66 research outputs found
Novel chemical hazard characterisation approaches
There is a fundamental change in thinking within the regulatory community due to a better understanding of the underlying biology of adverse effects to human health and the environment. The development of alternatives to use laboratory animals has become a priority. In addition, technological progress is impacting greatly on the amount of data available and on the ways to process and analyse it. Topics, such as identification of adverse outcome pathways (AOPs) and modes of action (MoA), together with integrated assessment and testing approaches (IATAs), represent fundamental tools for hazard identification and characterisation of a chemical. Complex endpoints cannot be predicted by a single standalone non-animal test; thus, a major challenge is the complex nature of biological systems. Microphysiological systems (MPS) will enable more complex in vitro human models that better simulate the organ's biology and function by combining different cell types in a specific three-dimensional configuration that simulates functional organs. The process of validation of new approaches needs to be considered in terms of efficiency and length. Regulators might still not have enough confidence to adopt and apply these new approaches: this phase is very challenging and the activities performed by assay developers are not yet addressing the regulatory requirements needs sufficiently. The IATAs provide a framework to consistently evaluate new approach data and could assist in understanding their relevance for specific endpoints. The data need to be reproducible, understandable and statistically sound: indeed, a major issue lies in the interpretation and integration of the results based on subjective assessment, which relies on expert judgement. A well-defined mechanistic characterisation is proposed as a way forward to ensure the relevance of new cell-based test systems
International STakeholder NETwork (ISTNET): creating a developmental neurotoxicity (DNT) testing road map for regulatory purposes
A major problem in developmental neurotoxicity (DNT) risk assessment is the lack of toxicological hazard information for most compounds. Therefore, new approaches are being considered to provide adequate experimental data that allow regulatory decisions. This process requires a matching of regulatory needs on the one hand and the opportunities provided by new test systems and methods on the other hand. Alignment of academically and industrially-driven assay development with regulatory needs in the field of DNT is a core mission of the International STakeholder NETwork (ISNET) in DNT testing. The first meeting of ISTNET was held in Zurich on 23-24 January 2014 in order to explore the concept of adverse outcome pathway (AOP) to practical DNT testing. AOPs were considered promising tools to promote test systems development according to regulatory needs. Moreover, the AOP concept was identified as an important guiding principle to assemble predictive integrated testing strategies (ITSs) for DNT.
The recommendations on a roadmap towards AOP-based DNT testing is considered a stepwise approach, operating initially with incomplete AOPs for compound grouping, and focussing on key events of neurodevelopment. Next steps to be considered in follow-up activities are the use of case studies to further apply the AOP concept in regulatory DNT testing, making use of AOP intersections (common key events) for economic development of screening assays, and addressing the transition from qualitative descriptions to quantitative network modelling.JRC.I.5-Systems Toxicolog
International STakeholder NETwork (ISTNET): creating a developmental neurotoxicity (DNT) testing road map for regulatory purposes
A major problem in developmental neurotoxicity (DNT) risk assessment is the lack of toxicological hazard information for most compounds. Therefore, new approaches are being considered to provide adequate experimental data that allow regulatory decisions. This process requires a matching of regulatory needs on the one hand and the opportunities provided by new test systems and methods on the other hand. Alignment of academically and industrially driven assay development with regulatory needs in the field of DNT is a core mission of the International STakeholder NETwork (ISTNET) in DNT testing. The first meeting of ISTNET was held in Zurich on 23-24 January 2014 in order to explore the concept of adverse outcome pathway (AOP) to practical DNT testing. AOPs were considered promising tools to promote test systems development according to regulatory needs. Moreover, the AOP concept was identified as an important guiding principle to assemble predictive integrated testing strategies (ITSs) for DNT. The recommendations on a road map towards AOP-based DNT testing is considered a stepwise approach, operating initially with incomplete AOPs for compound grouping, and focussing on key events of neurodevelopment. Next steps to be considered in follow-up activities are the use of case studies to further apply the AOP concept in regulatory DNT testing, making use of AOP intersections (common key events) for economic development of screening assays, and addressing the transition from qualitative descriptions to quantitative network modelling
Exposure of operators, workers, residents and bystanders in risk assessment for plant protection products calculator (Version 30MAR2015)
<p>The aim of exposure assessment in this context is to consider realistic and high exposure scenarios arising from the proposed Good Agricultural Practice for non-dietary systemic exposure that can be compared with appropriate toxicological reference values. The calculator can be used to assess exposures for operators (persons who are involved in activities relating to the application of a plant protection products (PPP), workers (persons who, as part of their employment, enter an area that has been treated previously with a PPP or who handle a crop that has been treated with a PPP), bystanders (persons who could be located within or directly adjacent to the area where PPP application or treatment is in process or has recently been completed) and residents (persons who live, work or attend school or any other institution adjacent to an area that is or has been treated with a PPP).<br>
The Data Entry form requires information about the plant protection product, toxicological reference values and a description of the intended use. The operator exposure uses the AOEM model (GroĂkopf, 2012) and includes application techniques and scenarios for outdoor treatment of low and high crops, by vehicle-mounted/trailed or self-propelled sprayers or by hand-held spray guns and knapsack sprayers. 75th and 95th centile exposures are estimated for both mixing and loading and application and these can be modified by applying suitable combinations of PPE. An additional sheet allows the estimation of operator exposure for granular formulations based on the Pesticide Handlers Exposure Database (PHED, 1992). The worker worksheet estimates dermal and inhalation exposure for indoor and outdoor worker scenarios. The Transfer Coefficients for dermal exposure were modified from EUROPOEM II (2002) considering US EPA (2012) and for inhalation exposure Task Specific Factors are taken from van Hemmen et al., 2002. For resident and bystander exposure four pathways are considered; spray drift at time of application, vapour inhalation after application, surface deposits and entry into treated crops. Resident exposure considers a 24-hour duration of exposure and calculates 75th centile and mean exposure values, whereas bystander exposure considers a 2 hour duration of exposure with 95th centile values. A vehicle-mounted sprayer scenario is used for resident and bystander exposure assessment and users parameters from BREAM for arable crops and from Rautmann/Ganzelmeier for orchards. The exposure estimates for all four groups are summarised and presented in a report, which can be copied or printed.</p
Modification of the existing maximum residue levels in various plant commodities resulting from the use of potassium phosphonates
Abstract In accordance with Article 6 of Regulation (EC) No 396/2005, the applicants De Sangosse SAS and TilcoâAlginure submitted two requests, respectively, to the competent national authorities in France and Germany to modify the existing maximum residue levels (MRLs) for the active substance potassium phosphonates in various plant commodities. The data submitted in support of the requests were found to be sufficient to derive MRL proposals for the commodities under assessment. For the derived MRL on baby leaf crops, further risk manager consideration is required to decide between two MRL options. Adequate analytical methods for enforcement are available to control the residues of potassium phosphonates in accordance with the residue definition âphosphonic acid and its salts expressed as phosphonic acidâ in the commodities under consideration. Based on the risk assessment results and assuming that the existing MRLs will be amended as proposed by EFSA in previous outputs, EFSA concluded that the longâterm intake of residues resulting from the existing uses of fosetyl and phosphonates (previously assessed in a joint MRL review) and new proposed uses of potassium phosphonates is unlikely to present a risk to consumer health. Considering the toxicological profile of the active substance, a shortâterm dietary risk assessment was not required. The risk assessment shall be regarded as indicative because some MRL proposals derived by EFSA in the framework of the MRL review according to Articles 12 and 43 of Regulation (EC) No 396/2005 require further consideration by risk managers
Review of the existing maximum residue levels for gammaâcyhalothrin according to Article 12 of Regulation (EC) No 396/2005
Abstract According to Article 12 of Regulation (EC) No 396/2005, EFSA has reviewed the maximum residue levels (MRLs) currently established at European level for the pesticide active substance gammaâcyhalothrin. To assess the occurrence of gammaâcyhalothrin residues in plants, processed commodities, rotational crops and livestock, EFSA considered the conclusions derived in the framework of Commission Regulation (EU) No 188/2011, as well as the European authorisations reported by Member States (including the supporting residues data) in the framework of this review. Based on the assessment of the available data, MRL proposals were derived, and a consumer risk assessment was carried out. Although no risk to consumers was identified, some information required by the regulatory framework was missing. The residue definition for monitoring (lambdaâcyhalothrin (includes gammaâcyhalothrin) (sum of R, S and S, R isomers)) covers both lambdaâ and gammaâcyhalothrin. Appropriate enantioselective techniques, which are not commonly used in routine analysis, are required to differentiate gammaâcyhalothrin residues from lambdaâcyhalothrin. According to the available data, it is expected that the MRLs currently set in Regulation (EC) No 396/2005 will cover the uses of gammaâcyhalothrin assessed in the present review. Therefore, risk managers can consider maintaining the existing EU MRLs
Evaluation of confirmatory data following the Article 12 MRL review for quizalofopâPâethyl, quizalofopâPâtefuryl and propaquizafop and modification of the existing maximum residue levels for quizalofopâPâtefuryl
Abstract The applicant Arysta Life Science Great Britain Limited submitted a request to the competent national authority in Croatia to evaluate the confirmatory data that were identified for quizalofopâPâtefuryl in the framework of the maximum residue level (MRL) review under Article 12 of Regulation (EC) No 396/2005 as not available. Since Article 12 data gaps were also set for the two other quizalofopâP variants sharing the same residue definitions for risk assessment and monitoring, EFSA included in the present assessment all quizalofopâP variants: quizalofopâPâethyl, quizalofopâPâtefuryl and propaquizafop. Moreover, in the application submitted to Croatia, the applicant also included a request to modify the existing MRLs for quizalofopâPâtefuryl in grapes, sunflower seeds and soyabeans in accordance with Article 6 of Regulation (EC) No 396/2005. To address the data gaps, new data on hydrolysis efficiency of quizalofopâPâtefuryl, quizalofop acid, quizalofopâpentanoic acid and quizalofopâPâglycerate in different matrices of animal origin in accordance with the guidance document SANTE/2020/12830 Rev.1 were submitted, along with a validated analytical method for animal commodities. EFSA concluded that the data gap on validation of the efficiency of the extraction and hydrolysis included in the enforcement method of residues in livestock animal commodities was only fully addressed for muscle, poultry liver and eggs. Regarding plant commodities, the remaining data gaps were not addressed. EFSA also considered data gaps for quizalofopâpâethyl in caraway as sufficiently addressed in the context of a previous MRL application. In general, the new information provided required a revision of the existing MRLs for several commodities of plant and animal origin. Further risk management considerations are required. Based on the risk assessment results, EFSA concluded that the shortâterm and longâterm intake of residues resulting from the use of quizalofopâPâtefuryl according to the reported agricultural practices is unlikely to present a risk to consumer health
Modification of the existing maximum residue levels and setting of import tolerances for flupyradifurone and DFA in various crops and animal commodities
Abstract In accordance with Article 6 of Regulation (EC) No 396/2005, the applicant Bayer CropScience SAâNV submitted a request to the competent national authority in the Netherlands to modify the existing maximum residue levels (MRLs) and to set import tolerances for the active substance flupyradifurone and its metabolite difluoroacetic acid (DFA) in various plant and animal commodities. The data submitted in support of the requests were found sufficient to derive MRL proposals for flupyradifurone and/or DFA in the crops under consideration. The calculated EU livestock dietary burden indicated that for several animal matrices the EU MRLs for flupyradifurone and/or DFA would need to be modified. Adequate analytical methods for enforcement are available to control the residues of both compounds in the plant and animal commodities under consideration, and in honey. Based on the risk assessment results, EFSA concluded that the proposed and authorised uses of flupyradifurone on various crops and subsequent residues of flupyradifurone and DFA in plant and animal commodities will not result in a consumer exposure exceeding the toxicological reference values and therefore is unlikely to pose a risk to consumers' health
Modification of the existing maximum residue level for clopyralid in honey
Abstract In accordance with Article 6 of Regulation (EC) No 396/2005, the applicant Corteva Agriscience International SĂ rl submitted a request to the competent national authority in Finland to modify the existing maximum residue levels (MRLs) for the active substance clopyralid in honey. The data submitted in support of the request were found to be sufficient to derive MRL proposals for honey. Adequate analytical methods for enforcement are available to control the residues of clopyralid (including potential conjugates) in honey at the validated limit of quantification (LOQ) of 0.001âmg/kg. Based on the risk assessment results, EFSA concluded that the shortâterm and longâterm intake of clopyralid residues in honey, resulting from the authorised use of clopyralid on oilseed rape notified in the present MRL assessment, is unlikely to present a risk to consumer health
Modification of the existing maximum residue levels for flonicamid in various crops
Abstract In accordance with Article 6 of Regulation (EC) No 396/2005, the applicant ISK Biosciences Europe N.V. submitted two requests to the competent national authority in Finland and Belgium, respectively, to modify the existing maximum residue levels (MRLs) for the active substance flonicamid in potatoes and in various crops. The data submitted in support of the requests were found to be sufficient to derive MRL proposals for potatoes, lettuces and salad plants, spinaches and similar leaves, beans (without pods), cardoons, celeries, Florence fennels and rhubarbs. Adequate analytical methods for enforcement are available to control the residues according to the residue definition as of the sum of flonicamid, TFNA and TFNG, expressed as flonicamid in the plant matrices under consideration at the validated limit of quantification (LOQ) of 0.01âmg/kg for each compound. Based on the risk assessment results, EFSA concluded that the shortâterm and longâterm intake of residues resulting from the uses of flonicamid according to the reported agricultural practices is unlikely to present a risk to consumer health
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