Are women more sensitive than men to 2-propanol and m-xylene vapours?

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 protein, 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.

Styrene oxide in blood, hemoglobin adducts, and urinary metabolites in human volunteers exposed to (13)C(8)-styrene vapors.

Styrene is used in the manufacture of plastics and polymers and in the boat-building industry. The major metabolic route for styrene in rats, mice, and humans involves conversion to styrene-7,8-oxide (SO). The purpose of this study was to evaluate blood SO, SO-hemoglobin (SO-Hb) adducts, and urinary metabolites in styrene-exposed human volunteers and to compare these results with data previously obtained for rodents. Four healthy male volunteers were exposed for 2 h during light physical exercise to 50 ppm (13)C(8)-styrene vapor via a face mask. Levels and time profiles of styrene in exhaled air, blood, and urine (analyzed by GC) and urinary excretion patterns of mandelic acid and phenylglyoxylic acid in urine (analyzed by HPLC) were comparable to previously published volunteer studies. Maximum levels of SO in blood (measured by GC-MS) of 2.5-12.2 (average 6.7) nM were seen after 2 h, i.e., in the first sample collected after exposure had ended. The styrene blood level in humans was about 1.5 to 2 times higher than in rats and 4 times higher than in mice for equivalent styrene exposures. In contrast the SO levels in human blood was approximately fourfold lower than in mice. The level of hydroxyphenethylvaline (determined by GC-MS-MS) in pooled blood collected after exposure was estimated as 0.3 pmol/g globin corresponding to a SO-Hb adduct increment of about 0.003 pmol/g and ppmh. NMR analyses of urine showed that a major portion (> 95%) of the excreted (13)C-derived metabolites was derived from hydrolysis of SO, while only a small percentage of the excreted metabolites (< 5%) was derived from metabolism via phenylacetaldehyde. Signals consistent with metabolites derived from other pathways of styrene metabolism in rodents (such as glutathione conjugation with SO or ring epoxidation) were not detected.

Distribution of dearomatised white spirit in brain, blood, and fat tissue after repeated exposure of rats.

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.

Toxicokinetic interactions between orally ingested chlorzoxazone and inhaled acetone or toluene in male volunteers.

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.

The effectiveness of respirators measured during styrene exposure in a plastic boat factory.

In a plastic boat company we studied workers' attitudes toward wearing respiratory protective equipment and differences in styrene exposure received with and without respirators. The workers studied used either half-facepiece air-purifying or full-face air-supplied respirators as much as possible during the first day of the study. On the second day respirators were used only for short periods or not at all. Individual styrene exposures were measured by personal air sampling in the breathing zone. When using respirators the exposure was measured both inside and outside the respirators. The styrene metabolites mandelic and phenylglyoxylic acids were determined in urine samples collected during the workday. The eleven workers studied used the respirators 52% of the time on the first day and 7% of the time on the second. The reasons for not wearing respirators were that they delayed work, were too tight and uncomfortable, made it difficult to breath, and/or became too warm. The use of respirators during work operations such as spraying, laminating, and painting reduced the styrene exposure by 56%-92%. The excretion rate of mandelic and phenylglyoxylic acids in urine collected at the end of the working day was 30%-99% lower when respirators were worn than when they were not.

Liquid/air partition coefficients of four terpenes.

The liquid/air partition coefficients of four common terpenes, alpha-pinene, beta-pinene, 3-carene, and limonene, have been determined in vitro using head space technique. The liquids used were water, human blood, and olive oil. alpha-Pinene, beta-pinene, and 3-carene were practically insoluble in water and limonene was slightly soluble; all were readily dissolved in olive oil. The oil/air partition coefficients ranged from 2900 to 5700 in the order alpha-pinene, beta-pinene, 3-carene, and limonene. The blood/air partition coefficients ranged from 15 to 42 in the same order as for oil/air.

Occurrence of styrene-7,8-oxide and styrene glycol in mouse after the administration of styrene.

Styrene-7,8-oxide and its hydrated product styrene glycol were determined in mouse tissues at different times (0.5-5 h) after the intraperitoneal administration of 7-[14C]-styrene (3.8 mmol/kg). In a study of the influence of dose on the metabolite pattern of styrene, mice were killed 2 h after a dose of 1.1, 2.3, 3.4, and 5.1 mmol/kg, respectively. The mouse tissues studied (blood, liver, kidney, lung, brain, subcutaneous adipose tissue) were isolated and extracted first with hexane to remove styrene and styrene-7,8-oxide and then with ethyl acetate to remove styrene glycol. beta-Glucuronidase was used to liberate conjugated styrene glycol. A gas-liquid chromatographic method based on the use of an electron capture detector (GLC-EC) was used to quantify styrene glycol, as well as styrene-7,8-oxide, after hydrolysis. In addition all homogenates and extracts were assayed by radioactivity counting. Styrene-7,8-oxide and styrene glycol reached maximum concentrations within 2 h. The highest levels of styrene-7,8-oxide were detected in the kidneys and subcutaneous adipose tissue, while the lungs showed the lowest levels. Styrene glycol was found in the highest concentrations in the kidneys, liver, blood, and lungs. The concentration of unmetabolized styrene increased exponentially at higher doses. There seemed to be a linear increase with the dose of styrene-7,8-oxide and styrene glycol in all the tissues studied. The more polar metabolites occurred at relatively lower levels in the liver and kidneys at higher doses. In a complementary study the epoxide hydratase inhibitor trichloropropene oxide was added to the removed tissues, and the hexane extracts were analyzed for styrene-7,8-oxide both by GLC-EC and mass spectrometry (GLC-MS).

Tissue distribution of styrene, styrene glycol and more polar styrene metabolites in the mouse.

A primary objective of the present investigation was to determine the tissue distribution of styrene, styrene glycol, and more polar metabolites in mice at different times (0.5-5 h) after the intraperitoneal administration of styrene (3.3 mmol/kg). Another aim was to determine the dose dependence of the metabolite pattern of styrene in the different tissues. The dose range chosen was 1.1-4.9 mmol of styrene/kg administered intraperitoneally, and the time delay 2 h after dosing. The highest initial concentrations of unchanged styrene were found in adipose tissue, pancreas, liver, and brain. Styrene glycol reached its maximum concentration within 1 h in most tissues. The levels in the kidneys, lungs, pancreas, and liver far exceeded those in subcutaneous adipose tissue. Only in the liver and kidneys was a notable amount of styrene glycol conjugated. Polar metabolites occurred to a considerable extent in the liver, kidneys, lungs, and plasma. The concentration of unmetabolized styrene seemed to increase exponentially with the dose in subcutaneous adipose tissue, liver, kidneys, lungs, and brain. No tendency towards a decreased relative occurrence of styrene glycol was observed at higher doses. However, when the dose was increased, the more polar metabolites occurred at relatively lower levels in all tissues except brain.