Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Benzene”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 19 recordsLinked to original sources
PubMed1990

Lung tumorigenicity of benzene oxide, benzene dihydrodiols and benzene diolepoxides in the BLU:Ha newborn mouse assay.

Metabolic activation of benzene may occur by a pathway analogous to that accepted for polynuclear aromatic hydrocarbons (PAHs) involving ring epoxidation, enzymatic hydrolysis to the dihydrodiol, and further epoxidation to the diolepoxide. This hypothesis was explored by testing benzene oxide (BzO) and enantiomers and racemates of benzene dihydrodiols and diolepoxides for their capacity to induce lung tumors in a newborn mouse assay. Although benzene and benzene diolepoxide-1 [(+/-)-BzDE-1] were inactive, BzO and racemates of benzene dihydrodiol [(+/-)-BzDh] and benzene diolepoxide-2 [(+/-)-BzDE-2] induced dose-dependent increases in lung tumor incidence and multiplicity. (+/-)-BzDE-2 may be an ultimate tumorigenic metabolite of benzene since it was the most active compound tested on a molar basis with an estimated ED50 (dose inducing lung tumors in 50% of mice) of 12.0 mumol and an estimated TM1.0 (total dose inducing 1.0 lung tumor/mouse) of 16.2 mumol. No stereoselectivity was apparent in the tumorigenic activity of dihydrodiol and diolepoxide enantiomers since at equimolar doses the resolved (+)-BzDh was equally tumorigenic as the (+/-)-BzDh racemate and the resolved (+)- and (-)-BzDE-2 were both equally active as (+/-)-BzDE-2.

Adenocarcinoma↗
PubMed1990

Effect of repeated benzene inhalation exposures on benzene metabolism, binding to hemoglobin, and induction of micronuclei.

Metabolism of benzene is thought to be necessary to produce the toxic effects, including carcinogenicity, associated with benzene exposure. To extrapolate from the results of rodent studies to potential health risks in man, one must know how benzene metabolism is affected by species, dose, dose rate, and repeated versus single exposures. The purpose of our studies was to determine the effect of repeated inhalation exposures on the metabolism of [14C]benzene by rodents. Benzene metabolism was assessed by characterizing and quantitating urinary metabolites, and by quantitating 14C bound to hemoglobin and micronuclei induction. F344/N rats and B6C3F1 mice were exposed, nose-only, to 600 ppm benzene or to air (control) for 6 hr/day, 5 days/week for 3 weeks. On the last day, both benzene-pretreated and control animals were exposed to 600 ppm, 14C-labeled benzene for 6 hr. Individual benzene metabolites in urine collected for 24 hr after the exposure were analyzed. There was a significant decrease in the respiratory rate of mice (but not rats) pretreated with benzene which resulted in lower levels of urinary [14C]benzene metabolites. The analyses indicated that the only effects of benzene pretreatment on the metabolite profile in rat or mouse urine were a slight shift from glucuronidation to sulfation in mice and a shift from sulfation to glucuronidation in rats. Benzene pretreatment also had no effect, in either species, on formation of [14C]benzene-derived hemoglobin adducts. Mice and rats had similar levels of hemoglobin adduct binding, despite the higher metabolism of benzene by mice. This indicates that hemoglobin adduct formation occurs with higher efficiency in rats. After 1 week of exposure to 600 ppm benzene, the frequency of micronucleated, polychromatic erythrocytes (PCEs) in mice was significantly increased. Exposure to the same level of benzene for an additional 2 weeks did not further increase the frequency of micronuclei in PCEs. These results indicate that repeated exposures to benzene, such as might be encountered by humans as a result of occupational or environmental exposures, are not likely to change or increase benzene metabolism.

Administration, Inhalation↗
PubMed1988

Benzene metabolism by ethanol-, acetone-, and benzene-inducible cytochrome P-450 (IIE1) in rat and rabbit liver microsomes.

Ethanol is known to exert a synergistic effect on the toxicity of benzene. In the present investigation it was found that benzene was metabolized at a rate 20-65-fold higher in liver microsomes from ethanol- or acetone-treated rats than in microsomes from control animals. One high affinity site [Km = 19 +/- 5 (SD) microM] and one low affinity site [Km = 0.3 +/- 0.1 mM] for benzene metabolism were present in microsomes of acetone-treated rats, and similar sites were seen in microsomes from control or ethanol-treated rats. Treatment of the animals with either ethanol or acetone mainly influenced the Vmax values for benzene metabolism. Also benzene treatment of rats caused an increased rate of microsomal benzene metabolism. The hepatic microsomal NADPH-dependent metabolism of benzene was inhibited by compounds known to interact with the ethanol-inducible form of P-450 such as imidazole, ethanol, aniline, and acetone but was unaffected by addition of metyrapone. Anti-IgG against ethanol-inducible cytochrome P-450 from rat (P-450j) or rabbit liver (P-450 LMeb) inhibited the microsomal benzene metabolism effectively in rat or rabbit liver microsomes, respectively, whereas preimmune IgG was without effect. The level of rat ethanol-inducible P-450 (P-450j) was induced to an extent similar to that for the microsomal benzene metabolism, by either benzene, acetone, or ethanol. The data indicate that benzene is metabolized mainly by the ethanol-inducible P-450 form in liver microsomes and that the induction of this isozyme by ethanol can provide an explanation for the synergistic action of ethanol on benzene toxicity.

Acetone↗
PubMed1986

Metabolism of benzene and phenol in macrophages in vitro and the inhibition of RNA synthesis by benzene metabolites.

Benzene may affect hemopoiesis by damaging the bone marrow stroma that provides the microenvironment for hemopoiesis. A possible target of benzene toxicity in the stroma is the macrophage, which is a major source of protein factors required for the proliferation and differentiation of progenitor cells. As an initial approach towards understanding whether benzene inhibits hemopoietic factor production in bone marrow stroma, the metabolism of benzene and phenol has been studied and the effect of benzene and its metabolites on macrophage RNA synthesis has been examined. Benzene is not metabolized in macrophages but phenol, the major metabolite of benzene in bone marrow, is converted by peroxidase in the macrophage to both free metabolites and species which covalently bind to cellular macromolecules. Benzene and its metabolites inhibited RNA synthesis in a dose-dependent manner, with 50% inhibitory concentrations of 5 X 10(-3) M for benzene, 2.5 X 10(-3) M for phenol, 2.5 X 10(-5) M for hydroquinone, and 6 X 10(-6) M for p-benzoquinone; this inhibition was not attributable to loss of cell viability. Benzene, possibly by an inhibition of uridine transport into macrophages, and phenol, by its conversion to covalently binding species, inhibit RNA synthesis in macrophages and thus may inhibit the synthesis of colony stimulating factors required for hemopoiesis.

Animals↗
PubMed1985

Low level benzene exposure in Sweden: effect on blood elements and body burden of benzene.

Measurements for benzene exposure were performed for different work places. In addition, breath benzene concentrations were measured in different occupations in order to establish toxico-kinetics of benzene in man; chromosomal aberrations in lymphocytes of exposed workers were also examined. Smoking appears to result in a large increase in benzene concentration in exhaled breath. The smoke from one cigarette contains 60-80 micrograms of benzene. It was found that exposure levels of 10 ppm are rather uncommon among workers handling gasoline or gasoline equipment. It was concluded that the gasoline load of road tankers cannot be responsible for chromosome changes of the driver, as milk truck drivers showed the same changes. These results did not prove that benzene was the cause of the observed changes. Smoking is the confounding factor, with a potency of at least the same order of magnitude as benzene. In addition, our present knowledge about mechanisms of benzene is not sufficiently developed to permit quantitative conclusions as to the human health risks.

Air Pollutants, Occupational↗
PubMed1988

Toxic effects of benzene and benzene metabolites on mononuclear phagocytes.

Benzene is a potent bone marrow toxin in animals and man. Animal studies have shown that exposure to benzene can alter T lymphocyte functions and decrease the resistance of animals to Listeria monocytogenes and transplanted tumor cells. Mononuclear phagocytes participate in host resistance to Listeria and tumor cells. The purpose of the studies presented here was to determine the effects of benzene and benzene metabolites on macrophage functions and the ability of macrophages to be activated for functions which are important in host defense. Benzene had no effects on macrophage function or activation for any of the functions tested. Conversely, metabolites of benzene, catechol (CAT), hydroquinone (HQ), benzquinone (BQ), and 1,2,4-benzenetriol (BT) had potent and varied effects on macrophage function and activation. BQ inhibited the broadest range of functions including release of H2O2, Fc receptor-mediated phagocytosis, interferon gamma priming for tumor cell cytolysis, and bacterial lipopolysaccharide (LPS) triggering of cytolysis. BQ was also the most potent metabolite causing inhibition at lower concentrations than the other metabolites. HQ inhibited H2O2 release and priming for cytolysis and BT inhibited phagocytosis and priming for cytolysis. CAT only inhibited the release of H2O2. None of the compounds tested inhibited the induction of class II histocompatibility antigens on the cell surface. All of the effects measured occurred using concentrations of compounds which did not disrupt the cell integrity or inhibit general functions such as protein synthesis. Taken together these data suggest that benzene metabolites alter macrophage function through several mechanisms including inhibition of output enzymes and disruption of signal transduction systems.

Animals↗
PubMed1979

Biological threshold limits for benzene based on pharmacokinetics of inhaled benzene in man.

Volunteers were exposed to benzene, 2--10 ppm, under controlled conditions up to 6 h a day during five consecutive days. The accumulation and elimination of benzene was measured by determination of benzene concentration -- down to 0.001 ppm -- in exhaled breath. From these observations, a multicompartment model, which approximately describes the kinetics of benzene elimination and accumulation has been designed. On the basis of this model, benzene concentrations in breath, corresponding to exposure levels of benzene, have been estimated. Thus, at a daily exposure to 10 ppm the exhaled benzene concentration in the morning after a day of exposure will not exceed 0.1 ppm.

Aerosols↗
PubMed1977

Benzene inhibition of in vitro rabbit reticulocyte haem synthesis at delta aminolaevulinic acid synthetase: reversal of benzene toxicity by pyridoxine.

Benzene (0.113 M) inhibited haem and protein synthesis in rabbit reticulocytes. This inhibition of haem synthesis was found when L-2-[14C]-glycine was used as the radioactive precursor. However, when 4-[14C]delta-aminolaevulinic acid (ALA) was used, there was no significant inhibition. Since ALA measures the haem synthetic pathway beyond the enzyme delta-aminolaevulinic acid synthetase (ALA synthetase), these results suggest that benzene inhibits haem synthesis at or before ALA synthetase. This was confirmed by demonstrating that 1 mM ALA both protected against and reversed the benzene inhibition of reticulocyte protein synthesis. In addition, 1 mM pyridoxine both protected against and reversed the benzene inhibition of reticulocyte protein synthesis. In addition, ImM pyridoxine both protected against and reversed the benzene inhibition of reticulocyte haem and protein synthesis. These results indicate that benzene (or a metabolite) either competes with pyridoxal phosphate at ALA synthetase or competes with pyridoxine for pyridoxal phosphokinase. These results are discussed in terms of their implications for the possible roles of ALA synthetase and the haemin-controlled repressor in benzene-induced aplastic anaemia.

5-Aminolevulinate Synthetase↗
PubMed1989

Peroxidase-dependent metabolism of benzene's phenolic metabolites and its potential role in benzene toxicity and carcinogenicity.

The metabolism of two of benzene's phenolic metabolites, phenol and hydroquinone, by peroxidase enzymes has been studied in detail. Studies employing horseradish peroxidase and human myeloperoxidase have shown that in the presence of hydrogen peroxide phenol is converted to 4,4'-diphenoquinone and other covalent binding metabolites, whereas hydroquinone is converted solely to 1,4-benzoquinone. Surprisingly, phenol stimulates the latter conversion rather than inhibiting it, an effect that may play a role in the in vivo myelotoxicity of benzene. Indeed, repeated coadministration of phenol and hydroquinone to B6C3F1 mice results in a dramatic and significant decrease in bone marrow cellularity similar to that observed following benzene exposure. A mechanism of benzene-induced myelotoxicity is therefore proposed in which the accumulation and interaction of phenol and hydroquinone in the bone marrow and the peroxidase-dependent formation of 1,4-benzoquinone are important components. This mechanism may also be responsible, at least in part, for benzene's genotoxic effects, as 1,4-benzoquinone has been shown to damage DNA and is shown here to induce multiple micronuclei in human lymphocytes. Secondary activation of benzene's phenol metabolites in the bone marrow may therefore play an important role in benzene's myelotoxic and carcinogenic effects.

Animals↗
PubMed1991

[Environmental and occupational exposure to benzene by investigation of expiratory benzene].

In this paper, expiratory benzene due to environmental and occupational benzene exposure during the work-shift and the morning after was studied by the analysing benzene concentrations in environmental air, in breathing air and in urinary phenol concentration. The results showed that the concentrations of expiratory benzene and urinary phenol correlated significantly with exposure to benzene. It is suggested that the expiratory benzene is a good indicator in biomonitoring of workers exposed to benzene.

Adolescent↗
PubMed1975

Comparative study of the activity of boric, benzene-boronic and methyl-benzene-boronic acids upon respiration, general metabolism and systemic hemodynamics of the anesthetized dog.

The authors compared the action of boric, benzene-boronic and p-methyl-benzene-boronic acids on respiration and general metabolism and on systemic hemodynamics of the anesthetized dog. They further investigated the effects on the arterial blood pressure in the rat and on the isolated rabbit heart. In the dogs, the three acids were shown to have no significant action on the systolic, diastolic and mean arterial blood pressures and a slight stimulating action on the differential arterial blood pressure. On the contrary, in the rat, all the acids were hypotensive. This action was dose dependent. In the entire animal, as well as in the isolated rabbit heart, benzene-boronic and p-methyl-benzene-boronic acids depressed the myocardial contractility. Whereas boric acid did not act on the heart contractility in situ in anesthetized dogs, it slightly stimulated the myocardial contractility of the isolated rabbit heart. The two acids seemed to be directly active on the myocardial cell. In the anesthetized dog, cardiac performances were first depressed then stimulated. Both benzene-boronic and p-methyl-benzene-boronic acids were ventilatory depressors: they reduced ventilatory output and rhythm, they first decreased then increased total O2 consumption and CO2 production.

Animals↗
PubMed1989

Inhibition of interferon-alpha/beta induction in L-929 cells by benzene and benzene metabolites.

Murine L-929 cells were treated with benzene or a series of benzene metabolites, washed and then interferon-alpha/beta was induced with polyriboinosinic-polyribocytidylic acid. Exposure of the cells to benzene or phenol, a monocyclic metabolite of benzene, did not affect interferon-alpha/beta induction. However, exposure of the cells to p-benzoquinone, hydroquinone or catechol, dihydroxy- and diketo-metabolites of benzene, resulted in a severe inhibition of interferon-alpha/beta production. There was no significant loss of viability of the cell cultures. Additional studies with p-benzoquinone indicated that inhibition of interferon-alpha/beta was reversible and could be abrogated by addition of reduced glutathione to the cell cultures.

Animals↗
PubMed1989

Effect of repeated benzene inhalation exposures on subsequent metabolism of benzene.

Benzene is a known human leukemogen and animal carcinogen. To better assess the risks associated with benzene exposure, it would be helpful to determine whether repeated inhalation exposures would affect the metabolism of benzene. The purpose of these experiments was to determine if exposure of F344 rats and B6C3F1 mice to 600 ppm benzene, 6 h/day, 5 days/week for 3 weeks, would affect the subsequent in vivo metabolism of inhaled [14C]benzene.

Administration, Inhalation↗
PubMed1990

The toxicodynamics of benzene, ethanol, and benzene plus ethanol based on the histopathological examination of selected organs in the rat.

The influence of ethanol on benzene toxicity in the course of prolonged 26-week intoxication was investigated in Wistar rats. A dose of 1/30 DL50/24h of benzene in oil solution was administered subcutaneously once daily, 5 days a week. Drinking water was replaced by a 10% water solution of ethanol ad libidum. Specimens of the liver, spleen, kidneys, lungs, and heart were taken for histopathological examination. Changes in the liver confirmed the hepatotoxic action of benzene and were unaffected by the simultaneous administration of ethanol. In the lungs and spleen the lymphatic system showed signs of damage which became more pronounced in joint exposure to benzene plus ethanol. The authors conclude that alcohol abuse by people professionally exposed to benzene and other lipophilic petroleum derivatives (as in the petrochemical industry) may increase the toxic effects of these substances.

Animals↗
PubMed1987

Kinetic studies on benzene metabolism in rat liver--possible presence of three forms of benzene metabolizing enzymes in the liver.

The effects of food deprivation, ethanol consumption and phenobarbital (PB) administration on in vitro benzene metabolism in rat liver were studied by using benzene concentration ranging from 0.0055 to 6.25 mM. The kinetic analysis suggested that the liver of normally-fed rats contained two forms of benzene hydroxylases each with a Km value of 0.01 mM or 0.07 mM. The isozyme with a Km of 0.01 mM disappeared following one-day food deprivation, but the deprivation enhanced the activity of the other isozyme. Ethanol treatment markedly increased the activity of both normally-existing enzymes. On the other hand, PB treatment induced the synthesis of another benzene-metabolizing enzyme with a high Km value of 4.5 mM, the presence of which was indistinct in normal rats. The treatment had no influence on the activity of either of the normally-occurring low-Km isozymes. The combined effects of PB with food deprivation were additive, suggesting that the induction of low- and high-Km isozymes is each independent of the other.

Alcohol Drinking↗
PubMed1991

Effects of benzene on DNA strand breaks in vivo versus benzene metabolite-induced DNA strand breaks in vitro in mouse bone marrow cells.

Previously, we identified p-benzoquinone (BQ) and 1,2,4-benzenetriol (BT) as toxic metabolites of benzene on the basis of their inhibitory effect on DNA synthesis. In the present study, the capability of benzene and the two metabolites to induce DNA strand breaks was investigated in either the in vivo or the in vitro system by comparing the DNA elution rate on a fine membrane filter at alkaline pH. In the in vitro system were bone marrow cells were reacted with test chemicals for 60 min, both BQ and BT induced a dose-related increase in alkali-labile DNA single-strand breaks (SSBs) of bone marrow cells. However, when glutathione (350 micrograms/ml) was added to the same reaction system, the DNA damaging effect of BQ (24 microM) and BT (24 microM) was blocked by 100 and 53%, respectively. Catalase (130 units/ml) completely blocked the DNA damaging effect of BT, while no protection was afforded with BQ. Consistent with these observations, no induction of alkali-labile DNA SSBs was observed in the in vivo system by an anesthetic dose of benzene (1760 mg/kg, ip or po) at 1, 24, and 36 hr postadministration in both male and female ICR mice. These results suggest that benzene exposure would not induce direct DNA strand breaks in vivo under realistic work-related or accidental exposure conditions and also indicate that caution should be exercised in the interpretation of in vitro data for whole-body toxicity evaluation.

Animals↗
PubMed1991

Mechanisms of benzene carcinogenesis: application of a physiological model of benzene pharmacokinetics and metabolism.

A physiological pharmacokinetic model for benzene, incorporating metabolic transformations, is used to explore why benzene, but not phenol--its primary metabolite--is carcinogenic at many sites in rats. The model has been parametrized using in vitro or in vivo experimental data. Ranges, rather than fixed values, were assigned to the parameters. The model-predicted levels of phenol and hydroquinone in the tissues are consistently higher when phenol, rather than benzene, is administered. This result demonstrates that the differential carcinogenicity of the two compounds is not explainable in the context of this pharmacokinetic analysis. It also indicates that the phenol-hydroquinone pathway alone is unlikely to account for the carcinogenic effects of benzene. Other metabolites must therefore also be involved.

Administration, Inhalation↗