1,2-二氯乙烷接触者尿液中生物指标监测的研究

目的探讨1,2-二氯乙烷接触者尿液中的生物标志物,以期及时发现DCE接触者,预防1,2-二氯乙烷职业中毒。方法抽取接触1,2-二氯乙烷的作业工人和明确非1,2-二氯乙烷接触工人为调查对象,收集调查对象的尿液进行预处理后进行气相色谱-质谱分析。结果与对照组相比,暴露组的尿液样本中多出几种组分:硫代二乙酸二甲酯、2-甲硫基乙酸甲酯、磷酸三甲酯,暴露组的尿样总离子流色谱图中硫代二乙酸二甲酯、柠檬酸三甲酯信号强度较大。结论硫代二乙酸二甲酯可以作为1,2-二氯乙烷接触生物标志物的初筛指标,值得进一步研究。     

气相色谱-质谱联用法测定硫代双乙酸二甲酯的研究

<正>二氯乙烷是一种卤代烃类化合物,是一种工业上广泛使用的有机溶剂,该物质产量高、毒性大、应用范围广,接触人数多,引起中毒的通常为1,2-二氯乙烷(简称DCE)[1]。国内学者陈红红通过对染毒大鼠的尿样预处理后进行气相色谱-质谱(GC-MS)分析,初步探讨硫代双乙酸二甲酯作为接触DCE的生物标志物的可行性[2]。在项目组前期研究中,通过比较暴露在DCE环境中作业的工人与明确不接触DCE的作     

1，2－二氯乙烷对大鼠神经细胞内钙离子浓度的影响

[目的]用体外实验方法研究1,2-二氯乙烷（1,2-DCE）染毒后大鼠神经细胞内钙离子（Ca^2＋）浓度的变化。[方法]体外培养新生SD大乳鼠脑皮质细胞,分别用0．5、1．0、2．0mL/L1,2-DCE染毒,另设对照组,观察各组神经细胞形态学变化。同时应用激光共聚焦显微镜测定各组细胞内Ca^2＋浓度,探讨1,2-DCE对大鼠神经细胞内Ca^2＋浓度的影响。[结果]神经细胞染毒后,神经细胞形态发生明显改变：胞体肿胀崩解、胞核模糊不清、突触变短变粗、细胞间连接减少、细胞膜不完整;随着染毒剂量的增高,神经细胞损伤的严重程度呈上升趋势。各染毒组神经细胞活力较对照组有所下降,差异有统计学意义（P〈0．01）;染毒2h后随着染毒剂量的增加,各组神经细胞内Ca^2＋浓度呈上升趋势,各染毒组细胞与对照组比较差异有统计学意义（P〈0．01）;染毒24h后,低、中剂量组与对照组细胞内Ca^2＋浓度比较差异有统计学意义（P〈0．01）,高剂量组与对照组比较差异无统计学意义（P〉0．05）。[结论]1,2-DCE可以导致神经细胞水肿坏死,有剂量依赖关系,神经细胞内Ca^2＋浓度亦见升高,提示Ca^2＋可能与1,2-DCE致神经细胞中毒性脑水肿有关。     

某皮革厂一起急性1,2-二氯乙烷中毒事故调查

[目的]调查引起一起急性1,2-二氯乙烷中毒事故的原因。[方法]调查1名急性职业性1,2-二氯乙烷中毒病人所在公司的各项职业卫生管理体制、生产作业场所有害物质浓度和同车间接触人员的职业健康检查情况。[结果]用人单位未建立职业卫生管理规章制度;上糊生产线岗位1,2-二氯乙烷浓度CTWA为23.6mg/m3、CSTEL为261.1mg/m3,分别超限2.4倍和16.4倍;应急医学健康检查人数为125人,其中有101名工人需进行职业性复查,其中有26名工人尿β2-微球蛋白≥1.8μg/ml,属重点复查人员,其他各种职业性异常(如尿β2-微球蛋白偏高、血白细胞偏低、主诉体征症状及神经系统检查异常者)共有75人。[结论]本次事件中上糊生产线岗位使用的5种胶粘剂中含高浓度1,2-二氯乙烷,上糊生产线岗位空气中1,2-二氯乙烷浓度超过国家卫生限值规定,结合临床表现,可以确认该起事件为急性职业性1,2-二氯乙烷中毒事件。     

在体微透析观察大鼠急性一氧化碳中毒后纹状体多巴胺及其代谢产物的变化

[目的]研究急性一氧化碳(carbon monoxide,CO)中毒对大鼠脑纹状体多巴胺(DA)及其代谢产物二羟苯乙酸(DOPAC)、高香草酸(HVA)水平的影响。[方法]将大鼠随机分成对照组和CO中毒组,采用腹腔注射CO法染毒,首次染毒剂量为120ml/kg,然后每隔4h注射一次,共3次维持剂量60ml/kg,对照组以同样方法和剂量注射空气。观察首次染毒后24h内各组动物血碳氧血红蛋白(HbCO)浓度变化,同时利用在体微透析技术观察脑纹状体DA及其代谢产物在末次染毒后11h内及第10d的变化特点。[结果]腹腔注射CO染毒后,大鼠血HbCO浓度迅速增高,在首次染毒后1～2h达高峰,维持剂量连续染毒时,血HbCO浓度可维持在55%以上达15h,末次染毒6h后降至正常水平;朱次染毒后,大鼠脑纹状体DA水平增加,其代谢产物明显减少,至第4～6h开始逐渐恢复,第11h恢复到正常水平;末次染毒后第10天中毒组动物纹状体DA水平与对照组比较再次明显降低,其代谢产物水平明显升高。[结论]CO中毒血HbCO浓度恢复正常水平后,提示DA及其代谢产物再次出现异常变化可能与急性CO中毒迟发性锥体外系神经精神症状有关。     

尿中甲氧基乙酸测定的柱前衍生-液液微萃取-气相色谱法

目的:建立乙二醇单甲醚的代谢产物尿中甲氧基乙酸的柱前衍生-液液微萃取-气相色谱测定法。方法:向尿样中加入磷酸盐缓冲液、叔丁氧基乙酸（内标物）、五氟苄基溴（衍生剂）,随后置于90 ℃水浴锅中衍生40 min,冷却后过滤,二氯甲烷萃取,振荡离心后吸取下层有机相注入气相色谱仪,DB-5毛细管色谱柱分离,ECD检测器检测。结果...     

氯乙烯代谢产物尿中硫撑双乙酸的气相色谱测定

S.Yllner,G.Muler等报导,氯乙烯进入机体后的主要代谢产物是硫撑双乙酸,Thiodiglycollic acid(TDGA)。本文参照陈震阳等报导,结合具体条件进行了实验,并做了尿样测定。一、操怍和测定1.仪器及试剂(1) 日立166型气相色谱仪及火焰光度检测     

亚急性重度1,2-二氯乙烷中毒救治体会

目的探讨亚急性重度1,2-二氯乙烷中毒的救治。方法对1例以中毒性脑病为主要临床表现的亚急性重度1,2-二氯乙烷中毒患者采取以防治"脑水肿"为治疗重点的综合治疗。结果患者住院第4天由昏迷转为轻度意识障碍,出现头颈部、双上肢不自主的震颤伴构音困难,住院第6天意识清醒,头颈部震颤缓解,双上肢持续性震颤,住院治疗1个月余病情好转出院。结论及时、恰当的脱水治疗是救治亚急性重度1,2-二氯乙烷中毒的关键。     

被动吸烟对孕妇尿中4种多环芳烃代谢物浓度的影响

[目的] 以尿中2-羟基萘(2-NAP)、2-羟基芴(2-FLU)、9-羟基菲(9-PHE)和1-羟基芘(1-PYR)作为生物标志物,评价太原市孕妇体内多环芳烃(PAHs)暴露水平,探讨被动吸烟对其浓度的影响. [方法]2009年4月-2010年4月,抽取太原市某医院住院分娩孕妇287人,对其工作生活环境等情况进行问卷调查.将符合纳入标准的264名孕妇根据被动吸烟指数等级分为3组:0、1～49、≥50组,收集各组产前尿样,利用高效液相色谱-荧光检测法测定尿中4种PAHs的羟基代谢产物(OH-PAHs)水平. [结果]符合纳入标准的孕妇尿样中均可检测到2-羟基萘、2-羟基芴、9-羟基菲和1-羟基芘,浓度中位数分别为0.47、0.24、0.23和0.10 μg/mmolCr.除9-羟基菲外,3组尿中2-羟基萘、2-羟基芴、1-羟基芘的差异均有统计学意义(P＜0.05);多元线性回归分析显示,被动吸烟、使用煤炉、采暖期、汽修厂加油站是影响孕妇尿中4种OH-PAHs水平的主要因素. [结论]被动吸烟可以增加孕妇尿中4种OH-PAHs含量,其中2-羟基萘可以作为反映被动吸烟对孕妇体内多环芳烃暴露水平影响的最佳指标.     

血中三硝基甲苯及代谢物的测定和应用

三硝基甲苯(TNT)为氧化应激毒物~[1,2]。其毒作用范围很广。因此,测定职业接触TNT工人血中TNT及代谢产物,对中毒机理研究及生物监测都具有重要意义。本文根据巳经建立的液相色谱分离、萃取和血样水解条件~[3],对现场接触和不接触TNT工人血中TNT及两种代谢产物4—氨基—2,6-二硝基甲苯(4A)和2—氨基—4,-二硝基甲苯(2A)分别进行了测定,并获得了满意的测定效果。     

1，2-二氯乙烷致中毒性脑病中神经细胞的变化

目的用体外实验方法研究1,2-二氯乙烷染毒后神经细胞形态学的变化。方法将体外培养的新生SD大鼠的脑皮质细胞,分为设对照组、低、中、高剂量组,观察各组细胞形态学、超微结构和细胞活力的变化。结果染毒后神经细胞形态和超微结构均发生明显变化：在荧光显微镜下随着染毒剂量的增高,细胞核由亮绿色变为桔红色,胞体胀大甚至消失;在透射电镜下染毒组神经细胞的细胞核核膜溶解消失,染色质聚集深染,线粒体和内质网等细胞器肿胀,崩解,且线粒体嵴排列紊乱甚至消失;各染毒组神经细胞活力比对照组有所下降,差异有统计学意义（P〈0．05）。结论1,2-二氯乙烷可以导致神经细胞水肿坏死,并且有剂量依赖关系,随着染毒剂量的增加神经细胞破坏程度越大。     

工作场所空气中1,2-二氯乙烷的毛细管柱气相色谱测定法

目的建立用活性炭管采集工作场所空气中1,2-二氯乙烷的毛细管气相色谱分析方法。方法用活性炭管吸附空气中1,2-二氯乙烷,样品经二硫化炭解吸,气相色谱检测。结果当1,2-二氯乙烷浓度范围在0～116.5μg/ml时,相关系数r0.999,检出限为:0.12μg/ml,以采集4.5L空气样品计,最低检出浓度为0.027mg/m3。平均解吸率96.0%,活性炭管吸附23.30μg1,2-二氯乙烷,样品放置7天后,回收率仍达94.9%。在该实验条件下与三氯甲烷等化合物有较好的分离。结论本方法可用于工作场所空气中1,2-二氯乙烷的检测。     

1,2-二氯乙烷急性吸入染毒脑组织损伤形态学研究

为了研究 1 ,2 二氯乙烷 (1 ,2 -DCE)在静式吸入染毒条件下对脑组织的急性损害。采用连续静式吸入染毒大鼠 1 2h后 ,观察不同染毒剂量下受试动物脑组织的形态学变化 ;测定脑组织干湿重及含水量。结果显示 :染毒剂量为 2 .5g m3 时 ,脑组织在形态学上无明显变化 ,含水量为 80 .41 % ,与对照组 (79.82 % )相比 ,无明显差异 ;5 .0g m3 染毒组在形态学上出现轻微脑水肿 ,脑组织含水量为 82 .1 4 % ,与对照组相比有显著性差异 (P <0 .0 5) ;1 0 .0g m3 组脑组织在形态学上水肿明显 ,其含水量 (83 .65 % )与各组之间差异显著 (P <0 .0 5)。结果提示 :1 ,2 -DCE在短期大量吸入的情况下可导致动物出现脑水肿。     

Disposition and metabolism of 1,2-dimethylnaphthalene in rats

The aim of this study was to investigate the distribution, excretion and metabolism of 1,2-dimethylnaphthalene-[ring-U-3H] in rats. The experiments were performed on 54 male outbred IMP:Wist rats with body weight of 200 g +/- 20%. The compound was given i.p. in olive oil in a single dose of 28 mg/kg (about 6.2 MBq per animal). 3H radioactivity was traced in selected organs and tissues, blood, urine and faeces, 1-72 h following the administration. The main metabolites were isolated from urine and identified by the GC-MS method. Faeces and urine proved to be the main route of tritium elimination. Over 93% of the given compound was excreted during the first 72 h. Maximum level of tritium in plasma was observed during the 4th h after the compound administration. The accretion of 3H proceeded with kinetic constant of 0.7 h, followed by monophasic decline with the half-life of about 19h. In organs and tissue, the highest concentration during the first hours after administration were detected in the fat, adrenals, liver, spleen and kidneys. Then gradual decline of tritium was noticed in all examined tissues. The following urinary metabolites were identified: 1. 1,2-dimethylthionaphthalene, 2. 1,2-dimethylnaphthol, 3. 1-methylnaphthalene-2-methanol, 4. 1-methyl-2-naphthoic acid and 5. 1,2-dimethylmethylthionaphthalene. In conclusion, 1,2-dimethylnaphthalene has a relatively rapid turnover rate in the rat organism and does not form deposits in the tissue. The metabolism encompasses ring hydroxylation and glutathione conjugation leading to thionaphthol and oxygenation, and then to naphthoic acid.     

某制鞋厂一起疑似职业性急性1，2-二氯乙烷中毒事故调查报告

目的调查引起一起疑似职业性急性1,2-二氯乙烷中毒事故的原因。方法调查1名疑似职业性1,2-二氯乙烷中毒病人所在公司的各项职业卫生管理体制、生产作业场所中有害物质浓度和同车间接触人员的职业健康检查情况。结果用人单位未建立职业卫生管理规章制度;插鞋操作位空气中1,2-二氯乙烷浓度CTMA为32．9mg／m^3、CSTEL为36．3mg／m^3,分别超限3．7和1．6倍;被检的29名底部车间工人中,有19名工人尿中β2-微球蛋白≥1．2ug／ml,异常率为65．5％;自诉症状头晕、头痛、烦燥、恶心、呕吐等15人,异常率为51．7％。结论该次事件中插鞋岗位使用的散装港宝水、309黄胶中含高浓度1,2-二氯乙烷,插鞋岗位空气中1,2-二氯乙烷浓度超过国家卫生限值规定,结合临床表现,可以确认该起事件为疑似职业性急性1,2-二氯乙烷中毒事件。     

Identification of potential biomarkers of exposure to di(isononyl)cyclohexane-1,2-dicarboxylate (DINCH), an alternative for phthalate plasticizers

Di(isononyl)cyclohexane-1,2-dicarboxylate (DINCH) is used as an alternative for some phthalate plasticizers. In rats, DINCH mostly eliminates in feces as cyclohexane-1,2-dicarboxylic acid (CHDA), mono isononyl ester (MINCH) or in urine as CHDA. However, CHDA is not a specific biomarker of DINCH and measuring MINCH in feces is impractical. To identify additional potential biomarkers, we administered DINCH (500?mg/kg body weight) in a single subcutaneous (SC) or oral dose to four adult female Sprague-Dawley rats. We collected 24-h urine samples before dosing (to be used as controls) and 24-h and 48-h after dosing, and serum at necropsy after 48?h. We positively identified and accurately quantified CHDA and cyclohexane-1,2-dicarboxylic [corrected] acid, mono hydroxyisononyl ester (MHNCH) using authentic standards. Moreover, we tentatively identified MINCH and 12 oxidative metabolites, including 4 cyclohexane ring oxidation products, based on their mass spectrometric-fragmentation patterns. CHDA and MHNCH levels were higher in the urine collected 24?h after oral than SC administration. By contrast, 48-h after dosing, CHDA urinary levels were similar regardless of the exposure route. We detected all but two of the urine metabolites also in serum. Levels of CHDA and MHNCH in serum were lower than in the two post-dose urine collections. Our results suggest that several urinary oxidative metabolites, specifically CHDA, mono oxoisononyl ester and MHNCH may be used as specific biomarkers of DINCH exposure in humans.     

Carcinogenicity and chronic toxicity in rats and mice exposed by inhalation to 1,2-dichloroethane for two years

Carcinogenicity and chronic toxicity of 1,2-dichloroethane (DCE) were examined by inhalation exposure of groups of 50 F344 rats and 50 BDF1 mice of both sexes to DCE vapor or clean air as control for 6 h/d, 5 d/wk and 104 wk. The rats were exposed to 10, 40 or 160 ppm (v/v) DCE, while the mice were exposed to 10, 30 or 90 ppm. The 2-yr exposure to DCE produced a dose-dependent increase in incidences of benign and malignant tumors, including subcutaneous fibroma, mammary gland fibroadenoma and peritoneal mesothelioma in male rats; subcutaneous fibroma and mammary gland adenoma, fibroadenoma and adenocarcinoma in female rats; and bronchiolo-alveolar adenoma and carcinoma, endometrial stromal polyp, mammary gland adenocarcinoma and hepatocellular adenoma in female mice. No exposure-related change in the incidence of non-neoplastic lesions or in any hematological, blood biochemical or urinary parameter occurred in any DCE-exposed rat or mouse group. The types of tumors and their target organs found in this study were consistent with those observed in rats and mice administered DCE by gavage in a NCI study. Selection of the exposure concentrations was considered appropriate with reference to the maximum tolerated dose for the highest doses and an occupational exposure limit of DCE for the lowest dose. The present findings suggest that those carcinogenic responses be primarily considered for standard setting of occupational and environmental exposure to DCE.     

Tryptophan-niacin metabolism in rat with puromycin aminonucleoside-induced nephrosis

We investigated the change of tryptophan-niacin metabolism in rats with puromycin aminonucleoside PAN-induced nephrosis, the mechanisms responsible for their change of urinary excretion of nicotinamide and its metabolites, and the role of the kidney in tryptophan-niacin conversion. PAN-treated rats were intraperitoneally injected once with a 1.0% (w/v) solution of PAN at a dose of 100 mg/kg body weight. The collection of 24-hour urine was conducted 8 days after PAN injection. Daily urinary excretion of nicotinamide and its metabolites, liver and blood NAD, and key enzyme activities of tryptophan-niacin metabolism were determined. In PAN-treated rats, the sum of urinary excretion of nicotinamide and its metabolites was significantly lower compared with controls. The kidney alpha-amino-beta-carboxymuconate-epsilon-semialdehyde decarboxylase (ACMSD) activity in the PAN-treated group was significantly decreased by 50%, compared with the control group. Although kidney ACMSD activity was reduced, the conversion of tryptophan to niacin tended to be lower in the PAN-treated rats. A decrease in urinary excretion of niacin and the conversion of tryptophan to niacin in nephrotic rats may contribute to a low level of blood tryptophan. The role of kidney ACMSD activity may be minimal concerning tryptophan-niacin conversion under this experimental condition.     

The disaccharide effect of sucrose feeding on excretion of intravenously injected [1,2-3H]aldosterone and conjugated glucuronic acid in normotensive rats

The hypothesis tested was that feeding rats sucrose rather than invert sugar (50:50 mixture of glucose and fructose) or cornstarch would result in a more rapid excretion of glucuronides and tritium from intravenously injected [1,2-3H]aldosterone. Thirty 56-d-old male rats of the Sprague-Dawley strain were fed for 8 wk one of three diets containing 45% of dietary energy from sucrose, invert sugar or cornstarch; 15% of energy was from protein and 40% from fat. Body weights and systolic blood pressures were measured weekly. After 60 d of feeding the diets ad libitum, all rats were injected intravenously with [1,2-3H]aldosterone and the percent recovery of tritium in both urine and feces was determined over the next 4 d. Urinary and fecal excretion of both free and conjugated glucuronic acid was determined over those 4 d. Urinary excretion of sodium and potassium (mg/d) was also determined. There were no differences between groups in food or water intakes, body weights, systolic blood pressures, daily fecal weights and daily urine volumes. The cornstarch-fed group excreted less sodium and potassium than did the other groups (P less than 0.05). The sucrose-fed group had a greater 4-d excretion of tritium (urinary + fecal) than did the invert sugar- or cornstarch-fed groups (P less than 0.01). The sucrose-fed group had a greater percentage of excreted glucuronic acid that was conjugated (urinary + fecal) than did the invert sugar- or cornstarch-fed groups (P less than 0.05). These results tended to confirm the hypothesis.