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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↗

Hydrogen-bonding adducts of benzenepolycarboxylic acids with N,N-dimethylformamide: benzene-1,4-dicarboxylic acid N,N-dimethylformamide disolvate, benzene-1,2,4,5-tetracarboxylic acid N,N-dimethylformamide tetrasolvate and benzene-1,2,3-tricarboxylic acid N,N-dimethylformamide disolvate monohydrate.

The N,N-dimethylformamide (DMF) solvates of terephthalic acid, H(2)TA.2DMF (C(8)H(6)O(6).2C(3)H(7)NO), pyromellitic acid, H(4)PMA.4DMF (C(10)H(6)O(8).4C(3)H(7)NO), and hemimellitic acid, H(3)HMA.2DMF.H(2)O (C(9)H(6)O(6).2C(3)H(7)NO.H(2)O), are reported. The DMF solvate of terephthalic acid is centrosymmetric, containing one complete formula unit in the asymmetric unit. Both carboxylic acid groups hydrogen bond to a DMF molecule via an R(2)(2)(7) O-H.O/C-H.O motif. Discrete H(2)TA.2DMF units are observed. The DMF solvate of pyromellitic acid is centrosymmetric and the asymmetric unit contains half a formula unit. One of the unique carboxylic acid groups forms an R(2)(2)(7) motif with a DMF molecule, while the other forms a linear O-H.O hydrogen bond to the second unique DMF molecule. Discrete H(4)PMA.4DMF units are observed. The DMF solvate of hemimellitic acid is non-centrosymmetric and includes a molecule of water per formula unit. Both DMF molecules form an R(2)(2)(7) motif with the two outer carboxylic acid groups of HMA. A one-dimensional ladder structure is formed via hydrogen bonding between the central carboxylic acid group and the water molecules. The carboxylic acid R(2)(2)(8) head-to-tail motif is not observed in any of these examples. The inclusion of DMF thereby has the effect of limiting the dimensionality of the structures.

Journal Article↗

Charge donation to and dearomatization of benzene attending complexation: DFT estimates of binding energies of TpMXO(L) with benzene, for Tp = hydridotris(pyrazolyl) borate, MXO = MoNO, ReCO, and WNO, and L = ammonia, N-methylimidazole, pyridine, phosphine, methyl isocyanide, and carbon monoxide.

By density functional methods we characterize the bonding and charge distribution in complexes of benzene with dearomatizing agents tpReCO(L), tpMoNO(L), and tpWNO(L), where tp = hydrido Tris (pyrazolyl)borate), for a range of ligands L. Our LSDA and B3LYP density functional calculations use the Spartan LACVP+ basis and pseudopotential on Re, Mo, and W and 6-31G* on light atoms. The binding energy is strongly dependent on the nature of the ligand L, being greatest for L = ammonia and N-methylimidazole and weakest for CH3NC and CO. We find a correlation between strength of binding and electron transfer from the dearomatizing agents toward benzene. For the most strongly bound systems we find substantial (up to 500 millielectrons) charge transfer towards benzene, while for the most weakly bound systems charge is withdrawn from benzene. Structural details illustrate the ability of Re, Mo, and W species to dearomatize complexed benzene, which is extensive for all but the most weakly bound species with L = MeNC and CO. Re and W dearomatizing agents, which are computed and observed to form stable complexes with benzene, may be economic alternatives to osmium dearomatizing agents.

Journal Article↗

Separation of benzene and deuterated benzenes by reversed-phase and recycle liquid chromatography using monolithic capillary columns.

An alternate pumping-recycle system utilizing a commercially available low dead-volume switching valve was developed for microcolumn LC. The recycle system had two separation columns, and the dead volume of the recycling lines was kept to a minimum by avoiding passage of the sample through the pump chamber, sample injector, and the normal path length of a conventional UV detector. The drawback of the high total back pressure caused by the second column that is placed after the detector was overcome by on-column detection, and this eliminated the need for a high pressure flow cell. The system was used for the separation of an authentic mixture of benzene, benzene-1,3,5-d3, and benzene-d6. Baseline separation was accomplished after six cycles and the calculated theoretical plate number for benzene was 230,000. It was observed that the theoretical plate number (N) increased linearly with increasing number of cycles, and the N per unit time increased with increasing inlet pressure. The separation conditions were optimized and the separation of benzene and benzene-d6 was accomplished within 75 min at 2.5 MPa inlet pressure.

Journal Article↗

Electrophilic mercuration and thallation of benzene and substituted benzenes in trifluoroacetic acid solution.

The mercuration and thallation of benzene and substituted benzenes was studied with mercuric and thallic trifluoroacetate, respectively, in trifluoroacetic acid. With the shortest reaction time (1 sec) at 0 degrees , the relative rate of mercuration of toluene compared to that of benzene was 17.5, with the isomer distribution in toluene of: ortho, 17.4%; meta, 5.9%; and para, 76.7%. The isomer distribution in toluene varied with the reaction time, significantly more at 25 degrees than at 0 degrees . The competitive thallation of benzene and toluene with thallic trifluoroacetate in trifluoroacetic acid at 15 degrees showed the relative rate, toluene/benzene, to be 33, with the isomer distribution in toluene of: ortho, 9.5%; meta, 5.5%; and para, 85.0%. With increasingly higher reaction temperatures in both mercuration and thallation reactions of aromatics, isomerization (both intramolecular and intermolecular) within the relevant ortho- and para-metallated intermediate ions and/or of the isomers becomes more important. Competitive rates and isomer distributions of mercuration and thallation of benzene and substituted benzenes were also determined. The predominant para substitution in both mercuration and thallation of methylbenzenes reflects, besides some steric factors, the strong stabilizing effect of para methyl groups on the arenium ion intermediates. Under predominantly kinetically controlled conditions, no anomalous increase in the amount of meta substitution was observed.

Journal Article↗

Benzene and benzene metabolites as embryotoxic agents: effects on cultured rat embryos.

Benzene and several of its metabolites were investigated for dysmorphogenic and embryotoxic effects after direct exposures of cultured whole rat conceptuses. Benzene produced no statistically significant effects at concentrations up to 1.6 mM. Inclusion with 1.6 mM benzene of an hepatic xenobiotic-biotransforming system (S9) resulted in only minor decreases in embryonic growth parameters and no detectable dysmorphogenesis. Phenol, a major benzene metabolite, also elicited only minimal embryotoxicity at 1.6 mM concentrations. However, inclusion of an S9 system with phenol resulted in significant dysmorphogenic and embryotoxic effects at concentrations as low as 0.01 mM. For phenol bioactivation, S9 from phenobarbital-induced rats was the most effective, with induction by pregnenolone-16 alpha-carbonitrile, isopropanol, Aroclor 1254, no inducer, and 3-methylcholanthrene following in order of effectiveness. Bioactivating activity resided solely in the microsomal fraction. Metabolites coeluting on HPLC with hydroquinone and catechol were the major metabolites generated from phenol by each S9 system, but no significant correlation between specific metabolite generation and embryotoxicity was apparent. Of the benzene metabolites studied, trans, trans-muconaldehyde exhibited the highest embryotoxic potency but was not detectably generated by any of the S9 systems. Hydroquinone, catechol, and benzoquinone were approximately equipotent, each producing 100% lethality at 0.1 mM. Combined additions to the culture medium of hydroquinone together with phenol resulted in greater than additive effects, indicating a possible synergistic interaction between these metabolites and suggesting that peroxidase activity may be important to the mechanism of phenol-elicited embryotoxicity.

Animals↗

Detection of DNA damage in human lymphocytes by alkaline single cell gel electrophoresis after exposure to benzene or benzene metabolites.

The alkaline single cell gel electrophoresis (Comet) assay was applied to study the occurrence of DNA damage in peripheral lymphocytes of human subjects with occupational exposure to low levels of benzene (twelve gasoline station attendants, with average benzene exposure of 0.3 mg/m3, 8 h TWA). The results obtained show a significant excess of DNA damage in lymphocytes of exposed workers, compared to matched unexposed controls (p = 0.028, Mann-Whitney U-test). Averaged tail moment values, based on 100 cells/individual, were 1.900 microns in the exposed and 0.936 micron in the unexposed group. In addition, exposed subjects showed a clearcut excess of heavily damaged cells, with tail moments > 90th percentile of the overall distribution (13.5 vs. 6.5%, p = 0.013, Mann-Whitney U-test). No correlation was found between the extent of DNA damage and the ages or smoking habits of the subjects. In order to assess the plausibility of the involvement of benzene in the results of the ex vivo study, further experiments were performed treating in vitro peripheral lymphocytes from unexposed donors with benzene metabolites hydroquinone, benzoquinone and benzenetriol. In these experiments, all benzene metabolites exerted a marked effect on resting lymphocytes, the lowest effective concentrations being below 1 microgram/ml. Conversely, far greater concentrations were required for the induction of significant DNA damage in parallel experiments with hydroquinone on mitogen stimulated lymphocytes. Addition of the DNA repair inhibitor cytosine arabinoside (Ara-C, 1-10 micrograms/ml) partially restored the sensitivity of stimulated cells to hydroquinone, an indication of the active processing of induced DNA lesions in growing cells. These results are discussed also in relation to the role of peripheral lymphocytes as target tissue in the biomonitoring of human exposure to genotoxic agents.

Age Factors↗

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↗

Benzene in blood and phenol in urine in monitoring benzene exposure in industry.

Determinations of benzene concentration in blood and of phenol in urine were made by head-space gas chromatography techniques on samples taken near the end of the work day from two groups of workers potentially exposed to low levels of benzene in the work-place atmosphere. Preliminary results suggest that benzene in blood is more reliable than phenol tests for assessing both exposure and uptake of benzene. Normal values of phenol in urine (10 mg/liter or less) were found in nearly all those cases in which benzene was detected in the blood.

Benzene↗

Effects of co-exposure to extremely low frequency (ELF) magnetic fields and benzene or benzene metabolites determined in vitro by the alkaline comet assay.

In the present study, we investigated in vitro the possible genotoxic and/or co-genotoxic activity of 50 Hz (power frequency) magnetic fields (MF) by using the alkaline single-cell microgel-electrophoresis (comet) assay. Sets of experiments were performed to evaluate the possible interaction between 50 Hz MF and the known leukemogen benzene. Three benzene hydroxylated metabolites were also evaluated: 1,2-benzenediol (1,2-BD, catechol), 1,4-benzenediol (1,4-BD, hydroquinone), and 1,2,4-benzenetriol (1,2,4-BT). MF (1 mT) were generated by a system consisting of a pair of parallel coils in a Helmholtz configuration. To evaluate the genotoxic potential of 50 Hz MF, Jurkat cell cultures were exposed to 1 mT MF or sham-exposed for 1h. To evaluate the co-genotoxic activity of MF, the xenobiotics (benzene, catechol, hydroquinone, and 1,2,4-benzenetriol) were added to Jurkat cells subcultures at the beginning of the exposure time. In cell cultures co-exposed to 1 mT (50 Hz) MF, benzene and catechol did not show any genotoxic activity. However, co-exposure of cell cultures to 1 mT MF and hydroquinone led to the appearance of a clear genotoxic effect. Moreover, co-exposure of cell cultures to 1 mT MF and 1,2,4-benzenetriol led to a marked increase in the genotoxicity of the ultimate metabolite of benzene. The possibility that 50 Hz (power frequency) MF might interfere with the genotoxic activity of xenobiotics has important implications, since human populations are likely to be exposed to a variety of genotoxic agents concomitantly with exposure to this type of physical agent.

Benzene↗

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↗

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↗

[Toxicokinetics of benzene in humans. Excretion of phenol with urine and benzene with expired air after single and 4-day inhalation exposure].

Five male volunteers were exposed to benzene vapour (100 mg X m-3) during 2 h singly and during 4 successive days. The mean retention of benzene in the lungs and mean dose amounted to 61% and 74 mg, respectively. Two phases of the excretion of unchanged benzene in the expired air (t 1/2 approximately 2 h and approximately 20 h) and phenol in the urine (t 1/2 approximately 3 h and approximately 12 h) were observed. The observed half time values were similar after single and repeated exposure. Respective values for 4-days experiment amounted to 28 and 47% of the dose absorbed during the last day of exposure. Concentrations of benzene in the expired air and the rate of excretion of phenol in urine were higher after 4-days exposure than after single exposure, which results from benzene toxicokinetics. Coefficients of kinetic processes rate amounted to k2 = 0,15; k3 = 0,07; k4 = 0,06 and sigma kEM = 0,16 X h-1.

Adult↗

The impact of reduction in the benzene limit value in gasoline on airborne benzene, toluene and xylenes levels.

Background benzene, toluene, xylenes (BTX) average concentrations have been measured over the urban agglomeration of Toulouse, France, during both springtime and summer periods of 1999 and 2001. The benzene average amount over the two Toulouse campaigns in 1999 is equal to 2.2 microg/m(3), very close to the French air quality standard and well under the average value of 5 microg/m(3) recommended by European Economic Community countries, recognising that those regulations are given for a whole year. BTX pollution over Toulouse has, in particular, been produced by motor vehicle exhaust gases. For the study conducted during the same periods of 2001, benzene concentrations were within the French quality value in the whole area. This is because the benzene limit value contained in gasoline went from 5% to 1% since 2000 January 1. It will be important to measure benzene over annual periods in order to know its exact values over such a period and to observe its potential seasonal variations.

Journal Article↗

Resonance Raman investigation of the short-time photodissociation dynamics of the charge-transfer absorption of the I2-benzene complex in benzene solution.

Resonance Raman spectra were obtained for the I2-benzene complex in benzene solvent with excitation wavelengths in resonance with the CT-band absorption. These spectra indicate that the Franck-Condon region photodissociation dynamics have multidimensional character with motion mainly along the nominal I-I stretch mode nu(18), the nominal symmetric benzene ring stretch mode nu5, and the nominal symmetric CCH bending nu7. There is also a small contribution from the nominal out-of-plane CH oop wag nu15. A preliminary resonance Raman intensity analysis was done, and the results for the I2-benzene complex were compared to results previously reported for the 1-hexene-I2 complex. We briefly discuss the differences and similarities in the CT-band absorption excitation of an I2-benzene complex relative to those of an I2-alkene complex.

Journal Article↗

Detection of benzene, toluene, ethyl benzene, and xylenes (BTEX) using toluene dioxygenase-peroxidase coupling reactions.

We have developed a simple, whole-cell bioassay for the detection of bioavailable benzene, toluene, ethyl benzene, and xylenes (BTEX) and similar compounds. A genetically engineered E. coli strain expressing toluene dioxygenase (TDO) and toluene dihydrodiol dehydrogenase (TodD) was constructed, enabling the conversion of BTEX into their respective catechols, which were quickly converted into colored products by a horseradish peroxidase (HRP)-coupled reaction. The intensity of the color formation was correlated to concentrations of the BTEX compounds. Under the optimized conditions, a detection limit (defined as three times the standard deviation of the response obtained from the blank) of 10, 10, 20, and 50 microM was observed for benzene, toluene, ethyl benzene, and xylene, respectively. The bioassay was selective toward BTEX-related compounds with no interference observed with commonly used pesticides, herbicides, and organic solvent. The bioassay was very stable with little change in response over a 10-week period. The excellent stability suggests that the reported bioassay may be suitable for field monitoring of BTEX to identify and track contaminated water and follow the bioremediation progress.

Benzene↗