Adherence self report assessment in solid-organ pre and post transplant recipients.

OBJECTIVE: There is strong evidence that many patients with chronic diseases have difficulties to adhere to the medical regimens. As to transplantation, nonadherence to the prescribed medical regimen has repeatedly been found to predict morbidity and mortality, both in adults and in children. Many instruments are available in order to assess nonadherence to immunosuppressive medication, whereas only few are available on behavioural components. Aim of the study was to present the Adherence Schedule in Transplantation (ASiT, in its three versions: ASiT-A, Adults; ASiT-PA, Proxy Adult and ASiT-PC, Proxy Child) that evaluates the Cognitive Relational Antecedents of adherence to treatment and the Self-efficacy in disease management in patients before and after transplantation. METHOD: (1) Review and construct analysis of the already existing adherence Schedules, on the basis of literature review and clinical experience; (2) Construction of the ASiT in its three versions from an adaptation of the already existing adherence Schedules; (3) Administration of the ASiT to pre and post transplant recipients followed by a semi-structured interview in order to discuss with the patients pros and cons; (4) ASiT correction on the basis of patients' comments; (5) Translation in English by a bilingual English mother tongue. RESULTS: On the whole 56 Schedules were administered to pre and post transplant (liver, heart, lung and kidney) recipients and their proxy and resulted to have good construct validity, were easily administered and were well accepted by patients. CONCLUSIONS: As to research the ASiT could cover a wide range of nonadherence sources. Within a clinical context our Schedule could be a not time consuming tool useful in favouring the communication about adherence and able to enhance patients' personal limits and resources.

Modification of the existing maximum residue levels and setting of import tolerances for metiram in various crops.

In accordance with Article 6 of Regulation (EC) No 396/2005, the applicant BASF Italia Srl submitted a request to the competent national authority in Italy to set import tolerances for the active substance metiram in passion fruits/maracujas, bananas, pineapples and to modify the existing maximum residue level (MRL) in celeriacs on the basis of intended northern Europe (NEU) use. The data submitted in support of the request were found sufficient to derive MRL proposals for pineapples and passion fruits/maracujas; according to the data provided, the existing EU MRL in bananas did not require modification and the data were not sufficient to derive an MRL proposal for celeriacs. A consumer exposure calculation, which considered only metiram uses, indicated no long-term consumer intake concerns, but is affected by several uncertainties related to the lack of residue data reflecting the existing uses of metiram. A second exposure scenario in which the lack of information was overcome by conservative assumptions indicated potential chronic exposure concerns for a number of diets. The contribution of residues in the crops under consideration to the long-term consumer exposure is low. The consumer exposure to ethylenethiourea (ETU) residues from the existing and intended metiram uses indicated no consumer intake concerns. However, the risk assessment is affected by a number of uncertainties that could not be addressed with the currently available data. EFSA therefore proposed that a comprehensive consumer exposure to ETU residues is performed in the framework of Article 12 MRL review, considering the existing uses of dithiocarbamates that are known to degrade to ETU in processed products. Considering the inconclusive results and overall uncertainties in the risk assessment, EFSA is of the opinion that further risk management discussions are required whether a modification of existing dithiocarbamate MRLs is justified prior to the finalisation of the MRL review on metiram and other dithiocarbamates.

Review of the existing maximum residue levels for thiram according to Article 12 of Regulation (EC) No 396/2005.

According to Article 12 of Regulation (EC) No 396/2005, EFSA has reviewed the maximum residue levels (MRLs) currently established at European level for the pesticide active substance thiram. Although this active substance is no longer authorised within the European Union, MRLs based on the use of thiram were established by the Codex Alimentarius Commission (codex maximum residue limits; CXLs) and import tolerances were reported by Member States (including the supporting residues data). Based on the assessment of the available data, EFSA assessed the existing import tolerances, and a consumer risk assessment was carried out for thiram only. Although no apparent risk to consumers was identified, the import tolerances were not fully supported by data. Hence, the consumer risk assessment is considered indicative only and further consideration by risk managers is needed.

Modification of the existing maximum residue levels for tebufenozide in apricots and peaches.

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

Modification of the existing maximum residue levels for bentazone in beans and peas with and without pods.

In accordance with Article 6 of Regulation (EC) No 396/2005, the applicant BASF SE submitted a request to the competent national authority in the Netherlands to modify the existing maximum residue levels (MRLs) for bentazone in beans and peas with and without pods. The data submitted in support of the request were found to be sufficient to derive MRL proposals for peas with pods. Results from the residue trials indicated that there is no need to modify the existing MRLs for beans with pods, beans without pods and peas without pods. Adequate analytical methods for enforcement are available to control the residues of bentazone and its metabolites in the commodity under consideration at the validated limit of quantification (LOQ) of 0.01 mg/kg. EFSA concluded that the proposed use of bentazone on peas with pods will not result in a consumer exposure exceeding the toxicological reference values and therefore is unlikely to pose a risk to consumers' health for parent bentazone. The risk assessment however is indicative and affected by additional, non-standard uncertainties resulting from the insufficient information related to the toxicological properties for 6-hydroxy-bentazone in the wheat metabolism study.

Focussed assessment of certain existing MRLs of concern for Spinosad.

In compliance with Article 43 of Regulation (EC) No 396/2005, the EFSA received from the European Commission a mandate to provide its reasoned opinion on the existing maximum residue levels (MRLs) for spinosad which might lead to consumers intake concerns on the basis of a new toxicological reference value established during the peer review and of the data currently available to EFSA. In order to identify the MRLs of potential concern that require a more detailed assessment, EFSA screened the existing MRLs for spinosad considering the new toxicological reference values and an acute risk could not be excluded for six commodities. Fall-back MRLs for all six commodities were proposed on the basis of the data received under the present assessment.

Modification of the existing maximum residue levels for cyflumetofen in various crops.

In accordance with Article 6 of Regulation (EC) No 396/2005, the applicants BASF Agro B.V. (represented by OAT Agrio Co. Ltd.) and Certis Europe B.V. submitted separate requests to the competent national authority in the Netherlands to modify the existing maximum residue levels (MRLs) for the active substance cyflumetofen in various crops. The data submitted in support of the requests were found to be sufficient to derive MRL proposals for citrus fruits, apricots, peaches, tomatoes, aubergines, cucumbers and hops. Adequate analytical methods for enforcement are available to control the residues of cyflumetofen on the fruit commodities under consideration at the validated limit of quantification (LOQ) of 0.01 mg/kg and on hops at the LOQ of 0.1 mg/kg. Based on the risk assessment results, EFSA concluded that the long-term intake of residues resulting from the use of cyflumetofen according to the reported agricultural practices is unlikely to present a risk to consumer health.

Review of the existing maximum residue levels for sulfuryl fluoride according to Article 12 of Regulation (EC) No 396/2005.

According to Article 12 of Regulation (EC) No 396/2005, EFSA has reviewed the maximum residue levels (MRLs) currently established at European level for the pesticide active substance sulfuryl fluoride. To assess the occurrence of sulfuryl fluoride and fluoride ion residues in plants, processed commodities and livestock, EFSA considered the conclusions derived in the framework of Directive 91/414/EEC, the MRLs established by the Codex Alimentarius Commission as well as the European authorisations reported by Member States (including the supporting residues data). Based on the assessment of the available data, MRLs were calculated, but a consumer risk assessment could be carried out for sulfuryl fluoride only. Although no apparent risk to consumers was identified for sulfuryl fluoride, a standard consumer risk assessment to fluoride ion could not be performed, lacking information on the toxicological reference values for fluoride. Hence, an 'overall' consumer risk assessment could not be performed, only tentative MRLs proposal could be derived and measures for reduction of the consumer exposure should also be considered. Nevertheless, considering that fluoride ion is naturally occurring in food of plant and animal origin, EFSA performed an indicative calculation of the consumer exposure to estimate whether the uses currently authorised will contribute significantly to the overall consumer exposure to fluoride.

Modification of the existing maximum residue levels for acibenzolar-S-methyl in beans with pods and peas with pods.

In accordance with Article 6 of Regulation (EC) No 396/2005, the applicant Syngenta France SAS submitted a request to the competent national authority in France to amend the residue definition for risk assessment and to modify the existing maximum residue levels (MRLs) for the active substance acibenzolar-S-methyl in beans (with pods) and peas (with pods). The toxicological data submitted in support of this MRL application were found to be sufficient to conclude that the plant metabolite 4-OH acibenzolar acid is not genotoxic in vitro, however lacking investigation of the general toxicity, a definitive conclusion cannot be derived whether 4-OH acibenzolar acid (free and conjugated) should be included or excluded from the residue definition for risk assessment for all commodities belonging to the groups of leafy crops and pulses/oilseeds. The data submitted in support of the request were found to be sufficient to derive MRL proposals on the basis of the current residue definition (sum of acibenzolar-S-methyl and acibenzolar acid (free and conjugated), expressed as acibenzolar-S-methyl) for the intended uses on lettuces and salad plants, beans (with pods) and peas (with pods). The available residue trials are sufficient to derive MRL proposals of 1 mg/kg for beans with pods and peas with pods. The submitted information did not provide evidence that the existing MRL has to be changed for the intended uses on lettuces and other salad plants. For herbs and edible flowers, data gaps were identified which precluded the derivation of MRL proposals. The consumer risk assessment for the current residue definition did not identify an unacceptable risk for consumers. The indicative exposure calculations performed for the metabolite 4-OH acibenzolar indicate that exposure to this metabolite is lower than the exposure to acibenzolar-S-methyl and acibenzolar acid (free and conjugated). However, considering the data gaps identified, a definitive conclusion cannot be derived by EFSA on the risk for consumers related to the intake of residues of 4-OH acibenzolar acid. The reliable end points appropriate for use in regulatory risk assessment are presented.

Setting of import tolerance for azoxystrobin in sugar beet roots.

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

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

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

Modification of the existing maximum residue levels for difenoconazole in leafy brassica.

In accordance with Article 6 of Regulation (EC) No 396/2005, the applicant Syngenta Crop Protection AG submitted a request to the competent national authority in the Netherlands to modify the existing maximum residue levels (MRLs) for the active substance difenoconazole in commodities belonging to the group of leafy brassica. The data submitted in support of the request were found to be sufficient to derive MRL proposals for leafy brassica. Adequate analytical methods for enforcement are available to control the residues of difenoconazole in plant matrices under consideration at the validated LOQ of 0.01 mg/kg and for difenoconazole and metabolite CGA205375 in animal matrices at the validated LOQ of 0.01 mg/kg for meat muscle, fat, liver, kidney and eggs and at the validated LOQ of 0.005 mg/kg for milk. Based on the risk assessment results, EFSA concluded that for the crops assessed in this application the short-term intake of residues resulting from the use of difenoconazole according to the reported agricultural practices is unlikely to present a risk to consumer health. Long-term consumer intake concerns cannot be excluded for the intended and existing difenoconazole uses as they are affected by uncertainties associated with the toxicity of metabolite CGA205375 and the lack of information on all existing difenoconazole uses in the EU. Overall, this risk assessment is considered provisional, pending the submission of confirmatory data on possible preferential metabolism/degradation of the four stereo isomers of difenoconazole in plants and has to be re-considered when the missing data become available. Additionally, this assessment does not take into consideration triazole derivative metabolites (TDMs) which may be generated by several pesticides belonging to the group of triazole fungicides as this application was submitted before September 2019 which is the date of application of the new strategy endorsed by the risk managers for the assessment of TDMs.

Reasoned opinion on the toxicological properties and maximum residue levels for propoxur.

In accordance with Article 43 of Regulation (EC) No 396/2005, the European Commission requested EFSA to prepare a reasoned opinion on the toxicological properties and the existing maximum residue levels (MRLs) set for propoxur. EFSA was requested to assess the toxicological properties of propoxur and derive toxicological reference values, based on the toxicological assessment performed by Health Canada. EFSA was also requested to review the information provided by Member States and the UK on the metabolism of propoxur in plants and animals and on the current MRLs, as well as the limit of quantification (LOQ) that can be achieved with analytical methods used in MRL enforcement. Based on the information available to EFSA, toxicological reference values could not be derived for propoxur. No evidence was provided by Member States and UK that the existing EU MRLs need to be maintained as import tolerances. Information to support the current MRLs or alternative MRLs have not been provided by Member States and the UK. Codex MRLs are not in place. EFSA therefore recommended lowering of all existing EU MRLs for propoxur to the LOQ. According to the EU Reference Laboratories, sufficiently validated analytical methods are available to analyse for propoxur residues in all plant and animal commodities. Lacking toxicological reference values derived at EU level, a conclusion cannot be derived whether the setting of MRLs at the LOQs is sufficiently protective for the European consumers.

Modification of the existing maximum residue levels for clopyralid in various commodities.

In accordance with Article 6 of Regulation (EC) No 396/2005, the applicant Corteva submitted a request to the competent national authority in Finland to modify the existing maximum residue levels (MRLs) for the active substance clopyralid in various commodities. The data submitted in support of the request were found to be sufficient to derive MRL proposals for wheat, oat and for animal commodities. An adequate analytical method for enforcement is available to control the residues of clopyralid in the plant commodities under consideration at the validated limit of quantification (LOQ) of 0.01 mg/kg. The analytical methods for animal commodities are validated at LOQ of 0.01 mg/kg, but demonstration of extraction efficiency is lacking. Based on the risk assessment results, EFSA concluded that the short-term and long-term intake of residues resulting from the use of clopyralid according to the reported agricultural practices is unlikely to present a risk to consumer health provided that risk mitigation measures are in place to avoid clopyralid residues in rotational and/or succeeding crops.

Evaluation of confirmatory data following the Article 12 MRL review and modification of the existing maximum residue levels for prothioconazole in celeriacs and rapeseeds.

In accordance with Article 6 of Regulation (EC) No 396/2005, the applicants Bayer SAS Crop Science and the Agriculture and Horticulture Development Board submitted two requests to the competent national authority in the United Kingdom to modify the existing maximum residue levels (MRLs) for prothioconazole in rapeseeds and celeriacs, respectively. The data submitted in support of the requests were found to be sufficient to derive MRL proposals for these crops. The applicant Bayer SAS Crop Science additionally submitted a request to the competent national authority in the United Kingdom to evaluate the confirmatory data identified in the framework of the MRL review under Article 12 of Regulation (EC) No 396/2005 as not available. To address the data gaps, residue trials on carrots, onions, rapeseeds and wheat, and storage stability studies were submitted. The data gaps are considered fully addressed for the root and tuber vegetables, the oilseeds concerned and wheat. The data gaps have been partially addressed for onions, shallots, flowering brassica, Brussels sprouts, head cabbages, leeks, rye, barely and oat. The data gaps were not addressed for pulses and grass. Based on the risk assessment results, EFSA concluded that the short-term and long-term intake of residues resulting from the existing and intended uses of prothioconazole according to the reported agricultural practices is unlikely to present a risk to consumer health. For the triazole derivative metabolites (TDMs), only an indicative exposure assessment was performed considering celeriacs and rapeseeds; the results showed that the expected exposure to TDMs in these commodities is well below the toxicological reference values derived for the TDMs.

Modification of the existing maximum residue level for pyridaben in sweet pepper/bell pepper and setting of an import tolerance in tree nuts.

In accordance with Article 6 of Regulation (EC) No 396/2005, the applicant Nissan Chemical Europe S.A.S. submitted two requests to the competent national authority in the Netherlands, respectively to modify the existing maximum residue level (MRL) in sweet pepper/bell pepper and to set an import tolerance in tree nuts for the active substance pyridaben. The data submitted in support of the requests were found to be sufficient to derive the MRL proposals of 0.3 mg/kg for sweet peppers/bell peppers and of 0.05* mg/kg for tree nuts. Adequate analytical methods for enforcement are available to control the residues of pyridaben in the commodities under consideration, at or above the validated limits of quantification (LOQs) of 0.01 mg/kg. Based on the risk assessment results, EFSA concluded that the short-term and long-term intake of residues resulting from the use of pyridaben on imported tree nuts from United States and from the indoor use on sweet peppers/bell peppers according to the reported agricultural practices, is unlikely to present a risk to consumer health. The reliable end points, appropriate for use in regulatory risk assessment are presented.

Evaluation of confirmatory data following the Article 12 MRL review for sodium 5-nitroguaiacolate, sodium o-nitrophenolate and sodium p-nitrophenolate (sodium nitrocompounds).

The applicant Asahi Chemical Europe s.r.o. submitted a request to the competent national authority in the Netherlands to evaluate the confirmatory data that were identified for the pesticide active substances sodium 5-nitroguaiacolate, sodium o-nitrophenolate and sodium p-nitrophenolate (sodium nitrocompounds) in the framework of the maximum residue level (MRL) review under Article 12 of Regulation (EC) No 396/2005 as not available. To address the data gap related to validated analytical enforcement method, the validation data of a method for the determination of sodium nitrocompounds in high acid content commodities, dry commodities and hops (dried) was submitted. The data gap was considered satisfactorily addressed. The new information provided does not require a revision of the existing MRLs; the risk assessment performed for the three active substances sodium 5-nitroguaiacolate, sodium o-nitrophenolate and sodium p-nitrophenolate in the framework of the MRL review remains valid.

Review of the existing maximum residue levels for fluopyram according to Article 12 of Regulation (EC) No 396/2005.

According to Article 12 of Regulation (EC) No 396/2005, EFSA has reviewed the maximum residue levels (MRLs) currently established at European level for the pesticide active substance fluopyram. To assess the occurrence of fluopyram residues in plants, processed commodities, rotational crops and livestock, EFSA considered the conclusions derived in the framework of Commission Regulation (EU) No 188/2011, the MRLs established by the Codex Alimentarius Commission as well as the import tolerances and European authorisations reported by Member States (including the supporting residues data). Based on the assessment of the available data, MRL proposals were derived and a consumer risk assessment was carried out. Some information required by the regulatory framework was missing and a possible chronic risk to consumers was identified. Hence, the consumer risk assessment is considered indicative only, some MRL proposals derived by EFSA still require further consideration by risk managers and measures for reduction of the consumer exposure should also be considered. Hence, the consumer risk assessment is considered indicative only and some MRL proposals derived by EFSA still require further consideration by risk managers.

Reasoned opinion on the setting of temporary maximum residue levels for chlorpropham in potatoes.

EFSA received from the European Commission a mandate to deliver a reasoned opinion according to Article 43 of Regulation (EC) No 396/2005 on the safety of a proposed temporary maximum residue level (tMRL) for chlorpropham in potatoes to consumers. Sprout inhibitors based on the active substance chlorpropham have been widely used in commercial storage facilities in Europe over multiple seasons. Following the non-renewal of approval of chlorpropham, representatives of potato trade organisations and manufacturers of chlorpropham reported an issue of cross-contamination above the limit of quantification (LOQ) of untreated potatoes stored in facilities with a history of applications of chlorpropham as a post-harvest treatment. The evaluating Member State (EMS) the Netherlands, in accordance with Articles 6(2) and 16 (1)(a) of Regulation (EC) No 396/2005, submitted an application for the setting of a tMRL for chlorpropham in potatoes in order to address the cross-contamination in commercial storages. The EMS proposed to set a tMRL for the active substance at a level ranging between 0.3 and 0.5 mg/kg. Based on the assessment of the available data and information with different methodologies, optional tMRL proposals of 0.3, 0.4 and 0.5 mg/kg were derived, and an indicative consumer risk assessment was carried out. The tMRL proposals require further consideration by risk managers, mainly with regard to identified uncertainties, and measures for further reduction of occurrence of chlorpropham residues will also need to be considered. With this prospect, EFSA concluded that the short-term and long-term intake of residues of chlorpropham and 3-chloroaniline resulting from cross-contamination in potatoes is unlikely to present a risk to consumer health.

Modification of the existing maximum residue levels for lambda-cyhalothrin in seed and fruit spices.

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