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Browsing by Author "Vasconcelos, Ana Luísa Teixeira Franco"

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  • Contribution to biomonitoring of a non-phthalate plasticizer: analysis of biomarkers of genotoxic effects of DINCH in human cells
    Publication . Vasconcelos, Ana Luísa Teixeira Franco; Dias, Deodália Maria Antunes; Louro, Henriqueta
    The human exposure to plasticizers is continuous, since their pervasiveness in a vast range of plastic consumer products (e.g. food packages, healthcare products and textiles). Their ability to migrate and leach to the environment or food was previously demonstrated, therefore, increasing the risk of exposure as well as the risk of potential adverse health outcomes, with a subsequent socioeconomical impact. During the last decades, the adverse health effects of phthalates (e.g. DEHP, DINP), which are the main group of plasticizers used by the industry, has been demonstrated namely the disruption of the male reproductive system development, and the onset of carcinogenesis in humans. So, their application in many consumer products was restricted or even prohibited, which lead to the development of greener alternative plasticizers; within this group, DINCH is the main alternant used to increase the flexibility and durability of polymeric matrices. Concomitantly, the detection of DINCH in human surroundings and in biological matrices has increased during the last decade. This prompt the establishment of biomonitoring guidance values for DINCH metabolites in urine, as a measure of precaution; however, the studies about potential adverse effects of DINCH in humans are still scarce. Given the broad applications and the increasing levels of human exposure, the aim of this study was to analyse the cytotoxicity and genotoxicity of DINCH in human liver (HepG2) and kidney (HK-2) cell lines. Accordingly, the assays used herein were the colorimetric MTT assay, to determine cell viabilities; the modified alkaline comet assay, to detect DNA damage and repair; and the micronucleus assay, to examine chromosomal permanent damages. The results showed that DINCH did not affect cell viabilities, however, was able to induce mild mitogenic effects in human renal cells. After a prolonged exposure, there were mild to moderate cytotoxic and cytostatic effects, in both cell lines. In human hepatic cells, the plasticizer caused transient oxidative DNA damaging effects, but did not cause primary DNA damage, in both cell lines, regardless the exposure periods. Concerning the chromosomal damage, DINCH and its metabolites did not increase the micronucleus levels in both cell lines, with and without metabolic activation. Other biomarkers of genotoxicity were significantly increased after exposure, without a dose-response effect. These results are in line with previous in vivo and in vitro studies, which concluded that DINCH is a non-genotoxic compound, but can induce cytotoxic effects after prolonged exposure. Furthermore, this work is a valuable contribute to the assessment risk of DINCH in humans, because it is the first genotoxic study, to the best of our knowledge, using human cell lines. Nonetheless, more studies are needed to confirm these results, as well as to further investigate the long-term effects of oxidative damage in human health, since the human exposure to DINCH is expected to increase in the future.
    2019Master thesis Restricted access Show more