牛乳中硝基苯检测方法及代谢物动力学研究
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摘要
硝基苯是一种无色或微黄色具苦杏仁味的油状液体，是一种有毒有害物质，损害神经系统，并能引起高铁血症甚至发生溶血，能够导致肝脏等器官的实质病变，而它的代谢产物毒性更强。2005年11月13日，中石油吉化双苯厂爆炸导致硝基苯泄漏，对松花江沿岸环境造成严重污染。目前牛乳中硝基苯的检测方法国内外还未见报道，本研究以气相色谱(GC)法作为硝基苯的定量手段，对松花江沿岸黑龙江省段主要奶牛场的鲜牛奶中是否存在硝基苯的残留进行了检测。结果表明：松花江沿岸从肇源县到佳木斯桦川县6个市县共8个牛场随机抽取的1000个奶样，均未检出硝基苯。本研究建立的气相色谱法能够迅速准确检测乳中硝基苯，为乳业的安全生产提供了保障。
本研究以高效液相色谱(High Performance Liquid Chromatography，HPLC)作为硝基苯代谢产物氨基酚、硝基苯胺和硝基酚的定量手段，采用MCPKP自动化药动学分析程序分析其浓度-时间数据，以不同剂量硝基苯一次和多次连续给奶牛经口染毒，分别研究了硝基苯的三种主要代谢产物氨基酚、硝基苯胺和硝基酚在奶牛乳中的动态变化规律和残留消除规律。结果表明：一次染毒硝基苯后乳中三种代谢产物浓度随时间而变化的规律符合一级吸收一室模型，其中，剂量为5mg／kg·b·w时，氨基酚的主要动力学参数为：C_(max)=0.1866μg·mL~(-1)，T_(1／2Ka)=0.7689h，T_(1／2K)=21.1291h，AUC=6.4492mg·L~(-1)·h~(-1)，Tp=3.8153h，Tcp=93.0460h；硝基苯胺的主要动力学参数为：Cmax=1.2112μg·mL~(-1)，T_(1／2Ka)=1.5375h，T_(1／2K)=9.0995h，AUC=22.8300mg·L~(-1)·h~(-1)，Tp=4.7469h，Tcp=67.7320h；硝基酚的主要动力学参数为：C_(max)=0.6741μg·mL~(-1)，T_(1／2Ka)=0.7351h，T_(1／2K)=9.7586h，AUC=11.8560mg·L~(-1)·h~(-1)，Tp=3.6196h，Tcp=62.4250h；剂量为10mg／kg·b·w时，氨基酚的主要动力学参数为：C_(max)=0.2174μg·mL~(-1)，T_(1／2Ka)=0.6919h，T_(1/2K)=20.4116h，AUC=7.2112mg·L~(-1)·h~(-1)，Tp=3.4974h，Tcp=94.1930h；硝基苯胺的主要动力学参数为：C_(max)=1.3398μg·mL~(-1)，T_(1／2Ka)=1.1862h，T_(1／2K)=9.1791h，AUC=24.0660mg·L~(-1)·h~(-1)，Tp=4.2309h，Tcp=68.9070h；硝基酚的主要动力学参数为：C_(max)=0.9518μg·mL~(-1)，T_(1／2Ka)=1.2016h，T_(1/2K)=8.6544h AUC=16.4010mg·L~(-1)·h~(-1)，Tp=4.3929h，Tcp=60.9140h。
以不同剂量连续染毒硝基苯，停止染毒后乳中三种代谢产物从乳中的消除服从一级动力学过程，其中，剂量为25mg／L时，氨基酚的主要动力学参数为：C_(max)=0.4486μg·mL~(-1)，T_(1/2)=1.7752d，AUC=1.1492mg·L~(-1)·d~(-1)，Tcp=9.7435d；硝基苯胺的主要动力学参数为：C_(max)=5.353μg·mL~(-1)，T_(1／2)=0.9824d，AUC=7.5888mg·L~(-1)·d~(-1)，Tcp=8.9069d；硝基酚的主要动力学参数为C_(max)=2.4467μg·mL~(-1)，T_(1／2)=1.0671d，AUC=3.7676mg·L~(-1)·d~(-1)，Tcp=8.4690d；剂量为50mg／L时，氨基酚的主要动力学参数为：C_(max)=0.5726μg·mL~(-1)，T_(1／2)=1.7049d，AUC=1.4086mg·L~(-1)·d~(-1)，Tcp=9.9571d；硝基苯胺的主要动力学参数为：C_(max)=5.4383μg·mL~(-1)，T_(1／2)=0.9888d，AUC=7.7596mg·L~(-1)·d~(-1)，Tcp=8.9872d；硝基酚的主要动力学参数为：C_(max)=2.7421μg·mL~(-1)，T_(1／2)=1.0639d，AUC=4.2098mg·L~(-1)·d~(-1)，Tcp=8.6185d；剂量为100mg／L时，氨基酚的主要动力学参数为：C_(max)=0.6363μg·mL~(-1)，T_(1／2)=1.6634d，AUC=1.5274mg·L~(-1)·d~(-1)，Tcp=9.9688d；硝基苯胺的主要动力学参数为：C_(max)=6.0906μg·mL~(-1)，T_(1／2)=0.9724d，AUC=8.5462mg·L~(-1)·d~(-1)，Tcp=8.9971d；硝基酚的主要动力学参数为：C_(max)=2.9304μg·mL~(-1)，T_(1／2)=1.0611d，AUC=4.4867mg·L~(-1)·d~(-1)，Tcp=8.6976d。
药动学研究结果表明：乳牛在染毒硝基苯以后，不论是一次染毒还是连续染毒，乳中三种代谢产物的消除服从一级动力学过程，但三者乳中浓度和消除速率不同，氨基酚的浓度最低，消除速率也最慢，三种代谢物的消除速率与染毒剂量相关性较小。
本试验探讨了乳中硝基苯的气相色谱检测方法，评价了该方法的快速准确性，并且探讨了高效液相色谱法同时检测硝基苯在动物体内的三种主要代谢产物氨基酚、硝基苯胺和硝基酚的色谱条件，克服了以往对每种物质单独检测费时费力的缺点，不但为以后的科研工作提供了科学依据，并且对乳业的安全生产具有理论和现实的意义。本试验揭示了硝基苯三种主要代谢产物在牛乳中的代谢动力学规律，阐述了三种代谢产物的半衰期及在乳中代谢物存在的时间，通过药动学结果可以看出，奶牛如果误饮了被硝基苯污染的水后，在十天后牛奶可以安全饮用，这一结果对科研和生产实践具有重要意义。
Nitrobenzene is a colourless or pale yellow oily liquid with an odour of bitter almonds, It is poisonous and noxious substance which can damage nervous system and cause hyperferremia andeven hemolysis. It also can cause the parenchymatous pathological change of hepar. Its metabolites have stronger toxicity. Nov. 13th 2005 the explosion happened in the Chemical DibenzeneFactory in Jilin of the Chinese Petroleum Company caused the leakage of nitrobenzene andheavily polluted the Songhua River. Now, there is no information about the detection method ofnitrobenzene in the cow's milk at home or abroad. The residues of the nitrobenzene in fresh milkcollected from the main dairy ranches along the Heilongjiang section of the Shonghua River havebeen detected in this study with method of the GC. The results indicate that the residues ofnitrobenzene has not been detected in the about 1,000 milk samples collected randomly from 8dairy ranches of the 6 counties from the Zhaoyuan to the Huachuan in Jiamusi city. The methodhas. been established to detect, quickly and accurately, the nitrobenzene, which can ensure thesafety of the milk products.
The study measured the quality of the nitrobenzene's with the HPLC and analyzed the concentration-time data with the automated pharmacokinetic computer program MCPKP.(chang thissentence into passive form)In this paper the pahrmacokinetis and the residues eliminations regularities of the Nitrobenzene s three metabolites (Aminophenol, Nitroamiline and Nitrophenol) inthe milk have been studied respectively with the different doses of the Nitrobenzene to exposurethe cow by mouth, one and successive many times. After the one exposure to the nitrobenzene theresults show that the concentration-time courses of the three metabolites in the milk fit to a onecompartment open model with the first order absorption. After given the dose of 5mg/kg ofnitrobenzene by oral, the main pharmacokinetic parameters of the aminophenol in dariy are as following: C_(max)=0.1866μg·mL~(-1), T_(1/2Ka)=0.7689h, T_(1/2K)=21.1291h, AUC=6.4492mg·L~(-1)·h~(-1), Tp=3.8153h, Tcp=93.0460h; the Nitroamiline: C_(max)=1.2112μg·mL~(-1), T_(1/2Ka)=1.5375h, T_(1/2K)=9.0995h,AUC=22.8300mg·L~(-1)·h~(-1), Tp=4.7469h, Tcp=67.7320h; the Nitrophenol: C_(max)=0.6741μg·mL~(-1),T_(1/2Ka)=0.7351h, T_(1/2K)=9.7586h, AUC=11.8560mg·L~(-1)·h~(-1), Tp=3.6196h, Tcp=62.4250h;After given the dose of 10 mg/kg of nitrobenzene by oral, the main pharmacokinetic parameters ofthe aminophenol are as following: C_(max)=0.2174μg·mL~(-1), T_(1/2Ka)=0.6919h, T_(1/2K)=20.4116h,AUC=7.2112mg·L~(-1)·h~(-1), Tp=3.4974h, Tcp=94.1930h; Nitroamiline: C_(max)=1.3398μg·mL~(-1), T_(1/2Ka)=1.1862h, T_(1/2K)=9.1791h, AUC=24.0660mg·L~(-1)·h~(-1), Tp=4.2309h, Tcp=68.9070h; Nitrophenol:C_(max)=0.9518μg·mL~(-1), T_(1/2Ka)=1.2016h, T_(1/2K)=8.6544h, AUC=16.4010mg·L~(-1)·h~(-1), Tp=4.3929h,Tcp=60.9140h.
After the successive exposure to the nitrobenzene with the different doses the results show thatthe elimination of the three metabolites in milks fit to the first-order absorption process Aftergiven the dose of 25mg/L of nitrobenzene each day by oral for 9 days, the main pharmacokineticparameters of the aminophenol are as following: C_(max)=0.4486μg·mL~(-1), T_(1/2)=1.7752d,AUC=1.1492mg·L~(-1)·d~(-1), Tcp=9.7435d; Nitroamiline: C_(max)=5.3531μg·mL~(-1), T_(1/2)=0.9824d,AUC=7.5888mg·L~(-1)·d~(-1), Tcp=8.9069d; Nitrophenol: C_(max)=2.4467μg·mL~(-1), T_(1/2)=1.0671d,AUC=3.7676mg·L~(-1)·d~(-1), Tcp=8.4690d; After given the dose of 50 mg/L of nitrobenzene each dayby oral for 9 days, the main pharmacokinetic parameters of the aminophenol are as following::C_(max)=0.5726μg·mL~(-1), T_(1/2)=1.7049d, AUC=1.4086mg·L~(-1)·d~(-1), Tcp=9.9571d; Nitroamiline: C_(max)=5.4383μg·mL~(-1), T_(1/2)=0.9888d, AUC=7.7596mg·L~(-1)·d~(-1), Tcp=8.9872d; Nitrophenlo: C_(max)=2.7421μg·mL~(-1), T_(1/2)=1.0639d, AUC=4.2098mg·L~(-1)·d~(-1), Tcp=8.6185d; When the dose is100mg/L, the main pharmacokinetic parameters of the aminophenol are as following: C_(max)=0.6363μg·mL~(-1), T_(1/2)=1.6634d, AUC=1.5274mg·L~(-1)·d~(-1), Tcp=9.9688d; Nitroamiline: C_(max)=6.0906μg·mL~(-1), T_(1/2)=0.9724d, AUC=8.5462mg·L~(-1)·d~(-1), Tcp=8.9971d; Nitrophenoh C_(max)=2.9304μg·mL~(-1), T_(1/2)=1.0611d, AUC=4.4867mg·L~(-1)·d~(-1), Tcp=8.6976d.
The results of pharmacokinetics show that the elimination of three metabolites in the milkconsistents with first order processes after the cows exposure to the nitrobenzene,either oral narcotics one timeor consecutively. But three metabolites have different concentration and elimination rate in milk,Aminophenol' concentration is the lowest and elimination rate is the slowest of all, eliminationrate of three metabolites is not correlate with oral narcotics dose.
In this paper the GC method to detect the nitrobenzene in the milk has been established andevaluated about its accuracy and the HLPC method to detect simultaneously its three metabolites(Aminophenol, Nitroamiline and Nitrophenol) in the animal bodies has been studied which hasovercome the time-consuming and laboursome disadvantage of detecting the each substancesrespectively. All these achievements provide the science bases for the future research works andhave the theoretical and actual significance for the safety of the milk productions.
The study has revealed metabolic and kinetics regularity of the nitrobenzene's three metabolites(Aminophenol, Nitroamiline and Nitrophenol) in the milk and explained their half life and existingtime in the milk. The significant, theoretical and actual, conclusion can be gained from theseresults that if cows drink accidentally the water polluted by the nitrobenzene the milk can beconsumed safely after ten days.
本研究以高效液相色谱(High Performance Liquid Chromatography，HPLC)作为硝基苯代谢产物氨基酚、硝基苯胺和硝基酚的定量手段，采用MCPKP自动化药动学分析程序分析其浓度-时间数据，以不同剂量硝基苯一次和多次连续给奶牛经口染毒，分别研究了硝基苯的三种主要代谢产物氨基酚、硝基苯胺和硝基酚在奶牛乳中的动态变化规律和残留消除规律。结果表明：一次染毒硝基苯后乳中三种代谢产物浓度随时间而变化的规律符合一级吸收一室模型，其中，剂量为5mg／kg·b·w时，氨基酚的主要动力学参数为：C_(max)=0.1866μg·mL~(-1)，T_(1／2Ka)=0.7689h，T_(1／2K)=21.1291h，AUC=6.4492mg·L~(-1)·h~(-1)，Tp=3.8153h，Tcp=93.0460h；硝基苯胺的主要动力学参数为：Cmax=1.2112μg·mL~(-1)，T_(1／2Ka)=1.5375h，T_(1／2K)=9.0995h，AUC=22.8300mg·L~(-1)·h~(-1)，Tp=4.7469h，Tcp=67.7320h；硝基酚的主要动力学参数为：C_(max)=0.6741μg·mL~(-1)，T_(1／2Ka)=0.7351h，T_(1／2K)=9.7586h，AUC=11.8560mg·L~(-1)·h~(-1)，Tp=3.6196h，Tcp=62.4250h；剂量为10mg／kg·b·w时，氨基酚的主要动力学参数为：C_(max)=0.2174μg·mL~(-1)，T_(1／2Ka)=0.6919h，T_(1/2K)=20.4116h，AUC=7.2112mg·L~(-1)·h~(-1)，Tp=3.4974h，Tcp=94.1930h；硝基苯胺的主要动力学参数为：C_(max)=1.3398μg·mL~(-1)，T_(1／2Ka)=1.1862h，T_(1／2K)=9.1791h，AUC=24.0660mg·L~(-1)·h~(-1)，Tp=4.2309h，Tcp=68.9070h；硝基酚的主要动力学参数为：C_(max)=0.9518μg·mL~(-1)，T_(1／2Ka)=1.2016h，T_(1/2K)=8.6544h AUC=16.4010mg·L~(-1)·h~(-1)，Tp=4.3929h，Tcp=60.9140h。
以不同剂量连续染毒硝基苯，停止染毒后乳中三种代谢产物从乳中的消除服从一级动力学过程，其中，剂量为25mg／L时，氨基酚的主要动力学参数为：C_(max)=0.4486μg·mL~(-1)，T_(1/2)=1.7752d，AUC=1.1492mg·L~(-1)·d~(-1)，Tcp=9.7435d；硝基苯胺的主要动力学参数为：C_(max)=5.353μg·mL~(-1)，T_(1／2)=0.9824d，AUC=7.5888mg·L~(-1)·d~(-1)，Tcp=8.9069d；硝基酚的主要动力学参数为C_(max)=2.4467μg·mL~(-1)，T_(1／2)=1.0671d，AUC=3.7676mg·L~(-1)·d~(-1)，Tcp=8.4690d；剂量为50mg／L时，氨基酚的主要动力学参数为：C_(max)=0.5726μg·mL~(-1)，T_(1／2)=1.7049d，AUC=1.4086mg·L~(-1)·d~(-1)，Tcp=9.9571d；硝基苯胺的主要动力学参数为：C_(max)=5.4383μg·mL~(-1)，T_(1／2)=0.9888d，AUC=7.7596mg·L~(-1)·d~(-1)，Tcp=8.9872d；硝基酚的主要动力学参数为：C_(max)=2.7421μg·mL~(-1)，T_(1／2)=1.0639d，AUC=4.2098mg·L~(-1)·d~(-1)，Tcp=8.6185d；剂量为100mg／L时，氨基酚的主要动力学参数为：C_(max)=0.6363μg·mL~(-1)，T_(1／2)=1.6634d，AUC=1.5274mg·L~(-1)·d~(-1)，Tcp=9.9688d；硝基苯胺的主要动力学参数为：C_(max)=6.0906μg·mL~(-1)，T_(1／2)=0.9724d，AUC=8.5462mg·L~(-1)·d~(-1)，Tcp=8.9971d；硝基酚的主要动力学参数为：C_(max)=2.9304μg·mL~(-1)，T_(1／2)=1.0611d，AUC=4.4867mg·L~(-1)·d~(-1)，Tcp=8.6976d。
药动学研究结果表明：乳牛在染毒硝基苯以后，不论是一次染毒还是连续染毒，乳中三种代谢产物的消除服从一级动力学过程，但三者乳中浓度和消除速率不同，氨基酚的浓度最低，消除速率也最慢，三种代谢物的消除速率与染毒剂量相关性较小。
本试验探讨了乳中硝基苯的气相色谱检测方法，评价了该方法的快速准确性，并且探讨了高效液相色谱法同时检测硝基苯在动物体内的三种主要代谢产物氨基酚、硝基苯胺和硝基酚的色谱条件，克服了以往对每种物质单独检测费时费力的缺点，不但为以后的科研工作提供了科学依据，并且对乳业的安全生产具有理论和现实的意义。本试验揭示了硝基苯三种主要代谢产物在牛乳中的代谢动力学规律，阐述了三种代谢产物的半衰期及在乳中代谢物存在的时间，通过药动学结果可以看出，奶牛如果误饮了被硝基苯污染的水后，在十天后牛奶可以安全饮用，这一结果对科研和生产实践具有重要意义。
Nitrobenzene is a colourless or pale yellow oily liquid with an odour of bitter almonds, It is poisonous and noxious substance which can damage nervous system and cause hyperferremia andeven hemolysis. It also can cause the parenchymatous pathological change of hepar. Its metabolites have stronger toxicity. Nov. 13th 2005 the explosion happened in the Chemical DibenzeneFactory in Jilin of the Chinese Petroleum Company caused the leakage of nitrobenzene andheavily polluted the Songhua River. Now, there is no information about the detection method ofnitrobenzene in the cow's milk at home or abroad. The residues of the nitrobenzene in fresh milkcollected from the main dairy ranches along the Heilongjiang section of the Shonghua River havebeen detected in this study with method of the GC. The results indicate that the residues ofnitrobenzene has not been detected in the about 1,000 milk samples collected randomly from 8dairy ranches of the 6 counties from the Zhaoyuan to the Huachuan in Jiamusi city. The methodhas. been established to detect, quickly and accurately, the nitrobenzene, which can ensure thesafety of the milk products.
The study measured the quality of the nitrobenzene's with the HPLC and analyzed the concentration-time data with the automated pharmacokinetic computer program MCPKP.(chang thissentence into passive form)In this paper the pahrmacokinetis and the residues eliminations regularities of the Nitrobenzene s three metabolites (Aminophenol, Nitroamiline and Nitrophenol) inthe milk have been studied respectively with the different doses of the Nitrobenzene to exposurethe cow by mouth, one and successive many times. After the one exposure to the nitrobenzene theresults show that the concentration-time courses of the three metabolites in the milk fit to a onecompartment open model with the first order absorption. After given the dose of 5mg/kg ofnitrobenzene by oral, the main pharmacokinetic parameters of the aminophenol in dariy are as following: C_(max)=0.1866μg·mL~(-1), T_(1/2Ka)=0.7689h, T_(1/2K)=21.1291h, AUC=6.4492mg·L~(-1)·h~(-1), Tp=3.8153h, Tcp=93.0460h; the Nitroamiline: C_(max)=1.2112μg·mL~(-1), T_(1/2Ka)=1.5375h, T_(1/2K)=9.0995h,AUC=22.8300mg·L~(-1)·h~(-1), Tp=4.7469h, Tcp=67.7320h; the Nitrophenol: C_(max)=0.6741μg·mL~(-1),T_(1/2Ka)=0.7351h, T_(1/2K)=9.7586h, AUC=11.8560mg·L~(-1)·h~(-1), Tp=3.6196h, Tcp=62.4250h;After given the dose of 10 mg/kg of nitrobenzene by oral, the main pharmacokinetic parameters ofthe aminophenol are as following: C_(max)=0.2174μg·mL~(-1), T_(1/2Ka)=0.6919h, T_(1/2K)=20.4116h,AUC=7.2112mg·L~(-1)·h~(-1), Tp=3.4974h, Tcp=94.1930h; Nitroamiline: C_(max)=1.3398μg·mL~(-1), T_(1/2Ka)=1.1862h, T_(1/2K)=9.1791h, AUC=24.0660mg·L~(-1)·h~(-1), Tp=4.2309h, Tcp=68.9070h; Nitrophenol:C_(max)=0.9518μg·mL~(-1), T_(1/2Ka)=1.2016h, T_(1/2K)=8.6544h, AUC=16.4010mg·L~(-1)·h~(-1), Tp=4.3929h,Tcp=60.9140h.
After the successive exposure to the nitrobenzene with the different doses the results show thatthe elimination of the three metabolites in milks fit to the first-order absorption process Aftergiven the dose of 25mg/L of nitrobenzene each day by oral for 9 days, the main pharmacokineticparameters of the aminophenol are as following: C_(max)=0.4486μg·mL~(-1), T_(1/2)=1.7752d,AUC=1.1492mg·L~(-1)·d~(-1), Tcp=9.7435d; Nitroamiline: C_(max)=5.3531μg·mL~(-1), T_(1/2)=0.9824d,AUC=7.5888mg·L~(-1)·d~(-1), Tcp=8.9069d; Nitrophenol: C_(max)=2.4467μg·mL~(-1), T_(1/2)=1.0671d,AUC=3.7676mg·L~(-1)·d~(-1), Tcp=8.4690d; After given the dose of 50 mg/L of nitrobenzene each dayby oral for 9 days, the main pharmacokinetic parameters of the aminophenol are as following::C_(max)=0.5726μg·mL~(-1), T_(1/2)=1.7049d, AUC=1.4086mg·L~(-1)·d~(-1), Tcp=9.9571d; Nitroamiline: C_(max)=5.4383μg·mL~(-1), T_(1/2)=0.9888d, AUC=7.7596mg·L~(-1)·d~(-1), Tcp=8.9872d; Nitrophenlo: C_(max)=2.7421μg·mL~(-1), T_(1/2)=1.0639d, AUC=4.2098mg·L~(-1)·d~(-1), Tcp=8.6185d; When the dose is100mg/L, the main pharmacokinetic parameters of the aminophenol are as following: C_(max)=0.6363μg·mL~(-1), T_(1/2)=1.6634d, AUC=1.5274mg·L~(-1)·d~(-1), Tcp=9.9688d; Nitroamiline: C_(max)=6.0906μg·mL~(-1), T_(1/2)=0.9724d, AUC=8.5462mg·L~(-1)·d~(-1), Tcp=8.9971d; Nitrophenoh C_(max)=2.9304μg·mL~(-1), T_(1/2)=1.0611d, AUC=4.4867mg·L~(-1)·d~(-1), Tcp=8.6976d.
The results of pharmacokinetics show that the elimination of three metabolites in the milkconsistents with first order processes after the cows exposure to the nitrobenzene,either oral narcotics one timeor consecutively. But three metabolites have different concentration and elimination rate in milk,Aminophenol' concentration is the lowest and elimination rate is the slowest of all, eliminationrate of three metabolites is not correlate with oral narcotics dose.
In this paper the GC method to detect the nitrobenzene in the milk has been established andevaluated about its accuracy and the HLPC method to detect simultaneously its three metabolites(Aminophenol, Nitroamiline and Nitrophenol) in the animal bodies has been studied which hasovercome the time-consuming and laboursome disadvantage of detecting the each substancesrespectively. All these achievements provide the science bases for the future research works andhave the theoretical and actual significance for the safety of the milk productions.
The study has revealed metabolic and kinetics regularity of the nitrobenzene's three metabolites(Aminophenol, Nitroamiline and Nitrophenol) in the milk and explained their half life and existingtime in the milk. The significant, theoretical and actual, conclusion can be gained from theseresults that if cows drink accidentally the water polluted by the nitrobenzene the milk can beconsumed safely after ten days.
引文
董贵凤，黄东．2001．还原—偶氮光度法测定废水中硝基苯类的改进[J]．环境检测管理与技术．13(4)：37
樊德方．1982．农药残留量分析与检测．上海科学技术出版社．
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李发美．2000．医药高效液相色谱技术[M]．人民卫生出版社．136～145
李浩春．1998．气相色谱法．科学出版社．4
李杰．．2003．气相色谱法测定水及空气中的苯胺和硝基苯[J]．广州化学．28(2)：23～26
李瑞琴．1998．高压液相色谱法测定废水中的苯胺和硝基苯胺[J]．环境科学研究．11(6)：34～38
李善茂，顾惠芬，郑明生，詹彦．1997．反相高效液相色谱法测定对氨基酚及其相关化合物．色谱．15(4)：324～327
牛玉梅，赵守国，王继刚，李洪霞．2006．气相色谱法测定达连河水中的硝基苯．测量与校准．26(5)：39～41
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沈德中．2006．污染环境的生物修复[M]．北京：化学工业出版社．6～7
宋雄英．2003．高浓度硝基苯类废水处理工艺[J]．污染防治技术．16(4)：95～96
王碧云．2006．反相高效液相色谱法测定饮用水中的酚类化合物[J]．福建分析测试．15(3)：20～22
王阳峰，吕玉新．2004．用水生态毒理学方法评价13种硝基苯类化合物的急性毒性[J]．新乡医学院学报．21(6)：456～458
徐镜波．2000．环境毒理学[M]．长春：东北师范大学出版社．98～155．
徐晓白，戴树桂，黄玉瑶．1998．典型化学污染物在环境中的变化及生态效应[M]．北京：科学出版社．239
张晓春，吴登胜，杨强生等．2001．低浓度苯胺、硝基苯对生产工人健康的影响[J]．中国工业医学杂志，14(1)：53～54
张秀忠．固相萃取．高效液相色谱法测定水中的酚类化合物[J]．给水排水．2004(2)：30～32
张玉玲，狄向阳．2002．一起硝基苯中毒的调查[J]．预防医学文献信息．8(4)：457
张遵真，衡正昌，廖艳．2000．彗星试验检测间接诱变剂对小鼠睾丸细胞的DNA损伤[J]．癌变，畸变，突变．13(1)：4～7
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邹淑珍，郭岩东，王斌等．2002．气相色谱法测定MDI废水中微量苯胺及硝基苯[J]．聚氨酯工业．17(3)：44～46
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Albrecht W & Neumann H-G. 1985.Biomonitoring of aniline and nitrobenzene: Hemoglobin-binding in rats and analysis of adducts. Arch Toxicol. 57: 1～5
Astier A. 1992. Simultaneous high-performance liquid chromatographic determination of urinary metabolites of benzene, nitrobenzene, toluene, xylene and styrene. [J]. Chromatogr. 573: 318～322
Bader M, Goen T, Muller J & Angerer J. 1998. Analysis of nitroaromatic compounds in urine by gas chromatography.mass spectrometry for the biological monitoring of explosives [J]. Chromatogr B, Biomed Sci Appl. 710(12): 91～99
Bartsch H, Malaveille C, Camus AM, et al. 1980. Validation and comparative studies on 180 chemicals with S. typhimurium strains and V79 Chinese hamster cells in the presence of various metabolizing systems. Mutat Res.76: 1-50
BASF, Bayer, & Zeneca. 1995. Cytogenic study in vivo of nitrobenzene in mice, micronucleus test, single intraperitoneal administration (unpublished report).
Beauchamp ROJ, Irons RD, Rickert DE, et al. 1982. A critical review of the literature on nitrobenzene toxicity. CRC Crit Rev Toxicol. 11: 33—84
Bio/dynamics Inc. 1983. A range-finding study to evaluate the toxicity of nitrobenzene in the pregnant rabbit. East Millstone. New Jersey, Bio/dynamics Inc. (Project No. 83-2723; unpublished).
Bio/dynamics Inc. 1984. An inhalation teratology study in rabbits with nitrobenzene. Conducted for the Nitrobenzene Association Toxicology Task Group. East Millstone, NewJersey, Bio/dynamics Inc., 16 August (Project No. 83-2725; unpublished).
Cattley RC, Everitt JI, Gross EA, et al. 1994. Carcinogenicity and toxicity of inhaled nitrobenzene in B6C3F1 mice and F344 and CD rats. Fundam Appl Toxicol. 22: 328—340
CIIT. 1993. A chronic inhalation toxicity study of nitrobenzene in B6C3F1 mice, Fischer 344 rats and Sprague-Dawley (CD) rats. Vols I & II. Research Triangle Park, North Carolina, Chemical Industry Institute of Toxicology.20 January 1993 (unpublished).
Eyer P & Lierheimer E. 1980. Biotransformation of nitrobenzene in the red blood cell and the role of glutathione. Xenobiotica. 10: 517.526.
Eyer P, Kampffmeyer H, Maister H, et al. 1980. Biotransformation of nitrosobenzene, phenylhydroxylamine, and aniline in the isolated perfused rat liver. Xenobiotica. 10: 499—516
Gilbert P, Rondelet J, Poncelet F, et al. 1980. Mutagenicity of p-nitrosophenol. Food Cosmet Toxicol, 18: 523-525
Goldstein RS & Rickert DE. 1985. Relationship between red blood cell uptake and methemoglobin production by nitrobenzene and dinitrobenzene in vitro. Life Sci, 36: 121 —125
Harmer D, Taylor MJ, Woollen BH, et al. 1989. The biological monitoring of workers exposed to nitrobenzene. In: Grandjean EC ed. Occupational health in the chemical industry. XVI Medichem Congress, Helsinki, Finland, 27.30 September 1988. Copenhagen, WHO Regional Office for Europe, pp 142—146
Hohn B and J Collins. 1980. A small cosmid for efficient cloning of large DNA fragments. Gene 11:291-298
Huang Q-G, Kong L-R, Liu Y-B, et al. 1996. Relationship between molecular structure and chromosomal aberrations in in vitro human lymphocytes induced by substituted nitrobenzenes. Bull Environ Contam Toxicol. 57: 349-353
Kawashima K, Momma J, Takagi A, et al. 1995a. Examination of sperm motility defects by nitrobenzene with an image processor. Teratology. 52: P-27 (Abstr).
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樊德方．1982．农药残留量分析与检测．上海科学技术出版社．
韩国柱．1999．中药药代动力学[M]．北京：中国医药科技出版社．197～208
李发美．2000．医药高效液相色谱技术[M]．人民卫生出版社．136～145
李浩春．1998．气相色谱法．科学出版社．4
李杰．．2003．气相色谱法测定水及空气中的苯胺和硝基苯[J]．广州化学．28(2)：23～26
李瑞琴．1998．高压液相色谱法测定废水中的苯胺和硝基苯胺[J]．环境科学研究．11(6)：34～38
李善茂，顾惠芬，郑明生，詹彦．1997．反相高效液相色谱法测定对氨基酚及其相关化合物．色谱．15(4)：324～327
牛玉梅，赵守国，王继刚，李洪霞．2006．气相色谱法测定达连河水中的硝基苯．测量与校准．26(5)：39～41
齐庆来，刘贵民．2006．急性间二硝基苯中毒18例临床分析[J]．工业卫生与职业病．32(3)：180～181
沈德中．2006．污染环境的生物修复[M]．北京：化学工业出版社．6～7
宋雄英．2003．高浓度硝基苯类废水处理工艺[J]．污染防治技术．16(4)：95～96
王碧云．2006．反相高效液相色谱法测定饮用水中的酚类化合物[J]．福建分析测试．15(3)：20～22
王阳峰，吕玉新．2004．用水生态毒理学方法评价13种硝基苯类化合物的急性毒性[J]．新乡医学院学报．21(6)：456～458
徐镜波．2000．环境毒理学[M]．长春：东北师范大学出版社．98～155．
徐晓白，戴树桂，黄玉瑶．1998．典型化学污染物在环境中的变化及生态效应[M]．北京：科学出版社．239
张晓春，吴登胜，杨强生等．2001．低浓度苯胺、硝基苯对生产工人健康的影响[J]．中国工业医学杂志，14(1)：53～54
张秀忠．固相萃取．高效液相色谱法测定水中的酚类化合物[J]．给水排水．2004(2)：30～32
张玉玲，狄向阳．2002．一起硝基苯中毒的调查[J]．预防医学文献信息．8(4)：457
张遵真，衡正昌，廖艳．2000．彗星试验检测间接诱变剂对小鼠睾丸细胞的DNA损伤[J]．癌变，畸变，突变．13(1)：4～7
周秋华，孙冲，陶建清．2005．高效液相色谱．质谱法测定废水中微量氯苯酚和硝基苯酚[J]．淮阴师范学院学报(自然科学版)．4(1)：51～53
周晓珍，肖熳．2005．高效液相色谱法测定水中六种酚类化合物[J]．南昌高专学报．1：103～105
邹淑珍，郭岩东，王斌等．2002．气相色谱法测定MDI废水中微量苯胺及硝基苯[J]．聚氨酯工业．17(3)：44～46
Adler B, Braun R, Schoeneich J, & Boehme H .1976.Repair-defective mutants of Proteus mirabilis as a prescreening system for the detection of potential carcinogens.Biol Zentraibl, 95: 463 [cited in Beauchamp et al., 1982]
Albrecht W & Neumann H-G. 1985.Biomonitoring of aniline and nitrobenzene: Hemoglobin-binding in rats and analysis of adducts. Arch Toxicol. 57: 1～5
Astier A. 1992. Simultaneous high-performance liquid chromatographic determination of urinary metabolites of benzene, nitrobenzene, toluene, xylene and styrene. [J]. Chromatogr. 573: 318～322
Bader M, Goen T, Muller J & Angerer J. 1998. Analysis of nitroaromatic compounds in urine by gas chromatography.mass spectrometry for the biological monitoring of explosives [J]. Chromatogr B, Biomed Sci Appl. 710(12): 91～99
Bartsch H, Malaveille C, Camus AM, et al. 1980. Validation and comparative studies on 180 chemicals with S. typhimurium strains and V79 Chinese hamster cells in the presence of various metabolizing systems. Mutat Res.76: 1-50
BASF, Bayer, & Zeneca. 1995. Cytogenic study in vivo of nitrobenzene in mice, micronucleus test, single intraperitoneal administration (unpublished report).
Beauchamp ROJ, Irons RD, Rickert DE, et al. 1982. A critical review of the literature on nitrobenzene toxicity. CRC Crit Rev Toxicol. 11: 33—84
Bio/dynamics Inc. 1983. A range-finding study to evaluate the toxicity of nitrobenzene in the pregnant rabbit. East Millstone. New Jersey, Bio/dynamics Inc. (Project No. 83-2723; unpublished).
Bio/dynamics Inc. 1984. An inhalation teratology study in rabbits with nitrobenzene. Conducted for the Nitrobenzene Association Toxicology Task Group. East Millstone, NewJersey, Bio/dynamics Inc., 16 August (Project No. 83-2725; unpublished).
Cattley RC, Everitt JI, Gross EA, et al. 1994. Carcinogenicity and toxicity of inhaled nitrobenzene in B6C3F1 mice and F344 and CD rats. Fundam Appl Toxicol. 22: 328—340
CIIT. 1993. A chronic inhalation toxicity study of nitrobenzene in B6C3F1 mice, Fischer 344 rats and Sprague-Dawley (CD) rats. Vols I & II. Research Triangle Park, North Carolina, Chemical Industry Institute of Toxicology.20 January 1993 (unpublished).
Eyer P & Lierheimer E. 1980. Biotransformation of nitrobenzene in the red blood cell and the role of glutathione. Xenobiotica. 10: 517.526.
Eyer P, Kampffmeyer H, Maister H, et al. 1980. Biotransformation of nitrosobenzene, phenylhydroxylamine, and aniline in the isolated perfused rat liver. Xenobiotica. 10: 499—516
Gilbert P, Rondelet J, Poncelet F, et al. 1980. Mutagenicity of p-nitrosophenol. Food Cosmet Toxicol, 18: 523-525
Goldstein RS & Rickert DE. 1985. Relationship between red blood cell uptake and methemoglobin production by nitrobenzene and dinitrobenzene in vitro. Life Sci, 36: 121 —125
Harmer D, Taylor MJ, Woollen BH, et al. 1989. The biological monitoring of workers exposed to nitrobenzene. In: Grandjean EC ed. Occupational health in the chemical industry. XVI Medichem Congress, Helsinki, Finland, 27.30 September 1988. Copenhagen, WHO Regional Office for Europe, pp 142—146
Hohn B and J Collins. 1980. A small cosmid for efficient cloning of large DNA fragments. Gene 11:291-298
Huang Q-G, Kong L-R, Liu Y-B, et al. 1996. Relationship between molecular structure and chromosomal aberrations in in vitro human lymphocytes induced by substituted nitrobenzenes. Bull Environ Contam Toxicol. 57: 349-353
Kawashima K, Momma J, Takagi A, et al. 1995a. Examination of sperm motility defects by nitrobenzene with an image processor. Teratology. 52: P-27 (Abstr).
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