三硝基甲苯和4-氨基-2,6二硝基甲苯的急性毒性和致突变性研究

三硝基甲苯和４－氨基－２，６二硝基甲苯的急性毒性和致突变性研究李斌，吴琼，戴敏，杨建会，王玉玲（西安兵器工业卫生研究所，西安７１００６１）为了明确三硝基甲苯（ＴＮＴ）经体内代谢转化后，其主要代谢产物４－氨基。２，６二硝基甲苯（４－Ａ）的致突变性，本实...     

TNT及其代谢产物的Ames试验研究

ＴＮＴ及其代谢产物的Ａｍｅｓ试验研究李斌，吴琼，鲁明华（西安兵器工业卫生研究所，西安７１００６１）实验采用预培养平板掺入法，将ＴＮＴ、４ＨＡ（４－羟氨基－２，６．二硝基甲苯）、４－Ａ（４－氨基２，６二硝基甲苯）、２－Ａ（２－氨基－４，６二硝基甲苯）和...     

三硝基甲苯代谢物的合成研究（Ⅲ） 4－氨基－2，6－二硝基甲苯合成方法的技术改进

三硝基甲苯代谢物的合成研究（Ⅲ）４－氨基－２，６－二硝基甲苯合成方法的技术改进马兆扬（中国预防医学科学院劳动卫生与职业病研究所，北京１０００５０）４－氨基－２，６－二硝基甲苯（４－Ａ）是ＴＮＴ在人体内最主要的代谢产物。在我国ＴＮＴ是应用广泛的炸药。职...     

三硝基甲苯和4—氨基—2,6—二硝基甲苯对小鼠睾丸染色体畸变率的影响

实验观察了三硝基甲苯１０、５０和１００ｍｇ／ｋｇ剂量及４－氨基－２，６－二硝基甲苯５０、１００和２００ｍｇ／ｋｇ剂量对６１５小鼠睾丸初级精母细胞染色体畸变率的影响，实验结果显示，ＴＮＴ和４－Ａ诱发小鼠睾丸初级精母细胞染色体与畸变率明显增高，呈剂量效应关系。表明它们都是性细胞染色体的诱变物，而且４－Ａ的诱发活性与ＴＮＴ相近。     

TNT代谢物尿4A的气相色谱最佳分析条件研究

ＴＮＴ代谢物尿４Ａ的气相色谱最佳分析条件研究上海医科大学公共卫生学院（２０００３２）刘静波潘志擎龚梓初接触工人体内的ＴＮＴ经代谢后以原形和氨基类代谢物（主要为４－氨基－２，６－二硝基甲苯，即４Ａ或ＤＮＡＴ）经尿排出。定量检测工人尿中４Ａ可作为职业接触...     

人血中三硝基甲苯血红蛋白加合物的结构鉴定和定量分析

建立高效液相色谱定量测定三硝基甲苯（ＴＮＴ）血红蛋白（Ｈｂ）加合物的方法，并用于分析人的Ｈｂ加合物。结果表明，ＴＮＴ在体外可与人Ｈｂ反应形成加合物，并发现至少有两种类型：酸不稳定型和稳定型。前者占所有ＴＮＴ－Ｈｂ加合物的７１％。接触ＴＮＴ工人的Ｈｂ水解后，用液相色谱／质谱／质谱（ＬＣ／ＭＳ／ＭＳ）首次鉴定出了个４－氨基－２，６－二硝基甲苯（４Ａ），但未检测出在大鼠实验中所发现的２－氨基－４，６－二硝基甲苯（２Ａ）；接触组加合物浓度范围为０．０１４～０．７９２μｇ／ｇＨｂ。对照组未检出Ｈｂ加合物。     

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。     

TNF作业工人尿中TNF及其代谢物含量的研究

寻找职业接触ＴＮＴ敏感,特异的生物监测指标及制订生物接触限值,方法对车间空气中ＴＮＦ浓度与接触者尿中ＴＮＴ、代谢物４－氨基－２,６－二硝基甲基和２－氨基－４,６－二硝基甲苯（２Ａ）含量的相关性进行了分析,。结论班后尿中４Ａ含量是职业接触ＴＮＴ生物监测的敏感指标。     

咖啡在SOS／Umu试验中对已知致癌物的抗诱变作用

应用ＳＯＳ／Ｕｍｕ试验研究ＴＭＡＸＷＥＬＬ速溶咖啡（美国产品）、亚洲咖啡（中国广东产品）和ＭＡＸＩＮ咖啡（日本产品）对已知致癌物４－硝基喹啉、ＡＦ－２及２－氨基蒽诱变性的抑制作用。结果表明３种咖啡提取物对４－硝基喹啉、ＡＦ—２及２－氨基蒽都有明显的抗诱变作用，ＭＡＸＩＮ咖啡抑制率为８０％以上，ＭＡＸＷＥＬＬ速溶咖啡抑制率为７０％以上，亚洲咖啡在５０％左右。其抑制率与咖啡的可溶性部分的多少成正比（ＭＡＸＩＮ咖啡可溶性部分为９７．３％、ＭＡＸＷＥＬＬ速溶咖啡为９２．２％、亚洲咖啡为３２．７％），表明３种咖啡在ＳＯＳ／Ｕｍｕ试验中抗诱变效果的差异可能是由于咖啡可溶性部分的多少所致。     

三硝基甲苯和4—氨基—2,6—二硝基甲苯对小鼠骨髓细胞染色体畸变…

观察了三硝基甲苯１０，５０，１００ｍｇ／ｋｇ和４－氨基－２，６－二硝基甲苯５０、１００、２００、４００ｍｇ／ｋｇ剂量组对Ｃ５７ＢＬ小鼠骨髓细胞染色体畸变率和嗜多染红细胞微核率的影响。     

三硝基甲苯及其代谢产物与脱氧核糖核酸的结合作用

运用吸收光谱移动法观察了三硝基甲苯（ＴＮＴ）及其代谢产物与脱氧核糖核酸（ＤＮＡ）的结合作用。结果表明：在ＴＮＴ及其代谢产物浓度一定的条件下，改变ＤＮＡ浓度，结果随着ＤＮＡ浓度的降低，ＴＮＴ及其代谢产物的最大吸收峰λｍａｘ出现短移，且吸收强度也随之增大。当ＤＮＡ浓度固定时，改变ＴＮＴ及其代谢产物浓度时，发现ＴＮＴ（１００μｍｏｌ／Ｌ）、４－Ａ（５０，２５μｍｏｌ／Ｌ）使ＤＮＡλｍａｘ２２８ｎｍ峰消失。提示：ＴＮＴ及其代谢产物与ＤＮＡ有不同程度的结合作用。     

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。     

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.     

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.     

Toxicological characterization of 2,4,6-trinitrotoluene, its transformation products, and two nitramine explosives

The soil and groundwater of former ordnance plants and their dumping sites have often been highly contaminated with the explosive 2,4,6-trinitrotoluene (2,4,6-TNT) leading to a potential hazard for humans and the environment. Further hazards can arise from metabolites of transformation, by-products of the manufacturing process, or incomplete combustion. This work examines the toxicity of polar nitro compounds relative to their parent compound 2,4,6-TNT using four different ecotoxicological bioassays (algae growth inhibition test, daphnids immobilization test, luminescence inhibition test, and cell growth inhibition test), three genotoxicological assays (umu test, NM2009 test, and SOS Chromotest), and the Ames fluctuation test for detection of mutagenicity. For this study, substances typical for certain steps of degradation/transformation of 2,4,6-TNT were chosen for investigation. This work determines that the parent compounds 2,4,6-TNT and 1,3,5-trinitrobenzene are the most toxic substances followed by 3,5-dinitrophenol, 3,5-dinitroaniline and 4-amino-2-nitrotoluene. Less toxic are the direct degradation products of 2,4,6-TNT like 2,4-dinitrotoluene, 2,6-dinitrotoluene, 2-amino-4,6-dinitrotoluene, and 4-amino-2,6-dinitrotoluene. A weak toxic potential was observed for 2,4,6-trinitrobenzoic acid, 2,4-diamino-6-nitrotoluene, 2,4-dinitrotoluene-5-sulfonic acid, and 2,6-diamino-4-nitrotoluene. Octahydro-l,3,5,7-tetranitro-l,3,5,7-tetrazocine and hexahydro-1,3,5-trinitro-l,3,5-triazine show no hint of acute toxicity. Based on the results of this study, we recommend expanding future monitoring programs of not only the parent substances but also potential metabolites based on conditions at the contaminated sites and to use bioassays as tools for estimating the toxicological potential directly by testing environmental samples. Site-specific protocols should be developed. If hazardous substances are found in relevant concentrations, action should be taken to prevent potential risks for humans and the environment. Analyses can then be used to prioritise reliable estimates of risk.     

Fate and metabolism of [15N]2,4,6-trinitrotoluene in soil

The fates of the labels from [14C] and [15N] trinitrotoluene were analyzed in bioreactors under aerobic conditions in soil treated by a fungal bioremediation process with Stropharia rugosoannulata and in control soil. Up to 17.5% of the 15N label had a different fate than the 14C label. Three N-mineralization processes were identified in detailed experiments with [15N]TNT. About 2% of the 15N label was found as NO3- and NH4+, showing simultaneous processes of direct TNT denitration (I) and reduction with cleavage of the amino groups (II). The enrichment of NO2-/NO3- (up to 7.5 atom% 15N abundance) indicates the formation of Meisenheimer complexes with a denitration of [15N]TNT. A 1.4% of the label was found distributed between N2O and N2. However, the 15N enrichment of the N2O (up to 38 atom%) demonstrated that both N atoms were generated from the labeled TNT and clearly indicates a novel formation process (III). We propose, as an explanation, the generation of N2O by cleavage from condensed azoxy metabolites. In addition, 1.7% of the 15N label was detected as biogenic amino acids in the wheat straw containing the fungus. Overall, 60 to 85% of the applied [15N]TNT was degraded and 52 to 64% was found as nonextractable residues in the soil matrix. Three percent was detected as 2-amino-4,6-dinitrotoluene and 4-amino-2,6-dinitrotoluene.     

三硝基甲苯和4-氨基-2,6-二硝基甲苯对小鼠骨髓细胞染色体畸变率和微核率的影响

观察了三硝基甲苯（TNT）10、50、100mg／kg和4-氨基-2，6-二硝基甲苯（4－A）50、100、200、40Cmg／kg剂量组对C57BL小鼠骨髓细胞染色体畸变率和嗜多染红细胞（PCE）微核率的影响。实验结果显示，TNT和4－A各剂量组小鼠骨髓细胞染色体畸变率明显增高，P<0．01而且呈剂量效应关系。相同剂量4－A诱发染色体畸变率明显低于TNT，P<0．01。小鼠骨髓PCE微核率10、50mg／kgTNT剂量组明显增高，而4－A剂量至400mg／kg其微核率的增高无统计学意义。表明三硝基甲苯进入体内并代谢转化为4－A之后，仍具有较强的体细胞诱变活性，但呈减弱趋势。     

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.