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Query: UMLS:C0002871 (anemia)
 52,094 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Toxicity of environmental pollutants may be expressed as combined effects of a chemicals. Benzene, a proven hematotoxic agent, frequently occurs with toluene in cocontaminated groundwater. Groups of CD-1 male mice were exposed continuously for 4 weeks to benzene (166 mg/l), toluene (80 and 325 mg/l), and combinations of benzene (166 mg/l) + toluene (80 mg/l or 325 mg/l) in drinking water. Benzene-induced anemia was alleviated by simultaneous toluene treatment. Leukopenia and lymphopenia were observed in the case of benzene only and benzene + toluene (80 mg/l)-treated mice. The cytopenia, however, was less severe in the benzene + toluene (325 mg/l)-treated group. Immunotoxicity induced by benzene treatment alone was characterized by involution of thymic mass and suppressions of both B- and T-cell mitogeneses, mixed lymphocyte culture response to alloantigens, the tumor lytic ability of cytotoxic T-lymphocytes as determined by 51Cr-release assay, and antibody production response to T-dependent antigen (sheep red blood cells). IL-2 secretion by Con A-stimulated mouse T-cells was decreased in the benzene-treated group. Toluene (325 mg/l) completely inhibited these adverse effects when it was coadministered with benzene, while the low dose of toluene (80 mg/l) did not protect against benzene-induced depressions of immune functions. Toluene administered alone at levels up to 325 mg/l showed no obvious immunotoxic effects. Results of this study demonstrated that toluene, in sufficient amounts, has an antagonistic effect on benzene immunotoxicity.
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PMID:Subclinical effects of groundwater contaminants. III. Effects of repeated oral exposure to combinations of benzene and toluene on immunologic responses in mice. 214 47

Benzene is one of the world's major commodity chemicals. It is derived from petroleum and coal and is used both as a solvent and as a starting material in chemical syntheses. The numerous industrial uses of benzene over the last century need not be recounted here, but the most recent addition to the list of uses of benzene is as a component in a mixture of aromatic compounds added to gasoline for the purpose of replacing lead compounds as anti-knock ingredients. The best known and longest recognized toxic effect of benzene is the depression of bone marrow function seen in occupationally exposed individuals. These people have been found to display anemia, leucopenia, and/or thrombocytopenia. When pancytopenia, i.e., the simultaneous depression of all three cell types, occurs and is accompanied by bone marrow necrosis, the syndrome is called aplastic anemia. In addition to observing this decrease in humans and relating it to benzene exposure, it has been possible to establish animal models which mimic the human disease. The result has been considerable scientific investigation into the mechanism of benzene toxicity. Although the association between benzene exposure and aplastic anemia has been recognized and accepted throughout most of this century, it is only recently that leukemia, particularly of the acute myelogenous type, has been related to benzene. The acceptance of benzene as an etiological agent in aplastic anemia in large measure derives from our ability to reproduce the disease in most animals treated with sufficiently high doses of benzene over the necessary time period. Unfortunately, despite extensive efforts in several laboratories, it has not been possible to establish a reproducible, reliable model for the study of benzene-induced leukemia. The recent demonstration that several animals exposed to benzene either by inhalation or in the drinking water during studies by Drs. B. Goldstein and C. Maltoni suggests that such a model may be forthcoming. Nevertheless, at this time it is not clear whether bone marrow damage of the type that leads to aplastic anemia is required for the development of leukemia. Most studies of benzene toxicity have involved dosing animals with benzene either by inhalation or by injection, using high doses to ensure a toxic response. Very few studies have concentrated on the oral route of administration and none have concentrated on administering benzene by mouth at the low doses occasionally detected in drinking water.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Chemical of current interest--benzene. 359 Feb 6

Benzene is ubiquitous and accepted as a human carcinogen by regulatory agencies. Proposed regulations assume without proof that the carcinogenic response to benzene exposure is "one hit" implying a linear with no threshold. There is no solid experimental proof for this concept. This research involves exposure of CBA/Ca male mice to benzene vapor in varying concentrations. Exposure to 300 ppm 6 hrs/day, 5 days/week, for 16 weeks is highly leukemogenic. Exposure for the same time to 100 ppm is also leukemogenic. Concentrations from 25 ppm to 400 ppm 6 hrs/day, 5 days/week, for 10 exposures produce an increasing lymphopenia. Exposure to 100 ppm for the same exposure time produces anemia, decrease in stem cell content of marrow, and marrow cellularity. Further dose-effect studies are required to test the "one hit hypothesis" and to determine whether the same integral dose of benzene administered over variable exposure has the same or different biological responses. It is of concern that biologic effects are observed at 25 ppm only 2.5 times the present permissible time-weighted average exposure during a working day and research by others (see Discussion) has demonstrated an effect (noncarcinogenic) at 10 ppm.
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PMID:Benzene hematotoxicity and leukemogenesis. 379 Jul 32

Benzene, an important industrial solvent, is also present in unleaded gasoline and cigarette smoke. The hematotoxic effects of benzene are well documented and include aplastic anemia and pancytopenia. Some individuals exposed repeatedly to cytotoxic concentrations of benzene develop acute myeloblastic anemia. It has been hypothesized that metabolism of benzene is required for its toxicity, although administration of no single benzene metabolite duplicates the toxicity of benzene. Several investigators have demonstrated that a combination of metabolites (hydroquinone and phenol, for example) is necessary to duplicate the hematotoxic effect of benzene. Enzymes implicated in the metabolic activation of benzene and its metabolites include the cytochrome P450 monooxygenases and myeloperoxidase. Since benzene and its hydroxylated metabolites (phenol, hydroquinone, and catechol) are substrates for the same cytochrome P450 enzymes, competitive interactions among the metabolites are possible. In vivo data on metabolite formation by mice exposed to various benzene concentrations are consistent with competitive inhibition of phenol oxidation by benzene. Other organic molecules that are substrates for cytochrome P450 can inhibit the metabolism of benzene. For example, toluene has been shown to inhibit the oxidation of benzene in a noncompetitive manner. Enzyme inducers, such as ethanol, can alter the target tissue dosimetry of benzene metabolites by inducing enzymes responsible for oxidation reactions involved in benzene metabolism. The dosimetry of benzene and its metabolites in the target tissue, bone marrow, depends on the balance of activation processes, such as enzymatic oxidation, and deactivation processes, like conjugation and excretion.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Critical issues in benzene toxicity and metabolism: the effect of interactions with other organic chemicals on risk assessment. 769 73

BDF1 mice were exposed in inhalation chambers to benzene (900 ppm, 300 ppm) and/or toluene (500 ppm, 250 ppm) 6 hr per day, 5 days per week, for up to 8 weeks. Benzene alone induced a slight anemia after 4 and 8 weeks and a reduction of BFU-E and CFU-E numbers in the marrow. The coexposure to toluene reduced the degree of anemia. These results confirm previous studies where toluene was found to reduce benzene toxicity. This protective effect was most pronounced when DNA damage was studied in peripheral blood cells, bone marrow, and liver using the single cell gel (SCG) assay. With benzene alone, either with 300 or 900 ppm, a significant increase in DNA damage was detected in cells sampled from all three organs. Toluene alone did not induce a significant increase in DNA damage. The coexposure of benzene and toluene reduced the extent of DNA damage to about 50% of benzene alone. This result is considered a clear indication for a protective effect of toluene on the genetic toxicity of benzene.
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PMID:Reduction of benzene toxicity by toluene. 785 40

A literature review of the impact on human health of exposure to benzene was conducted. Special emphasis in this report is given to the health effects reported in excess of national norms by participants in the Benzene Subregistry of the National Exposure Registry--people having documented exposure to benzene through the use of benzene-contaminated water for domestic purposes. The health effects reported in excess (p < or = .01) by some or all of the sex and age groups studied were diabetes, kidney disease, respiratory allergies, skin rashes, and urinary tract disorders; anemia was also increased for females, but not significantly so.
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PMID:Benzene--a review of the literature from a health effects perspective. 939 16

The purpose of the National Exposure Registry is to assess the long-term health consequences to a general population from long-term, low-level exposures to specific substances in the environment. This study investigates the health outcomes of 1,143 persons (1,127 living, 16 deceased) living in south central Texas who had documented environmental exposure to benzene (up to 66ppb) in tap water. As with all subregistries, face-to-face interviews were used to collect self-reported information for 25 general health status questions. Using computer-assisted telephone interviewing, the same health questions were asked 1 year (Followup 1, F1) and 2 years later (Followup 2, F2). The health outcome rates for Baseline and Followup 1 and 2 data collections for the Benzene Subregistry were compared with national norms, that is, the National Health Interview Survey (NHIS) rates. For at least one of the three reporting periods, specific age and sex groups of the Benzene Subregistry population reported more adverse health outcomes when compared with the NHIS population, including anemia and other blood disorders, ulcers, gall bladder trouble, and stomach or intestinal problems, stroke, urinary tract disorders, skin rashes, diabetes, kidney disease, and respiratory allergies. Statistically significant deficits for the Benzene Subregistry population overall were found for asthma, emphysema, or chronic bronchitis; arthritis, rheumatism, or other joint disorders; hearing impairment; and speech impairment. No statistically significant differences between the two populations were seen for the outcomes hypertension; liver disease; mental retardation; or cancer. These results do not identify a causal relationship between benzene exposure and adverse health effects; however, they do reinforce the need for continued followup of registrants.
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PMID:The National Exposure Registry: analyses of health outcomes from the benzene subregistry. 956 45

The present paper depicts salient features of environment and living conditions with the comparison of various diseases prevalent among underground coal miners, surface workers, asbestos mine workers and general population of Jharia-Dhanbad coalfield as conducted by CMRS during the past few years. The investigations on coal miners' community comprise of different morbid conditions with respiratory (22%), Pneumoconiosis (11.6%), Skin (35%), Eye (29%), Intestinal parasitic infestation (44.6%), Anaemia (42%), Immunostatus (V.D.R.L. Positive-19.9%), Status of injuries and Blood pressure, Water-borne diseases, housing facilities and excreta disposal. The paper also includes the analysis of disease pattern obtained from hospital records of two coal mines which depicts 19.1%, 24.7% and 16% members of coal miners' families suffering from disorder with respiratory, gastro-intestinal and fever respectively. With speedy industrialization of the country, the mining of coal resource comes first in the chain of socio-economic development. The speedy human industrial activities are based on 80% steam, metallurgical and thermal electrical energy which hinges on coal wings. The coal has also gradually occupied all the phases of social life, our clothes, books, newspapers, cooking gas, chemical paints, dye stuff, oil phenyl, Benzene, Naphthalene, Coal tar, scents and various types of unaccountable products come out from coal derivatives and pushed to serve in the today's market for our daily exigencies. Every day one finds a new coal based industry is coming up in the area. The coal is utilized in two hundred ways in our various walks of social life.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Health care challenge in coal mines community. 1013 Sep 26

p-Chloro-alpha,alpha,alpha trifluorotoluene (CTFT) is a volatile, aromatic liquid used as a chemical intermediate in the manufacture of dinitroaniline herbicides. To evaluate the toxicity of CTFT, groups of F344/N rats and B6C3F1 mice of each sex were administered CTFT by gavage once a day for 14 consecutive days in either corn oil or in an experimental molecular complex vehicle, a-cyclodextrin (alpha-CD). Dose levels selected for CTFT with the alpha-CD vehicle were 10, 50, and 400 mg/kg; dose levels used with the corn oil vehicle were 10, 50, 400, and 1000 mg/kg. The toxicokinetics of CTFT also were compared by gavage with the different vehicles and by i.v. administration. In genetic toxicity studies, CTFT was not mutagenic in Salmonella typhimurium. The elimination of an intravenous dose of CTFT from blood is best described by a triexponential equation. The data best fit a 3-compartment kinetic model with a very rapid distribution phase. A biexponential equation was found to best fit the elimination of CTFT from blood following a gavage dose in either corn oil or an aqueous molecular complex suspension, alpha-CD. However, the biological half-life (t 1/2) was the same in both routes, approximately 20 hours. Absorption of CTFT from the alpha-CD vehicle was found to be much faster than from corn oil. The average t 1/2 of the absorption phase for a 10 mg/kg dose of CTFT in the alpha-CD and corn oil vehicles was 7 and 150 minutes, respectively. Despite the differences in absorption, no statistical difference was observed in the calculated area under blood concentration versus time curves (AUC) obtained from rats dosed with CTFT in either vehicle. Blood concentrations of CTFT were proportional to dose, at levels as high as 400 mg/kg in both vehicles. The bioavailability of CTFT was shown to be complete in both vehicles, through comparing the AUC following oral and i.v. dosing. In 14-day toxicity studies, 1 of 10 female rats given the top dose of 1000 mg/kg CTFT in corn oil died on day 8; no deaths of male rats or of mice of either sex were attributable to the administration of CTFT. Body weight gains in all groups of rats and mice were similar with the exception of the top dose (1000 mg/kg) groups of male and female rats, which lost weight during the first week and resumed weight gain during the second. CTFT was found to accumulate in the kidneys of male rats, and there was a linear relationship between the kidney CTFT concentrations and the kidney levels of a2u-globulin, as determined by an ELISA assay. Microscopic changes in male rats included a dose-related toxic nephropathy consistent with that previously described as "hyaline droplet nephropathy." Dosed male and female rats also had hepatocyte hypertrophy and cytoplasmic vacuolization of the adrenal cortex. Clinical pathology findings suggested a mild anemia and cholestasis in rats. In contrast to rats, mice did not show appreciable CTFT concentrations in any tissue evaluated, suggesting a more rapid elimination of the chemical. However, hepatocellular hypertrophy, and clinical pathology findings consistent with cholestasis and mild liver injury, were noted in mice in the 400 and 1000 mg/kg dose groups. These studies demonstrated that oral doses of CTFT of 400 mg/kg or higher caused liver hypertrophy in rats and mice and adrenal changes in rats. Doses of 50 mg/kg or higher caused "hyaline droplet nephropathy" in male rats. The results were similar with CTFT administered either in corn oil or in alpha-CD (although absorption of CTFT was somewhat more rapid with alpha-CD), suggesting that alpha-CD may be an appropriate vehicle for toxicity studies with other chemicals. Synonyms: CTFT; p-Chloro-4-(trifluoromethyl) benzene; (p-chlorophenyl) trifluoromethane; 4-chlorobenzotrifluoride; Benzene, 1-chloro-4-(trifluoromethyl)-; p-(trifluoromethyl) chloro-benzene; p-chlorobenzotrifluoride; p-chlorotri-fluoromethylbenzene; p-trifluoromethylphenyl chloride; parachloro-alpha,alpha,alpha trifluorotoluene; parachlorobenzotrifluoride; parachlorotrifluoro-methylbenzene.
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PMID:NTP technical report on the toxicity studies of para-Chloro-alpha,alpha,alpha Trifluorotoluene (CAS NO: 98-56-6) Administered in Corn Oil and alpha-Cyclodextrin to F344/N Rats and B6C3F1 Mice in 14-Day Comparative Gavage Studies. 1220 72

Benzene is one of wildly used chemicals. Long-term exposure to benzene causes hematotoxicities and further, the development of including anemia, myelodysplastic syndrome (MDS), aplastic anemia, etc., with the leukemia as the worst. People vary greatly in their susceptibility to adverse health outcomes from benzene exposure. The author reviewed the relationship between genetic polymorphism of I metabolic enzymes(CYP2E1, NQO1, MPO) and II metabolic enzymes(GST, PST) involving benzene metabolite and interindividual variation in their genetic susceptibility to hematotoxicity from benzene exposure in this paper.
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PMID:[Individual susceptibility to hematotoxicity from benzene exposure and the genetic polymorphism of metabolic enzymes]. 1256 53


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