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1.  Toxicokinetics of toluene and urinary excretion of hippuric acid after human exposure to 2H8-toluene. 
Nine male volunteers were exposed to 2H8-toluene (200 mg/m3 for two hours during a workload of 50 W) via inspiratory air with the aid of a breathing valve and mouthpiece. Labelled toluene was used to differentiate between hippuric acid originating from exposure to toluene and hippuric acid normally excreted in urine. The total uptake of toluene was 2.2 (standard deviation (SD) 0.2) mmol, or 50% of the amount inhaled. Four hours after the end of exposure 1.4 (SD 0.3) mmol or 65% of the total uptake had been excreted in urine as 2H-hippuric acid and 20 hours after the end of exposure the cumulative excretion of 2H-hippuric acid was 1.8 (SD 0.3) mmol, or 78% of the total uptake. By contrast the cumulative excretion of labelled plus unlabelled hippuric acid exceeded the total uptake of toluene already after four hours. The excretion rate of 2H-hippuric acid was highest, about 5 mumol/min, during exposure and the SD between the subjects was low. The background concentrations of unlabelled hippuric acid in urine were high, however, and there were large differences between subjects. These findings confirm earlier indications that for low exposure, urinary hippuric acid concentration cannot be used for biological monitoring of exposure to toluene.
PMCID: PMC1061234  PMID: 8431392
2.  Effects of consumption of ethanol on the biological monitoring of exposure to organic solvent vapours: a simulation study with trichloroethylene. 
This study illustrates possible influences of consumption of ethanol on the pharmacokinetic behaviour of inhaled trichloroethylene (TRI) in relation to biological monitoring of exposure. The results were obtained for a standard male worker of 70 kg by physiologically based pharmacokinetic modelling. Depending on the pattern of consumption of ethanol, enzyme inhibition or induction was assumed to prevail in this worker. The inhibition and induction were modelled by assuming competitive metabolic interaction between TRI and ethanol and increased maximum velocity (Vmax) of TRI metabolism respectively. Ingestion of moderate amounts of ethanol before the start of work or at lunch time, but not at the end of work, caused pronounced increases in blood TRI concentrations and decreases in the urinary excretion rates of TRI metabolites, this effect lasting until the next day. The effects were smaller the higher the exposure concentration of TRI. Induction of TRI metabolism, supposedly by consumption of ethanol the previous evening, caused only small changes in the pharmacokinetic profile at 50 ppm, but appreciable changes at 500 ppm.
PMCID: PMC1035417  PMID: 1878312
3.  A simulation study of physiological factors affecting pharmacokinetic behaviour of organic solvent vapours. 
At a given external dose of an inhaled chemical the internal dose or the amount absorbed into the body varies depending on pulmonary ventilation and other physiological factors. Such variability is of concern in the development of biological indices of occupational exposure to organic solvent vapours. This paper discusses how physiological factors may influence the pharmacokinetic behaviour of inhaled organic solvent vapours, especially in relation to monitoring of biological exposure. To illustrate the discussion a computer based physiological pharmacokinetic model was used describing quantitatively the influence of body size, body fat content, and sex on the pharmacokinetic behaviour of trichloroethylene. Absorption, distribution, metabolism and excretion of trichloroethylene were found to vary according to the different anatomical features of men and women. Body build (body weight and body fat content) also affected the pharmacokinetic behaviour of this solvent.
PMCID: PMC1012045  PMID: 2039747
4.  Effects of chronic ethanol consumption on hepatic metabolism of aromatic and chlorinated hydrocarbons in rats. 
The activities of liver drug-metabolising enzymes for 16 aromatic or chlorinated hydrocarbons were measured in male rats after a three-week daily intake of ethanol amounting to 30% of total energy intake. Although the ethanol feeding produced only a slight increase in the microsomal cytochrome P-450 content, it increased the in-vitro metabolism of most hydrocarbons three-to six-fold. That a major part of this enhanced activity disappeared after one-day withdrawal of ethanol suggests that recent intake of ethanol plays an important part in accelerating the metabolism of hydrocarbons. The enzyme activity enhanced by ethanol was found to be related with changes occurring not in the soluble but in the microsomal fractions. A metabolism study using toluene as a model substrate indicated that chronic ethanol consumption increases the in-vivo metabolism of this hydrocarbon in rats.
PMCID: PMC1008756  PMID: 7192567
5.  Partition coefficients of some aromatic hydrocarbons and ketones in water, blood and oil. 
Water/air, blood/air, oil/air, oil/water, and oil/blood partition (or solubility) coefficients of 17 aromatic hydrocarbons and ketones were measured by a newly developed vial-equilibration method, which needs no direct measurements of the concentration either in the liquid or in the air phase, but only the gas chromatographic peak heights of the air in the sample (in which a test material is contained) and reference vessels (containing no test material). It was found that the blood/air partition coefficients for aromatic hydrocarbons are correlated closely with the product of water/air and oil/air partitiion coefficients, whereas those for ketones are almost in the same range as the water/air, irrespective of the oil/air partition coefficients.
PMCID: PMC1008570  PMID: 500783
6.  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.
PMCID: PMC1008083  PMID: 1103957
7.  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.
PMCID: PMC1008060  PMID: 1171695
8.  Differences following skin or inhalation exposure in the absorption and excretion kinetics of trichloroethylene and toluene. 
The concentrations of trichloroethylene in breath and blood and the urinary excretion of its metabolites following 30 minutes' direct immersion of one hand in the liquid, were compared with those obtained after four hours' inhalation exposure to the vapour of 100 ppm, described in a previous paper. The comparison shows that the end-tidal air concentrations during the first two hours of the post-exposure period were about twice as high in the case of skin exposure as in that of inhalation exposure, although the uptake of the solvent through the skin was only about one-third of the inhaled uptake. A kinetic approach suggested that differences in trichloroethylene movement in the body would be a principal cause of this discrepancy. The results of a similar series of experiments using toluene suggested that it is less readily taken up than trichloroethylene through the skin. It was concluded from the present investigation that analyses of not only breath but also of blood or urine are necessary and toluene would rarely be absorbed through the skin in toxic quantities during normal industrial use.
PMCID: PMC1008323  PMID: 629888
9.  A pharmacokinetic model to study the excretion of trichloroethylene and its metabolites after an inhalation exposure. 
For a better understanding of absorption, distribution, excretion, and metabolism of trichloroethylene the time-course of blood concentration of the vapour and urinary excretion of its metabolites was examined using a pharmacokinetic model. After a single experimental exposure in which four men inhaled 100 parts per million (ppm) of trichloroethylene for four hours an elimination curve showed three exponential components, that is, X=1-0005e(-16.71t)+0-449e(-1.710t)+0-255e(-0.2027t), where X is that blood concentration in mg/l and t the time in hours from 0 to 10. The overall rate constant for the disappearance of trichloroethylene was found to a agree with the theoretical one, estimated by means of a mathematical model for the blood concentration data. A D8- XD plot, developed from a mathematical model for urinary excretion, could also give a good estimate of rate constant for the transfer of trichloroethylene in the body. The rate constant thus estimated from urinary excretion was consistent with data on the blood concentration.
PMCID: PMC1008172  PMID: 843464

Results 1-9 (9)