Chlorfenapyr, a pyrrole insecticide that impairs mitochondrial activity[1]. Oxidative removal of the N-ethoxymethyl group of Chlorfenapyr by mixed function oxidases results in a toxic form known as CL 303268 that acts to uncouple oxidative phosphorylation in the mitochondria, leading to a disruption of ATP production and loss of energy leading to cell dysfunction and ultimately death of the organism[2]. Commercial applications of Chlorfenapyr include termite control and protection of crops from multiple insect and mite pests[3]. Chlorfenapyr has moderate oral toxicity (LD50 = 662mg/kg bw for mouse by mouth) and low transdermal toxicity in mammals (LD50 > 2000mg/kg bw for rabbit by skin)[4].
In vitro, Chlorfenapyr treatment for 24h can inhibit the viability of human A549 and L02 cells, with IC50 values of 83.14μg/mL for A549 cells and 84.42μg/mL for L02 cells[5]. Treatment with 10ng/ml Chlorfenapyr for 24 hours induced cell death in HepG2 cells, decreased the levels of SOD1 and GSH, and enhanced oxidative stress[6]. At a concentration of 4.08μM, Chlorfenapyr treatment for 24 hours led to chromosomal aberrations in CHOK1 cells, and significantly increased the frequency of micronuclei[7].
In vivo, exposure to 10μg/L Chlorfenapyr for 21 days caused zebrafish liver and brain oxidative damage, disturbing the metabolism profiles [8].
References:
[1] Yunta C, Ooi J M F, Oladepo F, et al. Chlorfenapyr metabolism by mosquito P450s associated with pyrethroid resistance identifies potential activation markers[J]. Scientific Reports, 2023, 13(1): 14124.
[2] Raghavendra K, Barik T K, Sharma P, et al. Chlorfenapyr: a new insecticide with novel mode of action can control pyrethroid resistant malaria vectors[J]. Malaria journal, 2011, 10(1): 16.
[3] Baek B H, Kim S K, Yoon W, et al. Chlorfenapyr-induced toxic leukoencephalopathy with radiologic reversibility: a case report and literature review[J]. Korean journal of radiology, 2016, 17(2): 277-280.
[4] Huang P, Yan X, Yu B, et al. A comprehensive review of the current knowledge of chlorfenapyr: synthesis, mode of action, resistance, and environmental toxicology[J]. Molecules, 2023, 28(22): 7673.
[5] Wang L, Qu Z, Xu Y, et al. Insecticide chlorfenapyr confers induced toxicity in human cells through mitochondria-dependent pathways of apoptosis[J]. Ecotoxicology and Environmental Safety, 2025, 289: 117502.
[6] Elalfy M, Abomosallam M S, Sleem F R, et al. The Cytotoxic Combined Effects of Mixtures of Copper Oxychloride and Chlorfenapyr in HepG2 Cells and Postnatal Model of Toxicity in Female Sprague Dawleyrats and its Pups[J]. International Journal of Zoology and Animal Biology, 2020, 3(3): 1-10.
[7] Al-Sarar A S, Abobakr Y, Bayoumi A E, et al. Cytotoxic and genotoxic effects of abamectin, chlorfenapyr, and imidacloprid on CHOK1 cells[J]. Environmental Science and Pollution Research, 2015, 22(21): 17041-17052.
[8] Chen X, Zheng J, Teng M, et al. Bioaccumulation, metabolism and the toxic effects of chlorfenapyr in zebrafish (Danio rerio)[J]. Journal of Agricultural and Food Chemistry, 2021, 69(29): 8110-8119.
Chlorfenapyr是一种吡咯类杀虫剂，可通过破坏线粒体功能发挥作用。Chlorfenapyr的N-乙氧甲基基团经混合功能氧化酶氧化脱除后，生成的代谢产物CL 303268能够解耦线粒体中的氧化磷酸化过程，导致ATP合成中断、能量耗竭，进而引发细胞功能障碍直至机体死亡[2]。Chlorfenapyr广泛应用于白蚁防治及作物害虫螨治理[3]。毒理学数据显示，Chlorfenapyr对哺乳动物具有中度经口毒性（小鼠经口LD50 = 662 mg/kg）和低经皮毒性（家兔经皮肤LD50 > 2000 mg/kg）[4]。
在体外，Chlorfenapyr处理24小时可抑制人A549和L02细胞活力，IC50值分别为83.14μg/mL和84.42μg/mL[5]。10ng/ml浓度的Chlorfenapyr处理24小时会诱导HepG2细胞死亡，降低SOD1和GSH水平并增强氧化应激[6]。4.08μM浓度的Chlorfenapyr处理24小时可导致CHOK1细胞发生染色体畸变及微核率升高[7]。
在体内，10μg/L浓度的Chlorfenapyr暴露21天可引起斑马鱼肝脏和脑部氧化损伤，并扰乱代谢谱[8]。