Eawag, Swiss Federal Institute of Aquatic Science and Technology, 8600 Dübendorf, Switzerland.
Fraunhofer Institute for Molecular Biology and Applied Ecology IME, 57392 Schmallenberg, Germany.
Environ Sci Technol. 2020 Apr 7;54(7):4400-4408. doi: 10.1021/acs.est.9b07127. Epub 2020 Mar 11.
Biotransformation plays a crucial role in regulating the bioaccumulation potential and toxicity of organic compounds in organisms but is, in general, poorly understood for emerging contaminants. Here, we have used diclofenac as a model compound to study the impact of biotransformation on the bioaccumulation potential and toxicity in two keystone aquatic invertebrates: and . In both species, diclofenac was transformed into several oxidation products and conjugates, including two novel products, that is, diclofenac taurine conjugate (DCF-M403) and unexpected diclofenac methyl ester (DCF-M310.03). The ratios of biotransformation products to parent compound were 12-17 for DCF-M403 and 0.01-0.7 for DCF-M310.03 after 24 h exposure. Bioconcentration factors (BCFs) of diclofenac were 0.5 and 3.2 L kg in and , respectively, whereas BCFs of DCF-M310.03 was 164.5 and 104.7 L kg, respectively, representing a 25- to 110-fold increase. Acute toxicity of DCF-M310.03 was also higher than the parent compound in both species, which correlated well with the increased bioconcentration potential. The LC of diclofenac in was 216 mg L, while that of metabolite DCF-M310.03 was reduced to only 0.53 mg L, representing a 430-fold increase in acute toxicity compared to diclofenac. DCF-M403 is less toxic than its parent compound toward , which may be linked to its slightly lower hydrophobicity. Furthermore, the transformation of diclofenac to its methyl ester derivative was explored in crude invertebrate extracts spiked with an -adenosylmethionine cofactor, revealing possible catalysis by an -adenosylmethionine-dependent carboxylic acid methyltransferase. Methylation of diclofenac was further detected in fish hepatocytes and human urine, indicating a broader relevance. Therefore, potentially methylated metabolites of polar contaminants should be considered for a comprehensive risk assessment in the future.
生物转化在调节有机化合物在生物体中的生物积累潜力和毒性方面起着至关重要的作用，但对于新兴污染物而言，一般来说人们对此知之甚少。在这里，我们以双氯芬酸为模型化合物，研究了生物转化对两种关键水生无脊椎动物（和）生物积累潜力和毒性的影响。在这两个物种中，双氯芬酸被转化为几种氧化产物和轭合物，包括两种新产物，即双氯芬酸牛磺酸轭合物（DCF-M403）和意想不到的双氯芬酸甲酯（DCF-M310.03）。在 24 小时暴露后，DCF-M403 相对于母体化合物的生物转化产物与母体化合物的比例为 12-17，而 DCF-M310.03 的比例为 0.01-0.7。双氯芬酸在和中的生物浓缩因子（BCF）分别为 0.5 和 3.2 L kg，而 DCF-M310.03 的 BCF 分别为 164.5 和 104.7 L kg，分别增加了 25-110 倍。在这两个物种中，DCF-M310.03 的急性毒性也高于母体化合物，这与增加的生物浓缩潜力密切相关。在中，双氯芬酸的 LC 为 216 mg L，而代谢物 DCF-M310.03 的 LC 仅降低至 0.53 mg L，与双氯芬酸相比，急性毒性增加了 430 倍。与母体化合物相比，DCF-M403 对毒性较低，这可能与其略低的疏水性有关。此外，在添加 -腺苷甲硫氨酸辅因子的无脊椎动物粗提取物中探索了双氯芬酸向其甲酯衍生物的转化，表明可能由 -腺苷甲硫氨酸依赖性羧酸甲酯转移酶催化。在鱼肝细胞和人尿中进一步检测到双氯芬酸的甲基化，表明其具有更广泛的相关性。因此，在未来的全面风险评估中，应考虑极性污染物的潜在甲基化代谢物。
