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Id Subject Object Predicate Lexical cue
T1 137-383 DRI_Background denotes Dibutyl phthalate is a phthalate ester with extensive use in industry in such products as plastic (PVC) piping, various varnishes and lacquers, safety glass, nail polishes, paper coatings, dental materials, pharmaceuticals, and plastic food wrap.
T2 384-632 DRI_Background denotes Concomitant with this extensive worldwide use is the high potential for human exposure to dibutyl phthalate in the workplace and the home environment through direct sources as well as indirectly, through contamination of water, air, and foodstuffs.
T3 633-828 DRI_Background denotes Because existing toxicity information was considered inadequate, the effects of exposure to dibutyl phthalate were examined in male and female F344/N rats and B6C3F1 mice in 13-week feed studies.
T4 829-1081 DRI_Background denotes Furthermore, due to concern over the potential for pervasive exposure of humans to dibutyl phthalate, additional perinatal studies examined rats and mice exposed as pups in utero, for the 4 weeks of lactation, and for an additional 4 weeks postweaning.
T5 1082-1183 DRI_Background denotes Additional studies examined the effects on rats of combining perinatal and adult subchronic exposure.
T6 1184-1401 DRI_Background denotes Due to the recognized biologic activity of this and other phthalates, hepatic peroxisome proliferation during the in utero and lactational phases and testicular toxicity during the perinatal period were also examined.
T7 1402-1568 DRI_Background denotes Finally, reproductive assessment by continuous breeding (including crossover mating trials and offspring assessment) and genetic toxicity studies were also conducted.
T8 1569-1855 DRI_Background denotes In the maximum perinatal exposure (MPE) determination study in rats, dibutyl phthalate was administered in the diet to dams during gestation and lactation, and to the pups postweaning for four additional weeks, at concentrations of 0, 1,250, 2,500, 5,000, 7,500, 10,000, and 20,000 ppm.
T9 1856-1988 DRI_Background denotes Decreased weight gains were noted in dams exposed to 20,000 ppm during gestation and to dams exposed to 10,000 ppm during lactation.
T10 1989-2261 DRI_Outcome denotes The gestation index (number of live pups per breeding female) was significantly lower in the 20,000 ppm group than in the controls, and pup mortality in this group was marked (100% by Day 1 of lactation); however, survival was 89% or greater in all other treatment groups.
T11 2262-2395 DRI_Outcome denotes The mean body weight of pups in the 10,000 ppm group at Day 28 of lactation was approximately 90% of the mean weight of control pups.
T12 2396-2492 DRI_Background denotes Pups were weaned onto diets containing dibutyl phthalate at the same concentrations fed to dams.
T13 2493-2686 DRI_Approach denotes After an additional 4 weeks of dietary administration, final mean body weights of pups in the 10,000 ppm groups were 92% of the control value for males and 95% of the control value for females.
T14 2687-2824 DRI_Background denotes Hepatomegaly (increased relative liver weight) was observed in males in all exposed groups and in females receiving 2,500 ppm or greater.
T15 2825-2868 DRI_Outcome denotes No gross lesions were observed at necropsy.
T16 2869-3064 DRI_Background denotes Moderate hypospermia of the epididymis was diagnosed in all male rats in the 7,500 and 10,000 ppm groups; mild hypospermia of the epididymis was diagnosed in 2 of 10 males in the 5,000 ppm group.
T17 3065-3149 DRI_Background denotes No degeneration of the germinal epithelium was detected in the testis of these rats.
T18 3150-3195 DRI_Background denotes Thus, although toxicologically important, the
T19 3219-3343 DRI_Background denotes was not considered to be life threatening, and 10,000 ppm was recommended as the MPE concentration for male and female rats.
T20 3344-3695 DRI_Background denotes In the subsequent subchronic toxicity study of dibutyl phthalate with perinatal exposure, dams were administered diets containing 0 or the MPE concentration (10,000 ppm) during gestation and lactation, and weaned pups were administered the same diets as their dams received for an additional 4 weeks, until the beginning of the 13-week exposure phase.
T21 3696-3848 DRI_Background denotes Male and female rats then received diets containing dibutyl phthalate at concentrations of 0, 2,500, 5,000, 10,000, 20,000, and 40,000 ppm for 13 weeks.
T22 3849-4066 DRI_Background denotes No mortality or toxicity was observed in dams during the perinatal phase of the study; however, before pups were culled at 4 days postpartum, the percentage of live pups per litter was 86% to 93% that of the controls.
T23 4067-4160 DRI_Background denotes Through weaning, litter weights of exposed pups ranged from 89% to 92% of the control values.
T24 4161-4454 DRI_Approach denotes Ten control and ten exposed pups per sex were examined at the time of trol and ten exposed pups per sex were examined at the time of weaning; hepatomegaly and markedly increased peroxisomal enzyme activities (approximately 9-fold greater than the control values) were observed in exposed pups.
T25 4455-4612 DRI_Approach denotes Body weights of the perinatally exposed pups remained lower than those of the controls throughout the 4-week period before the 13-week adult exposures began.
T26 4613-4810 DRI_Outcome denotes During the 13-week adult exposure phase, the final mean body weight of males in the MPE: 0 ppm control group (MPE rats, returned to the base diet for 13 weeks), was 95% that of the controls.
T27 4811-4975 DRI_Background denotes The body weight gain of females in the MPE:0 ppm group was greater than that of the unexposed controls, and the final body weights of these two groups were similar.
T28 4976-5289 DRI_Background denotes Body weight gains of rats treated with dibutyl phthalate as adults decreased with increasing exposure concentration; for rats that received the MPE concentration followed by 40,000 ppm for 13 weeks, final body weights were 51% of the control value for males and 74% of the control value for females.
T29 5290-5463 DRI_Background denotes Hepatomegaly apparently regressed in rats in the MPE:0 ppm groups but was observed in male rats receiving 5,000 ppm or greater and in females receiving 2,500 ppm or greater.
T30 5464-5650 DRI_Outcome denotes In males that received 20,000 ppm as adults, testis and epididymal weights were less than in the controls; males in the 40,000 ppm group also had a lower testis weight than the controls.
T31 5651-5867 DRI_Outcome denotes Results of hematologic analyses conducted at the end of the 13-week exposure period suggested a mild anemia in male rats administered 10,000 ppm or greater as adults and female rats administered 40,000 ppm as adults.
T32 5868-5988 DRI_Background denotes Hypocholesterolemia and hypotriglyceridemia were observed in male and female rats at the higher exposure concentrations.
T33 5989-6109 DRI_Background denotes Hypotriglyceridemia was detected in females receiving 20,000 or 40,000 ppm and in males receiving 10,000 ppm or greater.
T34 6110-6281 DRI_Background denotes Elevations in alkaline phosphatase activities and bile acid concentrations in male and female rats receiving 20,000 or 40,000 ppm as adults were indicative of cholestasis.
T35 6282-6465 DRI_Background denotes Microscopic examination revealed hepatocellular cytoplasmic alteration, consistent with glycogen depletion, in male and female rats receiving a concentration of 10,000 ppm or greater.
T36 6466-6595 DRI_Outcome denotes In the liver of rats receiving 40,000 ppm, small, fine, eosinophilic granules were also observed in the cytoplasm of hepatocytes.
T37 6596-6683 DRI_Background denotes Ultrastructural examination suggested the presence of increased numbers of peroxisomes.
T38 6684-6765 DRI_Background denotes Lipofuscin accumulation was detected in rats that received 10,000 ppm or greater.
T39 6766-6925 DRI_Outcome denotes Consistent with the regression of the hepatomegaly in rats in the MPE:0 and MPE:2,500 ppm groups, peroxisomal enzyme activity was not elevated in these groups.
T40 6926-7231 DRI_Approach denotes Marked elevations of peroxisomal enzyme activity were detected, however, in males receiving 5,000 ppm or greater and in females receiving 10,000 ppm or greater; at the 40,000 ppm concentration, the highest concentration tested, enzyme activities were approximately 20 fold greater than the control values.
T41 7232-7539 DRI_Outcome denotes Histopathologic examination of the testes revealed degeneration of the germinal epithelium, a mild to moderate focal lesion in rats in the 10,000 and 20,000 ppm groups and a marked, diffuse lesion in all males receiving 40,000 ppm; at 40,000 ppm, an almost complete loss of the germinal epithelium resulted.
T42 7540-7724 DRI_Approach denotes Testicular zinc concentrations were lower in the 40,000 ppm group than in the controls, a finding consistent with the marked loss of germinal epithelium at this exposure concentration.
T43 7725-7909 DRI_Approach denotes Spermatogenesis was evaluated in rats in the 0, 2,500, 10,000, and 20,000 ppm groups; rats administered 20,000 ppm had fewer spermatid heads per testis than the unexposed controls, and
T44 7934-7990 DRI_Approach denotes concentration was less than that in the MPE:0 ppm group.
T45 7991-8153 DRI_Outcome denotes For comparison with the perinatal subchronic study, a standard 13-week evaluation of the toxicity of dibutyl phthalate in male and female rats was also conducted.
T46 8154-8357 DRI_Background denotes In this study, rats received dibutyl phthalate at the same dietary concentrations used in the 13-week exposure phase of the study with perinatal exposure: 0, 2,500, 5,000, 10,000, 20,000, and 40,000 ppm.
T47 8358-8399 DRI_Approach denotes No deaths occurred in the standard study.
T48 8400-8715 DRI_Background denotes Markedly reduced final mean body weights were observed in males and females in the 40,000 ppm groups (45% and 73% of control body weights, respectively); final mean body weights of males receiving 10,000 ppm or greater and females receiving 20,000 ppm or greater were lower than those of the controls.
T49 8716-8837 DRI_Background denotes Hepatomegaly was observed in males that received 5,000 ppm or greater and in females that received 10,000 ppm or greater.
T50 8838-8951 DRI_Outcome denotes Testis and epididymal weights of males in the 20,000 and 40,000 ppm groups were lower than those of the controls.
T51 8952-9026 DRI_Background denotes A minimal anemia was detected in male rats receiving 5,000 ppm or greater.
T52 9027-9231 DRI_Background denotes Hypocholesterolemia was observed in male and female rats receiving 20,000 or 40,000 ppm, and hypotriglyceridemia was detected in males in all exposed groups and in females receiving 10,000 ppm or greater.
T53 9232-9370 DRI_Background denotes Elevations in alkaline phosphatase activity and bile acid concentration in male and female rats were considered indicative of cholestasis.
T54 9371-9476 DRI_Background denotes Morphologic evaluation again confirmed the toxicity of dibutyl phthalate to the liver and testes of rats.
T55 9477-9655 DRI_Background denotes Microscopic examination of the liver revealed hepatocellular cytoplasmic alterations, consistent with glycogen depletion, in male and female rats receiving 10,000 ppm or greater.
T56 9656-9789 DRI_Outcome denotes In the liver of rats in the 40,000 ppm groups, small, fine, eosinophilic granules were also observed in the cytoplasm of hepatocytes.
T57 9790-10166 DRI_Background denotes Ultrastructural examination suggested the presence of increased numbers of peroxisomes, and peroxisomal enzyme activity was elevated in the livers of male and female rats administered 5,000 ppm or greater; the enzyme activities in the 40,000 ppm groups were approximately 13-fold greater than the control value for males and 32-fold greater than the control value for females.
T58 10167-10244 DRI_Background denotes Lipofuscin accumulation was detected in rats receiving 10,000 ppm or greater.
T59 10245-10545 DRI_Outcome denotes Histopathologic examination of the testes revealed degeneration of the germinal epithelium, a mild to marked focal lesion in the 10,000 and 20,000 ppm groups and a marked, diffuse lesion in all males in the 40,000 ppm group; at 40,000 ppm, an almost complete loss of the germinal epithelium resulted.
T60 10546-10645 DRI_Background denotes Testicular zinc concentrations were lower in the 20,000 and 40,000 ppm groups than in the controls.
T61 10646-10733 DRI_Approach denotes Serum testosterone values were also lower at these concentrations than in the controls.
T62 10734-10883 DRI_Outcome denotes Spermatogenesis was evaluated in males in the 0, 2,500, 10,000, and 20,000 ppm groups; at 20,000 ppm, spermatid heads per testis and per gram testis,
T63 10908-11011 DRI_Outcome denotes motility, and the number of epididymal spermatozoa per gram epididymis were lower than in the controls.
T64 11012-11126 DRI_Outcome denotes All of these findings are consistent with the marked loss of germinal epithelium at these exposure concentrations.
T65 11127-11247 DRI_Background denotes In the continuous breeding study, Sprague-Dawley rats received 0, 1,000, 5,000, or 10,000 ppm dibutyl phthalate in feed.
T66 11248-11374 DRI_Background denotes Mean body weights of exposed dams at delivery and during lactation generally decreased with increasing exposure concentration.
T67 11375-11480 DRI_Outcome denotes The mean pup weight at birth in the 10,000 ppm group was significantly lower than the control pup weight.
T68 11481-11577 DRI_Approach denotes The average number of live pups per litter in all exposed groups was lower than in the controls.
T69 11578-11706 DRI_Outcome denotes Crossover mating trials in the F(0) generation revealed no effects on the fertility of male or female rats receiving 10,000 ppm.
T70 11707-11847 DRI_Approach denotes In contrast to the F(0) rats, mating, pregnancy, and fertility indices of F(1) rats were lower in the 10,000 ppm group than in the controls.
T71 11848-11997 DRI_Background denotes Germinal epithelial degeneration of the testes and absence or under development of the epididymides were noted in F(1) males in the 10,000 ppm group.
T72 11998-12079 DRI_Background denotes Interstitial cell hyperplasia was noted in 7 of 10 males in the 10,000 ppm group.
T73 12080-12277 DRI_Background denotes These effects document the male and female reproductive toxicity of dibutyl phthalate in F(1) rats receiving 10,000 ppm and do not exclude the possibility of developmental toxicity to F2 offspring.
T74 12278-12544 DRI_Background denotes In the MPE determination study in mice, dams received 0, 1,250, 2,500, 5,000, 7,500, 10,000, or 20,000 ppm dibutyl phthalate in feed during gestation and lactation; pups were weaned onto the same diets as the dams received and were exposed for an additional 4 weeks.
T75 12545-12737 DRI_Outcome denotes The gestation period was longer in dams that received 2,500 ppm or greater than in the controls, and gestational body weight gain depressions were noted in dams receiving 7,500 ppm or greater.
T76 12738-12872 DRI_Outcome denotes Only 5 of 20 females in the 10,000 ppm group delivered live pups, and none of the 20 females receiving 20,000 ppm delivered live pups.
T77 12873-13038 DRI_Outcome denotes Only one pup in the 10,000 ppm group survived past Lactation Day 1; the number of live pups per litter in the 7,500 ppm group also remained low throughout lactation.
T78 13039-13102 DRI_Background denotes No deaths of either male or female pups occurred after weaning.
T79 13103-13248 DRI_Background denotes Initial (postweaning) and final body weights of male pups receiving 2,500 ppm or greater were significantly less than those of the control group.
T80 13249-13401 DRI_Background denotes The mean body weights of exposed female pups were similar to the control body weight at weaning and remained similar throughout the 4 weeks postweaning.
T81 13402-13713 DRI_Background denotes Hepatomegaly was present in male mice in all exposed groups, and the absolute liver weight of males administered 7,500 ppm was greater than that of the controls; although a similar change was apparent in females, no statistical differences between the liver weights of exposed and control females were detected.
T82 13714-13909 DRI_Outcome denotes No treatment-related gross lesions were identified at necropsy, and no histopathologic lesions definitively associated with treatment were observed in male or female mice in the 7,500 ppm groups.
T83 13910-14043 DRI_Outcome denotes The one surviving male pup in the 10,000 ppm group had cytoplasmic alteration in the liver, consistent with peroxisome proliferation.
T84 14044-14148 DRI_Background denotes Developmental toxicity and fetal and pup mortality were suggested at concentrations as low as 7,500 ppm.
T85 14149-14296 DRI_Background denotes No subchronic toxicity study with prior MPE exposure was conducted with mice, although an MPE concentration of 5,000 ppm was suggested by the data.
T86 14297-14421 DRI_Background denotes In a standard 13-week toxicity study, mice received 0, 1,250, 2,500, 5,000, 10,000, or 20,000 ppm dibutyl phthalate in feed.
T87 14422-14459 DRI_Approach denotes No deaths occurred during this study.
T88 14460-14661 DRI_Background denotes Mean body weights and weight gains of male and female mice decreased with increasing exposure concentration, and the decreases were significant for males and females that received 5,000 ppm or greater.
T89 14662-14771 DRI_Background denotes Relative liver weights were greater in males and females receiving 5,000 ppm or greater than in the controls.
T90 14772-14842 DRI_Background denotes A minimal anemia was suggested in female mice in the 20,000 ppm group.
T91 14843-15086 DRI_Outcome denotes Although no gross lesions were observed at necropsy, microscopic examination revealed hepatocellular cytoplasmic alterations, consistent with glycogen depletion, in male mice receiving 10,000 or 20,000 ppm and female mice receiving 20,000 ppm.
T92 15087-15262 DRI_Outcome denotes Small, fine, eosinophilic granules, consistent with peroxisome proliferation, were also observed in the cytoplasm of hepatocytes in males and females in the 20,000 ppm groups.
T93 15263-15353 DRI_Background denotes Lipofuscin accumulation in the liver was detected in mice receiving 10,000 ppm or greater.
T94 15354-15487 DRI_Background denotes In a continuous breeding study using Swiss (CD-1®) mice, animals received 0, 300, 3,000, or 10,000 ppm dibutyl phthalate in feed.
T95 15488-15653 DRI_Outcome denotes The fertility index, average number of litters per breeding pair, and average number of live pups per litter in the 10,000 ppm group were lower than in the controls.
T96 15654-15854 DRI_Outcome denotes Crossover mating trials of mice receiving 10,000 ppm revealed effects on dams in the F(0) generation, with a lower fertility index, number of live pups per litter, and pup weight than in the controls.
T97 15855-15973 DRI_Background denotes Liver weights were greater in males and females, and the uterine weight was less in exposed dams than in the controls.
T98 15974-16051 DRI_Background denotes No other changes were observed at necropsy or on histopathologic examination.
T99 16052-16139 DRI_Background denotes These data document the female reproductive toxicity of dibutyl phthalate in F(0) mice.
T100 16140-16380 DRI_Background denotes Dibutyl phthalate was not mutagenic in Salmonella typhimurium strain TA98, TA100, TA1535, or TA1537 with or without exogenous metabolic activation but did induce mutations in L5178Y mouse lymphoma cells treated without metabolic activation.
T101 16381-16491 DRI_Background denotes In peripheral blood samples obtained from male and female mice at the end of the 13-week study, frequencies of
T102 16522-16581 DRI_Background denotes erythrocytes were similar between exposed and control mice.
T103 16582-16740 DRI_Background denotes Together, the studies in rodents suggest that young rodents (in utero and perinatal) respond in a manner qualitatively similar to that of adult rats and mice.
T104 16741-17076 DRI_Background denotes Dibutyl phthalate induced toxic effects in rodents as pups in utero and during the lactational phases of development and also affected young adults, as evidenced by fetotoxicity and lethality, body weight gain decrements, increased liver weights, hepatic peroxisome proliferation, testicular toxicity, and female reproductive toxicity.
T105 17077-17202 DRI_Background denotes Dibutyl phthalate was lethal to rat fetuses and rat and mouse neonates at dietary concentrations that were not toxic to dams.
T106 17203-17362 DRI_Outcome denotes Otherwise, there was no teratogenic or morphologic evidence that rodent young were uniquely sensitive to the effects of short-term dibutyl phthalate treatment.
T107 17363-17692 DRI_Background denotes Synonyms: 1,2-Benzenedicarboxylic acid dibutyl ester; benzene-o-dicarboxylic acid di-n-butyl ester; o-benzenedicarboxylic acid dibutyl ester; butyl phthalate; n-butyl phthalate; DBP; dibutyl 1,2-benzene dicarboxylate; dibutylphthalate; di-n-butylphthalate; di(n-butyl) phthalate; dibutyl-o-phthalate; phthalic acid dibutyl ester.
T108 17908-18178 DRI_Approach denotes (NOTE: These studies were supported in part by funds from the Comprehensive Environmental Response, Compensation, and Liability Act trust fund (Superfund) by an interagency agreement with the Agency for Toxic Substances and Disease Registry, U.S. Public Health Service.)