Syngenta Crop Protection AG Research Articles

Environmental Risk Assessment of Time-Variable Toxicant Exposure with Toxicokinetic-Toxicodynamic Modeling of Sublethal Endpoints and Moving Time Windows: A Case Study with Ceriodaphnia dubia.

Toxicokinetic-toxicodynamic (TKTD) modeling has received increasing attention in terms of the regulatory environmental risk assessment of chemicals. This type of mechanistic model can integrate all available data from individual-level bioassays into a single framework and enable refined risk assessments by extrapolating from laboratory results to time-variable exposure scenarios, based, for instance, on surface water exposure modeling (e.g., FOCUS). Dynamic energy budget (DEB) models coupled with TKTD modules (DEB-TKTD) constitute the leading approach to assess and predict sublethal effects of chemicals on individual organisms. However, thorough case studies are rare. We provide a state-of-the-art example with the standard aquatic test species Ceriodaphnia dubia and the fungicide azoxystrobin, including all steps, from bespoke laboratory toxicity tests to model calibration and validation, through to environmental risk assessment. Following the framework proposed in the European Food Safety Authority Scientific Opinion from 2018, we designed bespoke good laboratory practice-compliant laboratory toxicity studies based on test guideline 211 of the Organisation for Economic Co-operation and Development and then identified robust parameter values from those data for all relevant model parameters through model calibration. The DEB-TKTD model, DEBtox2019, then informed the design of the validation experiment. Once validated, the model was used to perform predictions for a time-variable exposure scenario generated by FOCUS. A moving time-window approach was used to perform the environmental risk assessment. This assessment method reduces uncertainty in the risk assessment while maintaining consistency with the traditional measures of risk. Environ Toxicol Chem 2024;43:2409-2421. © 2024 Syngenta Crop Protection AG. ibacon GmbH and The Author(s). Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.

THE INFLUENCE OF HERBICIDE PROTECTION TECHNOLOGIES ON ECONOMICALLY VALUABLE TRAITS AND YIELD OF SUNFLOWER HYBRIDS IN THE CENTRAL FOREST-STEPPE OF UKRAINE

In the conditions of the Central Forest-Steppe of Ukraine during 2021–2023, the influence of herbicide protection technologies on the formation of plant height, basket diameter, oil content and yield of sunflower hybrids was studied. Twelve sunflower hybrids were studied: SY Bacardi CLP, NK Kondi, SUZUKA (Syngenta Crop Protection AG), LG5555 CLP, LG5580, LG59580 (Limagrain Europe), ЕS GENESIS, ES Bellamis CL, ES AROMATIC SU (Euralis Semences), P64LP130, PR64F66, P64LE25 (Pioneer Overseas Corporation). Sunflower hybrids were studied using classical, Express (or SUMO), Clearfield® Plus (CLP) herbicide protection technologies. Taking into account the agrometeorological conditions of sunflower hybrids cultivation and their genetic potential, it was found that under the Express Sun (or SUMO) herbicide protection technology of Dupont (consisting of sunflower hybrids resistant to tribenuron-methyl-based products), the most stable was the height of sunflower plants in SUZUKA (194–197 cm) and P64LE25 (206–207 cm) hybrids. According to the technology of herbicide protection Clearfield® Plus (CLP) by BASF (based on the resistance of sunflower hybrids to herbicides of the imidazoline group), the highest stability in plant height was shown by the hybrid LG5555 CLP (175–177 cm). According to the classical technology, using soil and post-emergence herbicides and graminicides with elements of mechanical control, the hybrid ES Bellamis SL had the greatest variation in plant height from 177 cm to 223 cm during the three years of research. The most stable was the diameter of the sunflower basket in the hybrid SI Bacardi CLP (22.3–22.5 cm) with Clearfield® Plus (CLP) herbicide protection technology. According to the Express Sun (or SUMO) herbicide protection technology, high indicators of the basket diameter were obtained in the hybrids ES AROMATIC SU (20.7–23.2 cm) and SUZUKA (19.3–23.3 cm). The highest yields per plot were recorded for hybrids SUZUKA (11.15 kg), ES AROMATIC SU (11.05 kg) and P64LE25 (10.84 kg) using Clearfield® Plus (CLP) herbicide protection technology. The hybrids that provided the best yields and formed high quality seeds were P64LE25 (3.86 t/ha), with an oil content of 47.2%; ES AROMATIC SU (3.95 t/ha), with an oil content of 47.1%; and SUZUKA (3.98 t/ha), with an oil content of 47.7%, using Clearfield® Plus (CLP) herbicide protection technology. With Express Sun (or SUMO) technology, the best hybrid was LG5580 (4.0 t/ha), with an oil content of 48.6%.

Setting of an import tolerance for lambda-cyhalothrin in avocados.

In accordance with Article 6 of Regulation (EC) No 396/2005, the applicant Syngenta Crop Protection AG submitted a request to the competent national authority in Greece to set an import tolerance for the active substance lambda-cyhalothrin in avocados. The data submitted in support of the request were found to be sufficient to derive maximum residue level (MRL) proposals for avocados. Since the general data gap related to toxicity of degradation products formed under sterilisation conditions and identified in the framework of the MRL review has not yet been addressed, a risk management decision is required as to whether it is appropriate to take over the proposed MRLs in the MRL legislation. Adequate analytical methods for enforcement are available to control the residues of lambda-cyhalothrin in the commodity under consideration at the validated limit of quantification (LOQ) of 0.01 mg/kg. Based on the risk assessment results, EFSA concluded that the short-term and long-term intake of residues resulting from the use of lambda-cyhalothrin according to the reported agricultural practice is unlikely to present a risk to consumer health. However, the consumer exposure calculation shall be considered provisional, pending the toxicological assessment of the compounds formed under sterilisation conditions.

Modification of the existing maximum residue level for mandipropamid in radish leaves.

In accordance with Article 6 of Regulation (EC) No 396/2005, the applicant Syngenta Crop Protection AG submitted a request to the competent national authority in the Netherlands to modify the existing maximum residue level (MRL) for the active substance mandipropamid in radish leaves (classified under the subgroup of kales), based on an intended indoor use on radishes. The residue data in radish leaves submitted in support of the request were found to be sufficient to derive an MRL proposal for this commodity. Adequate analytical methods for enforcement are available to control the residues of mandipropamid on the commodity under consideration at the validated limit of quantification (LOQ) of 0.01 mg/kg. Based on the risk assessment results, EFSA concluded that long-term intake of residues resulting from the use of mandipropamid according to the reported agricultural practice is unlikely to present a risk to consumer health. The reliable end points, appropriate for use in regulatory risk assessment are presented.

Evaluation of confirmatory data following the Article 12 MRL review for S-metolachlor.

The applicant Syngenta Crop Protection AG submitted a request to the competent national authority in Germany to evaluate the confirmatory data that were identified for S-metolachlor in the framework of the maximum residue level (MRL) review under Article 12 of Regulation (EC) No 396/2005 as not available. To address the data gaps, a new freezer storage stability study for S-metolachlor in commodities with high acid content was submitted. However, the data gap on storage stability was considered only partially addressed for strawberries because, in the absence of information on the storage time interval of the samples of the residue trials performed on strawberries, no conclusion on the validity of these trials could be drawn. The data gap on the lack of trials to support the good agricultural practice (GAP) on pineapples was not addressed. Consequently, the existing tentative MRLs for strawberries and pineapple cannot be confirmed and EFSA recommends lowering these MRLs to the enforcement limit of quantification (LOQ). Since a new lower LOQ for enforcement in high acid content commodities of 0.01 mg/kg has been validated, it is proposed to change the existing MRL value from 0.05* to 0.01* mg/kg for these two commodities.

Modification of the existing maximum residue level for azoxystrobin in hops.

In accordance with Article 6 of Regulation (EC) No 396/2005, the applicant Syngenta Crop Protection AG submitted a request to the competent national authority in Germany to modify the existing maximum residue level (MRL) for the active substance azoxystrobin in hops. The data submitted in support of the request were found to be sufficient to derive an MRL proposal for hops. Adequate analytical methods for enforcement are available to control the residues of azoxystrobin on the commodity under consideration at the validated limit of quantification (LOQ) of 0.01 mg/kg. Based on the risk assessment results, noting that an acute risk assessment was not deemed necessary for azoxystrobin, EFSA concluded that the long-term intake of residues resulting from the use of azoxystrobin according to the reported agricultural practice is unlikely to present a risk to consumer health.

Modification of the existing maximum residue levels for difenoconazole in wheat and rye.

In accordance with Article 6 of Regulation (EC) No 396/2005, the applicant Syngenta Crop Protection AG submitted an application to the competent national authority in Germany (evaluating Member State, EMS) to modify the existing maximum residue levels (MRLs) for the active substance difenoconazole in wheat and rye grain. The data submitted in support of the request were found sufficient to derive MRL proposals for wheat and rye grain. Adequate analytical methods for enforcement are available to control the residues of difenoconazole in plant matrices under consideration at the validated limit of quantification (LOQ) of 0.01 mg/kg. The submitted data indicate no need to modify the EU MRLs in animal commodities for the existing enforcement residue definition. EFSA concluded that the dietary exposure to difenoconazole residues from the intake of wheat and rye grain is low, noting that the impact of intended uses on the residues in animal commodities and the consumer exposure could not be properly addressed. Overall, the present risk assessment confirms a very narrow margin of safety for the overall chronic exposure and is considered provisional, pending the submission of confirmatory data on possible preferential metabolism/degradation of the four stereo isomers of difenoconazole in plants and animals and the impact of isomerisation on the toxicity of difenoconazole. The assessment is also affected by uncertainties related to the toxicological profile of animal metabolite CGA205375 and, additionally, it does not take into consideration triazole derivative metabolites (TDMs).

Setting of import tolerances for metalaxyl-M in oil palms fruits and peppercorn.

In accordance with Article 6 of Regulation (EC) No 396/2005, the applicant Syngenta Crop Protection AG submitted a request to the competent national authority in Belgium to set an import tolerance for the active substance metalaxyl-M in oil palms fruits and peppercorn (black, green and white). The data submitted in support of the request were found to be sufficient to derive MRL proposals for oil palms fruits and peppercorn. Adequate analytical methods for enforcement are available to control the residues of metalaxyl-M in the commodities under consideration at the validated limit of quantification (LOQ) of 0.01 mg/kg. Based on the risk assessment results, EFSA concluded that the short-term and long-term intake of residues resulting from the use of metalaxyl-M according to the authorised agricultural practices is unlikely to present a risk to consumer health.

Evaluation of confirmatory data following the Article 12 MRL review and modification of the existing maximum residue levels for penconazole in various crops.

The applicant Syngenta Crop Protection AG submitted a request to the competent national authority in Germany to evaluate the confirmatory data that were identified for penconazole in the framework of the maximum residue level (MRL) review under Article 12 of Regulation (EC) No 396/2005 as not available. Moreover, in the application submitted to Germany, the applicant also included a request to raise the existing MRLs in pome fruits, raspberries and blackberries. To address the data gaps, detailed results on the metabolism substudy in tomato, a new storage stability on metabolites CGA127841, CGA132465 and CGA190503 and new residue trials were submitted. The data gap on metabolism was considered satisfactorily addressed. The data gap on complete sets of residue trials analysing simultaneously for monitoring and risk assessment residue definitions was considered addressed for raspberries, blackberries, pumpkins and watermelons; not addressed for pome fruits, stone fruits, grapes, gooseberries, tomatoes and aubergines. The new information provided justified an increase of the existing MRLs for pome fruits, plums, blackberries and raspberries and a revision of the risk assessment performed for penconazole. Adequate analytical methods for enforcement are available to control the residues of penconazole on the commodities under consideration at the validated limit of quantification (LOQ) of 0.01mg/kg. Based on the risk assessment results, EFSA concluded that the short-term and long-term intake of residues resulting from the use of penconazole according to the reported agricultural practices is unlikely to present a risk to consumer health.

Setting of import tolerances for mandipropamid in papayas.

In accordance with Article 6 of Regulation (EC) No 396/2005, the applicant Syngenta Crop Protection AG submitted a request to the competent national authority in Austria to set an import tolerance for the active substance mandipropamid in papayas. The data submitted in support of the request were found to be sufficient to derive an maximum residue level (MRL) proposal of 0.8mg/kg for papayas. Adequate analytical methods for enforcement are available to control the residues of mandipropamid on the commodity under consideration at the validated limit of quantification (LOQ) of 0.01mg/kg. Based on the risk assessment results, EFSA concluded that long-term intake of residues resulting from the use of mandipropamid according to the reported agricultural practice is unlikely to present a risk to consumer health. The reliable end points, appropriate for use in regulatory risk assessment are presented.

Evaluation of confirmatory data following the Article 12 MRL review for thiabendazole.

The applicant Syngenta Crop Protection AG submitted a request to the competent national authority in Spain to evaluate the confirmatory data that were identified for in the framework of the maximum residue level (MRL) review under Article 12 of Regulation (EC) No 396/2005 as not available. To address the data gaps, a new storage stability study, new residues trials and a validated analytical enforcement method for the determination of the relevant residues in animal products were submitted. The data gaps were considered satisfactorily addressed for the plant commodities. The new information provided required a revision of the existing MRL for avocados. As regards the commodities of animal origin, the data gaps were only partially addressed and therefore further risk management considerations are required regarding the revision of the existing MRLs which were derived from Codex MRLs. The risk assessment performed for thiabendazole was also updated. No risk was identified.

Modification of the existing maximum residue levels for prosulfocarb in herbs and edible flowers

In accordance with Article 6 of Regulation (EC) No 396/2005, the applicant Syngenta Crop Protection AG submitted a request to the competent national authority in Portugal to modify the existing maximum residue levels (MRLs) for the active substance prosulfocarb in herbs and edible flowers. The data submitted in support of the request were found to be sufficient to derive MRL proposals for the group of herbs and edible flowers. Adequate analytical methods for enforcement are available to control the residues of prosulfocarb in the commodities under consideration at the validated limit of quantification (LOQ) of 0.01 mg/kg. Based on the risk assessment results, EFSA concluded that the short‐term and long‐term intake of residues resulting from the use of prosulfocarb according to the reported agricultural practice is unlikely to present a risk to consumer health.

Evaluation of confirmatory data following the Article 12 MRL review for diquat.

The applicant Syngenta Crop Protection AG submitted a request to the competent national authority in Sweden to evaluate the confirmatory data that were identified for diquat in the framework of the MRL review under Article 12 of Regulation (EC) No 396/2005 as not available. The applicant provided sufficient data to address the data gaps related to plant metabolism studies and analytical methods for plant and animal products. The data gap requesting further studies to investigate the nature of residues of diquat and its metabolite TOPPS in processed products was not sufficiently addressed. Considering the new studies submitted under the current application and considering that the EU uses for diquat had to be withdrawn following a decision on non‐approval, EFSA proposed the lowering of the existing MRLs to the appropriate limit of quantifications for the commodities under assessment. In addition, EFSA proposed to perform a more comprehensive review of the existing MRLs that were not subject to the current assessment, taking into account the findings and conclusions of the peer review, the consequences of the non‐approval decision and the revisions of Codex MRLs.

Evaluation of confirmatory data following the Article 12 MRL review for metalaxyl-M.

The applicant Syngenta Crop Protection AG submitted a request to the competent national authority in Belgium to evaluate the confirmatory data that were identified for metalaxyl‐M in the framework of the MRL review under Article 43 and Article 12 of Regulation (EC) No 396/2005 as not available. To address the data gaps new data regarding analytical methods for enforcement (validation data for hops and cocoa beans, ILV for fat) and several residue trials data supporting adjusted GAPs for metalaxyl‐M on apples, pears, broccoli, cauliflower, herbs and edible flowers, soya beans and cocoa beans were submitted. Two data gaps concerning analytical methods for enforcement (validation data for hops and cocoa beans, ILV for fat) were considered satisfactorily addressed. However, the data gap on validation of the efficiency of the extraction, hydrolysis and derivatisation steps included in the proposed analytical method for enforcement of residues in livestock was not addressed. The data gap for residue trials supporting authorisations of metalaxyl‐M was partially addressed. The data gap for residue trials supporting authorisations of metalaxyl was not addressed. The new information provided may require a revision of the existing MRLs for several commodities of plant and animal origin. Further risk management considerations are required.

Setting of import tolerances for fludioxonil in sugar beet roots and bananas.

In accordance with Article 6 of Regulation (EC) No 396/2005, the applicant Syngenta Crop Protection AG submitted a request to the competent national authority in France to set import tolerances for the active substance fludioxonil in sugar beet roots and bananas. The data submitted in support of the request were found to be sufficient to derive maximum residue level (MRL) proposals for sugar beet roots and bananas. Adequate analytical methods for enforcement are available to control the residues of fludioxonil in the commodities under consideration at the validated limit of quantification (LOQ) of 0.01 mg/kg and in animal matrices at the validated LOQ of 0.01 mg/kg in milk and muscle and 0.05 mg/kg in liver, kidney, fat tissues and eggs. Based on the risk assessment results, EFSA concluded that the long‐term intake of residues resulting from the use of fludioxonil according to the reported agricultural practices is unlikely to present a risk to consumer health.

Setting of import tolerances for azoxystrobin in mangoes and oil palm fruits.

In accordance with Article 6 of Regulation (EC) No 396/2005, the applicant Syngenta Crop Protection AG submitted a request to the competent national authority in Austria to set an import tolerance for the active substance azoxystrobin in mangoes and oil palm fruits imported from Brazil and Colombia, respectively. The data submitted in support of the request were found to be sufficient to derive maximum residue level (MRL) proposals for mangoes and oil palm fruits. Adequate analytical methods for enforcement are available to control the residues of azoxystrobin on the commodities under consideration at the validated limit of quantification (LOQ) of 0.01 mg/kg. Based on the risk assessment results, noting that an acute risk assessment was not deemed necessary for azoxystrobin, EFSA concluded that the long‐term intake of residues resulting from the uses of azoxystrobin according to the reported agricultural practices is unlikely to present a risk to consumer health.

Modification of the existing maximum residue levels for benzovindiflupyr in leeks and spring onions/green onions/Welsh onions.

In accordance with Article 6 of Regulation (EC) No 396/2005, the applicant Syngenta Crop Protection AG submitted a request to the competent national authority in France to modify the existing maximum residue levels (MRLs) for the active substance benzovindiflupyr in leeks and spring onions, green onions and Welsh onions. The data submitted in support of the request were found to be sufficient to derive MRL proposals for the crops under assessment. Adequate analytical methods for enforcement are available to control the residues of benzovindiflupyr on the commodities under consideration at the validated limit of quantification (LOQ) of 0.01 mg/kg. Based on the risk assessment results, EFSA concluded that the short‐term and long‐term intake of residues resulting from the use of benzovindiflupyr 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 thiabendazole in various crops

In accordance with Article 6 of Regulation (EC) No 396/2005, the applicant Syngenta España S.A. submitted a request to the competent national authority in Spain to modify the existing maximum residue levels (MRLs) in citrus fruits, bananas and witloofs. Additionally, Syngenta Crop Protection AG submitted two applications to Spain to set import tolerances in mangoes and in sweet potatoes. The data submitted in support of the requests were found to be sufficient to derive MRL proposals for the commodities under evaluation and for commodities of animal origin. Adequate analytical methods for enforcement are available to control the residues of thiabendazole in the commodities under consideration and in animal matrices at the validated limit of quantification (LOQ) of 0.01 mg/kg. Based on the risk assessment results, EFSA concluded that the short‐term and long‐term intake of residues resulting from the use of thiabendazole according to the reported agricultural practices is unlikely to present a risk to consumer health.

Evaluation of confirmatory data following the Article 12 MRL review for propiconazole.

The applicant Syngenta Crop Protection AG submitted a request to the competent national authority in Finland to evaluate the confirmatory data that were identified for propiconazole in the framework of the MRL review under Article 12 of Regulation (EC) No 396/2005 as not available. Following the decision on the non‐renewal of the approval of propiconazole and the decision to lower the maximum residue levels (MRLs) for propiconazole to the limit of quantification (LOQ) for all commodities, the data gaps identified in the MRL review are no longer relevant. EFSA summarised some new studies on the toxicological profile of propiconazole metabolites CGA91305, SYN547889 and NOA436613, which were assessed by the rapporteur Member State. Overall, the available information is not sufficient to characterise the toxicological profile of metabolites convertible to 2,4‐dichlorobenzoic acid as data gaps still exist for SYN547889, NOA436613, CGA118244, CGA118245, CGA91304 and CGA91305.

Setting of import tolerance for azoxystrobin in sugar beet roots.

In accordance with Article 6 of Regulation (EC) No 396/2005, the applicant Syngenta Crop Protection AG submitted a request to the competent national authority in Austria to set an import tolerance for the active substance azoxystrobin in sugar beet roots. The data submitted in support of the request were found to be sufficient to derive maximum residue level (MRL) proposals for sugar beet roots. However, robust processing factors for Annex VI in view of monitoring of residues in processed commodities could not be derived. Adequate analytical methods for enforcement are available to control the residues of azoxystrobin in plant and animal matrices at the validated limit of quantification (LOQ) of 0.01 mg/kg. Based on the risk assessment results, EFSA concluded that the short‐term and long‐term intake of residues resulting from the use of azoxystrobin according to the reported agricultural practice is unlikely to present a risk to consumer health.