Profiling the endocrine disrupting properties of triazines, triazoles and short-chain PFAS.

IF 3.4 3区 医学 Q2 TOXICOLOGY Toxicological Sciences Pub Date : 2024-10-04 DOI:10.1093/toxsci/kfae131
Maxim P Carlier, Peter H Cenijn, Timur Baygildiev, Jenny Irwan, Sylvia E Escher, Majorie B M van Duursen, Timo Hamers
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Abstract

Persistent, mobile and toxic (PMT) compounds released to the environment are likely to pollute drinking water sources due to their slow environmental degradation (persistency) and high water solubility (mobility). The aim of the present study was to create in vitro hazard profiles for sixteen triazoles, nine triazines and eleven PFAS based on their agonistic and antagonistic effects in estrogen receptor (ER), androgen receptor (AR) and thyroid hormone receptor (TR) reporter gene assays, their ability to bind human transthyretin (TTR), and their effects on steroidogenesis. The triazole fungicides tetraconazole, bitertanol, fenbuconazole, tebuconazole, cyproconazole, difenoconazole, propiconazole, paclobutrazol and triadimenol had agonistic or antagonistic effects on the ER and AR. Difenoconazole, propiconazole and triadimenol were also found to be TR antagonists. The triazine herbicide ametryn was an ER, AR and TR antagonist. The same nine triazole fungicides and the triazines atrazine, deethyl-atrazine and ametryn affected the secretion of steroid hormones. Furthermore, PFAS compounds PFBS, PFHxS, PFHxA, PFOS, PFOA and GenX and the triazoles bitertanol, difenoconazole and 4-methyl benzotriazole were found to displace T4 from TTR. These results are in line with earlier in vitro and in vivo studies on the endocrine disrupting properties of triazines, triazoles and PFAS. The present study demonstrates that this battery of in vitro bioassays can be used to profile compounds from different classes based on their endocrine disrupting properties as a first step to prioritize them for further research, emission reduction, environmental remediation and regulatory purposes.

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分析三嗪类、三唑类和短链全氟辛烷磺酸的内分泌干扰特性。
释放到环境中的持久性、流动性和毒性(PMT)化合物由于其环境降解速度慢(持久性)和水溶性高(流动性),很可能会污染饮用水源。本研究的目的是根据 16 种三唑类化合物、9 种三嗪类化合物和 11 种全氟辛烷磺酸在雌激素受体(ER)、雄激素受体(AR)和甲状腺激素受体(TR)报告基因检测中的激动和拮抗作用、与人体转甲状腺素(TTR)结合的能力以及对类固醇生成的影响,建立它们的体外危害概况。三唑类杀菌剂四环唑、比特唑、芬布康唑、戊唑醇、环丙康唑、苯醚甲环唑、丙环唑、戊唑醇和三唑醇对ER和AR具有激动或拮抗作用。还发现二苯醚菌唑、丙环唑和三唑醇是 TR 拮抗剂。三嗪类除草剂莠去津是一种ER、AR和TR拮抗剂。同样的九种三唑类杀菌剂和三嗪类药物阿特拉津、脱乙基阿特拉津和莠去津也会影响类固醇激素的分泌。此外,还发现 PFAS 化合物 PFBS、PFHxS、PFHxA、PFOS、PFOA 和 GenX 以及三唑类化合物 bitertanol、difenoconazole 和 4-methyl benzotriazole 会取代 TTR 中的 T4。这些结果与早先对三嗪类、三唑类和全氟辛烷磺酸的内分泌干扰特性进行的体外和体内研究结果一致。本研究表明,这套体外生物测定方法可用于根据不同类别化合物的内分泌干扰特性对其进行剖析,作为进一步研究、减排、环境修复和监管的第一步。
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来源期刊
Toxicological Sciences
Toxicological Sciences 医学-毒理学
CiteScore
7.70
自引率
7.90%
发文量
118
审稿时长
1.5 months
期刊介绍: The mission of Toxicological Sciences, the official journal of the Society of Toxicology, is to publish a broad spectrum of impactful research in the field of toxicology. The primary focus of Toxicological Sciences is on original research articles. The journal also provides expert insight via contemporary and systematic reviews, as well as forum articles and editorial content that addresses important topics in the field. The scope of Toxicological Sciences is focused on a broad spectrum of impactful toxicological research that will advance the multidisciplinary field of toxicology ranging from basic research to model development and application, and decision making. Submissions will include diverse technologies and approaches including, but not limited to: bioinformatics and computational biology, biochemistry, exposure science, histopathology, mass spectrometry, molecular biology, population-based sciences, tissue and cell-based systems, and whole-animal studies. Integrative approaches that combine realistic exposure scenarios with impactful analyses that move the field forward are encouraged.
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