Normativa UEOct. 24, 2013
UE: revisan límites máximos de residuo para iprodione en duraznos, frutillas y otros
Iprodione was included in Annex I to Directive 91/414/EEC on 01 January 2004, which is before the entry into force of Regulation (EC) No 396/2005 on 02 September 2008. EFSA is therefore required to provide a reasoned opinion on the review of the existing MRLs for that active substance in compliance with Article 12(2) of the aforementioned regulation. In order to collect the relevant pesticide residues data, EFSA asked France, as the designated rapporteur Member State (RMS), to complete the Pesticide Residues Overview File (PROFile). The requested information was submitted to EFSA on 18 August 2009 and, after having considered several comments made by EFSA, the RMS provided on 10 December 2012 a revised PROFile.
Based on the conclusions derived in the framework of Directive 91/414/EEC, the MRLs established by the Codex Alimentarius Commission and the additional information provided by the RMS, EFSA issued on 22 March 2013 a draft reasoned opinion that was circulated to Member States’ experts for consultation. Comments received by 24 May 2013 were considered in the finalisation of this reasoned opinion. The following conclusions are derived.
The toxicological profile of iprodione was evaluated in the framework of Directive 91/414/EEC, which resulted in an ADI being established at 0.06 mg/kg bw per d. An ARfD was not deemed necessary.
Metabolism of iprodione was investigated for foliar and spray applications on fruits and fruiting vegetables (peaches and strawberries), leafy vegetables (lettuce), pulses and oilseeds (peanuts) and cereals (rice and wheat). The results of these studies, which were conducted before the GLP requirements became applicable, are not sufficiently detailed to get a clear understanding of the metabolism of iprodione in plants. In the absence of more appropriate data, available studies are considered on a tentative basis in the framework of this review. In the reported metabolism studies, a high level of the TRR remained unidentified. Further clarifications on the identity of the radioactive residues are therefore still required. Consequently, noting the deficiencies of the metabolism studies assessed in the peer review, it is proposed that the residue definition for enforcement and risk assessment in all plant commodities is defined on a tentative basis as iprodione only. Validated analytical methods for enforcement of the proposed residue definition are available with a LOQ of 0.01 mg/kg in high water content and high acid content commodities and a LOQ of 0.02 mg/kg in dry commodities. There are indications that an LOQ of 0.01 mg/kg could be achieved for high fat content commodities but further ILV data are required for this crop group.
Regarding the magnitude of residues in primary crops, the available residues data are considered sufficient to derive tentative MRLs in all commodities except for hazelnuts, celeriac, swedes, turnips, kale, kohlrabi, land cress, spinach, beet leaves, peas (fresh, without pods), asparagus, celery, fennel, leek, herbal infusions (dried flowers, leaves), spices and rape seed where the available data were insufficient to derive tentative MRLs or risk assessment values. Moreover, further investigation storage stability of iprodione in high oil, high acid content and dry commodities is still required in order to ensure that no degradation of residues occurred during storage of the trial samples other than those having high water content.
The effect of processing on the nature of iprodione was investigated in the framework of the peer review. Studies were conducted using four test conditions (30 minutes at 70°C, pH 4 and 6; 30 minutes at 130°C, pH 4 and 6). Whilst iprodione was found to be stable at 70°C (pH 4 and 6) and at 130°C (pH 4), iprodione degraded almost completely at 130°C (pH 6), conditions representative of sterilisation, with the notable formation of 3,5-dichloroaniline and a range of other metabolites. EFSA is of the opinion that 3,5-dichloroaniline might have a more severe toxicity than the parent compound because 3,5-dichloroaniline belongs to the group of chloroaniline compounds, several of which (e.g. 4-chloroaniline and 4,6-chloroaniline) are suspected to be carcinogenic. Due to a lack of sufficient information on the toxicological relevance of these degradation products, the residue definition for processed commodities cannot be concluded on. Characterisation of the toxicological relevance of 3,5-dichloroaniline and the other metabolites formed during the processing study should be conducted. In addition, a study investigating the effect of processing on the nature of iprodione residues under conditions simulating cooking/boiling is also desirable as the test conditions studied do not adequately reflect this. The magnitude of residues in processed commodities were also investigated in the framework of the peer review however due to limited information on the nature of residues in each processed commodity, tentative processing factors could be derived only.
All crops under consideration, except permanent crops (stone fruit, lemons, pome fruit, bush fruit), may be grown in rotation. Based on the soil degradation studies evaluated in the framework of the peer review the DT90 value of iprodione is expected to be lower than 100 days. Although not required, the metabolism of iprodione in rotational crops of legumes, cereals, root and tuber vegetables, pulses and oilseeds, fruit and fruiting vegetables was evaluated in the framework of the peer review. As for the primary crops, the results of these studies, which were conducted before the GLP requirements became applicable, are not sufficiently detailed to get a clear understanding of the metabolism of iprodione in rotational crops. Nevertheless, in the absence of more appropriate data, available studies are considered on a tentative basis in the framework of this review. Due to the large amount of unextracted residues observed in the rotational crops studies, EFSA recommends characterising and identifying the unextracted residues observed in the rotational crop studies to get a clear understanding of the nature and magnitude of residues in rotational and succeeding crops.
Based on the uses reported by the RMS, significant intakes were calculated for ruminants, pigs and poultry. Metabolism in lactating ruminant and laying hens was sufficiently investigated and findings can be extrapolated to pigs. The relevant residue definition for enforcement and risk assessment was defined as the sum of iprodione and all metabolites containing the 3,5-dichloroaniline moiety expressed as iprodione. However due to the lack of toxicological information on 3,5-dichloroaniline, EFSA proposes that these residue definitions should be considered as tentative only. EFSA notes that in the livestock metabolism studies, the 4-hydroxylated metabolites, RP36114 and DCHPU were the major metabolites detected in milk and kidney respectively. These metabolites were not detected in any other tissues. Due to the lack of toxicological information on DCHPU and RP36114 EFSA proposes to define the relevant residue definition for risk assessment in milk and kidney as the sum of iprodione and all metabolites containing the 3,5-dichloroaniline and 3,5-dichloro-4-hydroxy-aniline moieties expressed as iprodione. Tentative conversion factors of 3 and 2 were derived for risk assessment of kidney and milk respectively from the available metabolism studies. The RMS reported livestock feeding studies in lactating ruminants and poultry which allowed EFSA to tentatively estimate the magnitude of residues in ruminant, poultry and pig products and to derive tentative MRLs in these commodities but further data supporting the enforcement residue definition in milk and the risk assessment residue definition in kidney are still required. Validated analytical methods for enforcement of the proposed residue definition are available with a LOQ of 0.005 mg/kg in milk however a data gap exists with regard to the need for confirmatory validation data. Fully validated methods of analysis and ILV are required for eggs, meat, liver, fat and kidney.
Chronic consumer exposure resulting from the authorised uses reported in the framework of this review was calculated using revision 2 of the EFSA PRIMo. For those commodities where data were insufficient to derive an MRL, EFSA considered the existing EU MRL for an indicative calculation. The highest chronic exposure represented 42.6% of the ADI (German child).
Apart from the MRLs evaluated in the framework of this review, internationally recommended CXLs have also been established for iprodione. Additional calculations of the consumer exposure, considering these CXLs, were therefore carried out. The highest chronic exposure represented 57.8% of the ADI (German child).
Based on the above assessment, EFSA does not recommend inclusion of this active substance in Annex IV to Regulation (EC) No 396/2005. MRL recommendations were derived in compliance with the decision tree reported in Appendix D of the reasoned opinion (see summary table). None of the MRL values listed in the table are recommended for inclusion in Annex II to the Regulation as they are not sufficiently supported by data. In particular, all tentative MRLs and existing EU MRL need to be confirmed by the following data:
ILV for enforcement of iprodione in high oil content commodities;
confirmatory validation data for enforcement of iprodione (and all metabolites containing the 3,5-dichloroaniline moiety) in milk;
fully validated methods for enforcement of iprodione (and all metabolites containing the 3,5-dichloroaniline moiety) in eggs, meat, liver, fat and kidney;
primary and rotational crop metabolism studies conducted in line with current standards and according to GLP;
storage stability studies of iprodione in dry, acidic and high oil content commodities;
additional residue trials supporting a wide range of GAPs in hazelnuts, apricots and peaches, cherries, plums, cane fruit, spring onions, tomatoes and aubergines, peppers, cucurbits with edible peel, flowering brassica, lettuce and similar, herbs, spinach and beet leaves, fresh beans and peas (with and without pods), dry beans and peas, linseed, rape seed, leek Swedes and turnips, kale, kohlrabi, celery and fennel, asparagus herbal infusions and spices (detailed number of trials is reported in the reasoned opinion);
Information on the toxicological properties of 3,5-dichloroanline, the metabolites RP30228 and RP37176, and the 4-hydroxylated metabolites DCHPU and RP36114, which were observed in processed commodities and/or in commodities of animal origin;
a livestock feeding study in ruminants including analysis of according to the enforcement and risk assessment residue definitions in milk and kidney.
If the above reported data gaps are not addressed in the future, Member States are recommended to withdraw or modify the relevant authorisations at national level.
Minor deficiencies were also identified in the assessment but these deficiencies are not expected to impact either on the validity of the MRLs derived or on the national authorisations. The following data are therefore considered desirable but not essential:
additional trials supporting the southern GAP on apples and pears, the northern GAP on apricots and peaches, the northern GAP on plums, the southern GAP on strawberries, the southern GAP on cucurbits with inedible peel, the northern GAP on beans and peas (fresh with pods) (detailed number of trials is reported in the reasoned opinion);
processing studies investigating the nature of residues following cooking/boiling.
Although procymidone and vinclozolin, two compounds containing the same 3,5-dichloroaniline moiety as iprodione, are no longer authorised for use within the EU, EFSA notes that the use of iprodione may generate false positives for the residue definitions and MRLs currently established for these two compounds. EFSA therefore recommends a review of the existing MRLs of procymidone and vinclozolin.