Modulation of Detoxification, Immune, and Epigenetic Systems by Two Aryl Organophosphorus Flame Retardants During Early Development in Zebrafish.

IF 4.1 3区环境科学与生态学 Q2 ENVIRONMENTAL SCIENCES

Toxics Pub Date : 2025-09-18 DOI:10.3390/toxics13090794

Montserrat Solé, Sílvia Joly, Sergi Omedes, Isabel Forner-Piquer, Laia Ribas

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Abstract

Organophosphorus flame retardants (OPFRs) are emerging alternatives to halogenated compounds, yet their environmental toxicity remains underexplored. This study evaluated the developmental toxicity of two aryl-OPFRs, triphenyl phosphate (TPP) and tricresyl phosphate (TCP), in zebrafish (Danio rerio) from 2 h to 5 days post fertilization (hpf-dpf). Survival, hatching rate, and malformations were assessed across concentrations of 250-1000 µg/L, alongside with gene expression analysis at 5 dpf (250 and 500 µg/L) targeting detoxification (ces2), immune responses (il1β, casp9), and epigenetic markers (dnmt1, dnmt3). In vitro enzymatic assays evaluated interactions of both aryl-OPFRs with carboxylesterase (CE) and acetylcholinesterase (AChE) enzymes. While no significant morphological effects were observed, TPP showed higher toxicity than TCP. Notably, TCP (500 µg/L) downregulated genes linked to metabolism and immunity. CE activity and ces2 modulation may suggest CE as a potential biomarker for aryl-OPFR exposure. These findings, although at concentrations above the environmental ones, may be valuable for mechanistic purposes and underscore the need for further investigation in developmental toxicity given their lipophilic nature and distinct molecular responses.

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两种芳基有机磷阻燃剂对斑马鱼早期发育过程中解毒、免疫和表观遗传系统的调节。

有机磷阻燃剂（OPFRs）是卤化化合物的新兴替代品，但其环境毒性仍未得到充分研究。本研究评估了两种芳基opfrs，磷酸三苯酯（TPP）和磷酸三烷基酯（TCP）在斑马鱼受精后2 h ~ 5 d （hpf-dpf）的发育毒性。在250-1000µg/L浓度下评估存活率、孵化率和畸形，同时分析5 dpf（250和500µg/L）下针对解毒（ces2）、免疫应答（il -1 β、casp9）和表观遗传标记（dnmt1、dnmt3）的基因表达。体外酶分析评估了这两种芳基opfrs与羧酸酯酶（CE）和乙酰胆碱酯酶（AChE）的相互作用。虽然没有观察到明显的形态学影响，但TPP的毒性高于TCP。值得注意的是，TCP（500µg/L）下调了与代谢和免疫相关的基因。CE活性和ces2调节可能表明CE是芳基- opfr暴露的潜在生物标志物。这些发现，虽然在浓度高于环境，可能是有价值的机制目的和强调需要进一步研究发育毒性的亲脂性和独特的分子反应。

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来源期刊

Toxics Chemical Engineering-Chemical Health and Safety

CiteScore

4.50

自引率

10.90%

发文量

681

审稿时长

6 weeks

期刊介绍： Toxics (ISSN 2305-6304) is an international, peer-reviewed, open access journal which provides an advanced forum for studies related to all aspects of toxic chemicals and materials. It publishes reviews, regular research papers, and short communications. Our aim is to encourage scientists to publish their experimental and theoretical results in detail. There is, therefore, no restriction on the maximum length of the papers, although authors should write their papers in a clear and concise way. The full experimental details must be provided so that the results can be reproduced. Electronic files or software regarding the full details of calculations and experimental procedure can be deposited as supplementary material, if it is not possible to publish them along with the text.