Mouse micronucleus assay as a surrogate to assess genotoxic potential of arsenic at its human reference dose

Exposure to high contents of arsenic (a genotoxic carcinogen) in humans through drinking water is one of the most serious concerns in many parts of the world including India. The United States Environmental Protection Agency (USEPA) has recommended a permissible limit of daily exposure in humans to arsenic as its reference dose (0.3 μg kg(-1) d(-1)) with almost no likelihood of any adverse effect. The present work was a quantitative assessment of the genotoxic potential of arsenic at the exposure level of its human reference dose through micronucleus (MN) assay in mice. The animals were exposed to various doses of arsenic through oral gavaging for 15 consecutive days. Significant increases in the frequency of micronucleated erythrocytes were observed in mice upon exposure to arsenic which occurred even at its human reference dose and in a dose-dependent manner. The study of the genotoxic potential of arsenic in humans at lower exposure levels (including its human reference dose) is, therefore, highly desirable for risk assessment and hazard identification.