Uptake via the blood and elimination of 10 organic solvents following epicutaneous exposure of anesthetized guinea pigs

The concentration of 10 organic solvents in the blood was monitored during and, for some solvents, after epicutaneous exposure of anesthetized guinea pigs. The solvents studied were benzene, carbon tetrachloride, 1,2-dibromoethane, 1,2-dichloroethane, n-hexane, 1,1,2,2-tetrachloroethane, tetrachloroethylene, toluene, 1,1,1-trichloroethane, and trichloroethylene. With carbon tetrachloride, hexane, tetrachloroethylene, toluene, 1,1,1-trichloroethane, and trichloroethylene, the concentration in the blood increased during the first hour of expsure and then decreased despite ongoing exposure. With benzene and 1,2-dibromoethane, the blood concentration increased to a maximum during the first hour and then slowly decreased. The blood concentration of 1,2-dichloroethane and 1,1,2,2-tetrachloroethane also increased during the first half-hour, then decreased markedly, and later began to increase again. The elimination curves were nonlinear in all cases and corresponding to a kinetic model involving at least two compartments for benzene, 1,2-dibromoethane, 1,2-dichloroethane, 1,1,2,2-tetrachloroethane, and 1,1,1-trichloroethane.     

Tolerance during inhalation of organic solvents

Inhalation of several different halogenated solvents stimulated motor activity in mice. During prolonged exposure acute tolerance developed. The development of tolerance depended both on the schedule of exposure, and on the solvent. Exposure to trichloroethylene induced both stimulation and tolerance while the same degree of stimulation induced by 1,1,1-trichloroethane caused no tolerance. Thus the mechanisms which induce stimulation do not always initiate tolerance. Slow steady increases in the concentration of trichloroethylene could be maintained for several hours without any stimulation of motor activity. At the end of such exposures concentrations were reached which, if applied directly, would have induced considerable stimulation. Thus tolerance may develop without motor stimulation. Inhalation of ethanol also stimulated motor activity initially. During constant exposure the stimulation was followed by a considerable reduction in motor activity. This resulted in a hypoactive period, which in turn was followed by a second increase in motor activity, indicating the existence of not only two but several counteracting mechanisms. Development of metabolites with sedative effects counteracting the stimulating effect of the pure solvents seems to be one explanation for the results.     

Cholesterol solubility in organic solvents.

The 37 degree cholesterol solubilities in over 50 solvents, including the homologous n-alkanols through dodecanol and homologous ethyl carboxylates through the undecanoate, and the 37 degree beta-sitosterol solubilities in the n-alkanols through decanol are reported. Additionally, solubility data for cholesterol at 7, 17, and 27 degrees in the alcohol series were obtained. These measurements allowed the calculation of heats of solution for cholesterol in the alkanols, which range from 7.5 kcal for methanol to 4.3 kcal for decanol and which tend to decrease, although irregularly, with increasing alkanol chain length. A solubility maximum in all of these series for both solutes was observed between a chain length of six and seven. A surprisingly irregular, odd-even alternating solubility pattern was noted for cholesterol in the alkanols at all four temperatures. Experimental evidence indicated that this pattern was due to solvent-induced crystalline changes, presumably solvate formation, in each alkanol solvent through C10. Overall, the solubility studies screened solvents for their utility in dissolving cholesterol and, thus, cholesterol gallstones. To these ends, some limited dissolution experiments were performed, which indicated that the solution rate is directly related to the measured solubility in organic solvents. The dissolution behavior is thus different from micellar bile salt solutions, in which a significant interfacial barrier controls kinetics.     

Conformation of cyclosporin A in polar solvents

A major conformation of cyclosporin A in methanol and in aqueous methanol was revealed by some simple NMR experiments. Thus, a stepwise transition of cyclosporin A conformation from 100% CDCl₃ to 100% CD₃OD was followed by ¹H NMR, which showed that the chloroform conformation of cyclosporin A was still the major one in methanol. Employing the same technique, it was also shown that the chloroform conformation of cyclosporin A was one of the major conformations in 50% aqueous methanol. This may be the first experimental determination of a major conformation of cyclosporin A in polar solvents.     

Anticonvulsant and convulsant effects of organic solvents.

Previous studies suggest that organic solvents show anticonvulsant and convulsant effects, respectively at low and high doses. In the present study the first experiment was designed to determine low and high doses of injected acute n-hexane, ethyl acetate and toluene in mice through LD50 estimations. In the second experiment, high doses (around LD50) were employed to evaluate the convulsant effects. Finally, the third experiment evaluated the ability of low doses to prevent electroshock- and PTZ-induced convulsions. Results showed that n-hexane increased the severity of the electroshock-induced seizures only at low doses and had no anticonvulsant effects. Ethyl acetate produced generalized clonic seizures and deaths at high doses and was ineffective to prevent electroshock- and PTZ-induced seizures at low doses. Toluene induced forelimb clonus at high doses and protected against electroshock-induced seizures at low doses. Therefore, the biphasic property on convulsant activity seems to be a feature not shared among organic solvents.     

顶空气相色谱法同时测定硫酸特布他林中10种有机溶剂残留量

目的建立硫酸特布他林中甲醇、乙醇、丙酮、甲基叔丁基醚、乙酸乙酯、四氢呋喃、苯、乙酸、甲苯和氯化苄共10种有机溶剂残留量的测定方法。方法采用顶空气相色谱法,色谱柱为DB-624UI毛细管柱(30 m×0.32 mm,1.80μm),柱温采用程序升温;进样口温度为200℃;检测器为氢火焰离子化检测器,检测器温度为250℃,溶剂为体积分数为70%二甲基甲酰胺。结果 10种溶剂完全分离;在考察的质量浓度范围内线性关系良好,相关系数r>0.999 4,平均回收率为95.7%~102.4%。结论建立的顶空气相色谱法可用于硫酸特布他林中残留溶剂的测定。     

Prenatal exposure to organic solvents and child neurobehavioral performance.

The present study compared the cognitive and behavioral functioning of 3- to 7-year-old children (n=33) whose mothers worked with organic solvents during pregnancy with a group of unexposed children (n=28) matched on age, gender, parental socioeconomic status (SES), and ethnicity. Participants were recruited prospectively by the Motherisk Program, an antenatal counseling service in Canada. An exposure index was estimated using questionnaire data obtained at the time of initial contact. Groups were compared on a variety of tasks, including subtests from the NEPSY, a visual CPT, as well as on parent-rated measures of children's behavior. Regression analyses indicated lower composite scores in children with increased exposure on Receptive language (P<.01), Expressive language (P<.01), and Graphomotor ability (P=.001), adjusted for demographics. No group differences were observed on measures of Attention (P=.97), Visuo-spatial ability (P=.33), and Fine-motor ability (P=.33). On the Child Behavior Checklist (CBCL), overall mean differences on broad- and narrow-band scales were not significant, but significantly more exposed children were rated as having mild or severe problem behaviors. The findings suggest that maternal occupational exposure to organic solvents during pregnancy is associated with poorer outcome in selective aspects of cognitive and neuromotor functioning in offspring.     

Effect of some organic solvents on oxidative phosphorylation in rat liver mitochondria: Choice of organic solvents

The effect of acetone, acetonitrile, dimethyl sulfoxide (DMSO), ethanol and methanol on oxidative phosphorylation (ATP synthesis) in rat liver mitochondria has been studied. All the organic solvents inhibited the oxidative phosphorylation in a concentration dependent manner, but with differences in potencies. Among the tested organic solvents, acetonitrile and acetone were more potent than ethanol, methanol, and DMSO. There was no significant difference in oxidative phosphorylation, compared to controls, when the concentrations of acetone was below 1% (v/v), of acetonitrile below 2% (v/v), of DMSO below 10% (v/v), of ethanol below 5% or of methanol below 2%, respectively. There was complete inhibition of oxidative phosphorylation at 50% (v/v) of acetone, acetonitrile and ethanol. But in the case of DMSO and methanol there were some residual activities observed at the 50% concentration level. DMSO showed least effect on oxidative phosphorylation with an IC₅₀ value of 13.3 ± 1.1% (v/v), followed by methanol (IC₅₀ value 8.3 ± 1.0), ethanol (IC₅₀ value 4.6 ± 1.1), acetone (IC₅₀ value 4.3 ± 1.0) and finally acetonitrile (IC₅₀ value 2.1 ± 1.0).All the organic solvents showed modulatory effects on 2,4-dinitrophenol (DNP) mediated inhibition of oxidative phosphorylation with potentiation of the action of DNP. Acetonitrile showed the highest potentiation effect followed by acetone, ethanol, methanol, and DMSO in presence of DNP. The use of organic solvents for investigation of the effects of compounds on oxidative phosphorylation in mitochondria should therefore include the use of relevant concentrations of the organic solvent in order to validate the contribution.     

The decomposition of acidic and neutral cannabinoids in organic solvents.

High-pressure liquid chromatography was used to study (a) the relative efficiencies of methanol, chloroform, light petroleum (B.P. 40-60 degrees) and methanol-chloroform (9:1) for extracting neutral and acidic cannabinoids from cannabis resin; (b) the decomposition patterns of the resulting solutions under various storage conditions, and (c) the cannabinoid profile of a cross section through a block of cannabis resin. The results show that (a) methanol is the most effective extracting solvent of those tested; (b) acidic cannabinoids in solution decompose in darkness by varying amounts depending on the temperature, solvent, storage time and particular cannabinoid; (c) neutral cannabinoids in solution are relatively stable in darkness; (d) daylight causes appreciable decomposition of both acidic and neutral cannabinoids in solution, (e) the cannabinoid profile of a resin is complex with lower levels of acidic material in the outer layers.