Comparative toxicity analysis of corannulene and benzo[a]pyrene in mice

•COR and BaP are metabolized by hepatic Cyp1a isozymes•COR and BaP alter intestinal microbiota•COR is a weak inducer of aryl hydrocarbon receptor•COR has less toxicological effect than BaP in mice Increasing production of corannulene (COR), a non-planar polycyclic aromatic hydrocarbon (PAH) with promising applications in many fields, has raised a concern about its potential toxic effects. However, no study has been undertaken to evaluate its metabolism and toxicity in mammals. In this study, the acute toxicities of COR in mice were compared with benzo[apyrene (BaP), a typical planar PAH with almost the same molecular weight. After 3-day exposures, the concentrations of COR in both plasma and tissues of mice were higher than that of BaP. However, blood chemistry and tissue weight monitoring showed no observable toxicities in COR-exposed mice. Compared to BaP, exposure to COR resulted in less activation of the aryl hydrocarbon receptor (AhR) and thus less induction of hepatic cytochrome P450 1A(CYP1A) enzymes, which play a critical role in metabolism of both COR and BaP. Additionally, COR also elicited less oxidative stress and microbiota alteration in the intestine than did BaP. RNA-seq analysis revealed that liver transcriptomes are responsive to COR and BaP, with less alterations observed in COR-exposed mice. Unlike BaP, exposure to COR had no effects on hepatic lipid and xenobiotic metabolism pathways. Nonetheless, COR appeared to alter the mRNA expressions of genes involved in carcinogenicity, oxidative stress, and immune-suppression. To conclude, this study for the first time unveils a comparative understanding of the acute toxic effects of COR to BaP in mice, and provides crucial insights into the future safety assessment of COR.