Assessment of embryotoxic potential of mixtures of environmental chemicals using rat embryo limb bud cell cultures

本研究的目的是评价大鼠胚胎肢芽细胞培养（LBC）在分析环境中化学污染物联合胚胎毒性作用中的作用。化学物质在LBC中的联合作用模式可以用毒性单元模型和等孔图来可视化。采用LBC法对环境中常见的9种有机氯化合物的胚胎毒性进行了筛选。这些化学物质分别是对二氯苯（pDCB）、邻二氯苯（o-DCB）、对氯苯胺（pCA）、3,4-二氯苯胺（DCA）、三（2-氯乙基）磷酸、2,5-二氯苯酚（DP）、2,5-二氯苯甲醚（DA）、三氯生（IR）和三氯卡班（TC）。利用LBC和等孔图对这些化学物质二元混合物的胚胎毒性进行了筛选和分析。IR-TC混合物表现出加性联合作用。pDCB-TCEP和pDCB-pCA混合对细胞增殖的联合作用小于添加剂，而pDCB-DP混合对细胞分化的联合作用小于添加剂。由于LBC可以评估细胞增殖和细胞分化的共同作用，以及它们之间的比值（P/D比），因此LBC可以用于评估化学混合物的胚胎毒性潜能。

The objective of this study was to evaluate the usefulness of rat embryo limb bud cell cultures (LBC) for analyzing joint embryotoxic action of chemical contaminants in the environment. The mode of joint action of chemicals in LBC can be visualized using the toxic unit model and an isobole diagram.The embryotoxicity of nine organochlorine compounds commonly detected in the environment were screened using LBC.These chemicals were p-dichlorobenzene (pDCB), o-dichlorobenzene (o-DCB), p-chloroaniline(pCA), 3,4-dichloroaniline (DCA), tris(2-chloroethyl) phosphate, 2,5-dichlorophenol (DP), 2,5-dichloroanisole (DA), Triclosan (IR) and Triclocarban (TC). The embryotoxicity of binary mixtures of these chemicals were also screened and analyzed using LBC and isobole diagram. Mixture of IR-TC showed additive joint action. Mixtures of pDCB-TCEP and pDCB-pCA showed less than additive joint action for cell proliferation while mixture of pDCB-DP showed less than additive joint action for cell differentiation.As LBC can assess the joint action for cell proliferation, for cell differentiation and for their ratio of the former to the latter (P/D ratio), LBC is useful for evaluating embryotoxic potential of chemical mixtures.