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Teratogenicity of retinoids detected in surface waters in zebrafish embryos and its predictability by in vitro assays
Aquatic Toxicology ( IF 4.1 ) Pub Date : 2022-03-27 , DOI: 10.1016/j.aquatox.2022.106151
Marek Pípal 1 , Jiří Novák 1 , Aneta Rafajová 1 , Marie Smutná 1 , Klára Hilscherová 1
Affiliation  

Retinoids are newly detected compounds in aquatic ecosystems associated with cyanobacterial water blooms. Their potential health risks are only scarcely described despite numerous detections of all-trans retinoic acid (ATRA) and its derivatives in the environment. Besides the known teratogen ATRA there is only little or no information about their potency and namely their effects in vivo. We characterize ATRA and 8 other retinoids reported to occur in the environment for their bioactivity and teratogenicity using four in vitro reporter gene assays and zebrafish (Danio rerio) embryotoxicity assay. Our results document the ability of these compounds to interfere with retinoid signalling and cause teratogenicity at environmentally relevant levels with EC50 values at nM (hundreds of ng/L) levels and teratogenic indexes ranging from 2.8 (9cis retinoic acid) to 15.8 (retinal). The relative potency of individual compounds for teratogenicity ranged from 0.059 (retinal) to 0.96 (5,6-epoxy ATRA) when compared to ATRA. An environmentally relevant mixture of retinoids was tested showing good predictability of teratogenicity from the in vitro activities and additive toxicity of the mixture. The high teratogenicity of the newly described compounds associated with cyanobacteria presents a concern for developmental stages due to high conservation of the retinoid signalling across vertebrates.



中文翻译:

在斑马鱼胚胎地表水中检测到的类视黄醇的致畸性及其体外测定的可预测性

维甲酸是水生生态系统中新发现的与蓝藻水华相关的化合物。尽管在环境中检测到大量全反式维甲酸 (ATRA) 及其衍生物,但它们的潜在健康风险却很少被描述。除了已知的致畸剂 ATRA 外,关于它们的效力和体内作用的信息很少或没有。我们使用四种体外报告基因分析和斑马鱼 ( Danio rerio) 胚胎毒性试验。我们的结果记录了这些化合物在环境相关水平上干扰类视黄醇信号传导并导致致畸性的能力,EC 50值在 nM(数百 ng/L)水平,致畸指数从 2.8(9顺式视黄酸)到 15.8(视黄醛) )。与 ATRA 相比,单个化合物的致畸性相对效力范围为 0.059(视网膜)至 0.96(5,6-环氧 ATRA)。测试了与环境相关的类视黄醇混合物,显示出良好的体外致畸性可预测性混合物的活性和添加剂毒性。新描述的与蓝藻相关的化合物的高致畸性引起了对发育阶段的关注,因为脊椎动物的类视黄醇信号传导高度保守。

更新日期:2022-03-27
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