Assessment of mutagenic potential of puberulic acid contaminated in red yeast rice (beni-koji) health food supplements

In March 2024, a food poisoning incident in Japan was traced to red yeast rice (beni-koji) supplements contaminated with puberulic acid (PA), a mycotoxin produced by Penicillium adametzioides. Although PA was implicated in renal dysfunction in both humans and rats, its mutagenic potential had not been clarified. Here, we comprehensively assessed the mutagenicity of PA using a tiered approach that combined in silico, in vitro, and in vivo methods. In silico quantitative structure-activity relationship (QSAR) analyses predicted PA to be mutagenic, and in vitro Ames tests confirmed the positive finding. In contrast, in vivo assays, including the transgenic rodent gene mutation assay in mice and the Pig-a assay in rats, demonstrated no induction of mutations in kidney, glandular stomach and blood cells, even at high exposure levels. Collectively, these findings indicate that PA is mutagenic in vitro bacterial tests, but not in mammalian in vivo systems, suggesting that the overall concern for mutagenicity in humans is low.