Contribution to hazard characterization of the Next-Generation Plasticizer DINCH®: cytotoxicity and genotoxicity assessment in human cells

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

http://hdl.handle.net/10400.18/6768

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Authors

Vasconcelos, Ana Luísa

Silva, Maria João

Louro, Henriqueta

Abstract(s)

The chemical diisononyl cyclohexane-1,2-dicarboxylate (Hexamoll® DINCH®), a cyclohexanoate plasticizer, has been employed as a safer alternative to restricted phthalates, to increase flexibility and elasticity of many consumer products made of PVC or polystyrene, namely food packaging, children’s toys, and medical devices. 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. DINCH is not classified as reprotoxic nor genotoxic and mutagenic however, there are limited data available regarding safety assessment, especially regarding cytotoxic and genotoxic effects. Since liver and kidney are DINCH target organs in animal models, the aim of this study was to assess DINCH cytotoxic and genotoxic effects in a human liver (HepG2) and kidney cell lines (HK-2). The methodology included the MTT cell viability, micronucleus, conventional and FPG-modified comet assays to detect cytotoxicity and genotoxicity. The results showed that DINCH was moderately cytotoxic for kidney cells exposed for 48h, but not for liver cells. No chromosomal damage was induced after short-term or longer exposures of both cell lines. However, DINCH was able to induce oxidative DNA damage in liver cells exposed for 3h, which decreased after a more prolonged exposure. The occurrence of oxidative lesions, even transiently, implies that mutation fixation may occur leading to adverse effects in liver. Overall, the present work provides new insights into the potential toxicity of this next-generation plasticizer in kidney and liver cells, in spite of public reports in which DINCH is classified as non-genotoxic agent. On the other hand, human biomonitoring studies are fundamental to confirm the current levels of human internal exposure to DINCH, as well as to detect early biologic effects.