Inhalation toxicokinetics of 1,2,4-trimethylbenzene in volunteers: comparison between exposure to white spirit and 1,2,4-trimethylbenzene alone.
The objective of this study was to compare the toxicokinetics of inhaled 1,2,4-trimethylbenzene (1,2,4-TMB) in man after exposure to white spirit with that observed after exposure to 1,2,4-TMB alone. TMBs occur mainly in petroleum products and the TMBs or their metabolites have been suggested as suitable biomarkers of exposure to white spirit and other distillation products. The toxicokinetics were studied in 9 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 11 mg/m3 of 1,2,4-TMB on two occasions; during exposure to 1,2,4-TMB vapour alone and during exposure to 300 mg/m3 of white spirit. The 1,2,4-TMB isomer was analyzed in blood and exhaled air by gas chromatography. In addition, a major urinary metabolite of 1,2,4-TMB, 3,4-dimethylhippuric acid (3,4-DMHA), was analyzed by high performance liquid chromatography. Further the occurrence of acute effects was studied by means of a questionnaire. Irritation and central nervous system symptoms were recorded by ratings on a 100-mm visual analogue scale. Blood levels of 1,2,4-TMB and excretion rates of 3,4-DMHA in urine were markedly elevated both during and after exposure to white spirit as compared to exposure to TMB alone. Thus, it appears that components in white spirit inhibit the metabolic elimination of 1,2,4-TMB. This should be considered in biological exposure monitoring as well as in risk assessment. No irritation or central nervous system effects were reported at these conditions.
Järnberg
J
J
National Institute for Working Life, Department of Toxicology and Chemistry, Solna, Sweden. Jill.Jarnberg@niwl.se.
Johanson
G
G
Löf
A
A
Ståhlbom
B
B
D000280:Administration, Inhalation; D000328:Adult; D000704:Analysis of Variance; D001555:Benzene Derivatives / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D001944:Breath Tests; D002490:Central Nervous System / Q000187:drug effects; D002849:Chromatography, Gas; D002851:Chromatography, High Pressure Liquid; D015331:Cohort Studies; D004784:Environmental Monitoring; D006626:Hippurates / Q000652:urine; D006801:Humans; D006838:Hydrocarbons / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D008297:Male; D008875:Middle Aged; D016273:Occupational Exposure; D012997:Solvents / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D013055:Spectrophotometry, Infrared; D011795:Surveys and Questionnaires
D001555:Benzene Derivatives; D006626:Hippurates; D006838:Hydrocarbons; D012997:Solvents; C028524:3,4-dimethylhippuric acid; C010313:pseudocumene; C013089:ligroin