Modification of the existing maximum residue level for dodine in honey

Abstract

In accordance with Article 6 of Regulation (EC) No 396/2005, the applicant Arysta Lifescience Benelux Srl submitted a request to the competent national authority in Spain to modify the existing maximum residue level (MRL) for the active substance dodine in honey. The data submitted in support of the request were found to be sufficient to derive an MRL proposal for honey. An adequate analytical method for enforcement is available to control the residues of dodine in honey 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 the potential transfer of dodine residues in honey, in accordance with the reported agricultural practices on melliferous crops, is unlikely to present a risk to consumer health.

SUMMARY

In accordance with Article 6 of Regulation (EC) No 396/2005, Arysta Lifescience Benelux Srl submitted an application to the competent national authority in Spain (evaluating Member State, EMS) to modify the existing maximum residue level (MRL) for the active substance dodine in honey. The application, alongside the dossier containing the supporting data in IUCLID format, was submitted through the European Food Safety Authority (EFSA) Central Submission System on 11 December 2023. The appointed EMS Spain assessed the dossier and declared its admissibility on 29 January 2024. Subsequently, following the implementation of the EFSA's confidentiality decision, the non‐confidential version of the dossier was published by EFSA, and a public consultation launched on the dossier. The consultation aimed to consult stakeholders and the public on the scientific data, studies and other information part of, or supporting, the submitted application, to identify whether other relevant scientific data or studies are available. The consultation run from 27 February 2024 to 19 March 2024. No additional data nor comments were submitted in the framework of the consultation.

At the end of the commenting period, the EMS proceeded drafting the evaluation report, in accordance with Article 8 of Regulation (EC) No 396/2005. Initially, the assessment of the current MRL application was merged with the peer review process for renewal of approval. Then the assessment was split from the peer review, upon request from the applicant. Subsequently, a standalone Evaluation Report was submitted by the EMS Spain to the European Commission and to EFSA, on 3 December 2025.

To accommodate for residues in honey resulting from the treatment of melliferous crops according to authorised EU uses, the EMS proposed to raise the existing MRL for honey from the limit of quantification (LOQ) of 0.05 to 0.3 mg/kg.

EFSA assessed the dossier and the evaluation report as required by Article 10 of the MRL regulation. EFSA identified points which needed a further clarification and requested the EMS to address them. The applicant provided the requested information in an updated IUCLID dossier. The additional information was duly considered by the EMS who submitted a revised evaluation report to EFSA on 16 February 2026, which replaced the previously submitted evaluation report.

Based on the conclusions derived by EFSA in the framework of Directive 91/414/EEC, the data evaluated under previous MRL assessments and the additional data provided by the EMS in the framework of this application, the following conclusions are derived.

In the absence of specific metabolism studies on honey and considering that the metabolic profile of dodine was elucidated in primary fruit crops only and that no degradation was observed under standard hydrolysis conditions for pasteurisation, EFSA concluded that the same residue definitions for enforcement and risk assessment derived for fruits crops (tentative for tree nuts) in the framework of the review of existing MRLs according to Article 12 of Regulation (EC) No 396/2005‐ of the active substance dodine are also applicable for honey. It is further noted that the residue definitions proposed for honey may need to be reconsidered in case an authorisation for the use of dodine on a tree nut or on any other crops belonging to plant groups different than fruits and classified as melliferous crops is proposed in the future.

A sufficiently validated analytical method based on high‐performance liquid chromatography with tandem mass spectrometry (HPLC–MS/MS) is available to quantify residues in the commodity assessed in this application according to the enforcement residue definition. The method enables quantification of dodine residues at or above the LOQ of 0.01 mg/kg in the commodity assessed (honey).

The available residue trials are sufficient to derive an MRL proposal of 0.3 mg/kg for honey. The MRL was derived based on a dataset of four semi‐field (tunnel) trials (two in Germany and two in Spain), performed on Phacelia tanacetifolia as surrogate crop and according to the most critical scenario for residues expected in honey from the authorised EU uses.

Residues of dodine in commodities of animal origin were not assessed since honey – the commodity under consideration in this MRL application‐ is not normally used as feed item to livestock.

The toxicological profile of dodine was assessed in the framework of the EU pesticides peer review under Directive 91/414/EEC and the data were sufficient to derive an acceptable daily intake (ADI) of 0.1 mg/kg body weight (bw) per day and an acute reference dose (ARfD) of 0.1 mg/kg bw.

The consumer risk assessment was performed with revision 3.1 of the EFSA Pesticide Residues Intake Model (PRIMo). The consumer risk assessment did not identify concerns related to the acute exposure to dodine from honey, which was estimated for 0.4% of the ARfD (NL toddler diet). The total calculated chronic intake accounted for a maximum of 7% of the ADI (GEMS/Food G08 diet), with a contribution of residues expected in honey to the overall long‐term exposure accounting for 0.003% of the ADI (DE child).

EFSA concluded that the short‐term and long‐term intake of the potential transfer of dodine residues in honey, in accordance with the reported agricultural practices on melliferous crops, is unlikely to present a risk to consumer health.

It needs to be noted that the peer review for renewal of approval of the active substance dodine in accordance with Regulation (EC) No 1107/2009 is ongoing and therefore the conclusions reported in this reasoned opinion might need to be reconsidered in the light of the outcome of the peer review.

EFSA proposes to amend the existing MRL as reported in the summary table below.

Full details of all end points and the consumer risk assessment can be found in Appendices B, C, D.

Code a	Commodity	Existing EU MRL (mg/kg)	Proposed EU MRL (mg/kg)	Comment/justification
Enforcement residue definition: Dodine
1040000	Honey and other apiculture products b	0.05*	0.3	The submitted data are sufficient to derive an MRL proposal for honey. Risk for consumers unlikely

Abbreviation: MRL, maximum residue level.

^*Indicates that the MRL is set at the limit of analytical quantification (LOQ).

^a Commodity code number according to Annex I of Regulation (EC) No 396/2005.

^b According to Regulation (EC) No 396/2005 (as amended by Commission Regulation (EU) 2018/62) MRLs are not applicable to other apiculture products until individual products have been identified and listed within this group.

ASSESSMENT

The European Food Safety Authority (EFSA) received an application to modify the existing maximum residue level (MRL) for dodine in honey. The current MRL application is not linked to one specific good agricultural practice (GAP) but is related to the existing uses in crops that might be attractive to bees and that are a potential source for residues of dodine in honey. The critical GAPs identified by the applicant and EFSA are reported in Appendix A.

Dodine is the ISO common name for 1‐dodecylguanidinium acetate (IUPAC). The chemical structures of the active substance and its main metabolites is reported in Appendix E.

Dodine was evaluated in the framework of Directive 91/414/EEC ¹ with Portugal designated as rapporteur Member State (RMS) for the representative uses as a foliar treatment on apples, pears, peaches and cherries. The draft assessment report (DAR) prepared by the RMS has been peer reviewed by EFSA (2010). Dodine was approved ² for the use as fungicide on 1 June 2011. The process of peer review for the renewal of the first approval is currently ongoing. ³

The EU MRLs for dodine are established in Annex II of Regulation (EC) No 396/2005. ⁴ The review of existing MRLs according to Article 12 of Regulation (EC) No 396/2005 (MRL review) has been performed (EFSA, 2015) and the proposed modifications have been implemented in the MRL legislation. After completion of the MRL review, EFSA has issued two reasoned opinions on the modification of MRLs for dodine, in citrus and grapes respectively (EFSA, 2021, 2025). Recent MRL regulation ⁵ has considered the proposals of the reasoned opinion on citrus (EFSA, 2021), however, the latest assessment of dodine in grapes (EFSA, 2025) has not yet been implemented.

In accordance to Article 6 of Regulation (EC) No 396/2005 and following the provisions set by the ‘Transparency Regulation’ (EU) 2019/1381, ⁶ the applicant Arysta Lifescience Benelux Srl submitted on 11 December 2023 an application to the competent national authority in Spain, alongside the dossier containing the supporting data using the IUCLID format.

The appointed evaluating Member State (EMS) Spain assessed the dossier and declared its admissibility on 29 January 2024. Subsequently, following the implementation of the EFSA's confidentiality decision, the non‐confidential version of the dossier was published by EFSA, and a public consultation launched on the dossier. The consultation aimed to consult stakeholders and the public on the scientific data, studies and other information part of, or supporting, the submitted application, to identify whether other relevant scientific data or studies are available. The consultation run from 27 February 2024 to 19 March 2024. No additional data nor comments were submitted in the framework of the consultation.

At the end of the commenting period, the EMS proceeded drafting the evaluation report, in accordance with Article 8 of Regulation (EC) No 396/2005. The assessment of the MRL application was initially merged with the peer review process for renewal of approval, and then split, upon request from the applicant, in December 2025. The new Evaluation Report was submitted to the European Commission and to EFSA on 3 December 2025.

To accommodate for residues in honey resulting from the treatment of melliferous crops according to authorised EU uses, the EMS proposed to raise the existing MRL for honey from the limit of quantification (LOQ) to 0.3 mg/kg.

EFSA assessed the dossier and the evaluation report as required by Article 10 of the MRL regulation. EFSA identified points which needed further clarification and requested the EMS to address them. The applicant provided the requested information in an updated IUCLID dossier. The additional information was duly considered by the EMS who submitted a revised evaluation report to EFSA on 16 February 2026, which replaced the previously submitted evaluation report.

EFSA based its assessment on the evaluation report submitted by the EMS, the draft assessment report (DAR) and its addendum (Portugal, 2006, 2009) prepared under Directive 91/414/EEC, the Commission review report on dodine (European Commission, 2010b), the conclusion on the peer review of the pesticide risk assessment of the active substance dodine (EFSA, 2010), as well as the conclusions from previous EFSA opinions on dodine, including the reasoned opinion on the MRL review according to Article 12 of Regulation No 396/2005 (EFSA, 2013a, 2013b, 2015, 2021, 2025).

For this application, the data requirements established in Regulation (EU) No 544/2011 and the guidance documents applicable at the date of submission of the IUCLID application are applicable (European Commission, 1997a, 1997b, 1997c, 1997d¸1997e, 1997f, 1997g, 2010a, 2018, 2023a, 2023b, 2023c; OECD, 2007, 2011). The assessment is performed in accordance with the legal provisions of the Uniform Principles for the Evaluation and the Authorisation of Plant Protection Products adopted by Commission Regulation (EU) No 546/2011. ⁷

As the EU pesticides peer review of the active substance in accordance with Regulation (EC) No 1107/2009 is not yet finalised, the conclusions reported in this reasoned opinion may need to be reconsidered in the light of the outcome of the peer review.

An updated list of end points including the studies assessed by EFSA in the framework of this MRL application, is presented in Appendix B.

The evaluation report submitted by the EMS (Spain, 2025) and the exposure calculations using the EFSA Pesticide Residues Intake Model (PRIMo) are made publicly available as background documents to this reasoned opinion. ⁸

1. RESIDUES IN PLANTS

1.1. Nature of residues and methods of analysis in plants

1.1.1. Nature of residues in primary crops

The metabolism of dodine was assessed in the framework of the EU pesticides peer review under Directive 91/414/EEC (EFSA, 2010) and in the framework of the MRL review (EFSA, 2015). Metabolism of dodine in primary crops was investigated after foliar applications on fruit crop group (apples, strawberries, pecans) using ¹⁴C‐labelled dodine at the guanidine carbon. While the metabolic pattern of dodine was shown to be similar, parent dodine was predominant in apples and strawberries, while in nutmeat, dodine accounted for 13% of the total radioactive residue (TRR) only. Metabolite guanidine was the major compound recovered (36% TRR) and the other significant part of the radioactivity was associated to fatty acid fractions. Thus, the residue definition for monitoring and risk assessment was defined as dodine only, with exception of nuts (EFSA, 2010, 2015).

For the uses on the fruit crops triggering this honey assessment, the metabolic behaviour in primary crops is considered as sufficiently addressed.

1.1.2. Nature of residues in rotational crops

The uses related to this assessment of dodine are on permanent crops, and in addition dodine exhibits low persistence in soil, below the trigger value of 100 days (EFSA, 2010). Therefore, an investigation of the nature of residues in rotational crops is not required (European Commission, 1997c).

1.1.3. Nature of residues in processed commodities

The effect of processing on the nature of dodine was investigated in the framework of the EU pesticides peer review (EFSA, 2010). Dodine is hydrolytically stable under the representative processing conditions of pasteurisation, baking, brewing, boiling, and sterilisation.

1.1.4. Analytical methods for enforcement purposes in plant commodities

Analytical methods for the determination of dodine residues in plant commodities were assessed during the EU pesticides peer review under Directive 91/414/EEC (EFSA, 2010) and in the previously issued EFSA reasoned opinions (EFSA, 2013a, 2013b, 2015, 2021, 2025). These analytical methods are sufficiently validated to enforce dodine residues with a LOQ of 0.01 mg/kg in high acid and high oil content plant commodities and a LOQ of 0.05 mg/kg in high water content plant commodities.

Therefore, EFSA previously concluded that sufficiently validated analytical methods are available to monitor residues of dodine in the plant commodities for currently authorised uses at or above the LOQ of 0.01 and 0.05 mg/kg, depending on the matrix. Since extraction efficiency for the analytical methods for enforcement (and used for the residue trials) in plants was not proven, EFSA recommended reconsidering this point in the broader framework of the EU pesticide peer review for the ongoing renewal assessment of approval of the active substance (EFSA, 2025).

1.1.5. Storage stability of residues in plants

The storage stability of dodine in plants stored under frozen conditions was investigated in the framework of previous EFSA assessments in high water and high oil content groups (EFSA, 2010, 2013b). Dodine residues were shown to be stable for up to 18 months when stored frozen at −18°C in high water content matrices (apples, peaches, cherries) (EFSA, 2010). Moreover, storage stability of dodine was demonstrated for a period of 9 months at −20°C in high oil content commodities (peanuts) (EFSA, 2013b). Within a previous application, a storage stability study was considered valid and demonstrated that dodine is stable in high acid, high water, high oil content (orange peel, orange pulp, apples, carrots, olives) and in dry commodities (dry beans) at a temperature of −20°C for at least 24 months (EFSA, 2025).

1.1.6. Proposed residue definitions

Based on the metabolic pattern identified in the metabolism studies, the results of the hydrolysis studies, and the capabilities of enforcement analytical methods, the following residue definitions were proposed for fruit crops (EFSA, 2015):

• residue definition for risk assessment: dodine (for fruit crops; tentative for tree nuts).

• residue definition for enforcement: dodine (for fruit crops, tentative for tree nuts).

The same residue definitions are applicable to processed products.

The residue definition for enforcement set in Regulation (EC) No 396/2005 is identical with the above‐mentioned residue definition.

Since in pecan parent compound underwent extensive metabolism, with guanidine being the predominant compound (see Section 1.1.1), the setting of residue definitions for enforcement and risk assessment, considering the possible inclusion of this metabolite, remains open and will be re‐considered should an authorisation for use of dodine on a tree nut be proposed in the future (EFSA, 2015).

1.1.7. Magnitude of residues in plants

Not relevant for the present MRL application on honey.

2. RESIDUES IN LIVESTOCK

Not relevant for the present MRL application on honey.

3. RESIDUES IN HONEY

3.1. Nature of residues in honey

Honey is produced by bees from sugary secretions of plants (floral nectar mainly) through regurgitation, enzymatic conversion and water evaporation and followed by storage in the bee hives.

In the absence of specific metabolism studies with honeybees, studies investigating the nature of residues in primary crops and rotational crops and studies investigating the degradation during pasteurisation should be considered to determine the nature of residues in honey (European Commission, 2018). It is likely that the nature of residues in pollen and nectar collected from primary and rotational crops, as well as in honey (resulting from the residues in floral nectar), is the same as in primary and rotational crops.

Considering that sufficient data investigating the metabolic profile in primary fruit crops and the degradation of the active substance dodine under standard hydrolysis conditions are available, no further information is considered as necessary for the current application on honey according to the guidelines.

3.1.1. Analytical methods for enforcement in honey

In the framework of the present assessment the applicant submitted the validation results for a method for enforcement of dodine residues in honey which was assessed by the EMS (Spain, 2025). The method, based on liquid chromatography with tandem mass spectrometry (LC–MS/MS), was validated in honey at the LOQ of 0.01 mg/kg. For confirmation, an additional mass transition was measured and evaluated quantitatively. An independent laboratory validation (ILV) was provided (Spain, 2025).

Information on extraction efficiency of the analytical method for enforcement of residues in honey is not required according to the guidance document on extraction efficiency (European Commission, 2023c).

EFSA concludes that a sufficiently validated analytical method for monitoring dodine residues in honey at the LOQ of 0.01 mg/kg is available.

3.1.2. Storage stability of residues in honey

The storage stability of residues of dodine in honey samples stored under frozen conditions was investigated in the current MRL application (Spain, 2025). The applicant submitted the results of a storage stability study investigating the stability of dodine residues in honey over a period of 179 days. Honey samples were fortified at a concentration of 1 mg/kg and stored frozen at −18°C. Triplicate samples were analysed at the start of storage and after 179 days. The analytical method used was fully validated and considered fit for purpose.

It was demonstrated that residues of dodine were stable for at least 6 months (179 days) when stored at −18°C in honey.

3.1.3. Proposed residue definitions

In the absence of specific metabolism studies on honey, the studies investigating the nature of residues in primary crops and studies investigating the degradation of dodine during standard hydrolysis conditions for pasteurisation are considered to derive the residue definitions for honey; the same residue definitions as mentioned for plant (fruits) commodities (see Section 1.1.6) are therefore proposed for honey: Dodine.

The residue definitions for enforcement and risk assessment in honey might need to be reconsidered in the context of proposed future uses of dodine on tree nuts or on any other crops belonging to plant groups ⁹ different than fruits and classified as melliferous crop (European Commission, 2018) and in light of the outcome of the ongoing renewal of the approval assessment.

3.2. Magnitude of residues in honey

Studies investigating the magnitude of residues in honey were submitted with the current application.

The applicant submitted the results of four semi‐field (tunnel) trials (two in Germany and two in Spain), performed on Phacelia tanacetifolia. In these trials, dodine was applied as foliar application twice, each application at 0.9 kg dodine per hectare, on Phacelia tanacetifolia at growth stages between BBCH 61 and 63 (beginning of flowering) for the first application and the second application was carried out 7–8 days thereafter (BBCH 67–69). Phacelia has a high melliferous capacity and may represent a worst‐case scenario in terms of attractiveness to bees compared to pome fruits (European Commission, 2018).

It is noted that the interval between applications in the trials is shorter than in the Good Agricultural Practice (GAP) on peaches selected by the EMS, which is currently assessed as a representative use in the ongoing peer review renewal assessment (Spain, 2025). According to the EMS, the northern Europe (NEU) GAP on peaches with 21 days interval between the two applications is also authorised (Poland, Slovakia, Slovenia). However, noting that the trials are fully compliant with the southern Europe (SEU) GAP on peaches assessed in a previous application and in the context of the MRL review (critical minimum interval between applications of 7 days) (EFSA, 2013b, 2015), EFSA is of the opinion that this SEU GAP on peaches shall be selected to assess the potential transfer of residues of dodine in honey. Therefore, the submitted trials are considered to fully support the critical use authorised on peaches, which triggers the honey assessment in the context of this application (see Appendix A).

The honeybee colonies were introduced in the tunnels the evening before the first application. In the evening before or in the morning prior to the application, two to three empty combs were placed in the brood body and marked. Honey was collected only from these combs at maturity (water content < 20%), within 7–14 days after the last application. In one honey sample from a control plot, the water content was above 20% and this sample was dried before analysis. The weight of treated samples (ranged between 102.8 and 178.8 g) was sufficient. Honey specimens were analysed for residues of dodine only. Residues of dodine ranged from < 0.01 to 0.12 mg/kg. Results of control samples were all below the LOQ of dodine in honey. There were no major deviations that could affect the validity of the study results. These studies were assessed by the EMS and concluded as valid (Spain, 2025). EFSA supports this conclusion.

The analytical method used is sufficiently validated for the quantification of residues of dodine and is fit for purpose. The analytical method used in the trials was based on LC–MS/MS detector with a LOQ of 0.01 mg/kg for determination of dodine in honey (Spain, 2025). Information on extraction efficiency of the analytical methods for data generation in honey samples is not available and is not required according to the guidance document on extraction efficiency (European Commission, 2023c).

The samples of these residue trials were stored for no more than 6 months before analysis, which are the conditions for which integrity of the samples has been demonstrated.

The dataset is sufficient to derive an MRL proposal of 0.3 mg/kg for honey based on the critical GAP currently authorised on melliferous crops (SEU use assessed during the MRL review, EFSA, 2015) covering the NEU/SEU uses on peaches reported in the current assessment (see Appendix A).

It should be noted that currently, the MRLs set for honey are not applicable to other apicultural products following Commission Regulation (EU) 2018/62. ¹⁰

3.2.1. Proposed MRLs

The available data are considered sufficient to derive an MRL proposal of 0.3 mg/kg as well as risk assessment input values for honey (see Appendix B.3.2.1). In Section 4, EFSA assessed whether residues on honey resulting from the currently authorised uses are likely to pose a consumer health risk.

It should be noted that currently, MRLs set for honey are not applicable to other apicultural products according to Annex I of Regulation (EC) No 396/2005 as amended by Commission Regulation (EU) 2018/62.¹⁰

4. CONSUMER RISK ASSESSMENT

EFSA performed a dietary risk assessment using revision 3.1 of the EFSA PRIMo (EFSA, 2018, 2019). This exposure assessment model contains food consumption data for different sub‐groups of the EU population and allows the acute and chronic exposure assessment to be performed in accordance with the internationally agreed methodology for pesticide residues (FAO, 2016).

The calculations were based on the highest residue (HR) or median residue values (STMR) derived from residue data and the complete list of input values that can be found in Appendix D.1. Peeling factors were applied for banana and citrus fruits (EFSA, 2013a, 2015, 2021, 2025).

The toxicological profile of dodine was assessed in the framework of the EU pesticides peer review under Directive 91/414/EEC and the data were sufficient to derive an acceptable daily intake (ADI) of 0.1 mg/kg body weight (bw) per day and an acute reference dose (ARfD) of 0.1 mg/kg bw (European Commission, 2010b).

The short‐term exposure, which was performed only for honey using the HR, did not exceed the ARfD for honey assessed in this application (see Appendix B.4). The consumer risk assessment did not identify concerns from acute exposure to dodine in honey (0.4% of the ARfD, NL toddler diet).

For the calculation of the chronic exposure to dodine from honey, EFSA used the STMR value derived from the four residue trials on Phacelia tanacetifolia compliant with the critical GAPs on peaches triggering the honey assessment (see Section 3.2; Appendix B.3.2.1). For the remaining products of plant and animal origin, the STMR values as reported by a previous MRL assessment (EFSA, 2021) ¹¹ which updated the dietary consumer risk assessment of the comprehensive MRL review (EFSA, 2015) were used. EFSA also included the STMR from a recent MRL proposal on grapes which is not yet considered by risk manager for implementation in EU legislation (EFSA, 2025). The Codex MRLs implemented in the EU MRL legislation and the STMR values derived by JMPR were considered in the risk assessment (EFSA, 2015; FAO & WHO, 2003). For blueberries, cranberries, currants, gooseberries and celery, the MRLs were lowered to the LOQ of 0.01 mg/kg in the Commission Regulation (EU) 2016/1002 ¹² and were therefore not considered in the calculations.

No concerns from long‐term exposure to dodine were identified for any of the European diets incorporated in the EFSA PRIMo. The total calculated intake accounted for a maximum of 7% of the ADI (GEMS/Food G08 diet). The contribution of residues in honey was low (0.003% of ADI for DE child diet).

EFSA concluded that the short‐term and long‐term intake of the potential transfer of dodine residues in honey, in accordance with the reported agricultural practices on melliferous crops, is unlikely to present a risk to consumer health.

For further details on the exposure calculations, a screenshot of the Report sheet of the PRIMo is presented in Appendix C.

5. CONCLUSION AND RECOMMENDATIONS

The data submitted in support of this MRL application were found to be sufficient to derive an MRL proposal of 3 mg/kg for honey.

EFSA concluded that the short‐term and long‐term intake of the potential transfer of dodine residues in honey, following use in accordance with the reported agricultural practices on melliferous crops, is unlikely to present a risk to consumer's health.

The peer review for renewal of approval of the active substance dodine in accordance with Regulation (EC) No 1107/2009 is ongoing and therefore the conclusions reported in this reasoned opinion might need to be reconsidered in the light of the outcome of the peer review.

The MRL recommendations are summarised in Appendix B.5.

ABBREVIATIONS

a.s.

active substance

ADI

acceptable daily intake

ARfD

acute reference dose

BBCH

growth stages of mono‐ and dicotyledonous plants

bw

body weight

CF

conversion factor for enforcement to risk assessment residue definition

CXL

Codex maximum residue limit

DALA

days after last application

DAR

draft assessment report

DAT

days after treatment

DT₉₀

period required for 90% dissipation (define method of estimation)

EMS

evaluating Member State

FAO

Food and Agriculture Organization of the United Nations

GAP

Good Agricultural Practice

GC–MS

gas chromatography with mass spectrometry

HPLC–MS/MS

high‐performance liquid chromatography with tandem mass spectrometry

HR

highest residue

IEDI

international estimated daily intake

IESTI

international estimated short‐term intake

ILV

independent laboratory validation

ISO

International Organisation for Standardisation

IUPAC

International Union of Pure and Applied Chemistry

JMPR

Joint FAO/WHO Meeting on Pesticide Residues

LC–MS/MS

liquid chromatography with tandem mass spectrometry

LOQ

limit of quantification

MRL

maximum residue level

MS

Member States

NEU

northern Europe

OECD

Organisation for Economic Co‐operation and Development

PBI

plant‐back interval

PHI

pre‐harvest interval

PRIMo

(EFSA) Pesticide Residues Intake Model

RA

risk assessment

RAC

raw agricultural commodity

RD

residue definition

RMS

rapporteur Member State

SANCO

Directorate‐General for Health and Consumers

SC

suspension concentrate

SEU

southern Europe

STMR

supervised trials median residue

TRR

total radioactive residue

WHO

World Health Organization

REQUESTOR

European Commission

QUESTION NUMBER

EFSA‐Q‐2023‐00874

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APPENDIX A. Critical GAP triggering the assessment of an MRL in honey

The GAP on peaches below has been identified by the applicant as the worst‐case authorised EU GAP of dodine on primary crops for the residue carry‐over to honey. However, EFSA identified an authorised SEU use on peaches assessed during the MRL review considered as more critical because the interval between applications is shorter (7–10 days instead of 21 days) (highlighted in bold). This worst‐case treatment pattern (application rate and timing) was selected to design tunnel trials with a melliferous surrogate crop (Phacelia tanacetifolia) and to investigate magnitude of residues in honey (Spain, 2025). Since the assessment of the current MRL application on honey was initially merged with the ongoing renewal assessment and subsequently split, additional representative uses are listed which are currently reported under this process for information purposes.

Crop and/or situation	NEU, SEU, MS or country	F, G or I a	Pests or group of pests controlled	Preparation		Application				Application rate per treatment				PHI (days) d	Remarks
				Type b	Conc.a.s.	Method kind	Range of growth stages & season c	Number min–max	Interval between application (days) min–max	g a.s./hL min–max	Water (L/ha) min–max	Rate min–max	Unit
Peach	SEU	F	Peach leaf curl (Taphrina deformans)	SC	400 g/L	Foliar treatment – spraying	BBCH 1‐69	2	7–10			0.9	kg/ha	75	Critical GAP assessed by EFSA (EFSA, 2013b, 2015)
Peach e	NEU	F	Peach leaf curl (Taphrina deformans (TAPHDE))	SC	544 g/L	Air‐assisted broadcast spraying/broadcast on foliage/plant	BBCH 01‐69	1–2	21		600–1500	0.9–0.9	kg/ha	n.a.
Peach f	SEU	F	Peach leaf curl (Taphrina deformans (TAPHDE))	SC	544 g/L	Air assisted broadcast spraying/broadcast on foliage/plant	BBCH 01‐69	1–2	21		600–1500	0.9–0.9	kg/ha	n.a.
Apple	NEU	F	Scab of pear (Venturia pyrina (VENTPI))	SC	544 g/L	Air‐assisted broadcast spraying/broadcast on foliage/plant	BBCH 01‐74	1–2	21		500–1500	0.68–0.68	kg/ha	60	Crop destination: grown for human consumption (3HCOND) App. rate product: 1.25–1.25 L/ha. Max. annual a.s.: 1.36 kg/ha
Apple	SEU	F	Scab of pear (Venturia pyrina (VENTPI))	SC	544 g/L	Air‐assisted broadcast spraying/broadcast on foliage/plant	BBCH 01‐74	1–2	21		500–1500	0.68–0.68	kg/ha	60
Pears	NEU	F	Scab of pear (Venturia pyrina (VENTPI))	SC	544 g/L	Air‐assisted broadcast spraying/broadcast on foliage/plant	BBCH 01‐ till 74 days before harvest	1–2	21		500–1500	0.68–0.68	kg/ha	60	Crop destination: grown for human consumption (3HCOND) App. rate product: 1.25–1.25 L/ha. Max. annual a.s.: 1.36 kg/ha
Pears	SEU	F	Scab of pear (Venturia pyrina (VENTPI))	SC	544 g/L	Air‐assisted broadcast spraying/broadcast on foliage/plant	BBCH 01‐ till 74 days before harvest	1–2	21		500–1500	0.68–0.68	kg/ha	60
Cherries	NEU	F	Cherry leaf spot (Blumeriella jaapii (BLUMJA))	SC	544 g/L	Air‐assisted broadcast spraying/broadcast on foliage/plant	BBCH 60‐79	1–2	21		500–1500	0.68–0.68	kg/ha	14	Crop destination: grown for human consumption (3HCOND) App. rate product: 1.25–1.25 L/ha Max. annual a.s.: 1.36 kg/ha
Cherries	SEU	F	Cherry leaf spot (Blumeriella jaapii (BLUMJA))	SC	544 g/L	Air‐assisted broadcast spraying/broadcast on foliage/plant	BBCH 60‐79	1–2	21		500–1500	0.68–0.68	kg/ha	14

Abbreviations: a.s., active substance; GAP, Good Agricultural Practice; MRL, maximum residue level; MS, Member State; NEU, northern European Union; SC, suspension/flowable concentrate; SEU, southern European Union.

^a Outdoor or field use (F), greenhouse application (G) or indoor application (I).

^b CropLife International Technical Monograph no 2, 7th Edition. Revised March 2017. Catalogue of pesticide formulation types and international coding system.

^c Growth stage range from first to last treatment (BBCH Monograph, Growth Stages of Plants, 1997, Blackwell, ISBN 3‐8263‐3152‐4), including, where relevant, information on season at time of application.

^d PHI – minimum pre‐harvest interval. EFSA note that according to the table 4 of the guidance SANTE/2019/12752 for fruits a significant part of the edible part is present from full blossom (BBCH 65) onwards and the setting of a PHI is needed.

^e A NEU use on peaches was not assessed during the MRL review (EFSA, 2015), however the EMS reported to EFSA that ‘the following GAP was meanwhile authorised in Poland, Slovakia and Slovenia and this use is among the representative uses of the AIR procedure and, according to the information provided by the applicant in the AIR dossier’ (GAP clarification; February 2026).

^f EFSA assessed a GAP with a shorter interval between applications for a SEU use on peaches with 2 × 0.90 kg a.i./ha, BBCH 01‐69; min interval between applications 7 days; PHI 75 days (EFSA, 2013b, 2015). The GAP on peaches assessed by the MRL review (EFSA, 2015) is the most critical use in mellifluous crops for transfer of residues in honey and covers the use on peach reported by the EMS (Spain, 2025).

APPENDIX B. List of end points

B.1. RESIDUES IN PLANTS

B.1.1. Nature of residues and analytical methods for enforcement purposes in plant commodities

B.1.1.1. Metabolism studies, analytical methods and residue definitions in plants

	Crop groups	Crops	Applications	Sampling (DALA)	Comment/source
Primary crops (available studies)	Fruit crops	Apples	Foliar spray; 3 × 0.90 kg a.s./ha	7	Radiolabelled active substance: phenyl‐UL‐14C‐guanidine in dodine molecule. Only fruits were sampled (EFSA, 2010)
		Strawberries	Foliar spray; 4 × 3 kg a.s./ha	14	Radiolabelled active substance: phenyl‐UL‐14C‐guanidine in dodine molecule. Only fruits were sampled (EFSA, 2010)
		Pecans	Foliar spray; 3 × 5.7 kg a.s./ha	9	Radiolabelled active substance: phenyl‐UL‐14C‐guanidine in dodine molecule. At maturity, only fruits (nuts) were sampled (EFSA, 2010)

	Crop groups	Crop(s)	Application(s)	PBI (DAT)	Comment/source
Rotational crops (available studies)	Not available and not triggered (EFSA, 2015) According to the laboratory degradation studies DT90 values of dodine range between 10.6–27.2 days which is far below the trigger value of 100 days (European Commission, 1997c); Furthermore, the authorised uses assessed in the MRL review are on permanent crops

	Conditions	Stable?	Comment/source
Processed commodities (hydrolysis study)	Pasteurisation (20 min, 90°C, pH 4)	Yes	Radiolabelled active substance: phenyl‐UL‐14C‐guanidine in dodine molecule EFSA (2010)
	Baking, brewing and boiling (60 min, 100°C, pH 5)	Yes
	Sterilisation (20 min, 120°C, pH 6)	Yes

B.1.1.2. Stability of residues in plants

	Category	Commodity	T (°C)	Stability period		Compounds covered	Comment/source
				Value	Unit
Plant products (available studies)	High water content	Apples	−18/−20	18	Months	Dodine	EFSA (2010)
		Peaches	−18/−20	18	Months	Dodine
		Cherries	−18/−20	18	Months	Dodine
		Apples	−20	24	Months	Dodine	Two years (24 months) storage stability study (EFSA, 2025)
		Carrots	−20	24	Months	Dodine
	High oil content	Peanuts	−20	9	Months	Dodine	EFSA (2013b)
		Olives	−20	24	Months	Dodine	Two years (24 months) storage stability study (EFSA, 2025)
	High protein content	Beans, dry	−20	24	Months	Dodine
	Dry/high starch	–	–	–	–	–	–
	High acid content	Orange, pulp	−20	24	Months	Dodine	Two years (24 months) storage stability study (EFSA, 2025)
	Processed products	Apple, juice	−18/−20	18	Months	Dodine	EFSA (2010)
		Apple, wet pomace	−18/−20	18	Months	Dodine
	Others	Orange, peel	−20	24	Months	Dodine	Two years (24 months) storage stability study (EFSA, 2025)

Note: General remark: It should be noted that the OECD Guideline 506 on the stability of pesticides has since been updated (OECD, 2025). In this revision, the previously used matrix group ‘high starch’ and ‘high protein’ (OECD, 2007) are no longer applicable. Instead, root and tuber vegetables are now classified under the ‘high‐water’ matrix group, while pulses, cereal grains, straw and dried fruits fall under the ‘dry’ matrix group.

B.1.2. Magnitude of residues in plants

B.1.2.1. Summary of residues data from the supervised residue trials

Not relevant for the present MRL application on honey.

B.1.2.2. Residues in rotational crops

B.1.2.3. Processing factors

Not relevant for the present MRL application on honey and no processing studies were submitted in the framework of the present MRL application.

B.2. RESIDUES IN LIVESTOCK

Not relevant for the present MRL application on honey.

B.3. RESIDUES IN HONEY

B.3.1. Nature of residues and analytical methods for enforcement purposes in honey

B.3.1.1. Metabolism studies, analytical methods and residue definitions in honey

B.3.1.2. Storage stability of residues in honey

	Category	Commodity	T (°C)	Stability period		Compounds covered	Comment/source
				Value	Unit
Products of animal origin (available studies)	Bee products	Honey	−18	6	Months	Dodine	Six months (179 days) storage stability study (Spain, 2025)

B.3.2. Magnitude of residues in honey

B.3.2.1. Summary of residues data from the supervised residue trials

Commodity	Region a	Residue levels observed in the residue trials (mg/kg)	Comments/source	Calculated MRL(mg/kg)	HR b (mg/kg)	STMR c (mg/kg)	CF d
Honey	n.r.	2 × ≤ 0.01; 0.056; 0.12	Residue levels of dodine in honey from 4 tunnel trials performed on Phacelia tanacetifolia supporting the critical GAP on melliferous crops identified in the present application (2 × 900 g a.s./ha). Two trials were performed in Germany and two in Spain (underlined) (Spain, 2025)	0.3	0.12	0.03	n.a.

Abbreviations: GAP, Good Agricultural Practice; Mo, monitoring; MRL, maximum residue level; n.a., not applicable; n.r., not relevant; RA, risk assessment.

^a NEU: Outdoor trials conducted in northern Europe, SEU: Outdoor trials conducted in southern Europe, EU: indoor EU trials or Country code: if non‐EU trials.

^b Highest residue.

^c Supervised trials median residue.

^d Conversion factor to recalculate residues according to the residue definition for monitoring to the residue definition for risk assessment.

B.4. CONSUMER RISK ASSESSMENT

B.5. RECOMMENDED MRLS

Code a	Commodity	Existing EU MRL (mg/kg)	Proposed EU MRL (mg/kg)	Comment/justification
Enforcement residue definition: Dodine
1040000	Honey and other apiculture products b	0.05*	0.3	The submitted data are sufficient to derive an MRL proposal for honey. Risk for consumers unlikely

Abbreviations: GAP, Good Agricultural Practice; MRL, maximum residue level; NEU, northern Europe; SEU, southern Europe.

^*Indicates that the MRL is set at the limit of analytical quantification (LOQ).

^a Commodity code number according to Annex I of Regulation (EC) No 396/2005.

^b According to Regulation (EC) No 396/2005 (as amended by Commission Regulation (EU) 2018/62) MRLs are not applicable to other apiculture products until individual products have been identified and listed within this group.

APPENDIX C. Pesticide Residue Intake Model (PRIMo)

APPENDIX D. Input values for the exposure calculations

D.1. CONSUMER RISK ASSESSMENT

Commodity	Existing/proposed MRL (mg/kg)	Source	Chronic risk assessment		Acute risk assessment
			Input value (mg/kg)	Comment	Input value (mg/kg)	Comment a
Risk assessment residue definition: dodine
Honey	0.3	Proposed	0.03	STMR‐RAC	0.12	HR‐RAC
Grapefruits	1.5	EFSA (2021)	0.04	STMR‐RAC × PeF (0.17)	0.15	HR‐RAC × PeF (0.17)
Oranges	1.5	EFSA (2021)	0.04	STMR‐RAC × PeF (0.17)	0.15	HR‐RAC × PeF (0.17)
Lemons	1.5	EFSA (2021)	0.04	STMR‐RAC × PeF (0.17)	0.15	HR‐RAC × PeF (0.17)
Limes	1.5	EFSA (2021)	0.04	STMR‐RAC × PeF (0.17)	0.15	HR‐RAC × PeF (0.17)
Mandarins	1.5	EFSA (2021)	0.04	STMR‐RAC × PeF (0.17)	0.15	HR‐RAC × PeF (0.17)
Other citrus fruits	1.5	EFSA (2021)	0.04	STMR‐RAC × PeF (0.17)	–	–
Apples	0.9	EFSA (2015)	0.25	STMR‐RAC	0.48	HR‐RAC
Pears	0.9	EFSA (2015)	0.25	STMR‐RAC	0.48	HR‐RAC
Quinces	5	EFSA (2015)	1.70	STMR CXL (2005)	2.43	HR‐RAC (CXL)
Medlar	5	EFSA (2015)	1.70	STMR CXL (2005)	2.43	HR‐RAC (CXL)
Loquats/Japanese medlars	5	EFSA (2015)	1.70	STMR CXL (2005)	2.43	HR‐RAC (CXL)
Other pome fruits	0.9	EFSA (2015)	0.25	STMR‐RAC	–	–
Apricots	0.1	EFSA (2015)	0.05	STMR‐RAC	0.07	HR‐RAC
Cherries (sweet)	3	EFSA (2015)	1.21	STMR CXL (2005)	2.11	HR‐RAC (CXL)
Peaches	0.1	EFSA (2015)	0.05	STMR‐RAC	0.07	HR‐RAC
Table grapes b	2	EFSA (2025)	0.54	STMR‐RAC	1.03	HR‐RAC
Wine grapes b	2	EFSA (2025)	0.54	STMR‐RAC	1.03	HR‐RAC
Table olives	20	EFSA (2015)	6.50	STMR‐RAC	11.2	HR‐RAC
Bananas	0.05	EFSA (2015)	0.01	STMR‐RAC × PeF (0.06)	0.016	HR‐RAC x PeF (0.06)
Olives for oil production's	20	EFSA (2015)	6.50	STMR‐RAC	6.5	STMR‐RAC
Swine: Muscle/meat	0.01 *	EFSA (2015)	0.01	LOQ	0.01	LOQ
Swine: Fat tissue	0.01 *	EFSA (2015)	0.01	LOQ	0.01	LOQ
Swine: Liver	0.01 *	EFSA (2015)	0.01	LOQ	0.01	LOQ
Swine: Kidney	0.01 *	EFSA (2015)	0.01	LOQ	0.01	LOQ
Swine: Edible offal (other than liver and kidney)	0.01 *	EFSA (2015)	0.01	LOQ	0.01	LOQ
Swine: Other products	0.01 *	EFSA (2015)	0.01	LOQ	0.01	LOQ
Bovine: Muscle/meat c	0.01 *	EFSA (2015)	0.01	LOQ	0.01	LOQ
Bovine: Fat tissue c	0.01 *	EFSA (2015)	0.01	LOQ	0.01	LOQ
Bovine: Liver c	0.01 *	EFSA (2015)	0.01	LOQ	0.01	LOQ
Bovine: Kidney c	0.01 *	EFSA (2015)	0.01	LOQ	0.01	LOQ
Bovine: Edible offal (other than liver and kidney)	0.01 *	EFSA (2015)	0.01	LOQ	0.01	LOQ
Bovine: Other products	0.01 *	EFSA (2015)	0.01	LOQ	0.01	LOQ
Sheep: Muscle/meat c	0.01 *	EFSA (2015)	0.01	LOQ	0.01	LOQ
Sheep: Fat tissue c	0.01 *	EFSA (2015)	0.01	LOQ	0.01	LOQ
Sheep: Liver c	0.01 *	EFSA (2015)	0.01	LOQ	0.01	LOQ
Sheep: Kidney c	0.01 *	EFSA (2015)	0.01	LOQ	0.01	LOQ
Sheep: Edible offal (other than liver and kidney)	0.01 *	EFSA (2015)	0.01	LOQ	0.01	LOQ
Sheep: other products	0.01 *	EFSA (2015)	0.01	LOQ	–	–
Goat: Muscle/meat c	0.01 *	EFSA (2015)	0.01	LOQ	0.01	LOQ
Goat: Fat tissue c	0.01 *	EFSA (2015)	0.01	LOQ	0.01	LOQ
Goat: Liver c	0.01 *	EFSA (2015)	0.01	LOQ	0.01	LOQ
Goat: Kidney c	0.01 *	EFSA (2015)	0.01	LOQ	0.01	LOQ
Goat: Edible offal (other than liver and kidney)	0.01 *	EFSA (2015)	0.01	LOQ	0.01	LOQ
Goat: other products	0.01 *	EFSA (2015)	0.01	LOQ
Equine: Muscle/meat	0.01 *	EFSA (2015)	0.01	LOQ	0.01	LOQ
Equine: Fat tissue	0.01 *	EFSA (2015)	0.01	LOQ	0.01	LOQ
Equine: Liver	0.01 *	EFSA (2015)	0.01	LOQ	0.01	LOQ
Equine: Kidney	0.01 *	EFSA (2015)	0.01	LOQ	0.01	LOQ
Equine: Edible offal (other than liver and kidney)	0.01 *	EFSA (2015)	0.01	LOQ	0.01	LOQ
Equine: Other products	0.01 *	EFSA (2015)	0.01	LOQ	–	–
Other farmed animals: Muscle/meat	0.01 *	EFSA (2015)	0.01	LOQ	0.01	LOQ
Other farmed animals: Fat tissue	0.01 *	EFSA (2015)	0.01	LOQ	0.01	LOQ
Other farmed animals: Liver	0.01 *	EFSA (2015)	0.01	LOQ	0.01	LOQ
Other farmed animals: Kidney	0.01 *	EFSA (2015)	0.01	LOQ	0.01	LOQ
Other farmed animals: Edible offal (other than liver and kidney)	0.01 *	EFSA (2015)	0.01	LOQ	0.01	LOQ
Other farmed animals: Other products	0.01 *	EFSA (2015)	0.01	LOQ	–	–
Milk: Cattle c	0.01 *	EFSA (2015)	0.01	LOQ	0.01	LOQ
Milk: Sheep c	0.01 *	EFSA (2015)	0.01	LOQ	0.01	LOQ
Milk: Goat c	0.01 *	EFSA (2015)	0.01	LOQ	0.01	LOQ
Milk: Horse	0.01 *	EFSA (2015)	0.01	LOQ	0.01	LOQ
Milk: Others	0.01 *	EFSA (2015)	0.01	LOQ	0.01	LOQ

Abbreviations: CXL, Codex maximum residue limit: HR‐RAC, highest residue in raw agricultural commodity; LOQ, limit of quantification; PeF, Peeling factor; STMR‐RAC, supervised trials median residue in raw agricultural commodity.

^*Indicates that the MRL is set at the limit of analytical quantification (LOQ).

^a Input values for the commodities which are not under consideration for the acute risk assessment are reported in grey.

^b MRLs and input values for the risk assessment as proposed by EFSA (EFSA, 2025), and not considered by risk managers for implementation in the EU legislation yet. Existing MRL is set at the LOQ of 0.01 mg/kg.

^c MRLs tentatively derived, due to the data gap identified on the analytical methods in livestock commodities (EFSA, 2015).

APPENDIX E. Used compound codes

Code/trivial name a	IUPAC name/SMILES notation/InChiKey b	Structural formula c
Dodine	1‐dodecylguanidinium acetate CC(=O)O.N=C(N)NCCCCCCCCCCCC YIKWKLYQRFRGPM‐UHFFFAOYSA‐N
Guanidine	Guanidine N=C(N)N ZRALSGWEFCBTJO‐UHFFFAOYSA‐N

Abbreviations: IUPAC, International Union of Pure and Applied Chemistry; InChiKey, International Chemical Identifier Key; SMILES, simplified molecular‐input line‐entry system.

^a The metabolite name in bold is the name used in the conclusion.

^b ACD/Name 2024.2.3 ACD/Labs 2024.2.3 (File Version N25E41, Build 142837, 21 Jan 2025).

^c ACD/ChemSketch 2024.2.3 ACD/Labs 2024.2.3 (File Version C45H41, Build 142855, 23 Jan 2025).

EFSA (European Food Safety Authority) , Bellisai, G. , Bernasconi, G. , Castellan, I. , del Aguila, M. , Ferreira, L. , Leuschner, R. , Mioč, A. , Szot, M. , Tiramani, M. , & Verani, A. (2026). Modification of the existing maximum residue level for dodine in honey. EFSA Journal, 24(5), e10109. 10.2903/j.efsa.2026.10109