The purpose of this review is to evaluate the literature on the genotoxicity of
cumene (CAS # 98-82-8) and to assess the role of mutagenicity, if any, in the mode of action for
cumene-induced rodent
tumors. The studies reviewed included microbial mutagenicity, DNA damage/ repair, cytogenetic effects, and gene mutations. In reviewing these studies, attention was paid to their conformance to applicable OECD test guidelines which are considered as internationally recognized standards for performing these assays.
Cumene was not a bacterial
mutagen and did not induce
Hprt mutations in CHO cell cultures. In the primary rat hepatocyte cultures,
cumene induced unscheduled
DNA synthesis in one study but this response could not be reproduced in an independent study using a similar protocol. In a study that is not fully compliant to the current OECD guideline, no increase in
chromosomal aberrations was observed in CHO cells treated with
cumene. The weight of the evidence (WoE) from multiple in vivo studies indicates that
cumene is not a
clastogen or
aneugen. The weak positive response in an in vivo comet assay in the rat liver and mouse lung tissues is of questionable significance due to several study deficiencies. The genotoxicity profile of
cumene does not match that of a classic
DNA-reactive molecule and the available data does not support a conclusion that
cumene is an in vivo
mutagen. As such, mutagenicity does not appear to be an early key event in
cumene-induced rodent
tumors and alternate hypothesized non-mutagenic modes-of-action are presented. Further data are necessary to rule in or rule out a particular MoA.