title: Biological monitoring of experimental human exposure to trimethylbenzene.
abstract: Trimethylbenzene (TMB) is a component of numerous commercial preparations of organic solvents (Farbasol, Solvesso, Shellsol) used in the chemical, plastics, printing and other industries. TMB is a mixture of three isomers (pseudocumene-1,2,4-TMB; mesitylene-1,3,5-TMB; hemimellitene-1,2,3-TMB). The proportion of individual isomers in the mixture differs. The aim of this study was to obtain toxicokinetic data on the absorption and elimination of trimethylbenzene and its metabolites in biological fluids and to investigate the relationship between the biological indices of exposure and the absorbed dose. Eight-hour inhalation tests were performed in a toxicological chamber, The subjects were eight volunteers aged 20-39 with no history of exposure to TMB. They were exposed to pseudocumene, mesitylene or hemimellitene at concentrations ranging from 5 to 150 mg/m3 air. Exhaled air, capillary blood and urine samples were collected before, during and after the exposure. The determinations of TMB or its metabolites were performed using gas chromatography (HP 5890 II Plus, MSD, FID). Pulmonary ventilation in the volunteers ranged from 0.56 to 1.0 m3/h. The retention of 1,2,4-TMB; 1,3,5-TMB; 1,2,3-TMB in the lungs was 68%, 67% and 71%, respectively. The elimination of TMB from capillary blood occurred in accordance with the open three-compartment model. Urinary excretion of dimethylbenzoic acids (DMBA) proceeded according to the open two-compartment model. Based on the toxicokinetic data, a simulation model of accretion and excretion of DMBA in urine during a 14-day period was developed. The highest rates of metabolite excretion and the highest quantities of DMBA in urine during 24-h intervals were observed on day 5 of exposure. The relationship between the levels of TMB or DMBA in biological material and TMB air concentration or absorbed dose were determined. To select the urine fraction suitable for determining occupational TMB exposure, linear regression analysis was performed. The biological exposure limit (BEL) for TMB has been proposed, with the current maximum allowable concentration (MAC) value of 100 mg/m3 (Polish standard) baseline value.
authors.affiliation: Department of Biological Monitoring, Institute of Occupational Medicine, Lódź, Poland.
authors.forename: P
authors.initials: P
authors.lastname: Kostrzewski
authors.forename: A
authors.initials: A
authors.lastname: Wiaderna-Brycht
authors.forename: B
authors.initials: B
authors.lastname: Czerski
mesh_terms: D000042:Absorption; D000280:Administration, Inhalation; D000328:Adult; D001555:Benzene Derivatives / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D001565:Benzoates / Q000652:urine; D001944:Breath Tests; D002849:Chromatography, Gas; D004305:Dose-Response Relationship, Drug; D004784:Environmental Monitoring; D006801:Humans; D008168:Lung / Q000378:metabolism; D016273:Occupational Exposure; D012123:Pulmonary Ventilation / Q000187:drug effects; D012015:Reference Standards; D015203:Reproducibility of Results; D013329:Structure-Activity Relationship
chemical_list: D001555:Benzene Derivatives; D001565:Benzoates; C010313:pseudocumene; C094650:3,5-dimethylbenzoic acid; C010179:hemimellitene; C010219:mesitylene