In vitro embryotoxicity of a series of para-substituted phenols: structure, activity, and correlation with in vivo data.
In vitro embryotoxicity of a series of para-substituted phenols: structure, activity, and correlation with in vivo data.
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一系列对位取代酚的体外胚胎毒性：结构、活性以及与体内数据的相关性。
DOI：
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发表时间：
1992
期刊：
影响因子：
--
通讯作者：
R. Kavlock
中科院分区：
文献类型：
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作者：
Linda A. Oglesby;Marian T. Ebron;Tina R. Logsdon;Frank Copeland;P. E. Beyer;R. Kavlock
本文研究了苯酚及其12种对位取代同系物对孕中期大鼠胚胎的体外毒性。通过应用相关程序和逐步回归，方程描述的物理化学性质和各种措施的活动之间的关系。通过降低选定生长参数和诱导四种形态缺陷的效价估计值的倒数的对数来量化胚胎毒性。一般而言，共培养的肝细胞改善胚胎毒性;只有苯酚诱导的胚胎毒性通过肝细胞的存在而增强。在没有肝细胞的情况下，生长迟缓的措施与酚类的摩尔代谢活性呈正相关。对于肝细胞，亲脂性对于描述诱导生长缺陷的潜力变得重要。结构缺陷在两种培养体系中具有不同的相关模式。还将这些同系物的体外效力与体内观察到的母体和发育效力进行了比较（Kavlock，Teratology，41：43-59，'90）。其中两种同系物在两个系统中都具有剧毒。对于其余同系物，发现一项母体毒性指标与体外无肝细胞生长和发育的胚胎毒性呈正相关。对于肝细胞，在体内发育毒性终点和体外胚胎毒性之间观察到广泛的正相关和负相关。初步剂量测定研究的数据表明，苯酚同系物在体外接触的胚胎中比在体内接触的胚胎中更容易积累。基于剂量测定信息的效力计算可以证明数据之间更好的相关性，并允许开发化学结构和活性之间的其他关系。
The embryotoxicity of phenol and twelve para-substituted congeners on mid-gestation rat embryos was evaluated in vitro. Through application of correlative procedures and stepwise regression, equations describing the relationship between physical-chemical properties and various measures of activity were developed. Embryotoxicity was quantified by the log of the reciprocal of the potency estimates for reduction in selected growth parameters and induction of four morphological defects. In general, co-cultured hepatocytes ameliorated embryotoxicity; only phenol-induced embryotoxicity was enhanced by the presence of hepatocytes. In the absence of hepatocytes, measures of growth retardation were positively correlated with molar refractivity of the phenols. With hepatocytes, lipophilicity became important for describing the potential to induce growth deficits. The structural defects had varying correlation patterns in both culture systems. Potencies of these congeners in vitro were also compared to maternal and developmental potencies observed in vivo (Kavlock, Teratology, 41:43-59, '90). Two of the congeners were very toxic in both systems. For the remaining congeners, one maternal toxicity measure was found to be positively correlated with embryotoxicity for growth and development in vitro without hepatocytes. With hepatocytes, a broad spectrum of correlations, both positive and negative, were observed between in vivo developmental toxicity endpoints and in vitro embryotoxicity. Data from preliminary dosimetry studies suggest that phenol congeners may accumulate in embryos exposed in vitro more readily than with in vivo exposure. Potency calculations based on dosimetry information may demonstrate better correlations between data and allow additional relationships between chemical structure and activity to be developed.
五种直接作用烷化剂在啮齿动物胚胎中的体外发育毒性：结构-活性模式。
DOI：
10.1002/tera.1420400303
发表时间：
1989
期刊：
Teratology
影响因子：
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作者：
Faustman,EM;Kirby,Z;Gage,D;Varnum,M
通讯作者：
Varnum,M