职业性接触三氯乙烯引起多器官损害的分析

目的　对职业接触三氯乙烯 (TCE)引起多器官损害的临床表现进行分析。方法　对 2 0 0 2～ 2 0 0 3年深圳发生的 12例典型TCE中毒病人进行调查 ,记录每个病人的职业接触情况、主要临床症状和体征 ,对血常规、肝功能、尿常规、尿三氯乙酸(TCA)、心电图进行检查分析。结果　 12例中毒病人中 11人发生在电子厂与五金制品厂 ;TCE接触工龄 16～ 3 9d ,平均 2 8.4d ;具有头晕、头痛、皮肤瘙痒、发热的病人分别为 91.6%、83 .3 %、10 0 %和 66.7% ;具有皮肤红斑、皮疹、水疱任意 1项者分别为 83 .3 %、91.6%和 41.6% ;肝肿大 3人 (2 5 % ) ,尿蛋白阳性 2人 (16.7% ) ;丙氨酸转氨酶、天冬氨酸转氨酶、总胆红素异常率分别为 91.6%、66.7%、41.6% :8人检查心电图 3人异常 ,10人测定尿TCA升高 7人。结论　TCE可引起神经系统、皮肤、肝脏损害 ,同时对心脏、肾脏也有一定影响。     

EB病毒转化人外周血B淋巴细胞的影响因素研究

目的探讨人类疱疹病毒(EBV)转化外周血B淋巴细胞试验的影响因素。方法用B95-8细胞制备EBV,实时荧光定量-PCR(realtime-PCR)法测定EBV滴度以确保病毒有效性,Ficoll密度梯度离心法分离外周血单个核细胞,研究环孢霉素A(CSA)的浓度、CSA加入时间、淋巴细胞浓度3个因素对EBV转化外周血B淋巴细胞试验的影响,选择最优化条件对三氯乙烯接触工人的B淋巴细胞进行转化。结果制备的病毒滴度分别为5.45×106/ml和1.06×106/ml。不同浓度CSA(0.2、1和2μg/ml)作用以及不同加入时间(同时加入或2h后)B淋巴细胞均成功永生化;正常人B淋巴细胞转化时淋巴细胞浓度不低于2×106/ml时方能成功永生化,而接触三氯乙烯工人的淋巴细胞在1×106/ml浓度下亦转化成功。不同条件下转化成功的B淋巴细胞永生化细胞系在形态上无明显差别,显微镜下可见B淋巴细胞体积增大并聚集成团。结论在建立B淋巴细胞永生化细胞系的过程中,CSA浓度和加入时间对转化结果未见影响,而淋巴细胞与EBV接触时的细胞浓度是影响实验成败的关键因素,接触三氯乙烯工人的B淋巴细胞在1×106/ml浓度下亦转化成功,推测与淋巴细胞致敏状态有关。     

A heroic struggle to understand the risk of cancers among workers in the electronics industry: the case of Samsung

Abstract

Occupational and environmental determinants of benign thyroid disease and follicular thyroid cancer were evaluated in a series of cases in 1977–1987. Of the cases initially diagnosed as follicular thyroid cancer, only 31 remained after a reclassification, whereas 44 were found to be benign thyroid disease. Both series were compared with 387 randomly selected population controls. Occupational solvent exposure was strongly associated with benign thyroid disease (odds ratio, OR, 2.8; 95% confidence interval, 95% CI, 0.9–9.0 for women and OR 18.9; 95% CI 2.2–161 for men). Eight of the nine men found to have benign disease had been exposed to solvents, and six of them to trichloroethylene. For both types of cases, a private well at the birth address increased the risk, OR 2.0; 95% CI 0.9–4.0 and OR 3.0; 95% CI 1.2–7.2, respectively, whereas the risk was lower for those living in coastal areas. Less fish and shellfish in the diet increased the risk for malignant thyroid disease only. Although based on small numbers, the study indicates etiologic roles of occupational and environmental factors for both conditions studied. The influences of occupation and diet differ, however, for the two outcomes.     

Development of an animal model of solvent abuse for use in evaluation of extreme tricholoroethyylene inhalation

Self-intoxication by inhalation of vapors of trichloroethylene (TCE) and other solvents in widespread. In order to develop exposure protocols which typify episodes of TCE “sniffing”, male Wistar-Munich rats were exposed to TCE vapor levels ranging from 9000 to 16 000 ppm. TCE in concentrations of 14 000 ppm and greater quickly produced loss of righting reflex. Recovery from the narcosis was very rapid. Central nervous system (CNS) depression was found to be cumulative in rats subjected for 5 h to alternating periods of 5 min of 15 000 ppm TCE and 15 min of fresh air. Ethanol markedly potentiated depression in these subjects. No evidence of liver or kidney damage was seen in rats subjected to the repetitive 5-h TCE inhalation regimen, nor in rats fasted for 16 h before the TCE-exposure session. Oral admnistration of 5 ml/kg body wt of ethanol 1 h, 16 h, or once daily for 3 days before the TCE-exposure regimen had little if any potentiating effect on hepatorenal toxicity potential. Animals that received ethanol and were fasted before TCE exposure exhibited slight elevations in SGOT and SGPT levels.     

Visualization-Based Analysis for a Mixed-Inhibition Binary PBPK Model: Determination of Inhibition Mechanism

A physiologically based pharmacokinetic (PBPK) model incorporating mixed enzyme inhibition was used to determine the mechanism of metabolic interactions occurring during simultaneous exposures to the organic solvents chloroform and trichloroethylene (TCE). Visualization-based sensitivity and identifiability analyses of the model were performed to determine the conditions under which four inhibitory parameters describing inhibitor binding could be estimated. The sensitivity methods were used to reduce the 4-parameter estimation problem into two distinct 2-parameter problems. The inhibitory parameters were then estimated from multiple closed-chamber gas-uptake experiments using graphical methods. The estimated values of the four inhibitory parameters predicted that chloroform and TCE interact in a competitive manner. Based on the model analysis, we present recommendations for the design of experiments for determination of inhibition mechanism in binary chemical mixtures. We assert that a thorough analysis of the parameter-dependent sensitivity and identifiability characteristics can be used to plan efficient experimental protocols for the quantitative analysis of inhalation pharmacokinetics.     

Anaesthetic vapour concentrations in the EMO system

Measurements of the vapour concentrations delivered by the EMO and Oxford Miniature Vaporizers (OMV) were made with both continuous (plenum mode) and intermittent (drawover mode) air flows. Leakage of ether, halothane and trichloroethylene vapours through the corrugated elephant tubing was also measured. Both vaporizers performed most consistently with the intermittent flows for which they were designed. Outputs were minimal at very low carrier gas flows, reached their greatest at the higher settings in the middle flow range and tended to be low at the highest flows. These effects were far more notable with continuous than with intermittent flows. Minimal amounts of ether were lost through the tubing but halothane losses were appreciable, while losses of trichloroethylene were enough to reduce the concentrations available to the patient. The EMO is not suitable for plenum use with carrier gas flows below about 10 litres/min. The OMV is a useful plenum vaporizer although the outputs are generally lower than indicated at higher flows.     

Estimated effects of solvents and mineral oils on cancer incidence and mortality in a cohort of aerospace workers

BACKGROUND: A retrospective cohort study of workers employed at a California aerospace company between 1950 and 1993 was conducted; it examined cancer mortality from exposures to the rocket fuel hydrazine. METHODS: In this study, we employed a job exposure matrix (JEM) to assess exposures to other known or suspected carcinogens-including trichloroethylene (TCE), polycyclic aromatic hydrocarbons (PAHs), mineral oils, and benzene-on cancer mortality (1960-2001) and incidence (1988-2000) in 6,107 male workers. We derived rate- (hazard-) ratios estimates from Cox proportional hazard models with time-dependent exposures. RESULTS: High levels of TCE exposure were positively associated with cancer incidence of the bladder (rate ratio (RR): 1.98, 95% confidence interval (CI) 0.93-4.22) and kidney (4.90; 1.23-19.6). High levels of exposure to mineral oils increased mortality and incidence of lung cancer (1.56; 1.02-2.39 and 1.99; 1.03-3.85), and incidence of melanoma (3.32; 1.20-9.24). Mineral oil exposures also contributed to incidence and mortality of esophageal and stomach cancers and of non-Hodgkin's lymphoma and leukemia when adjusting for other chemical exposures. Lagging exposure measures by 20 years changed effect estimates only minimally. No associations were observed for benzene or PAH exposures in this cohort. CONCLUSIONS: Our findings suggest that these aerospace workers who were highly exposed to mineral oils experienced an increased risk of developing and/or dying from cancers of the lung, melanoma, and possibly from cancers of the esophagus and stomach and non-Hodgkin's lymphoma and leukemia. These results and the increases we observed for TCE and kidney cancers are consistent with findings of previous studies.     

低浓度三氯乙烯对接触者免疫功能的影响

[目的]观察低浓度三氯乙烯(TCE)接触对人体体液免疫与细胞免疫功能的影响。[方法]测定作业环境空气中的TCE浓度。以48名接触TCE的工人及45名非接触TCE的工人为测试对象,测定尿中TCA浓度和血清中的IgG、IgA、IgM、IgE及外周血T淋巴细胞亚群。接触TCE的工人按尿中TCA浓度分为2组:低暴露组(≤50mg/L)和高暴露组(>50mg/L)。[结果]①低暴露组和高暴露度组IgM分别为(1.22±0.35)g/L和(1.27±0.58)g/L与对照组IgM(1.48±0.61)g/L相比,IgM水平下降,差异有显著性(P<0.05)。②低暴露组和高暴露度组IgG和IgA水平有下降的趋势。③对照组、低暴露组及高暴露组的CD3 分别为(81.28±9.17)%,(71.26±13.23)%和(61.80±12.33)%;CD4 分别为(70.27±13.82)%,(39.61±10.22)%和(36.28±7.29)%;CD8 分别为(31.48±11.95)%,(50.87±12.80)和(46.20±9.17)%。低暴露组及高暴露组CD3 、CD4 及CD4 /CD8 均低于对照组(P<0.01);CD8 高于对照组(P<0.01)。[结论]低浓度三氯乙烯可抑制接触者的体液免疫和细胞免疫功能。