三硝基甲苯及其代谢产物对兔肝匀浆谷胱甘肽水平的影响

三硝基甲苯（ＴＮＴ）及其代谢产物与兔肝匀浆于３７℃孵育１ｈ。随着ＴＮＴ、４－ＡＨ浓度的增大，肝匀浆中ＧＳＨ的含量呈明显的下降趋势，而２－Ａ、４－Ａ及２，４－ＤＡ之肝匀浆中ＧＳＨ的水平与对照相比无显著性差异。５６０μｍｏｌ／ＬＴＮＴ及５６０μｍｏｌ／Ｌ４－ＡＨ与肝匀浆孵育不同时间，肝匀浆中ＧＳＨ含量随着时间的延长而降低，结果表明：在ＴＮＴ及其代谢产物中，除ＴＮＴ外，４－ＡＨ对动物肝也表现出毒性作用。     

甲基叔丁醚及其代谢产物对HL—60细胞的遗传毒性测定

应用单细胞凝胶电泳法（ＳＣＧＥ）测定新型汽油添加剂甲基叔丁醚（ＭＴＢＥ）及其代谢产物叔丁醇（ＴＢＡ）、α－羟基异丁酸（ＨＩＢＡ）和甲醛引起的人白血病细胞（ＨＬ－６０细胞）ＤＮＡ损伤，以乳酸脱氢酶的释放评价其细胞毒性。结果显示，ＭＴＢＥ、ＴＢＡ和ＨＩＢＡ在１～３０ｍｍｏｌ／Ｌ浓度范围内能够引起ＤＮＡ损伤并有明显的剂量反应关系；另一代谢产物甲醛在浓度５μｍｏｌ／Ｌ时即可产生ＤＮＡ损伤，但浓度升高时出现ＤＮＡ迁移减少。提示ＭＴＢＥ及其代谢产物可能具有遗传毒性。然而在引起ＤＮＡ损伤的剂量范围内却没有观察到ＭＴＢＥ、ＴＢＡ和ＨＩＢＡ的细胞毒性，而甲醛则表现明显的细胞毒性作用     

镉对硒引起的离体大鼠肝细胞DNA损伤作用的影响

应用单细胞凝胶电泳研究氯化镉对亚硒酸钠引起的大鼠肝细胞ＤＮＡ损伤作用的影响。结果表明，在８７５μｍｏｌ／Ｌ、１７５０μｍｏｌ／Ｌ、３５００μｍｏｌ／Ｌ的剂量下，亚硒酸钠单独作用时，可引起肝细胞ＤＮＡ损伤。当氯化镉与亚硒酸钠联合作用时，８７５μｍｏｌ／Ｌ的氯化镉对８７５μｍｏｌ／Ｌ、１７５０μｍｏｌ／Ｌ、３５００μｍｏｌ／Ｌ的亚硒酸钠引起的ＤＮＡ损伤存在明显的拮抗作用，而３５００μｍｏｌ／Ｌ的氯化镉对８７５μｍｏｌ／Ｌ、１７５０μｍｏｌ／Ｌ、３５００μｍｏｌ／Ｌ亚硒酸钠引起的ＤＮＡ损伤不但未显示出拮抗作用，反而使得ＤＮＡ损伤程度加重。１７５０μｍｏｌ／Ｌ的氯化镉与１７５０μｍｏｌ／Ｌ的亚硒酸钠联合作用，拮抗作用最为明显。本研究结果提示，在一定剂量条件下，氯化镉对亚硒酸钠引起的大鼠肝细胞ＤＮＡ损伤存在拮抗作用，并与镉和硒的相对剂量有关     

硒和镉对大鼠肝细胞DNA损伤的联合作用

应用单细胞凝胶电泳研究硒和镉对大鼠肝细胞ＤＮＡ损伤的联合作用。结果表明，硒和镉在浓度超过８．７５μｍｏｌ／Ｌ时，均可引起细胞ＤＮＡ损伤，硒引起的损伤程度较镉轻。在８．７５、１７．５μｍｏｌ／Ｌ浓度条件下，当硒和镉联合作用时所致ＤＮＡ损伤程度明显低于相同剂量下硒、镉的单独作用，而在３５μｍｏｌ／Ｌ浓度条件下，硒镉联合作用所致ＤＮＡ损伤与硒、镉单独作用时比较，差异无显著性。本研究结果提示，在一定剂量时，硒和镉致大鼠肝细胞ＤＮＡ损伤存在拮抗作用。     

四种锌化合物的生物利用率的比较

目的：以边缘性锌缺乏的大鼠和幼鼠为模型，观察硫酸锌、葡萄糖酸锌、乳酸锌和甘氨酸锌四种锌化合物在０～７２０分钟消化吸收的动态变化；四种锌化合物在不同剂量（７．６、１５、３０、６０ｍｇ／ｋｇＨ２Ｏ）时组织中的储存。结果：以相同浓度的锌灌胃（６．０ｍｇ／ｋｇｂｗ），甘氨酸锌入血快于其它三个锌化合物，在１５分钟时达到最高峰（１００μｍｏｌ／Ｌ），乳酸锌和葡萄糖酸锌３０ｍｇ／ｋｇ时吸收峰值最大（６６．０μｍｏｌ／Ｌ，７９．５μｍｏｌ／Ｌ）；硫酸锌则在６０分钟到达高峰（７８．９μｍｏｌ／Ｌ）。用不同剂量锌（１５、３０、６０ｍｇ／ｋｇＨ２Ｏ）喂养幼鼠，甘氨酸锌在１５ｍｇ／ｋｇ、乳酸锌和葡萄糖酸锌３０ｍｇ／ｋｇ时血和组织中吸收峰值最大，且成直线关系；而３０、６０ｍｇ／ｋｇ时血和组织中浓度则基本保持恒定。而硫酸锌的吸收与剂量浓度关系成正比。以硫酸锌的吸收为１００％，用药物代谢动力学软件３Ｐ８７计算葡萄糖酸锌、乳酸锌和甘氨酸锌相对生物利用率分别为：１３２％、７３％和１２４％。     

铅接触对神经行为功能和单胺类神经递质代谢的影响

对接铅工人的血铅、锌卟啉水平，行为功能和尿液中单胺类神经递质及其代谢产物的含量进行了研究。结果显示：血铅、锌卟啉的平均含量分别为３．４０μｍｏｌ／Ｌ和４．７μｍｏｌ／Ｌ，比对照组明显增高；尿液中高香草酸（ＨＶＡ）和肾上腺素（Ｅ）的含量显著高于对照组；工人的行为功能受到一定影响，表现为简单反应时、利手提转捷度、数字译码、视觉保留时间、目标追踪和情感状态的改变。结果提示：运用神经行为核心测试组合以及检测尿中肾上腺素、多巴胺及其代谢产物高香草酸和３，４－双羟苯乙酸的变化，有助于及早发现铅对神经系统的损害，以及探索铅致行为功能改变的生物学基础。     

镉对巨噬细胞毒性及DNA损伤作用的研究

应用ＭＴＴ 比色、琼脂糖凝胶电泳方法研究氯化镉对小鼠腹腔巨噬细胞（ ＭΦ） 的毒性及ＤＮＡ 的损伤作用。结果表明,染毒６ 小时,氯化镉对ＭΦ活性产生抑制效应,染毒２４ 小时,抑制效应最大;镉浓度与ＭΦ活性抑制率之间存在剂量反应关系。染毒２４ 小时,镉浓度为１０ 、２０ 、４０ 、８０μｍｏｌ／Ｌ时,ＭΦＤＮＡ 电泳呈现“梯子”条带（ 凋亡特征） ;镉浓度为１６０ 、３２０μｍｏｌ／Ｌ 时,ＤＮＡ 电泳呈现“膜”状（ 坏死特征） 。本研究提示,氯化镉可抑制离体ＭΦ的活性,而且可引起ＤＮＡ 的降解,不同浓度的氧化镉引起ＭΦ损伤的方式不同。     

TNT接触对神经行为功能影响的研究

目的 为探讨ＴＮＴ接触对神经行为功能的影响。方法 采用ＷＨＯ神经行为核心测试组合（ＮＣＴＢ）并结合因子分析方法研究ＴＮＴ接触对神经行为的功能的影响,ＴＮＴ接触工人共５９名,平均尿ＤＮＡＴ浓度为２．７７ｍｇ／Ｌ对照工人共５３名,平均尿ＤＮＡＴ浓度为０．６３ｍｇ／Ｌ,结果 ＴＮＴ接触对工人的记忆力及心理运动有影响,尿ＤＮＡＴ水平与第三因子得分存在剂量－反应关系。结论 提示ＴＮＴ对心理运动稳定度的影响有     

三硝基甲苯中毒性肝病的血清透明质酸,结合甘胆酸含量分析

本文对慢性病毒性肝炎、ＴＮＴ中毒性肝病患者进行了血清ＨＡ、ＣＧ的实验研究，发现中毒性肝病组ＨＡ、ＣＧ含量分别为２６７．４２μｇ／Ｌ和１６．２３μｍｏｌ／Ｌ；慢性病毒性肝炎组为７００．６２μｇ／Ｌ和３６．９７μｍｏｌ／Ｌ；正常对照组仅为８９．４７μｇ／Ｌ和３．７０μｍｏｌ／Ｌ。ＨＡ、ＣＧ诊断ＴＮＴ中毒的敏感度分别为６２．５％和７５．０％，特异变为８８．３％和７５．５％；二者结合使用可使敏感度与特异度     

单细胞凝胶电泳法测定镍化物对人血细胞的DNA损伤

为研究镍化物对人血细胞ＤＮＡ的损伤情况，用单细胞凝胶电泳法测定了不同剂量的Ｎｉ３Ｓ２、ＮｉＣｌ２在２、４、２４小时诱导人全血细胞ＤＮＡ单链断裂的作用。结果表明：当Ｎｉ３Ｓ２染毒剂量为２．５、５．０、１０．０μｇ／ｃｍ２、３７℃作用２小时，即可引起血细胞“慧星”尾长、ＤＮＡ断裂分级较对照有显著改变（Ｐ＜０．０１）。血细胞分别与５００～２０００μｍｏｌ／Ｌ的ＮｉＣｌ２、４０～８０μｍｏｌ／Ｌ的Ｈ２Ｏ２一起孵育２４小时，除了ＤＮＡ断裂分级有显著改变外，慧星尾长与对照差异无显著性。提示：在实验条件下，ＮｉＣｌ２致ＤＮＡ单链断裂作用较Ｎｉ３Ｓ２弱。血液中的某些抗氧化物质可能减弱了镍化物的ＤＮＡ氧化损伤。     

Ames试验检测三硝基甲苯及其还原代谢产物的诱变性

应用Ａｍｅｓ试验检测系统观察了三硝基甲苯及其还原代谢产物４－羟氨基－２，６－二硝基甲苯（４－ＨＡ），４－氨基－２，６－二硝基甲苯（４－Ａ），２－氨基－４，６－二硝基甲苯（２－Ａ）和２，４－二氨基－６－硝基甲苯（２，４－ＤＡ）的诱变活性，实验结果显示，三硝基甲苯及其代谢产物具有明显的致突变作用，４－Ａ的直接诱变活性最强，而且移码型诱变性更为显著，在微粒体酶系统的参与下，ＴＮＴ的诱变活性增强，其代谢产     

Cytotoxicity and Mutagenicity of 2,4,6-Trinitrotoluene and Its Metabolites

Composting has been advocated and is being used as an economical method for remediating 2,4,6-trinitrotoluene (TNT)-contaminated soils. However, evidence suggests that TNT is transformed into products of unknown toxicity during the process. This study was undertaken to examine thein vitrocytotoxicity and mutagenicity of TNT and several of its degradation products/metabolites. TNT was equally cytotoxic to H4IIE cells and Chinese hamster ovary-K1 (CHO) cells (LC₅₀of 4 g/ml vs 24 μg/ml, with overlapping 95% prediction intervals), indicating that TNT does not need to be metabolized to exhibit cytotoxicity. Four metabolites studied, 4-hydroxylamino-2,6-dinitrotoluene; 2-amino-4,6-dinitrotoluene; 4,4′,6,6′-tetranitro-2,2′-azoxytoluene; and 2,2′,6,6′-tetranitro-4,4′-azoxytoluene, were equally cytotoxic to both H4IIE and CHO cells. The LC₅₀s were in the 3- to 18-μg/ml range and were not significantly different from TNT cytotoxicity in both cell lines. 4-Amino-2,6-dinitrotoluene (4-A) was moderately less cytotoxic than TNT to H4IIE cells, but was noncytotoxic to CHO cells. This result indicates that 4-A is metabolized to a cytotoxic compound. Both TNT and its metabolites exhibited only slight mutagenicity at high doses in one or both of the mutagenicity assays. While composting may reduce the levels of TNT in composted material, the hazard associated with TNT-contaminated soils is probably lower, but still uncertain.     

三硝基甲苯的代谢物—2-氨基-4,6-二硝基甲苯和2,4-二氨基-6-硝基甲苯的合成

本文报告了2,4,6-三硝基甲苯(TNT)的代谢物,2-氨基-4,6-二硝基甲苯2和2,4-二氨基-6-硝基甲苯3的合成。以邻甲基苯甲酸为原料,经硝化(HNO_3-H_2SO_4)和Schmidt反应(NaN_3-H_2SO_4)得到2,用NaHS还原TNT的方法合成化合物3。     

Exposure to nitroaromatic explosives and health effects during disposal of military waste

Aims: To investigate the exposure to dinitrotoluene (DNT) and trinitrotoluene (TNT) and the resulting effects in workers which occur during the disposal of military waste.

Methods: Eighty two employees from a mechanical plant in Germany were studied, of whom 51 were regularly exposed to ammunition containing TNT and DNT, 19 occasionally, and 12 not at all.

Results: Air analyses yielded maximum concentrations of 20 µg/m³ for 2,4-DNT and 3250 µg/m³ for 2,4,6-TNT, respectively. The maximum concentrations in the urine of workers regularly exposed amounted to 5.0 µg/l of 2,4,6-TNT, 1464.0 µg/l of 2-amino-4,6-dinitrotoluene, 6693.0 of µg/l 4-amino-2,6-dinitrotoluene, 2.1 µg/l of 2,4-DNT, 95.0 µg/l of 2,4-dinitrobenzoic acid, and 3.6 µg/l of 2,6-DNT. There was a highly significant linear correlation between the urinary concentrations of the two main metabolites of TNT, 2-amino-4,6-dinitrotoluene and 4-amino-2,6-dinitrotoluene. In 63 persons TNT or DNT or metabolite concentrations above the analytical detection limit were found in urine. These persons reported more frequently symptoms like bitter taste, burning eyes, and discoloration of the skin and hair than persons (n = 19) without detectable TNT and/or DNT exposure.

Conclusion: During the disposal of military waste containing relevant TNT and DNT, exposure can occur of occupational-medical relevance. Biological monitoring is suitable for the early detection of possible adverse effects at workplaces exposed to TNT. Protective measures should be improved, together with adequate occupational-medical surveillance of persons exposed to nitroaromatic explosives. Further studies are necessary to exclude possible long term effects.

     

Potential of activated carbon to decrease 2,4,6-trinitrotoluene toxicity and accelerate soil decontamination

Activated carbon can be used to decrease 2,4,6-trinitrotoluene (TNT) toxicity and promote bioremediation of highly contaminated soil. Adding activated carbon at 0.25, 0.75, and 1.0% (w/w) to Sharpsburg soil contaminated with 500, 1,000, and 2,000 mg TNT/kg decreased concentrations of TNT and its transformation products in soil solution to 5 mg/L or less, resulting in low toxicity to corn plants (Zea mays L.) and soil microorganisms. As much as 50% of the added TNT was rapidly bound to the soil-activated carbon matrix. Simultaneous accumulation of 2,4,6-trinitrobenzaldehyde (TNBAld) indicated that the activated carbon promoted oxidation of TNT. Some of the TNBAld was further oxidized to 1,3,5-trinitrobenzene, followed by reduction to 3,5-dinitroaniline. Reversibly bound TNT was gradually transformed to 2-amino-4,6-dinitrotoluene and 4-amino-2,6-dinitrotoluene, and both were bound to the soil-activated carbon matrix. The transformation and binding of TNT to soil were further promoted by incorporating shredded corn plants after growing for 52 d in the activated carbon-amended soil. After 120 d, these amendments reduced extractable TNT and transformation products by 91% in soil containing 2,000 mg TNT/kg, compared to 55% in unamended soil. These results demonstrate the potential use of activated carbon in combination with plants to promote in situ bioremediation of soils highly contaminated with explosives.     

Mutagenicity of nitroaromatic degradation compounds

The mutagenicity of 2,4-dinitrotoluene (24DNT), and 2,6-dinitrotoluene (26DNT), and their related transformation products such as hydroxylamine and amine derivatives, which are formed by Clostridium acetobutylicum, were tested in crude cell extracts using Salmonella typhimurium TA100. A previous publication already reported the mutagenic activities of 2,4,6-trinitrotoluene (TNT) and its related hydroxylamine derivatives in this test system. A time course of the mutagenicity during the anaerobic transformation of TNT, 24DNT, and 26DNT was also investigated under the same conditions to compare with the results from the pure compounds. The monohydroxylamino intermediates 2-hydroxylamino-4-nitrotoluene (2HA4NT), 4-hydroxylamino-2-nitrotoluene (4HA2NT) and 2-hydroxylamino-6-nitrotoluene (2HA6NT) formed during anaerobic transformation of dinitrotoluenes were proven to be mutagenic in the Ames test using Salmonella typhimurium TA100. This study reports that 4HA2NT is the most stable derivative, whereas 2HA4NT and 2HA6NT are less stable and these intermediates are mutagenic in the Ames test. Both 24DNT and 26DNT and their final metabolites 2,4-diaminotoluene (24DAT) and 2,6-aminotoluene (26DAT) appeared nonmutagenic. In a time-course study of TNT degradation, the temporal sample containing 85% of 2,4-dihydroxylamino-6-nitrotoluene (24HA6NT) is most mutagenic. These observations suggest that the bioremediation approach for treatment of 24DNT and 26DNT should be carried past the hydroxylamino intermediate.     

Genotoxicity and potential carcinogenicity of 2,4,6-TNT trinitrotoluene: structural and toxicological considerations

Environmental contamination with 2,4,6-TNT (trinitrotoluene) represents a worldwide problem. Concern for carcinogenicity can be derived from chemically related compounds, especially the dinitrotoluenes. In the metabolism of TNT, the reductive routes are preponderant. The main urinary metabolites of TNT are 4-amino-2,6-dinitrotoluene and 2-amino-4,6-dinitrotoluene. In humans exposed to TNT, the formation of hemoglobin adducts of the amino-dinitrotoluenes is in general concordance with the ratio of urinary excretion. The variations in quantities of excreted metabolites among the different occupational cohorts studied are likely explained by the different routes of exposure to TNT, including dermal uptake. Most studies show that urinary excretion of the amino-dinitrotoluenes (4-amino-dinitrotoluene plus 2-amino-dinitrotoluene) in a range of 1 to 10 mg L(-1) (5-50 microM) are not uncommon--for instance in persons employed with the disposal of military waste. Trinitotoluene is mutagenic in Salmonella typhimurium strains TA98 and TA100, with and without exogenous metabolic activation. Mutagenic activity has been found in urine from workers who were occupationally exposed to TNT. An unpublished 2-year study was reported in 1984 by the IIT Research Institute, Chicago, IL. Fischer 344 rats were fed diets containing 0.4, 2.0, 10, or 50 mg/kg TNT per day. In the urinary bladder, hyperplasia (12 of 47 animals p < .01) and carcinoma (11 of 47 animals, p < .05) were observed at significant levels in high-dose (50 mg kg(-1)) females and in one or two females, respectively, at 10 mg kg(-1). Taking all the available evidence together, the appropriate precautions should be taken.     

工人尿中三硝基甲苯及五种代谢物的质谱鉴定和高效液相色谱测定

为阐明TNT对肝脏损伤的机理,搞清尿中代谢物的种类,结构及含量有着十分重要的意义。将工人尿样加酸水解使代谢物游离,用苯提取液做色谱/质谱分析。鉴定出两个-氨基二硝基甲苯(4-A,2-A);两个二氨基-硝基甲苯(2,4-DA,2,6-DA)。又用化学电离源质谱/质谱法鉴定出易分解的羟氨基二硝基甲苯(4-HA)。用高效液相色谱法测定了某化工厂9名工人尿样。其含量顺序为4-A,4-HA,2-A,2,4-DA,2,6-DA。大多数尿样未检出TNT原形。4-A浓度最大值7.7mg/L,仍低于ILO规定的生物阈限值。     

Some altered concentrations of elements in semen of workers exposed to trinitrotoluene.

OBJECTIVES--A cross sectional study was performed to find the concentrations of elements contained in the semen of workers exposed to trinitrotoluene (TNT). SUBJECTS AND METHODS--Semen of exposed workers in two TNT plants located in He-Nan Province in 1992 were examined. RESULTS--The average TNT concentrations in the workplace, except the packing site, were found to have exceeded the maximal allowable concentration (MAC, 1 mg/m3); skin contaminations of male workers exposed to TNT were higher after a shift than in controls, and correlated with the total blood concentrations of TNT, 4-amino-2, 6-dinitrotoluene (4A), and 2-amino-4, 6-dinitrotoluene (2A). Cu, Zn, Na, Mg, and Se concentrations were significantly decreased, but K, Ca, Co, Mn and Li contents were not significantly changed in the semen of workers exposed to TNT. Compared with the control group, the percentage of liquifying time of semen, the sperm malformation incidence, and viability in the men exposed to TNT were all significantly changed. CONCLUSIONS--Men exposed to TNT have decreased concentrations of some elements is semen and altered semen physiology.