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。     

三氯乙烯接触工人外周血淋巴细胞染色体畸变分析

目的探讨三氯乙烯(TCE)对接触工人有否致淋巴细胞染色体畸变作用.方法选接触TCE工人32名,另选对照工人30名.用人外周血体外培养法检测淋巴细胞染色体畸变(CA)率,并用气相色谱法测定车间空气中TCE浓度和分光光度吡啶法测定尿中三氯乙酸(TCA)含量.结果车间空气中TCE浓度分别为41.2mg/m3和83.1mg/m3,均超过国家最高容许浓度,接触组尿中TCA含量为对照组的81.5倍,并与个体接触TCE浓度成正相关(r＝0.761,P＜0.001);接触组人外周血淋巴细胞CA率(1.15±0.84)%与对照组CA率(1.06±0.78)%比较差异无显著性(P＞0.05).结论未见接触TCE工人外周血淋巴细胞染色体畸变率增加.接触人群尿中TCA含量随接触TCE浓度的增加而升高,有较好的相关,提示暴露者尿中TCA含量能反映TCE的接触水平.     

珠海市长期接触三氯乙烯作业人员的健康调查

目的对长期接触三氯乙烯(TCE)的作业人员进行健康调查,为确定接触TCE人员的职业性健康检查项目,及时发现中毒患者提供科学依据。方法选择连续直接接触TCE 3个月以上工人142人(女性121人,男性21人)为TCE接触组,并设立对照组(66人),对观察对象采用自行设计的调查表逐项进行问诊,并进行全面体格检查和尿中三氯乙酸(TCA)的测定。结果TCE接触组男、女的平均尿中TCA浓度分别为48.70、54.12 mg/L,均高于对照组(P<0.01)。工龄2年以上或尿中TCA浓度大于50 mg/L时,应激反应时间显著长于对照组(P<0.05或P<0.01);工龄2年以上的职业接触者应激反应时间显著长于工龄2年以下的(P<0.01)。接触组中不管接触时间长短、尿中TCA浓度多少,神经衰弱、皮肤疾患、三叉神经感觉迟钝、共济运动失调的检出率明显高于对照组(P<0.05或P<0.01)。工龄2年以上或尿中TCA浓度大于50 mg/L时,生殖系统疾患检出率明显高于对照组(P<0.05或P<0.01)。结论反应灵敏性、神经系统、皮肤、三叉神经感觉、共济运动、生殖系统的检查和精神症状的问诊可以作为TCE职业接触人群的职业性健康检查的重点检查项目,对及时发现中毒患者具有一定的意义。可以认为控制职业人群接触TCE的时间和浓度,对减少TCE对人体损害具有一定的意义。     

三氯乙烯作业人群外周血淋巴细胞染色体损伤研究

目的探讨三氯乙烯(TCE)致作业人群外周血淋巴细胞染色体损伤的作用。方法以91名TCE暴露工人和59名对照作为研究对象,调查职业史、年龄、性别、吸烟和饮酒等信息。收集班后尿,测定尿中三氯乙酸(TCA)水平反映TCE暴露内剂量。抽取肘静脉血,胞质分裂阻滞微核法制备外周血淋巴细胞涂片,计数微核、核质桥和核芽发生率,评价染色体损伤水平。结果两组研究对象在年龄、性别、吸烟、饮酒状况等方面均无显著性差异。暴露组平均TCE作业工龄为1.8年。暴露组尿中TCA水平为57.5mg/L,远远高于对照组0.9mg/L。两组研究对象的微核率及核质桥率无显著差异,但暴露组核芽率[(1.6±1.0)‰]显著高于对照组[(1.2±0.8)‰,P=0.05]。核芽率的升高在尿TCA≥50.0 mg/L组和TCE作业工龄≥1.8年组中表现更为明显。同时,尿TCA≥50.0 mg/L的工人,其微核率[(1.8±0.9)‰]也显著高于对照组[(1.4±0.7)‰,P=0.05]。未发现年龄、性别、吸烟、饮酒对微核率、核质桥率、核芽率的显著影响。结论 TCE暴露可致作业工人染色体损伤增加,核芽可以较为敏感的检出由TCE职业暴露所引发的基因组不稳定性。     

三氯乙烯作业人群尿中小分子蛋白水平研究

目的探讨三氯乙烯(TCE)职业接触对尿中3种小分子蛋白水平的影响。方法以112名TCE接触工人和70名对照作为调查对象,收集职业史、年龄、性别、吸烟和饮酒等信息。收集班后尿,测定三氯乙酸(TCA)水平及α1微球蛋白(α1-M)、β2微球蛋白(β2-M)、视黄醇结合蛋白(RBP)的水平。结果3种小分子蛋白α1-M、β2-M、RBP水平在两组调查对象中比较,差异均无统计学意义。以作业工龄、TCE浓度、尿中TCA水平分组后,作业工龄≥1.9a的工人α1-M水平明显高于对照组,差异有统计学意义(P<0.05);高TCE浓度(198.0～257.0mg/m3)组及尿中TCA水平≥50mg/L组的工人RBP水平均明显高于对照组,差异有统计学意义(P<0.05)。结论长时间和高水平TCE职业接触可致作业工人尿中α1-M、RBP水平增高。     

三氯乙烯致敏豚鼠体液免疫变化

目的 探讨三氯乙烯(TCE)致敏豚鼠血清中补体(C)和免疫球蛋白(Ig)的变化.方法 选用体重250～300 g的雌性豚鼠36只,随机分成空白对照组(5只),溶剂(橄榄油)对照组(5只),TCE实验组(26只).根据豚鼠最大值试验(GPMT)方法对豚鼠进行染毒.激发接触后24 h观察和记录豚鼠背部受试区的皮肤反应情况,进行评分.按皮肤致敏反应积分将TCE处理组豚鼠分为致敏组(积分≥1)和未致敏组(积分为0).分别在实验结束后24、72 h采血,检测血清中C3、C4、IgA、IgG、IgM浓度.结果 TCE处理组豚鼠致敏率为65.38％(17/26).TCE致敏24、72 h组C3含量[24 h:(99.75±1.45)μg/ml,72 h:(93.28±3.61) μg/ml]均明显低于溶剂对照组[(112.30±9.10)μg/ml],差异均有统计学意义(P＜0.05);与溶剂对照组比较,致敏24、72 h组C4含量[24 h:(34.63±2.53) μg/ml,72 h:(33.82±2.76) μg/ml]均明显低于溶剂对照组[(43.87±3.65) μg/ml],差异均有统计学意义(P＜0.05).TCE致敏24、72 h组、TCE未致敏24、72 h组IgA、IgM含量均明显低于溶剂对照组,差异均有统计学意义(P＜0.05).与TCE未致敏组比较,TCE致敏24、72 h组血清中IgA水平均降低,差异有统计学意义(P＜0.05).各组血清中IgG的含量无明显改变.结论 TCE致敏豚鼠皮肤后,血清中C3、C4含量降低,体液免疫功能发生紊乱.     

三氯乙烯对职业人群遗传指标的影响

目的确定三氯乙烯(Trichloroethylene,TCE)对人体遗传指标的影响,为控制TCE中毒的危害和确定早期诊断指标提供一定的依据.方法按调查表格逐项进行问诊、全面体格检查、尿中三氯乙酸(TCA)和遗传指标的测定.结果SCE细胞和慧里细胞(%)在接触TCE工龄小于2年时,与对照组并无统计学上的差异,P＞0.05;但在接触TCE工龄大于2年时,以上指标均显著高于对照组(P＜0.05).尿中TCA浓度小于50mg/L时,双微核率、微核率、SCE细胞与对照组并无统计学上的差异,P＞0.05;但在尿中TCA浓度大于50 mg/L时,以上指标均显著高于对照组(P＜0.05).结论TCE对职业接触人群的遗传指标确实产生了有统计学意义的改变,TCE具有一定的遗传毒性.可以考虑把遗传指标测定作为职业接触TCE人员职业性健康检查的检查项目,但需对更大人群的遗传指标进行测定,以确定正常参考值和早期损害的阚值.     

三氯乙烯对职业人群尿中α1-微球蛋白的影响

目的探讨三氯乙烯(Trichloroethylene,TCE)对职业人群尿中α1-微球蛋白(α1-M)含量的影响。方法选择51名接触TCE的职业工人及不接触TCE的20人作为对照,通过问卷调查收集每人的一般情况和职业史等。按调查表格逐项进行问诊、全面体格检查,尿中三氯乙酸(TCA)浓度和尿中α1-M的测定。结果接触组内男性比女性接触TCE的时间长(P<0.01),尿中TCA的浓度大(P<0.05)。接触组中男性和女性的尿中TCA的浓度均显著高于对照组(P<0.01)。对测定结果按接触TCE工龄或尿中TCA浓度进行多次分组,尿中α1-M含量未发现有统计意义的变化。结论TCE对职业接触人群的尿中α1-M未产生有统计意义的改变,因此我们认为尿中α1-M不能作为TCE对人体损害的早期观察指标。至于接触TCE更长时间或更高浓度是否会产生有统计意义的变化,需要作进一步的研究。     

三氯乙烯对接触工人神经行为功能影响的初步研究

目的：了三氯乙烯（TCE）低浓度、长时间的暴露条件下对暴露人群的早期影响。方法：运用WHO推荐的神经行为功能测试组合（WHO－NCTB）对我国南方某市一区65名TCE作业工人及115名对照工人进行了神经行为功能测试,同时测定研究对象尿中TCE的代谢产物三氯乙酸（TCA）的含量。结果：接触工人车间空气中TCE平均浓度为90．8mg/m^3,接触工人班后尿TCA平均值为52．1mg/g肌酐;接触组NCTB测试项目中数字译码、简单反应时的标准差、优势手提转敏捷度、目标追踪错误数及总数得分显著差于对照组,通过等级相关分析,发现接触组班后尿TCA水平与目标追踪正确数、总数呈显著负相关;与情感问卷中困惑－迷茫项、目标追踪错误数呈显著正相关。结论：长时间接触较低浓度TCE早期可对暴露者神经行为功能产生明显影响,主要表现在短时间记忆力、注意力降低、手运动速度下降,手－眼运动协调性和稳定性差,并有一定的消极情感状态改变;尿TCA水平与以上改变呈一定的剂量－反应关系。     

三氯乙烯作业工人神经行为功能的研究

目的了解三氯乙烯职业接触对作业工人的神经行为功能的影响.方法世界卫生组织(WHO)推荐的神经行为功能测试组合(WHO-NCTB).结果本调查研究了65名三氯乙烯(TTCE)作业工人和115名对照;接触人群车间空气TCE平均浓度为90.8mg/m3,接触工人班后尿二氯乙酸(TCA)平均值为52.1mg/L.肌酐;多因素分析后发现接触组工人NCTB测试项目中数字译码、简单反应时的标准差、非利手提转敏捷度、目标追踪错误数及总数得分显著差于对照组;等级相关分析表明接触组工人班后尿TCA水平与目标追踪正确数、总数呈显著负相关,与情感问卷中困惑一迷茫项、目标追踪错误数呈显著正相关.结论长时间接触较低浓度TCE作业工人早期即可对其神经行为功能产生明显影响,主要表现在短时记忆力、注意力降低,手运动速度下降,手一眼运动协调性和稳定性差,并有一定的消极情感状态改变;接触水平与以上改变呈一定的剂量一反应关系.     

Mutagenicity of trichloroethylene and its metabolites: implications for the risk assessment of trichloroethylene

This article addresses the evidence that trichloroethylene (TCE) or its metabolites might mediate tumor formation via a mutagenic mode of action. We review and draw conclusions from the published mutagenicity and genotoxicity information for TCE and its metabolites, chloral hydrate (CH), dichloroacetic acid (DCA), trichloroacetic acid (TCA), trichloroethanol, S-(1, 2-dichlorovinyl)-l-cysteine (DCVC), and S-(1, 2-dichlorovinyl) glutathione (DCVG). The new U.S. Environmental Protection Agency proposed Cancer Risk Assessment Guidelines provide for an assessment of the key events involved in the development of specific tumors. Consistent with this thinking, we provide a new and general strategy for interpreting genotoxicity data that goes beyond a simple determination that the chemical is or is not genotoxic. For TCE, we conclude that the weight of the evidence argues that chemically induced mutation is unlikely to be a key event in the induction of human tumors that might be caused by TCE itself (as the parent compound) and its metabolites, CH, DCA, and TCA. This conclusion derives primarily from the fact that these chemicals require very high doses to be genotoxic. There is not enough information to draw any conclusions for trichloroethanol and the two trichloroethylene conjugates, DCVC and DCVG. There is some evidence that DCVC is a more potent mutagen than CH, DCA, or TCA. Unfortunately, definitive conclusions as to whether TCE will induce tumors in humans via a mutagenic mode of action cannot be drawn from the available information. More research, including the development and use of new techniques, is required before it is possible to make a definitive assessment as to whether chemically induced mutation is a key event in any human tumors resulting from exposure to TCE.     

Metabolism of trichloroethylene

A major focus in the study of metabolism and disposition of trichloroethylene (TCE) is to identify metabolites that can be used reliably to assess flux through the various pathways of TCE metabolism and to identify those metabolites that are causally associated with toxic responses. Another important issue involves delineation of sex- and species-dependent differences in biotransformation pathways. Defining these differences can play an important role in the utility of laboratory animal data for understanding the pharmacokinetics and pharmacodynamics of TCE in humans. Sex-, species-, and strain-dependent differences in absorption and distribution of TCE may play some role in explaining differences in metabolism and susceptibility to toxicity from TCE exposure. The majority of differences in susceptibility, however, are likely due to sex-, species-, and strain-dependent differences in activities of the various enzymes that can metabolize TCE and its subsequent metabolites. An additional factor that plays a role in human health risk assessment for TCE is the high degree of variability in the activity of certain enzymes. TCE undergoes metabolism by two major pathways, cytochrome P450 (P450)-dependent oxidation and conjugation with glutathione (GSH). Key P450-derived metabolites of TCE that have been associated with specific target organs, such as the liver and lungs, include chloral hydrate, trichloroacetate, and dichloroacetate. Metabolites derived from the GSH conjugate of TCE, in contrast, have been associated with the kidney as a target organ. Specifically, metabolism of the cysteine conjugate of TCE by the cysteine conjugate ss-lyase generates a reactive metabolite that is nephrotoxic and may be nephrocarcinogenic. Although the P450 pathway is a higher activity and higher affinity pathway than the GSH conjugation pathway, one should not automatically conclude that the latter pathway is only important at very high doses. A synthesis of this information is then presented to assess how experimental data, from either animals or from (italic)in vitro (/italic)studies, can be extrapolated to humans for risk assessment. (italic)Key words(/italic): conjugate beta-lyase, cysteine glutathione, cytochrome P450, glutathione (italic)S(/italic)-transferases, metabolism, sex dependence, species dependence, tissue dependence, trichloroethylene.     

Exposure assessment of trichloroethylene

This article reviews exposure information available for trichloroethylene (TCE) and assesses the magnitude of human exposure. The primary sources releasing TCE into the environment are metal cleaning and degreasing operations. Releases occur into all media but mostly into the air due to its volatility. It is also moderately soluble in water and can leach from soils into groundwater. TCE has commonly been found in ambient air, surface water, and groundwaters. The 1998 air levels in microg/m(3) across 115 monitors can be summarized as follows: range = 0.01-3.9, mean = 0.88. A California survey of large water utilities in 1984 found a median concentration of 3.0 microg/L. General population exposure to TCE occurs primarily by inhalation and water ingestion. Typical average daily intakes have been estimated as 11-33 microg/day for inhalation and 2-20 microg/day for ingestion. A small portion of the population is expected to have elevated exposures as a result of one or more of these pathways: inhalation exposures to workers involved in degreasing operations, ingestion and inhalation exposures occurring in homes with private wells located near disposal/contamination sites, and inhalation exposures to consumers using TCE products in areas of poor ventilation. More current and more extensive data on TCE levels in indoor air, water, and soil are needed to better characterize the distribution of background exposures in the general population and elevated exposures in special subpopulations.     

Diverse manifestations of trichloroethylene

Trichloroethylene, a solvent used in a variety of industrial settings for more than 60 years, has caused adverse health effects on the central and peripheral nervous system, the skin, liver, kidney, and heart. Three men have shown relatively unusual manifestations secondary to exposure to trichloroethylene in degreasing operations in the jewelry industry. Toxic encephalopathy, hepatitis, and carpal spasm occurred among young, healthy workers. Clinical and laboratory data, including measurement of urinary trichloroacetic acid concentrations, are presented.     

Genotoxicity of trichloroethylene in the natural milieu

Trichloroethylene (TCE) is a suspected genotoxic and carcinogenic compound which is usually present in the air, soil and water as pollutant. To estimate the genotoxic potential of TCE in a pure chemical form as well as an ingredient of the complex sample, Ames fluctuation test using TA98 and TA100 strains and Allium cepa genotoxicity assay were performed. For the genotoxicity analysis of TCE in natural milieu, the above mentioned tests were performed on the waste waters collected from two different stations of northern India namely Saharanpur and Aligarh, U.P., and these waste waters were supplemented with 50 and 100 mg/l of trichloroethylene. TCE alone was found to be non-genotoxic by both the testing system up to the range of 1000 mg/l concentration (data not shown). However, the test water samples supplemented with 100 mg/l of TCE, exhibited a significant increase in the genotoxicity compared with control by both the testing systems. In Ames fluctuation test, Mi(f) value was found to be increased by 41% and 53% with 100 mg/l of TCE supplemented Saharanpur and Aligarh waste water samples respectively, in the presence of S9 fraction compared with their respective controls. Allium cepa genotoxicity test also showed around 25% increase in total chromosomal aberration frequency following 100 mg/l TCE supplementation. However, supplementation of 50 mg/l TCE to the test water samples could not enhance the genotoxicity to a significant extent. From these results, we can conclude that TCE itself was non-genotoxic but it may promote mutation and/or DNA damage at a concentration of 100 mg/l under certain environmental conditions. We suggest that some chemicals in the test water samples might be interacting with TCE and/or metabolite(s) to cause the enhancement in genotoxicity. The mechanism of these synergistic effects should be explored further.     

Diverse manifestations of trichloroethylene.

Trichloroethylene, a solvent used in a variety of industrial settings for more than 60 years, has caused adverse health effects on the central and peripheral nervous system, the skin, liver, kidney, and heart. Three men have shown relatively unusual manifestations secondary to exposure to trichloroethylene in degreasing operations in the jewelry industry. Toxic encephalopathy, hepatitis, and carpal spasm occurred among young, healthy workers. Clinical and laboratory data, including measurement of urinary trichloroacetic acid concentrations, are presented.