Zhang Furong, Liu Ruifang, Lou Jianwei, Song Fuyong
Department of Toxicology, School of Public Health, Cheeloo College of Medicine, Shandong University, 44 Wenhuaxi Road, Jinan, Shandong, 250012, People's Republic of China.
Department of Neurology, Qilu Hospital of Shandong University, No. 107 Wenhuaxi Road, Jinan, Shandong, 250012, People's Republic of China.
Arch Toxicol. 2025 Sep 13. doi: 10.1007/s00204-025-04184-z.
Organophosphate flame retardants (OPFRs), widely used as primary alternatives to banned brominated flame retardants, have been extensively applied across various industries worldwide. In recent years, OPFRs have increasingly emerged as significant environmental pollutants and have been shown to possess potential developmental neurotoxicity. This review systematically synthesizes current research on their environmental distribution, bioaccumulation, and neurodevelopmental effects. Studies indicate OPFRs are widely detected in air, water, soil, and organisms, demonstrating high environmental persistence and mobility. Humans are exposed through inhalation, ingestion, and dermal absorption, with infants and young children at higher risk due to frequent hand-to-mouth behavior and prolonged indoor exposure. Epidemiological studies suggest that prenatal exposure to OPFRs may be associated with low birth weight, behavioral abnormalities, and cognitive deficits, with evidence of sex-specific susceptibility. Experimental studies using model organisms, such as zebrafish and rodents, have further elucidated the potential mechanisms underlying OPFR-induced developmental neurotoxicity. Chemicals such as TDCPP, TPhP, and TCEP have been found to disrupt neural cell proliferation and differentiation, dysregulate gene expression, induce neuroinflammation, increase oxidative stress, and impair endocrine homeostasis. Despite significant progress in understanding the toxicity of OPFRs, critical scientific challenges remain unresolved. For example, the long-term effects of low-dose OPFR exposure on the nervous system are not yet fully understood. Furthermore, there is a lack of systematic analysis regarding the combined effects of multiple pollutants. Therefore, a deeper understanding of the toxicological mechanisms of OPFRs is essential to provide a stronger scientific foundation for the formulation of evidence-based environmental and public health policies.
有机磷酸酯阻燃剂(OPFRs)作为被禁用的溴化阻燃剂的主要替代品被广泛使用,已在全球各个行业中广泛应用。近年来,OPFRs日益成为重要的环境污染物,并已被证明具有潜在的发育神经毒性。本综述系统地综合了目前关于其环境分布、生物累积和神经发育影响的研究。研究表明,OPFRs在空气、水、土壤和生物体中广泛被检测到,显示出高环境持久性和流动性。人类通过吸入、摄入和皮肤吸收接触OPFRs,由于婴幼儿频繁的手口行为和长时间的室内接触,他们面临的风险更高。流行病学研究表明,产前接触OPFRs可能与低出生体重、行为异常和认知缺陷有关,并有性别特异性易感性的证据。使用斑马鱼和啮齿动物等模式生物的实验研究进一步阐明了OPFRs诱导发育神经毒性的潜在机制。已发现诸如TDCPP、TPhP和TCEP等化学物质会破坏神经细胞增殖和分化、调节基因表达失调、诱导神经炎症、增加氧化应激并损害内分泌稳态。尽管在理解OPFRs的毒性方面取得了重大进展,但关键的科学挑战仍未得到解决。例如,低剂量OPFRs暴露对神经系统的长期影响尚未完全了解。此外,对于多种污染物的联合影响缺乏系统分析。因此,更深入地了解OPFRs的毒理学机制对于为制定基于证据的环境和公共卫生政策提供更坚实的科学基础至关重要。