Aims: To evaluate possible differences between men and women in acute health effects after controlled short term chamber exposure to vapours of two common organic solvents. Methods: Fifty six healthy volunteers (28 per sex) were exposed to 150 ppm 2-propanol, 50 ppm m-xylene, and clean air for two hours at rest. The subjects rated symptoms on a visual analogue scale before, during, and after the exposure. Blinking frequency was measured continuously during exposure. Pulmonary function, nasal swelling, inflammatory markers (lysozyme, eosinophilic cationic potein, myeloperoxidase, albumin) in nasal lavage and colour vision (Lanthony D-15 desaturated panel) were measured before and at 0 and 3 hours after the exposure. Results: There were no significant sex differences in response to solvent exposure with respect to blinking frequency, lung diffusing capacity, nasal area and volume, inflammatory markers in nasal lavage, and colour vision. Increased symptoms were rated by both sexes for nearly all 10 questions during exposure to 2-propanol or m-xylene, most increases being significant at one time point at least. The rating of "discomfort in the throat or airways" increased more in women during exposure to 2-propanol or m-xylene. During exposure to 2-propanol the rating of "fatigue" was more increased in men after one hour, but more increased in women after two hours of exposure. With regard to pulmonary function, women had small but significant decreases in FVC, FEV 1 /FVC, and FEF 75 three hours after exposure to m-xylene, but only the decrease in FVC was significantly different from that in men. Conclusion: Our results suggest that women are slightly more sensitive than men to the acute irritative effects of 2-propanol and m-xylene vapours.

The liquid/air partition coefficients of four common terpenes, a-pinene, ,B-pinene, 3-carene, and limonene, have been determined in vitro using head space technique. The liquids used were water, human blood, and olive oil. a-Pinene, P-pinene, and 3-carene were practically insoluble in water The aim of the present study was to determine the in vitro blood/air, oil/air, and water/air partition coefficients of four common terpenes: a-pinene, ,Bpinene, 3-carene, and limonene. Materials and methods CHEMICALSThe chemicals used were sodium chloride (analytical grade, Merck), olive oil (purum, Kebo Lab AB), apinene (98%, Aldrich), a-pinene (98%, Aldrich), 3-carene (95%, Aldrich), and limonene (99%, Fluka Chemie AG). All chemicals were used without further purification. SAMPLE PREPARATIONBlood was collected from the brachial vein of ten healthy volunteers (five men and five women) in heparinised 10 ml Vacutainer tubes (Beckton Dickinson, Paramus, NJ) and were pooled immediately before the experiment. Aliquots of 0 5 ml olive oil, 2 ml water (containing 0 3 M sodium chloride), or 2 ml pooled fresh human blood were added to a head space vial (22-4 ml, SD = 0 2). A reference vial was filled with glass beads to a volume corresponding to the sample volume (0-5 and 2 ml, respectively) and treated exactly the same way as the sample; this was done to reduce the difference in pressure which could affect the partition coefficient.To obtain the desired concentrations (0-84-354 uM in oil and 0-21-89 jM in blood and water) 3, 30, or 250 pl of each terpene was added to a thermostated (37°C) air chamber of 4-445 1 volume. After 20 minutes equilibration (37C) a sample of0 1, 0-25, or 0-5 ml was taken out with a gas tight syringe and added into a head space vial. Before the standards were made, the head space vials were thermostated (37C) and capped with Teflon lined rubber stoppers. An air volume (corresponding to the sampling volume later added to each vial) was taken from each vial with a gas tight syringe. Blanks ofblood, olive oil, and water were made without added terpenes. Double samples were made, in each liquid, for all the concentrations. GAS CHROMATOGRAPHIC ANALYSISThe terpenes in the gas phase of the headspace vials were determined by gas chromatography (Perkin Elmer 8700) using a head space autosampler (Perkin Elmer HS-101) and a flame ionisation detection. A polar, wide bore capillary glass column (Supelcowax 10, Supelco inc 30 m, 0 75 mm inner diameter,

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The aim of this study was to examine if the drug chlorzoxazone has any influence on the toxicokinetics of acetone and toluene. Chlorzoxazone is mainly metabolized by the same enzyme (Cytochrome P450 2E1) as ethanol and many other organic solvents. Ten male volunteers were exposed to solvent vapor (2 h, 50 watt) in an exposure chamber. Each subject was exposed to acetone only (250 ppm), acetone + chlorzoxazone, toluene (50 ppm) only, toluene + chlorzoxazone, and chlorzoxazone only. Chlorzoxazone (500 mg) was taken as two tablets 1 h prior to solvent exposure. Samples of blood, urine and exhaled air were collected before, during and until 20 h post exposure. The samples were analyzed by head-space gas chromatography (acetone and toluene) and high-performance liquid chromatography (chlorzoxazone, 6-hydroxychlorzoxazone and hippuric acid). The time-concentration curves of acetone and toluene in blood were fitted to one- and four-compartment toxicokinetic models, respectively. Intake of chlorzoxazone was associated with slight but significant increases in the area under the blood concentration-time curve (AUC) and steady state concentration of acetone in blood, along with non significant tendencies to an increased half time in blood and an increased AUC in urine. Except for a delayed excretion of hippuric acid in urine, no effects on the toluene toxicokinetics were seen after chlorzoxazone treatment. Small increases in chlorzoxazone plasma levels were seen after exposure compared to chlorzoxazone alone. These interactions, although statistically significant, seem to be small compared to the interindividual variability on metabolism and toxicokinetics.

Petroleum products with low content of aromatics have been increasingly used during the past years. This study investigates tissue disposition of dearomatised white spirit. In addition, brain neurotransmitter concentrations were measured. Male rats were exposed by inhalation to 0, 400 (2.29 mg/1), or 800 p.p.m. (4.58 mg/l) of dearomatised white spirit, 6 hr/day, 5 days/week up to 3 weeks. Five rats from each group were sacrificed immediately after the exposure for 1, 2, or 3 weeks and 2, 4, 6, or 24 hr after the end of 3 weeks' exposure. After 3 weeks of exposure the concentration of total white spirit was 1.5 and 5.6 mg/kg in blood; 7.1 and 17.1 mg/kg in brain; 432 and 1452 mg/kg in fat tissue at the exposure levels of 400 and 800 p.p.m., respectively. The concentrations of n-nonane, n-decane, n-undecane, and total white spirit in blood and brain were not affected by the duration of exposure. Two hours after the end of exposure the n-decane concentration decreased to about 25% in blood and 50% in brain. A similar pattern of elimination was also observed for n-nonane, n-undecane and total white spirit in blood and brain. In fat tissue the concentrations of n-nonane, n-decane, n-undecane, and total white spirit increased during the 3 weeks of exposure. The time to reach steady-state concentrations is longer than 3 weeks. After the 3 weeks' exposure the fat tissue concentration of n-nonane, n-decane, n-undecane, and total white spirit decreased very slowly compared with the rate of decrease in blood and brain suggesting that long-lasting redistribution from fat to brain may occur. One week of exposure at 800 p.p.m. caused a statistically significant increase in whole brain dopamine concentration while the noradrenaline concentration was unaffected. Exposure at both exposure levels for 1 week caused a statistically significantly decreased concentration of 5-hydroxytryptamine in whole brain. The reduction was related to the exposure concentration. These changes in neurotransmitter concentrations were normalised after 2 and 3 weeks' exposure. In conclusion, after 3 weeks of exposure the fat:brain:blood concentration coefficients for total white spirit were approximately 250:3:1, and redistribution from fat to brain is possible. As total white spirit behaved similarly to the n-alkanes in blood, brain, and fat tissue, we suggest that the non-n-alkane white spirit components possess toxicokinetic properties similar to the n-alkanes.