Modification of the existing maximum residue levels for picloram in animal commodities and honey

Abstract

In accordance with Article 6 of Regulation (EC) No 396/2005, the applicant Corteva Agriscience International Sàrl submitted a request to the competent national authority in the Netherlands to modify the existing maximum residue levels (MRLs) in certain animal commodities (fat and liver) and honey. The data submitted in support of the request were found to be sufficient to derive an MRL proposal for honey. Adequate analytical methods for enforcement are available to control the residues according to the residue definition for enforcement proposed as ‘picloram, free and conjugated, expressed as picloram’ in honey at the validated limit of quantification (LOQ) of 0.01 mg/kg. For the commodities of animal origin, although the submitted data were found to be sufficient, EFSA concluded that no change of the existing MRLs was necessary. Based on the risk assessment results, EFSA concluded that the short‐term and long‐term intake of residues expected in honey, resulting from the existing uses of picloram on melliferous crops, is unlikely to present a risk to consumer health.

SUMMARY

In accordance with Article 6 of Regulation (EC) No 396/2005, Corteva Agriscience International Sàrl submitted an application to the competent national authority in the Netherlands (evaluating Member State, (EMS)) to modify maximum residue levels (MRLs) for the active substance picloram in animal commodities (fat and liver) and 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 29 June 2023. The appointed EMS the Netherlands assessed the dossier and declared its admissibility on 12 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, in order to identify whether other relevant scientific data or studies are available. The consultation run from 5 February 2024 to 28 February 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, which was submitted to the European Commission and to the European Food Safety Authority (EFSA) on 22 May 2024. To consider the possible transfer of residues from melliferous crops to honey, the EMS proposed to raise the existing MRL in honey from the limit of quantification (LOQ) of 0.05 to 0.06 mg/kg. Regarding the existing EU MRLs in animal commodities, the EMS did not support the new MRL proposals of the applicant and proposed to maintain the current EU MRL set in Commission Regulation (EU) 2021/1531.

On 18 June 2024 the European Commission sent a mandate to EFSA to assess the application 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 additional information was provided by the applicant and duly considered by the EMS, who submitted a revised evaluation report to EFSA in August 2024 (Netherlands, 2024), which replaced the previously submitted evaluation report.

Based on the conclusions derived by EFSA in the framework of the peer review of the pesticide risk assessment of the active substance picloram under 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.

The metabolism of picloram following foliar application was investigated in crops belonging to the groups of cereals and pulses/oilseeds. The metabolism of picloram in rotational crops was assessed in the EFSA conclusion on the peer review on the active substance. It was concluded that the metabolism of the active substance in rotational crops is similar to the pathway observed in the tested primary crops. Standard hydrolysis studies on the active substance under conditions representative for pasteurisation, boiling/cooking and sterilisation are not available and not triggered for the use under assessment.

Based on the metabolic pattern identified in metabolism studies, the residue definition for enforcement in plant products (oilseeds and cereals) should include picloram and its conjugated forms. During the confirmatory data assessment, it has been demonstrated that the analytical methods for enforcement was able to determine both free and conjugated forms of picloram. The existing residue definition for enforcement set in Regulation (EC) No 396/2005 still refers to ‘picloram’ only. The wording of this existing residue definition for enforcement may need to be updated with the inclusion of conjugates. For risk assessment, the residue definition refers to picloram, free and conjugated, expressed as picloram. These conclusions are applicable to primary crops (oilseed and cereals) and rotational crops. For honey, the same residue definitions are proposed. Therefore, both enforcement and risk assessment residue definitions are proposed as picloram (free and conjugated) expressed as picloram. It is noted that the analytical methods for enforcement in honey allow to quantify the total residue of picloram (free and conjugated forms).

Sufficiently validated analytical methods based on gas chromatography with mass spectrometry (GC–MS) are available to quantify residues of picloram and its conjugates, expressed as picloram, in the plant commodities assessed in previous applications. The methods enable quantification of residues at or above 0.01 mg/kg for the total residue (sum of picloram and its conjugates) in crops belonging to the group of high‐water content, high‐oil content and dry matrices. This analytical method is not fully in line with the residue definition for enforcement currently set in Regulation (EC) No 396/2005 (picloram only).

The magnitude of picloram residues in plant commodities was not assessed in the current application as no new intended uses were proposed.

The applicant submitted new MRL proposals for swine fat and liver, bovine liver, sheep liver, goat liver and equine fat and liver, based on an update of the livestock dietary burden and the results of a new feeding study. The metabolism of picloram in livestock was sufficiently assessed in the framework of the EU pesticides peer review, which defined residues in animal products as ‘picloram’ for both risk assessment and monitoring purposes. In support of the new MRL request, a new enforcement method, a new storage stability study and a new feeding study on lactating cows were submitted in the current application. The EMS did not consider the enforcement method as valid because of the use of the hazardous reagent dichloromethane (DCM) for sample partitioning during the extraction process. A conclusion on the validity of the enforcement method will be delivered in the conclusion on the on‐going assessment of the renewal of picloram. The storage stability study and the feeding study were validated. However, considering the results of the four dose groups investigated in the feeding study, the EMS and EFSA did not support the applicant proposal to derive MRLs from the linear regression, taking into account all feeding levels. Instead, the EMS and EFSA recommended to calculate the MRL values in different tissues by using the transfer factor approach at the closest feeding level. Following this approach, the MRL increases proposed by the applicant were not supported.

Studies investigating the magnitude of residues in honey, storage stability studies and a method of analysis with its validation data were submitted in the current application. The available residue trials are sufficient to derive an MRL proposal of 0.05 mg/kg for honey.

The toxicological profile of picloram 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 0.3 mg/kg body weight (bw) per day and an acute reference dose (ARfD) of 0.3 mg/kg bw.

The consumer risk assessment was performed with revision 3.1 of the EFSA Pesticide Residues Intake Model (PRIMo). The short‐term exposure did not exceed the ARfD for the commodities assessed in this application. The highest estimated long‐term dietary intake was 2% of the ADI (NL toddler). The contribution of residues expected in the commodities assessed in this application to the overall long‐term exposure is less than 0.01% of ADI. The chronic consumer risk assessment shall be regarded as indicative since performed considering existing MRLs for all the commodities listed in Annex I of the Regulation, except for honey, assessed in the present application and for rape seeds, mustard seeds, borage seeds and flowering brassica for which risk assessment values were available. A more refined consumer risk assessment will be conducted in the framework of the MRL review.

EFSA concluded that the authorised use of picloram will not result in a consumer exposure from animal commodities and honey exceeding the toxicological reference values and therefore is unlikely to pose a risk to consumers' health.

As the renewal of the approval of the active substance picloram and the review of the existing MRLs under Article 12 of Regulation 396/2005 (MRL review) are not yet finalised, the conclusions reported in this reasoned opinion are indicative and may need to be reconsidered in the light of the outcome of these reviews.

EFSA proposes to amend the existing MRL on honey. In addition, a new residue definition for enforcement in honey is proposed as ‘picloram, free and conjugated, expressed as picloram’.

However, no changes are proposed for the commodities of animal origin (see summary table below).

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

Code a	Commodity	Existing EU MRL (mg/kg)	Proposed EU MRL (mg/kg)	Comment/justification
Enforcement residue definition (existing): Picloram
1011020	Swine fat	0.01*	No change	The submitted data do not provide evidence that the existing MRL has to be modified
1011030	Swine liver	0.01*	No change	The submitted data do not provide evidence that the existing MRL has to be modified
1011990	Swine, Others	0.01*	No change	The submitted data do not provide evidence that the existing MRL has to be modified
1012030	Bovine liver	0.01*	No change	The submitted data do not provide evidence that the existing MRL has to be modified
1012990	Bovine, Others	0.01*	No change	The submitted data do not provide evidence that the existing MRL has to be modified
1013030	Sheep liver	0.01*	No change	The submitted data do not provide evidence that the existing MRL has to be modified
1013990	Sheep, others	0.01*	No change	The submitted data do not provide evidence that the existing MRL has to be modified
1014030	Goat liver	0.01*	No change	The submitted data do not provide evidence that the existing MRL has to be modified
1014990	Goat, Others	0.01*	No change	The submitted data do not provide evidence that the existing MRL has to be modified
1015020	Equine fat	0.01*	No change	The submitted data do not provide evidence that the existing MRL has to be modified
1015030	Equine liver	0.01*	No change	The submitted data do not provide evidence that the existing MRL has to be modified
1015990	Equine, others	0.01*	No change	The submitted data do not provide evidence that the existing MRL has to be modified
1017020	Other farmed terrestrial animals fat	0.01*	No change	The submitted data do not provide evidence that the existing MRL has to be modified
1017030	Other farmed terrestrial animals liver	0.01*	No change	The submitted data do not provide evidence that the existing MRL has to be modified
1017990	Other farmed terrestrial animals, Others	0.01*	No change	The submitted data do not provide evidence that the existing MRL has to be modified
Enforcement residue definition (existing): Picloram
Enforcement residue definition (proposed): Picloram, free and conjugated, expressed as picloram
1040000	Honey and other apiculture products b	0.05*	0.05 c	The submitted data are sufficient to derive a MRL proposal. Samples were analysed for the sum of picloram and its conjugates, expressed as picloram, in line with the proposed residue definition for enforcement. The MRL value of 0.05 mg/kg reflects the proposed residue definition for enforcement including conjugates. 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.

^c The proposed EU MRL differs from the MRL derived by the EMS (i.e. 0.06 mg/kg), due to rounding.

ASSESSMENT

The European Food Safety Authority (EFSA) received an application to modify the existing maximum residue levels (MRLs) for picloram in animal commodities and honey. The proposed MRLs for animal commodities are not triggered by new uses of picloram but by a new dietary burden calculation performed using an updated animal model and a new feeding study. Therefore, there is no new Good Agricultural Practice (GAP) reported for crops having an impact on animal commodities. Regarding the MRL request for honey, the critical GAP, identified by the applicant among the existing authorised EU uses in melliferous crops, is reported in Appendix A.

Picloram is the ISO common name for 4‐amino‐3,5,6‐trichloropyridine‐2‐carboxylic acid (IUPAC). The chemical structure of the active substance is reported in Appendix E.

Picloram was evaluated in the framework of Directive 91/414/EEC ¹ with United Kingdom designated as rapporteur Member State (RMS) for the representative use as a spray treatment on winter or spring oilseed rape. The draft assessment report (DAR) prepared by the RMS has been peer reviewed by EFSA (EFSA, 2009). Picloram was approved ² for the use as herbicide on 1 January 2009. The process of renewal of the first approval is on‐going but has not yet been completed.

The EU MRLs for picloram are established in Annex III of Regulation (EC) No 396/2005. ³ The review of existing MRLs according to Article 12 of Regulation (EC) No 396/2005 (MRL review) has not yet been performed. EFSA has issued three reasoned opinions on the modification of MRLs for picloram (EFSA, 2013, 2015, 2020). The proposals from these reasoned opinions have been in recent MRL regulations. ⁴

In accordance Article 6 of Regulation (EC) No 396/2005 and following the provisions set by the ‘Transparency Regulation’ (EU) 2019/1381, ⁵ the applicant Corteva Agriscience International Sàrl submitted on 29 June 2023 an application to the competent national authority in the Netherlands, alongside the dossier containing the supporting data using the IUCLID format.

The appointed EMS, the Netherlands, assessed the dossier and declared its admissibility on 12 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, in order to identify whether other relevant scientific data or studies are available. The consultation run from 5 February 2024 to 28 February 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, which was submitted to the European Commission and to the European Food Safety Authority (EFSA) on 22 May 2024. To consider the possible transfer of residues from melliferous crops to honey, the EMS proposed to raise the existing MRL in honey from the limit of quantification (LOQ) of 0.05–0.06 mg/kg. However, regarding the existing EU MRLs in animal commodities, the EMS did not support the new MRL proposals of the applicant and proposed to maintain the current EU MRL set in Commission Regulation (EU) 2021/1531. ⁶

On 18 June 2024 the European Commission sent a mandate to EFSA to assess the application 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 additional information was provided by the applicant and duly considered by the EMS, who submitted a revised evaluation report to EFSA in August 2024 (Netherlands, 2024), which replaced the previously submitted evaluation report.

EFSA based its assessment on the evaluation report submitted by the EMS (Netherlands, 2024), the draft assessment report (DAR) and its addenda (United Kingdom, 2007, 2009) prepared under Directive 91/414/EEC, the Commission review report on picloram (European Commission, 2018a), the conclusion on the peer review of the pesticide risk assessment of the active substance picloram (EFSA, 2009) and the assessment of the requested confirmatory information (EFSA, 2017), as well as the conclusions from previous EFSA opinions on picloram (EFSA, 2013, 2015, 2020).

For this application, the data requirements established in Regulation (EU) No 544/2011 ⁷ 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, 2010, 2018b, 2021, 2023a, 2023b; OECD, 2013, 2014). 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. ⁸

As the renewal of the approval of the active substance picloram and the review of the existing MRLs under Article 12 of Regulation 396/2005 are not yet finalised, the conclusions reported in this reasoned opinion are indicative and may need to be reconsidered in the light of the outcome of these reviews.

A selected list of end points of the studies assessed by EFSA in the framework of this MRL application including the end points of relevant studies assessed previously, is presented in Appendix C.

The evaluation report submitted by the EMS (Netherlands, 2024) and the exposure calculations using the EFSA Pesticide Residues Intake Model (PRIMo) are considered as supporting documents to this reasoned opinion and, thus, are made publicly available as background documents to this reasoned opinion. ⁹

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 picloram in primary crops belonging to the groups of cereals/grass and pulses/oilseeds has been investigated in the framework of the EU pesticides peer review (EFSA, 2009). Both the oilseed rape and wheat studies demonstrate that picloram is not degraded but quickly forms conjugates in plant material. These conjugates released parent picloram upon hydrolytic extraction conditions.

No additional studies were submitted or requested, as residues in primary crops are out of the scope of the current MRL application.

1.1.2. Nature of residues in rotational crops

According to the soil degradation studies evaluated in the framework of the peer review, the maximum field DT₉₀ value of picloram was 163 days (EFSA, 2009). The trigger value of 100 days was exceeded and therefore further studies investigating the nature and magnitude of residues in rotational crops are required.

The metabolism of picloram in rotational crops was investigated in the framework of the EU pesticides peer review (EFSA, 2009). It was concluded that the metabolism of the active substance in rotational crops is similar to the pathway observed in primary crops.

No further information is required for the current MRL application.

1.1.3. Nature of residues in processed commodities

Standard hydrolysis studies regarding the stability of the active substance under conditions representative for pasteurisation, boiling/cooking and sterilisation are not available and not required for the MRL application under assessment (EFSA, 2009, 2020; European Commission, 1997d).

1.1.4. Analytical methods for enforcement purposes in plant commodities

Analytical methods for the determination of picloram residues were assessed during the EU pesticides peer review and its confirmatory data assessment (EFSA, 2009, 2017). The method GRM 00.19, based on gas chromatography with mass spectrometry (GC–MS) allows quantifying residues at or above the LOQ of 0.01 mg/kg for the total residue (sum of picloram and its conjugates) in crops belonging to the group of high‐water content (forage), high‐oil content (oilseed rape seed) and dry matrices (straw). Particular attention was given to the extraction step of the method, and it was recommended to test by cross‐validation any modification in extraction solvent composition or conditions compared to the procedure validated in method GRM 00.19 (EFSA, 2017). Extraction efficiency of the analytical method in accordance with the current guidance document (European Commission, 2023b) was not investigated; EFSA would therefore recommend re‐assessing the extraction efficiency in the framework of the peer review for the renewal of approval of the active substance.

It should be noted that the available method for enforcement is quantifying residues of picloram and its conjugates and, thus, is not fully in line with the residue definition for enforcement currently set in Regulation (EC) No 396/2005 (picloram only).

1.1.5. Storage stability of residues in plants

The storage stability of picloram in plants stored under frozen conditions was investigated in the framework of the EU pesticides peer review (EFSA, 2009). Residues of picloram were found to be stable at ≤ −20°C for up to 24 months in high‐water content (wheat forage), high‐oil content (rape seed), dry (wheat grain) commodities, and in wheat straw and oilseed rape hay samples.

1.1.6. Proposed residue definitions

Based on the metabolic pattern identified in metabolism studies and the capabilities of enforcement analytical methods (confirmed in the context of the confirmatory data assessment (EFSA, 2017)), the following residue definitions were proposed in the framework of the EU pesticides peer review (EFSA, 2009, 2017):

• residue definition for risk assessment: picloram, free and conjugated, expressed as picloram;

• residue definition for enforcement (proposed): picloram, free and conjugated, expressed as picloram.

These residues definitions are applicable to oilseeds and cereal crops. The same residue definitions are applicable to rotational crops.

The residue definition for enforcement set in Regulation (EC) No 396/2005 refers to the active substance picloram only. The wording of this existing residue definition for enforcement may need to be updated with the inclusion of conjugates.

It is also noted that EFSA has previously derived MRL proposals on the basis of residue trials analysed for the wider residue definition (sum of picloram and its conjugates, expressed as picloram) (EFSA, 2013, 2015, 2020). These MRL proposals have been implemented in the EU legislation.

The residue definition for enforcement and risk assessment will be reconsidered in the framework of the renewal of the approval of the active substance picloram.

1.2. Magnitude of residues in plants

In the framework of the current application the applicant requested MRLs for honey and for certain commodities on animal origin. Since there are no new intended uses to be assessed in the present application, the section on magnitude of residues in plants is not relevant.

2. RESIDUES IN LIVESTOCK

There are no intended uses on crops that may be used as feed items in the present application. However, the applicant submitted new MRL proposals on several commodities of animal origin, for which the existing MRLs are currently set at LOQ: swine fat and liver, bovine liver, sheep liver, goat liver and equine fat and liver. The applicant proposals are based on an update of the livestock dietary burden ¹⁰ and were derived from a new feeding study on lactating cows.

It should be noted that existing MRLs for commodities of animal origin were set during the process of harmonisation of the EU MRLs which started in 2008. Since the MRL review has not yet been performed for picloram and since the MRLs on livestock commodities have not been reassessed since 2008, there is currently no available background information for the existing MRLs.

The assessment of the animal dietary burden performed in the context of the present assessment should only be considered as provisional because, in the absence of an MRL review, there is no clear picture of which are the current authorisations of picloram as a plant protection product. For certain major contributors such as cereal grains, it was only possible to consider the existing MRL as an input value, because of the absence of supportive residue trials for these commodities. Besides this, confirmation that residues were analysed according to the residue definition for risk assessment in cereals, which includes picloram conjugates, is also missing at this stage. Furthermore, residue data on feed matrices such as cereals straw are missing, and the current dietary burden calculations do not consider the potential impact from of residue uptakes in rotational crops.

EFSA assessed the calculations performed by the EMS and confirmed the results presented in the evaluation report (Netherlands, 2024). The input values for the exposure calculations for livestock are presented in Appendix E.1. The results of the dietary burden calculation are presented in Section B.2. The exposures of all species were found to exceed the trigger values defined in Regulation (EU) 544/2011.

2.1. Nature of residues and methods of analysis in livestock

Metabolism studies in livestock (lactating goat and laying hens) have been assessed previously in the framework of the EU pesticides peer review (EFSA, 2009). Picloram was not metabolised to any significant degree in goats and poultry. Based on these results, residues in animal products were defined as ‘picloram’ for both risk assessment and monitoring purposes. This conclusion may be revised in the context of the Renewal of the active substance, which is currently ongoing.

During the EU pesticides peer review, it was concluded that picloram in foodstuff of animal origin could be determined by GC–MS with a LOQ of 0.01 mg/kg in all relevant animal products. It should be noted that this method was only validated for the analysis of picloram (free) (EFSA, 2009). A new method of analysis and its independent laboratory validation (ILV) for products of animal origin (bovine muscle, bovine fat, bovine liver, bovine kidney and milk) have been submitted in the present dossier and assessed by the EMS (Netherlands, 2024). It is noted that this method is also assessed during the on‐going Renewal of the active substance. The method involves liquid chromatography with tandem mass spectrometry detector (LC–MS/MS). However, the EMS did not consider this method valid for monitoring purpose in accordance with the requirements in SANTE/2020/12830, Rev.1 (European Commission, 2021) because of the use of a hazardous reagent (dichloromethane) for sample partitioning during the extraction process. A conclusion on the validity of the enforcement method will be delivered in the conclusion on the on‐going assessment of the renewal of picloram.

During the EU pesticides peer review, it was concluded that picloram was stable in milk (14 months) and egg white (18 months) (EFSA, 2009). A new study investigating the storage stability of picloram in commodities of animal origin was also submitted in the present dossier and assessed by the EMS (Netherlands, 2024). The study is also under assessment in the Renewal of the active substance. Storage stability of picloram was demonstrated for a period of at least 2 months at −18°C in the commodities of animal origin (milk, muscle, fat, liver, kidney) (Netherlands, 2024). The demonstrated frozen storage stability supports the maximum storage duration of residue samples from the livestock feeding study.

2.2. Magnitude of residues in livestock

To support the new MRL requests, a new feeding study with lactating cows was submitted in the present dossier and assessed by the EMS (Netherlands, 2024). This study was also assessed as part of the Renewal of the active substance. An expert meeting for the residue section held in 2023 ¹¹ where all concerns regarding the new submitted studies were discussed and addressed. It was concluded that the feeding study was valid.

Lactating cows were orally exposed to picloram at levels of 0.022 mg/kg bw per day (level 1), 2.607 mg/kg bw per day (level 2), 7.446 mg/kg bw per day (level 3) and 24.758 mg/kg bw per day (level 4) over a period of 28–29 consecutive days. It is noted that level 1 is the closest level compared to the updated dietary burden of ruminants and swine as the highest calculated dietary burdens are 0.022 mg/kg bw per day (cattle), 0.039 mg/bg bw per day (sheep) and 0.027 mg/kg bw per day (swine). It should be noted that the three other tested levels (2, 3 and 4) are exaggeratedly higher compared to level 1 (118N, 338N and 1125N) and to the calculated dietary burdens as well.

Residues of picloram were determined using a validated analytical method (GRM 03.06), which consists in capillary gas chromatography with negative‐ion chemical ionisation mass spectrometry (GC/NCI‐MS).

Residues above the LOQ of 0.01 mg/kg were found in muscle, fat, liver and kidney, fat from animals exposed to dose levels 2, 3 and 4. Regarding samples taken from dose level 1, residues above the LOQ were only found in kidney (max value: 0.04 mg/kg). From all other samples taken from dose level 1 (muscle, liver, fat and milk), residues of picloram were below the limit of detection (LOD), i.e. below 0.003 mg/kg.

Based on this study, the applicant proposed to raise the existing MRLs (currently at the LOQ of 0.01 mg/kg) for swine fat (0.08 mg/kg), swine liver (0.02 mg/kg), bovine liver (0.02 mg/kg), sheep liver (0.02 mg/kg), goat liver (0.02 mg/kg), equine fat (0.08 mg/kg) and equine liver (0.02 mg/kg). However, considering that residues in fat and liver were below the LOD for the animal treated at dose level 1, which is 1N for cattle, 0.6N for sheep and 0.8N for swine, these new MRL proposals seems overestimated and were not supported by the EMS (Netherlands, 2024).

The new MRL proposals seem to be derived from a straightforward use from the EFSA Animal Model (2017). ¹² It should be noted that the MRL proposals were all derived by the applicant using the linear regression. A linear dose response is generally observed in milks and tissues and the estimated dietary burdens are in the range where the use of linear regression is relevant. However, considering that dose level 1 is the closest level compared to the calculated dietary burdens (0.6 to 1N), and considering the huge gap between dose level 1 (0.022 mg/kg bw per day) and the other dose groups (2.607–24.758 mg/kg bw per day), it is not deemed appropriate to use the results obtained at dose levels 2, 3 and 4 to estimate the residues expected around dose level 1. Consequently, EFSA agrees with the EMS that using the linear regression in the present case was not a reliable approach (Netherlands, 2024). Instead, by expert judgement it is recommended to calculate the HR and MRL values in different tissues by using the transfer factor approach with the closest feeding level 1.

In Appendix B.2.2.1, EFSA has reported the calculations performed with the Animal Model 2017 for the supervised trials median residue (STMR), highest residue (HR) and MRL for each ruminant and swine commodities. In the first table (a), results are calculated with the linear regression; this table is reported for information. In the second table (b), the MRLs are estimated by the transfer factor methodology; this table supports the EMS and EFSA's conclusion that the new MRL increases proposed by the applicant are not supported.

Consequently, no change of the existing MRLs for livestock tissues are proposed by EFSA. However, EFSA recommends performing a full assessment of the MRL in livestock commodities during the MRL review, where an updated calculation of the livestock dietary burden will be possible based on the collection of authorised uses and supporting residue trials data.

Magnitude of residues from EU national monitoring programme

Furthermore, EFSA cross checked the available monitoring data submitted in the framework of Article 32 of Regulation (EC) No 396/2005 (official national control programmes). ¹³ Considering all samples available from 2013 to 2023 ¹⁴ monitoring programmes, a total of 2386 samples (all originating from EU Member States) are available on fat and liver from bovine, equine, sheep and swine. In all samples, picloram residue levels were below the LOQs reported by the laboratories (1538 samples with LOQ of 0.01 mg/kg; 848 samples with LOQ of 0.1 mg/kg). Based on the 1538 samples with LOQ of 0.01 mg/kg, no MRL exceedances are expected with the existing MRLs of 0.01 mg/kg (LOQ). The remaining 848 samples analysed with an LOQ of 0.1 mg/kg do not allow to draw any conclusion. Overall, the available monitoring data provide additional evidence that the existing MRLs for picloram (currently at LOQ) in swine fat, swine liver, bovine liver, sheep liver, goat liver, equine fat and equine liver do not need to be modified.

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 for a certain time period. In the absence of specific metabolism studies with honey bees, 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, 2018b). 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 oilseed crops (cereals, except buckwheat, are currently not considered as melliferous crops) and rotational crops are available, no further information is required for the current application according to the guidelines.

3.1.1. Analytical methods for enforcement in honey

In the framework of the present assessment, the applicant submitted a new method for enforcement of picloram residues (free and conjugated forms, expressed as picloram) in honey, which was assessed in the evaluation report (Netherlands, 2024). The method, coded 220349, based on LC–MS/MS, is sufficiently validated, including ILV, for the extraction of picloram residues (both free and conjugated forms) in honey, using methanol/10 M NaOH (100/1, v/v) and overnight hydrolysis at room temperature, and allows quantification of residues at or above the LOQ of 0.01 mg/kg for the total picloram residues (both free and hydrolysed conjugates) in honey.

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

3.1.2. Storage stability of residues in honey

The storage stability of residues of picloram in honey samples stored under frozen conditions was investigated in the current MRL application (Netherlands, 2024). It was demonstrated that residues of picloram were stable for at least 5.5 months when stored at −18°C in honey.

3.1.3. Proposed residue definitions

In the absence of specific metabolism studies on honey, the available studies investigating the nature of residues in primary and rotational crops are considered to derive the residue definitions for honey; the same residue definitions as mentioned for plant commodities are therefore proposed. Considering that conjugates of picloram are potentially present in plants, and therefore in honey, and considering that the available methods for enforcement in honey is expected to analyse for total picloram (free and conjugates), it is considered that the residue definition in honey includes picloram, free and conjugated.

3.2. Magnitude of residues in honey

In support of the MRL application in honey, the Applicant submitted six independent and GAP‐compliant semi‐field tunnel trials conducted with winter oilseed rape. The EU critical GAPs selected by the applicant were for oilseed rapes, mustard seed and borage seed, consisting of one foliar application at a nominal application rate of 25 g a.s./ha and at growth stages of mono‐ and dicotyledonous plants (BBCH) 30–50.

The trials were performed in Austria (1), Germany (2), Spain (2) and southern France (1) in 2022. Among these, four trials were considered valid, while two trials (one in Austria and one in Germany) were disregarded: the trial conducted in Austria yielded no honey at the time of sampling, and the trial conducted in Germany produced a sample with an extremely low weight (3.04 g) and a high‐water content (26.4%), not being compliant with the recommendations of the Technical Guidelines on Pesticide Residues in Honey (European Commission, 2018b).

Each trial consisted of two plots, one treated and one untreated. In the treated plot, the picloram‐olamine was applied once as a soluble concentrate formulation via foliar application, before flowering (BBCH 31–50). The nominal rate expressed as acid equivalent (picloram) is 25 g a.i./ha. One bee colony was introduced in each plot between 16 and 44 days after the treatment. Although the timing of the bee colony introduction in the plots deviates from the recommendations of the Technical Guidelines on Pesticide Residues in Honey (European Commission, 2018b), this is considered a minor adjustment made to ensure the availability of sufficient floral sources for bees.

Honey was sampled between 35 and 78 days after application. The amount of honey collected from the four valid trials ranged from 14 to 70 g, with water content ranging from 17.5% to 19.7%. It is noted that all collected samples were below the recommended minimum amount of 100 g (European Commission, 2018b). However, it is commonly acknowledged that obtaining the recommended sample weight is difficult under semi‐field conditions; therefore, lower sample weights are generally accepted, with this deviation being considered minor and not affecting the validity of the trials.

According to the assessment of the EMS, the methods used are sufficiently validated for the quantification of residues of picloram and its conjugates and are fit for purpose. 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, 2023b). The samples of these residue trials were stored under conditions for which integrity of the samples has been demonstrated.

The number of trials is sufficient to derive an MRL proposal of 0.05 mg/kg for honey. The MRL proposal derived by EFSA differs from the MRL derived by the EMS (i.e. 0.06 mg/kg), probably due to rounding. Samples were analysed for the sum of picloram and its conjugates, expressed as picloram, according to the proposed residue definition for enforcement.

Magnitude of residues from EU national monitoring programme

In the framework of Article 32 of Regulation (EC) No 396/2005 (official national control programmes)¹³, monitoring data were submitted to EFSA. Considering all samples available from 2013 to 2023 ¹⁵ monitoring programmes, a total of 185 samples are available (85% originating from EU Member States). EFSA is not in the position to confirm whether the method used in the monitoring programmes involved a hydrolysis step that would release the conjugated forms of picloram. However, it is noted that all samples had picloram residue levels below the LOQs reported by the laboratories (157 samples with LOQs of 0.005–0.01 mg/kg; 28 samples with LOQ of 0.1 mg/kg). Based on the 157 samples with LOQs of 0.005–0.01 mg/kg, no MRL exceedances are expected with the proposed MRL of 0.05 mg/kg. The remaining 28 samples analysed with an LOQ of 0.1 mg/kg do not allow to draw any conclusion. Overall, the available monitoring data indicate that picloram concentrations found in honey in the available semi‐field/tunnel residue trials presented in this application are comparable to the residues found in market samples of honey. It also indicates that an MRL proposal of 0.05 mg/kg is expected to be sufficient to cover the existing residue concentrations in honey.

3.2.1. Proposed MRLs

The available data are considered sufficient to derive an MRL proposal of 0.05 mg/kg, according to the proposed residue definition for enforcement (i.e. ‘picloram, free and conjugated, expressed as picloram’) as well as risk assessment values for honey (see Appendix B.3.2.1).

It should be noted that this MRL proposal was derived based on residue trials analysed for the wider residue definition (sum of picloram and its conjugates, expressed as picloram), which differs from the residue definition for enforcement set in Regulation (EC) No 396/2005, but is in line with the proposed residue definition for enforcement.

In Section 4, EFSA assessed whether residues on honey resulting from the above assessment is 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. ¹⁶

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 subgroups 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 toxicological reference values for picloram used in the risk assessment (i.e. ADI and ARfD values) were derived in the framework of the EU pesticides peer review (European Commission, 2018a).

Short‐term (acute) dietary risk assessment

The short‐term exposure assessment focused on the commodities assessed in this application (Netherlands, 2024).

For honey, the calculation was based on the HR derived from the available semi‐field/tunnel residue trials used in this application to derive the MRL proposal of 0.05 mg/kg.

For the commodities of animal origin for which the applicant has requested a new MRL (swine fat, swine liver, bovine liver, sheep liver, goat liver, equine fat and equine liver), EFSA used the existing MRLs (set at the LOQ) to perform the risk assessment. EFSA agreed with the EMS conclusion that a change of the existing MRLs is not required based on the current information (see Section 2.2). The complete list of input values can be found in Appendix D.2.

There are no specific data for the acute consumption of sheep other products, goat liver, goat other products, equine fat tissue, equine liver, equine other products, other farmed animal fat tissue, other farmed animal liver, other farmed animal other products. The absence of consumption data confirms that the contribution of these commodities to the overall human dietary exposure is of minor relevance.

The short‐term exposure did not exceed the ARfD for any of the crops assessed in this application.

Long‐term (chronic) dietary risk assessment

The long‐term exposure assessment was performed taking into account the STMR values derived for honey and the existing MRLs (=LOQ) for the animal commodities assessed in this application. For the remaining commodities covered by the MRL regulation, the existing EU MRLs and STMR values derived in previous MRL applications were selected as input values (EFSA, 2013, 2015, 2020). The complete list of input values is presented in Appendix D.2.

The highest estimated long‐term dietary intake was 2% of the ADI (NL toddler diet). The respective contributions of residues expected in the commodities assessed in this application to the overall long‐term exposure is very low and are presented in more detail in Appendix B.4. Although the calculation is based on MRLs for certain commodities, which may lead to an overestimation of chronic consumer exposure, the overall exposure remains very low.

EFSA concluded that the long‐term intake of residues of picloram resulting from the existing uses (including residues in products of animal origin) and from the intended MRL on honey is unlikely to present a risk to consumer health.

The consumer risk assessment shall be regarded as indicative. A more realistic consumer risk assessment will be performed in the framework of the Article 12 MRL review, when additional information on authorised uses of picloram will be available to EFSA. Additionally, the peer review of the active substance 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.

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 for honey. EFSA concluded that the new MRL of picloram in honey will not result in a consumer exposure exceeding the toxicological reference values and therefore is unlikely to pose a risk to consumers' health. The chronic consumer risk assessment shall be regarded as indicative and a more realistic intake assessment will be performed in the framework of the MRL review.

Regarding the MRL requests on animal commodities (swine fat, swine liver, bovine liver, sheep liver, goat liver, equine fat and equine liver), EFSA agrees with the conclusion reached by the EMS that the new MRLs proposed by the applicants were not justified based on the current information. Therefore, no change of the existing MRLs for livestock tissues are proposed by EFSA.

The MRL recommendations are summarised in Appendix 5. Furthermore, it is highlighted that the existing residue definition for enforcement set in the Regulation (EC) No 396/2005, which refers to picloram only, needs to be updated for plant commodities and honey with the inclusion of conjugated forms of picloram.

As the renewal of the approval of the active substance picloram and the review of the existing MRLs under Article 12 of Regulation 396/2005 (MRL review) are not yet finalised, the conclusions reported in this reasoned opinion are indicative and may need to be reconsidered in the light of the outcome of these reviews.

ABBREVIATIONS

ADI

acceptable daily intake

ARfD

acute reference dose

a.s.

active substance

BBCH

growth stages of mono‐ and dicotyledonous plants

bw

body weight

CAS

Chemical Abstract Service

cGAP

critical GAP

CXL

Codex maximum residue limit

DAR

draft assessment report

DAT

days after treatment

DM

dry matter

DT₉₀

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

dw

dry weight

EC

emulsifiable concentrate

EMS

evaluating Member State

eq

residue expressed as a.s. equivalent

ESI

electrospray ionisation

EURL

EU Reference Laboratory (former Community Reference Laboratory (CRL))

FAO

Food and Agriculture Organization of the United Nations

GAP

Good Agricultural Practice

GC–MS

gas chromatography with mass spectrometry

GC–MS/MS

gas chromatography with tandem mass spectrometry

GR

granule

GS

growth stage

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

K _oc

organic carbon adsorption coefficient

LOD

limit of detection

LOQ

limit of quantification

MRL

maximum residue level

MS

Member States

MS/MS

tandem mass spectrometry detector

NEU

northern Europe

OECD

Organisation for Economic Co‐operation and Development

PBI

plant back interval

PF

processing factor

PHI

pre‐harvest interval

P _ow

partition coefficient between n‐octanol and water

PRIMo

(EFSA) Pesticide Residues Intake Model

QuEChERS

Quick, Easy, Cheap, Effective, Rugged, and Safe (analytical method)

RA

risk assessment

RAC

raw agricultural commodity

RD

residue definition

RMS

rapporteur Member State

SC

suspension concentrate

SEU

southern Europe

SG

water‐soluble granule

SL

soluble concentrate

SP

water‐soluble powder

STMR

supervised trials median residue

TMDI

theoretical maximum daily intake

TRR

total radioactive residue

UV

ultraviolet (detector)

WG

water‐dispersible granule

WHO

World Health Organization

REQUESTOR

European Commission

QUESTION NUMBER

EFSA‐Q‐2023‐00797

COPYRIGHT FOR NON‐EFSA CONTENT

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

A.1.

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. (g/kg)	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
Oilseed rape, mustard seed, borage seed	NEU	F	Broad‐leaved weeds	SL	80 g/L	Foliar	BBCH 30–50	1	–	–	–	24	g a.s./ha	NA	Authorised EU uses assessed in EFSA, 2013 (rape seed and mustard seed) and EFSA, 2015 (borage seed)

Abbreviations: a.s., active substance; GAP, Good Agricultural Practice; MS, Member State; MRL, maximum residue level; NEU: northern European Union; NR, not applicable; SEU, southern European Union; xx, formulation type.

^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.

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

Primary crops (available studies)	Crop groups	Crop(s)	Application(s)	Sampling (DAT)	Comment/source
	Fruit crops	–	–	–	–
	Root crops	–	–	–	–
	Leafy crops	–	–	–	–
	Cereals/grass	Wheat	Foliar, 1 × 26 & 53 g a. s./ha, BBCH 13–22	0 (forage), 28 (forage), 104 (grain, chaff and straw)	Label position: 2‐ and 6‐ 14C pyridine ring (EFSA, 2009)
	Pulses/oilseeds	Oilseed rape	Foliar, 1 × 40 g a. s./ha, BBCH 33	0 (whole plant), 30 (leaves, stems, flower buds), 50 (leaves, stems, pods) and 84 (stem, chaff and seeds)	Label position: 2‐ and 6‐ 14C pyridine ring (EFSA, 2009)
	Miscellaneous	–	–	–	–

Rotational crops (available studies)	Crop groups	Crop(s)	Application(s)	PBI (DAT)	Comment/Source
	Root/tuber crops	Turnip	583 g a.s./ha to bare soil	30, 120, 365	Label position: 2‐ and 6‐ 14C pyridine ring (EFSA, 2009)
	Leafy crops	Mustard greens	583 g a.s./ha to bare soil	30, 120, 365	Label position: 2‐ and 6‐ 14C pyridine ring (EFSA, 2009)
	Cereal (small grain)	Wheat, maize	583 g a.s./ha to bare soil	30, 120, 365	Label position: 2‐ and 6‐ 14C pyridine ring (EFSA, 2009)
	Other	–	–	–	–

Processed commodities (hydrolysis study)	Conditions	Stable?	Comment/Source
	Pasteurisation (20 min, 90°C, pH 4)	Not triggered	EFSA (2009)
	Baking, brewing and boiling (60 min, 100°C, pH 5)	Not triggered	EFSA (2009)
	Sterilisation (20 min, 120°C, pH 6)	Not triggered	EFSA (2009)
	Other processing conditions	–	–

B.1.1.2. Storage stability of residues in plants

Plant products (available studies)	Category	Commodity	T (°C)	Stability period		Compounds covered	Comment/source
				Value	Unit
	High‐water content	Wheat forage	≤ −20	24	Months	Picloram	EFSA (2009)
	High‐oil content	Rape seed	≤ −20	24	Months	Picloram	EFSA (2009)
	Dry/High‐protein content	–	–	–	–	–	–
	Dry/High starch	Wheat grain	≤ −20	24	Months	Picloram	EFSA (2009)
	High‐acid content	–	–	–	–	–	–
	Processed products	–	–	–	–	–	–
	Others	Wheat straw	≤ −20	24	Months	Picloram	EFSA (2009)
		Oilseed rape hay	≤ −20	24	Months	Picloram	EFSA (2009)

B.1.2. Magnitude of residues in plants

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

Not relevant.

B.1.2.2. Residues in rotational crops

B.1.2.3. Processing factors

No processing studies were submitted in the framework of the present MRL application and are not required.

B.2. Residues in livestock

Dietary burden calculation according to OECD, 2013.

Relevant groups (subgroups)	Dietary burden expressed in				Most critical subgroup a	Most critical commodity b	Trigger exceeded (Y/N)
	mg/kg bw per day		mg/kg DM
	Median	Maximum	Median	Maximum
Cattle (all)	0.022	0.022	0.64 c	0.64 c	Dairy cattle	Wheat milled by products	Y
Cattle (dairy only)	0.022	0.022	0.57	0.57	Dairy cattle	Wheat milled by products	Y
Sheep (all)	0.039	0.039	0.91	0.91	Lamb	Wheat milled by products	Y
Sheep (ewe only)	0.024	0.024	0.73	0.73	Ram/Ewe	Wheat milled by products	Y
Swine (all)	0.027	0.027	0.91	0.91	Swine (finishing)	Wheat milled by products	Y
Poultry (all)	0.034	0.034	0.50	0.50	Poultry layer	Wheat milled by products	Y
Poultry (layer only)	0.034	0.034	0.50	0.50	Poultry layer	Wheat milled by products	Y
Fish	N/A	N/A	N/A	N/A	N/A	N/A	N/A

Abbreviations: bw, body weight; DM, dry matter.

^a When one group of livestock includes several subgroups (e.g. poultry ‘all’ including broiler, layer and turkey), the result of the most critical subgroup is identified from the maximum dietary burdens expressed as ‘mg/kg bw per day’.

^b The most critical commodity is the major contributor identified from the maximum dietary burden expressed as ‘mg/kg bw per day’.

^c The highest dietary burden expressed in mg/kg DM result from beef cattle.

B.2.1. Nature of residues and methods of analysis in livestock

B.2.1.1. Metabolism studies, methods of analysis and residue definitions in livestock

Livestock (available studies)	Animal	Dose	Duration (days)	Comment/Source
	Laying hen	45 mg/kg feed (as received)	7	EFSA (2009)
	Lactating ruminants	17.4 mg/kg bw/day (1200 mg/ kg dry feed)	4	EFSA (2009)

B.2.1.2. Stability of residues in livestock

Animal products (available studies)	Animal	Commodity	T (°C)	Stability period		Compounds covered	Comment/ source
				Value	Unit
	Dairy cow	Muscle	−18°C	2	Months	Picloram	Netherlands (2024)
	Dairy cow	Fat	−18°C	2	Months	Picloram	Netherlands (2024)
	Dairy cow	Liver	−18°C	2	Months	Picloram	Netherlands (2024)
	Dairy cow	Kidney	−18°C	2	Months	Picloram	Netherlands (2024)
	Dairy cow	Milk	−18°C	14	Months	Picloram	EFSA (2009)
	Poultry	Egg white	−18°C	18	Months	Picloram	EFSA (2009)

B.2.2. Magnitude of residues in livestock

B.2.2.1. Summary of the residue data from livestock feeding studies

Calculations performed with Animal model 2017. ¹⁷

a – Results of the calculations, considering linear regression (not supported by EMS and EFSA):

Animal commodity	Residues at the closest feeding level (mg/kg)		Estimated value at 1N		MRL proposal (mg/kg)	CF
	Mean	Highest	STMR a (mg/kg)	HR b (mg/kg)
Cattle (all) – Closest feeding level (0.022 mg/kg bw; 1 N rate) c
Muscle	0.01	0.01	0.01	0.01	0.015	n.a.
Fat	0.01	0.01	0.04	0.08	0.08	n.a.
Liver	0.01	0.01	0.02	0.02	0.02	n.a.
Kidney	0.03	0.04	0.47	0.45	0.5	n.a.
Cattle (dairy only) – Closest feeding level (0.022 mg/kg bw; 1 N rate) c
Milk d	0.01	0.01	0.01	0.01	0.01	n.a.
Sheep (all) e – Closest feeding level (0.022 mg/kg bw; 0.6 N rate) c
Muscle	0.01	0.01	0.01	0.01	0.015	n.a.
Fat	0.01	0.01	0.04	0.08	0.08	n.a.
Liver	0.01	0.01	0.02	0.02	0.02	n.a.
Kidney	0.03	0.04	0.48	0.47	0.5	n.a.
Sheep (ewe only) e – Closest feeding level (0.022 mg/kg bw; 0.9 N rate) c
Milk d	0.01	0.01	0.01	0.01	0.01	n.a.
Swine (all) e – Closest feeding level (0.022 mg/kg bw; × 0.8 rate) c
Muscle	0.01	0.01	0.01	0.01	0.015	n.a.
Fat	0.01	0.01	0.01	0.08	0.08	n.a.
Liver	0.01	0.01	0.01	0.02	0.02	n.a.
Kidney	0.03	0.04	0.03	0.46	0.5	n.a.
Poultry (all) –
Muscle	n.r.	n.r.	n.r.	n.r.	n.r.	n.a.
Fat	n.r.	n.r.	n.r.	n.r.	n.r.	n.a.
Liver	n.r.	n.r.	n.r.	n.r.	n.r.	n.a.
Poultry (layer only) –
Eggs	n.r.	n.r.	n.r.	n.r.	n.r.	n.a.

Abbreviations: bw, body weight; CF, conversion factor; HR, highest residue; n.a., not applicable; n.r., not reported; STMR, supervised trials median residue.

^a The mean residue level for milk and the mean residue levels tissues were recalculated at the 1N rate for the median dietary burden.

^b The mean residue level in milk and the highest residue levels in tissues, were recalculated at the 1N rate for the maximum dietary burden.

^c Closest feeding level and N dose rate related to the maximum dietary burden.

^d Highest residue level from day 1 to day 28 (daily mean of 3 cows).

^e Since extrapolation from cattle to other ruminants and swine is acceptable, results of the livestock feeding study on ruminants were relied upon to derive the MRL and risk assessment values in sheep and swine.

b – Results of the calculations, disregarding the linear regression (EMS and EFSA recommendation)

Animal commodity	Residues at the closest feeding level (mg/kg)		Estimated value at 1N		MRL proposal (mg/kg)	CF
	Mean	Highest	STMR a (mg/kg)	HR b (mg/kg)
Cattle (all) ‐ Closest feeding level (0.022 mg/kg bw; 1 N rate) c
Muscle	< 0.01	< 0.01	< 0.01	< 0.01	0.01*	n.a.
Fat	< 0.01	< 0.01	< 0.01	< 0.01	0.01 *	n.a.
Liver	< 0.01	< 0.01	< 0.01	< 0.01	0.01 *	n.a.
Kidney	0.03	0.04	0.03	0.04	0.04	n.a.
Cattle (dairy only) ‐ Closest feeding level (0.022 mg/kg bw; 1 N rate) c
Milk d	< 0.01	< 0.01	< 0.01	< 0.01	0.01*	n.a.
Sheep (all) e ‐ Closest feeding level (0.022 mg/kg bw; 0.6 N rate) c
Muscle	< 0.01	< 0.01	< 0.01	< 0.01	0.01*	n.a.
Fat	< 0.01	< 0.01	< 0.01	< 0.01	0.01 *	n.a.
Liver	< 0.01	< 0.01	< 0.01	< 0.01	0.01 *	n.a.
Kidney	0.03	0.04	0.05	0.08	0.08	n.a.
Sheep (ewe only) e ‐Closest feeding level (0.022 mg/kg bw; 0.9 N rate) c
Milk d	< 0.01	< 0.01	< 0.01	< 0.01	0.01*	n.a.
Swine (all) e ‐ Closest feeding level (0.022 mg/kg bw; 0.8 N rate) c
Muscle	< 0.01	< 0.01	< 0.01	< 0.01	0.01*	n.a.
Fat	< 0.01	< 0.01	< 0.01	< 0.01	0.01 *	n.a.
Liver	< 0.01	< 0.01	< 0.01	< 0.01	0.01 *	n.a.
Kidney	0.03	0.04	0.05	0.03	0.05	n.a.
Poultry (all) ‐
Muscle	n.r.	n.r.	n.r.	n.r.	n.r.	n.a.
Fat	n.r.	n.r.	n.r.	n.r.	n.r.	n.a.
Liver	n.r.	n.r.	n.r.	n.r.	n.r.	n.a.
Poultry (layer only) ‐
Eggs	n.r.	n.r.	n.r.	n.r.	n.r.	n.a.

Abbreviations: bw, body weight; CF, conversion factor; HR, highest residue; n.a., not applicable; n.r., not reported; STMR, supervised trials median residue.

^*Indicates that the MRL is proposed at the limit of quantification.

^a The mean residue level for milk and the mean residue levels tissues were recalculated at the 1N rate for the median dietary burden.

^b The mean residue level in milk and the highest residue levels in tissues, were recalculated at the 1N rate for the maximum dietary burden.

^c Closest feeding level and N dose rate related to the maximum dietary burden.

^d Highest residue level from day 1 to day 28 (daily mean of 3 cows).

^e Since extrapolation from cattle to other ruminants and swine is acceptable, results of the livestock feeding study on ruminants were relied upon to derive the MRL and risk assessment values in sheep and swine.

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

Products of animal origin (available studies)	Category	Commodity	T (°C)	Stability period		Compounds covered	Comment/source
				Value	Unit
	Bee products	Honey	−18	5.5	Months	picloram	Netherlands (2024)

B.3.2. Magnitude of residues in honey

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

Commodity	Residue levels observed in the supervised residue trials (mg/kg)	Comments/Source	Calculated MRL (mg/kg)	HR a (mg/kg)	STMR b (mg/kg)	CF c
Honey	2 × < 0.01; 0.015; 0.028	Residue trials on honey compliant with authorised cGAP for melliferous oilseed crops Samples were analysed for the sum of picloram and its conjugates, expressed as picloram	0.05	0.028	0.012	–

Abbreviations: GAP, Good Agricultural Practice; Mo, monitoring; MRL, maximum residue level; RA, risk assessment.

^a Highest residue.

^b Supervised trials median residue.

^c 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 (existing): Picloram
1011020	Swine fat	0.01*	No change	The submitted data do not provide evidence that the existing MRL has to be modified
1011030	Swine liver	0.01*	No change	The submitted data do not provide evidence that the existing MRL has to be modified
1011990	Swine, Others	0.01*	No change	The submitted data do not provide evidence that the existing MRL has to be modified
1012030	Bovine liver	0.01*	No change	The submitted data do not provide evidence that the existing MRL has to be modified
1012990	Bovine, Others	0.01*	No change	The submitted data do not provide evidence that the existing MRL has to be modified
1013030	Sheep liver	0.01*	No change	The submitted data do not provide evidence that the existing MRL has to be modified
1013990	Sheep, Others	0.01*	No change	The submitted data do not provide evidence that the existing MRL has to be modified
1014030	Goat liver	0.01*	No change	The submitted data do not provide evidence that the existing MRL has to be modified
1014990	Goat, Others	0.01*	No change	The submitted data do not provide evidence that the existing MRL has to be modified
1015020	Equine fat	0.01*	No change	The submitted data do not provide evidence that the existing MRL has to be modified
1015030	Equine liver	0.01*	No change	The submitted data do not provide evidence that the existing MRL has to be modified
1015990	Equine, Others	0.01*	No change	The submitted data do not provide evidence that the existing MRL has to be modified
1017020	Other farmed terrestrial animals fat	0.01*	No change	The submitted data do not provide evidence that the existing MRL has to be modified
1017030	Other farmed terrestrial animals liver	0.01*	No change	The submitted data do not provide evidence that the existing MRL has to be modified
1017990	Other farmed terrestrial animals, Others	0.01*	No change	The submitted data do not provide evidence that the existing MRL has to be modified
Enforcement residue definition (existing): Picloram Enforcement residue definition (proposed): Picloram, free and conjugated, expressed as picloram
1040000	Honey and other apiculture products b	0.05*	0.05 c	The submitted data are sufficient to derive a MRL proposal. Samples were analysed for the sum of picloram and its conjugates, expressed as picloram, in line with the proposed residue definition for enforcement. The MRL value of 0.05 mg/kg reflects the proposed residue definition for enforcement including conjugates. 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.

^c The proposed EU MRL differs from the MRL derived by the EMS (i.e. 0.06 mg/kg), due to rounding.

APPENDIX C. Pesticide Residue Intake Model (PRIMo)

C.1.

APPENDIX D. Input values for the exposure calculations

D.1. Livestock dietary burden calculations

Feed commodity	Median dietary burden		Maximum dietary burden
	Input value a (mg/kg)	Comment	Input value a (mg/kg)	Comment
Barley grain	0.2	Existing MRL	0.2	Existing MRL
Maize grain	0.2	Existing MRL	0.2	Existing MRL
Oat grain	0.2	Existing MRL	0.2	Existing MRL
Sorghum grain	0.2	Existing MRL	0.2	Existing MRL
Wheat grain	0.2	Existing MRL	0.2	Existing MRL
Brewer's grain dried	0.66	Existing MRL × default PF (3.3) b	0.66	Existing MRL × default PF (3.3) b
Rapeseed and canola, meal	0.02	STMR × default PF (2) b (EFSA, 2013)	0.02	STMR × default PF (2) b (EFSA, 2013)
Corn field, milled by products	0.2	Existing MRL × default PF (1) b	0.2	Existing MRL × default PF (1) b
Corn field, hominy meal	1.2	Existing MRL × default PF (6) b	1.2	Existing MRL × default PF (6) b
Corn field, gluten feed	0.5	Existing MRL × default PF (2.5) b	0.5	Existing MRL × default PF (2.5) b
Corn field, gluten meal	0.2	Existing MRL × default PF (1) b	0.2	Existing MRL × default PF (1) b
Distiller's grain, dried	0.66	Existing MRL × default PF (3.3) b	0.66	Existing MRL × default PF (3.3) b
Sugar cane, molasses	1.6	Existing MRL × default PF (32) b	1.6	Existing MRL × default PF (32) b
Wheat gluten, meal	0.36	Existing MRL × default PF (1.8) b	0.36	Existing MRL × default PF (1.8) b
Wheat, milled by products	1.4	Existing MRL × default PF (7) b	1.4	Existing MRL × default PF (7) b

Abbreviations: HR, highest residue; PF, processing factor; STMR, supervised trials median residue.

^a Figures in the table are rounded to 2 digits, but the calculations are normally performed with the actually calculated values (which may contain more digits). To reproduce dietary burden calculations, the unrounded values need to be used.

^b In the absence of processing factors supported by data, default processing factors (in bracket) were respectively included in the calculation to consider the potential concentration of residues in these commodities.

D.2. Consumer risk assessment

Commodity	Existing/proposed MRL (mg/kg)	Source	Chronic risk assessment		Acute risk assessment
			Input value a (mg/kg)	Comment	Input value a (mg/kg)	Comment b
Risk assessment residue definition: picloram
Broccoli	0.08	EFSA (2020)	0.01	STMR‐RAC	0.05	HR‐RAC
Cauliflowers	0.08	EFSA (2020)	0.01	STMR‐RAC	0.05	HR‐RAC
Other flowering brassica	0.08	EFSA (2020)	0.01	STMR‐RAC	0.05	HR‐RAC
Rapeseeds/canola seeds	0.03	EFSA (2013)	0.01	STMR‐RAC	0.01	STMR‐RAC
Mustard seeds	0.03	EFSA (2013)	0.01	STMR‐RAC	0.01	STMR‐RAC
Borage seeds	0.03	EFSA (2015)	0.01	STMR‐RAC	0.01	STMR‐RAC
Swine fat	0.01*	Reg. (EU) 2021/1531	0.01*	MRL = LOQ	0.01*	MRL = LOQ
Swine liver	0.01*	Reg. (EU) 2021/1531	0.01*	MRL = LOQ	0.01*	MRL = LOQ
Swine, Others	0.01*	Reg. (EU) 2021/1531	0.01*	MRL = LOQ	0.01*	MRL = LOQ
Bovine liver	0.01*	Reg. (EU) 2021/1531	0.01*	MRL = LOQ	0.01*	MRL = LOQ
Bovine, Others	0.01*	Reg. (EU) 2021/1531	0.01*	MRL = LOQ	0.01*	MRL = LOQ
Sheep liver	0.01*	Reg. (EU) 2021/1531	0.01*	MRL = LOQ	0.01*	MRL = LOQ
Sheep, Others	0.01*	Reg. (EU) 2021/1531	0.01*	MRL = LOQ	0.01*	MRL = LOQ
Goat liver	0.01*	Reg. (EU) 2021/1531	0.01*	MRL = LOQ	0.01*	MRL = LOQ
Goat, Others	0.01*	Reg. (EU) 2021/1531	0.01*	MRL = LOQ	0.01*	MRL = LOQ
Equine fat	0.01*	Reg. (EU) 2021/1531	0.01*	MRL = LOQ	0.01*	MRL = LOQ
Equine liver	0.01*	Reg. (EU) 2021/1531	0.01*	MRL = LOQ	0.01*	MRL = LOQ
Equine, Others	0.01*	Reg. (EU) 2021/1531	0.01*	MRL = LOQ	0.01*	MRL = LOQ
Other farmed terrestrial animals fat	0.01*	Reg. (EU) 2021/1531	0.01*	MRL = LOQ	0.01*	MRL = LOQ
Other farmed terrestrial animals liver	0.01*	Reg. (EU) 2021/1531	0.01*	MRL = LOQ	0.01*	MRL = LOQ
Other farmed terrestrial animals, Others	0.01*	Reg. (EU) 2021/1531	0.01*	MRL = LOQ	0.01*	MRL = LOQ
Honey and other apiculture products c	0.05	MRL proposal	0.012	STMR (semi‐field/tunnel residue trials)	0.028	HR (semi‐field/tunnel residue trials)
Other crops/commodities	See Reg. (EU) 2021/1531	Reg. (EU) 2021/1531	MRL	See Reg. (EU) 2021/1531	Acute risk assessment undertaken only for the commodities under assessment

Abbreviations: HR‐RAC, highest residue in raw agricultural commodity; 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 Figures in the table are rounded to 2 digits, but the calculations are normally performed with the actually calculated values (which may contain more digits). To reproduce dietary burden calculations, the unrounded values need to be used.

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

^c According to Regulation (EC) No 396/2005 MRLs are not applicable to other apiculture products until individual products have been identified and listed within this group.

APPENDIX E. Used compound codes

E.1.

Code/trivial name a	IUPAC name/SMILES notation/InChiKey b	Structural formula c
Picloram	4‐amino‐3,5,6‐trichloropyridine‐2‐carboxylic acid Clc1nc(C(O) = O)c(Cl)c(N)c1Cl NQQVFXUMIDALNH‐UHFFFAOYSA‐N
Picloram‐olamine	4‐amino‐3,5,6‐trichloropyridine‐2‐carboxylic acid—2‐aminoethan‐1‐ol Clc1nc(C(O) = O)c(Cl)c(N)c1Cl.OCCN IFYBRLPVVJLYIF‐UHFFFAOYSA‐N

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

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

^b ACD/Name 2023.2.4 ACD/Labs 2023.2.4 (File Version N25E41, Build 137185, 31 January 2024).

^c ACD/ChemSketch 2023.2.4 ACD/Labs 2024.2.4 (File Version C45H41, Build 137017, 18 January 2024).

EFSA (European Food Safety Authority) , Bellisai, G. , Bernasconi, G. , Cabrera, L. C. , Castellan, I. , del Aguila, M. , Ferreira, L. , Greco, L. , Jarrah, S. , Leuschner, R. , Mioč, A. , Nave, S. , Reich, H. , Ruocco, S. , Scarlato, A. P. , Szot, M. , Theobald, A. , Tiramani, M. , Verani, A. , & Zioga, E. (2024). Modification of the existing maximum residue levels for picloram in animal commodities and honey. EFSA Journal, 22(10), e9067. 10.2903/j.efsa.2024.9067