One of the regulatory toxicology assays used to assess the genotoxic potential of ENDS products is the in vitro micronucleus (ivtMN) test. The hazard assessment of aerosol generated from various E-Liquids was assessed by in vitro genotoxicity testing. None of the test articles were mutagenic in Ames assay. The ivtMN assay was conducted according to OECD guidelines Test No. 487 in human lymphoblast TK6 cells. Three E-Liquid test articles induced a weak but statistically significant increase in micronuclei, suggesting positive or equivocal result. According to ICH guidance S2 (R1), to determine the biological relevance of ivtMN results, a follow-up in vivo micronucleus (ivoMN) test should be conducted. Following OECD Guidelines Test No. 474 male Crl:CD(SD) rats were exposed nose-only to a Limit dose of 5 mg/L aerosol for 4 hours per day for three consecutive days. Negative and positive control groups were included. The aerosol chemistry confirmed that the aerosol mass concentration and for rats. There was no evidence of bone marrow cytotoxicity for the test article-treated groups. There were no statistically significant increases in micronucleated polychromatic erythrocytes for any of the test article- treated groups compared to control group. Therefore, under the tested in vivo condition, the tested E-Liquids were negative for genotoxicity, implying no biological relevance of the weak in vitro genotoxicity results. In summary, the absence of mutagenicity in Ames test and negative for genotoxicity in the in vivo MN assays demonstrated absence of significant genotoxic risk for E-Liquids.