Excretion of unchanged volatile organic compounds (toluene, ethylbenzene, xylene and mesitylene) in urine as result of experimental human volunteer exposure.

OBJECTIVES: To investigate elimination of unchanged volatile organic compounds (VOC's) through urine and the use of respective data for occupational exposure assessment, six volunteers were exposed under controlled conditions to toluene (TOL), ethylbenzene (EB), xylene (XYL) and mesitylene (MES) at concentrations ranging from 20 to 200 mg/m(3). The study was to elicit the toxicokinetic data and compare the precision of VOC's exposure assessment based on determining unchanged compounds in blood, urine and their metabolites in urine. METHODS: During and after exposure blood and urine samples were analysed by gas chromatography using the headspace and SPME headspace technique RESULTS: The kinetics of VOC's elimination in urine complied with an open two-compartment model. The (half-time) T (1/2 )values varied from 0.45 to 0.88 h for phase I and from 6.7 to 19.2 h for phase II. The precision of the method for unchanged VOC's was similar to that based on unchanged compounds in blood and better than their main metabolites in urine. CONCLUSION: The obtained result indicate that determining unchanged VOC's in urine can be used as an exposure test even in the ranges of VOC's in the air that are much lower than the current TWA for occupational exposure.

Physiologically-based toxicokinetic modeling of durene (1,2,3,5-tetramethylbenzene) and isodurene (1,2,4,5-tetramethylbenzene) in humans.

OBJECTIVES: Physiologically-based toxicokinetic (PB-TK) models are developed to simulate absorption, distribution and excretion of xenobiotics. PB-TK models consist of several groups of compartments, where tissues are grouped together according to physiological parameters (tissue blood flows, tissue group volumes) and physicochemical properties (partition coefficients, metabolic constants). Tetramethylbenzene (TETMB), a mixture of its three isomers: prenitene (1,2,3,4-TETMB), isodurene (1,2,3,5-TETMB), and durene (1,2,4,5-TETMB) is an essential component of numerous commercial preparations of organic solvents. The aim of the study was to develop the PB-TK model for two TETMB isomers, durene and isodurene, in humans. MATERIALS AND METHODS: The assumed PB-TK model groups organs and tissues into five physiological compartments: fat tissue, muscles, organs, liver, and brain. The brain has been considered as a separate compartment due to the potential neurotoxicity of TETMB. Water/air, oil/air and blood/air partition coefficients for durene and isodurene were measured in vitro. Tissue/air partition coefficients were calculated from values of olive/air and water/air partition coefficients and the average fat and water content in different tissues. Tissue/blood partition coefficients were calculated as a tissue/air quotient and the blood/air partition coefficient measured in vitro. The Michaelis-Menten constant (KM) values and maximum metabolism rate constant (VMAX) for selected metabolites of durene and isodurene were obtained in vitro using microsomal fraction of the human liver. RESULTS: The developed model was validated against experimental data obtained earlier as a result of an 8-h exposure of volunteers to durene and isodurene vapors of 10 and 25 mg/m3. The prediction of both TETMB isomers concentration in blood as well as of the elimination rates of 2,4,5-TMBA and 2,3,5-TMBA were close to the results of experimental exposures. CONCLUSIONS: Simulations of one working week inhalation exposure to aromatic hydrocarbons indicate that the elaborated PB-TK model may be used to predict the chemical distribution in different body compartments, based on physicochemical properties.