Effects of toluene inhalation on brain biogenic amines in the rat

The effects of toluene exposure on the biogenic amine concentrations in the central nervous system were investigated in the rat. Toluene was administered via inhalation to groups of rats at concentrations of 0, l00, 300, or 1000 ppm. After an 8-h continuous exposure, animals were sacrificed and whole brain concentrations of dopamine (DA), norepinephrine (NE), and 5-hydroxytryptamine (5-HT) were determined. The data indicated a significant increase in whole brain concentrations of DA following the 100-ppm exposure. A regional analysis of DA, NE, and 5-HT concentrations in rats exposed to 1000 ppm of toluene for 8-h indicated a significant increase in DA concentration in the striatum. A significant increase in NE concentrations was detected in the medulla and midbrain while 5-HT concentrations were significantly increase in the cerebellum, medulla, and striatum. The results indicate that toluene action results in elevated concentrations of behaviorally significant neuro-transmitters.     

Excretion of methylhippuric acids in urine of workers exposed to a xylene mixture: comparison among three xylene isomers and toluene

Summary The correlation between exposure to three xylene isomers and resulting urinary excretion of corresponding methylhippuric acid (MHA) isomers was studied among 175 Chinese workers of both sexes who had been predominantly exposed to xylenes (exposure to xylenes accounting for 70% or more of the total exposure on a ppm basis). Nonexposed controls (281 men and women) were also studied to define the background level of MHAs in urine. The solvent exposure of xylene-exposed workers during their workshift was monitored by diffusive sampling of breathing zone air, and MHAs in shift-end urine were determined by high-performance liquid chromatography. Regression analysis showed that the concentration of each MHA isomer correlated significantly with the time-weighted average intensity of exposure to the corresponding xylene isomer, and therefore the correlation between the sum of three xylene isomers in air and that of three MHA isomers in urine was also significant; the slope of the regression line was essentially the same among the three isomers. The calculated regression line suggested that the urinary MHA level after hypothetical exposure to xylenes at 100 ppm will be somewhat less than the proposed biological exposure index and biological tolerance value. Two social habits of smoking and drinking in combination suppressed the conversion of xylenes to MHAs in male workers.     

Effects of ethylbenzene,toluene, and xylene on the induction of micronuclei in bone marrow polychromatic erythrocytes of mice

Genotoxic effects of five widely used aromatic industrial solvents, ethylbenzene, methylbenzene (toluene), o-, m-, and p-dimethylbenzene (xylene), on bone marrow cells of male NMRI mice were studied using micronucleus test. Each compound was given to animals by IP administration of two similar doses 24 h apart. Increased formation of micronuclei within polychromatic erythrocytes of femoral bone marrow 30 h after the first injection was conducted to be due to the clastogenic effect of the test compound. Of the chemicals tested, only toluene gave a dose-dependent increase in the frequency of micronucleated polychromatic erythrocytes. This genotoxic activity of toluene was confirmed in male B6C3F1 mice.     

二苯甲烷二异氰酸酯作业工人血清中抗原特异性IgG抗体测定

观察２５例二苯甲烷二异氰酸酯（ＭＤＩ）作业工人、８例ＭＤＩ哮喘患者和３０例正常非接触者的血中抗原特异性ＩｇＧ水平，用ＭＤＩ－ＨＳＡ（人血清白蛋白）作抗原，ＥＬＩＳＡ法测定特异性ＩｇＧ抗体，三组的ＯＤ均值分别为０．５１±０．３１、０．７３±０．２９和０．２７±０．１０，阳性率分别为４４％（１１例）、８７．５％（７例）和６．７％（２例）。表明ＭＤＩ接触者血清特异性ＩｇＧ水平明显增高，且与呼吸道症状高度相关（ｒ＝０．８８，Ｐ＜０．００１），此指标可作为ＭＤＩ的接触标志和ＭＤＩ哮喘的病因诊断依据。     

Breath analysis by API/MS—human exposure to volatile organic solvents

Summary The expired breath of subjects, exposed for periods of ca. 90 min to atmospheres artificially contaminated with low levels of methanol, (ca. 100 ppm) toluene (ca. 50 ppm) or tetrachloroethylene, (ca. 50 ppm) was monitored during and after the exposure period using an atmospheric pressure ionization mass spectrometer, fitted with a direct breath analysis system. The retention of solvent by the subjects, estimated from steady state levels in the expired breath, averaged 82% of the inspired level for methanol, 83% for toluene and 87% for tetrachloroethylene. The elimination of unchanged solvent via respiration during the post exposure period followed first order kinetics with mean half life values of 24 min for methanol, 27 min for toluene and 79 min for tetrachloroethylene.     

Analysis of biomarkers in rats and dogs exposed to polymeric methylenediphenyl diisocyanate (pMDI) and its glutathione adduct

Hemoglobin adducts (Hb-MDX) of monomeric methylenediphenyl diisocyanate (MDI) are often interpreted as indirect evidence of hydrolysis of the diisocyanate moiety to the respective amine (diphenylmethane-4,4'-diamine, 4,4'-MDA) which constitutes the rationale of using this biomarker as an internal dosimeter of exposure to putatively formed MDA. In contrast, more recently published data suggest that following inhalation the high concentration of glutathione (GSH) present in lungs favor an adduct formation with GSH and/or peptides/proteins rather than hydrolysis. The focus of this study was to test this alternate hypothesis, viz. whether Hb-MDX can also be formed by the GSH bis-adduct of monomeric MDI. The synthesized mMDI-GSH bis-adduct was administered to rats by single intratracheal instillation. Additional groups were dosed by gavage and intraperitoneal injection. Biomarkers of exposure were determined in blood (plasma protein and hemoglobin adducts) and urine after harsh alkaline and acid hydrolysis, respectively. Data from previous single inhalation exposure studies with aerosols of MDI and 4,4'-MDA in rats served as reference. As to whether N-acetylation plays any modifying role to yield these mMDI-specific biomarkers was addressed in similarly head-only exposed dogs, a species with no appreciable N-acetylation capacity whereas rats are strong N-acetylators. The results obtained suggest that biomarkers in blood from controlled exposures above current workplace standards of mMDI appear not to be suitable for reliable assessments of past exposures. The biomarkers typically used to assess past exposures to MDI were also identified following exposure to the MDI-GSH bis-adduct. Their yield was low but quite similar for MDI aerosol and the MDI-GSH bis-adduct, whilst that of MDA was distinctively higher. The findings of this study are supportive of a conceptual pathway that the MDI-derived biomarkers of exposure are formed through MDI-GSH adducts rather than MDA. Data from dogs support the findings from rats and show that N-acetylation does not appear to be an essential modifying factor. It is concluded that the yield of MDI-related markers of exposure is relatively low and dependent on the exposure dose (and route). MDA originating from hydrolyzed serum protein or hemoglobin appear to be confounded by false-positive background levels which are surmised to be associated with the method of hydrolysis. The determination of urinary biomarkers might be a useful tool to identify recent exposures (by any route). Due methodological uncertainties associated with the harsh hydrolysis of biological specimens may be reduced substantially when using incremental pre- to post-shift changes rather than relying solely on absolute data.     

空气中正己烷、苯系物同时测定的热解吸气相色谱法

目的建立工作场所空气中正己烷、苯、甲苯、二甲苯同时测定的热解吸气相色谱方法。方法按照《车间空气监测检验方法研究规范》的要求进行实验室实验及现场实验。结果正己烷、苯、甲苯、二甲苯方法的平均相对标准偏差在4．9％以内,方法的最低检测浓度均在2．4mg/m^3以内,热解吸效率均在80％以上,空气中正己烷、苯、甲苯、二甲苯等在该方法条件下可同时分别测定。结论该方法各项指标均达到《车间空气监测检验方法研究规范》的要求,适用于工作场所空气中正己烷、苯、甲苯、二甲苯的同时监测。     

Forced turning induced by toluene

Repeated daily toluene inhalation produces circling in rats. This effect may be specific to toluence since xylene fails to elicit turning. The turning follows toluence nhalation and is not associated with histological lesions of the brain. Forced circling can be reestablished more rapidly 15 days after last toluene inhalation than 21 or 34 days thereafter These latter conditions require about as many exposures to toluene as were required to institute turning originally.     

A simple analysis of 5 thinner components in human body fluids by headspace solid-phase microextraction (SPME)

A simple method for the extraction of 5 thinner components from human whole blood and urine, using the headspace solid-phase microextraction (SPME) method is presented. After heating a vial containing the samples with 5 compounds (toluene, benzene,n-butyl acetate,n-butanol andn-isoamyl acetate) at 80°C, a polydimethylsiloxane-coated SPME fiber was exposed to the headspace of the vial to allow adsorption of the compounds. The fiber needle was then injected into a capillary gas chromatography (GC) port. The headspace SPME-GC gave intense peaks for each compound and a low level of background noise was seen only for whole blood. Recovery rates o the 5 compounds by use of the headspace SPME-GC were 50–70%. Reproducibility for headspace SPME-GC data were excellent for both body fluids. The calibration curves showed linearity in the range 2–100 ng/0.5 ml whole blood or urine. The detection limits of each compound were 1.1–2.4 ng/0.5 ml sample. The present results on the analysis of 5 thinner components by headspace SPME-GC suggest its applicability to a number of other volatile compounds in forensic toxicology.     

A computational study on the mechanism and the kinetics of urethane formation

The reaction of n-butanol with several aromatic diisocyanates – 2,4 toluene diisocyanate (2,4 TDI), 2,6 toluene diisocyanate (2,6 TDI), 2,4′ dibenzyl diisocyanate (2,4′ DBDI), 4,4′ stilbene diisocyanate, (4,4′ SBDI), m-phenylene diisocyanate (m-PDI), and p-phenylene diisocyanate (p-PDI) – resulting in the production of urethane is studied by using density functional theory (DFT) calculations (B3LYP/6-31 + G(d,p)). The addition of alcohol to isocyanate follows either a concerted or stepwise path. The obtained product differs in two mechanisms. Single point solvent calculations were carried out in benzene, by means of the polarizable continuum model (PCM) at the B3LYP/6-31 + G(d,p) level of theory. The calculated free energy profiles showed that the concerted path is more likely to occur than the stepwise route. Natural bond orbital analysis was performed to provide an insight into charge delocalization and the stabilization energies of the molecules. The calculated rate constant ratios (k₁/k₂) of the two consecutive alcoholysis reactions of aromatic diisocyanates agree strongly with the experimental results.