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.
Department of Occupational Medicine, National Institute for Working Life, Solna, Sweden.
J
J
Järnberg
G
G
Johanson
A
A
Löf
B
B
Ståhlbom
D000328:Adult; D019540:Area Under Curve; D001555:Benzene Derivatives / Q000737:chemistry / Q000493:pharmacokinetics* / Q000633:toxicity*; D002493:Central Nervous System Diseases / Q000139:chemically induced; D006207:Half-Life; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D006838:Hydrocarbons / Q000737:chemistry / Q000493:pharmacokinetics* / Q000633:toxicity*; D007509:Irritants / Q000493:pharmacokinetics / Q000633:toxicity; D008297:Male; D008875:Middle Aged; D015656:Respiratory Mechanics / Q000187:drug effects; D012997:Solvents / Q000737:chemistry / Q000493:pharmacokinetics* / Q000633:toxicity*
D001555:Benzene Derivatives; D006838:Hydrocarbons; D007509:Irritants; D012997:Solvents; C010313:pseudocumene; C013089:ligroin