Occupational exposure to organic solvents and sleep-disordered breathing

STUDY OBJECTIVE: To investigate whether people with occupational exposure to organic solvents have a higher prevalence of obstructive sleep apnea syndrome (OSAS) than the general population and to examine the relationship between snoring and exposure to organic solvents. DESIGN AND PARTICIPANTS: Consecutive patients, aged 30-64 years, referred during a 3-year period to the sleep laboratory at Avesta Hospital, Sweden, because of suspected OSAS made up the patient groups. Following admission, patients underwent a simplified sleep apnea investigation and were divided into two groups, OSAS (n = 320) and snorers (n = 443). A random sample of 296 men and 289 women aged 30-64 years obtained from a register of all country residents maintained by the county tax authority served as referents (controls). Both patients and referents responded to two questionnaires, including questions about occupation, exposure to organic solvents, and other chemical and physical agents. RESULTS: Men with OSAS or snoring and women with snoring had more often been occupationally exposed to organic solvents than the referents, showing an almost twofold increase in risk for those exposed during whole workdays. For men, the risk of OSAS or snoring increased with increasing exposure. CONCLUSION: The result indicates that occupational exposure to organic solvents might cause sleep apnea. A new observation is that even snoring could be caused by exposure to organic solvents. It is important to elucidate whether exposure to organic solvents is a cause of OSAS, because such a finding may have important implications for prevention and treatment of sleep disturbances.     

Neurotoxicity of chronic low-dose exposure to organic solvents: a skeptical review

The absolute configuration of the acyclic side chain of heptopyranosides and heptofuranosides was determined by exciton coupled CD, employing the strongly fluorescent 2-anthroate chromophore. The usage of this chromophore offers significant improvements over previous chemical and spectroscopic procedures since its intense fluorescence greatly facilitates the isolation and HPLC purification at the nanogram scale. The large amplitudes of the bisignate spectra allow CD manipulations in the 1 x 10(-7) M range.     

A study on the neurobehavioral effects of occupational exposure to organic solvents in Korean workers

Atomic absorption spectroscopy was used to assess uptake of Ag+1, Au+4, Cd+2, Cu+2, In+3, Ni+2, Pd+2, and Zn+2 by in vitro cultures of Balb/c 3T3 fibroblasts as a function of concentration of the cations in cell-culture medium. Reversibility of this uptake was also measured. Metal cations exhibited a 400-fold difference in their tendency to accumulate in the cells; In+3 tended to accumulate the most, whereas Pd+2 accumulated the least. Uptake of the cations in the cells increased linearly with the concentration of the cation in the medium for all cations up to their 50% toxicity concentrations. Reversal of this uptake was slower than that of the initial uptake for three cations studied in more detail (Cd+2, In+3, and Ni+2). The duration of the initial exposure affected the proportion of the metal cations that were retained by the cells 5 h after the cations were removed from the medium. The proportion of retained Cd+2 did not change when the initial exposure was increased from 2 h to 6 h, whereas the proportion of retained In+3 decreased and Ni+2 increased over the same period. The tendency of the cells to accumulate these cations correlated with their cytotoxic potency (measured previously).     

Partition behavior of tropane alkaloids between organic solvents and water

The partition behavior of tropane alkaloids (TrA) between organic solvent and water was studied under various conditions. The apparent partition coefficient, log P', increases with pH with a slope of +1 in the acidic to neutral pH range, then tends to approach to a constant value in the alkaline region. Thus the partition of TrA to the organic phase is based on the neutral form of TrA. From the pH dependency of the partition and pH titration of TrA, the intrinsic partition coefficients log P0 and pKa values for each TrA were estimated. Values of pKa and log P0 for scopolamine were smaller than those for atropine or homatropine. It was considered that the presence of the epoxide ring in scopolamine molecule reduces the log P0 and pKa because of its polar and electro-inductive effect. It was also expected from the results of pH-dependent partition behavior that in the low pH region some portion of TrA cations is transferred to the organic phase by forming an ion-pair complex with an anion, in the aqueous phase. The log P' of TrA was measured in the presence of various kinds of anions (halides and alkyl sulfonates, C5-C8) at about pH 2, where almost all TrA are present as a protonated form. The relations between the log P' and the logarithmic concentration of anions is linear at low concentrations of anions as expected from the ion-pair partition equation.(ABSTRACT TRUNCATED AT 250 WORDS)     

Wettability of ferromagnetic powders of the Fe-Co-Ni system by organic solvents

Quantitative data on the wettability of the surface of particles of thermochemically prepared ferromagntic powders have been obtained for the first time. It is established that their wettability can be enhanced by the introduction of surfactant substances. This makes it possible to create different nanostructured materials, for example, glues and sealants in which nanocomposite ferromagnetics serve as fillers. These materials are used to seal cracks, and eliminate defects in active main gas pipelines operating under extreme conditions.     

Preparation of mouse monoclonal antibodies to okadaic acid and their binding activity in organic solvents

Seven of 20 mouse monoclonal antibodies to OA, OA8-2, OA10-8, OA22-22, OA227-11, OA296-1, OA423-3, and OA958-2, were studied as to their binding to OA in organic solvents. OA423-3 (IgG1-kappa) and OA958-2 (IgG1-kappa) in 90-100% methanol retained their binding activities with both immobilized and free antibodies. Whereas OA8-2 (IgG2a-kappa), OA10-8 (IgG1-kappa), OA22-22 (IgG2a-kappa), OA227-11 (IgG1-kappa), and OA296-1 (IgM-kappa) did not bind to OA in over 50-60% methanol. The results of a non-competitive inhibition assay for OA indicated that in a methanolic or ethanolic solution, the binding ability of immobilized OA423-3 decreased as the concentration of each alcohol increased. The concentration of OA at the midpoint between the upper and lower plateaus of the inhibition curve was 0.18 ng/ml in 0% methanol and 570 ng/ml in 100%, respectively. In 0-50% of each of acetone, diethyl ether, and benzene in methanol, the binding ability of OA423-3 remained at the level in 100% methanol. OA958-2 showed similar binding properties to OA423-3. No relationship between the subclass of the immunoglobulin and the binding activity of the antibody in organic solvents was observed. These results indicate that the OA423-3 and OA958-2 antibodies are useful for the development of a new ELISA method for OA in organic solvents.     

Occupational exposure to paint, lacquer and solvents, and cancer risk in the area of the upper aero-digestive tract

So far, only few studies exist that have investigated the influence of occupational exposure to paint and lacquer on the risk of cancer in the upper aerodigestive tract. Based on data from the Heidelberg case control study which enrolled 369 patients with carcinomas of the upper aerodigestive tract and 1476 randomized control subjects, the relative risk of head and neck cancer in patients exposed to paint, lacquer and varnish was analyzed. The relative risk (RR) of squamous cell cancer (after adjustment for possible alcohol and tobacco effects) was significantly increased for the larynx (RR = 2.3) and the oral cavity (RR = 3.6). However, this risk was not increased for the pharynx. Our findings and a critical analysis of the literature provide evidence that chronic exposure to paint, varnish and lacquer is a definite risk factor for cancer of the upper aerodigestive tract. Further studies are required to confirm these findings, and to identify more precisely toxic substances encountered in the workplace.     

Effect of water-miscible organic solvents on the catalytic activity of cytochrome c

The effect of five water-miscible organic solvents (tetrahydrofuran, N,N-dimethylformamide, acetonitrile, 2-propanol, and methanol) on the oxidation of pinacyanol chloride (Quinaldine Blue) by horse heart cytochrome c was determined. Hydrogen peroxide was used as the oxidant, and a change in catalytic property of the dissolved protein was observed after a certain threshold concentration of the organic solvent had been reached. The maximum specific activity was correlated with the Dimroth-Reichardt parameter for the solvents, which is directly related to the free energy of the solvation process. The kinetic constants for the oxidation of pinacyanol chloride were determined in systems containing different proportions of tetrahydrofuran. The best catalytic efficiency (kcat/KM,app) was obtained in a system containing 50% tetrahydrofuran in phosphate buffer. In a mixture containing 90% tetrahydrofuran, cytochrome c showed 18% of its maximum activity. The inactivation of cytochrome c was mainly due to the presence of hydrogen peroxide, and a direct correlation was found between the inactivation constant and the concentration of hydrogen peroxide in the system. The chemical modifications and immobilization of cytochrome c were able to change its biocatalytic activity and stability in the organic solvent system. The kinetic constants and the inactivation of three other type c cytochromes, from Saccharomyces cerevisiae, Pseudomonas aeruginosa, and Desulfovibrio vulgaris Hildenborough in a system containing 90% tetrahydrofuran were compared with those of cytochrome c from horse heart. Cytochrome c551 from P. aeruginosa showed the best stability against hydrogen peroxide and a higher catalytic efficiency than that of horse heart cytochrome c.     

Thermophilic proteins: stability and function in aqueous and organic solvents

The molecular stability of thermophilic and hyperthermophilic enzymes generally reflects the growth temperatures of the parent organisms. Extracellular enzymes from the hyperthermophilic Archaea typically show very high levels of thermal stability and a number of enzymes with Tm values of greater than 100 degrees C have been reported. The mechanisms responsible for high molecular stability are typically intrinsic characteristics of the protein, as shown by the comparative stabilities of many native and recombinant proteins. However, some extrinsic stabilisation mechanisms have been demonstrated. High levels of thermal stability are positively correlated with stability in the presence of other denaturing agents, including detergents and organic solvents. This correlation suggests a common denaturation pathway where molecular mobility/flexibility is the prime determinant of susceptibility to irreversible denaturation. In single phase organic-aqueous solvents, protein destabilisation occurs via solvent-induced alteration to the protein hydration shell. However, correlations between protein stability and solvent hydrophobicity are unreliable. In two-phase organic-aqueous systems, interfacial denaturation predominates and is a function of both interfacial tension and interfacial surface area. Intracellular enzymes are protected from interfacial denaturation but are potentially susceptible to direct organic solvent effects, possibly depending on the role of the cell wall and cell membrane in the partitioning of the organic solvent into the cell cytoplasm. Immobilisation of thermophilic enzymes provides a method for enhancing both the thermal and solvent stabilities of thermophilic and mesophilic enzymes. Multi-point covalent immobilisation to glyoxal-agarose enhances thermal stability and limits protein-protein inactivation mechanisms. Miscible organic solvents have a profound influence on the specificities of enzyme reactions. The presence of high concentrations of miscible organic solvents may induce gross changes in substrate specificity and/or more subtle alterations in chiral selectivity. Correlations between the variation in enantioselectivity and both solvent hydrophobicity and solvent dielectric constant have been demonstrated although some recent studies implicate the formation of specific solvent-enzyme complexes which directly affect reaction kinetics.     

Toxicokinetics of organic solvents: a review of modifying factors

This article reviews, with an emphasis on human experimental data, factors known or suspected to cause changes in the toxicokinetics of organic solvents. Such changes in the toxicokinetic pattern alters the relation between external exposure and target dose and thus may explain some of the observed individual variability in susceptibility to toxic effects. Factors shown to modify the uptake, distribution, biotransformation, or excretion of solvent include physical activity (work load), body composition, age, sex, genetic polymorphism of the biotransformation, ethnicity, diet, smoking, drug treatment, and coexposure to ethanol and other solvents. A better understanding of modifying factors is needed for several reasons. First, it may help in identifying important potential confounders and eliminating negligible ones. Second, the risk assessment process may be improved if different sources of variability between external exposures and target doses can be quantitatively assessed. Third, biological exposure monitoring may be also improved for the same reason.     

Exposure to isocyanates and organic solvents, and pulmonary-function changes in workers in a polyurethane molding process

The extent of adverse health effects of isocyanates when combined with other chemicals is not well documented. This study was conducted as a 2.5-year follow-up as well as to determine daily and weekly effects of exposure to isocyanates and organic solvents on pulmonary function. The concentrations of chemicals sampled were below the recommended exposure criteria. No daily or weekly reduction in the subjects' pulmonary function was observed. The isocyanate/solvent-exposed subjects showed significant long-term reduction in their forced vital capacity (P < 0.05) and expiratory volume in 1 second (P < 0.001). No such changes were observed in non-exposed subjects or in those exposed only to organic solvents. The proportion of subjects who developed respiratory symptoms in the isocyanate-exposed group was not significantly greater than that of the non-exposed group. The results of this study indicate that long-term exposure to isocyanates, even in very low concentrations, may contribute to impaired pulmonary function.     

Selectivity of organic solvents in micellar liquid chromatography of amino acids and peptides

The influence of the type of organic modifiers on retention behavior in micellar liquid chromatography is studied. A group of amino acids and small peptides was used as the test mixture. It is shown that the chromatographic selectivities of 2-propanol, acetonitrile and tetrahydrofuran which belong to three different groups in Snyder's classification, are considerably similar in the presence of micelles for the test mixture. On the other hand, the selectivities of 2-propanol and butanol which belong to the same solvent selectivity group are different for these solutes in the micellar mobile phases.     

Breath monitoring in workers in contact with vapors of organic solvents

Large concentrations of solvents vapour were determined in occupational air. Individual monitor was effective in the assessment of personal exposure of workers to the solvents.     

Chromatographic determination of volatile solvents and their metabolites in urine for monitoring occupational exposure

The determination of volatile solvents and their metabolites in biological materials such as expired air, blood or urine allows the estimation of the degree of exposure of these chemicals. Chromatographic methods are now universally employed for this purpose and numerous analytical procedures are available for the determination of the most commonly used volatile solvents and their metabolites in urine. GC methods appear well adapted to the determination of the parent volatile solvents in blood and urine and may be used for the determination of their urinary metabolites, but these methods often require several prechromatographic steps. However, HPLC is becoming a powerful tool for the accurate and easy determination of urinary metabolites of volatile solvents, considering its decisive advantages for routine monitoring. Further, recent developments in HPLC could widen the usefulness of this method for most complex analytical problems that could be encountered during this measurement. However, despite the relative neglect of planar chromatography in this area of concern and considering the great interest in methods that could permit the simultaneous assay of numerous samples often required by routine monitoring, new approach using improved methods such as overpressured TLC could be very fruitful in the future.