Rerkamnuaychoke Wuttiporn, Sreevidya Virinchipuram S, Svoboda Kurt R
Joseph J. Zilber College of Public Health, University of Wisconsin-Milwaukee, Milwaukee, WI 53205, USA.
Joseph J. Zilber College of Public Health, University of Wisconsin-Milwaukee, Milwaukee, WI 53205, USA.
Ecotoxicol Environ Saf. 2025 Apr 15;295:117993. doi: 10.1016/j.ecoenv.2025.117993. Epub 2025 Apr 10.
Chloroxylenol (CHX) and benzethonium chloride (BEC) are replacement compounds being used after the ban (U.S. FDA) of triclosan and triclocarban in 2016 from personal care products. These two compounds are also recommended by the World Health Organization (WHO) as disinfectants against COVID-19. Toxicity data for both CHX and BEC are available, however, neurotoxicity studies for both compounds are still limited. Here, we determined the consequences of CHX and BEC exposure in a static exposure paradigm during embryogenesis on neurodevelopment using the zebrafish model (Danio rerio). CHX exposure (1-5 mg/L) dramatically impacted nervous system development without increasing mortality. The exposure altered embryonic motor output, primary motoneuron cell size, spinal interneuron cell size, primary motoneuron (PMN) axon pathfinding and secondary motoneuron (SMN) axon pathfinding. CHX exposure also altered slow muscle fiber development. Changes in neural activity as revealed by the induced changes in embryonic motor output (spontaneous coiling) may underlie the errors in PMN axon pathfinding as well as the changes in spinal interneuron morphology. Errors in SMN axon pathfinding resulting from CHX exposure were directly linked to errors in PMN axon pathfinding. Similar to CHX, BEC exposure (1-5 mg/L) altered embryonic motor output, spinal interneuron development, and slow muscle fiber development. In contrast to CHX, BEC exposure did not alter PMN or SMN axon pathfinding. Moreover, we found that BEC exposure (5 mg/L) from 5 to 96 hpf was lethal, resulting in almost 100 % mortality. Thus, these two triclosan replacement compounds exhibited markedly different modes of toxicity.
对氯间二甲苯酚（CHX）和苄索氯铵（BEC）是2016年三氯生和三氯卡班被美国食品药品监督管理局（FDA）禁止用于个人护理产品后所使用的替代化合物。世界卫生组织（WHO）也推荐这两种化合物作为对抗新型冠状病毒肺炎（COVID-19）的消毒剂。CHX和BEC的毒性数据均已可得，然而，针对这两种化合物的神经毒性研究仍然有限。在此，我们使用斑马鱼模型（Danio rerio）确定了在胚胎发育期间的静态暴露模式下CHX和BEC暴露对神经发育的影响。CHX暴露（1 - 5毫克/升）显著影响神经系统发育，但未增加死亡率。该暴露改变了胚胎运动输出、初级运动神经元细胞大小、脊髓中间神经元细胞大小、初级运动神经元（PMN）轴突寻路和次级运动神经元（SMN）轴突寻路。CHX暴露还改变了慢肌纤维发育。胚胎运动输出（自发卷曲）的诱导变化所揭示的神经活动变化可能是PMN轴突寻路错误以及脊髓中间神经元形态变化的基础。CHX暴露导致的SMN轴突寻路错误与PMN轴突寻路错误直接相关。与CHX类似，BEC暴露（1 - 5毫克/升）改变了胚胎运动输出、脊髓中间神经元发育和慢肌纤维发育。与CHX不同的是，BEC暴露未改变PMN或SMN轴突寻路。此外，我们发现5至96小时胚胎期（hpf）的BEC暴露（5毫克/升）具有致死性，导致近100%的死亡率。因此，这两种三氯生替代化合物表现出明显不同的毒性模式。
