Laboratory of Transcriptional Regulation, Institute of Medical Biology PAS, Lodz, Poland; Bio-Med-Chem Doctoral School of the University of Lodz and Lodz Institutes of the Polish Academy of Sciences, Lodz, Poland.
Laboratory of Transcriptional Regulation, Institute of Medical Biology PAS, Lodz, Poland; Department of Biochemistry and Molecular Biology, Federal University of São Paulo, São Paulo, Brazil.
Sci Total Environ. 2023 Nov 1;897:165272. doi: 10.1016/j.scitotenv.2023.165272. Epub 2023 Jul 3.
Flame retardants (FRs) are chemical substances used to inhibit the spread of fire in numerous industrial applications, and their abundance in modern manufactured products in the indoor and outdoor environment leads to extensive direct and food chain exposure of humans. Although once considered relatively non-toxic, FRs are demonstrated by recent literature to have disruptive effects on many biological processes, including signaling pathways, genome stability, reproduction, and immune system function. This review provides a summary of research investigating the impact of major groups of FRs, including halogenated and organophosphorus FRs, on animals and humans in vitro and/or in vivo. We put in focus those studies that explained or referenced the modes of FR action at the level of cells, tissues and organs. Since FRs are highly hydrophobic chemicals, their biophysical and biochemical modes of action usually involve lipophilic interactions, e.g. with biological membranes or elements of signaling pathways. We present selected toxicological information about these molecular actions to show how they can lead to damaging membrane integrity, damaging DNA and compromising its repair, changing gene expression, and cell cycle as well as accelerating cell death. Moreover, we indicate how this translates to deleterious bioactivity of FRs at the physiological level, with disruption of hormonal action, dysregulation of metabolism, adverse effects on male and female reproduction as well as alteration of normal pattern of immunity. Concentrating on these subjects, we make clear both the advances in knowledge in recent years and the remaining gaps in our understanding, especially at the mechanistic level.
阻燃剂（FRs）是用于抑制许多工业应用中火灾蔓延的化学物质，它们在室内和室外环境中现代制造产品中的丰富存在导致了人类广泛的直接和食物链暴露。尽管曾经被认为相对无毒，但最近的文献表明，FRs 对许多生物过程具有干扰作用，包括信号通路、基因组稳定性、生殖和免疫系统功能。
本综述总结了研究主要 FRs 组，包括卤代和有机磷 FRs，对动物和人类的体外和/或体内影响的研究。我们重点介绍了那些解释或参考 FR 作用模式的研究，这些模式在细胞、组织和器官水平上。由于 FRs 是高度疏水性化学物质，它们的生物物理和生化作用模式通常涉及亲脂相互作用，例如与生物膜或信号通路的元素相互作用。我们介绍了这些分子作用的一些毒理学信息，以显示它们如何导致破坏膜完整性、破坏 DNA 及其修复、改变基因表达和细胞周期以及加速细胞死亡。
此外，我们还指出了这如何在生理水平上转化为 FRs 的有害生物活性，包括激素作用的中断、代谢的失调、对男性和女性生殖的不利影响以及正常免疫模式的改变。
我们专注于这些主题，明确了近年来知识的进步和我们理解上的剩余差距，特别是在机制水平上。
