Sustainable Horizons Cover Article: Risk assessment of pyridaben exposure on neurodevelopment of offspring by using TRAEC strategy
Rapid industrialization has significantly increased chemical diversity and quantity, exacerbating environmental pollution. Pyridaben, as an efficient broad-spectrum acaricide, has been widely used in agriculture to prevent and control mites and to ensure the growth of fruits, vegetables and ornamental plants. However, extensive and prolonged use of pyridaben has resulted in extensive residues in soil, water, agricultural products, and even in human blood and urine, posing significant health risks. Fetal neurodevelopment is complex and highly sensitive, and is particularly susceptible to environmental chemicals during pregnancy. Studies have shown that exposure to pesticides during pregnancy may increase the risk of neurodegenerative diseases, ADHD and autism in offspring. Although neurotoxicity of pyridaben has been reported, studies on its developmental neurotoxicity in offspring remain limited, and current risk assessment methods have notable limitations. Therefore, it is essential to establish a systematic data integration and analysis approach to accurately evaluate the potential neurodevelopmental risks of pyridaben exposure in offspring.
On March 1, 2025, a research team led by Professors Xia Yankai and Shen Rong from Nanjing Medical University published a cover article entitled"Risk assessment of pyridaben exposure on neurodevelopment of offspring by using TRAEC strategy" in Sustainable Horizons. The study systematically assessed the neurodevelopmental risks associated with pyridaben exposure in offspring. Utilizing the Targeted Risk Assessment of Environmental Chemicals (TRAEC)strategy, the researchers integrated epidemiological, in vivo, and in vitro evidence, supplemented by additional experimental analyses, to elucidate the mechanisms underlying pyridaben-induced neurodevelopmental toxicity, thereby providing a critical scientific basis for pyridaben risk management.
The researchers comprehensively searched six authoritative databases, including PubMed and Web of Science, and identified epidemiological, in vivo, and in vitro evidence based on rigorous inclusion and exclusion criteria, supplemented by additional experimental validation. Epidemiological studies indicated that despite the declining trend of pyridaben exposure over recent years, its potential neurodevelopmental toxicity in children remains a significant concern, highlighting the risks associated with environmental exposure. In vivo studies demonstrated that pyridaben inhibited the expression of vitamin B6 metabolism-related genes (Pdxk and Gad1), reducing the concentrations of neurotransmitter GABA and pyridoxal 5’-phosphate (PLP), consequently inducing anxiety-like behavior in offspring mice. In vitro experiments revealed that pyridaben significantly inhibited viability and proliferation of mouse neuroepithelial cells (NE-4C), disrupted cell-cycle regulation, and markedly increased apoptosis. Moreover, pyridaben exposure altered the expression of neuronal and glial markers , as well as methyltransferase anddemethylase, suggesting potential epigenetic interference with chromatin structure and gene regulation, thereby impairing neural development.
The comprehensive evidence score calculated by the TRAEC online assessment tool was 5.64, indicating a moderate neurodevelopmental risk of pyridaben exposure in offspring. Results from existing toxicity evaluation tools aligned closely with those from the TRAEC approach, confirming their reliability and effectiveness in neurodevelopmental toxicity risk assessment. Compared to traditional evaluation methods, the TRAEC strategy demonstrated notable advantages in evidence comprehensiveness, ease of implementation, reliability evaluation, and balanced integration of multiple evidence types, thus presenting itself as a promising and sustainable framework for chemical risk assessment.
In summary, this study systematically assessed the neurodevelopmental risk of pyridaben exposure in offspring using the TRAEC strategy, integrating published evidence and supplementary experimental data, and confirmed a moderate risk level. Specifically, pyridaben exposure induced anxiety-like behaviors in offspring mice, significantly inhibited viability and proliferation of neuroepithelial cells, disrupted the cell cycle, increased apoptosis, and altered neuronal and glial marker expression, underscoring its potential neurodevelopmental hazards. Enhanced risk management strategies are therefore recommended to minimize pyridaben exposure among vulnerable groups, particularly pregnant women. Future research should involve large-scale epidemiological studies with larger cohorts and extended follow-up periods to further clarify the association between pyridaben exposure and offspring neurodevelopment. Additionally, the TRAEC strategy has established an open-access platform (https://traec.njmu.edu.cn/) to facilitate efficient integration and analysis of extensive evidence, advancing systematic and comprehensive environmental chemical risk assessment.
Original article link: https://www.sciencedirect.com/science/article/pii/S2772737825000057
SH｜南医大夏彦恺、沈嵘封面文章：应用TRAEC策略评估哒螨灵暴露对后代神经发育的风险
随着工业化的快速推进，化学物的种类和数量显著增加，环境化学污染问题日益突出。哒螨灵（Pyridaben）作为一种高效广谱杀螨剂，被广泛用于农业防治害螨、保障果蔬及观赏植物的生长。然而，哒螨灵的大量长期使用导致其在土壤、水体和农产品中广泛残留，甚至在人体血液、尿液中亦有检出，严重威胁人类健康。胎儿神经发育过程复杂且高度敏感，孕期尤其容易受环境化学物影响。已有研究表明，孕期接触农药可能增加后代罹患神经退行性疾病、多动症及自闭症的风险。尽管已有报道指出哒螨灵具备神经毒性，但目前关于其对后代神经发育毒性的研究仍较缺乏，现有风险评估方法亦存在明显局限性。因此，亟需建立一种系统的数据整合与分析方法，科学准确地评估哒螨灵暴露对后代神经发育的潜在风险。
2025年3月1日，南京医科大学夏彦恺教授、沈嵘教授团队在Sustainable Horizons上发表封面文章Risk assessment of pyridaben exposure on neurodevelopment of offspring by using TRAEC strategy，综合评估了哒螨灵暴露对后代神经发育的风险。研究基于环境化学物目标风险评估（Targeted Risk Assessment of Environmental Chemicals，TRAEC）策略框架，全面整合流行病学、体内和体外研究证据并开展系列补充实验，深入探究了哒螨灵神经发育毒性的机制，为哒螨灵的风险管理提供了重要科学依据。
研究全面检索了PubMed、Web of Science等六个权威数据库，依据严格的纳入和排除标准，最终获得了流行病学、体内和体外研究三类证据，并开展了系列补充实验。流行病学表明，虽然哒螨灵暴露逐年降低，但其对儿童神经发育的潜在毒性仍不可忽视，初步揭示了环境暴露风险。体内研究表明，哒螨灵可抑制维生素B6代谢相关基因（Pdxk、Gad1）的表达，降低神经递质GABA及吡哆醛5’-磷酸（PLP）的浓度，导致后代小鼠出现焦虑样行为。体外研究则显示，哒螨灵能显著抑制小鼠神经上皮细胞（NE-4C）的活力与增殖，使细胞周期发生紊乱，细胞凋亡显著增加。此外，哒螨灵暴露改变了神经元与神经胶质细胞标记物以及甲基转移酶和去甲基化酶的表达，提示其可能通过表观遗传修饰途径，干扰染色质结构和基因表达，进一步影响神经细胞的正常发育。
最终通过TRAEC策略的在线计算工具得出综合证据得分5.64，表明哒螨灵对后代神经发育存在中等风险。现有毒性评价工具的评估结果与TRAEC策略基本一致，充分验证了TRAEC策略在评估哒螨灵神经发育毒性风险方面的可靠性和有效性。相较其他毒性评价方法，TRAEC策略在证据收集完整性、易操作性、可靠性评价维度以及多证据均衡性上均具有较好表现，是一个可持续发展的新型化学物风险评价体系。
综上，本研究基于TRAEC策略，综合文献证据与补充实验数据，首次系统评估了哒螨灵暴露对后代神经发育的风险，明确其神经发育毒性处于中等风险水平。研究发现，哒螨灵暴露可引起后代小鼠出现焦虑样行为，显著抑制神经上皮细胞（NE-4C）的活力与增殖，干扰细胞周期并促进细胞凋亡，同时改变神经元和神经胶质细胞标记物的表达，提示其暴露对后代神经发育存在潜在风险。基于上述发现，应加强哒螨灵的风险管理，减少孕妇等高敏感人群的暴露。未来需进一步开展大规模流行病学研究，扩大队列规模和延长随访时间，更精准地明确哒螨灵暴露与后代神经发育之间的关联。此外，TRAEC策略已构建开放平台（https://traec.njmu.edu.cn/），有助于科研人员高效整合并分析海量证据，推动更系统深入地开展环境化学物风险评估。
原文链接：https://www.sciencedirect.com/science/article/pii/S2772737825000057