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PubMed_ArguminSci

Id Subject Object Predicate Lexical cue
T1 147-255 DRI_Approach denotes 4,4'-Thiobis(6- t -butyl- m -cresol) (TBBC) is used in the rubber and plastics industries as an antioxidant.
T2 256-356 DRI_Background denotes TBBC is also used as a stabilizer in polyethylene and polyolefin packaging materials for foodstuffs.
T3 357-543 DRI_Background denotes Toxicology and carcinogenesis studies were conducted by administering TBBC (99% pure) in feed to groups of male and female F344/N rats and B6C3F1 mice for 15 days, 13 weeks, and 2 years.
T4 544-653 DRI_Background denotes Genetic toxicology studies were conducted in Salmonella typhimurium and cultured Chinese hamster ovary cells.
T5 654-808 DRI_Background denotes 15-DAY STUDY IN RATS: Groups of 10 male and 10 female F344/N rats were fed diets containing 0, 1,000, 2,500, 5,000, 10,000 or 25,000 ppm TBBC for 15 days.
T6 809-1006 DRI_Outcome denotes Rats given to 1,000, 2,500, 5,000, or 10,000 ppm received approximate doses of 95, 235, 335, or 365 mg TBBC per kilogram body weight per day (males) or 85, 220, 325, or 270 mg/kg per day (females).
T7 1007-1099 DRI_Outcome denotes Approximate doses for rats receiving 25,000 ppm could not be calculated due to early deaths.
T8 1100-1172 DRI_Approach denotes All 25,000 ppm rats and three male and four female 10,000 ppm rats died.
T9 1173-1372 DRI_Background denotes Surviving rats in the 10,000 ppm groups had a significant weight loss and the final mean body weights of 5,000 and 10,000 ppm male and female rats were significantly lower than those of the controls.
T10 1373-1485 DRI_Background denotes Male and female rats exposed to 5,000, 10,000, or 25,000 ppm TBBC consumed markedly less feed than the controls.
T11 1486-1555 DRI_Background denotes Diarrhea occurred in 5,000, 10,000, and 25,000 ppm males and females.
T12 1556-1694 DRI_Background denotes The principal lesions attributed to the administration of TBBC were renal papillary and tubule necroses which occurred in 10,000 ppm rats.
T13 1695-1785 DRI_Background denotes Focal necrosis or erosions of the glandular stomach also occurred in some 10,000 ppm rats.
T14 1786-1956 DRI_Background denotes Changes observed in the thymus and spleen were attributed to debilitation or stress; bone marrow depletion was attributed to nutrient deficiency accompanying weight loss.
T15 1957-2113 DRI_Background denotes 15-DAY STUDY IN MICE: Groups of 10 male and 10 female B6C3F1, mice were fed diets containing 0, 1,000, 2,500, 5,000, 10,000, or 25,000 ppm TBBC for 15 days.
T16 2114-2294 DRI_Background denotes Mice given 1,000, 2,500, or 5,000 ppm received approximate doses of 285, 585, or 475 mg TBBC per kilogram body weight per day (males) or 360, 950, or 1,030 mg/kg per day (females).
T17 2295-2393 DRI_Background denotes Approximate doses for mice given 10,000 or 25,000 ppm could not be calculated due to early deaths.
T18 2394-2484 DRI_Outcome denotes All 10,000 and 25,000 ppm mice died, as did eight males and eight females given 5,000 ppm.
T19 2485-2698 DRI_Background denotes A significant weight loss occurred in surviving 5,000 ppm males and females and the final mean body weights of 2,500 ppm females and 5,000 ppm males and females were significantly lower than those of the controls.
T20 2699-2780 DRI_Background denotes Feed consumption by mice given 5,000, 10,000, or 25,000 ppm was markedly reduced.
T21 2781-2881 DRI_Background denotes Diarrhea occurred in all 25,000 ppm mice and in most male and female mice given 5,000 or 10,000 ppm.
T22 2882-2970 DRI_Background denotes Renal tubule necrosis occurred in eight males and three females in the 5,000 ppm groups.
T23 2971-3142 DRI_Background denotes Lymphocytic depletion of Iymphoid tissues in many 5,000 ppm males and females was attributed to debilitation and stress or to nutrient deficiency accompanying weight loss.
T24 3143-3294 DRI_Background denotes 13-WEEK STUDY IN RATS: Groups of 10 male and 10 female F344/N rats were fed diets containing 0, 250, 500, 1,000, 2,500, or 5,000 ppm TBBC for 13 weeks.
T25 3295-3472 DRI_Background denotes These exposure levels delivered approximate doses of 15, 30, 60, 165, or 315 mg TBBC per kilogram body weight per day (males) or 15, 35, 70, 170, or 325 mg/kg per day (females).
T26 3473-3515 DRI_Approach denotes All rats survived to the end of the study.
T27 3516-3691 DRI_Outcome denotes The final mean body weight of 5,000 ppm males was 40% lower than that of the controls; the final mean body weight of 5,000 ppm females was 27% lower than that of the controls.
T28 3692-3825 DRI_Background denotes Feed consumption by male and female rats exposed to 5,000 ppm TBBC was markedly lower than that by the controls throughout the study.
T29 3826-3941 DRI_Background denotes The absolute and relative liver weights of 5,000 ppm females were significantly greater than those of the controls.
T30 3942-4078 DRI_Background denotes Serum alkaline phosphatase (ALP) levels were significantly higher in 2,500 and 5,000 ppm males and slightly higher in 5,000 ppm females.
T31 4079-4184 DRI_Background denotes Serum alanine aminotransferase levels were significantly higher in 2,500 and 5,000 ppm males and females.
T32 4185-4430 DRI_Approach denotes Hematocrit and hemoglobin concentrations and mean erythroions and mean erythrocyte volume (MCV) values were significantly lower in 1,000, 2,500, and 5,000 ppm males than in controls; MCV values were also significantly lower in 5,000 ppm females.
T33 4431-4551 DRI_Background denotes A dose-related significant increase in forelimb and hindlimb grip strength was observed in exposed male and female rats.
T34 4552-4836 DRI_Background denotes Histopathologic findings in the liver of 2,500 and 5,000 ppm males and females included hypertrophy of Kupffer cells, bile duct hyperplasia, and individual cell necrosis of hepatocytes; centrilobular hepatocyte hypertrophy also occurred in males and females exposed to 5,000 ppm TBBC.
T35 4837-5013 DRI_Outcome denotes Macrophages were increased in size and number in the mesenteric Iymph nodes of males and females exposed to 5,000 ppm, and to a lesser extent in 2,500 ppm male and female rats.
T36 5014-5228 DRI_Background denotes Pigmentation and degeneration of the renal cortical tubule epithelial cells was also present in males and females in the 2,500 and 5,000 ppm groups; cortical tubule necrosis occurred in 5,000 ppm males and females.
T37 5229-5384 DRI_Background denotes 13-WEEK STUDY IN MICE: Groups of up to 10 male and 10 female B6C3F1 mice were fed diets containing 0, 100, 250, 500, 1,000, or 2,500 ppm TBBC for 13 weeks.
T38 5385-5562 DRI_Background denotes These exposure levels delivered approximate doses of 15, 30, 65, 145, or 345 mg TBBC per kilogram body weight per day (males) or 10, 35, 60, 165, or 340 mg/kg per day (females).
T39 5563-5605 DRI_Approach denotes All mice survived to the end of the study.
T40 5606-5744 DRI_Outcome denotes The final mean body weights of 2,500 ppm males and of 500,1,000, or 2,500 ppm females were significantly lower than those of the controls.
T41 5745-5911 DRI_Approach denotes Feed consumption by 2,500 ppm males averaged 24% lower than that by controls through week 3 and was similar to that by controls for the remainder of the study.
T42 5912-6036 DRI_Approach denotes Feed consumption by females receiving 2,500 ppm averaged 27% less than that by the controls during most of the study.
T43 6037-6191 DRI_Background denotes The absolute and relative liver weights of males and females exposed to 2,500 ppm TBBC were slightly but significantly greater than those of the controls.
T44 6192-6332 DRI_Approach denotes Males exposed to 500, 1,000, or 2,500 ppm and females exposed to 2,500 ppm had significantly increased absolute and relative spleen weights.
T45 6333-6395 DRI_Background denotes No clinical findings in mice were considered chemical related.
T46 6396-6692 DRI_Outcome denotes Hematocrit concentrations and erythrocyte counts of males receiving 1,000 or 2,500 ppm were significantly less than those of the controls; hemoglobin concentration in males receiving 2,500 ppm was significantly less and mean erythrocyte volume was significantly less in males receiving 2,500 ppm.
T47 6693-6919 DRI_Outcome denotes Females in the 1,000 and 2,500 ppm groups had significantly decreased hematocrit concentrations and erythrocyte counts; 2,500 ppm females also had significantly decreased hemoglobin concentrations and mean erythrocyte volumes.
T48 6920-7092 DRI_Background denotes Kupffer cell hypertrophy, bile duct hyperplasia, and an increase in size and number of macrophages in mesenteric Iymph nodes were present in 2,500 ppm male and female mice.
T49 7093-7269 DRI_Approach denotes 2-YEAR STUDY IN RATS: Doses selected for the 2-year study of TBBC were based on the lower body weights and liver and kidney toxicity observed at 5,000 ppm in the 13-week study.
T50 7270-7386 DRI_Background denotes Groups of 115 male and 75 female F344/N rats were fed diets containing 0, 500, 1,000, or 2,500 ppm TBBC for 2 years.
T51 7387-7597 DRI_Outcome denotes Based on average daily feed consumption, these exposure levels resulted in a daily ingestion of TBBC of approximately 20, 40, or 100 mg/kg body weight for males and 20, 45, or 120 mg/kg body weight for females.
T52 7598-7741 DRI_Background denotes Hematology, clinical chemistry, and urinalysis evaluations were performed on 15 male and 15 female rats from each group at 3, 9, and 15 months.
T53 7742-7888 DRI_Background denotes Also at 15 months, an additional 10 male and 10 female rats from each group were evaluated for histopathology, hematology, and clinical chemistry.
T54 7889-7953 DRI_Background denotes Forty male rats per group were evaluated for neurotoxic effects.
T55 7954-8145 DRI_Background denotes Survival, Body Weights, Feed Consumption, and Clinical Findings: Two-year survival rates and mean body weights of exposed male and female rats were generally similar to those of the controls.
T56 8146-8259 DRI_Approach denotes The mean body weights of 2,500 ppm male rats were slightly lower than those of the controls throughout the study.
T57 8260-8458 DRI_Outcome denotes At week 65, the mean body weight of 2,500 ppm females was 14% lower than that of the controls, but the final mean body weight of this group was 6% lower than that of the control group.
T58 8459-8591 DRI_Background denotes Feed consumption, behavior, and general health and appearance of exposed male and female rats were similar to those of the controls.
T59 8592-8814 DRI_Approach denotes Hematology and Clinical Chemistry: Results of the hematology evaluation were not uniformly consistent at 3, 9, and 15 months in one set of rats, nor were they consistent between the two sets of rats evaluated at 15 months.
T60 8815-9001 DRI_Background denotes Slight but significant decreases in hematocrit levels, hemoglobin concentrations, and erythrocyte counts were observed in the 1,000 and 2,500 ppm groups in one set of males at 15 months.
T61 9002-9123 DRI_Background denotes Similar significant decreases in hematocrit level and hemoglobin concentration occurred in 2,500 ppm females at 9 months.
T62 9124-9339 DRI_Approach denotes Mean erythrocyte hemoglobin and mean erythrocyte hemoglobin concentration of 2,500 ppm females were also significantly lower than those of controls at 9 months and in both sets of female rats evaluated at 15 months.
T63 9340-9470 DRI_Background denotes Platelet counts of 2,500 ppm male and female rats were slightly but significantly higher than those of controls at 3 and 9 months.
T64 9471-9654 DRI_Outcome denotes Platelet counts were also slightly but significantly increased in 2,500 ppm males of one set evaluated at 15 months, and in 2,500 ppm females of the second set evaluated at 15 months.
T65 9655-9846 DRI_Background denotes Serum activities of alkaline phosphatase, alanine aminotransferase, and sorbitol dehydrogenase in 2,500 ppm males were significantly greater than those in the controls at 3, 9, and 15 months.
T66 9847-9989 DRI_Outcome denotes Alkaline phosphatase activities in both sets of 1,000 ppm males evaluated at 15 months were also significantly greater than those of controls.
T67 9990-10161 DRI_Background denotes Serum activities of alanine aminotransferase and sorbitol dehydrogenase in 2,500 ppm females were also significantly greater than those in controls at 3, 9, and 15 months.
T68 10162-10334 DRI_Background denotes Neurotoxicity Findings: There were no significant inhibitory effects of TBBC on motor nerve excitability or conduction, neuromuscular transmission, or muscle contractility.
T69 10335-10504 DRI_Challenge denotes There were no microscopic lesions in the sciatic nerve, quadriceps muscle, or teased nerve preparations of sciatic nerve that could be attributed to TBBC administration.
T70 10505-10855 DRI_Outcome denotes Pathology Findings: At the 15-month interim evaluation, the absolute and relative liver weights of 2,500 ppm female rats were significantly greater than those of controls; at 15 months and at the end of the study, the incidences of Kupffer cell hypertrophy, hepatocyte cytoplasmic vacuolization, and mixed cell foci were also significantly increased.
T71 10856-10975 DRI_Outcome denotes At the end of the study, the incidence of hepatocellular fatty change was significantly increased in 2,500 ppm females.
T72 10976-11472 DRI_Outcome denotes The incidence of Kupffer cell hypertrophy was significantly increased in 2,500 ppm males at 15 months and at 2 years; the incidence of cytoplasmic vacuolization was significantly increased in all exposed males at 15 months but only moderately increased in 1,000 and 2,500 ppm males at 2 years; the incidence of basophilic foci was significantly increased in 2,500 ppm males at 15 months and the incidence of mixed cell foci was significantly increased in 1,000 and 2,500 ppm male rats at 2 years.
T73 11473-11763 DRI_Background denotes The incidences of hepatocellular adenoma or carcinoma (combined) in exposed male rats were not significantly greater than that in the controls (0 ppm, 1/50; 500 ppm, 3/50; 1,000 ppm, 3/50; 2,500 ppm, 5/49), were within the historical control range, and were not considered chemical related.
T74 11764-11845 DRI_Outcome denotes The severity of nephropathy was significantly increased in 2,500 ppm female rats.
T75 11846-12127 DRI_Outcome denotes There was a significant negative trend in the incidence of mammary gland fibroadenoma, adenoma, or carcinoma (combined) in female rats (32/50, 24/50, 11/50, 16/50), and the incidences of fibroadenoma in 1,000 and 2,500 ppm females were significantly less than that of the controls.
T76 12128-12417 DRI_Background denotes 2-YEAR STUDY IN MICE: Because of the reduction in body weights, the increase in liver and spleen weights, and the accompanying histopathologic changes in the liver of 2,500 ppm male and female mice in the 13-week study, the doses selected for the 2-year study were 250, 500, and 1,000 ppm.
T77 12418-12524 DRI_Background denotes Groups of 80 male and 80 female mice were fed diets containing 0, 250, 500, or 1,000 ppm TBBC for 2 years.
T78 12525-12740 DRI_Outcome denotes Based on average daily feed consumption, these exposure levels resulted in the daily ingestion of approximately 30, 60, or 145 mg TBBC/kg body weight for males and 45, 110, or 255 mg TBBC/kg body weight for females.
T79 12741-12823 DRI_Background denotes Nine or 10 animals from each exposure group were evaluated at 3, 9, and 15 months.
T80 12824-12983 DRI_Background denotes Survival, Body Weights, Feed Consumption, and Clinical Findings: Two-year survival rates of exposed male and female mice were similar to those of the controls.
T81 12984-13134 DRI_Background denotes The final mean body weights of male and female mice exposed to 1,000 ppm were 8% and 18% lower than those of the controls, respectively.
T82 13135-13260 DRI_Approach denotes The final mean body weights of females exposed to 250 or 500 ppm were 8% to 9% lower than that of the controls.
T83 13261-13398 DRI_Background denotes Feed consumption by exposed males was similar to that by controls, and there were no clinical findings attributed to TBBC administration.
T84 13399-13606 DRI_Background denotes Hematology and Clinical Chemistry: Hematocrit level, hemoglobin concentration, and erythrocyte count in 1,000 ppm male mice were significantly lower than those in controls at the 15-month interim evaluation.
T85 13607-13826 DRI_Outcome denotes Serum alkaline phosphatase activities in 1,000 ppm males were slightly but significantly greater than those in controls at 3 and 9 months, as was the serum alkaline phosphatase activity in 1,000 ppm females at 9 months.
T86 13827-13959 DRI_Background denotes Serum levels of total bilirubin in all exposed groups of males were significantly greater than those in controls at 9 and 15 months.
T87 13960-14149 DRI_Background denotes Pathology Findings: In the liver of male mice, negative trends in the incidences of fatty change, clear cell foci, and adenoma or carcinoma combined occurred at the end of the 2-year study.
T88 14150-14275 DRI_Background denotes There were no compound-related increased incidences of neoplasms or nonneoplastic lesions in mice receiving TBBC for 2 years.
T89 14276-14379 DRI_Outcome denotes A negative trend in the incidence of fatty change in the liver of male mice also occurred at 15 months.
T90 14380-14572 DRI_Approach denotes GENETIC TOXICOLOGY: 4,4'-Thiobis(6- t -butyl- m -cresol) was not mutagenic in Salmonella typhimurium strains TA98, TA100, TA1535, or TA1537 with or without exogenous metabolic activation (S9).
T91 14573-14814 DRI_Background denotes Sister chromatid exchanges were induced in cultured Chinese hamster ovary cells treated with TBBC, with and without S9, but no increases in chromosomal aberrations were noted in cultured Chinese hamster ovary cells after treatment with TBBC.
T92 14815-15104 DRI_Background denotes CONCLUSIONS: Under the conditions of these 2-year feed studies, there was no evidence of carcinogenic activity of 4,4'-thiobis(6- t -butyl- m -cresol) in male or female F344/N rats administered 500, 1,000, or 2,500 ppm or in male or female B6C3F1, mice administered 250, 500, or 1,000 ppm.
T93 15105-15400 DRI_Background denotes Nonneoplastic lesions associated with exposure to TBBC included: Kupffer cell hypertrophy, cytoplasmic vacuolization, and mixed cell foci in the liver of male and female rats, fatty change in the liver of female, rats, and an increase in the severity of nephropathy in the kidney of female rats.
T94 15401-15535 DRI_Background denotes In addition, decreased incidences of fibroadenoma, adenoma, or carcinoma (combined) were observed in the mammary gland of female rats.
T95 15536-15674 DRI_Outcome denotes Decreases also occurred in the incidences of fatty change, clear cell foci, and adenoma or carcinoma (combined) in the liver of male mice.