> top > docs > PubMed:12692653 > annotations

PubMed:12692653 JSONTXT

Annnotations TAB JSON ListView MergeView

Inflammaging

Id Subject Object Predicate Lexical cue
T1 0-86 Sentence denotes NTP Toxicology and Carcinogenesis Studies of 1-Amino-2,4-Dibromoanthraquinone (CAS No.
T2 87-142 Sentence denotes 81-49-2) in F344/N Rats and B6C3F1 Mice (Feed Studies).
T3 143-292 Sentence denotes 1-Amino-2,4-dibromoanthraquinone is an anthraquinone-derived vat dye, a member of a class of insoluble dyes that are impregnated into textile fibers.
T4 293-479 Sentence denotes Five anthraquinone-derived dyes with representative and diverse structures, as well as the parent chemical, anthraquinone, were selected for NTP Toxicology and Carcinogenesis evaluation.
T5 480-782 Sentence denotes Similar to the benzidine dye initiative, the rationale for selecting these vat dyes was to generate sufficient toxicologic data to permit more reliable predictions of carcinogenicity to be made on other chemicals in this class, thereby eliminating or reducing the need to study every anthraquinone dye.
T6 783-882 Sentence denotes 1-Amino-2,4-dibromoanthraquinone is the last anthraquinone-derived dye in this group to be studied.
T7 883-1044 Sentence denotes Groups of male and female F344/N rats and B6C3F1 mice were exposed to 1-amino-2,4-dibromoanthraquinone (87% to 97% pure) for 13 weeks or for 9, 15, or 24 months.
T8 1045-1211 Sentence denotes Because 1-amino-2,4-dibromoanthraquinone was predicted to be carcinogenic, these studies were designed to evaluate the potential for tumor progression and regression.
T9 1212-1282 Sentence denotes Absorption and excretion studies were carried out in male F344/N rats.
T10 1283-1394 Sentence denotes Genetic toxicity was determined in vitro using Salmonella typhimurium and cultured Chinese hamster ovary cells.
T11 1395-1540 Sentence denotes Extensive chemical analyses were performed to identify and characterize impurities of the 1-amino-2,4-dibromoanthraquinone used in these studies.
T12 1541-1563 Sentence denotes 13-WEEK STUDY IN RATS:
T13 1564-1713 Sentence denotes Groups of 10 male and 10 female rats were given 0, 2,500, 5,000, 10,000, 25,000, or 50,000 ppm 1-amino-2,4-dibromoanthraquinone in feed for 13 weeks.
T14 1714-1889 Sentence denotes These levels correspond to approximately 150 to 3,200 mg 1-amino-2,4-dibromoanthraquinone/kg body weight per day for males and to approximately 170 to 3,200 mg/kg for females.
T15 1890-1981 Sentence denotes Chemical-related mortality was limited to one male and one female in the 50,000 ppm groups.
T16 1982-2110 Sentence denotes Final mean body weights and body weight gains of all exposed groups of rats were significantly lower than those of the controls.
T17 2111-2269 Sentence denotes Feed consumption by all exposed groups was less than that by the controls throughout the study and generally decreased with increasing exposure concentration.
T18 2270-2343 Sentence denotes Pink-red staining of the fur and tail was observed in all exposed groups.
T19 2344-2466 Sentence denotes Absolute and relative liver weights of all exposed groups were generally significantly greater than those of the controls.
T20 2467-2562 Sentence denotes Chemical-related lesions were present in the liver, kidney, and spleen of male and female rats.
T21 2563-2785 Sentence denotes Nonneoplastic lesions in the liver included foci of hepatocellular alteration, diffuse hepatocellular hypertrophy (cytomegaly), hepatocellular cytoplasmic vacuolation, bile duct hyperplasia, inflammation, and pigmentation.
T22 2786-3109 Sentence denotes These differences were observed primarily in the 25,000 and 50,000 ppm groups of males and females; the spectrum of proliferative lesions of the bile ducts (hyperplasia, fibrosis, and necrotizing cholangitis) in the 25,000 and 50,000 ppm groups was morphologically consistent with the lesion described as cholangiofibrosis.
T23 3110-3307 Sentence denotes Pigmentation was present in the renal tubule epithelium of all groups of exposed rats; nuclear enlargement (karyomegaly) was also present in the renal tubule epithelium in some of the exposed rats.
T24 3308-3465 Sentence denotes Accumulation of hyaline droplets in the cytoplasm of the renal tubule epithelium and tubule lumina was present in 2,500, 5,000, 10,000, and 25,000 ppm males.
T25 3466-3596 Sentence denotes Incidences of hematopoiesis of the spleen in exposed groups of males and females were increased compared to those in the controls.
T26 3597-3619 Sentence denotes 13-WEEK STUDY IN MICE:
T27 3620-3769 Sentence denotes Groups of 10 male and 10 female mice were given 0, 2,500, 5,000, 10,000, 25,000, or 50,000 ppm 1-amino-2,4-dibromoanthraquinone in feed for 13 weeks.
T28 3770-3952 Sentence denotes These levels correspond to approximately 500 to 10,600 mg 1-amino-2,4-dibromoanthraquinone/kg body weight per day for males and approximately 660 to 11,700 mg/kg per day for females.
T29 3953-3993 Sentence denotes There was no chemical-related mortality.
T30 3994-4095 Sentence denotes Feed consumption and final mean body weights of exposed groups were similar to those of the controls.
T31 4096-4155 Sentence denotes Red staining of the fur was observed in all exposed groups.
T32 4156-4324 Sentence denotes Absolute and relative liver weights of the exposed groups were greater than those er than those of the controls except for the absolute liver weight of 2,500 ppm males.
T33 4325-4431 Sentence denotes Absolute and relative kidney weights of 25,000 and 50,000 ppm males were lower than those of the controls.
T34 4432-4648 Sentence denotes Chemical-related lesions were limited to the livers of males and consisted of pigmentation of hepatocytes at all exposure concentrations and centrilobular hepatocellular hypertrophy at 10,000, 25,000, and 50,000 ppm.
T35 4649-4770 Sentence denotes Minimal pigment was present in the liver of one female in the 25,000 ppm group and in one female in the 50,000 ppm group.
T36 4771-4792 Sentence denotes 2-YEAR STUDY IN RATS:
T37 4793-4920 Sentence denotes Groups of 70 male and 70 female rats were given 0, 5,000, or 10,000 ppm 1-amino-2,4-dibromoanthraquinone in feed for 103 weeks.
T38 4921-5047 Sentence denotes In addition, groups of 50 male and 50 female rats were given 2,000 ppm 1-amino-2,4-dibromoanthraquinone in feed for 104 weeks.
T39 5048-5222 Sentence denotes These exposure concentrations were approximately equal to 90, 240, or 490 mg 1-amino-2,4-dibromoanthraquinone/kg body weight for males and 110, 285, or 600 mg/kg for females.
T40 5223-5297 Sentence denotes Ten animals from each group were evaluated for histopathology at 9 months.
T41 5298-5410 Sentence denotes Additional groups of 10 animals from the 0 and 10,000 ppm groups were evaluated for histopathology at 15 months.
T42 5411-5591 Sentence denotes Survival, Body Weights, Feed Consumption, and Clinical Findings In the 2-year study, survival of the 10,000 ppm males and females was significantly lower than that of the controls.
T43 5592-5671 Sentence denotes Survival of the 2,000 and 5,000 ppm groups was similar to that of the controls.
T44 5672-5888 Sentence denotes During the last year of the study, the mean body weights of exposed males were 80% to 91% those of controls, and the mean body weights of exposed females were 67% to 84% those of controls.
T45 5889-5985 Sentence denotes Feed consumption among exposed groups was generally similar, but was less than that by controls.
T46 5986-6058 Sentence denotes The fur and urine of all exposed male and female groups were discolored.
T47 6059-6323 Sentence denotes Pathology Findings In the 2-year study, 1-amino-2,4-dibromoanthraquinone was associated with significant chemical-related increases in the incidences of benign and malignant neoplasms in the liver, large intestine, kidney, and urinary bladder of males and females.
T48 6324-6479 Sentence denotes Chemical-related nonneoplastic proliferative and degenerative lesions occurred in the liver, kidney, urinary bladder, and forestomach of males and females.
T49 6480-6696 Sentence denotes The incidences of foci of hepatocellular alteration and pigmentation in the liver of males and females were increased at the 9-month interim evaluation, and a hepatocellular adenoma was present in one 5,000 ppm male.
T50 6697-6844 Sentence denotes At the 15-month interim evaluation, hepatocellular adenoma or carcinoma (combined) occurred in all males and nine females in the 10,000 ppm groups.
T51 6845-7017 Sentence denotes By the end of the 2-year study, hepatocellular adenoma, carcinoma, cholangioma, or cholangiocarcinoma were observed in males and females in the 5,000 and 10,000 ppm groups.
T52 7018-7140 Sentence denotes In the 2,000 ppm groups, similar liver neoplasms were present in 63% of the males and in 83% of the females.
T53 7141-7300 Sentence denotes Of the hepatocellular carcinomas in the 5,000 and 10,000 ppm groups of males and females, 31% to 49% were metastatic to the lungs or other sites.
T54 7301-7497 Sentence denotes Increases in the incidences of foci of hepatocellular alteration (basophilic, eosinophilic, and clear cell) and pigmentation of the liver were also observed in exposed groups of males and females.
T55 7498-7622 Sentence denotes Adenomatous polyps (adenoma) of the large intestine were present in six 10,000 ppm males at the 15-month interim evaluation.
T56 7623-7872 Sentence denotes Incidences of adenomatous polyp (adenoma) and carcinoma of the large intestine were significantly increased in exposed groups of males and females after 2 years; multiple benign and malignant intestinal neoplasms were observed in many of these rats.
T57 7873-8019 Sentence denotes In the kidney, incidences of renal tubule adenoma and carcinoma were significantly increased in exposed groups of males and females after 2 years.
T58 8020-8092 Sentence denotes Renal tubule adenomas were present in two 10,000 ppm males at 15 months.
T59 8093-8292 Sentence denotes There were also chemical-related increases in the incidences and severities of renal tubule epithelial hyperplasia, pigmentation, and transitional cell hyperplasia in the kidney of males and females.
T60 8293-8371 Sentence denotes Hyaline droplet accumulation was present in all exposed male rats at 9 months.
T61 8372-8523 Sentence denotes Incidences of transitional cell papilloma and carcinoma of the urinary bladder were increased at 2 years in males and females in the 10,000 ppm groups.
T62 8524-8631 Sentence denotes Transitional cell hyperplasia was observed in exposed males and females at the 15-month interim evaluation.
T63 8632-8784 Sentence denotes Other nonneoplastic lesions observed in the urinary bladder at 2 years included metaplasia of the transitional epithelium and submucosal stromal tissue.
T64 8785-9039 Sentence denotes In the forestomach, the incidences and severities of inflammation, ulceration, hyperkeratosis, and hyperplasia of the squamous mucosa were increased in all exposed groups of males and females at 2 years, but not at the 9- or 15-month interim evaluations.
T65 9040-9143 Sentence denotes In exposed males and females, the incidences of mononuclear cell leukemia were significantly decreased.
T66 9144-9249 Sentence denotes The incidences of atrophy of the seminal vesicle were increased in exposed male rats in the 2-year study.
T67 9250-9402 Sentence denotes Stop-Exposure Evaluation in Rats Groups of 40 male and 40 female rats were given 20,000 ppm 1-amino-2,4-dibromoanthraquinone in feed for 9 or 15 months.
T68 9403-9510 Sentence denotes At 9 months, 10 males and 10 females were evaluated for histopathology (9-month interim evaluation groups).
T69 9511-9824 Sentence denotes After 9 months of exposure, an additional 10 males and 10 females were fed control diet until the end of the 15-month evaluation (9-month stop-exposure groups), and 20 males and 20 females continued to receive 20,000 ppm 1-amino-2,4-dibromoanthraquinone until the end of the evaluation (15-month exposure groups).
T70 9825-10071 Sentence denotes The approximate daily consumption of 1-amino-2,4-dibromoanthraquinone was 1,335 mg/kg for males and 1,790 mg/kg for females in the 9-month stop-exposure groups and 1,115 mg/kg for males and 1,435 mg/kg for females in the 15-month exposure groups.
T71 10072-10224 Sentence denotes Survival was similar among groups except for the females in the 15-month exposure group; the survival of this group was lower than that of the controls.
T72 10225-10293 Sentence denotes Lower mean body weights were related to increased exposure duration.
T73 10294-10473 Sentence denotes The mean body weights of exposed males were 76% to 82% that of controls, and the mean body weights of exposed females were 73% to 84% that of controls.
T74 10474-10690 Sentence denotes For the stop-exposure evaluation, similar chemical-related neoplasms and nonneoplastic lesions were observed in the same sites as in the 2-year study: liver, large intestine, kidney, urinary bladder, and forestomach.
T75 10691-10860 Sentence denotes After 9 months of dietary exposure to a concentration of 20,000 ppm 1-amino-2,4-dibromoanthraquinone, hepatocellular adenoma and carcinoma occurred in males and females.
T76 10861-11011 Sentence denotes Nonneoplastic chemical-related lesions in the liver of exposed rats included pigmentation, focal hepatocellular alteration, and bile duct hyperplasia.
T77 11012-11169 Sentence denotes Neoplasms at other sites in males included one adenomatous polyp (adenoma) in the large intestine and one transitional cell papilloma in the urinary bladder.
T78 11170-11254 Sentence denotes Hyaline droplet accumulation was present in the kidney of exposed males at 9 months.
T79 11255-11382 Sentence denotes In the stop-exposure groups examined at 15 months, hepatocellular adenoma and carcinoma were present in most males and females.
T80 11383-11549 Sentence denotes Adenomatous polyp (adenoma) of the colon, renal tubule cell adenoma, and urinary bladder transitional cell papilloma and carcinoma also occurred in males and females.
T81 11550-11736 Sentence denotes Nonneoplastic chemical-related lesions included foci of hepatocellular alteration in the liver and hyperplasia of the renal tubule epithelium and urinary bladder transitional epithelium.
T82 11737-11892 Sentence denotes Hyperplasia, hyperkeratosis, inflammation, and ulceration were observed in the forestomach of some male and female rats continuously exposed for 15 months.
T83 11893-11914 Sentence denotes 2-YEAR STUDY IN MICE:
T84 11915-12043 Sentence denotes Groups of 60 male and 60 female mice were given 0, 10,000, or 20,000 ppm 1-amino-2,4-dibromoanthraquinone in feed for 104 weeks.
T85 12044-12206 Sentence denotes The daily compound consumption was approximately 1,690 or 3,470 mg 1-amino-2,4-dibromoanthraquinone/kg body weight for males and 1,950 or 4,350 mg/kg for females.
T86 12207-12282 Sentence denotes Ten animals from each group were evaluated for histopathology at 15 months.
T87 12283-12444 Sentence denotes Survival, Body Weights, Feed Consumption, and Clinical Findings In the 2-year study, survival of exposed males was significantly lower than that of the controls.
T88 12445-12509 Sentence denotes Survival of exposed females was similar to that of the controls.
T89 12510-12701 Sentence denotes The final mean body weights of exposed males were 83% to 85% that of controls, and the final mean body weights of exposed females were 81% to 86% that of controls.
T90 12702-12779 Sentence denotes Feed consumption by exposed groups was generally similar to that by controls.
T91 12780-12858 Sentence denotes Discoloration of the fur, urine, and feces was observed in all exposed groups.
T92 12859-13100 Sentence denotes Pathology Findings In the 2-year study, 1-amino-2,4-dibromoanthraquinone was associated with significant chemical-related increases in the incidences of benign and malignant neoplasms in the liver, forestomach, and lung of males and females.
T93 13101-13235 Sentence denotes Incidences of hepatocellular adenoma and carcinoma were increased in exposed groups at the 15-month interim evaluation and at 2 years.
T94 13236-13418 Sentence denotes At 2 years, there were significant increases in the incidences of multiple hepatocellular adenoma and carcinoma in males and females and in the incidences of hepatoblastoma in males.
T95 13419-13593 Sentence denotes Centrilobular hypertrophy of hepatocytes in males and foci of hepatocellular alteration and pigmentation in the liver of males and females were also chemical-related changes.
T96 13594-13882 Sentence denotes Sqamous cell papilloma of the forestomach mucosa occurred in 10,000 ppm females and 20,000 ppm males and females at the 15-month interim evaluation, and the incidences of squamous cell papilloma and carcinoma were significantly increased in exposed groups of males and females at 2 years.
T97 13883-13983 Sentence denotes Chemical-related hyperplasia of forestomach epithelium was also present at 15 months and at 2 years.
T98 13984-14209 Sentence denotes Alveolar/bronchiolar adenomas were present only in the exposed groups of males and females at 15 months, and the incidences of alveolar/bronchiolar adenoma were significantly increased in exposed males and females at 2 years.
T99 14210-14304 Sentence denotes The incidences of multiple alveolar/bronchiolar adenomas were also increased in exposed males.
T100 14305-14405 Sentence denotes In the kidney, pigmentation was present in the renal tubules of most mice after 2 years of exposure.
T101 14406-14441 Sentence denotes DISPOSITION AND METABOLISM STUDIES:
T102 14442-14637 Sentence denotes Adult male F344/N rats were given [14C]-labeled 1-amino-2,4-dibromoanthraquinone as a single intravenous dose of 0.4 mg/kg body weight or as a single oral dose of 2, 23, 118, 814, or 1,473 mg/kg.
T103 14638-14689 Sentence denotes A 6-hour bile cannulation study was also performed.
T104 14690-14858 Sentence denotes From day 0 through day 3 after intravenous administration, about 50% of the 14C was excreted in the feces, 15% in the urine, and 6% in expired air.
T105 14859-14993 Sentence denotes Unmetabolized 1-amino-2,4-dibromoanthraquinone accounted for less than 3% of the excreted 14C after intravenous administration.
T106 14994-15114 Sentence denotes For oral doses administered, the amount of the dose that was absorbed fit the equation: absorbed dose = 6.6 x log(dose).
T107 15115-15292 Sentence denotes After intravenous administration, the metabolites of 1-amino-2,4-dibromoanthraquinone in blood were primarily in the plasma fraction (blood:plasma ratio of approximately 0.5:1).
T108 15293-15472 Sentence denotes The highest concentrations of 14C in tissues 15 minutes after intravenous dosing were in excretory organs, lung, kidney, small intestine, liver, adipose tissue, and adrenal gland.
T109 15473-15492 Sentence denotes GENETIC TOXICOLOGY:
T110 15493-15666 Sentence denotes 1-Amino-2,4-dibromoanthraquinone was mutagenic in Salmonella typhimurium strains TA98 and TA1537 in the absence of S9; with S9, an equivocal response was observed in TA1537.
T111 15667-15822 Sentence denotes 1-Amino-2,4-dibromoanthraquinone resulted in an equivocal response in TA100 with and without S9, and no mutagenic activity was detected with strain TA1535.
T112 15823-16011 Sentence denotes In cultured Chinese hamster ovary cells, 1-amino-2,4-dibromoanthraquinone induced sister chromatid exchanges with and without S9; chromosomal aberrations were induced in the absence of S9.
T113 16012-16024 Sentence denotes CONCLUSIONS:
T114 16025-16295 Sentence denotes Under the conditions of these 2-year feed studies, there was clear evidence of carcinogenic activity of 1-amino-2,4-dibromoanthraquinone in male and female F344/N rats based on increased incidences of neoplasms in the liver, large intestine, kidney, and urinary bladder.
T115 16296-16492 Sentence denotes There was clear evidence of carcinogenic activity of 1-amino-2,4-dibromoanthraquinone in male and female B6C3F1 mice based on increased incidences of neoplasms in the liver, forestomach, and lung.
T116 16493-17032 Sentence denotes Exposure of male and female rats to 1-amino-2,4-dibromoanthraquinone for 2 years was associated with basophilic focus (males only), clear cell focus, eosinophilic focus, and pigmentation in the liver; renal tubule hyperplasia, renal tubule pigmentation, and transitional cell hyperplasia in the kidney; transitional cell hyperplasia, squamous metaplasia, and stromal metaplasia (females only) in the urinary bladder; squamous hyperplasia, hyperkeratosis, ulceration, and inflammation of the forestomach mucosa; and seminal vesicle atrophy.
T117 17033-17419 Sentence denotes Exposure of male and female mice to 1-amino-2,4-dibromoanthraquinone for 2 years was associated with centrilobular hepatocellular hypertrophy (males only), basophilic focus, clear cell focus (females only), eosinophilic focus, and pigmentation in the liver; pigmentation in the kidney; and hyperplasia, basal cell hyperplasia, hyperkeratosis, and inflammation of the forestomach mucosa.
T118 17420-17434 Sentence denotes Synonym: ADBAQ
T1 0-86 Sentence denotes NTP Toxicology and Carcinogenesis Studies of 1-Amino-2,4-Dibromoanthraquinone (CAS No.
T2 87-142 Sentence denotes 81-49-2) in F344/N Rats and B6C3F1 Mice (Feed Studies).
T3 143-292 Sentence denotes 1-Amino-2,4-dibromoanthraquinone is an anthraquinone-derived vat dye, a member of a class of insoluble dyes that are impregnated into textile fibers.
T4 293-479 Sentence denotes Five anthraquinone-derived dyes with representative and diverse structures, as well as the parent chemical, anthraquinone, were selected for NTP Toxicology and Carcinogenesis evaluation.
T5 480-782 Sentence denotes Similar to the benzidine dye initiative, the rationale for selecting these vat dyes was to generate sufficient toxicologic data to permit more reliable predictions of carcinogenicity to be made on other chemicals in this class, thereby eliminating or reducing the need to study every anthraquinone dye.
T6 783-882 Sentence denotes 1-Amino-2,4-dibromoanthraquinone is the last anthraquinone-derived dye in this group to be studied.
T7 883-1044 Sentence denotes Groups of male and female F344/N rats and B6C3F1 mice were exposed to 1-amino-2,4-dibromoanthraquinone (87% to 97% pure) for 13 weeks or for 9, 15, or 24 months.
T8 1045-1211 Sentence denotes Because 1-amino-2,4-dibromoanthraquinone was predicted to be carcinogenic, these studies were designed to evaluate the potential for tumor progression and regression.
T9 1212-1282 Sentence denotes Absorption and excretion studies were carried out in male F344/N rats.
T10 1283-1394 Sentence denotes Genetic toxicity was determined in vitro using Salmonella typhimurium and cultured Chinese hamster ovary cells.
T11 1395-1540 Sentence denotes Extensive chemical analyses were performed to identify and characterize impurities of the 1-amino-2,4-dibromoanthraquinone used in these studies.
T12 1541-1563 Sentence denotes 13-WEEK STUDY IN RATS:
T13 1564-1713 Sentence denotes Groups of 10 male and 10 female rats were given 0, 2,500, 5,000, 10,000, 25,000, or 50,000 ppm 1-amino-2,4-dibromoanthraquinone in feed for 13 weeks.
T14 1714-1889 Sentence denotes These levels correspond to approximately 150 to 3,200 mg 1-amino-2,4-dibromoanthraquinone/kg body weight per day for males and to approximately 170 to 3,200 mg/kg for females.
T15 1890-1981 Sentence denotes Chemical-related mortality was limited to one male and one female in the 50,000 ppm groups.
T16 1982-2110 Sentence denotes Final mean body weights and body weight gains of all exposed groups of rats were significantly lower than those of the controls.
T17 2111-2269 Sentence denotes Feed consumption by all exposed groups was less than that by the controls throughout the study and generally decreased with increasing exposure concentration.
T18 2270-2343 Sentence denotes Pink-red staining of the fur and tail was observed in all exposed groups.
T19 2344-2466 Sentence denotes Absolute and relative liver weights of all exposed groups were generally significantly greater than those of the controls.
T20 2467-2562 Sentence denotes Chemical-related lesions were present in the liver, kidney, and spleen of male and female rats.
T21 2563-2785 Sentence denotes Nonneoplastic lesions in the liver included foci of hepatocellular alteration, diffuse hepatocellular hypertrophy (cytomegaly), hepatocellular cytoplasmic vacuolation, bile duct hyperplasia, inflammation, and pigmentation.
T22 2786-3109 Sentence denotes These differences were observed primarily in the 25,000 and 50,000 ppm groups of males and females; the spectrum of proliferative lesions of the bile ducts (hyperplasia, fibrosis, and necrotizing cholangitis) in the 25,000 and 50,000 ppm groups was morphologically consistent with the lesion described as cholangiofibrosis.
T23 3110-3307 Sentence denotes Pigmentation was present in the renal tubule epithelium of all groups of exposed rats; nuclear enlargement (karyomegaly) was also present in the renal tubule epithelium in some of the exposed rats.
T24 3308-3465 Sentence denotes Accumulation of hyaline droplets in the cytoplasm of the renal tubule epithelium and tubule lumina was present in 2,500, 5,000, 10,000, and 25,000 ppm males.
T25 3466-3596 Sentence denotes Incidences of hematopoiesis of the spleen in exposed groups of males and females were increased compared to those in the controls.
T26 3597-3619 Sentence denotes 13-WEEK STUDY IN MICE:
T27 3620-3769 Sentence denotes Groups of 10 male and 10 female mice were given 0, 2,500, 5,000, 10,000, 25,000, or 50,000 ppm 1-amino-2,4-dibromoanthraquinone in feed for 13 weeks.
T28 3770-3952 Sentence denotes These levels correspond to approximately 500 to 10,600 mg 1-amino-2,4-dibromoanthraquinone/kg body weight per day for males and approximately 660 to 11,700 mg/kg per day for females.
T29 3953-3993 Sentence denotes There was no chemical-related mortality.
T30 3994-4095 Sentence denotes Feed consumption and final mean body weights of exposed groups were similar to those of the controls.
T31 4096-4155 Sentence denotes Red staining of the fur was observed in all exposed groups.
T32 4156-4324 Sentence denotes Absolute and relative liver weights of the exposed groups were greater than those er than those of the controls except for the absolute liver weight of 2,500 ppm males.
T33 4325-4431 Sentence denotes Absolute and relative kidney weights of 25,000 and 50,000 ppm males were lower than those of the controls.
T34 4432-4648 Sentence denotes Chemical-related lesions were limited to the livers of males and consisted of pigmentation of hepatocytes at all exposure concentrations and centrilobular hepatocellular hypertrophy at 10,000, 25,000, and 50,000 ppm.
T35 4649-4770 Sentence denotes Minimal pigment was present in the liver of one female in the 25,000 ppm group and in one female in the 50,000 ppm group.
T36 4771-4792 Sentence denotes 2-YEAR STUDY IN RATS:
T37 4793-4920 Sentence denotes Groups of 70 male and 70 female rats were given 0, 5,000, or 10,000 ppm 1-amino-2,4-dibromoanthraquinone in feed for 103 weeks.
T38 4921-5047 Sentence denotes In addition, groups of 50 male and 50 female rats were given 2,000 ppm 1-amino-2,4-dibromoanthraquinone in feed for 104 weeks.
T39 5048-5222 Sentence denotes These exposure concentrations were approximately equal to 90, 240, or 490 mg 1-amino-2,4-dibromoanthraquinone/kg body weight for males and 110, 285, or 600 mg/kg for females.
T40 5223-5297 Sentence denotes Ten animals from each group were evaluated for histopathology at 9 months.
T41 5298-5410 Sentence denotes Additional groups of 10 animals from the 0 and 10,000 ppm groups were evaluated for histopathology at 15 months.
T42 5411-5591 Sentence denotes Survival, Body Weights, Feed Consumption, and Clinical Findings In the 2-year study, survival of the 10,000 ppm males and females was significantly lower than that of the controls.
T43 5592-5671 Sentence denotes Survival of the 2,000 and 5,000 ppm groups was similar to that of the controls.
T44 5672-5888 Sentence denotes During the last year of the study, the mean body weights of exposed males were 80% to 91% those of controls, and the mean body weights of exposed females were 67% to 84% those of controls.
T45 5889-5985 Sentence denotes Feed consumption among exposed groups was generally similar, but was less than that by controls.
T46 5986-6058 Sentence denotes The fur and urine of all exposed male and female groups were discolored.
T47 6059-6323 Sentence denotes Pathology Findings In the 2-year study, 1-amino-2,4-dibromoanthraquinone was associated with significant chemical-related increases in the incidences of benign and malignant neoplasms in the liver, large intestine, kidney, and urinary bladder of males and females.
T48 6324-6479 Sentence denotes Chemical-related nonneoplastic proliferative and degenerative lesions occurred in the liver, kidney, urinary bladder, and forestomach of males and females.
T49 6480-6696 Sentence denotes The incidences of foci of hepatocellular alteration and pigmentation in the liver of males and females were increased at the 9-month interim evaluation, and a hepatocellular adenoma was present in one 5,000 ppm male.
T50 6697-6844 Sentence denotes At the 15-month interim evaluation, hepatocellular adenoma or carcinoma (combined) occurred in all males and nine females in the 10,000 ppm groups.
T51 6845-7017 Sentence denotes By the end of the 2-year study, hepatocellular adenoma, carcinoma, cholangioma, or cholangiocarcinoma were observed in males and females in the 5,000 and 10,000 ppm groups.
T52 7018-7140 Sentence denotes In the 2,000 ppm groups, similar liver neoplasms were present in 63% of the males and in 83% of the females.
T53 7141-7300 Sentence denotes Of the hepatocellular carcinomas in the 5,000 and 10,000 ppm groups of males and females, 31% to 49% were metastatic to the lungs or other sites.
T54 7301-7497 Sentence denotes Increases in the incidences of foci of hepatocellular alteration (basophilic, eosinophilic, and clear cell) and pigmentation of the liver were also observed in exposed groups of males and females.
T55 7498-7622 Sentence denotes Adenomatous polyps (adenoma) of the large intestine were present in six 10,000 ppm males at the 15-month interim evaluation.
T56 7623-7872 Sentence denotes Incidences of adenomatous polyp (adenoma) and carcinoma of the large intestine were significantly increased in exposed groups of males and females after 2 years; multiple benign and malignant intestinal neoplasms were observed in many of these rats.
T57 7873-8019 Sentence denotes In the kidney, incidences of renal tubule adenoma and carcinoma were significantly increased in exposed groups of males and females after 2 years.
T58 8020-8092 Sentence denotes Renal tubule adenomas were present in two 10,000 ppm males at 15 months.
T59 8093-8292 Sentence denotes There were also chemical-related increases in the incidences and severities of renal tubule epithelial hyperplasia, pigmentation, and transitional cell hyperplasia in the kidney of males and females.
T60 8293-8371 Sentence denotes Hyaline droplet accumulation was present in all exposed male rats at 9 months.
T61 8372-8523 Sentence denotes Incidences of transitional cell papilloma and carcinoma of the urinary bladder were increased at 2 years in males and females in the 10,000 ppm groups.
T62 8524-8631 Sentence denotes Transitional cell hyperplasia was observed in exposed males and females at the 15-month interim evaluation.
T63 8632-8784 Sentence denotes Other nonneoplastic lesions observed in the urinary bladder at 2 years included metaplasia of the transitional epithelium and submucosal stromal tissue.
T64 8785-9039 Sentence denotes In the forestomach, the incidences and severities of inflammation, ulceration, hyperkeratosis, and hyperplasia of the squamous mucosa were increased in all exposed groups of males and females at 2 years, but not at the 9- or 15-month interim evaluations.
T65 9040-9143 Sentence denotes In exposed males and females, the incidences of mononuclear cell leukemia were significantly decreased.
T66 9144-9249 Sentence denotes The incidences of atrophy of the seminal vesicle were increased in exposed male rats in the 2-year study.
T67 9250-9402 Sentence denotes Stop-Exposure Evaluation in Rats Groups of 40 male and 40 female rats were given 20,000 ppm 1-amino-2,4-dibromoanthraquinone in feed for 9 or 15 months.
T68 9403-9510 Sentence denotes At 9 months, 10 males and 10 females were evaluated for histopathology (9-month interim evaluation groups).
T69 9511-9824 Sentence denotes After 9 months of exposure, an additional 10 males and 10 females were fed control diet until the end of the 15-month evaluation (9-month stop-exposure groups), and 20 males and 20 females continued to receive 20,000 ppm 1-amino-2,4-dibromoanthraquinone until the end of the evaluation (15-month exposure groups).
T70 9825-10071 Sentence denotes The approximate daily consumption of 1-amino-2,4-dibromoanthraquinone was 1,335 mg/kg for males and 1,790 mg/kg for females in the 9-month stop-exposure groups and 1,115 mg/kg for males and 1,435 mg/kg for females in the 15-month exposure groups.
T71 10072-10224 Sentence denotes Survival was similar among groups except for the females in the 15-month exposure group; the survival of this group was lower than that of the controls.
T72 10225-10293 Sentence denotes Lower mean body weights were related to increased exposure duration.
T73 10294-10473 Sentence denotes The mean body weights of exposed males were 76% to 82% that of controls, and the mean body weights of exposed females were 73% to 84% that of controls.
T74 10474-10690 Sentence denotes For the stop-exposure evaluation, similar chemical-related neoplasms and nonneoplastic lesions were observed in the same sites as in the 2-year study: liver, large intestine, kidney, urinary bladder, and forestomach.
T75 10691-10860 Sentence denotes After 9 months of dietary exposure to a concentration of 20,000 ppm 1-amino-2,4-dibromoanthraquinone, hepatocellular adenoma and carcinoma occurred in males and females.
T76 10861-11011 Sentence denotes Nonneoplastic chemical-related lesions in the liver of exposed rats included pigmentation, focal hepatocellular alteration, and bile duct hyperplasia.
T77 11012-11169 Sentence denotes Neoplasms at other sites in males included one adenomatous polyp (adenoma) in the large intestine and one transitional cell papilloma in the urinary bladder.
T78 11170-11254 Sentence denotes Hyaline droplet accumulation was present in the kidney of exposed males at 9 months.
T79 11255-11382 Sentence denotes In the stop-exposure groups examined at 15 months, hepatocellular adenoma and carcinoma were present in most males and females.
T80 11383-11549 Sentence denotes Adenomatous polyp (adenoma) of the colon, renal tubule cell adenoma, and urinary bladder transitional cell papilloma and carcinoma also occurred in males and females.
T81 11550-11736 Sentence denotes Nonneoplastic chemical-related lesions included foci of hepatocellular alteration in the liver and hyperplasia of the renal tubule epithelium and urinary bladder transitional epithelium.
T82 11737-11892 Sentence denotes Hyperplasia, hyperkeratosis, inflammation, and ulceration were observed in the forestomach of some male and female rats continuously exposed for 15 months.
T83 11893-11914 Sentence denotes 2-YEAR STUDY IN MICE:
T84 11915-12043 Sentence denotes Groups of 60 male and 60 female mice were given 0, 10,000, or 20,000 ppm 1-amino-2,4-dibromoanthraquinone in feed for 104 weeks.
T85 12044-12206 Sentence denotes The daily compound consumption was approximately 1,690 or 3,470 mg 1-amino-2,4-dibromoanthraquinone/kg body weight for males and 1,950 or 4,350 mg/kg for females.
T86 12207-12282 Sentence denotes Ten animals from each group were evaluated for histopathology at 15 months.
T87 12283-12444 Sentence denotes Survival, Body Weights, Feed Consumption, and Clinical Findings In the 2-year study, survival of exposed males was significantly lower than that of the controls.
T88 12445-12509 Sentence denotes Survival of exposed females was similar to that of the controls.
T89 12510-12701 Sentence denotes The final mean body weights of exposed males were 83% to 85% that of controls, and the final mean body weights of exposed females were 81% to 86% that of controls.
T90 12702-12779 Sentence denotes Feed consumption by exposed groups was generally similar to that by controls.
T91 12780-12858 Sentence denotes Discoloration of the fur, urine, and feces was observed in all exposed groups.
T92 12859-13100 Sentence denotes Pathology Findings In the 2-year study, 1-amino-2,4-dibromoanthraquinone was associated with significant chemical-related increases in the incidences of benign and malignant neoplasms in the liver, forestomach, and lung of males and females.
T93 13101-13235 Sentence denotes Incidences of hepatocellular adenoma and carcinoma were increased in exposed groups at the 15-month interim evaluation and at 2 years.
T94 13236-13418 Sentence denotes At 2 years, there were significant increases in the incidences of multiple hepatocellular adenoma and carcinoma in males and females and in the incidences of hepatoblastoma in males.
T95 13419-13593 Sentence denotes Centrilobular hypertrophy of hepatocytes in males and foci of hepatocellular alteration and pigmentation in the liver of males and females were also chemical-related changes.
T96 13594-13882 Sentence denotes Sqamous cell papilloma of the forestomach mucosa occurred in 10,000 ppm females and 20,000 ppm males and females at the 15-month interim evaluation, and the incidences of squamous cell papilloma and carcinoma were significantly increased in exposed groups of males and females at 2 years.
T97 13883-13983 Sentence denotes Chemical-related hyperplasia of forestomach epithelium was also present at 15 months and at 2 years.
T98 13984-14209 Sentence denotes Alveolar/bronchiolar adenomas were present only in the exposed groups of males and females at 15 months, and the incidences of alveolar/bronchiolar adenoma were significantly increased in exposed males and females at 2 years.
T99 14210-14304 Sentence denotes The incidences of multiple alveolar/bronchiolar adenomas were also increased in exposed males.
T100 14305-14405 Sentence denotes In the kidney, pigmentation was present in the renal tubules of most mice after 2 years of exposure.
T101 14406-14441 Sentence denotes DISPOSITION AND METABOLISM STUDIES:
T102 14442-14637 Sentence denotes Adult male F344/N rats were given [14C]-labeled 1-amino-2,4-dibromoanthraquinone as a single intravenous dose of 0.4 mg/kg body weight or as a single oral dose of 2, 23, 118, 814, or 1,473 mg/kg.
T103 14638-14689 Sentence denotes A 6-hour bile cannulation study was also performed.
T104 14690-14858 Sentence denotes From day 0 through day 3 after intravenous administration, about 50% of the 14C was excreted in the feces, 15% in the urine, and 6% in expired air.
T105 14859-14993 Sentence denotes Unmetabolized 1-amino-2,4-dibromoanthraquinone accounted for less than 3% of the excreted 14C after intravenous administration.
T106 14994-15114 Sentence denotes For oral doses administered, the amount of the dose that was absorbed fit the equation: absorbed dose = 6.6 x log(dose).
T107 15115-15292 Sentence denotes After intravenous administration, the metabolites of 1-amino-2,4-dibromoanthraquinone in blood were primarily in the plasma fraction (blood:plasma ratio of approximately 0.5:1).
T108 15293-15472 Sentence denotes The highest concentrations of 14C in tissues 15 minutes after intravenous dosing were in excretory organs, lung, kidney, small intestine, liver, adipose tissue, and adrenal gland.
T109 15473-15492 Sentence denotes GENETIC TOXICOLOGY:
T110 15493-15666 Sentence denotes 1-Amino-2,4-dibromoanthraquinone was mutagenic in Salmonella typhimurium strains TA98 and TA1537 in the absence of S9; with S9, an equivocal response was observed in TA1537.
T111 15667-15822 Sentence denotes 1-Amino-2,4-dibromoanthraquinone resulted in an equivocal response in TA100 with and without S9, and no mutagenic activity was detected with strain TA1535.
T112 15823-16011 Sentence denotes In cultured Chinese hamster ovary cells, 1-amino-2,4-dibromoanthraquinone induced sister chromatid exchanges with and without S9; chromosomal aberrations were induced in the absence of S9.
T113 16012-16024 Sentence denotes CONCLUSIONS:
T114 16025-16295 Sentence denotes Under the conditions of these 2-year feed studies, there was clear evidence of carcinogenic activity of 1-amino-2,4-dibromoanthraquinone in male and female F344/N rats based on increased incidences of neoplasms in the liver, large intestine, kidney, and urinary bladder.
T115 16296-16492 Sentence denotes There was clear evidence of carcinogenic activity of 1-amino-2,4-dibromoanthraquinone in male and female B6C3F1 mice based on increased incidences of neoplasms in the liver, forestomach, and lung.
T116 16493-17032 Sentence denotes Exposure of male and female rats to 1-amino-2,4-dibromoanthraquinone for 2 years was associated with basophilic focus (males only), clear cell focus, eosinophilic focus, and pigmentation in the liver; renal tubule hyperplasia, renal tubule pigmentation, and transitional cell hyperplasia in the kidney; transitional cell hyperplasia, squamous metaplasia, and stromal metaplasia (females only) in the urinary bladder; squamous hyperplasia, hyperkeratosis, ulceration, and inflammation of the forestomach mucosa; and seminal vesicle atrophy.
T117 17033-17419 Sentence denotes Exposure of male and female mice to 1-amino-2,4-dibromoanthraquinone for 2 years was associated with centrilobular hepatocellular hypertrophy (males only), basophilic focus, clear cell focus (females only), eosinophilic focus, and pigmentation in the liver; pigmentation in the kidney; and hyperplasia, basal cell hyperplasia, hyperkeratosis, and inflammation of the forestomach mucosa.
T118 17420-17434 Sentence denotes Synonym: ADBAQ

PubMed_ArguminSci

Id Subject Object Predicate Lexical cue
T1 143-292 DRI_Background denotes 1-Amino-2,4-dibromoanthraquinone is an anthraquinone-derived vat dye, a member of a class of insoluble dyes that are impregnated into textile fibers.
T2 293-479 DRI_Background denotes Five anthraquinone-derived dyes with representative and diverse structures, as well as the parent chemical, anthraquinone, were selected for NTP Toxicology and Carcinogenesis evaluation.
T3 480-782 DRI_Challenge denotes Similar to the benzidine dye initiative, the rationale for selecting these vat dyes was to generate sufficient toxicologic data to permit more reliable predictions of carcinogenicity to be made on other chemicals in this class, thereby eliminating or reducing the need to study every anthraquinone dye.
T4 783-882 DRI_Background denotes 1-Amino-2,4-dibromoanthraquinone is the last anthraquinone-derived dye in this group to be studied.
T5 883-1044 DRI_Background denotes Groups of male and female F344/N rats and B6C3F1 mice were exposed to 1-amino-2,4-dibromoanthraquinone (87% to 97% pure) for 13 weeks or for 9, 15, or 24 months.
T6 1045-1211 DRI_Background denotes Because 1-amino-2,4-dibromoanthraquinone was predicted to be carcinogenic, these studies were designed to evaluate the potential for tumor progression and regression.
T7 1212-1282 DRI_Background denotes Absorption and excretion studies were carried out in male F344/N rats.
T8 1283-1394 DRI_Background denotes Genetic toxicity was determined in vitro using Salmonella typhimurium and cultured Chinese hamster ovary cells.
T9 1395-1540 DRI_Background denotes Extensive chemical analyses were performed to identify and characterize impurities of the 1-amino-2,4-dibromoanthraquinone used in these studies.
T10 1541-1713 DRI_Background denotes 13-WEEK STUDY IN RATS: Groups of 10 male and 10 female rats were given 0, 2,500, 5,000, 10,000, 25,000, or 50,000 ppm 1-amino-2,4-dibromoanthraquinone in feed for 13 weeks.
T11 1714-1889 DRI_Outcome denotes These levels correspond to approximately 150 to 3,200 mg 1-amino-2,4-dibromoanthraquinone/kg body weight per day for males and to approximately 170 to 3,200 mg/kg for females.
T12 1890-1981 DRI_Background denotes Chemical-related mortality was limited to one male and one female in the 50,000 ppm groups.
T13 1982-2110 DRI_Approach denotes Final mean body weights and body weight gains of all exposed groups of rats were significantly lower than those of the controls.
T14 2111-2269 DRI_Approach denotes Feed consumption by all exposed groups was less than that by the controls throughout the study and generally decreased with increasing exposure concentration.
T15 2270-2343 DRI_Background denotes Pink-red staining of the fur and tail was observed in all exposed groups.
T16 2344-2466 DRI_Background denotes Absolute and relative liver weights of all exposed groups were generally significantly greater than those of the controls.
T17 2467-2562 DRI_Background denotes Chemical-related lesions were present in the liver, kidney, and spleen of male and female rats.
T18 2563-2785 DRI_Background denotes Nonneoplastic lesions in the liver included foci of hepatocellular alteration, diffuse hepatocellular hypertrophy (cytomegaly), hepatocellular cytoplasmic vacuolation, bile duct hyperplasia, inflammation, and pigmentation.
T19 2786-3109 DRI_Background denotes These differences were observed primarily in the 25,000 and 50,000 ppm groups of males and females; the spectrum of proliferative lesions of the bile ducts (hyperplasia, fibrosis, and necrotizing cholangitis) in the 25,000 and 50,000 ppm groups was morphologically consistent with the lesion described as cholangiofibrosis.
T20 3110-3307 DRI_Background denotes Pigmentation was present in the renal tubule epithelium of all groups of exposed rats; nuclear enlargement (karyomegaly) was also present in the renal tubule epithelium in some of the exposed rats.
T21 3308-3465 DRI_Background denotes Accumulation of hyaline droplets in the cytoplasm of the renal tubule epithelium and tubule lumina was present in 2,500, 5,000, 10,000, and 25,000 ppm males.
T22 3466-3596 DRI_Background denotes Incidences of hematopoiesis of the spleen in exposed groups of males and females were increased compared to those in the controls.
T23 3597-3769 DRI_Background denotes 13-WEEK STUDY IN MICE: Groups of 10 male and 10 female mice were given 0, 2,500, 5,000, 10,000, 25,000, or 50,000 ppm 1-amino-2,4-dibromoanthraquinone in feed for 13 weeks.
T24 3770-3952 DRI_Outcome denotes These levels correspond to approximately 500 to 10,600 mg 1-amino-2,4-dibromoanthraquinone/kg body weight per day for males and approximately 660 to 11,700 mg/kg per day for females.
T25 3994-4095 DRI_Approach denotes Feed consumption and final mean body weights of exposed groups were similar to those of the controls.
T26 4096-4155 DRI_Approach denotes Red staining of the fur was observed in all exposed groups.
T27 4156-4324 DRI_Background denotes Absolute and relative liver weights of the exposed groups were greater than those er than those of the controls except for the absolute liver weight of 2,500 ppm males.
T28 4325-4431 DRI_Background denotes Absolute and relative kidney weights of 25,000 and 50,000 ppm males were lower than those of the controls.
T29 4432-4648 DRI_Outcome denotes Chemical-related lesions were limited to the livers of males and consisted of pigmentation of hepatocytes at all exposure concentrations and centrilobular hepatocellular hypertrophy at 10,000, 25,000, and 50,000 ppm.
T30 4649-4770 DRI_Background denotes Minimal pigment was present in the liver of one female in the 25,000 ppm group and in one female in the 50,000 ppm group.
T31 4771-4920 DRI_Background denotes 2-YEAR STUDY IN RATS: Groups of 70 male and 70 female rats were given 0, 5,000, or 10,000 ppm 1-amino-2,4-dibromoanthraquinone in feed for 103 weeks.
T32 4921-5047 DRI_Background denotes In addition, groups of 50 male and 50 female rats were given 2,000 ppm 1-amino-2,4-dibromoanthraquinone in feed for 104 weeks.
T33 5048-5222 DRI_Background denotes These exposure concentrations were approximately equal to 90, 240, or 490 mg 1-amino-2,4-dibromoanthraquinone/kg body weight for males and 110, 285, or 600 mg/kg for females.
T34 5223-5297 DRI_Approach denotes Ten animals from each group were evaluated for histopathology at 9 months.
T35 5298-5410 DRI_Approach denotes Additional groups of 10 animals from the 0 and 10,000 ppm groups were evaluated for histopathology at 15 months.
T36 5411-5591 DRI_Background denotes Survival, Body Weights, Feed Consumption, and Clinical Findings In the 2-year study, survival of the 10,000 ppm males and females was significantly lower than that of the controls.
T37 5592-5671 DRI_Background denotes Survival of the 2,000 and 5,000 ppm groups was similar to that of the controls.
T38 5672-5888 DRI_Outcome denotes During the last year of the study, the mean body weights of exposed males were 80% to 91% those of controls, and the mean body weights of exposed females were 67% to 84% those of controls.
T39 5889-5985 DRI_Background denotes Feed consumption among exposed groups was generally similar, but was less than that by controls.
T40 5986-6058 DRI_Background denotes The fur and urine of all exposed male and female groups were discolored.
T41 6059-6323 DRI_Challenge denotes Pathology Findings In the 2-year study, 1-amino-2,4-dibromoanthraquinone was associated with significant chemical-related increases in the incidences of benign and malignant neoplasms in the liver, large intestine, kidney, and urinary bladder of males and females.
T42 6324-6340 REPLACED denotes Chemical-related
T43 6355-6479 DRI_Background denotes proliferative and degenerative lesions occurred in the liver, kidney, urinary bladder, and forestomach of males and females.
T44 6480-6696 DRI_Background denotes The incidences of foci of hepatocellular alteration and pigmentation in the liver of males and females were increased at the 9-month interim evaluation, and a hepatocellular adenoma was present in one 5,000 ppm male.
T45 6697-6844 DRI_Background denotes At the 15-month interim evaluation, hepatocellular adenoma or carcinoma (combined) occurred in all males and nine females in the 10,000 ppm groups.
T46 6845-7017 DRI_Background denotes By the end of the 2-year study, hepatocellular adenoma, carcinoma, cholangioma, or cholangiocarcinoma were observed in males and females in the 5,000 and 10,000 ppm groups.
T47 7018-7140 DRI_Outcome denotes In the 2,000 ppm groups, similar liver neoplasms were present in 63% of the males and in 83% of the females.
T48 7141-7300 DRI_Background denotes Of the hepatocellular carcinomas in the 5,000 and 10,000 ppm groups of males and females, 31% to 49% were metastatic to the lungs or other sites.
T49 7301-7497 DRI_Outcome denotes Increases in the incidences of foci of hepatocellular alteration (basophilic, eosinophilic, and clear cell) and pigmentation of the liver were also observed in exposed groups of males and females.
T50 7623-7872 DRI_Background denotes Incidences of adenomatous polyp (adenoma) and carcinoma of the large intestine were significantly increased in exposed groups of males and females after 2 years; multiple benign and malignant intestinal neoplasms were observed in many of these rats.
T51 7873-8019 DRI_Background denotes In the kidney, incidences of renal tubule adenoma and carcinoma were significantly increased in exposed groups of males and females after 2 years.
T52 8020-8092 DRI_Background denotes Renal tubule adenomas were present in two 10,000 ppm males at 15 months.
T53 8093-8292 DRI_Background denotes There were also chemical-related increases in the incidences and severities of renal tubule epithelial hyperplasia, pigmentation, and transitional cell hyperplasia in the kidney of males and females.
T54 8293-8371 DRI_Background denotes Hyaline droplet accumulation was present in all exposed male rats at 9 months.
T55 8372-8523 DRI_Background denotes Incidences of transitional cell papilloma and carcinoma of the urinary bladder were increased at 2 years in males and females in the 10,000 ppm groups.
T56 8524-8631 DRI_Background denotes Transitional cell hyperplasia was observed in exposed males and females at the 15-month interim evaluation.
T57 8632-8784 DRI_Background denotes Other nonneoplastic lesions observed in the urinary bladder at 2 years included metaplasia of the transitional epithelium and submucosal stromal tissue.
T58 8785-9039 DRI_Background denotes In the forestomach, the incidences and severities of inflammation, ulceration, hyperkeratosis, and hyperplasia of the squamous mucosa were increased in all exposed groups of males and females at 2 years, but not at the 9- or 15-month interim evaluations.
T59 9040-9143 DRI_Background denotes In exposed males and females, the incidences of mononuclear cell leukemia were significantly decreased.
T60 9144-9249 DRI_Outcome denotes The incidences of atrophy of the seminal vesicle were increased in exposed male rats in the 2-year study.
T61 9250-9402 DRI_Background denotes Stop-Exposure Evaluation in Rats Groups of 40 male and 40 female rats were given 20,000 ppm 1-amino-2,4-dibromoanthraquinone in feed for 9 or 15 months.
T62 9403-9510 DRI_Approach denotes At 9 months, 10 males and 10 females were evaluated for histopathology (9-month interim evaluation groups).
T63 9511-9824 DRI_Approach denotes After 9 months of exposure, an additional 10 males and 10 females were fed control diet until the end of the 15-month evaluation (9-month stop-exposure groups), and 20 males and 20 females continued to receive 20,000 ppm 1-amino-2,4-dibromoanthraquinone until the end of the evaluation (15-month exposure groups).
T64 9825-10071 DRI_Outcome denotes The approximate daily consumption of 1-amino-2,4-dibromoanthraquinone was 1,335 mg/kg for males and 1,790 mg/kg for females in the 9-month stop-exposure groups and 1,115 mg/kg for males and 1,435 mg/kg for females in the 15-month exposure groups.
T65 10072-10224 DRI_Approach denotes Survival was similar among groups except for the females in the 15-month exposure group; the survival of this group was lower than that of the controls.
T66 10225-10293 DRI_Background denotes Lower mean body weights were related to increased exposure duration.
T67 10294-10473 DRI_Background denotes The mean body weights of exposed males were 76% to 82% that of controls, and the mean body weights of exposed females were 73% to 84% that of controls.
T68 10474-10690 DRI_Background denotes For the stop-exposure evaluation, similar chemical-related neoplasms and nonneoplastic lesions were observed in the same sites as in the 2-year study: liver, large intestine, kidney, urinary bladder, and forestomach.
T69 10691-10860 DRI_Background denotes After 9 months of dietary exposure to a concentration of 20,000 ppm 1-amino-2,4-dibromoanthraquinone, hepatocellular adenoma and carcinoma occurred in males and females.
T70 10861-10874 REPLACED denotes Nonneoplastic
T71 10892-11011 DRI_Background denotes lesions in the liver of exposed rats included pigmentation, focal hepatocellular alteration, and bile duct hyperplasia.
T72 11012-11169 DRI_Background denotes Neoplasms at other sites in males included one adenomatous polyp (adenoma) in the large intestine and one transitional cell papilloma in the urinary bladder.
T73 11170-11254 DRI_Background denotes Hyaline droplet accumulation was present in the kidney of exposed males at 9 months.
T74 11255-11382 DRI_Background denotes In the stop-exposure groups examined at 15 months, hepatocellular adenoma and carcinoma were present in most males and females.
T75 11383-11549 DRI_Background denotes Adenomatous polyp (adenoma) of the colon, renal tubule cell adenoma, and urinary bladder transitional cell papilloma and carcinoma also occurred in males and females.
T76 11550-11563 REPLACED denotes Nonneoplastic
T77 11581-11736 DRI_Background denotes lesions included foci of hepatocellular alteration in the liver and hyperplasia of the renal tubule epithelium and urinary bladder transitional epithelium.
T78 11737-11892 DRI_Background denotes Hyperplasia, hyperkeratosis, inflammation, and ulceration were observed in the forestomach of some male and female rats continuously exposed for 15 months.
T79 11893-12043 DRI_Background denotes 2-YEAR STUDY IN MICE: Groups of 60 male and 60 female mice were given 0, 10,000, or 20,000 ppm 1-amino-2,4-dibromoanthraquinone in feed for 104 weeks.
T80 12044-12206 DRI_Outcome denotes The daily compound consumption was approximately 1,690 or 3,470 mg 1-amino-2,4-dibromoanthraquinone/kg body weight for males and 1,950 or 4,350 mg/kg for females.
T81 12207-12282 DRI_Approach denotes Ten animals from each group were evaluated for histopathology at 15 months.
T82 12283-12444 DRI_Background denotes Survival, Body Weights, Feed Consumption, and Clinical Findings In the 2-year study, survival of exposed males was significantly lower than that of the controls.
T83 12445-12509 DRI_Background denotes Survival of exposed females was similar to that of the controls.
T84 12510-12701 DRI_Outcome denotes The final mean body weights of exposed males were 83% to 85% that of controls, and the final mean body weights of exposed females were 81% to 86% that of controls.
T85 12702-12779 DRI_Background denotes Feed consumption by exposed groups was generally similar to that by controls.
T86 12780-12858 DRI_Background denotes Discoloration of the fur, urine, and feces was observed in all exposed groups.
T87 12859-13100 DRI_Challenge denotes Pathology Findings In the 2-year study, 1-amino-2,4-dibromoanthraquinone was associated with significant chemical-related increases in the incidences of benign and malignant neoplasms in the liver, forestomach, and lung of males and females.
T88 13101-13235 DRI_Background denotes Incidences of hepatocellular adenoma and carcinoma were increased in exposed groups at the 15-month interim evaluation and at 2 years.
T89 13236-13418 DRI_Background denotes At 2 years, there were significant increases in the incidences of multiple hepatocellular adenoma and carcinoma in males and females and in the incidences of hepatoblastoma in males.
T90 13419-13593 DRI_Background denotes Centrilobular hypertrophy of hepatocytes in males and foci of hepatocellular alteration and pigmentation in the liver of males and females were also chemical-related changes.
T91 13594-13882 DRI_Outcome denotes Sqamous cell papilloma of the forestomach mucosa occurred in 10,000 ppm females and 20,000 ppm males and females at the 15-month interim evaluation, and the incidences of squamous cell papilloma and carcinoma were significantly increased in exposed groups of males and females at 2 years.
T92 13883-13983 DRI_Background denotes Chemical-related hyperplasia of forestomach epithelium was also present at 15 months and at 2 years.
T93 13984-14209 DRI_Background denotes Alveolar/bronchiolar adenomas were present only in the exposed groups of males and females at 15 months, and the incidences of alveolar/bronchiolar adenoma were significantly increased in exposed males and females at 2 years.
T94 14210-14304 DRI_Outcome denotes The incidences of multiple alveolar/bronchiolar adenomas were also increased in exposed males.
T95 14305-14405 DRI_Background denotes In the kidney, pigmentation was present in the renal tubules of most mice after 2 years of exposure.
T96 14406-14481 DRI_Background denotes DISPOSITION AND METABOLISM STUDIES: Adult male F344/N rats were given [14C]
T97 14523-14637 DRI_Background denotes as a single intravenous dose of 0.4 mg/kg body weight or as a single oral dose of 2, 23, 118, 814, or 1,473 mg/kg.
T98 14638-14689 DRI_Background denotes A 6-hour bile cannulation study was also performed.
T99 14859-14872 REPLACED denotes Unmetabolized
T100 14906-14993 DRI_Approach denotes accounted for less than 3% of the excreted 14C after intravenous administration.
T101 14994-15114 DRI_Background denotes For oral doses administered, the amount of the dose that was absorbed fit the equation: absorbed dose = 6.6 x log(dose).
T102 15115-15292 DRI_Background denotes After intravenous administration, the metabolites of 1-amino-2,4-dibromoanthraquinone in blood were primarily in the plasma fraction (blood:plasma ratio of approximately 0.5:1).
T103 15293-15472 DRI_Background denotes The highest concentrations of 14C in tissues 15 minutes after intravenous dosing were in excretory organs, lung, kidney, small intestine, liver, adipose tissue, and adrenal gland.
T104 15473-15666 DRI_Approach denotes GENETIC TOXICOLOGY: 1-Amino-2,4-dibromoanthraquinone was mutagenic in Salmonella typhimurium strains TA98 and TA1537 in the absence of S9; with S9, an equivocal response was observed in TA1537.
T105 15667-15822 DRI_Outcome denotes 1-Amino-2,4-dibromoanthraquinone resulted in an equivocal response in TA100 with and without S9, and no mutagenic activity was detected with strain TA1535.
T106 15823-16011 DRI_Approach denotes In cultured Chinese hamster ovary cells, 1-amino-2,4-dibromoanthraquinone induced sister chromatid exchanges with and without S9; chromosomal aberrations were induced in the absence of S9.
T107 16012-16295 DRI_Background denotes CONCLUSIONS: Under the conditions of these 2-year feed studies, there was clear evidence of carcinogenic activity of 1-amino-2,4-dibromoanthraquinone in male and female F344/N rats based on increased incidences of neoplasms in the liver, large intestine, kidney, and urinary bladder.
T108 16296-16492 DRI_Background denotes There was clear evidence of carcinogenic activity of 1-amino-2,4-dibromoanthraquinone in male and female B6C3F1 mice based on increased incidences of neoplasms in the liver, forestomach, and lung.
T109 16493-17032 DRI_Background denotes Exposure of male and female rats to 1-amino-2,4-dibromoanthraquinone for 2 years was associated with basophilic focus (males only), clear cell focus, eosinophilic focus, and pigmentation in the liver; renal tubule hyperplasia, renal tubule pigmentation, and transitional cell hyperplasia in the kidney; transitional cell hyperplasia, squamous metaplasia, and stromal metaplasia (females only) in the urinary bladder; squamous hyperplasia, hyperkeratosis, ulceration, and inflammation of the forestomach mucosa; and seminal vesicle atrophy.
T110 17033-17419 DRI_Background denotes Exposure of male and female mice to 1-amino-2,4-dibromoanthraquinone for 2 years was associated with centrilobular hepatocellular hypertrophy (males only), basophilic focus, clear cell focus (females only), eosinophilic focus, and pigmentation in the liver; pigmentation in the kidney; and hyperplasia, basal cell hyperplasia, hyperkeratosis, and inflammation of the forestomach mucosa.