In silico study by using ProTox-II webserver for oral acute toxicity, organ toxicity, immunotoxicity, genetic toxicity endpoints, nuclear receptor signalling and stress response pathways of synthetic pyrethroids
Till date, it is well-known that synthetic pyrethroids are safe to mammal but toxic to non-mammals. The present objective was an in silico study to detect oral acute toxicity, organ toxicity, immunotoxicity, genetic toxicity endpoints, nuclear receptor signalling, and stress response pathways of common synthetic pyrethroids by using ProTox-II webserver. The chemical compounds especially different synthetic pyrethroids such as pyrethrin I, Cinerin I and Jasmolin I (esters of Chrysanthemic acid), Pyrethrin-II, Cinerin II and Jasmolin II (Esters of Pyrethric acid), type I pyrethroids (esters without alpha-cyano group) such as allethrin, resmethrin, permethrin and bifenthrin and type II pyrethroids (esters with alpha-cyano group) such as fenvalerate, cyhalothrin, cypermethrin and deltamethrinwere selected from available literature. ProTox-II webserver was used for toxicological assessment in organism, organs, cell and gene level along with molecular mechanisms of toxicity. The predictive results for the toxicity of common synthetic pyrethroids compounds, Deltamethrin showed highly toxic compound among 14 compounds as fatal if swallowed as class II followed by Cypermethrin, Cyhalothrin, Bifenthrin, Resmethrin, Fenvalerate and Permethrin but hepatotoxic potential was only Deltamethrin and Fenvalerate while immunotoxic was obtained Permethrin. On the other hand, none of the compounds were obtained cytotoxic and carcinogenic but 9 compounds viz. Pyrethrin I, II Cinerin I, II, Jasmolin I, II, Allethrin, Resmethrin and Permethrin were observed mutagenic active. In case of NR signalling pathways, all compounds were inactive but eight compounds such as Pyrethrin I, II, Cinerin I, II, Jasmolin I, II, Allethrin and Resmethrin were obtained nrf2/ARE and HSE active while MMP active compounds were obtained Fenvalerate, Cyhalothrin and Deltamethrin respectively. For p53 and ATAD5 parameters, all fourteen compounds such as were obtained inactive. In conclusion, the present predictive results are suitable for academician, researchers, industries, etc. those who are making drugs and environmental chemicals. This web server helps faster screening of large numbers of compounds within short duration and no animal testing. This present in silico study easily detects toxin(s), which can be validated in future through in vitro and in vivo experimental assay.
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Financed by the National Centre for Research and Development under grant No. SP/I/1/77065/10 by the strategic scientific research and experimental development program:
SYNAT - “Interdisciplinary System for Interactive Scientific and Scientific-Technical Information”.