Quantitative analysis of benzene by selected ion monitoring/gas chromatography/mass spectrometry.

A selected ion monitoring gas chromatographic/mass spectrometric method for the quantitative determination of benzene in air, breath, and blood was developed utilizing a headspace assay with benzene-d3 as an internal standard. Limits of detection for 2 ng/mL in blood and 0.1 ppb in a 5-L sample of air or breath were attained. The influence of contamination by background benzene on the analytical process was studied carefully. For cases where background contamination could not be adequately controlled, the assay was modified for the quantitative determination of labelled benzenes six mass units heavier than natural benzene (benzene-d6 or benzene-13C6). Use of the method for the analysis of natural benzene was illustrated for the measurement of background levels in urban smokers and nonsmokers.

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.

Placental transfer and distribution of toluene, xylene and benzene, and their metabolites during gestation in mice.

The distribution of radioactivity in pregnant mice was registered at different time intervals (0-24 h) after a 10 min period of inhalation of 14C-toluene, -xylene, and -benzene. Autoradiographic and liquid scintillation methods were used to make possible the distinction between volatile, water-soluble and firmly tissue-bound radioactivity. Toluene, xylene, as well as benzene reached high concentrations immediately after inhalation in lipid-rich tissues (brain and fat) and well perfused organs (e.g., liver and kidney) but were rapidly eliminated resulting in low concentrations at 1 h in all maternal tissues, except fat. Metabolites reached peak levels around 30 min to 1 h after inhalation, but were also relatively rapidly eliminated. One exception from this general trend was a retention of firmly tissue-bound metabolites in maternal liver and kidney after benzene inhalation. Another exception was the very strong accumulation of water-soluble metabolites at 4 and 24 h in the nasal mucosa and olfactory bulb after inhalation of toluene and xylene. Volatile radioactivity was observed in the placenta and fetuses immediately and up to 1 h after inhalation of all the three studied solvents at all stages of gestation. The fetal levels were, however, much lower than in maternal tissues. In early gestation an even distribution pattern was observed, while the fetal liver reached higher concentration than other fetal tissues in late gestation. In similarity with maternal tissues, fetal tissues reached the highest levels of metabolites 30 min to 1 h after inhalation. A retention in uterine fluid was seen at 4 h. Otherwise no retention of metabolites was observed in the feto-placental unit.(ABSTRACT TRUNCATED AT 250 WORDS)

Determination of benzene and toluene in blood by means of a syringe-equilibration method using a small amount of blood.

A gas chromatographic determination of benzene and toluene in blood with a small amount of blood sample, 0.02 or 0.1 ml, is described. In the method an aliquot of the blood sample in a sealed hypodermic syringe of 2 ml capacity is equilibrated at 37 degrees C in a thermo-regulated water-bath. After establishing equilibrium 1 ml of overlying air is submitted to gas chromatographic analysis. The value of this method was verified by experiments in which men, rabbits, and rats were exposed to benzene and toluene mixtures of various concentrations.

An extractive method for determination of benzene in blood by gas chromatography.

A gas chromatographic procedure has been developed using toluene extraction for the analysis of benzene in hemolyzed blood. No sample incubation is required and only small quantities of blood (0.2 to 0.5 g) are needed. Levels as low as 0.5 mug benzene per gram of blood have been determined.

Conversion of benezene to toluene by methyl donors in man.

The level of benzene in blood can be efficiently reduced by the concurrent administration of two groups of organic compounds: (1) methyl donors, such as choline, betaine and methionine; (2) SH-amino-acids such as cysteine and methionine. Methionine belongs to both categories of anti-benzene compounds in man. The appearance of toluene was demonstrated after the ingestion of choline and betaine followed by the ingestion of a unique dose of pure benzene (free from toluene).

Biological monitoring of workers exposed to benzene in the coke oven industry.

Workers in the coke oven industry are potentially exposed to low concentrations of benzene. There is a need to establish a well validated biological monitoring procedure for low level benzene exposure. The use of breath and blood benzene and urinary phenol has been explored in conjunction with personal monitoring data. At exposures of about 1 ppm benzene, urinary phenol is of no value as an indicator of uptake/exposure. Benzene in blood was measured by head space gas chromatography but the concentrations were only just above the detection limit. The determination of breath benzene collected before the next shift is non-specific in the case of smokers. The most useful monitor at low concentrations appears to be breath benzene measured at the end-of-shift.

Breath and blood levels of benzene, toluene, cumene and styrene in non-occupational exposure.

Benzene, toluene, cumene and styrene were measured in the breath and blood of two groups of individuals. The first group included individuals belonging to a hospital staff, the second group included chemical workers who were not exposed to the abovementioned chemicals. The chemical workers were examined in plant infirmaries on the morning before the start of the workshift, and the hospital staff in the hospital infirmaries. One environmental air sample was taken in the infirmaries for each individual at the moment of the biological samplings. The environmental concentrations of benzene and styrene were significantly higher in the infirmaries of the chemical plant than in the infirmaries of the hospital. On the other hand, the environmental concentrations of toluene and cumene were not significantly different in the plant infirmaries and in the hospital infirmaries. In the hospital staff the alveolar concentrations of benzene, toluene and styrene were significantly lower than those in the chemical workers. In the hospital staff the blood concentrations of benzene, toluene and styrene were not significantly different from those in the chemical workers. Only the blood cumene concentration was significantly higher in the chemical workers. In hospital staff, smokers showed alveolar and blood concentrations of benzene and toluene that were significantly higher than those measured in the non smoker hospital staff. With reference to chemical workers, only alveolar benzene concentration was significantly higher in smokers than in non smokers.(ABSTRACT TRUNCATED AT 250 WORDS)

The transplacental migration and accumulation in blood of volatile organic constituents.

Gas chromatographic-mass spectrometric analysis of profiles of low molecular weight volatile organic constituents obtained from cord blood and maternal blood samples collected at birth reflect transplacentally acquired compounds. The transplacental passage of halogenated hydrocarbons, plastic components, and abnormal accumulations of compounds have been demonstrated. In the 11 paired cord blood-maternal blood samples analyzed, the relative amounts of constituents in cord blood closely correspond to those quantities present in the maternal blood. However, some of the over 100 components are present in the cord blood in significantly higher concentrations than in the maternal blood, suggesting a possible selective one-way transfer of certain constituents into the fetus. Benzene, carbon tetrachloride, and chloroform are present in quantities equal to or greater than in maternal blood. In one infant with a lumbosacral meningomyelocele abnormally high concentrations of acetone, other components, and the food preservative 2, 6-di-tert-butyl-4-methylphenol (BHT) were identified.

An extraction method for determination of benzene in tissue by gas chromatography.

An extraction procedure has been developed for the determination of benzene by gas chromatography in tissues following inhalation. Results are reproducible using very small quanities of sample (0.05 g for tissue and 0.02 ml for blood). The procedure has been applied to the analysis of blood and tissue of A.K.R. mice following a single exposure to levels similar to those that may be found in industrial hygiene atmospheres.

Kinetic studies on sex difference in susceptibility to chronic benzene intoxication--with special reference to body fat content.

The sex difference in the susceptibility to haematopoietic disorders induced by benzene was studied kinetically with a special reference to its relation with the body fat content. In rats of both sexes with a large body fat content, benzene was eliminated more slowly and remained in the body for a longer time than in rats with a small body fat content. In accord with this finding, the decrease in white blood cell numbers during a chronic benzene exposure was observed only in the groups of rats which had a large volume of fat tissue. In an experimental human exposure, the elimination of benzene was slower in the females than in the males. The kinetic study revealed that the slower elimination in the females is due primarily to the bulky distribution of body fat tissue in that sex. From these results obtained from the experimental exposure of men and rats to benzene, it was concluded that the human female, with her massive body fat tissue, shows an inherent disposition to be susceptible to a chemical such as benzene which has a high affinity with fat tissue.

Antidote effect of liquid paraffin in oral solvent intoxication.

The antidote efficacy of liquid paraffin in oral solvent intoxications was investigated in dogs. Groups of 3 to 4 animals each received 1 ml/kg of methylchloroform, 0.3 ml/kg of benzene, or 3 ml/kg of a synthetic gasoline mixture (hexane/heptane/octane, ratio 30:50:20) by gastric intubation. After a prolonged interval the same animals were given 5 ml/kg of liquid paraffin by a separate tube in addition to one of the above solvents. The solvent concentrations in the blood were determined by gas chromatography at appropriate intervals. Administration of liquid paraffin in conjunction with methylchloroform does not significantly affect the absorption process. In the case of benzene and the synthetic gasoline mixture, however, liquid paraffin produces a distinct reduction in the rate of absorption. It is thus concluded that in the therapy of oral solvent-intoxication, liquid paraffin exhibits favorable antidote properties which may however differ from one solvent to the other. In clinically relevant situations involving coadministration of purgatives, the antidote effect must be assessed as being of a higher order than in our animal experiments in which purgatives had to be omitted for external reasons.

The effects of ethanol ingestion and repeated benzene exposures on benzene pharmacokinetics.

Two groups of C57Bl/6J mice were exposed to 300-ppm benzene vapor, 6 hr/day, 5 days/week for 20 exposures. One group received 10% ethanol (EtOH) in the drinking water commencing 20 hr prior to the initial exposure and continuing 5 days/week throughout the study. The second group received tap water. The uptake and clearance of benzene was followed in the blood during and after the 1st and 20th exposures. During the first benzene exposures, the mean steady state benzene concentrations in benzene/EtOH-treated mice and benzene/water-treated mice were 5.2 and 10.7 micrograms/ml, respectively. The mean elimination rate constants for the benzene/EtOH- and benzene/water-treated groups were 0.124 and 0.042 min-1, respectively. By 20 exposures, the benzene/EtOH group showed no change in mean blood steady state concentration (Css); however, the Css of the benzene/water group was reduced to 7.9 micrograms/ml. The mean elimination rate constants for the two groups were not different after the 20th exposure. The benzene/water mice exhibited a shift from mono-to biexponential clearance between the 1st and 20th exposures. Monoexponential clearances were observed for the benzene/EtOH group at both time points. These results indicate that 1 day of 10% EtOH consumption causes dramatic effects on benzene kinetics. After 20 days of treatment, the benzene/water and benzene/EtOH animals are kinetically similar. These changes in kinetics can be explained by the ability of ethanol and benzene to alter benzene metabolism.