Hassold Enken, Backhaus Thomas
University of Bremen, Department of Biology and Chemistry, Leobener Strasse, 28359 Bremen, Germany.
Environ Toxicol Chem. 2009 Jun;28(6):1218-26. doi: 10.1897/08-339.1.
Demethylase inhibitors (DMIs) are broad-spectrum fungicides that are ubiquitously used in agriculture and medicine. They comprise chemically heterogeneous substances that share a common biochemical target in fungi, the inhibition of a specific step in sterol biosynthesis. Several DMIs are suspected to disrupt endocrine-mediated processes in a range of organisms and to inhibit ecdysteroid biosynthesis in arthropods. It is unclear, however, whether and, if so, to what extent different DMI fungicides have a similar mode of action in nontarget organisms, which in turn would lead to a common chronic toxicity profile. Therefore, we selected a representative of each of the major DMI classes--the piperazine triforine, the pyrimidine fenarimol, the pyridine pyrifenox, the imidazole prochloraz, and the triazole triadimefon--and comparatively investigated their chronic toxicity to Daphnia magna. No toxicity was detectable up to the limit of solubility of triforine (61 micromol/L). All other DMIs reduced reproductive success by delaying molting and development and by causing severe developmental abnormalities among offspring. Prochloraz was most toxic (median effective concentration [EC50] for fecundity reduction, 0.76 micromol/L), followed by fenarimol (EC50, 1.14 micromol/L), pyrifenox (EC50, 3.15 micromol/L), and triadimefon (EC50, 5.13 micromol/L). Mean effect concentrations for fecundity reduction were related to lipophilicity and followed baseline toxicity. However, triadimefon and fenarimol (but none of the other tested DMIs) caused severe eye malformations among exposed offspring. Affected neonates did survive, but a reduced ecological fitness can be assumed. Offspring exposed to fenarimol in mater matured earlier. The investigated different life-history parameters were affected in a substance-specific manner. These qualitatively different toxicity profiles suggest additional, substance-specific mechanisms of action in D. magna that probably are related to an antiecdysteroid action.
脱甲基酶抑制剂(DMIs)是一类广泛应用于农业和医学领域的广谱杀菌剂。它们由化学性质各异的物质组成,这些物质在真菌中具有共同的生化靶点,即抑制甾醇生物合成中的特定步骤。有几种DMIs被怀疑会干扰一系列生物体中由内分泌介导的过程,并抑制节肢动物中的蜕皮甾体生物合成。然而,尚不清楚不同的DMI杀菌剂在非靶标生物中是否具有相似的作用模式,以及如果有,其程度如何,而这反过来又会导致共同的慢性毒性特征。因此,我们选择了各主要DMI类别中的一种代表物质——哌嗪类的嗪氨灵、嘧啶类的氯苯嘧啶醇、吡啶类的粉锈宁、咪唑类的咪鲜胺和三唑类的三唑酮——并比较研究了它们对大型溞的慢性毒性。在达到嗪氨灵的溶解度极限(61微摩尔/升)之前均未检测到毒性。所有其他DMIs均通过延迟蜕皮和发育以及导致后代出现严重的发育异常来降低繁殖成功率。咪鲜胺毒性最大(降低繁殖力的半数有效浓度[EC50]为0.76微摩尔/升),其次是氯苯嘧啶醇(EC50为1.14微摩尔/升)、粉锈宁(EC50为3.15微摩尔/升)和三唑酮(EC50为5.13微摩尔/升)。降低繁殖力的平均效应浓度与亲脂性有关,并遵循基线毒性。然而,三唑酮和氯苯嘧啶醇(但其他测试的DMIs均未)在暴露的后代中导致严重的眼部畸形。受影响的幼体确实存活了下来,但可以推测其生态适应性有所降低。在母体中接触氯苯嘧啶醇的后代成熟得更早。所研究的不同生活史参数受到物质特异性方式的影响。这些在性质上不同的毒性特征表明,在大型溞中存在额外的、物质特异性的作用机制,这可能与抗蜕皮甾体作用有关。