The metaplastic effects of NMDA receptors blockade on reactivation of instrumental memories in rats.

Metaplasticity, defined as the plasticity of synaptic plasticity, could affect learning and memory at different neural levels. It was hypothesized that metaplasticity changes on glutamate receptors may affect memory destabilization, promoting or preventing reconsolidation. We investigated the metaplastic effect of NMDA channel blocker MK-801 on sucrose instrumental memory reconsolidation in a behavioural rat model associated to the assessment of molecular markers of metaplasticity, memory retrieval, destabilization and reconsolidation. Following instrumental conditioning and forced abstinence, rats were intraperitoneally treated with MK-801 or vehicle 24 h before the exposure to memory retrieval or not-retrieval. Separate groups were tested for in-vivo extinction of responding (24 h and 7 d after reactivation) or ex-vivo assessment of transcription factor Zif268 and ribosomal protein rpS6 phosphorylation in nucleus accumbens (NAc) and amygdala (Amy). MK-801 significantly inhibited instrumental responding at extinction test, suggesting reconsolidation blockade of instrumental memory. The decrease of Zif268 and phosphorylated-rpS6 levels in NAc and Amy in MK-801/Retrieval vs. Vehicle/Retrieval group supported the behavioural findings. An increase of GluN2B, GluA1 and mGluR5 in NAc, and GluN2B in Amy, 24 h after MK-801 indicated the trigger of associated metaplastic changes. Our findings show that metaplastic changes induced by NMDA receptors blockade affected sucrose instrumental memory retrieval as shown by both behavioural and molecular changes. We hypothesize that these findings however suggested a switch to extinction rather than a reconsolidation.

The modulation of BDNF expression and signalling dissects the antidepressant from the reinforcing properties of ketamine: Effects of single infusion vs. chronic self-administration in rats.

Ketamine is a drug of abuse with a unique profile, which besides its inherent mechanism of action as a non-competitive antagonist of the NMDA glutamate receptor, displays both antidepressant and reinforcing properties. The major aim of our study was to find a molecular signature of ketamine that may help in discriminating between its reinforcing and antidepressant effects. To this end, we focused our attention on BDNF, a neurotrophin that has been shown to play a role in both antidepressant and reinforcing properties of several drugs. Rats were exposed to self-administer intravenous (IV) ketamine (S/A) for 43 days or to receive a single IV ketamine 0.5mg/kg, or vehicle infusion. Although the dose we employed is lower than that reported by the literature, it however yields Cmax values that correspond to those achieved in humans after antidepressant treatment. Our results show that while the single infusion of ketamine increased the neurotrophin expression in the hippocampus while reducing it in the ventral striatum, a feature shared with other antidepressants, the repeated self-administration reduced mBDNF expression and its downstream signalling in both ventral striatum and hippocampus. Further, we here show that phosphorylation of Akt is oppositely regulated by ketamine, pointing to this pathway as central to the different actions of the drug. Taken together, we here point to BDNF and its downstream signalling pathway as a finely tuned mechanism whose modulation might subserve the different features of ketamine.

Updated peer review of the pesticide risk assessment of the active substance pydiflumetofen.

The conclusions of the EFSA following the peer review of the initial risk assessments carried out by the competent authority of the rapporteur Member State, France, and co-rapporteur Member State, Austria, for the pesticide active substance pydiflumetofen and the assessment of applications for maximum residue levels (MRLs) are reported. The context of the peer review was that required by Regulation (EC) No 1107/2009 of the European Parliament and of the Council. The conclusions were reached on the basis of the evaluation of the representative uses of pydiflumetofen as a fungicide field application on pome fruits, grapes, potato, fruiting vegetables, cucurbits and Brassica vegetables and updated following the request from Commission to consider additional information submitted and review the risk assessment. The reliable endpoints, appropriate for use in regulatory risk assessment and the proposed MRLs, are presented. Missing information identified as being required by the regulatory framework is listed. Concerns are reported where identified.

Peer review of the pesticide risk assessment of the active substance clove oil.

The conclusions of the EFSA following the peer review of the initial risk assessments carried out by the competent authority of the rapporteur Member State, Malta, for the pesticide active substance clove oil are reported. The context of the peer review was that required by Regulation (EC) No 1107/2009 of the European Parliament and of the Council. The conclusions for the amendment of approval were reached on the basis of the evaluation of the representative use of clove oil as a preharvest nematicide on tomatoes and cucumbers (permanent greenhouse use). The representative use evaluated for the renewal of approval of clove oil was as post-harvest fungicide and bactericide on apples, pears and peaches (indoor uses). The reliable endpoints appropriate for use in regulatory risk assessment are presented. Endpoints not relevant to the scope of the proposed amendment of approval conditions will be addressed in the context of the renewal of approval procedure of clove oil running in parallel (AIR IV, EFSA Q-2016-00809). Missing information identified as being required by the regulatory framework is listed. Concerns are reported where identified.

Updated peer review of the pesticide risk assessment of the active substance dichlorprop-P and variant dichlorprop-P-2-ethylhexyl.

The conclusions of the EFSA following the peer review of the initial risk assessments carried out by the competent authorities of the rapporteur Member State, Ireland, and co-rapporteur Member State, Poland, for the pesticide active substance dichlorprop-P and the variant dichlorprop-P-2-ethylhexyl and the assessment of applications for maximum residue levels (MRLs) are reported. The context of the peer review was that required by Commission Implementing Regulation (EU) No 844/2012. The conclusions were reached on the basis of the evaluation of the representative uses of dichlorprop-P as a herbicide on cereals, grassland and grass seed crops and of the variant dichlorprop-P-2-ethylhexyl as a plant growth regulator on citrus. MRLs were assessed in mandarin and lemon. The conclusions from 2018 were updated in 2024 following the request from the European Commission with regard to the endocrine-disrupting properties. The reliable end points, appropriate for use in regulatory risk assessment and the proposed MRLs, are presented. Missing information identified as being required by the regulatory framework is listed. Concerns are reported where identified.

Peer review of the pesticide risk assessment of the active substance quinolin-8-ol.

The conclusions of the European Food Safety Authority (EFSA) following the peer review of the initial risk assessments carried out by the competent authorities of the rapporteur Member State, Spain, and co-rapporteur Member State, the Netherlands, for the pesticide active substance quinolin-8-ol are reported. The context of the peer review was that required by Commission Implementing Regulation (EU) No 844/2012. The conclusions were reached on the basis of the evaluation of the representative use of quinolin-8-ol as a fungicide and bactericide against soil-borne pathogens in tomato cultivation in permanent greenhouses applied by drip irrigation. The reliable end points, appropriate for use in regulatory risk assessment are presented. Missing information identified as being required by the regulatory framework is listed. Concerns are reported where identified.

Revised guidance on the risk assessment of plant protection products on bees (Apis mellifera, Bombus spp. and solitary bees).

The European Commission asked EFSA to revise the risk assessment for honey bees, bumble bees and solitary bees. This guidance document describes how to perform risk assessment for bees from plant protection products, in accordance with Regulation (EU) 1107/2009. It is a review of EFSA's existing guidance document, which was published in 2013. The guidance document outlines a tiered approach for exposure estimation in different scenarios and tiers. It includes hazard characterisation and provides risk assessment methodology covering dietary and contact exposure. The document also provides recommendations for higher tier studies, risk from metabolites and plant protection products as mixture.

Peer review of the pesticide risk assessment of the active substance ethephon.

The conclusions of the European Food Safety Authority (EFSA) following the peer review of the initial risk assessments carried out by the competent authorities of the rapporteur Member State, the Netherlands and co-rapporteur Member State, the United Kingdom, for the pesticide active substance ethephon are reported. The context of the peer review was that required by Commission Implementing Regulation (EU) No 844/2012, as amended by Commission Implementing Regulation (EU) No 2018/1659. The conclusions were reached on the basis of the evaluation of the representative use of ethephon as a plant growth regulator on cereals (winter and spring barley, winter and spring wheat, winter rye, winter triticale, spelt, durum wheat). The reliable endpoints appropriate for use in regulatory risk assessment are presented. Missing information identified as being required by the regulatory framework is listed. Concerns are reported where identified.

Peer review of the pesticide risk assessment of the active substance fat distillation residues.

The conclusions of the European Food Safety Authority (EFSA) following the peer review of the initial risk assessments carried out by the competent authorities of the rapporteur Member State, Czech Republic, and co-rapporteur Member State, France, for the pesticide active substance fat distillation residues are reported. The context of the peer review was that required by Commission Implementing Regulation (EU) No 844/2012, as amended by Commission Implementing Regulation (EU) No 2018/1659. The conclusions were reached on the basis of the evaluation of the representative uses of fat distillation residues as a repellent on seedlings of coniferous and deciduous trees. The reliable end points, appropriate for use in regulatory risk assessment, are presented. Missing information identified as being required by the regulatory framework is listed. Concerns were not identified.

Peer review of the pesticide risk assessment of the active substance S-metolachlor excluding the assessment of the endocrine disrupting properties.

The conclusions of the European Food Safety Authority (EFSA) following the peer review of the initial risk assessments carried out by the competent authorities of the rapporteur Member State Germany and co-rapporteur Member State France for the pesticide active substance S-metolachlor are reported. The context of the peer review was that required by Commission Implementing Regulation (EU) No 844/2012, as amended by Commission Implementing Regulation (EU) No 2018/1659. In September 2022, the European Commission asked EFSA to deliver its conclusion on the available outcomes of the assessments in all areas excluding the full assessment of endocrine disrupting properties as several critical areas of concern related to the protection of the environment were identified. The conclusions were reached on the basis of the evaluation of the representative uses of S-metolachlor as a herbicide on maize and sunflower. The reliable end points, appropriate for use in regulatory risk assessment are presented. Missing information identified as being required by the regulatory framework is listed. The concerns identified are presented.

Peer review of the pesticide risk assessment of the active substance glyphosate.

The conclusions of EFSA following the peer review of the initial risk assessments carried out by the Assessment Group on Glyphosate (AGG), consisting of the competent authorities of France, the Netherlands, Sweden and Hungary, acting jointly as rapporteur Member State for the pesticide active substance glyphosate are reported. The context of the peer review was that required by Commission Implementing Regulation (EU) No 844/2012. The conclusions were reached on the basis of the evaluation of the representative uses of glyphosate as a herbicide as proposed by the applicants, covering uses pre-sowing, pre-planting and pre-emergence plus post-harvest in vegetables and sugar beet; post-emergence of weeds in orchards, vineyards, row vegetables, railway tracks against emerged annual, biennial and perennial weeds. Moreover, uses as spot treatment against invasive species in agricultural and non-agricultural areas, and in vegetables and sugar beet against couch grass are also included. The reliable endpoints, appropriate for use in regulatory risk assessment, are presented. Missing information identified as being required by the regulatory framework is listed. Concerns are reported where identified.

Peer review of the pesticide risk assessment of the active substance sulfur.

The conclusions of EFSA following the peer review of the initial risk assessments carried out by the competent authorities of the rapporteur Member State France and co-rapporteur Member State Slovenia for the pesticide active substance sulfur and the considerations as regards the inclusion of the substance in Annex IV of Regulation (EC) No 396/2005 are reported. The context of the peer review was that required by Commission Implementing Regulation (EU) No 844/2012, as amended by Commission Implementing Regulation (EU) No 2018/1659. The conclusions were reached on the basis of the evaluation of the representative uses of sulfur as a fungicide and acaricide on grapevine and cereals (wheat, barley, oat, rye, triticale). The reliable end points, appropriate for use in regulatory risk assessment, are presented. Missing information identified as being required by the regulatory framework is listed. Concerns are reported where identified.

Peer review of the pesticide risk assessment of the active substance metiram.

The conclusions of EFSA following the peer review of the initial risk assessments carried out by the competent authorities of the rapporteur Member State Italy and co-rapporteur Member State the United Kingdom for the pesticide active substance metiram are reported. The context of the peer review was that required by Commission Implementing Regulation (EU) No 844/2012, as amended by Commission Implementing Regulation (EU) No 2018/1659. The conclusions were reached on the basis of the evaluation of the representative uses of metiram as a fungicide on grapes (wine table) and potatoes (all being field uses). It was concluded that following the guidance on this topic, metiram has endocrine disrupting potential, which is a cut-off criterion for non-approval of an active substance. Considerations are also provided on whether exposure to humans and the environment from the representative use of metiram on potatoes can be considered negligible, taking into account information from the applicant and the European Commission's draft technical guidance on this topic. The information available indicated this exposure was not negligible. The reliable end points, appropriate for use in regulatory risk assessment are presented. Missing information identified as being required by the regulatory framework is listed. Concerns are reported where identified. An evaluation of data concerning the necessity of metiram as a fungicide to control a serious danger to plant health which cannot be contained by other available means, including non-chemical methods is also presented.

Peer review of the pesticide risk assessment of the active substance metrafenone.

The conclusions of the European Food Safety Authority (EFSA) following the peer review of the initial risk assessments carried out by the competent authorities of the rapporteur Member State Latvia and co-rapporteur Member State Slovakia for the pesticide active substance metrafenone are reported. The context of the peer review was that required by Commission Implementing Regulation (EU) No 844/2012, as amended by Commission Implementing Regulation (EU) No 2018/1659. The conclusions were reached on the basis of the evaluation of the representative uses of metrafenone as a fungicide on wheat, rye, triticale, oats, barley and grapes (field use). The reliable end points, appropriate for use in regulatory risk assessment, are presented. Missing information identified as being required by the regulatory framework is listed. Concerns are reported where identified.

Peer review of the pesticide risk assessment of the active substance (3E)-dec-3-en-2-one.

The conclusions of the European Food Safety Authority (EFSA) following the peer review of the initial risk assessments carried out by the competent authority of the rapporteur Member State, the Netherlands, for the pesticide active substance (3E)-dec-3-en-2-one and the considerations as regards the inclusion of the substance in Annex IV of Regulation (EC) No 396/2005 are reported. The context of the peer review was that required by Regulation (EC) No 1107/2009 of the European Parliament and of the Council. The conclusions were reached on the basis of the evaluation of the representative post-harvest use of (3E)-dec-3-en-2-one on potato as a sprouting inhibitor applied by hot fogging in potato storage rooms. The reliable endpoints, appropriate for use in regulatory risk assessment, are presented. Missing information identified as being required by the regulatory framework is listed. Concerns are reported where identified.

Updated conclusion on the peer review of the pesticide risk assessment of the active substance mecoprop-P.

The conclusions of the European Food Safety Authority (EFSA) following the peer review of the initial risk assessments carried out by the initial competent authorities of the rapporteur Member State, the United Kingdom, and co-rapporteur Member State, Ireland, for the pesticide active substance mecoprop-P are reported. Due to the UK leaving the EU, the renewal of approval dossier on mecoprop-P was reallocated to Ireland, as RMS. The context of the peer review was that required by Commission Implementing Regulation (EU) No 844/2012. The conclusions were reached on the basis of the evaluation of the representative uses of mecoprop-P as a herbicide on winter and spring wheat (including durum and spelt), barley, rye, oats and triticale. The conclusions were updated following the request from the European Commission to review the risk assessment as regards non-dietary exposure and the endocrine-disrupting properties of mecoprop-P. The reliable end points, appropriate for use in regulatory risk assessment are presented. Missing information identified as being required by the regulatory framework is listed. Concerns are reported where identified.

Peer review of the pesticide risk assessment of the active substance hydrolysed proteins.

The conclusions of EFSA following the peer review of the initial risk assessments carried out by the competent authorities of the rapporteur Member State Spain and co-rapporteur Member State Greece for the pesticide active substance hydrolysed proteins and the considerations as regards the inclusion of the substance in Annex IV of Regulation (EC) No 396/2005 are reported. The context of the peer review was that required by Commission Implementing Regulation (EU) No 844/2012, as amended by Commission Implementing Regulation (EU) No 2018/1659. The conclusions were reached on the basis of the evaluation of the representative uses of hydrolysed proteins as an insect attractant on olive tree, deciduous fruit tree, stone fruit tree, pome fruit tree, walnut tree, citrus tree, fig tree, persimmon tree, kiwi and blueberry crops. The reliable end points, appropriate for use in regulatory risk assessment, are presented. Missing information identified as being required by the regulatory framework is listed. Concerns are reported where identified.

Peer review of the pesticide risk assessment of the active substance dimethomorph.

The conclusions of EFSA following the peer review of the initial risk assessments carried out by the competent authorities of the rapporteur Member State The Netherlands and co-rapporteur Member State Germany for the pesticide active substance dimethomorph and the assessment of applications for maximum residue levels (MRLs) are reported. The context of the peer review was that required by Commission Implementing Regulation (EU) No 844/2012, as amended by Commission Implementing Regulation (EU) No 2018/1659. The conclusions were reached on the basis of the evaluation of the representative uses of dimethomorph as a fungicide applied via foliar spraying on field strawberry and grapevine crops and permanent greenhouse lettuce crops; via drenching on field and permanent greenhouse strawberry crops and via dripping on permanent greenhouse strawberry crops. The peer review also provided considerations on whether exposure to humans and the environment from the representative uses of dimethomorph can be considered negligible, taking into account the European Commission's draft guidance on this topic. MRLs were assessed in potatoes, other root and tuber vegetables (except radishes), stem vegetables (except celery, leeks, globe artichokes, sugar beet, cereal forage and straw). The reliable end points, appropriate for use in regulatory risk assessment and the proposed MRLs, are presented. Missing information identified as being required by the regulatory framework is listed. The concerns are reported where identified.

Peer review of the pesticide risk assessment of the active substance flutolanil.

The conclusions of the European Food Safety Authority (EFSA) following the peer review of the initial risk assessments carried out by the competent authorities of the rapporteur Member State, the Netherlands, and co-rapporteur Member State, the United Kingdom, for the pesticide active substance flutolanil, and the assessment of applications for maximum residue levels (MRLs) are reported. The context of the peer review was that required by Commission Implementing Regulation (EU) No 844/2012, as amended by Commission Implementing Regulation (EU) No 2018/1659. The conclusions were reached on the basis of the evaluation of the representative uses of flutolanil as a fungicide on potatoes, tulips and iris (field uses). MRLs were assessed for a potato in-furrow treatment. The reliable end points, appropriate for use in regulatory risk assessment are presented. Missing information identified as being required by the regulatory framework is listed. Concerns are reported where identified.

Peer review of the pesticide risk assessment of the active substance metribuzin.

The conclusions of the EFSA following the peer review of the initial risk assessments carried out by the competent authorities of the rapporteur Member State, Estonia, and co-rapporteur Member State, Germany, for the pesticide active substance metribuzin and the assessment of application to amend existing residue definition are reported. The context of the peer review was that required by Commission Implementing Regulation (EU) No 844/2012, as amended by Commission Implementing Regulation (EU) No 2018/1659. The conclusions were reached on the basis of the evaluation of the representative use of metribuzin as a herbicide on potato and soybean (field use). The reliable end points, appropriate for use in regulatory risk assessment, are presented. Missing information identified as being required by the regulatory framework is listed. Concerns are reported where identified.