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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

Species differences in benzene hydroxylation to phenol by pulmonary and hepatic microsomes.

The metabolism of benzene to phenol by microsomal preparations from lung and liver has been compared in hamsters, rats, and rabbits. There were wide differences in the apparent Vmax of benzene hydroxylation among the various species and tissues and smaller differences in the apparent KM values for benzene hydroxylase. Benzene can inhibit its own metabolism in vitro when present in high concentrations. Phenol was the only metabolite of benzene identified, under the conditions of the assay, in incubation mixtures containing microsomes from lung or liver of any of the three animal species. When incubated with microsomes under the conditions used to measure benzene metabolism, phenol was further metabolized in liver but not in lung preparations. Phenol metabolism was almost completely inhibited when 11.2 mM benzene was included in the incubation mixture containing hepatic microsomes. The variation in rates of benzene hydroxylation by microsomal preparations from lungs or livers of the three animal species was similar to the variation in rates of benzypyrene hydroxylation in the same preparations.

Aniline Hydroxylase

Microbial diversity and metabolic pathways linked to benzene degradation in petrochemical-polluted groundwater.

The rapid advance in shotgun metagenome sequencing has enabled us to identify uncultivated functional microorganisms in polluted environments. While aerobic petrochemical-degrading pathways have been extensively studied, the anaerobic mechanisms remain less explored. Here, we conducted a study at a petrochemical-polluted groundwater site in Henan Province, Central China. A total of twelve groundwater monitoring wells were installed to collect groundwater samples. Benzene appeared to be the predominant pollutant, detected in 10 out of 12 samples, with concentrations ranging from 1.4 μg/L to 5,280 μg/L. Due to the low aquifer permeability, pollutant migration occurred slowly, resulting in relatively low benzene concentrations downstream within the heavily polluted area. Deep metagenome sequencing revealed Proteobacteria as the dominant phylum, accounting for over 63 % of total abundances. Microbial α-diversity was low in heavily polluted samples, with community compositions substantially differing from those in lightly polluted samples. dmpK encoding the phenol/toluene 2-monooxygenase was detected across all samples, while the dioxygenase bedC1 was not detected, suggesting that aerobic benzene degradation might occur through monooxygenation. Sequence assembly and binning yielded 350 high-quality metagenome-assembled genomes (MAGs), with 30 MAGs harboring functional genes associated with aerobic or anaerobic benzene degradation. About 80 % of MAGs harboring functional genes associated with anaerobic benzene degradation remained taxonomically unclassified at the genus level, suggesting that our current database coverage of anaerobic benzene-degrading microorganisms is very limited. Furthermore, two genes integral to anaerobic benzene metabolism, i.e, benzoyl-CoA reductase (bamB) and glutaryl-CoA dehydrogenase (acd), were not annotated by metagenome functional analyses but were identified within the MAGs, signifying the importance of integrating both contig-based and MAG-based approaches. Together, our efforts of functional annotation and metagenome binning generate a robust blueprint of microbial functional potentials in petrochemical-polluted groundwater, which is crucial for designing proficient bioremediation strategies.

Groundwater

Activity of lysosomal beta-glucuronidase in leukocytes of rats exposed to benzene and sodium selenate.

Chronic exposure to benzene results in rats in the decrease of the lymphocyte count in the peripheral blood, the decrease of the beta-glucuronidase (BG) activity both in lymphocytes and neutrophilic granulocytes as well as in the damage to lysosomal apparatus of lymphocytes expressed in diffusion of the enzyme within the cell cytoplasm. Administration of selenium (sodium selenate) in dosis of 1.0 microgram/Kg during consecutive 10 days prior the exposure to benzene resulted in prevention of benzene-induced decrease of the BG activity in granulocytes and of a damage to lymphocyte lysosomes. Application of selenium in dosis of 5.0 microgram/Kg during the same time prior the exposure to benzene prevented the benzene-induced lymphocytopenia, induced the reactive increase of the granulocyte number, and caused, moreover, the prevention of the BG activity decrease in granulocytes. Simultaneously the increase of the BG-positive lymphocyte percentage was noted which was related to the increase of cells exhibiting the cytoplasmatic and extralysosomal localization of the enzyme. The results suggest that only smaller doses of sodium selenate prevented the damage to lysosomal membrane of lymphocytes induced by toxic effect of benzene.

Animals

Environmental benzene exposure induces a conserved neutrophil degranulation program across species.

Immune systems have evolved under constant pressure from pathogens and environmental challenges, leading to the emergence of conserved defense mechanisms across diverse organisms. Evidence indicates that environmental exposures perturb immune regulatory networks, particularly during development, when transcriptional programs governing hematopoiesis, immune cell differentiation, and inflammatory signaling are highly dynamic and sensitive to external stressors. Volatile organic compounds represent an important but incompletely understood source of immunological perturbation. Among these, benzene is a ubiquitous environmental contaminant associated with hematotoxicity and immune dysregulation; however, transcriptional responses to environmentally relevant low-level exposures during development remain poorly characterized. To determine whether benzene exposure engages conserved cross-species immune regulatory pathways, we performed a comparative transcriptomic analysis integrating developmental tissues from 3 vertebrate systems: human placenta, murine placenta, and zebrafish larvae. Bulk RNA sequencing datasets were analyzed to identify transcriptional responses associated with benzene exposure in experimental models (≤5 ppm) and with benzene adduct levels in maternal plasma for human samples. Because placental gene expression exhibits strong sexual dimorphism, murine datasets were stratified by fetal sex. Pathway- and network-level analyses were used to identify conserved biological responses. We observed a striking convergence on activation of innate immune pathways associated with neutrophil degranulation, IL-8 signaling, and Rho GTPase-mediated inflammatory responses. Further, network analyses identified CXCL8 and ERK1/2 as shared regulatory hubs linking transcriptional responses across datasets. Together, these findings uncover an evolutionarily conserved innate immune signature associated with benzene exposure during vertebrate development, suggesting that environmental chemical perturbations may disrupt fundamental immune regulatory programs across species.

Animals

Leukaemia in benzene workers.

Workers occupationally exposed to benzene in 1940-49 were followed for vital status up to 1975. In comparison with two control populations, a significant (P less than 0-002) excess of leukaemia was observed. A five-old excessive risk of all leukaemias and a ten-fold excess of deaths from myeloid and monocytic leukaemias combined are demonstrated in the study population compared with controls. These figures under-estimate the true leukaemia risk to benzene-exposed workers, because follow-up is only 75% complete and the untraced 25% of the study population were all regarded, in the statistical analysis, as being alive at the end of the study period. The environment of the workers in the study population was not contaminated with solvents other than benzene, and existing records indicate that the benzene levels themselves were generally below the limits recommended at the time of their measurement.

Adult

Purification and some properties of a soluble benzene-oxidizing system from a strain of Pseudomonas.

1. A soluble enzyme system which oxidizes benzene to cis-1,2-dihydroxycyclohexa-3,5-diene (cis-benzene glycol) was obtained from a species of Pseudomonas grown on benzene as the major carbon source. 2. The system was shown to consist of three protein components. Two of these were non-haem-iron proteins of molecular weight approx. 21,000 and approx. 186,000 and the other was a flavoprotein of molecular weight approx. 60,000. 3. Fe2+ and NADH were essential cofactors for benzene oxidation.

Bacterial Proteins

Transcutaneous gamma benzene hexachloride absorption and toxicity in infants and children.

A premature, malnourished infant had seizures and abnormal neurological function associated with topical gamma benzene hexachloride (lindane) therapy. The level of gamma benzene hexachloride in his blood was 17 times greater than expected after a single topical application of 1% gamma benzene hexachloride. Significant levels developed in another child's blood after repeated applications of small amounts to areas of dermatitis and excoriations on the skin. The use of topical gamma benzene hexachloride in pediatric patients is reviewed because of increased evidence of unpredictable absorption and toxicity.

Administration, Topical

Petit mal and grand mal seizures produced by toluene or benzene intoxication in the cat.

Motor incoordination, euphoria and hallucinations are symptoms reported for humans voluntarily intoxicated by industrial solvents. An epileptic-like consciousness impairment has also been noted. The present paper describes a technique used for the experimental study of solvent intoxication in which toluene and benzene can be applied directly into the trachea of freely moving cats with chronically implanted electrodes. This technique permits the control of solvent dose and time of exposure. Results showed a 3 Hz spike-wave activity in the gyrus cinguli recording with both toluene or benzene intoxication. Furthermore, benzene inhalation produced generalized tonic-clonic seizures. These effects were dose-related. However, a sensitization period was essential for the development of such alterations, and effects showed a tendency to shortening through chronic exposures. These alterations were correlated with behavioral disturbances such as nodding, twitching and apparent hallucinations. Results are discussed regarding the sensitization period, the optimal peak of effects, and the period of tolerance development relevant to an earlier found amygdalar activation that could be correlated with other methods inducing experimental seizures, such as repetitive stimulation of the brain (kindling).

Amygdala

The dynamics of histoenzymatic changes in the kidney in acute poisoning with benzene.

The experiments were carried out in mice which were divided into 4 experimental groups and a control group. In the course of the experiment SD, NADH2-tetrazolium reductase; ATP-ase, G-6-P-ase and AP were observed. It was found that acute benzene intoxication causes the disturbances in the enzymatic activities of the cells of the main segment of the nephron. The impairment of tissue respiration and oxygen phosphorylation and of active transport is due to benzene intoxication. Benzene leads to injury of the endoplasmatic reticulum in the cells of the kidney.

Acid Phosphatase

The behaviour of some enzymes in the mouse liver due to chronic benzene intoxication.

1. Long trem benzene action brings about a permanent decrease in oxidoreductive enzymes and active transport as well as an inactivation of the lysosomal apparatus in liver-cells. 2. Particular liver lobule zones show different sensitivity to toxic action of benzene which might result from their different role in the processes of benzene biotransformation.

Acid Phosphatase

[Effect of phenobarbital stimulation on morphological and cytoenzymatic changes in the liver of benzene intoxicated rats (author's transl)].

The experiments were carried out on male Wistar-Rats. They were divided into 2 groups. The rats of the control groups were treated to Phenobarbital intraperitoneally for 3 consecutive days. The animals of the experimental group were additionaly injected with Benzen intraperitoneally on the 4th day of experiment. It has been found that Phenobarbital brought about the formation of 2 types of bright and dark cells in the liver. The action of Phenobarbital is carried on by Benzene. The authors discuss morphological and functional evaluation of bright and dark cells from the point of view of stimulating action of Phenobarbital as well as the course of Benzene biotransformation in liver cells.

Adenosine Triphosphatases

Influence of 1,2,3-benzene-tricarboxylate on pyruvate metabolism in rat-liver mitochondria.

1,2,3-Benzene-tricarboxylate, a known inhibitor of the mitochondrial tricarboxylate carrier, was found to inhibit pyruvate carboxylation as well as the transport of citrate out of the matrix in rat liver mitochondria incubated with pyruvate. The inhibition of pyruvate carboxylation was observed with both intact mitochondria and with the solubilized pyruvate carboxylase. The inhibition of the pyruvate carboxylase by 1,2,3-benzene-tricarboxylase was not mediated via one of the parameters known to regulate the activity of the enzyme and therefore a direct inhibition of the enzyme by the tricarboxylate was assumed. Since the pyruvate carboxylase is exclusively localized in the mitochondrial matrix space it was concluded that 1,2,3-benzene-tricarboxylate penetrates into this compartment.

Acetyl Coenzyme A

Mutagenic effects of petrol in Drosophila melanogaster I. Effects of benzene and 1,2-dichloroethane.

Commercial petrol and two of its components, benzene and 1,2-dichloroethane, were tested for mutagenicity in Drosophila melanogaster. The chemicals were given to larvae through their food supply. A genetically unstable sexlinked test system caused by a transposable genetic element was used. Mutagenicity was measured by the frequency of somatic mutations for eye pigmentation. Commercial petrol and 1,2-dichloroethane showed mutagenic activity. With the system used, benzene did not show any mutagenic activity. The high frequency of mutations induced by 1,2-dichloroethane indicate the existence in Drosophila of a metabolic activating system.

Animals

Histochemical and histoenzymatic changes in mouse liver in subacute benzene intoxication.

The investigations were performed on mice. They were divided into a control group and 4 experimental groups. The experimental animals were administered intraperitoneally benzene 6 X every 24 h. The animals were decapitated 30 min. 4, 12 and 24 h after the last benzene administration. During the experiment, dyeing for neutral lipids and glycogen was carried out, and the activity of NADH2-r.t., SDH, G-6-Pase, ATP-ase and ACP was estimated. A decrease of glycogen content in liver cells, deviations in the amount of neutral lipids, reversible decrease of mitochondrial enzymes activity, and intensification of the processes of intracellular catabolism were found.

Acid Phosphatase

Lymphomas and occupational benzene exposure.

There was a significant excess of deaths caused by major lymphomas in men employed in occupations where benzene and/or coal tar fractions are used. The increase in risk was limited to those who were 45 years of age and older at death, an observation which is consistent with the possibility that chronic exposure might be important. Evidence from other studies suggests that benzene may adversely affect the immunological system.

Adult