hematocrit, hemoglobin concentration, and/or erythrocyte count in male and female rats receiving 45 mg/kg or greater were slightly higher than those of the control groups.
T28 3333-3421 Sentence denotes In general, these changes were most prominent in rats in the 400 and 1,200 mg/kg groups.
T29 3422-3569 Sentence denotes Higher hematocrit, hemoglobin concentration, and erythrocyte count were likely due to hemoconcentration from dehydration (relative erythrocytosis).
T30 3570-3717 Sentence denotes A minimal to mild mature neutrophilia, evidenced by higher segmented neutrophil numbers than in the control group, occurred in all dosed male rats.
T31 3718-3825 Sentence denotes Sperm morphology and vaginal cytology parameters in dosed rats were similar to those in the control groups.
T32 3826-3962 Sentence denotes Nine male and five female dosed rats died from esophageal obstructions consisting of feed and bedding material in the posterior pharynx.
T33 3963-4091 Sentence denotes Tracheal obstruction occurred concurrently with esophageal obstruction as a result of food build-up in the oropharyngeal region.
T34 4092-4293 Sentence denotes This condition is considered to be secondary to the inhibitory effects of scopolamine hydrobromide trihydrate on salivary gland secretions and on esopon esophageal smooth muscle involved in swallowing.
T35 4294-4374 Sentence denotes There were no other significant treatment-related gross or microscopic findings.
T36 4375-4397 Sentence denotes 14-WEEK STUDY IN MICE:
T37 4398-4579 Sentence denotes Groups of 10 male and 10 female mice were administered 0, 15, 45, 135, 400, or 1,200 mg scopolamine hydrobromide trihydrate/kg body weight in distilled water by gavage for 14 weeks.
T38 4580-4682 Sentence denotes One male receiving 135 mg/kg and two males and one female receiving 1,200 mg/kg died during the study.
T39 4683-4862 Sentence denotes The final mean body weights and mean body weight gains of all dosed male groups and females receiving 45 mg/kg and above were significantly lower than those of the control groups.
T40 4863-4956 Sentence denotes Clinical observations included bilateral pupillary dilation, hyperactivity, and hypoactivity.
T41 4957-5105 Sentence denotes A minimal to mild mature neutrophilia, similar to that which occurred in the 14-week rat study, occurred in male mice receiving 45 mg/kg or greater.
T42 5106-5217 Sentence denotes As in the rat study, there was no microscopic evidence of inflammation that could account for the neutrophilia.
T43 5218-5323 Sentence denotes The estrous cycle length of 1,200 mg/kg females was significantly greater than that in the control group.
T44 5324-5397 Sentence denotes There were no significant treatment-related gross or microscopic lesions.
T45 5398-5419 Sentence denotes 2-YEAR STUDY IN RATS:
T46 5420-5587 Sentence denotes Groups of 60 male and 60 female rats were administered 0, 1, 5, or 25 mg scopolamine hydrobromide trihydrate/kg body weight in distilled water by gavage for 104 weeks.
T47 5588-5700 Sentence denotes Ten males and ten females from each dose group, excluding the 1 mg/kg female group, were evaluated at 15 months.
T48 5701-5780 Sentence denotes Survival, Body Weights, Clinical Findings, and Ophthalmic Examination Findings:
T49 5781-5896 Sentence denotes The survival rates of female rats receiving 1 and 25 mg/kg were significantly lower than that of the control group.
T50 5897-6009 Sentence denotes Mean body weights of 1 and 5 mg/kg males and females were similar to those of the controls throughout the study.
T51 6010-6141 Sentence denotes However, mean body weights of 25 mg/kg males and females were generally lower than those of the control groups after about week 25.
T52 6142-6229 Sentence denotes Clinical findings included bilateral pupillary dilation in all dosed males and females.
T53 6230-6286 Sentence denotes Ophthalmic examination revealed no significant findings.
T54 6287-6298 Sentence denotes Hematology:
T55 6299-6500 Sentence denotes Compared to controls, hematocrit was slightly higher in the 25 mg/kg male rats, similar to the effects observed in the 14-week study; this is consistent with dehydration resulting in hemoconcentration.
T56 6501-6597 Sentence denotes Reticulocyte numbers in the 25 mg/kg female rats were slightly lower than those in the controls.
T57 6598-6721 Sentence denotes This result is consistent with the lower body weights, and thus a decreased nutritional status, exhibited by these animals.
T58 6722-6756 Sentence denotes Plasma Scopolamine Determinations:
T59 6757-6930 Sentence denotes The serum scopolamine concentrations were 6 ng scopolamine/mL serum for the 5 mg/kg female sample and 12 and 28 ng/mL for the 25 mg/kg male and female samples, respectively.
T60 6931-7057 Sentence denotes The amounts of scopolamine in the other serum samples were below the minimum detection limit (4 ng/mL) of the analysis method.
T61 7058-7083 Sentence denotes Neurobehavioral Findings:
T62 7084-7212 Sentence denotes Horizontal motor activity of 25 mg/kg females was significantly greater than that of the control group on days 90, 180, and 360.
T63 7213-7321 Sentence denotes Startle response of 5 and 25 mg/kg females was significantly lower than that of the control group on day 90.
T64 7322-7425 Sentence denotes On day 180, passive avoidance of 25 mg/kg males was significantly lower than that of the control group.
T65 7426-7445 Sentence denotes Pathology Findings:
T66 7446-7709 Sentence denotes The incidences of adenoma of the pituitary gland pars distalis decreased with increasing dose in both male and female rats; however, this trend was only significant in males (males: vehicle control, 19/49; 1 mg/kg, 17/49; 5 mg/kg, 13/50; 25 mg/kg, 10/50; females:
T67 7710-7738 Sentence denotes 20/50, 13/60, 14/50, 10/50).
T68 7739-7896 Sentence denotes The incidences of adenoma of the pituitary gland pars distalis in 25 mg/kg males and all groups of dosed females were below the NTP historical control range.
T69 7897-7993 Sentence denotes The incidences of hyperplasia were not significantly different from those in the control groups.
T70 7994-8133 Sentence denotes The incidences of mononuclear cell leukemia in 25 mg/kg males and females were significantly lower than those of the control groups (males:
T71 8134-8170 Sentence denotes 33/50, 21/50, 26/50, 24/50; females:
T72 8171-8197 Sentence denotes 20/50, 6/60, 13/50, 4/50).
T73 8198-8311 Sentence denotes The incidence of mononuclear cell leukemia in females receiving 25 mg/kg was well below the NTP historical range.
T74 8312-8333 Sentence denotes 2-YEAR STUDY IN MICE:
T75 8334-8508 Sentence denotes Groups of 70 male and 70 female mice were administered 0, 1, 5, or 25 mg scopolamine hydrobromide trihydrate/kg body weight in distilled water by gavage for 104 to 105 weeks.
T76 8509-8594 Sentence denotes Ten control animals and ten animals from each dose level were evaluated at 15 months.
T77 8595-8746 Sentence denotes Survival, Body Weights, Clinical Findings, and Ophthalmic Examination Findings Survival of dosed males and females was similar to that of the controls.
T78 8747-8889 Sentence denotes The mean body weights of males and females receiving 1 mg/kg were similar to those of the control groups throughout the majority of the study.
T79 8890-8988 Sentence denotes The mean body weights of 5 mg/kg males and females were slightly lower than those of the controls.
T80 8989-9109 Sentence denotes The mean body weights of males and females receiving 25 mg/kg were lower than those of the control groups after week 13.
T81 9110-9202 Sentence denotes Clinical findings included bilateral pupillary dilation in all dosed male and female groups.
T82 9203-9259 Sentence denotes Ophthalmic examination revealed no significant findings.
T83 9260-9271 Sentence denotes Hematology:
T84 9272-9408 Sentence denotes Hematocrit, hemoglobin concentration, and erythrocyte count in 25 mg/kg female mice were slightly lower than those in the control group.
T85 9409-9514 Sentence denotes These results are consistent with development of a minimal normocytic, normochromic nonresponsive anemia.
T86 9515-9655 Sentence denotes The anemia may be related to the lower body weights exhibited by these animals and are presumed to be due to a decreased nutritional status.
T87 9656-9675 Sentence denotes Pathology Findings:
T88 9676-9904 Sentence denotes The combined incidences of hepatocellular neoplasms (adenoma or carcinoma) occurred with a significant negative trend in males and females (males: vehicle control, 30/50; 1 mg/kg, 33/50; 5 mg/kg, 14/50; 25 mg/kg, 15/50; females:
T89 9905-9932 Sentence denotes 22/51, 21/50, 16/50, 9/51).
T90 9933-10054 Sentence denotes The combined incidences of hepatocellular neoplasms in 5 and 25 mg/kg males were within the NTP historical control range.
T91 10055-10234 Sentence denotes The incidences of clear cell foci and eosinophilic foci in dosed male groups, and eosinophilic foci in 25 mg/kg females, were significantly lower than those of the control groups.
T92 10235-10413 Sentence denotes The incidences of many spontaneously occurring nonneoplastic lesions were significantly lower in dosed mice than in the control groups and usually decreased with increasing dose.
T93 10414-10682 Sentence denotes These included kidney nephropathy, alveolar epithelial hyperplasia, hyperplasia of the pancreatic islets, bone marrow myelofibrosis, hyperplasia of the pituitary gland pars distalis, cystic hyperplasia of the uterus, and hematopoietic cell proliferation of the spleen.
T94 10683-10802 Sentence denotes The decreased incidences of these spontaneous lesions were most likely a result of lower body weights in dosed animals.
T95 10803-10822 Sentence denotes GENETIC TOXICOLOGY:
T96 10823-11089 Sentence denotes Scopolamine hydrobromide trihydrate did not induce mutations in any of five strains of Salmonella typhi murium, with or without S9 metabolic activation enzymes, nor did it induce sister chromatid exchanges in cultured Chinese hamster ovary cells, with or without S9.
T97 11090-11356 Sentence denotes A weakly positive response was obtained, however, in a chromosomal aberrations test conducted in cultured Chinese hamster ovary cells with very high doses of scopolamine hydrobromide trihydrate in the presence of S9; without S9, no increase in aberrations was noted.
T98 11357-11631 Sentence denotes Despite the evidence for chromosomal damage observed in vitro, no increase in the frequencies of micronucleated normochromatic erythrocytes was observed in peripheral blood samples of male or female mice exposed to scopolamine hydrobromide trihydrate for 14 weeks by gavage.
T99 11632-11644 Sentence denotes CONCLUSIONS:
T100 11645-11860 Sentence denotes Under the conditions of these 2-year gavage studies, there was no evidence of carcinogenic activity of scopolamine hydrobromide trihydrate in male or female F344/N rats or B6C3F1 mice administered 1, 5, or 25 mg/kg.
T101 11861-11870 Sentence denotes Synonyms:
T102 11871-12103 Sentence denotes Scopolamine hydrobromide, 6,7-epoxytropan-3-yl, euscopol, hydroscine hydrobromide, hyoscine bromide, (-)-hyoscine hydrobromide, hysco, isoscopil, scopolammonium bromide, (s)-tropate hydrobromide trihydrate, lα-tropyl-a-scopine
T1 0-89 Sentence denotes NTP Toxicology and Carcinogenesis Studies of Scopolamine Hydrobromide Trihydrate (CAS No.
T2 90-147 Sentence denotes 6533-68-2) in F344 Rats and B6C3F1 Mice (Gavage Studies).
T3 148-251 Sentence denotes Scopolamine hydrobromide trihydrate is used in ophthalmic preparations and as a preanesthetic sedative.
T4 252-329 Sentence denotes Its major use is in transdermal patches for the treatment of motion sickness.
T5 330-501 Sentence denotes Scopolamine hydrobromide trihydrate was selected for study because of considerable human exposure resulting from its use in prescription and over-the-counter preparations.
T6 502-634 Sentence denotes Scopolamine was a suspect carcinogen because it contains an aliphatic epoxide moiety which may act as a biological alkylating agent.
T7 635-798 Sentence denotes Male and female F344/N rats and B6C3F1 mice received scopolamine hydrobromide trihydrate (89% pure) in distilled water by gavage for 16 days, 14 weeks, or 2 years.
T8 799-946 Sentence denotes Genetic toxicology studies were conducted in Salmonella typhimurium, cultured Chinese hamster ovary cells, and mouse peripheral blood erythrocytes.
T9 947-968 Sentence denotes 16-DAY STUDY IN RATS:
T10 969-1154 Sentence denotes Groups of five male and five female rats were administered 0, 75, 150, 300, 600, or 1,200 mg scopolamine hydrobromide trihydrate/kg body weight in distilled water by gavage for 16 days.
T11 1155-1197 Sentence denotes All rats survived to the end of the study.
T12 1198-1403 Sentence denotes The final mean body weights and body weight gains of males receiving 600 and 1,200 mg/kg and the mean body weight gain of males receiving 300 mg/kg were significantly lower than those of the control group.
T13 1404-1540 Sentence denotes Clinical findings included bilateral pupillary dilation in all dosed animals and red eyelids in males and females receiving 1,200 mg/kg.
T14 1541-1614 Sentence denotes There were no significant treatment-related gross or microscopic lesions.
T15 1615-1636 Sentence denotes 16-DAY STUDY IN MICE:
T16 1637-1823 Sentence denotes Groups of five male and five female mice were administered 0, 150, 250, 450, 900, or 1,800 mg scopolamine hydrobromide trihydrate/kg body weight in distilled water by gavage for 16 days.
T17 1824-1928 Sentence denotes One male and two females receiving 1,800 mg/kg and one female receiving 150 mg/kg died during the study.
T18 1929-2037 Sentence denotes The final mean body weights and body weight gains of dosed mice were similar to those of the control groups.
T19 2038-2201 Sentence denotes Clinical findings related to scopolamine hydrobromide trihydrate administration included bilateral pupillary dilation and squinting in all dosed males and females.
T20 2202-2355 Sentence denotes The relative liver weights of males receiving 1,800 mg/kg and of females in all dosed groups were significantly greater than those of the control groups.
T21 2356-2429 Sentence denotes There were no significant treatment-related gross or microscopic lesions.
T22 2430-2452 Sentence denotes 14-WEEK STUDY IN RATS:
T23 2453-2634 Sentence denotes Groups of 10 male and 10 female rats were administered 0, 15, 45, 135, 400, or 1,200 mg scopolamine hydrobromide trihydrate/kg body weight in distilled water by gavage for 14 weeks.
T24 2635-2835 Sentence denotes One female receiving 45 mg/kg, one male and one female receiving 135 mg/kg, six males and one female receiving 400 mg/kg, and eight males and seven females receiving 1,200 mg/kg died during the study.
T25 2836-2980 Sentence denotes The final mean body weights and mean body weight gains of all dosed males and females were significantly lower than those of the control groups.
T26 2981-3160 Sentence denotes Clinical findings included bilateral pupillary dilation in all dosed males and females and reddening of the eyes in 15 mg/kg males and 135, 400, and 1,200 mg/kg males and females.
T27 3161-3332 Sentence denotes Hematocrit, hemoglobin concentration, and/or erythrocyte count in male and female rats receiving 45 mg/kg or greater were slightly higher than those of the control groups.
T28 3333-3421 Sentence denotes In general, these changes were most prominent in rats in the 400 and 1,200 mg/kg groups.
T29 3422-3569 Sentence denotes Higher hematocrit, hemoglobin concentration, and erythrocyte count were likely due to hemoconcentration from dehydration (relative erythrocytosis).
T30 3570-3717 Sentence denotes A minimal to mild mature neutrophilia, evidenced by higher segmented neutrophil numbers than in the control group, occurred in all dosed male rats.
T31 3718-3825 Sentence denotes Sperm morphology and vaginal cytology parameters in dosed rats were similar to those in the control groups.
T32 3826-3962 Sentence denotes Nine male and five female dosed rats died from esophageal obstructions consisting of feed and bedding material in the posterior pharynx.
T33 3963-4091 Sentence denotes Tracheal obstruction occurred concurrently with esophageal obstruction as a result of food build-up in the oropharyngeal region.
T34 4092-4293 Sentence denotes This condition is considered to be secondary to the inhibitory effects of scopolamine hydrobromide trihydrate on salivary gland secretions and on esopon esophageal smooth muscle involved in swallowing.
T35 4294-4374 Sentence denotes There were no other significant treatment-related gross or microscopic findings.
T36 4375-4397 Sentence denotes 14-WEEK STUDY IN MICE:
T37 4398-4579 Sentence denotes Groups of 10 male and 10 female mice were administered 0, 15, 45, 135, 400, or 1,200 mg scopolamine hydrobromide trihydrate/kg body weight in distilled water by gavage for 14 weeks.
T38 4580-4682 Sentence denotes One male receiving 135 mg/kg and two males and one female receiving 1,200 mg/kg died during the study.
T39 4683-4862 Sentence denotes The final mean body weights and mean body weight gains of all dosed male groups and females receiving 45 mg/kg and above were significantly lower than those of the control groups.
T40 4863-4956 Sentence denotes Clinical observations included bilateral pupillary dilation, hyperactivity, and hypoactivity.
T41 4957-5105 Sentence denotes A minimal to mild mature neutrophilia, similar to that which occurred in the 14-week rat study, occurred in male mice receiving 45 mg/kg or greater.
T42 5106-5217 Sentence denotes As in the rat study, there was no microscopic evidence of inflammation that could account for the neutrophilia.
T43 5218-5323 Sentence denotes The estrous cycle length of 1,200 mg/kg females was significantly greater than that in the control group.
T44 5324-5397 Sentence denotes There were no significant treatment-related gross or microscopic lesions.
T45 5398-5419 Sentence denotes 2-YEAR STUDY IN RATS:
T46 5420-5587 Sentence denotes Groups of 60 male and 60 female rats were administered 0, 1, 5, or 25 mg scopolamine hydrobromide trihydrate/kg body weight in distilled water by gavage for 104 weeks.
T47 5588-5700 Sentence denotes Ten males and ten females from each dose group, excluding the 1 mg/kg female group, were evaluated at 15 months.
T48 5701-5780 Sentence denotes Survival, Body Weights, Clinical Findings, and Ophthalmic Examination Findings:
T49 5781-5896 Sentence denotes The survival rates of female rats receiving 1 and 25 mg/kg were significantly lower than that of the control group.
T50 5897-6009 Sentence denotes Mean body weights of 1 and 5 mg/kg males and females were similar to those of the controls throughout the study.
T51 6010-6141 Sentence denotes However, mean body weights of 25 mg/kg males and females were generally lower than those of the control groups after about week 25.
T52 6142-6229 Sentence denotes Clinical findings included bilateral pupillary dilation in all dosed males and females.
T53 6230-6286 Sentence denotes Ophthalmic examination revealed no significant findings.
T54 6287-6298 Sentence denotes Hematology:
T55 6299-6500 Sentence denotes Compared to controls, hematocrit was slightly higher in the 25 mg/kg male rats, similar to the effects observed in the 14-week study; this is consistent with dehydration resulting in hemoconcentration.
T56 6501-6597 Sentence denotes Reticulocyte numbers in the 25 mg/kg female rats were slightly lower than those in the controls.
T57 6598-6721 Sentence denotes This result is consistent with the lower body weights, and thus a decreased nutritional status, exhibited by these animals.
T58 6722-6756 Sentence denotes Plasma Scopolamine Determinations:
T59 6757-6930 Sentence denotes The serum scopolamine concentrations were 6 ng scopolamine/mL serum for the 5 mg/kg female sample and 12 and 28 ng/mL for the 25 mg/kg male and female samples, respectively.
T60 6931-7057 Sentence denotes The amounts of scopolamine in the other serum samples were below the minimum detection limit (4 ng/mL) of the analysis method.
T61 7058-7083 Sentence denotes Neurobehavioral Findings:
T62 7084-7212 Sentence denotes Horizontal motor activity of 25 mg/kg females was significantly greater than that of the control group on days 90, 180, and 360.
T63 7213-7321 Sentence denotes Startle response of 5 and 25 mg/kg females was significantly lower than that of the control group on day 90.
T64 7322-7425 Sentence denotes On day 180, passive avoidance of 25 mg/kg males was significantly lower than that of the control group.
T65 7426-7445 Sentence denotes Pathology Findings:
T66 7446-7709 Sentence denotes The incidences of adenoma of the pituitary gland pars distalis decreased with increasing dose in both male and female rats; however, this trend was only significant in males (males: vehicle control, 19/49; 1 mg/kg, 17/49; 5 mg/kg, 13/50; 25 mg/kg, 10/50; females:
T67 7710-7738 Sentence denotes 20/50, 13/60, 14/50, 10/50).
T68 7739-7896 Sentence denotes The incidences of adenoma of the pituitary gland pars distalis in 25 mg/kg males and all groups of dosed females were below the NTP historical control range.
T69 7897-7993 Sentence denotes The incidences of hyperplasia were not significantly different from those in the control groups.
T70 7994-8133 Sentence denotes The incidences of mononuclear cell leukemia in 25 mg/kg males and females were significantly lower than those of the control groups (males:
T71 8134-8170 Sentence denotes 33/50, 21/50, 26/50, 24/50; females:
T72 8171-8197 Sentence denotes 20/50, 6/60, 13/50, 4/50).
T73 8198-8311 Sentence denotes The incidence of mononuclear cell leukemia in females receiving 25 mg/kg was well below the NTP historical range.
T74 8312-8333 Sentence denotes 2-YEAR STUDY IN MICE:
T75 8334-8508 Sentence denotes Groups of 70 male and 70 female mice were administered 0, 1, 5, or 25 mg scopolamine hydrobromide trihydrate/kg body weight in distilled water by gavage for 104 to 105 weeks.
T76 8509-8594 Sentence denotes Ten control animals and ten animals from each dose level were evaluated at 15 months.
T77 8595-8746 Sentence denotes Survival, Body Weights, Clinical Findings, and Ophthalmic Examination Findings Survival of dosed males and females was similar to that of the controls.
T78 8747-8889 Sentence denotes The mean body weights of males and females receiving 1 mg/kg were similar to those of the control groups throughout the majority of the study.
T79 8890-8988 Sentence denotes The mean body weights of 5 mg/kg males and females were slightly lower than those of the controls.
T80 8989-9109 Sentence denotes The mean body weights of males and females receiving 25 mg/kg were lower than those of the control groups after week 13.
T81 9110-9202 Sentence denotes Clinical findings included bilateral pupillary dilation in all dosed male and female groups.
T82 9203-9259 Sentence denotes Ophthalmic examination revealed no significant findings.
T83 9260-9271 Sentence denotes Hematology:
T84 9272-9408 Sentence denotes Hematocrit, hemoglobin concentration, and erythrocyte count in 25 mg/kg female mice were slightly lower than those in the control group.
T85 9409-9514 Sentence denotes These results are consistent with development of a minimal normocytic, normochromic nonresponsive anemia.
T86 9515-9655 Sentence denotes The anemia may be related to the lower body weights exhibited by these animals and are presumed to be due to a decreased nutritional status.
T87 9656-9675 Sentence denotes Pathology Findings:
T88 9676-9904 Sentence denotes The combined incidences of hepatocellular neoplasms (adenoma or carcinoma) occurred with a significant negative trend in males and females (males: vehicle control, 30/50; 1 mg/kg, 33/50; 5 mg/kg, 14/50; 25 mg/kg, 15/50; females:
T89 9905-9932 Sentence denotes 22/51, 21/50, 16/50, 9/51).
T90 9933-10054 Sentence denotes The combined incidences of hepatocellular neoplasms in 5 and 25 mg/kg males were within the NTP historical control range.
T91 10055-10234 Sentence denotes The incidences of clear cell foci and eosinophilic foci in dosed male groups, and eosinophilic foci in 25 mg/kg females, were significantly lower than those of the control groups.
T92 10235-10413 Sentence denotes The incidences of many spontaneously occurring nonneoplastic lesions were significantly lower in dosed mice than in the control groups and usually decreased with increasing dose.
T93 10414-10682 Sentence denotes These included kidney nephropathy, alveolar epithelial hyperplasia, hyperplasia of the pancreatic islets, bone marrow myelofibrosis, hyperplasia of the pituitary gland pars distalis, cystic hyperplasia of the uterus, and hematopoietic cell proliferation of the spleen.
T94 10683-10802 Sentence denotes The decreased incidences of these spontaneous lesions were most likely a result of lower body weights in dosed animals.
T95 10803-10822 Sentence denotes GENETIC TOXICOLOGY:
T96 10823-11089 Sentence denotes Scopolamine hydrobromide trihydrate did not induce mutations in any of five strains of Salmonella typhi murium, with or without S9 metabolic activation enzymes, nor did it induce sister chromatid exchanges in cultured Chinese hamster ovary cells, with or without S9.
T97 11090-11356 Sentence denotes A weakly positive response was obtained, however, in a chromosomal aberrations test conducted in cultured Chinese hamster ovary cells with very high doses of scopolamine hydrobromide trihydrate in the presence of S9; without S9, no increase in aberrations was noted.
T98 11357-11631 Sentence denotes Despite the evidence for chromosomal damage observed in vitro, no increase in the frequencies of micronucleated normochromatic erythrocytes was observed in peripheral blood samples of male or female mice exposed to scopolamine hydrobromide trihydrate for 14 weeks by gavage.
T99 11632-11644 Sentence denotes CONCLUSIONS:
T100 11645-11860 Sentence denotes Under the conditions of these 2-year gavage studies, there was no evidence of carcinogenic activity of scopolamine hydrobromide trihydrate in male or female F344/N rats or B6C3F1 mice administered 1, 5, or 25 mg/kg.
T101 11861-11870 Sentence denotes Synonyms:
T102 11871-12103 Sentence denotes Scopolamine hydrobromide, 6,7-epoxytropan-3-yl, euscopol, hydroscine hydrobromide, hyoscine bromide, (-)-hyoscine hydrobromide, hysco, isoscopil, scopolammonium bromide, (s)-tropate hydrobromide trihydrate, lα-tropyl-a-scopine