In Vitro Assessment of Pesticides Toxicity and Data Correlation with Pesticides Physicochemical Properties for Prediction of Toxicity in Gastrointestinal and Skin Contact Exposure

• Tipo: Artigo em Revista Científica Internacional
• Data: 2022

Autores

Silva, AM (Autor) Outra; Martins-Gomes, C (Autor) Outra; Silva, TL (Autor) Outra; Coutinho, TE (Autor) Outra; Souto, EB (Autor) FFUP; Andreani, T (Autor) Outra

Revista

Título: Toxics

Vol. 10

Página Final: 378

Editora: MDPI

Indexação

ISI Web of Knowledge - 7 Citações

Scopus

Outras Informações

ID Authenticus: P-00X-0DZ

DOI: 10.3390/toxics10070378

Abstract (EN): In this work, three pesticides of different physicochemical properties, namely, glyphosate (herbicide), imidacloprid (insecticide) and imazalil (fungicide), were selected to assess their cytotoxicity against distinct cell models (Caco-2, HepG2, A431, HaCaT, SK-MEL-5 and RAW 264.7 cells) to mimic gastrointestinal and skin exposure with potential systemic effect. Cells were subjected to different concentrations of selected pesticides for 24 h or 48 h. Cell viability was assessed by Alamar Blue assay, morphological changes by bright-field microscopy and the IC50 values were calculated. Cytotoxic profiles were analysed using the physico-chemical parameters of the pesticides, namely: molecular weight, water solubility, the partition coefficient in the n-octanol/water (Log P-ow) system, the topological polar surface area (TPSA), and number of hydrogen-bonds (donor/acceptor) and rotatable bonds. Results showed that glyphosate did not reduce cell viability (up to 1 mM), imidacloprid induced moderate toxicity (IC50 > 1 mM for Caco-2 cells while IC50 = 305.9 +/- 22.4 mu M for RAW 264.7 cells) and imazalil was highly cytotoxic (IC50 > 253.5 +/- 3.37 for Caco-2 cells while IC50 = 31.3 +/- 2.7 mu M for RAW 264.7 cells) after 24 h exposure. Toxicity was time-dependent as IC50 values at 48 h exposure were lower, and decrease in cell viability was accompanied by changes in cell morphology. Pesticides toxicity was found to be directly proportional with their Log P-ow, indicating that the affinity to a lipophilic environment such as the cell membranes governs their toxicity. Toxicity is inverse to pesticides TPSA, but lower TPSA favours membrane permeation. The lower toxicity against Caco-2 cells was attributed to the physiology and metabolism of cell barriers equipped with various ABC transporters. In conclusion, physicochemical factors such as Log P-ow, TPSA and H-bond are likely to be directly correlated with pesticide-induced toxicity, thus being key factors to potentially predict the toxicity of other compounds.

Idioma: Inglês

Tipo (Avaliação Docente): Científica

Nº de páginas: 17