Ugazio G, Bosio A, Burdino E, Ghigo L, Nebbia C
Dipartimento di Medicina e Oncologia Sperimentale, Sezione di Patologia Ambientale, Torino, Italy.
Res Commun Chem Pathol Pharmacol. 1991 Dec;74(3):349-61.
Previous findings from our laboratory suggested a possible interaction of atrazine, bentazon and molinate with other environmental and/or occupational poisons. The aim of this research was to obtain further toxicological information by using phenobarbital-induced rats and to characterize the effects of these herbicides on the hepatic microsomal metabolism of xenobiotics. Acute experiments have shown that the LD50 is augmented by the barbiturate pretreatment when atrazine is used, remains unchanged in the case of bentazon, but is lowered when molinate is given. Recrystallized atrazine, in the absence of the wetting compounds, elicits the same acute toxicity found when animals are challenged with a commercial preparation. No significant sex-related differences have been observed. In long-term treatment with these toxicants, atrazine shortened the hexobarbital narcosis, but no effect was observed after administration of either bentazon or molinate. Further studies on hexobarbital sleeping time demonstrated that females are more susceptible than males to the narcotic effect of this compound. The induction-like effect of atrazine exposure has been confirmed, mainly in young animals. At the end of the sleeping time, the actual serum concentration of hexobarbital is practically the same, and is not related to the length of the sleeping time. The absence of behavioral alterations in the open field tests exclude possible neurological effects of the triazine herbicide. In conclusion, these data demonstrate that atrazine by itself induces the hepatic pharmacometabolic system, while its metabolites result less toxic than the parent compound. On the contrary, metabolic transformations render the toxic effects of bentazon more severe.
我们实验室之前的研究结果表明，莠去津、苯达松和禾草敌可能与其他环境和/或职业毒物存在相互作用。本研究的目的是通过使用苯巴比妥诱导的大鼠获取更多毒理学信息，并描述这些除草剂对异生物质肝微粒体代谢的影响。急性实验表明，使用莠去津时，巴比妥酸盐预处理会提高其半数致死剂量（LD50）；使用苯达松时，LD50保持不变；而使用禾草敌时，LD50会降低。在没有湿润剂的情况下，重结晶的莠去津引发的急性毒性与用市售制剂对动物进行攻击时所发现的相同。未观察到明显的性别差异。在用这些毒物进行长期治疗时，莠去津缩短了己巴比妥麻醉时间，但使用苯达松或禾草敌后未观察到效果。对己巴比妥睡眠时间的进一步研究表明，雌性比雄性对该化合物的麻醉作用更敏感。莠去津暴露的诱导样效应已得到证实，主要在幼龄动物中。在睡眠时间结束时，己巴比妥的实际血清浓度基本相同，且与睡眠时间长短无关。在旷场试验中未出现行为改变，排除了三嗪类除草剂可能的神经学效应。总之，这些数据表明，莠去津本身可诱导肝脏药物代谢系统，而其代谢产物的毒性低于母体化合物。相反，代谢转化使苯达松的毒性作用更严重。
