Impact of DINCH® in human cells: evaluation of its potential cytotoxic and genotoxic effects

Vasconcelos, Ana Luisa; Silva, Maria João; Louro, Henriqueta

http://hdl.handle.net/10400.18/5598

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Authors

Vasconcelos, Ana Luisa

Silva, Maria João

Louro, Henriqueta

Abstract(s)

The chemical Di-(iso-nonyl)-cyclohexane-1,2-dicarboxylate (DINCH) has been applied as a non-aromatic plasticizer and substitute for other phthalate plasticizers such as di-(2-ethylhexyl) phthalate (DEHP) and di-(iso-nonyl) phthalate (DINP), that have shown to have adverse effects. Since DINCH detected in indoor dust has increased after the market introduction of this plasticizer in 2002, the human exposure is a concern. Health-related guidance values have been derived for children and adults, namely 3 mg/L and 4.5 mg/L of DINCH metabolites in the urine, respectively. Recently, the exposure of Portuguese children to DINCH was reported, in spite the low levels detected in children’s urine, which were below the established health guidance levels. Conversely, few studies have addressed the potential toxicity of DINCH but in vivo studies suggest its bioavailability, leading to concerns in respect to systemic exposure or longer term consequences of its use, namely to liver or kidney cells. To contribute to the hazard characterization of DINCH, its potential cytotoxicity and genotoxicity was investigated in human liver cells, following the exposure of HepG2 cells to a range of concentrations of this chemical agent. The methodology included the MTT assay for cytoxicity determination, the comet assay for the detection of DNA damage and the micronucleus assay for determination of chromosomal damage, based on the OECD TG 487 guideline (2016). The results showed that concentrations ranging from 1 to 500 µg/mL were neither cytotoxic following 24h exposure of HepG2 cells, nor had impact on DNA or chromosome damage. Underway studies focus on the effects under the presence of exogenous liver metabolic enzymes (S9 fraction) and on the detection of oxidative DNA damage. Further ongoing investigation is addressing the potential nephrotoxic effects of DINCH using kidney cells.