VKM assessed the plant protection product Frupica SC with the active substance mepanipyrim in 2010. The Norwegian Food Safety Authority has asked the applicant for further testing of the metabolite M11 of mepanipyrim for genotoxicity. The applicant has now submitted a Comet assay of the metabolite and concluded that M11 should not be regarded to be genotoxic in vivo.

New information

The Norwegian Food Safety Authority has asked VKM to assess the result of a Comet assay of the metabolite M11 of mepanipyrim. VKM was also requested to consider if the question of genotoxic properties of metabolite M11 is adequately documented.

The metabolite M11 caused positive findings in in vitro studies for bacterial mutation and chromosomal aberrations. Three in vivo studies (Micronucleus, unscheduled DNA synthesis and Comet assay) did not show evidence of genotoxicity.

Based on the documentation available, VKM concludes that mepanipyrim and the metabolite M11 should not be considered genotoxic in vivo.

The lack of demonstrated in vivo genotoxicity makes it likely that mepanipyrim induces liver tumors in rats and mice by a mechanism that involves a threshold below which tumors are not expected to develop. This conclusion is strengthened by the finding of a promoter-like behavior of mepanipyrim for induction of gamma-glutamyl-transpeptidase positive foci in rat liver.

VKM’s Panel on Plant Protection Products has conducted the risk assessment.