Neurotoxic compounds can interfere with active gill ventilation in fish, which might lead to premature death in adult fish, but not in skin-breathing embryos of zebrafish, since these exclusively rely on passive diffusion across the skin. Regarding lethality, this respiratory failure syndrome (RFS) has been discussed as one of the main reasons for the higher sensitivity of adult fish in the acute fish toxicity test (AFT), if compared to embryos in the fish embryo toxicity test (FET). To further elucidate the relationship between the onset of gill respiration and death by a neurotoxic mode of action, a comparative study into oxygen consumption (MO₂), breathing frequency (f_v) and amplitude (f_ampl) was performed with 4 d old skin-breathing and 12 d old early gill-breathing zebrafish. Neurotoxic model substances with an LC₅₀ FET/AFT ratio of > 10 were used: chlorpyrifos, permethrin, aldicarb, ziram, and fluoxetine. Exposure to hypoxia served as a positive control, whereas aniline was tested as an example of a narcotic substance interfering non-specifically with gill membranes. In 12 d old larvae, all substances caused an increase in MO₂, f_v and partly f_ampl, whereas effects were minor in 4 d old embryos. An increase of f_v in 4 d old embryos following exposure to chlorpyrifos, aldicarb and hypoxia could not be correlated with an increased MO₂ and might be attributed either to (1) to the successfully postponed decrease of arterial partial pressure of oxygen (PO₂) through support of skin respiration by increased f_v, (2) to an unspecific stimulation of the sphincter muscles at the base of the gill filaments, or (3) to the establishment of oxygen sensing for later stages. In gill-breathing 12 d old zebrafish, a concentration-dependent increase of f_v was detected for aniline and chlorpyrifos, whereas for aldicarb, fluoxetine and permethrin, a decline of f_v at higher substance concentrations was measured, most likely due to the onset of paralysis and/or fatigue of the gill filament sphincter muscles. Since alterations of f_v serve to postpone the decrease in arterial PO₂ and MO₂ increased with decreasing f_v, the respiratory failure syndrome could clearly be demonstrated in 12 d old zebrafish larvae. Passive respiration across the skin in zebrafish embryos could thus be confirmed as a probable reason for the lower sensitivity of early life-stages to neurotoxicants. Integration of respiratory markers into existing testing protocols with non-protected developmental stages such as embryos might help to not underestimate the toxicity of early life-stages of fish.

神经毒性化合物会干扰鱼类的主动鳃通气，这可能会导致成年鱼过早死亡，但不会导致斑马鱼的皮肤呼吸胚胎过早死亡，因为这些胚胎完全依赖于皮肤上的被动扩散。关于致死率，与鱼胚胎毒性试验（FET）中的胚胎相比，这种呼吸衰竭综合征（RFS）被认为是成鱼在急性鱼毒性试验（AFT）中敏感性更高的主要原因之一。为了进一步阐明神经毒性作用模式引起的鳃呼吸开始与死亡之间的关系，对4天龄皮肤的耗氧量（MO ₂）、呼吸频率（f _v）和幅度（f _ampl ）进行了比较研究-呼吸和12日龄早期鳃呼吸斑马鱼。使用LC ₅₀ FET/AFT比率> 10的神经毒性模型物质：毒死蜱、氯菊酯、涕灭威、齐拉姆和氟西汀。暴露于缺氧作为阳性对照，而苯胺作为非特异性干扰鳃膜的麻醉物质的例子进行测试。_{在 12 日龄幼虫中，所有物质均导致 MO 2}、f _v和部分 f _ampl增加，而在 4 日龄胚胎中影响较小。暴露于毒死蜱、涕灭威和缺氧后 4 日龄胚胎中f _{v的增加与 MO 2}的增加无关，可能归因于 (1) 成功推迟了动脉氧分压 (PO ₂）通过增加 f _v支持皮肤呼吸，（2）对鳃丝底部的括约肌进行非特异性刺激，或（3）为后期建立氧气感应。_{在用鳃呼吸的 12 日龄斑马鱼中，检测到苯胺和毒死蜱的 f v}呈浓度依赖性增加，而对于涕灭威、氟西汀和氯菊酯，在较高物质浓度下测量到 f _v下降，很可能是由于开始鳃丝括约肌的麻痹和/或疲劳。由于 f _{v的改变可以推迟动脉 PO 2}和 MO ₂的下降，因此随着 f _{v 的降低而增加}，在 12 d 龄斑马鱼幼鱼中可以清楚地表现出呼吸衰竭综合征。因此，斑马鱼胚胎中跨皮肤的被动呼吸可能被证实是生命早期阶段对神经毒物敏感性较低的一个可能原因。将呼吸标记物整合到现有的非受保护发育阶段（例如胚胎）的测试方案中可能有助于不低估鱼类早期生命阶段的毒性。