对二氯苯的毒理学研究进展
Research Progress in Bio- and Eco-toxicity Caused by p-dichlorobenzene:A Mini Review
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摘要: 对二氯苯是一种含卤素的挥发性有机污染物，是钢铁烧结烟气中的主要芳烃类化合物之一。该化合物也是合成药物、人造树脂及精细化学品的重要原料，可用于制备家用防蛀防霉剂。对二氯苯挥发性较强，可通过大气传输，已经广泛出现在人和动物的食物链中，对于人体和生态环境具有潜在的危害。体外毒理学研究证实，对二氯苯主要是通过线粒体凋亡途径引起细胞损伤。对二氯苯不具有遗传毒性，其致突变作用仍需进一步研究。体内毒理学研究表明，对二氯苯会引起肝脏和神经系统的损害，并且会出现抽搐、贫血、厌食和皮肤色素沉积等一系列症状，对人致癌的证据不充分。活体动物的研究表明，在大剂量灌胃条件下，对二氯苯可诱发动物的肝细胞增殖，并可能引发肿瘤。当小鼠暴露于极低浓度的对二氯苯时，小鼠海马神经元中相关的基因表达被强烈抑制。对二氯苯在哺乳动物体内的Ⅰ相代谢产物主要是2，5-二氯苯酚，Ⅱ相代谢产物为2，5-二氯苯酚的硫酸盐和葡萄糖醛酸等形式。在代谢中产生的环氧化物和二氯氢醌中间体是该化合物体内毒性的来源之一。对二氯苯生态毒性研究表明，对二氯苯对环境中的动植物具有毒害作用。低浓度的对二氯苯会抑制植物根际微域土壤脱氢酶和脲酶活性，而高浓度的对二氯苯则表现为促进作用。对二氯苯可以通过抑制细胞生长的G1期来抑制植物细胞分裂，从而影响植物的生长。本文综述了对二氯苯在体内外的毒性、代谢转化及生态毒理效应，为对二氯苯的污染控制及毒害作用的阻控研究提供依据。Abstract: p-dichlorobenzene, a volatile halogen-containing organic pollutant, was characterized as one of the major aromatic compounds in flue gas of iron ore sintering plants. It remained an important raw material for the synthesis of drugs, commodity, artificial resins, and fine chemicals. It has been used for the preparation of household mothballs for more than 40 years. Due to its high volatility, quick spread in air diffusion and wide chain transfer in ecosystem could be found, which exhibited potential harms and toxicity to human bodies and animals. In this paper, the toxicity of p-dichlorobenzene has been comprehensively reviewed from the stand point of cellular and living animal experiment levels, respectively. The results of in vitro toxicological studies confirmed that p-dichlorobenzene caused cellular damage mainly through mitochondrial apoptosis. p-dichlorobenzene exhibited no genotoxicity and its mutagenicity still underwent further investigations. In vivo toxicological investigations implied that p-dichlorobenzene caused damage to liver and nervous systems, leading to convulsions, anemia, anorexia, skin pigmentation, and other symptoms. The results of animal experiments demonstrated that oral administration of p-dichlorobenzene in higher doses induced the quicker proliferation of liver cells and tumor initiation. Mice experiments also confirmed that when mice were exposed to relatively low concentrations of p-dichlorobenzene, the expression of neuron-related genes in the hippocampus were strongly suppressed. 2,5-dichlorophenol, and sulfate and glucuronic acid of 2,5-dichlorophenol, were further characterized as one of the major phase Ⅰ and phase Ⅱ metabolites of p-dichlorobenzene in mammals, respectively. Both of epoxide and dichlorohydroquinone, being an intermediates in metabolism, contributed to the toxicity of p-dichlorobenzene in vivo. The ecotoxicity study of p-dichlorobenzene also confirmed the toxicity of halogen-containing compound to both animals and plants in the environment. Low concentrations of p-dichlorobenzene inhibited the activity of dehydrogenase and urease in rhizosphere soil, while high concentrations of p-dichlorobenzene up-regulated the enzymatic activity. p-dichlorobenzene inhibited plant cell division by cell cycle arrest at G1 phase, thus affecting plant growth. In summary, this paper reviewed the latest update on toxicity, metabolism and ecotoxicological effects of p-dichlorobenzene both in vivo and in vitro, which also provided the basis for the pollution control and chemoprevention of p-dichlorobenzene.
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Key words:
- p-dichlorobenzene /
- cytotoxicity /
- health risk /
- ecotoxicity
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陆荣柱, 金锡鹏, 顾学箕. 对二氯苯毒性研究的概况[J]. 中国公共卫生, 1995, 11(9):428-430 Alaufi K, Kiernan E, Dupont S, et al. Case report of paradichlorobenzene abuse that resulted in death[J]. The Journal of Emergency Medicine, 2020, 58(5):849-850 Zhang H J, Wu Z J, Zhou Q X, et al. Dicyandiamide sorption-desorption behavior on soils and peat humus[J]. Pedosphere, 2004, 14(3):395-399 马承银, 杨翠纯. 含氯氟烃与大气环境[J]. 环境保护, 1996, 24(9):40-42 尹伊伟, 林嘉, 朱永安. 苯、氯苯及酚、氯酚对大鳞副泥鳅(Paramisgurnus dabryanus Sauvage)鱼苗的急性毒性效应[J]. 暨南大学学报:自然科学与医学版, 1994, 15(3):106-109 Yin Y W, Lin J, Zhu Y A. Acute toxicity of benzene, chlorobenzenes and phenol, chlorophenols to the fry of loach (Paramisgurnus dabrayanus Sauvage) induced by artificial ovulation[J]. Journal of Jinan University:Natural Science & Medicine Edition, 1994, 15(3):106-109(in Chinese)
Harkov R, Gianti S J, Bozzelli J W, et al. Monitoring volatile organic compounds at hazardous and sanitary landfills in New Jersey[J]. Journal of Environmental Science and Health. Part A:Environmental Science and Engineering, 1985, 20(5):491 European Chemicals Agency (ECHA). Proposal for a restriction in annex ⅩⅤ restriction report[R]. Helsinki:ECHA, 2012 Newhart K. Environmental fate of paradichlorobenzene[R]. California Environmental Protection Agency, California Department of Pesticide Regulation, 2007 Hil R H. 美国1000例成人对二氯苯暴露程度分析[J]. 国外医学:卫生学分册, 1996(6):277-280 Komae S, Sekiguchi K, Suzuki M, et al. Secondary organic aerosol formation from p-dichlorobenzene under indoor environmental conditions[J]. Building and Environment, 2020, 174:106758 Loeser E, Litchfield M H. Review of recent toxicology studies on p-dichlorobenzene[J]. Food and Chemical Toxicology, 1983, 21(6):825-832 李明, 赵海梅, 陆英, 等. 对二氯苯职业危害的研究[J]. 中国工业医学杂志, 2001, 14(3):143-145 Li M, Zhao H M, Lu Y, et al. Studies on occupational hazards caused by para-dichlorobenzene[J]. Chinese Journal of Industrial Medicine, 2001, 14(3):143-145(in Chinese)
吴艳萍, 郑晶, 王明秋, 等. 对二氯苯吸入染毒致小鼠血中微量元素和免疫功能变化的研究[J]. 环境与健康杂志, 2011, 28(10):914-916 沈蕴秀. 国内对二氯苯生产使用情况[J]. 氯碱工业, 1995, 31(10):1-2 蔡建利, 龙建银, 杨斌, 等. 对二氯苯的生产、技术及市场前景[J]. 中国氯碱, 2009(7):1-4 Cai J L, Long J Y, Yang B, et al. Production, technology and market prospect of p-dichlorobenzene[J]. China Chlor-Alkali, 2009 (7):1-4(in Chinese)
李义沣. 警惕萘丸与"对二氯苯"对人体的危害"[J]. 林产化工通讯, 1995, 29(5):28-29 薛荣泰. 警惕芳香杀手——慎选慎用含对二氯苯樟脑丸[J]. 福建质量管理, 2011(Z3):37-39 尹先仁. 对-二氯苯使用的安全性[J]. 中国公共卫生, 1997, 13(6):377-379 United States Environmental Protection Agency (US EPA). 1,4-dichlorobenzene[R]. Washinton DC:US EPA, 2021 Hissink A M, Dunnewijk R, van Ommen B, et al. Kinetics and metabolism of 1,4-dichlorobenzene in male Wistar rats:No evidence for quinone metabolites[J]. Chemico-Biological Interactions, 1997, 103(1):17-33 李玉梅, 孙凯, 任智勇. 卤代苯的分子连接性指数与其毒性的QSAR研究[J]. 安徽农业科学, 2010, 38(17):9172-9174 Li Y M, Sun K, Ren Z Y. QSAR study on connectivity index and toxicity of halogenated benzenes[J]. Journal of Anhui Agricultural Sciences, 2010, 38(17):9172-9174(in Chinese)
樊廷俊, 夏兰. 线粒体与细胞凋亡[J]. 生物化学与生物物理学报, 2001, 33(1):7-12 杨长永, 周毅, 龚建平. 膜受体介导的细胞凋亡与细胞增殖[J]. 中华肿瘤防治杂志, 2006, 13(13):986-989 Yang C Y, Zhou Y, Gong J P. Membrane receptor-mediated apoptosis and proliferation[J]. Chinese Journal of Cancer Prevention and Treatment, 2006, 13(13):986-989(in Chinese)
Smith M J, Salvendy G. Human Interface and the Management of Information. Interacting in Information Environments[M]. Berlin, Heidelberg:Springer Berlin Heidelberg, 2007:1060 Canonero R, Campart G B, Mattioli F, et al. Testing of p-dichlorobenzene and hexachlorobenzene for their ability to induce DNA damage and micronucleus formation in primary cultures of rat and human hepatocytes[J]. Mutagenesis, 1997, 12(1):35-40 左派欣, 杨卫超, 姜红, 等. 对二氯苯致突变性的实验研究[J]. 职业与健康, 2003, 19(10):53-55 Zuo P X, Yang W C, Jiang H, et al. Experimental study on the mutagenicity of p-dichlorobenzene[J]. Occupation and Health, 2003, 19(10):53-55(in Chinese)
Carbonell E, Puig M, Xamena N, et al. Sister-chromatid exchanges (SCE) induced by p-dichlorobenzene in cultured human lymphocytes[J]. Mutation Research Letters, 1991, 263(1):57-59 den Besten C, Vet J J R M, Besselink H T, et al. The liver, kidney, and thyroid toxicity of chlorinated benzenes[J]. Toxicology and Applied Pharmacology, 1991, 111(1):69-81 李明, 陆英, 杜丽秋, 等. 职业性接触对二氯苯对作业工人健康的影响[J]. 工业卫生与职业病, 2002, 28(5):260-263 Li M, Lu Y, Du L Q, et al. Health effects of occupational exposure to p-dichlorobenzene[J]. Industrial Health and Occupational Diseases, 2002, 28(5):260-263(in Chinese)
Dubey D, Sharma V D, Pass S E, et al. para-dichlorobenzene toxicity-A review of potential neurotoxic manifestations[J]. Therapeutic Advances in Neurological Disorders, 2014, 7(3):177-187 Malcolm W. Toxicological profile for dichlorobenzenes[M]//Dichlorobenzenes. Springer, 2006:242-272 王兰. 对二氯苯的毒性和致癌性研究近况[J]. 职业卫生与病伤, 1996, 14(3):27-29 Hsiao P K, Lin Y C, Shih T S, et al. Effects of occupational exposure to 1,4-dichlorobenzene on hematologic, kidney, and liver functions[J]. International Archives of Occupational and Environmental Health, 2009, 82(9):1077-1085 Kondo F, Ikai Y, Goto T, et al. Two sensitive sick-building syndrome patients possibly responding to p-dichlorobenzene and 2-ethyl-1-hexanol:Case report[J]. Journal of Health Science, 2007, 53(1):119-123 丁海琴, 沈维伟, 陈飞, 等. 浅谈实施防蛀防霉剂风险监测的重要性[J]. 化工管理, 2017(8):132 Hollingsworth R, Hoyle H, Oyen F, et al. Toxicity of paradichlorobenzene[J]. Archives of Industrial Health, 1956, 14:138-147 Reygagne A, Garnier R, Chataigner D. Encéphalopathie due á l'inhalation volontaire répétée de paradichlorob-enzéne[J]. Presse Médicale, 1992, 21:267 Cheong R, Wilson R K, Cortese I C M, et al. Mothball withdrawal encephalopathy-Case report and review of paradichlorobenzene neurotoxicity[J]. Substance Abuse, 2007, 27(4):63-67 Passov V, Milliner E K, Rundell J R. Partially reversible dementia associated with the use of para-dichlorobenzene in the case of pica[J]. Psychosomatics, 2011, 52(3):283-285 Lofchie A, Eison K, Gjombalaj I, et al. Looking for light:para-dichlorobenzene toxicity in a 30 year-old woman following long term ingestion of mothballs (1955)[J]. Neurology, 2020, 94(15):1955 Yau Leong J, Gianniosis M, Zafar S, et al. Mothball ingestion as a manifestation of pica, leading to paradichlorobenzene CNS toxicity[J]. African Health Sciences, 2020, 20(2):932-935 Pisano C, Gavino C A, Reichenberg J. Ichthyosiform eruption caused by paradichlorobenzene toxicity from toilet freshener inhalation[J]. JAAD Case Reports, 2019, 5(4):346-347 International Agency for Research on Cancer (IARC) monographs on the evaluation of the carcinogenic risk of chemicals to humans[R]. Lyon:IARC, 1980 Campbell D M, Davidson R J L. Toxic haemolytic anaemia in pregnancy due to a pica for paradichlorobenzene[J]. BJOG:An International Journal of Obstetrics and Gynaecology, 1970, 77(7):657-659 张秀珍, 李延平, 尹先仁, 等. 室内空气中对二氯苯卫生标准的研究[J]. 环境与健康杂志, 2005, 22(1):9-12 Zhang X Z, Li Y P, Yin X R, et al. Study on the health standard of p-dichlorobenzene in indoor air[J]. Journal of Environment and Health, 2005, 22(1):9-12(in Chinese)
Bomhard E, Luckhaus G, Voigt W H, et al. Induction of light hydrocarbon nephropathy by p-dichlorobenzene[J]. Archives of Toxicology, 1988, 61(6):433-439 Charbonneau M, Strasser J, Lock E A, et al. Involvement of reversible binding to alpha 2u-globulin in 1,4-dichlorobenzene-induced nephrotoxicity[J]. Toxicology and Applied Pharmacology, 1989, 99(1):122-132 United States Environmental Protection Agency (US EPA). Chemical assessment summary[R]. Washington DC:US EPA, 1994 Zupko A G, Edwards L D. A toxicological study of p-dichlorobenzene[J]. Journal of the American Pharmaceutical Association American Pharmaceutical Association, 1949, 38(3 Pt. 1):124-131 Weintraub E, Gandhi D, Robinson C. Medical complications due to mothball abuse[J]. Southern Medical Journal, 2000, 93(4):427-429 王苏华, 陆荣柱. 对二氯苯对大鼠和小鼠的13周吸入毒性[J]. 环境与职业医学, 2006, 23(2):177 Wang S H, Lu R Z, Yin C Q, et al. Lipid peroxidation and changes of trace elements in mice treated with paradichlorobenzene[J]. Biological Trace Element Research, 2010, 136(3):320-336 王苏华, 尹常庆, 陆荣柱, 等. 对二氯苯对小鼠肝肾抗氧化功能的影响[J]. 江苏大学学报:医学版, 2007, 17(6):478-480 Wang S H, Yin C Q, Lu R Z, et al. Effects of 1,4-DCB on lipid peroxidation and antioxidants in mice[J]. Journal of Jiangsu University:Medicine Edition, 2007, 17(6):478-480(in Chinese)
Umemura T, Saito M, Takagi A, et al. Isomer-specific acute toxicity and cell proliferation in livers of B6C3F1 mice exposed to dichlorobenzene[J]. Toxicology and Applied Pharmacology, 1996, 137(2):268-274 Aiso S, Takeuchi T, Arito H, et al. Carcinogenicity and chronic toxicity in mice and rats exposed by inhalation to para-dichlorobenzene for two years[J]. The Journal of Veterinary Medical Science, 2005, 67(10):1019-1029 Umemura T, Takada K, Schulz C, et al. Cell proliferation in the livers of male mice and rats exposed to the carcinogen p-dichlorobenzene:Evidence for thresholds[J]. Drug and Chemical Toxicology, 1998, 21(1):57-66 Butterworth B E, Aylward L L, Hays S M. A mechanism-based cancer risk assessment for 1,4-dichlorobenzene[J]. Regulatory Toxicology and Pharmacology, 2007, 49(2):138-148 Kitajima S, Aisaki K I, Kanno J. Percellome project on sick-building syndrome level inhalation for the prediction of lung and brain involvement[J]. Toxicology Letters, 2016, 259:S70 李明, 陆英, 成淑梅. 对二氯苯的毒物动力学研究概况[J]. 职业卫生与应急救援, 1998, 16(4):210-211 Hissink E, van Ommen B, Bogaards J J, et al. Hepatic Epoxide Concentrations during Biotransformation of 1,2- and 1,4-Dichlorobenzene[M]//Advances in Experimental Medicine and Biology. Boston, MA:Springer US, 1996:129-133 Hallowell M. Acute haemolytic anaemia following the ingestion of para-dichlorobenzene[J]. Archives of Disease in Childhood, 1959, 34(173):74-75 Bomhard E M, Schmidt U, L ser E. Time course of enzyme induction in liver and kidneys and absorption, distribution and elimination of 1,4-dichlorobenzene in rats[J]. Toxicology, 1998, 131(2-3):73-91 王桂燕, 胡筱敏, 周启星, 等. 对二氯苯和镉对草鱼(Ctenopharyngodon idellus)的联合毒性效应研究[J]. 环境科学, 2007, 28(1):156-159 Wang G Y, Hu X M, Zhou Q X, et al. Joint toxicity of 1,4-dichlorobenze and cadmium on Ctenopharyngodon idellus[J]. Environmental Science, 2007, 28(1):156-159(in Chinese)
刘晓宛, 张平, 龚霞, 等. 对二氯苯、四氯乙烯和镉联合污染对草鱼的毒性效应研究[J]. 环境科学与技术, 2020, 43(1):217-221 Liu X W, Zhang P, Gong X, et al. Joint toxicity of 1,4-dichlorobenze, perchloroethylene and Cd2+ on grass carp[J]. Environmental Science & Technology, 2020, 43(1):217-221(in Chinese)
潘伟槐. 对二氯苯和苯对蚕豆(Vicia faba L.)根尖有丝分裂及微核率的效应[J]. 绍兴师专学报:哲学社会科学版, 1995, 15(6):58-62 Pan W H. The effect of p-dichlorobenzene and benzene on Vicia faba root-pit cells' mitosis and micronucleus frequency[J]. Journal of Shaoxing Teachers College, 1995, 15(6):58-62(in Chinese)
田秀梅. 对二氯苯的环境行为与生态毒性效应研究[D]. 沈阳:东北大学, 2006:40-42 Tian X M. Environmental behavior and ecotoxicological effects of p-dichlorobenzene[D]. Shenyang:Northeastern University, 2006:40 -42(in Chinese)
孙福红, 周启星, 陈艳卿. 对二氯苯与Cd复合污染对毫米级根际微域土壤酶活性的联合毒性效应评价[J]. 环境工程技术学报, 2016, 6(6):571-578 Sun F H, Zhou Q X, Chen Y Q. Assessment on joint toxic effects of combined pollution of 1,4-DCB and Cd on enzyme activities in millimeter rhizosphere[J]. Journal of Environmental Engineering Technology, 2016, 6(6):571-578(in Chinese)
Hu X Y, Yang T, Liu C, et al. Distribution of aromatic amines, phenols, chlorobenzenes, and naphthalenes in the surface sediment of the Dianchi Lake, China[J]. Frontiers of Environmental Science & Engineering, 2020, 14(4):1-13 -
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