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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