Dorough H W
J Toxicol Clin Toxicol. 1982 Aug;19(6-7):637-59. doi: 10.3109/15563658208990396.
Products formed by the reaction of pesticides and their metabolites with endogenous chemicals (glucose, glucuronic acid, sulfate, glutathione, amino acid, etc.) are referred to as pesticide conjugates. Evidence to date suggests that this is a detoxification process since the resulting products are polar and usually rapidly eliminated from the body. However, very little is known about their acute toxicity, and almost nothing concerning the effects of chronic dietary exposure of animals to these materials. Though conjugates may be formed in vivo by animals administered the parent pesticide, this hardly can be considered an adequate means of assessing their toxic properties. Pesticide metabolites formed by primary metabolic reactions are often evaluated individually in both acute and subchronic toxicity tests, but similar experiments are not conducted with conjugates. To assume that pesticide conjugates are toxicologically insignificant is unsound scientifically, although the rationale for such an assumption is not completely without merit. Many polar compounds are inactive but many, including some conjugates, are biologically active and indeed may be very toxic. While elaborate toxicological investigations of all pesticide conjugates do not appear warranted, there is a clear need to strengthen the data base relative to their potential toxicological significance. Extensive investigations of selected model compounds, representing different pesticide groups and conjugate types, are in order if the issue is to be placed in proper perspective relative to the total safety evaluation of pesticidal chemicals.
农药及其代谢物与内源性化学物质(葡萄糖、葡萄糖醛酸、硫酸盐、谷胱甘肽、氨基酸等)反应形成的产物被称为农药轭合物。迄今为止的证据表明,这是一个解毒过程,因为生成的产物具有极性,通常会迅速从体内排出。然而,关于它们的急性毒性知之甚少,而且几乎没有关于动物长期饮食接触这些物质的影响的信息。尽管给予母体农药的动物可能在体内形成轭合物,但这很难被认为是评估其毒性特性的充分方法。由初级代谢反应形成的农药代谢物通常在急性和亚慢性毒性试验中单独进行评估,但对于轭合物则不进行类似的实验。认为农药轭合物在毒理学上无足轻重的假设在科学上是不合理的,尽管这种假设的理由并非完全没有道理。许多极性化合物是无活性的,但许多化合物,包括一些轭合物,具有生物活性,实际上可能具有很高的毒性。虽然似乎没有必要对所有农药轭合物进行详尽的毒理学研究,但显然需要加强关于其潜在毒理学意义的数据库。如果要从农药化学品的总体安全评估的适当角度看待这个问题,就需要对代表不同农药类别和轭合物类型的选定模型化合物进行广泛研究。