Datta Sandipan, He Guochun, Tomilov Alexey, Sahdeo Sunil, Denison Michael S, Cortopassi Gino
Department of Molecular Bioscience, School of Veterinary Medicine, University of California , Davis, Davis, California, USA.
Department of Environmental Toxicology, University of California , Davis, Davis, California, USA.
Environ Health Perspect. 2017 Aug 22;125(8):087015. doi: 10.1289/EHP1404.
Quaternary ammonium salts (QUATS), such as cetylpyridinium chloride (CPC) and benzalkonium chloride (BAK), are frequently used in antiseptic formulations, including toothpastes, mouthwashes, lozenges, throat and nasal sprays, and as biocides. Although in a recent ruling, the U.S. Food and Drug Administration (FDA) banned CPC from certain products and requested more data on BAK's efficacy and safety profile, QUATS, in general, and CPC and BAK, in particular, continue to be used in personal health care, food, and pharmaceutical and cleaning industries.
We aimed to assess CPC's effects on mitochondrial toxicity and endocrine disruption .
Mitochondrial O consumption and adenosine triphosphate (ATP) synthesis rates of osteosarcoma cybrid cells were measured before and after CPC and BAK treatment. Antiestrogenic effects of the compounds were measured by a luciferase-based assay using recombinant human breast carcinoma cells (VM7Luc4E2, ERalpha-positive).
CPC inhibited both mitochondrial O consumption [half maximal inhibitory concentration (IC): 3.8μM] and ATP synthesis (IC: 0.9μM), and additional findings supported inhibition of mitochondrial complex 1 as the underlying mechanism for these effects. In addition, CPC showed concentration-dependent antiestrogenic activity half maximal effective concentration [(EC): 4.5μM)]. BAK, another antimicrobial QUATS that is structurally similar to CPC, and the pesticide rotenone, a known complex 1 inhibitor, also showed mitochondrial inhibitory and antiestrogenic effects. In all three cases, there was overlap of the antiestrogenic activity with the mitochondrial inhibitory activity.
Mitochondrial inhibition occurred at a CPC concentration that may be relevant to human exposures. The antiestrogenic activity of CPC, BAK, rotenone, and triclosan may be related to their mitochondrial inhibitory activity. Our findings support the need for additional research on the mitochondrial inhibitory and antiestrogenic effects of QUATS, including CPC and BAK. https://doi.org/10.1289/EHP1404.
季铵盐（QUATS），如西吡氯铵（CPC）和苯扎氯铵（BAK），常用于抗菌配方中，包括牙膏、漱口水、含片、咽喉和鼻腔喷雾剂，以及作为杀菌剂。尽管在最近的一项裁决中，美国食品药品监督管理局（FDA）禁止在某些产品中使用CPC，并要求提供更多关于BAK疗效和安全性的数据，但一般来说，季铵盐，特别是CPC和BAK，仍继续用于个人医疗保健、食品、制药和清洁行业。
我们旨在评估CPC对线粒体毒性和内分泌干扰的影响。
在CPC和BAK处理前后，测量骨肉瘤杂交细胞的线粒体氧消耗和三磷酸腺苷（ATP）合成速率。使用重组人乳腺癌细胞（VM7Luc4E2，雌激素受体α阳性），通过基于荧光素酶的测定法测量这些化合物的抗雌激素作用。
CPC抑制线粒体氧消耗[半数最大抑制浓度（IC）：3.8μM]和ATP合成（IC：0.9μM），其他研究结果支持线粒体复合物1的抑制是这些作用的潜在机制。此外，CPC显示出浓度依赖性的抗雌激素活性[半数最大有效浓度（EC）：4.5μM]。BAK是另一种与CPC结构相似的抗菌季铵盐，以及农药鱼藤酮（一种已知的复合物1抑制剂），也显示出线粒体抑制和抗雌激素作用。在所有三种情况下，抗雌激素活性与线粒体抑制活性存在重叠。
在可能与人体接触相关的CPC浓度下发生了线粒体抑制。CPC、BAK、鱼藤酮和三氯生的抗雌激素活性可能与其线粒体抑制活性有关。我们的研究结果支持有必要对包括CPC和BAK在内的季铵盐的线粒体抑制和抗雌激素作用进行更多研究。https://doi.org/10.1289/EHP1404
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