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EUROPE – EFSA: Database on processing techniques and factors

EFSA is conducting pan-European dietary exposure and risk assessments related to actual levels of pesticide residues in food commodities. These assessments use the pesticide occurrence data generated under the official monitoring programs of Member States, the consumption data from EFSA’s comprehensive food consumption database and pesticide-specific information such as processing factors. Currently no harmonised list of processing factors is available within Europe and worldwide.

EFSA therefore launched the project “Database of processing techniques and processing factors compatible with the EFSA food classification and description system FoodEx 2”. The main overall objective of the project is to develop a database of processing types and processing factors compatible with the EFSA food classification and description system FoodEx 2.

On 26 November 2018, EFSA published a series of 3 external scientific reports as part of this project. Each report corresponds to one of the three objectives:

– Objective 1: Compendium of Representative Processing Techniques investigated in regulatory studies for pesticides

– Objective 2: Linking the processing techniques investigated in regulatory studies with the EFSA food classification and description system FoodEx2

– Objective 3: European database of processing factors for pesticides in food

The coding system (objective 2) and the  database (objective 3) are also provided as Excel spreadsheets.

 

To download:

Database of processing techniques and processing factors compatible with the EFSA food classification and description system FoodEx 2 Objective 1: Compendium of Representative Processing Techniques investigated in regulatory studies for pesticides

Database of processing techniques and processing factors compatible with the EFSA food classification and description system FoodEx2 related to pesticide residues Objective 2: Linking the processing techniques investigated in regulatory studies with the EFSA food classification and description system FoodEx2

Appendix A -FoodEx 2 Coding system

Database of processing techniques and processing factors compatible with the EFSA food classification and description system FoodEx 2 Objective 3: European database of processing factors for pesticides in food

EU processing factors database

 

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EUROPE – EFSA: Database of Ecological and Residue Data Used in Assessments for Birds and Mammals

EFSA published the outcome of the data collection conducted with the aim of developing a unified database of ecological data and residue data to be used for the risk assessment of plant protection products for birds and mammals. This data collection, outsourced to a consortium consisting of the Alterra institute (Wageningen University, the Netherlands), the Austrian Agency for Health & Food Safety (AGES) and the French Agency for Food, Environmental and Occupational Health & Safety (ANSES), was initiated in 2015.

Data were collected among the data submitted in active substance and plant protection product dossiers and via a systematic literature review. Data were scored on the basis of quality criteria and organised in 3 Excel spreadsheets (one for birds, one for mammals and one for residue studies), that can be downloaded as Supplements to the report.

The ecological information collected for birds and mammals consisted of data used (or that could be used) for the determination of focal species (notably, the frequency of observation in the field and the frequency of observation per survey), the estimation of the proportion of an animal’s daily diet obtained in a treated habitat (PT) and the assessment of the composition of the diet obtained from a treated area (PD). Entries for 18-21 crop groups, 150 bird species and 70 mammal species were collected. Nearly half of the records for birds come from protected company study reports while it is less than 10% for mammals.

The information gathered on residues focussed on initial residue levels and on residue decline (notably, DT50 and DT90). Entries for 190 substances and 18 crop groups were collected. Around 75% of these records come from protected company study reports.

In a first step, the databases may be used by EFSA and Member states for the peer review of active substances and for the registration of plant protection products in order to reach a higher level of harmonisation and more robust assessments. In a second step, EFSA planned to use the databases as inputs for the revision of the guidance on birds and mammals (EFSA Journal 2009; 7(12):1438).

 

To download:

Lahr et al., 2018 – EFSA Supporting publication 2018:EN-1513: Data collection for the estimation of ecological data (specific focal species, time spent in treated areas collecting food, composition of diet), residue level and residue decline on food items to be used in the risk assessment for birds and mammals (the report and the 3 databases as supplements).

 

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EUROPE: EFSA Public consultation – threshold of toxicological concern approach

The public consultation on the guidance document proposed by EFSA for the use of the threshold of toxicological concern (TTC) is opened from 13 November 2018 to 08 January 2019.

This document updates the Scientific Committee opinion of 2012 by considering the latest developments in the field. This is a guidance for EFSA’s scientific panels and staff for the use of the TTC approach as a screening and prioritisation tool for the safety assessment of chemicals, when hazard data are incomplete and human exposure can be estimated as low.

The TTC approach is not applicable where substance-specific data exist or where they are required under EU legislation.

To download: Public consultation: guidance on threshold of toxicological concern approach (en anglais)

 

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EUROPE – EFSA: Recurring issues in mammalian toxicology

During the EFSA peer review of pesticide active substances under Regulation (EC) No. 1107/2009, several aspects in the area of mammalian toxicology were identified by EFSA that needed discussion with experts from National Authorities in order to enhance the harmonisation of the risk assessment of active substances.

A new discussion was held at the Pesticide Peer Review Meeting 170 of December 2017. Recommendations were made on:

  • Genotoxicity of plant protection products
  • Use of (Q)SARs
  • Use of Read-Across approaches for metabolites

These recommendations will be applied during the EFSA peer review of the active substances.

 

In addition, brief discussions of the following topics were also made:

  • EFSA guidance 2016 on the residue definition
  • EFSA guidance 2017 on dermal absorption
  • Current and planned EFSA activities in the area of pesticides:
    • Developmental neurotoxicity
    • Cumulative assessment groups
    • Epidemiology
    • Planned workshops (in vitro comparative metabolism, phototoxicity, historical control data)
    • Update of EFSA guidance 2014 on the assessment of exposure of operators, workers, residents and bystanders

 

To download:

EFSA Technical Report – Outcome of the pesticides peer review meeting on general recurring issues in mammalian toxicology (25 August 2018)

 

See also our previous articles:

EUROPE – EFSA: Recurring issues in mammalian toxicology

 

Lynxee consulting’s team is at your disposal to answer your questions.

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EFSA: Issues in physical-chemical properties and analytical methods

During the EFSA peer review of pesticide active substances under Regulation (EC) No 1107/2009, several aspects in the area of identity and analytical methods were identified by EFSA and Member States that needed discussion with experts from national Authorities in order to enhance the harmonisation of the risk assessment of active substances.

The main issues identified were related to the quality and level of details of the assessment reports and the adherence to the new data requirements, in particular regarding analytical methods and issues related to the assessment of the impurity profiles and the proposed specifications.

All these issues were discussed in a general meeting. Recommendations were compiled on the basis of the discussions and conclusions achieved at the meeting. These recommendations will be applied during the EFSA peer review of the active substances, and are expected to provide additional clarifications to applicants and rapporteur Member States regarding the scientific interpretation of the relevant guidance documents when preparing the dossiers and the draft/renewal assessment reports.

 

To download:  Outcome of the pesticides peer review meeting on general recurring issues in physical and chemical properties and analytical methods

 

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EFSA Public consultation: effects of pesticides on amphibians and reptiles

The public consultation on the Draft Scientific Opinion of the EFSA Panel on Plant Protection Products and their Residues (PPR) on the state of the science on pesticide risk assessment for amphibians and reptiles is opened until 27 May 2017.

The PPR Panel therefore considers that initial suspicion is given for a thoughtful examination of actual risk-assessment schemes, in order to provide the fundamentals for an operational assessment of active substances and PPPs. The PPR panel recommended already in the scientific opinion on the update of the data requirements (EFSA 2007) that an appropriate risk assessment approach for amphibians should be developed. The aim is to ensure that those products are authorized that have no unacceptable effects on non-target species, biodiversity and the ecosystem as required by current legislation (Regulation (EU) 1107/2009).

The current opinion aims at providing the scientific basis for developing a future risk assessment scheme and covers the following topics:

– Ecology and biology of amphibians and sources of environmental exposure,

– Definition of spatial aspects to be considered in the risk assessment,

– Population dynamics and modelling approach to support the setting of Specific Protection Goals (SPG),

– Specific protection goal options for amphibians and reptiles,

– General framework for developing a risk assessment scheme,

– Uncertainties in the risk assessment for amphibians and reptiles,

– Toxicological endpoints and standard tests relevant for amphibians and reptiles,

– Exposure assessment in the environment,

– Coverage of amphibians and reptiles by existing risk assessment schemes for other groups of organisms.

 

For more information, see EFSA website.

 

EFSA Public consultation: Guidance for the identification of biological relevance of adverse/ positive health effects from experimental animal and human studies

The public consultation on the draft guidance document of the EFSA Scientific Committee on the identification of biological relevance of adverse/ positive health effects from experimental animal and human studies is opened until 1st May 2017.

Generic issues and criteria are given to consider biological relevance, particularly when deciding on whether an observed effect is of biological relevance, i.e. is adverse (or shows a positive health effect) or not. The opinion clarifies a number of definitions and concepts, such as, responses of a biological system to exposure, mode of action and adverse outcome pathways, thresholds, critical effect, modelling approaches, etc. It also proposes several case studies.

For more information, see EFSA website.

 

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EFSA Public consultation: Guidance on The Use of the Weight of Evidence Approach in Scientific Assessments

The public consultation on the draft guidance document of the EFSA Scientific Committee on The Use of the Weight of Evidence Approach in Scientific Assessments is opened until 1st May 2017.

The guidance document addresses the use of the weight of evidence in scientific assessments using both qualitative and quantitative approaches. Several case studies covering the various areas under EFSA’s remit are annexed to the guidance document to illustrate the applicability of the proposed approach.

 

For more information, see EFSA website.

Lynxee consulting’s team is at your disposal to answer your questions.

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EUROPE – EFSA: Recurring issues in mammalian toxicology

During the EFSA peer review of pesticide active substances under Regulation (EC) No. 1107/2009, several aspects in the area of mammalian toxicology were identified by EFSA that needed discussion with experts from national Authorities in order to enhance the harmonisation of the risk assessment of active substances.

  • Renewal assessment report (RAR)

The majority of experts agreed with EFSA proposal to re-open old studies: applicants should provide updated robust OECD summary reports and RMS should re-evaluate them. Changes to first approval conclusion should be clearly indicated in the RAR.

  • Good Laboratory Practice (GLP) requirement status

The experts agreed that studies for active substances conducted before July 1993, although not fully compliant with GLP requirements or with current test methods, may be integrated into the assessment, when accepted by the competent authorities as scientifically valid, appropriate (e.g. mechanistic data) and acceptable (pending availability of raw data and well documented study report).

  • Analytical methods

For the 3rd renewal programme following Regulation (EU) No. 283/2013, analytical methods for body fluids and tissues have always to be provided. Furthermore, according to Regulation (EU) No. 283/2013 the analytical methods to be used in toxicity studies shall be specific for the entity to be measured and shall be adequately validated, both for old and new studies.

The experts agreed that the assessment of the analytical methods and of their validation data should be included in the volume 3 of the RAR

For old studies, it was clarified that, in the section about physicochemical properties and analytical methods, it can be concluded that the method is not validated according to current guidance but is nevertheless fit-for-purpose and supports the toxicological studies. In the cases where the method is not considered fit-for-purpose, a case-by-case evaluation should be performed and the experts agreed that repeating a study would be an extreme case (generally not required).

  • Toxicokinetic parameters and in vitro comparative metabolism study

The experts supported the EFSA proposal to ask for additional toxicokinetic parameters and in vitro metabolism data in the renewal dossier, according to the data requirement in Regulation (EU) No. 283/2013.

As a first step, the experts supported the need for guidance on in vitro metabolism, in order to satisfy the data requirement.EFSA could be mandated for that. As a second step, other toxicokinetic endpoints should be addressed in further guidance, in order to address inter-species and intra-species variability (e.g. in relationship with bioavailability, phase 2 metabolism, transporters, etc.).

  • Phototoxicity/photomutagenicity

The UK Committee on Mutagenicity (2013) recommends that if there is a negative response from the phototoxicity test, no photomutagenicity test is required; in the case the test is positive, no specific guidance is provided. The experts agreed that the concern regarding positive results in the phototoxicity test should be raised to the risk managers in the conclusion of the peer review. In addition, the experts agreed that photomutagenicity testing is not required for the time being, unless further guidance is provided.

The experts proposed that the phototoxicity test should not be performed if it has been demonstrated that the test material only absorbs at wavelengths lower than 313 nm and there is insufficient absorption at longer wavelengths to trigger testing in the absence of further guidance.

  • In vivo follow-up for in vitro gene mutation

The majority of experts overall agreed that the applicant can provide a Comet assay or a test with transgenic rodent gene mutation assay according to the EFSA Scientific opinion on genotoxicity testing strategies applicable to food and feed safety assessment (EFSA Scientific Committee, 2011). One expert maintained that the in vivo UDS assay may still be a valid and acceptable test under certain circumstances.

  • Aneugenicity

The experts agreed with the EFSA proposal to investigate the nature of the positive response in the in vitro and in vivo micronucleus test and to require an in vitro micronucleus test if the test battery did not address properly aneugenicity.

  • Tissue exposure

Exposure to the test tissue (such as cell toxicity or toxicokinetic data) should be demonstrated in the in vivo genotoxicity tests.

The discussion was mainly focussed on metabolites since for active substances toxicokinetic studies can be used to demonstrate exposure of the target tissue (e.g. bone marrow).

The experts did not reach a consensus. EFSA commented that the genotoxic potential of a metabolite should be clearly excluded, in particular when carcinogenicity and reproductive toxicity studies on the metabolite are not available. Information regarding validation of the method of analysis should be provided when toxicokinetic investigations (e.g. plasma concentrations of non-radiolabelled compound) are conducted.

  • Assessment of the toxicological profile of metabolites

The relevance of groundwater metabolites needs to be assessed according to the EU guidance (European Commission, 2003) and will not be further discussed under this point.

For the assessment of the toxicological profile of metabolites found as residues (plant and livestock), no guidance document is currently implemented and a case-by-case approach is used.

The list of metabolites, candidates to be considered for a toxicological assessment, should be identified by the residue experts. The metabolic pathway of the parent and specific toxicity data for the metabolite, including genotoxicity, should guide how the decision is taken. The conclusion that the metabolite is of equal or lower toxicity than the parent would imply that reference values of the parent could apply to the metabolite for the consumer’s risk assessment. If the toxicological profile of the metabolite is qualitatively different from the parent or if the metabolite is quantitatively of higher toxicity than the parent, this would imply that specific reference values should be derived for the metabolite.

The guidance for the residue definition is under finalisation. It was noted that it will be difficult to match the guidance on residue definition with the guidance on groundwater metabolites, since different tools are used in each of them.

  • Impurities

Compliance of the batches used in toxicity studies compared to the technical specification:

The experts agreed that a critical area of concern should be raised when no information is provided on the detailed composition of batches used in toxicity studies, and the toxicological relevance of the impurities in the technical specification cannot be clearly excluded.

Monitoring of product quality for manufacturing and trading:

Some experts considered that the toxicological relevance of impurities is covered when the batches used in toxicity studies are representative of the technical specification. EFSA pointed out that the relevance of impurities should be assessed with alternative tools to animal models (e.g. (Q)SAR).

  • Endocrine disruptive properties

The majority of experts considered that interim criteria will be applied until final criteria are implemented.

A case-by-case basis approach is suggested for the time being. In case the data is very poor during the renewal process, a data gap may be identified in the EFSA Conclusion.

  • Proposals for classification

The approval criteria in the Regulation (EC) No. 1107/2009 (Annex II) take into consideration classification for CMR. EFSA considers that a detailed comparison with CLP criteria (ECHA, 2015) at least for the CMR hazard classes should be done. The comparison with CLP criteria should be provided both in the case of classification and non-classification proposals. The experts agreed with the EFSA proposal. Some experts indicated that detailed assessment of classification should be limited to CMR properties.

For substances with harmonised classification and labelling as carcinogen category 1A or 1B and/or as toxic for reproduction category 1A or 1B the applicant should clearly indicate at the time of application if they apply for negligible exposure or/and essential use (article 4(7)) and evidence should be provided to demonstrate it. EFSA acknowledged that no final agreed guidance is currently available. A draft technical guidance is available for negligible exposure (European Commission, 2015). Protocols under development and close to finalisation will be available for essential use.

EFSA would recommend RMS to submit CLH report to ECHA before RAR is submitted, so RAC Opinion is available before EFSA Conclusion is finalised.

  • Literature search

The experts discussed the issues of peer reviewed papers and GLP studies. The ToxRTool is considered a useful tool for an independent quality assessment, but further improvement would be welcome since ToxRTool lacks assessment of bias. BfR is intending to publish a similar tool taking into the limitations.

For the mammalian toxicology section, the literature would mainly indicate alerts that would need to be clarified by the applicant. Literature should be considered in a weight of evidence approach, on a case-by-case basis.

 

These recommendations will be applied during the EFSA peer review of the active substances, and are expected to provide additional clarifications to applicants and rapporteur Member States regarding the scientific interpretation of the relevant guidance documents when preparing the dossiers and the renewal assessment reports.

 

To download:

EFSA Technical Report – Outcome of the pesticides peer review meeting on general recurring issues in mammalian toxicology – 25 July 2016

Background documents

 

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