Kim Jiwan, Choi Jinhee
School of Environmental Engineering, University of Seoul, 163 Seoulsiripdae-ro, Dongdaemun-gu, Seoul 02504, Republic of Korea.
Toxics. 2023 Apr 20;11(4):388. doi: 10.3390/toxics11040388.
The mixture of 5-chloro-2-methylisothiazol-3(2H)-one and 2-methylisothiazol-3(2H)-one, CMIT/MIT, is an isothiazolinone biocide that is consistently detected in aquatic environments because of its broad-spectrum usage in industrial fields. Despite concerns about ecotoxicological risks and possible multigenerational exposure, toxicological information on CMIT/MIT is very limited to human health and within-generational toxicity. Furthermore, epigenetic markers altered by chemical exposure can be transmitted over generations, but the role of these changes in phenotypic responses and toxicity with respect to trans- and multigenerational effects is poorly understood. In this study, the toxicity of CMIT/MIT on was evaluated by measuring various endpoints (mortality, reproduction, body size, swimming behavior, and proteomic expression), and its trans- and multigenerational effects were investigated over four consecutive generations. The genotoxicity and epigenotoxicity of CMIT/MIT were examined using a comet assay and global DNA methylation measurements. The results show deleterious effects on various endpoints and differences in response patterns according to different exposure histories. Parental effects were transgenerational or recovered after exposure termination, while multigenerational exposure led to acclimatory/defensive responses. Changes in DNA damage were closely associated with altered reproduction in daphnids, but their possible relationship with global DNA methylation was not found. Overall, this study provides ecotoxicological information on CMIT/MIT relative to multifaceted endpoints and aids in understanding multigenerational phenomena under CMIT/MIT exposure. It also emphasizes the consideration of exposure duration and multigenerational observations in evaluating ecotoxicity and the risk management of isothiazolinone biocides.
5-氯-2-甲基异噻唑-3(2H)-酮与2-甲基异噻唑-3(2H)-酮的混合物（CMIT/MIT）是一种异噻唑啉酮类杀生剂，由于其在工业领域的广泛使用，在水生环境中一直能检测到。尽管人们担心其生态毒理学风险以及可能的多代暴露问题，但关于CMIT/MIT对人类健康和代内毒性的毒理学信息非常有限。此外，化学暴露引起的表观遗传标记可以代代相传，但这些变化在表型反应和跨代及多代效应毒性方面的作用却知之甚少。在本研究中，通过测量各种终点指标（死亡率、繁殖率、体型大小以及游泳行为和蛋白质组表达）评估了CMIT/MIT对[具体对象未给出]的毒性，并在连续四代中研究了其跨代和多代效应。使用彗星试验和全基因组DNA甲基化测量来检测CMIT/MIT的遗传毒性和表观遗传毒性。结果显示，根据不同的暴露历史，CMIT/MIT对各种终点指标有有害影响，且反应模式存在差异。亲代效应是跨代的，或者在暴露终止后恢复，而多代暴露则导致适应性/防御性反应。水蚤的DNA损伤变化与繁殖改变密切相关，但未发现它们与全基因组DNA甲基化之间可能存在的关系。总体而言，本研究提供了关于CMIT/MIT相对于多方面终点指标的生态毒理学信息，有助于理解CMIT/MIT暴露下的多代现象。它还强调了在评估异噻唑啉酮类杀生剂的生态毒性和风险管理时，要考虑暴露持续时间和多代观察。
