Genotoxic Assessment of the Metabolite M-11 of Mepanipyrim, the Active Ingredient in the Plant Protection Product FRUPICA SC
Hubert Dirven *
Norwegian Scientific Committee for Food Safety (VKM), Norwegian Institute of Public Health (FHI), Norway.
Jan Ludvig Lyche
Norwegian Scientific Committee for Food Safety (VKM), Norwegian University of Life Sciences, Norway.
Marit Låg
Norwegian Scientific Committee for Food Safety (VKM), University of Oslo, Norwegian Institute of Public Health (FHI), Norway.
Asbjørn Magne Nilsen
Norwegian Scientific Committee for Food Safety (VKM), Norwegian University of Science and Technology, Norway.
Katrine Borgå
Norwegian Scientific Committee for Food Safety (VKM), University of Oslo, Norwegian Institute for Water Research, Norway.
Ole Martin Eklo
Norwegian Scientific Committee for Food Safety (VKM), Norwegian University of Life Sciences, Norwegian Institute for Bioeconomy Research, Norway.
Merete Grung
Norwegian Scientific Committee for Food Safety (VKM), Norwegian Institute for Water Research, Norway.
Line Emilie Sverdrup
Norwegian Scientific Committee for Food Safety (VKM), University of Oslo, Det Norske Veritas, Norway.
Torsten Källqvist
Norwegian Scientific Committee for Food Safety (VKM), Norway.
*Author to whom correspondence should be addressed.
Abstract
The VKM Panel for plant protection products considered Frupica SC in a meeting on 25.11.2010, and found the active ingredient problematic with regard to carcinogenic effects and possible genotoxicity. M11 is a metabolite of mepanipyrim which is the active ingredient the plant protection product Frupica SC. The Norwegian Food Safety Authority has asked the applicant for further assessment of the genotoxic potential of the metabolite M11. The applicant has submitted a rat liver in vivo Comet assay of the metabolite, and the panel has been requested to consider if the genotoxic properties of mepanipyrim and the 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, VKMs Panel on Plant Protection Products 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.
Keywords: VKM, risk assessment, Norwegian Scientific Committee for Food Safety, Frupica SC, mepanipyrim, metabolite M11, genotoxicity.