The disposition and metabolism of naphthalene in rats.

The aim of this study was to investigate the distribution, excretion and metabolism of naphthalene-[ring-U-3H] in rats. The experiments were performed on 54 male outbred IMP: Wist rats with body weight of 200-220 g. The compound was administered intraperitoneally in olive oil in a single dose of 20 mg/kg (about 540 kBq per animal). 3H radioactivity was traced in selected organs and tissues, blood, urine and faeces, 1-72 h following the administration. The main metabolites were isolated from urine and identified by the GC-MS method. Urine and faeces proved to be the main route of tritium elimination. Over 88% of the compound was excreted during the first 72 hours. Maximum level of tritium in plasma was observed at the 2nd h after administration following a biphasic decline. Half-lifes for phases I and II were 0.8 and 99 h, respectively. In erythrocytes 3H-decline was monophasic with the half-life of about 9 h. In organs and tissues, the highest concentrations during the first hours after administration were detected in the fat, liver and kidneys. Then, gradual decline of tritium was noticed in all examined tissues. In urine of rats the following substances were identified: (1) naphthalene, (2) 1-naphthol, (3) 2-naphthol, (4) 1,2-naphthalenediol-1,2-dihydro, (5) methylthionaphthalenes (two isomers). In conclusion, naphthalene has a relatively rapid turnover rate in the rat organism and does not form considerable deposits in the tissue. The metabolism encompasses ring hydroxylation, hydration and glutathione conjugation.

The disposition and metabolism of 1,3-dibromobenzene in the rat.

The distribution, excretion and metabolism of 1,3-dibromobenzene following a single i.p. administration to rats 100 or 300 mg/kg was investigated using radiotracer [3H] and GC-MS technique. After 72 hours about 74 to 90% were excreted in urine. The highest radioactivity was observed in the liver, kidneys and fat tissue. Later on a steady decline of radioactivity was apparent in all investigated tissues except for blood cells and the sciatic nerve, where constant levels were noted. In urine the following substances were identified and quantified by GC peak areas: unchanged 1,3-DBB (18%), dibromophenols (34%), dibromothiophenols (28%), dibromothioanisole (1.8%), bromophenol (5.5%), bromohydroxythiophenols (5%), and bromohydroxythioanisole (7.5%).

Biological monitoring of experimental human exposure to trimethylbenzene.

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.

Elimination of 1-hydroxypyrene after human volunteer exposure to polycyclic aromatic hydrocarbons.

The aim of this study was to estimate the kinetics of 1-hydroxypyrene (1-HP) elimination after inhalation exposure to polycyclic aromatic hydrocarbons (PAHs). Samples of inhaled and exhaled air were collected on glass fiber filters backed with tubes filled with Amberlit XAD-2 resin. The filters were extracted by cyclohexane and Amberlit--by acetonitrile. Extracts for the determination of pyrene and benzo[a]pyrene (B[a]P) concentrations were analyzed by high-performance liquid chromatography (HPLC). 1-Hydroxypyrene in urine was determined after its preconcentration on a C-18 column (solid phase extraction method) using the same analytical technique. Five male volunteers were exposed for 6 h (two times, with a 1-month interval) to a PAH mixture at an aluminium plant. The volunteers were breathing at rest through facial mask equipped with a 1000-ml compensation container which allows collection of the exhaled air. Inhaled air samples were collected in the breathing zone of each volunteer. Urine samples were collected until the 71st hour after the onset of exposure. The average respiratory retention of pyrene was found to be 61%. The 1-HP elimination process could be described by one-compartment model with the half-live of 9.8 hour (95% CI 7.9-11.7 h). The simulation of 1-HP elimination in urine during a working week (4 days) indicates that the balance between absorption and elimination is achieved at the end of the second day.

[Comparison of standard methods for determination of pseudocumene in urine using gas chromatography with the headspace technique and a new method using a headspace automatic sampler]. / Porównanie metody standardowej oznaczania pseudokumenu w moczu z zastosowaniem chromatografii gazowej oraz techniki headspace z metoda, w której wykorzystano automatyczna przystawke headspace.

The biological indicators that have been proposed for monitoring occupational exposure are: concentration of the solvent or metabolized compounds in alveolar or expired air samples, in venous or arterial capillary blood samples and in urine samples. Recently, many researches have reported significant relationships between the time-weighted average exposure and the urinary concentrations for various solvents. The aim of our study was to compare two methods in which urinary concentrations of pseudocumene were determined by gas chromatography using headspace technique. The standard method was based on determining concentration of organic solvents in 100 mm3 or 1 cm3 samples of urine. The incubation conditions were as follows: equilibration temperature and time: 70 degrees C, 30 min., respectively. 1 cm3 of gas phase was sampled with a gas-tight syringe and injected into a gas chromatograph. The new method using Headspace Sampler was based on determining concentrations of solvents in 10 cm3 samples of urine. The operating conditions were: equilibration time 30 min.; equlibration temperature 80 degrees C; pressurization time 0.1 min.; loop fill time 0.1 min.; loop equilibration 0.1 min.; loop equilibration time 0.05 min.; inject time 1 min.; loop temperature 150 degrees C, transfer line temperature 150 degrees C. HP 7694 Headspace Sampler minimizes sample degradation with a chemically inert pathway extending from the sample loop to the column head. The analytical parameters of both methods (linearity, precision, reproducibility, stability and sensitivity) are fully compatible with the principles of biological monitoring. Application of the headspace autosampler eliminated interference from the biological matrix and made it possible to achieve very low detection limit.

[Alkyl derivatives of benzene, indene, naphthalene, diphenyl and fluorene as a potential source of occupational and environmental exposure]. / Alkilowe pochodne benzenu, indenu, naftalenu, difenylu oraz fluorenu jako potencjalne zródla narazenia zawodowego i srodowiskowego.

Mixtures of organic solvents are used extensively in industry. The aim of this study was to develop a method for the determination of components of commercial multi-component solvent mixtures, and to perform qualitative and quantitative analyses of the mixtures. Farbasol, Solvesso and Shellsol mixtures were analysed by gas chromatography with a mass spectrometry detector (GC/MS). The composition of mixtures was determined using the mass spectrum computer analysis. Fractions of alkyl benzene, naphthalene and diphenyl derivatives were isolated. The proportions of the individual fractions in the mixtures differed. A predominant fraction was present in each mixture. Solvents (trimethylbenzene, tetramethylbenzene, ethyltoluene, diethylbenzene, isopropylotoulene) which significantly increase health risk due to their suspected neurotoxicity, were identified in each mixture.

[Determination of dimethylbenzoic acid isomers in urine by gas chromatography]. / Oznaczanie izomerów kwasów dimetylobenzoesowych w moczu metoda chromatografii gazowej.

Trimethylobenzene (TMB) is a main ingredient of many organic solvents used in industry. In Farbasol (Polish trade name of the solvent) TMB occurs as a mixture of three isomers: pseudocumene (1, 2, 4-TMB) 30%; mesitylene (1, 3, 5-TMB) 15%; hemimellitene (1,2,3-TMB) 5%. As it is known in human organism, TMB is metabolized mainly to dimethylbenzoic (DMBA) and dimethylhippuric (DMHA) acids, and some authors suggest, that the acids excreted in urine can be biological indicators of exposure to TMB. This study was aimed at developing the method of determination of DMBA isomers in urine. Biological material was hydrolyzed with sodium hydroxide and next extracted with diethyl ether. DMBA concentration in urine was determined by gas chromatography using a variant of quantitative analysis with internal standard (5-methyl-2-isopropylphenol, thymol). Analytical parameters of the developed method of determination of DMBA isomers in urine such as linearity, precision, reproducibility, stability (192 days, when urine samples stored at-18 degrees C), detectability limit (400 micrograms/dm3) have been fully compatible with the requirements of biological monitoring. In order to confirm the presence of DMBA isomers in urine, four volunteers were exposed (8 hours) to Farbasol in toxicological chamber. The TMB concentration in the air, determined by means of gas chromatograph (HP 5890), amounted to 100 mg/m3 (MAC value in Poland). In urine samples collected 2,3-; 2,4-; 2,5-; 2,6-; 3,4-; 3,5-dimethylbenzoic acids were identified by means of GC/MSD.(ABSTRACT TRUNCATED AT 250 WORDS)

[Exposure to organic solvent vapors during production of lacquers for automobile painting]. / Narazenie na pary rozpuszczalników organicznych podczas produkcji lakierów samochodowych.

This study was aimed at the development and improvement of the methods for determining solvent vapours to estimate occupational exposure in paint and varnish shops. Gas chromatographic method and mass spectrometry (GC-MS) were applied respectively for quantitative determination and identification of toxic substances in the work-room air in plants manufacturing carbamide car paints and commonly used phthalic paints. Particular attention was paid to aromatic hydrocarbon components of farbasol: ethyltoluenes, propylbenzene, isopropylbenzene, mesitylene, hemimelitene, pseudocumene, diethylbenzenes and cymene. These hydrocarbons constitute about 95% of farbasol. At present, the evaluation of exposure in paint and varnish factories and in paint shops in Poland is insufficient because of the lack of TLV values for the above solvents, as well as inadequate methods of determination used in majority of laboratories.