Toxicity Assessment Of Glycofurol In Zebrafish And In Silico Admet Profiling
353 / 35
Keywords:
Glycofurol, embryotoxicity, zebrafish, In silico predictionAbstract
This study assessed glycofurol's embryo and adult toxicity in zebrafish, a solvent widely used in pharmaceuticals. Despite its common use, limited toxicity data exists in rodents, prompting the examination of acute toxicity in adult zebrafish and developmental toxicity in embryos. Following OECD guidelines 236 and 203, Fish Embryo Acute Toxicity (FET) and Fish Acute Toxicity Testing were conducted. Results showed concentration-dependent embryo mortality with LC50 based on the Probit method of analysis is 0.36%. The adverse effects in embryos like coagulation, lack of somite formation and various such changes were observed at 0.4% and above. Adult zebrafish exhibited no mortality or abnormal signs at the 0.2 ml/L concentration of glycofurol. Based on the results obtained, glycofurol is safe at concentration of 0.2% in zebrafish FET and 0.2 ml/L in adult zebrafish acute toxicity test. In silico prediction of pharmacokinetics and toxicity profiles showed that the glycofurol has favourable PK (pharmacokinetics) properties and no serious toxicities were predicted.
Downloads
References
Banerjee, P., Eckert, A. O., Schrey, A. K., and Preissner, R. (2018). ProTox-II: a webserver for the prediction of toxicity of chemicals. Nucleic Acids Res.,46(W1), W257–W263.
Benfenati, E., Manganaro, A., and Gini, G. C. (2013). VEGA-QSAR: AI inside a platform for predictive toxicology. PAI@ AI* IA, 1107, 21–28.
Boongird, A., Nasongkla, N., Hongeng, S., Sukdawong, N., Sa-Nguanruang, W., and Larbcharoensub, N. (2011). Biocompatibility study of glycofurol in rat brains. Exp. Biol. Med.,236(1), 77–83. https://doi.org/10.1258/ebm.2010.010219
Bury, R. W., Breen, K. J., Desmond, P. V., Raymond, K., and Mashford, M. L. (1984). Disposition of intravenous glycofurol: Effect of hepatic cirrhosis. Clin. Pharmacol. Thera., 36(1), 82–84. https://doi.org/10.1038/clpt.1984.143
Chan, P. K., Lin, C. C., and Cheng, S. H. (2009). Noninvasive technique for measurement of heartbeat regularity in zebrafish (Danio rerio) embryos. BMC Biotechnol.,9(1). https://doi.org/10.1186/1472-6750-9-11
Chemspider. (2024). Glycofurol (2-((tetrahydrofurfuryl)oxy)ethanol) CSID:99372. Chemspider. https://www.chemspider.com/Chemical-Structure.99372.html
Daina, A., Michielin, O., and Zoete, V. (2017). SwissADME: A free web tool to evaluate pharmacokinetics, drug-likeness and medicinal chemistry friendliness of small molecules. Sci. Rep., 7(1). https://doi.org/10.1038/srep42717
Gini, G., Franchi, A. M., Manganaro, A., Golbamaki, A., and Benfenati, E. (2014). ToxRead: A tool to assist in read across and its use to assess mutagenicity of chemicals. SAR QSAR Environ Res ., 25(12), 999–1011. https://doi.org/10.1080/1062936x.2014.976267
Ivaturi, V. D., Riss, J. R., Kriel, R. L., Siegel, R. A., and Cloyd, J. C. (2009). Bioavailability and tolerability of intranasal diazepam in healthy adult volunteers. J. Epilepsy Res., 84(2–3), 120–126. https://doi.org/10.1016/j.eplepsyres.2009.01.001
Martin, T. (2016). Toxicity Estimation Software Tool (TEST) US Environmental Protection Agency. Washington, DC, USA.
Organisation for Economic Co-operation and Development. (2013). Test guideline no. 236: Fish embryo acute toxicity (FET) test. OECD. http://dx.doi.org/10.1787/9789264203709-en
Organisation for Economic Co-operation and Development. (2019). Test guideline no. 203: Fish, acute toxicity test. OECD. http://dx.doi.org/10.1787/9789264069961-en
Patlewicz, G., Jeliazkova, N., Safford, R. J., Worth, A. P., and Aleksiev, B. (2008). An evaluation of the implementation of the Cramer classification scheme in the Toxtree software. SAR QSAR Environ Res ., 19(5–6), 495–524. https://doi.org/10.1080/10629360802083871
Xiong, G., Wu, Z., Yi, J., Fu, L., Yang, Z., Hsieh, C., Yin, M., Zeng, X., Wu, C., Lu, A., Chen, X., Hou, T., and Cao, D. (2021). ADMETlab 2.0: An integrated online platform for accurate and comprehensive predictions of ADMET properties. Nucleic Acids Res., 49(W1), W5–W14. https://doi.org/10.1093/nar/gkab255
Yang, H., Lou, C., Sun, L., Li, J., Cai, Y., Wang, Z., Li, W., Liu, G., and Tang, Y. (2018). admetSAR 2.0: Web-service for prediction and optimization of chemical ADMET properties. J. Bioinform., 35(6), 1067–1069. https://doi.org/10.1093/bioinformatics/bty707
Downloads
Submitted
Published
Versions
- 2025-12-27 (2)
- 2024-04-25 (1)