n-Hexane urine elimination and weighted exposure concentration

Summary The concentration of n-hexane in urine was determined in 30 subjects occupationally exposed to n-hexane (median value 59.6 mg/m³) in a shoe factory. The measurement of the substance was performed by means of a Hewlett-Packard 5880 gas chromatograph supplied with a Hewlett-Packard 5970 Mass Selective Detector. The analyses were performed by the head space method (constant volume method, after determination of the urine partition coefficient by the multiple phase equilibration method). The authors found a significant correlation between the n-hexane urine concentrations (g/1, Cu) and the n-hexane environmental concentrations (mg/m³, Ci) (r = 0.84; Cu = 0.0669 x Ci + 0.8396).This work was supported by the research funds given to Fondazione Clinica del Lavoro, Pavia by the Health Council     

接触正已烷致工人周围神经损害的研究

目的研究接触正己烷致工人周围神经损害的影响。方法对206名接触正己烷的工人和128名对照组进行问卷、内科体检和神经传导速度及尿中2,5-己二酮、血清神经特异性烯化酶(NSE)水平测定。结果上帮车间正己烷浓度超过国家接触限值;下帮车间未超标。上帮车间组工人有乏力、肢麻、行走不便、下蹲起立困难、肌肉萎缩、跨越步态、肌力下降、浅感觉减退、腱反射减退等症状体征,与下帮车间组及对照组相比,差异有显著性(P<0.01)。测定248根运动神经传导速度中172根(69.3%)传导速度减慢,62根(25.0%)波幅下降;32根(12.9%)远端潜伏期延长;186根感觉神经中141根(75.8%)传导速度减慢;班后尿中均检出2,5-己二酮;血清NSE水平测定,异常率为22.6%。结论接触超限值正己烷浓度对工人的神经系统症状体征、神经传导速度、2,5-己二酮以及血清NSE水平均有影响。     

正己烷接触人群神经生长因子mRNA表达水平研究

目的建立一种人神经生长因子(NGF)mRNA荧光定量聚合酶链反应(PCR)检测方法,探讨接触时间对正己烷接触人群NGF mRNA表达水平的影响。方法以接触正己烷工龄分组。设计引物、探针,检测对照组和接触正己烷各组之间的NGF mRNA水平。结果利用该荧光定量PCR检测结果显示工龄<2年组、2～6年组、>6年组以及对照组的NGF mRNA以10为底的对数分别为(8.88±0.08)、(8.68±0.08)、(8.53±0.11)和(8.90±0.07)copies/L。2～6年组和>6年组的NGF mRNA表达水平均低于对照组。各组内男女之间NGF mRNA表达水平比较,差异无统计学意义(P>0.05)。结论正己烷的毒性对于NGF mRNA的表达有明显的时间依赖关系,随着接触时间加长,NGF的表达逐渐减弱;所建立的检测方法特异性强,完全符合检测要求。     

Solvent exposure in a shoe upper factory

Summary Acetone and n-Hexane concentrations were determined in the environmental air of a shoe upper factory and in the alveolar air and venous blood of the workers employed. The ratio between alveolar and environmental n-hexane concentration (Ca/Ci) was found to be steady during the 4.5 hours of exposure studied, and independent of alveolar ventilation and n-hexane environmental concentration. Lung uptake per minute was correlated with environmental concentration.In the case of acetone the Ca/Ci ratio was found to increase with exposure time, but to be independent of alveolar ventilation and environmental acetone concentration. A correlation was still found between lung uptake and environmental acetone concentration.The correlation found between Ca and Ci suggests the hypothesis that occupational exposure can be studied by testing the alveolar air concentration of individual exposed workers in the case of hexane. Since in the case of acetone the Ca/Ci ratio increases with exposure time, it is necessary to know the time of exposure in order to estimate environmental exposure from alveolar acetone concentration. Blood concentration was correlated with environmental and alveolar concentration in the case of hexane, correlated with alveolar concentration in the case of acetone.     

Changes of n-hexane neurotoxicity and its urinary metabolites by long-term co-exposure with MEK or toluene

Summary It is well known that the neurotoxicity of n-hexane may be modified upon co-exposure with other organic solvents. In order to elucidate this mechanism further, rats were exposed to 500ppm n-hexane, 500ppm n-hexane plus 500ppm methyl ethyl ketone (MEK), 500ppm n-hexane plus 500ppm toluene, or air only for 8h per day for 33 weeks. The body weight, motor nerve conduction velocity (MCV) and distal latency (DL) were determined before exposure and after 4, 8, 12, 16, 20, 24, 29, and 33 weeks of exposure. From each group one rat was histologically examined after 33 weeks of exposure. To establish a relationship between the n-hexane neurotoxicity and changes in biotransformation, urinary metabolites (2-hexanol, methyl n-butyl ketone (MBK), 2,5-hexanedione, 2,5-dimethylfuran, and -valerolactone) were measured by gas chromatography on the first exposure day, and after 1, 2, 4, 8, 12, 16, 20, 24, 29, and 33 weeks of exposure. The total amounts of metabolites of n-hexane in the urine significantly decreased upon co-exposure of n-hexane, with MEK as well as with toluene, in comparison with those of animals exposed to n-hexane alone. 2,5-Hexanedione, which is considered the ultimate neurotoxic metabolite of n-hexane, also decreased. Electrophysiological and histological studies did not reveal statistically significant differences between any two groups among the four groups. It is considered that the present results might explain the combined effects of n-hexane and toluene which decrease n-hexane neurotoxicity, but do not explain those of n-hexane and MEK. Therefore, other mechanisms of the combined effects of n-hexane and MEK should be studied.     

正己烷致大鼠过氧化损伤及肝细胞凋亡的实验研究

目的研究正己烷(n-hexane)对大鼠的脂质过氧化损伤和肝细胞凋亡的影响。方法40只雄性SD大鼠随机分成5组,即阴性对照组、染毒组(75、150、300 mg/kg)和阳性对照组(环磷酰胺),每组8只。经腹腔注射染毒4周后,检测肝组织匀浆超氧化物歧化酶(SOD)和谷胱甘肽过氧化物酶(GSH-Px)的活力,血清还原型谷胱甘肽(GSH)和丙二醛(MDA)含量;用流式细胞仪检测肝细胞凋亡情况。结果随着染毒剂量的增加,肝组织匀浆中SOD、GSH-Px活力、血清GSH含量降低,而血清MDA含量增大,组间比较差异有统计学意义(P<0.05或P<0.01),流式细胞仪检测结果显示,肝细胞凋亡率(AV /PI-)组间比较差异有统计学意义(P<0.01),与染毒剂量作相关分析,相关系数为0.913,无明显的相关性(P>0.05)。结论正己烷可引起或增强机体氧自由基反应,导致脂质过氧化损伤,引起肝细胞凋亡和坏死。     

胆红素对正己烷致体外外周血淋巴细胞DNA损伤的拮抗作用

目的 研究胆红素(bilirubin)对正己烷(n-hexane)致DNA损伤的影响。方法 应用单细胞凝胶电泳(SCGE)技术和彗星图像分析系统,检测不同浓度正己烷对人外周血淋巴细胞DNA损伤,同时观察10umol／L胆红素对正己烷所致的DNA损伤的保护作用。结果 尾长、尾／头(长)、尾／头(光强)、迁移率、尾DNA％、Olive尾矩等指标与正己烷浓度存在明显的剂量一效应关系,发现胆红素能抑制正己烷的DNA断裂能力。结论 胆红素有抑制正己烷致DNA损伤的作用。     

牛黄及制剂对正己烷致小鼠肝、肾脂质过氧化的保护作用研究

目的探讨牛黄和以其为主药的3个中药制剂对正己烷所致小鼠脂质过氧化性组织损伤的拮抗作用。方法36只CD小鼠分为6组,用牛黄和3个中药制剂对正己烷急性染毒的小鼠进行干预,分别观察小鼠的肝、肾脏器系数,肝、肾组织中丙二醛(MDA)水平及组织病理变化情况。结果正己烷染毒小鼠肝、肾组织中MDA增高并伴有明显的组织病理损伤。采用牛黄和中药制剂进行干预可明显降低肝、肾组织中MDA水平并减轻组织病理损伤程度。结论牛黄及其中药制剂对正己烷诱发肝、肾组织脂质过氧化作用具有一定保护效应。     

正己烷诱发红细胞血影蛋白共价交联的研究

目的研究正己烷对红细胞血影蛋白(Spectrin,Sp)共价交联的影响.方法 SD大鼠灌胃给予正己烷0、168、675、2 700 mg/kg,连续8周(5 d/周).抽提红细胞膜蛋白,用双缩脲法测定蛋白浓度,用聚丙烯酰胺凝胶电泳(SDS-PAGE)后以硝酸银染色,吸光度扫描计算蛋白含量,用免疫印迹法(Western blot)鉴定血影蛋白.结果染毒8 周后,2 700 mg/kg 组动物红细胞膜蛋白浓度为:(5.88±0.89)g/L,经SDS-PAGE,硝酸银染色见相对分子质量460 kD (≈460ku)异常蛋白条带,经Western blot证实为Sp共价交联产物,带形为连续"拖尾"状.结论正己烷可能会引起Sp共价交联.     

Experimental data from closed chamber gas uptake studies in rodents suggest lower uptake rate of chemical than calculated from literature values on alveolar ventilation

Experimental data obtained in vivo with the closed-chamber gas uptake technique have been reported for a series of volatile chemicals. Pharmacokinetic analyses of these data have been performed either by using a two-compartment model or physiological models. In the former the transfer rate of chemical from ambient air to body is defined by the clearance of uptake. In the latter models the transfer rate depends on alveolar ventilation, cardiac output, and blood: air partition coefficient. In this communication we describe the quantitative relationship between clearance of uptake and alveolar ventilation, cardiac output, and blood: air partition coefficient. Theoretical values of clearance of uptake were calculated for a variety of volatile chemicals using literature data on alveolar ventilation, cardiac output, and blood: air partition coefficient. For most chemicals the experimentally determined values in rats and mice were about 60% of the theoretical values. This suggests that the inhalatory uptake rate of chemical may be overestimated if literature values of alveolar ventilation are used in physiological pharmacokinetic models for rodents.