Neurobehavioral performance in volunteers after inhalation of white spirits with high and low aromatic content.

The content of aromatic hydrocarbons in solvent mixtures, such as white spirits (WS), has been assumed a major contributor to the neurotoxic effects of these compounds. Hence, dearomatized WS have been introduced to the market rapidly in the last decade. Studies investigating other aromatic hydrocarbons (toluene) and animal models have supported the aforementioned assumption, but the current study is the first one to compare acute neurobehavioral effects of exposure to aromatic and dearomatized WS (aWS, daWS) content in human volunteers at current occupational exposure limit values. In a pseudo-randomized crossover design, six female and six male healthy volunteers were exposed to aWS and daWS at two concentrations (100 and 300 mg/m(3)) and to clean air for 4 h at rest. During each of the five exposure conditions, volunteers performed five neurobehavioral tasks that were selected following a multidisciplinary approach that accounted for findings from the cognitive neurosciences and mechanisms of solvent toxicity. Two of the tasks indicated performance changes during aromatic WS exposure, the working memory (WM) and the response shifting task, but both effects are difficult to interpret due to low mean accuracy in the WM task and due to a lack of dose-response relationship in the response shifting task. Healthy human volunteers showed weak and inconsistent neurobehavioral impairment after 4-h exposures to 100 and 300 mg/m(3) aromatic or dearomatized WS. Our multidisciplinary approach of selecting neurobehavioral test methods may guide the test selection strategies in future studies.

Acute effects of exposure to vapors of 3-methyl-1-butanol in humans.

UNLABELLED: The secondary alcohol 3-methyl-1-butanol (3MB, isoamyl alcohol) is used, for example, as a solvent in a variety of applications and as a fragrance ingredient. It is also one of the microbial volatile organic compounds (MVOCs) found in indoor air. There are little data on acute effects. The aim of the study was to assess the acute effects of 3MB in humans. Thirty healthy volunteers (16 men and 14 women) were exposed in random order to 1 mg/m(3) 3MB or clean air for 2 h at controlled conditions. Ratings with visual analogue scales revealed slightly increased perceptions of eye irritation (P = 0.048, Wilcoxon) and smell (P < 0.0001) compared with control exposure. The other ratings were not significantly affected (irritation in nose and throat, dyspnea, headache, fatigue, dizziness, nausea, and intoxication). No significant exposure-related effects were found in blinking frequency, tear film break-up time, vital staining of the eye, nasal lavage biomarkers, lung function, and nasal swelling. In conclusion, this study suggests that 3MB is not a causative factor for health effects in damp and moldy buildings. PRACTICAL IMPLICATIONS: 3-Methyl-1-butanol (3MB) is one of the most commonly reported MVOCs in damp and moldy buildings and in occupational settings related to agriculture and composting. Our study revealed no irritation effects at 1 mg/m3, a concentration higher than typically found in damp and moldy buildings. Our study thus suggests that 3MB is not a causative factor for health effects in damp and moldy buildings.

Acute effects of exposure to 1 mg/m(3) of vaporized 2-ethyl-1-hexanol in humans.

The objective was to assess acute effects from controlled exposure of volunteers to 2-ethyl-1-hexanol, a volatile organic compound that is often found in indoor air. Sixteen males and fourteen females were in random order exposed to 1 mg/m(3) of vapors of 2-ethyl-1-hexanol or to clean air (control exposure) in an exposure chamber during 2 h at rest. The subjects performed symptom ratings on Visual Analog Scales. During exposure to 2-ethyl-1-hexanol subjective ratings of smell and eye discomfort were minimally but significantly increased. Ratings of nasal irritation, throat irritation, headache, dyspnoea, fatigue, dizziness, nausea, and intoxication were not significantly affected. No exposure-related effects on measurement of blinking frequency by electromyography, measurement of the eye break-up time, vital staining of the eye, nasal lavage biomarkers, transfer tests, spirometric and rhinometric measures were seen. No differences in response were seen between sexes or between atopics and non-atopics. Practical Implications It is important to assess acute effects in volatile organic compounds like 2-ethyl-1-hexanol. 2-ethyl-1-hexanol is often found in indoor air generated by degradation of plastic building materials or in new buildings. There are associations between 2-ethyl-1-hexanol in indoor air and respiratory effects, eye irritation, headache, and blurred vision. A controlled chamber exposure study in acute effects was performed. In conclusion, this study showed weak subjective symptom of irritation in the eyes.

Acute effects of exposure to vapours of dioxane in humans.

Information on the acute effects associated with the handling of 1,4-dioxane is sparse. Our aim was to evaluate the acute effects of 1,4-dioxane vapours. In a screening study, six healthy volunteers rated symptoms on a visual analogue scale (VAS), while exposed to stepwise increasing levels of 1,4-dioxane, from 1 to 20 ppm. The initial study indicated no increased ratings at any of the exposure levels; we decided to use 20 ppm (72 mg/m3) as a tentative no observed adverse effect level (NOAEL). In the main study, six female and six male healthy volunteers were exposed to 0 (control exposure) and 20 ppm 1,4-dioxane vapour, for 2 hours at rest. The volunteers rated 10 symptoms on VAS before, during, and after the exposure. Blink frequency was monitored during exposure. Pulmonary function, and nasal swelling, was measured before, and at 0 and 3 hours after exposure. Inflammatory markers in plasma (C-reactive protein, and interleukin-6) were measured before and at 3 hours after exposure. In conclusion, exposure to 20 ppm 1,4-dioxane for 2 hours did not significantly affect symptom ratings, blink frequency, pulmonary function, nasal swelling, or inflammatory markers in the plasma of the 12 volunteers in our study.

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.

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.