Chemical name: 6-methyl-4-{(E)-pyridin-3-ylmethylidene]amino}-4,5-dihydro-1,2,4-triazin-3(2H)-one Final regulatory action has been taken for the category: Pesticide Final regulatory action: The chemical is Banned Use or uses prohibited by the final regulatory action: All formulations and uses as a pesticide. Pymetrozin has never been used in Norway. The application for registration of the plant protection product Plenum 50 WG was for use Plenum is an insecticide against different pests in ornamentals, lettuce, cucumber and tomato in greenhouses and against pollen beetles in oilseed- and turnip rape. The final regulatory action was based on a risk or hazard evaluation: Yes Summary of the final regulatory action: The application for registration of the plant protection product Plenum 50 WG was rejected due to the lack of demonstration of a clear mechanism of action regarding the oncongenic effects seen in rats and mice, as well as the possible genotoxic effects and ionability to establish an AOEL for the metabolite CGA 300407. The reasons for the final regulatory action were relevant to: Human health Summary of known hazards and risks to human health: The Norwegian scientific committee for food safety (VKM) concluded with the following: exposure to pymetrozine resulted in increased incidences of liver tumours in female rats that were above the historical control data and in male and female mice. An increase in lung adenoma plus carcinoma was reported in female mice that were above the historical control data. Several arguments are presented to suggest that the tumors observed are not related to the exposure to pymetrozine. VKM has however not been convinced by these arguments, and have the opinion that it cannot be excluded that the observed tumors are relevant to human exposure. A central question is whether the tumors result from a non-genotoxic mechanism, considering that pymetrozine has not been shown to be genotoxic. A complicating finding is however that of a genotoxic metabolite, CGA 300407. The metabolite CGA 300407 gave positive response in vitro for chromosomal aberrations in CHO cells and human lymphocytes, and in vivo in a Comet assay in mouse forestomach. It is argued that the metabolite could be considered as a locally acting genotoxin in the forestomach, and thus not be involved in the formation of the liver tumors. However, the metabolite may also be formed by direct transformation of the mother substance in the liver. It is the opinion of VKM that it cannot be excluded that a genotoxic mechanism could be involved in the formation of the liver tumors, which would have implications for risk assessment. It should therefore be considered to test pymetrozine in more sensitive in vivo genotoxic endpoints in liver. The metabolite is found as residue in the plant metabolism studies. The notifier has submitted an exposure assessment, considering that this metabolite acts through a threshold process with the possibility to set an AOEL. The metabolite is however not sufficiently studied in vivo and a possible genotoxic effect cannot be ruled out. It is at the moment not possible to set an AOEL for this metabolite. A risk assessment for the metabolite CGA 300407 cannot be performed as it is not sufficiently studied and a possible in vivo genotoxic effect cannot be ruled out. Expected effect of the final regulatory action in relation to human health: Precautionary approach to protect human health. Date of entry into force of the final regulatory action: 01/10/2013 |