Induction of aneuploidy by the metal-chelating agent neodecanoid acid in mammalian cells in vitro.

Abstract

Neodecanoic acid (NDA) is an industrial chemical used in food packaging, considered a food contact material. To assess whether its use may pose concern for public health, this study was conducted to investigate in vitro the genotoxicity of NDA, previously identified as a gap-of-knowledge in toxicological risk assessment. No induction of gene mutations was observed in bacterial cells (Ames test) at concentrations ranging from 10 to 1000 µg/plate. Conversely, a statistically significant increase in the frequency of micronuclei was observed in Chinese Hamster Ovary cells, and confirmed in peripheral blood human lymphocytes, in a range from 100 to 500 µg/ml of NDA. An aneugenic mode of action was supported by evidence showing, in the same range of concentrations, a high frequency of chromosome loss in NDA-treated samples associated with mitotic spindle defects, such as multipolar mitotic spindles and cytoskeleton disruption. Study of nuclear lamina organization revealed irregular and deformed nuclei after NDA treatment. Furthermore, the metallomic analysis, performed at 200 and 400 µg/ml NDA, showed that NDA interfered with intracellular metal homeostasis, crucial for the dynamic morphology and mechanics of the cytoskeleton. In conclusion, this study provided evidence showing a thresholded genotoxic activity for NDA in vitro possibly resulting from its property of metal ion chelator affecting microtubule and microfilament network.