Toxicokinetics of 1,2,4-trimethylbenzene in humans exposed to vapours of white spirit: comparison with exposure to 1,2,4-trimethylbenzene alone. 1998

J Järnberg, and G Johanson, and A Löf, and B Ståhlbom
Department of Occupational Medicine, National Institute for Working Life, Solna, Sweden.

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.

UI MeSH Term Description Entries
D007509 Irritants Drugs that act locally on cutaneous or mucosal surfaces to produce inflammation; those that cause redness due to hyperemia are rubefacients; those that raise blisters are vesicants and those that penetrate sebaceous glands and cause abscesses are pustulants; tear gases and mustard gases are also irritants. Counterirritant,Counterirritants,Irritant,Pustulant,Pustulants,Rubefacient,Rubefacients,Vesicant,Vesicants
D008297 Male Males
D008875 Middle Aged An adult aged 45 - 64 years. Middle Age
D002493 Central Nervous System Diseases Diseases of any component of the brain (including the cerebral hemispheres, diencephalon, brain stem, and cerebellum) or the spinal cord. CNS Disease,Central Nervous System Disease,Central Nervous System Disorder,CNS Diseases,Central Nervous System Disorders
D006207 Half-Life The time it takes for a substance (drug, radioactive nuclide, or other) to lose half of its pharmacologic, physiologic, or radiologic activity. Halflife,Half Life,Half-Lifes,Halflifes
D006339 Heart Rate The number of times the HEART VENTRICLES contract per unit of time, usually per minute. Cardiac Rate,Chronotropism, Cardiac,Heart Rate Control,Heartbeat,Pulse Rate,Cardiac Chronotropy,Cardiac Chronotropism,Cardiac Rates,Chronotropy, Cardiac,Control, Heart Rate,Heart Rates,Heartbeats,Pulse Rates,Rate Control, Heart,Rate, Cardiac,Rate, Heart,Rate, Pulse
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D006838 Hydrocarbons Organic compounds that primarily contain carbon and hydrogen atoms with the carbon atoms forming a linear or circular structure. Hydrocarbon,Saturated Hydrocarbons,Unsaturated Hydrocarbons,Hydrocarbons, Saturated,Hydrocarbons, Unsaturated
D000328 Adult A person having attained full growth or maturity. Adults are of 19 through 44 years of age. For a person between 19 and 24 years of age, YOUNG ADULT is available. Adults
D001555 Benzene Derivatives Organic compounds derived from BENZENE. Derivatives, Benzene

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