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Biomedical subjects

G Johanson

Publications and source records attributed to G Johanson.

78 records · Page 5Linked to original sources

Toxicokinetics of 1,2,4-trimethylbenzene in humans exposed to vapours of white spirit: comparison with exposure to 1,2,4-trimethylbenzene alone.

This study compares the toxicokinetics of inhaled 1,2,4-trimethylbenzene (124TMB) in men exposed to white spirit with that previously observed in the same individuals exposed to 124TMB alone. The appropriateness of using dimethylhippuric acid (DMHA) metabolites of 124-, 123- and 135TMB in urine as biomarkers of exposure is also addressed and the kinetics of n-decane, n-undecane and 123TMB is investigated. The toxicokinetics of 124TMB was studied in nine male, healthy volunteers exposed to solvent vapours in an exposure chamber for 2 h during a work load of 50 W. The subjects were exposed to 2 ppm (11 mg/m3) of 124TM B during exposure to 300 mg/m3 of white spirit. The 124TMB isomer was analysed in blood, urine and exhaled air by gas chromatography. The DMHA metabolites of all three TMB isomers were analysed in urine by high-performance liquid chromatography. The results were compared with previously published exposures to 2 and 25 ppm (120 mg/m3) of 124TMB vapour alone. In addition, the occurrence of acute effects was studied by means of a questionnaire. Irritation and central nervous system (CNS) symptoms were recorded by ratings on a 100 mm visual analogue scale. Blood levels of 124TMB and excretion rates of 3,4-DMHA in urine were markedly elevated both during and after exposure to white spirit compared to the same exposure level of 124TMB alone. No irritation or CNS effects were reported in the questionnaire at any exposure condition. It appears that components in white spirit interfere with the metabolic elimination of 124TMB. This should be considered in biological exposure monitoring as well as in risk assessment.

Adult↗

Liquid/air partition coefficients of the trimethylbenzenes.

Liquid/air partition coefficients (lambda) of the three isomers of trimethylbenzene (1,2,3-,1,2,4-, and 1,3,5-TMB) were determined in vitro using automated head space gas chromatography. The liquids used were water (physiological saline), fresh human blood, and olive oil. The lambda water/air were 1.23 (95% confidence interval 1.11-1.35) for 1,3,5-TMB, 1.61 (1.47-1.75) for 1,2,4-TMB, and 2.73 (2.54-2.92) for 1,2,3-TMB. Corresponding lambda blood/air were 43.0 (40.8-45.2), 59.1 (56.9-61.3), and 66.5 (63.7-69.3). As expected, the TMBs have a high affinity for olive oil, the lambda oil/air being 9,880 (9,620-10,140), 10,200 (9,900-10,400), and 10,900 (10,500-11,300), respectively. It is notable that all partition coefficients increase in the order 1,3,5-TMB < 1,2,4-TMB < 1,2,3-TMB.

Air↗

Liquid/air partition coefficients of methyl and ethyl T-butyl ethers, T-amyl methyl ether, and T-butyl alcohol.

Partition coefficients are essential to a description of the uptake and distribution of volatile substances in humans and in the development of physiologically based pharmacokinetic models. Liquid/air partition coefficients (lambda) of three ethers, methyl t-butyl ether (MTBE), ethyl t-butyl ether (ETBE), and t-amyl methyl ether (TAME) were determined in vitro by head space-gas chromatography. These ethers, and especially MTBE, are used in unleaded gasoline to enhance the oxygen and octane content, and to reduce the output of carbon monoxide during combustion. Partition coefficients of t-butyl alcohol (TBA), a metabolite of MTBE, were determined also. The liquids tested were fresh human blood, water (physiological saline), and olive oil. The (lambda)blood/air values were: 17.7 (95% confidence interval 17.0-18.4) for MTBE; 11.7 (11.3-12.1) for ETBE; and 17.9 (17.3-18.5) for TAME. Corresponding (lambda)water/air values were 15.2 (14.9-15.5), 8.39 (8.19-8.59), and 11.9 (11.7-12.1). The ethers have a higher affinity for oil, the values for (lambda)oil/air being 120 (114-125), 190 (183-197), and 337 (320-354), respectively. As expected, the (lambda)blood/air and (lambda)water/air for TBA were much higher than for the ethers, 462 (440-484) and 603 (590-617), respectively. The (lambda)oil/air was 168 (161-174) for TBA. The interindividual variability of the (lambda)blood/air (10 subjects) was calculated as the coefficient of variation, and estimated as: 14% for MTBE, 20% for ETBE, 20% for TAME, and 30% for TBA. No significant difference was seen in the (lambda)blood/air between the sexes.

Analysis of Variance↗