Abstract：
Bis(2-ethylhexyl) phthalate is the most abundant phthalate used as plasticizer to soften plastics and polymers included in medical devices. Human and environmental exposure may occur because DEHP is not chemically bound to plastics and can easily leach out of the materials. This phthalate is classified as reproductive toxicant and possible carcinogen to humans. The genotoxic potential has still to be clarified, but there are indications suggesting that DEHP may have aneugenic effects. To further investigate DEHP genotoxicity, the cytochalasin-block micronucleus assay was applied and combined with the CREST staining to characterise micronucleus content and gain insights on its genotoxic mode of action. Chromosomal damage was also analysed in metaphase and ana-telophase cells and the morphology of the mitotic spindle was investigated to evaluate the possible involvement of this cellular apparatus as a target of DEHP. Our findings indicated that DEHP induced a statistically significant increase in the frequency of micronuclei as well as in the frequency of CREST-positive micronuclei. Consistently, disturbance of chromosome segregation and induction of numerical chromosome changes were observed together with changes in spindle morphology, formation of multipolar spindles and alteration of the microtubule network. Experiments performed without metabolic activation demonstrated a direct action of DEHP on chromosome segregation not mediated by its metabolites. In conclusion, there is consistent evidence for an aneugenic activity of DEHP. A thresholded genotoxic activity was identified for DEHP, disclosing possible implications for risk assessment.
摘要：
邻苯二甲酸二(2-乙基己基)酯是用作增塑剂以软化包括在医疗装置中的塑料和聚合物的最丰富的邻苯二甲酸酯。因为DEHP不与塑料化学结合并且容易从材料中浸出,所以可能发生人类和环境暴露。这种邻苯二甲酸酯被归类为生殖毒物和对人类可能的致癌物。基因毒性潜力仍有待澄清，但有迹象表明DEHP可能具有不良作用。为了进一步研究DEHP的遗传毒性，应用细胞松弛素阻滞微核试验并结合CREST染色来表征微核含量并获得对其基因毒性作用模式的见解.还分析了中期和晚期细胞中的染色体损伤，并研究了有丝分裂纺锤体的形态，以评估该细胞装置作为DEHP靶标的可能参与。我们的发现表明，DEHP诱导了微核频率以及CREST阳性微核频率的统计学显着增加。始终如一，观察到染色体分离的干扰和染色体数量变化的诱导，以及纺锤体形态的变化，多极纺锤体的形成和微管网络的改变。在没有代谢激活的情况下进行的实验表明，DEHP对染色体分离的直接作用不是由其代谢物介导的。总之,有一致的证据表明DEHP具有不良活性。确定了DEHP的遗传毒性活性阈值，披露对风险评估的可能影响。
