RESIDUE AND ANALYTICAL ASPECTS
Clethodim was first evaluated by the 1994 JMPR which recommended a number of MRLs. At the 28th Session of the CCPR opinions were expressed that the 1994 monographs were unclear and over-summarized. Detailed written comments were submitted by some governments, to which the manufacturer has provided an item-by-item response.
In response to the submitted comments, the Meeting evaluated the previously reviewed data in more detail. The comments and the responses of the Meeting are given below.
(i) "There are no data on the kinds and quantities of metabolites in the goat study. Therefore, it cannot be established whether the definition of residues for cattle kidney, liver, meat, milk is acceptable."
The study was re-evaluated. Milk contained 0.02-0.05 mg/kg clethodim equivalents and the highest tissue concentrations were found in the liver (0.414 mg/kg clethodim equivalents) and kidney (0.378 mg/kg). In milk, the extracted radioactivity was mostly associated with lactose and clethodim sulfoxide. In the blood and tissues the major compounds were clethodim sulfoxide (33-52% of the substrate radioactivity) and 5-methyl-clethodim sulfoxide (6-37%). Clethodim was only found above 4% of the substrate radioactivity in blood (28%) and liver (28%).
(ii) "There are no data on quantities concerning the metabolism in plants, i.e. there are no data indicating the determined quantities of the metabolites referred to."
The metabolism studies on carrots, soya beans and cotton have been re-evaluated and information on the quantities of individual metabolites is provided in the monograph. The identified metabolites were clethodim sulfoxide, clethodim sulfone, the imine sulfoxide and sulfone, and 5-hydroxyclethodim sulfoxide and sulfone. Clethodim was not present or was found at very low levels. Clethodim sulfoxide and the imine sulfoxide were the major metabolites in both leaves and edible parts.
Methods of analysis
(iii) "According to the method of residue analysis referred to, two compounds have to be determined simultaneously, therefore it is doubtful whether a determination limit of 0. 05 mg/kg for both compounds is practicable, also in view of the dissolution of isomers into several peaks which is possible under certain circumstances."
In the "common moiety" method referred to, clethodim and its metabolites containing the 2-cyclohexen-l-one moiety are determined as dimethyl 3-[2-(ethylsulfonyl)propyl]pentanedioate (DME) and its 3-hydroxy analogue (DME-OH) as described in the 1994 monograph. The manufacturer has supplied several typical chromatograms which showed two resolved peaks with some tailing, for labelled DME and DME-OH standards in clean solvent at concentrations of 0.5 m g/ml and 0.75 m g/ml or 10 or 25 ng. The reports of the trials included data showing acceptable recoveries (generally 70-110%) for a range of crop commodities; these were usually at fortification levels above 0.2 mg/kg each of clethodim, clethodim sulfoxide and 5-hydroxyclethodim sulfone. Some acceptable recoveries of clethodim sulfoxide and sulfone at 0.05 mg/kg were submitted, e.g. for dried peas. Some of the residue trials (e.g. on succulent beans) reported "limits of quantification" of 0.1 mg/kg.
A revised confirmatory method was submitted to the present Meeting. The recovery data for the revised method, which is necessary to differentiate clethodim from related compounds such as sethoxydim, indicated that 0.05 mg/kg could not be achieved routinely. The Meeting noted that the lowest fortification level at which acceptable individual recoveries could be achieved was generally about 0.5 mg/kg. Acceptable recoveries were obtained from sugar beet, potatoes and liver at 0.1, 0.2 and 0.2 mg/kg respectively however. The Meeting agreed that it will be necessary for monitoring and enforcement laboratories to use the amended confirmatory method to differentiate residues of clethodim from those of sethoxydim if measurable residues are found with the "common moiety" method reviewed by the 1994 Meeting. The Meeting also agreed that the limit of determination appropriate for routine monitoring and enforcement should be that of the confirmatory method.
On the basis of the information on the revised confirmatory method, the Meeting concluded that the practical limit of determination appropriate for routine monitoring and enforcement should be 0.5 mg/kg, with lower levels only for sugar beet, fodder beat, potatoes, liver, kidney and milk. For milk a practical limit of determination of 0.1 mg/kg was considered appropriate. Accordingly the Meeting recommended that some of the low maximum residue levels estimated by the 1994 Meeting be raised to 0.5* mg/kg and that these should be recommended as MRLs.
(iv) "The method of analysis referred to does not make it possible to distinguish between residues from sethoxydim and a clethodim treatment. A verification method for the determination of clethodim and its metabolites has not been published and is thus not available for food inspection purposes."
The revised confirmatory method mentioned above is evaluated in the monograph. It is specific for the determination of clethodim and its metabolites in crops, animal tissues, milk and eggs, and can distinguish residues of clethodim from those of sethoxydim. The Meeting expressed concern that details of the revised confirmatory method were not currently in the public domain, but was informed that the manufacturer would make full details of the method available to monitoring and enforcement laboratories on request.
(v) "The residue trials for beans (dry), field peas (dry), potatoes and sugar beets are summarized too strongly. Obviously, in some cases only summaries of trials have been available to the JMPR; we hold the view that an evaluation on such a basis should be refused."
The trials data for dry beans, dry peas, potatoes and sugar beets reviewed by the 1994 Meeting are given in more detail in the monograph. The Meeting agreed that summaries of data should not be used when not accompanied by the full study reports, but full study reports were available to the Meeting on all the trials about which concern had been expressed except two potato trials, one each in the Ukraine and Belgium, for which only summaries were available.
(vi) "It cannot be understood in all cases on which GAPs (use pattern) and which residue data the proposed MRLs are based. We hold the view that the residue data for potatoes are insufficient, irrespective thereof they do not justify an MRL of 0.2 mg/kg since the data from Canada cannot be used as a basis of comparison with the treatment in Belgium, Ecuador, Peru and Switzerland for climatic reasons." In addition, it was stated that "The data is only available in summarized form. The number of trials that are within GAP is rather limited. The proposal is based on Canadian trials."
The Meeting agreed that outdoor trials data in Canada would not normally be related to GAP in Europe or South America. Additional information was provided to the current Meeting on GAP for potatoes in Australia, Belgium, Bulgaria, Canada, Czech Republic, Dominican Republic, Ecuador, Germany, Israel, Peru, Poland, Russia, Switzerland and Yugoslavia. This indicated slight changes from the GAP reported in 1994 for Belgium and Switzerland. The maximum application rates are 0.12-0.36 kg ai/ha with PHIs of 7-60 days. Canadian GAP was reported to the current Meeting. Although the Meeting agreed that the data were rather limited, a number of trials were available which indicated that residues resulting from a number of use patterns were low and often below the LOD. The Meeting confirmed that the previously estimated maximum residue level of 0.2 mg/kg was appropriate.
(vii) "The MRL for sugar beet seems to be based on two Italian trials the results of which deviate from all other trials without any explanation being given."
GAP for sugar beet in Belgium, Morocco, Spain and Switzerland was reported to the 1994 Meeting. The maximum application rates were 0.20-0.36 kg ai/ha with PHIs from 50-90 days or not specified.
Nine French trials and one German trial were considered comparable to the German GAP reported to the current Meeting, with residue levels of<0.03 (9) and 0.05 mg/kg. Four Italian trials reported to the 1994 Meeting had originally been considered to comply with Spanish GAP, with reported residue levels of 0.06 (2) and 0.17 (2) mg/kg at 59 or 60 days. However, the Meeting was informed that treatment of sugar beet was at about the 2-8 leaf stage and that the minimum PHI was "about 90 days in practice."
In view of this new information the Meeting agreed to revise the previous recommendation and estimated a maximum residue level of 0.1* mg/kg, based on the trials according to German GAP. The Meeting concluded that the limit of determination in sugar beet was 0.1 mg/kg because acceptable recovery data for the revised confirmatory method had been submitted at this level.
(viii) "The MRLs of 0.1 mg/kg cattle kidney and liver are obviously based on a dosage of 10 mg/kg feed. But there are no reports on residues in potential feeding stuffs which would lead to such residues in everyday feed. Soya beans (MRL 10 mg/kg) usually only reach a percentage of 25-30 % in everyday feed: for cotton seed and rape seed an MRL of only 0.5 mg/kg has been envisaged. The MRL of 0.1 ing/kg cattle kidney, liver thus is unnecessarily high."
The Meeting observed that the highest residues (DME, S-methyl-DME and DME-OH) found in cows at the lowest dosing level were 0.059, <0.05 and <0.05 mg/kg, and 0.051, <0.05 and <0.05 mg/kg in liver and kidney respectively. Since clethodim residues are calculated by the summation of the DME and DME-OH peaks in the common moiety method, the Meeting agreed that the maximum residue levels of 0.1 mg/kg estimated for cattle liver and kidney by the 1994 Meeting had been appropriate. However, in view of the new information provided on the limit of determination of the revised confirmatory method, the Meeting agreed to increase the estimates to 0.2* mg/kg. The Meeting recognised that acceptable data on recoveries from kidney by the revised confirmatory method were not available but considered that the limit of determination in kidney was likely to be similar to that in liver, from which recoveries were satisfactory at 0.2 mg/kg.
(ix) The comment was made for beans (dry) "The data is only available in summarized form. The number of trials is not specified. There are only trials from one country (Brazil) where clethodim is not registered. The trials are in accordance with GAP of other countries in the region. The proposal is based on a PHI of 65 days (pp. 358, 1994 Evaluations). Taking this PHI into account, 0.05 mg/kg is more appropriate."
In response, the supervised trials data for dry beans reviewed by the 1994 Meeting are given in more detail in the monograph. The Meeting reassessed the data which were available to the 1994 Meeting, concluded that they were insufficient to estimate a maximum residue level, and withdrew the previous recommendation for an MRL.
(x) "Although a minor point, the table on pp 346 (1994 Evaluations) does not specify the levels in refined oil, and clarification is sought on the statement in the text (pp 347) that processing reduces levels to 10% in refined oil."
Additional information is provided in the monograph. The residue in the refined oil was <0.08 mg/kg and in the unprocessed cotton seed 0.8 mg/kg. A processing factor of <0.1 for cotton seed to refined oil is therefore appropriate.
(xi) Comments on dry field peas were that "There is only registered use in Australia. The proposal is based on a PHI of 50-110 days (pp 358, 1994 Evaluations). On the basis of the Australian trial data (number of trials not specified, dosage 0.06-0.24 kg ai/ha, PHI 110 days) a limit of 0.05 mg/kg is sufficient. Also UK data (0.36 kg ai/ha [six times Australian registered dose], PHI 53 and 85 days) and Belgium data (up to three times registered dose in Australia, PHI 41 days) support this latter level. Only the French trials (0.18kg ai/ha, PHI 67-82 days) points to a level of 0.1 mg/kg, but this is not in accordance with GAP."
A re-evaluation of the data on dry field peas has been carried out (see below), since new information on GAP and data from residue trials were reported to the present Meeting.
(xii) "The proposal for sunflower seed is based on data from Argentina taking into account a PHI of 106 days. However, such a long PHI is not in accordance with the PHI reported for Argentina and other countries in table 4 of the Evaluations. The Netherlands therefore reserves its position for these proposals. For oil, crude and oil edible 0.05 mg/kg are reasonable when 0.2 mg/kg is a appropriate level for sunflower seed."
GAP for sunflower in Argentina, Bolivia, Ecuador, Israel, Morocco, Paraguay and Spain was reported in the 1994 monograph, where the maximum application rate in Spain was stated to be 0.2 kg ai/ha with an unspecified PHI. The manufacturer informed the Meeting that the use was post-emergence and that the Spanish PHI was "60 days in practice". Residues from applications 60-74 days before harvest were 0.03-0.13 mg/kg in three Italian trials.
The maximum application rate in South America was 0.12-0.34 kg ai/ha with PHIs of 5-56 days or not specified. The PHIs in all of the Argentinean trials were longer at 102-106 days. The manufacturer stated that "although the PHI from the Argentina trials exceeded the GAP of 75 days, we believe that we would not detect any greater than what we have observed at a 75 day PHI." The Meeting concluded that there were insufficient data from trials according to GAP to estimate a maximum residue level and withdrew the previous estimate.
GAP for such broad categories as "fruit" or "vegetables" has been ignored in evaluating the results of the other supervised trials reviewed below.
Peaches. Conflicting information on GAP in Spain had been reported, with application rates of 0.096-0.192 or 0.036-0.24 kg ai/ha. The timing of the application was also unclear. The Meeting was informed that the application was directed around the base of the tree.
GAP for "fruit trees" was reported for Chile, Ecuador and Saudi Arabia and for "orchard crops" for New Zealand. The maximum application rates were 0.06-0.24 kg ai/hl and 0.18-0.72 kg ai/ha with PHIs ranging from 15-60 days or not specified.
The Meeting noted that although all the residues in the trials on peaches were below the limit of determination of 0.03 mg/kg, only one trial included a PHI longer than 21 days. Since longer intervals between treatment and harvest might lead to determinable residues owing to uptake, and in view of the conflicting information on GAP, the Meeting concluded that there were insufficient data to estimate a maximum residue level.
Onions and garlic. Information on GAP for garlic in Saudi Arabia, Spain and the USA was reported. The maximum application rates were 0.192- 0.28 kg ai/ha with PHIs of 30, 45 or 60 days. The maximum number of applications was not stated for any country.
Only two trials on garlic were considered to comply with US GAP. Although the DME-OH residue levels were described by the manufacturer as "not considered to be clethodim-related, due to matrix interference peak" this could not be confirmed by the Meeting and the results were therefore included; the residues (sum of DME and DME-OH) were 0.36 and 0.1 mg/kg.
GAP for onions was reported for Australia, Belize, Dominican Republic, Guatemala, Honduras, Israel, New Zealand, Russia, Saudi Arabia, Turkey, the USA and Uzbekistan, and pending GAP in Brazil. The maximum application rates were 0.12-0.28 kg ai/ha (0.108 kg/ha in the pending Brazilian GAP) with PHIs of 7-65 days.
The residues in trials considered to comply with US GAP were <0.05, £ 0.1 (4), 0.13 and 0.15 mg/kg. The residues in trials considered to be in accord with GAP in New Zealand or pending GAP in Brazil were all below the limit of determination, as were other residues from exaggerated application rates in some of these trials. The residues from the trials according to GAP were <0.01, <0.02, <0.03 (4) and <0.05 (6) mg/kg. Only one trial accorded with Australian GAP, with a residue of 0.05 mg/kg.
The Meeting agreed that the results of the garlic and onion trials could be combined, but noted that the US residues formed a different population from those in the Brazilian and New Zealand trials. The combined US residues in rank order were 0.05, 0.1 (4), 0.1, 0.13, 0.15 and 0.36 mg/kg. The Meeting estimated maximum residue levels of 0.5 mg/kg and STMRs of 0.1 mg/kg, based on US GAP, for both onion and garlic.
Cabbage. GAP was reported for Australia and Poland. The maximum application rates are 0.12 and 0.24 kg ai/ha with PHIs of 7 and 60 days respectively.
Only one residue trial was considered to comply with Australian GAP and one with Polish. The residues were 0.07 and 0.15 mg/kg respectively. There were insufficient data to estimate a maximum residue level.
Cauliflower. GAP was reported only for New Zealand, with a maximum application rate of 0.24 kg ai/ha and a PHI of 35 days. Only one trial was considered to comply with this, with a residue of 0.28 mg/kg. There were insufficient data to estimate a maximum residue level.
Cucumber. GAP for cucumbers was reported only for Poland, with a maximum application rate of 0.24 kg ai/ha and a PHI of 60 days, and for cucurbits in Paraguay with the same maximum application rate and an unstated PHI.
A single trial was considered to be comparable to Polish GAP, because although the PHI was shorter the residue level was <0.05 mg/kg. In six US trials all residues were <0.14 mg/kg at the short PHI of 13-14 days, but none of the trials was according to GAP. There were insufficient data to estimate a maximum residue level.
Summer squash. GAP for cucurbits was reported for Paraguay, but none of the three trials in the USA were considered to conform to it. There were insufficient data to estimate a maximum residue level.
Tomatoes. GAP for tomatoes was reported for Belize, Bulgaria, Dominican Republic, Israel, Italy, Nicaragua, Spain and the USA, and pending GAP for Brazil. The maximum application rates are 0.12-0.28 kg ai/ha (0.108 kg/ha for the pending GAP) with PHIs of 7-30 days, "unrestricted" or unstated.
The residues in two trials considered to comply with the pending Brazilian GAP were <0.05 mg/kg.
The residues in trials considered to comply with Spanish GAP were <0.03 (5), 0.03, 0.08 and 0.13 mg/kg, and with US GAP <0.1 (3), 0.11, 0.12, 0.15 (2), 0.16, 0.17, 0.21, 0.27, 0.34, 0.35 (2), 0.43, 0.46, 0.50, 0.52, 0.54, 0.65, 0.71, 0.76 (2) and 0.82 mg/kg. The Meeting estimated a maximum residue level of 1 mg/kg and an STMR of 0.35 mg/kg, based on the trials according to US GAP.
Lettuce. GAP was reported for Australia and Israel. The maximum application rates are 0.12 kg ai/ha with PHIs of 28 days and unstated respectively.
The residues in trials considered to comply with Australian GAP were 0.04 and 0.21 mg/kg. There were insufficient data to estimate a maximum residue level.
Beans (fresh). GAP was reported for beans for Belgium, Bolivia, Bulgaria, Paraguay, Peru, Spain and Turkey, for mung and fava beans for Australia and for legumes for Chile. The maximum application rates are 0.06-0.48 kg ai/ha with PHIs of 0-65 days or unstated.
The residues in fresh beans from trials considered to comply with Belgian GAP were <0.025 and <0.05 (4) mg/kg. Although some of the Belgian results were at shorter PHIs than GAP, the residues were all below the limit of determination. In addition one trial on "green beans" with a residue of 0.21 mg/kg and one on "French beans" with a residue of <0.03 mg/kg were considered to comply with Spanish GAP. Although data on a number of US trials were also submitted, no GAP was reported for the North American continent. A trial on broad (fava) beans in Spain did not conform to reported GAP.
The Meeting estimated a maximum residue level of 0.5* mg/kg and an STMR of 0.05 mg/kg for beans, except broad bean and soya bean, based on the trials according to Belgian GAP.
Lentils. GAP for lentils was reported to the current Meeting for Canada, New Zealand and Turkey, and to the 1994 Meeting for New Zealand and Spain. GAP for beans and legumes would presumably cover lentils.
Although two Spanish trials were reported, they could not be evaluated against the Spanish GAP recorded in 1994 because the GAP did not include the PHI. Neither of the trials was considered to comply with relevant GAP. There were insufficient data to estimate a maximum residue level.
Lupins. GAP for lupins was reported for Australia, with a maximum application rate of 0.12 kg ai/ha; no PHI was specified.
Only one trial was considered to comply with Australian GAP with a residue of <0.1 mg/kg. The Meeting could not estimate a maximum residue level.
Carrots. GAP for carrots was reported for Israel and Russia, and pending GAP for Brazil. The maximum application rates were 0.108 (Brazil) - 0.24 kg ai/ha with PHIs of 40-75 days.
The residues in two trials which complied with the pending Brazilian GAP were <0.05 mg/kg. None of the other trials were considered to accord with any other reported GAP. There were insufficient data to estimate a maximum residue level.
Celery. GAP for celery was reported for Australia. The maximum application rate is 0.12 kg ai/ha with a PHI of 9 weeks.
The only trial which complied with Australian GAP showed a residue of 0.04 mg/kg. There were insufficient data to estimate a maximum residue level.
Linseed (flax). GAP was reported for Canada, Russia and the Ukraine. The maximum application rates were 0.09-0.24 kg ai/ha. PHIs were 60-80 days or not specified.
One trial was considered to be in accord with Russian GAP, with a residue of <0.01 mg/kg. Several Canadian trials were reported in which exaggerated rates had been used with all residues below the limit of determination at PHIs of 84-119 days, but since no samples were taken at the Canadian PHI of 60 days the Meeting concluded that there were insufficient data to estimate a maximum residue level.
Peanuts. GAP was reported for Argentina, Australia, Bolivia, Israel, Taiwan and the USA. The maximum application rates were 0.09-0.336 kg ai/ha with PHIs of 40-70 days or not specified. GAP for "vegetables" was also reported for Chile, Ecuador, New Zealand, Paraguay and Peru.
The residues in trials considered to comply with US GAP were 0.05, 0.34, 0.56, 0.79, 1.3 (2), 1.8, 2.7 and 3.5 mg/kg in the kernels and 0.17, 0.20, 0.24, 0.24, 0.3, 0.60, 0.75 and 0.81 mg/kg in the hulls. The Meeting estimated a maximum residue of 5 mg/kg and an STMR of 1.3 mg/kg for peanut.
Alfalfa. GAP was reported for Argentina, Canada, Chile, Ecuador, Israel, Peru and the USA. The maximum application rates were 0.09-0.48 kg ai/ha with PHIs of 15-30 days or not specified.
Trials according to national GAP were carried out in Canada and the USA with residues of <0.02 (7) and 0.02 mg/kg in Canada, and 0.27, 0.53, 0.61, 0.62, 0.67, 0.85, 1.2, 1.4 (3), 1.5, 1.6, 1.9, 2.0, 2.6, 2.7 (2), 3.0, 4.4, 4.5, 5.4 and 8.9 mg/kg in the USA. The Meeting estimated a maximum residue level of 10 mg/kg and an STMR of 1.6 mg/kg, based on US GAP.
White Clover. GAP for clover was reported for Israel and New Zealand. The maximum application rates are both 0.12 kg ai/ha with a PHI of 63 days in New Zealand and not specified in Israel. GAP for "vegetables" was reported for Chile, Ecuador, New Zealand, Paraguay and Peru
The two residues in trials considered to comply with New Zealand GAP were 0.07 and 0.26 mg/kg. The samples analysed were described as "young plants" and "silage". There were insufficient data to estimate a maximum residue level.
Field peas (dry). GAP for field peas was reported for Australia and Canada. The maximum application rate in Canada is 0.09 kg ai/ha with a PHI of 75 days. The maximum rate reported by the Australian government, supported by a product label, was 0.06 kg ai/ha and differed from that reported by the manufacturer.
All the residues in six trials in Australia were 0.1 mg/kg after 110 days even at exaggerated doses. The residues in several further trials which were considered to comply with Canadian GAP were <0.02 (4), 0.06, 0.08, <0.10, 0.18 (2), 0.31, 0.65 and 1.8 mg/kg. The Meeting estimated a maximum residue level of 2 mg/kg and an STMR of 0.08 mg/kg, based on Canadian GAP.
Peas. GAP for peas was reported for Belgium, the Czech Republic, Israel, New Zealand and Spain, and for "proteaginous peas" for France. The maximum application rates are 0.06-0.36 kg ai/ha with PHIs of 30 or 60 days, or not specified. No trials were considered to comply with relevant GAP and no maximum residue level could be estimated.
Fodder beet. GAP was reported for Belgium, the Czech Republic, Germany, Italy, Russia and Switzerland. The maximum application rates are 0.14-0.36 kg ai/ha with PHIs of 60-90 days or not specified. The Meeting was informed that application is at about the 2-8 leaf growth stage.
The residues in three trials in France which were considered to comply with Belgian GAP were all below the LOD of 0.03 mg/kg in both roots and tops. In additional trials at the same sites with exaggerated application rates the residues were also all below 0.03 mg/kg. The Meeting estimated a maximum residue level of 0.1* mg/kg and an STMR of 0.03 mg/kg. The Meeting established the limit of determination for fodder beet at 0.1 mg/kg because acceptable recovery data for the revised confirmatory method had been submitted for sugar beet at this level.
Other commodities. Residue trials data were also submitted for leeks, spinach, artichokes, sweet peppers and "non-bell peppers" but no specific GAP was reported to the present or the 1994 Meeting. The Meeting agreed that it would be appropriate to evaluate these trials against a general GAP for vegetables in the case of this compound, since it is a post-emergence herbicide, but there were no trials on any of these commodities according to GAP from which to estimate maximum residue levels.
FURTHER WORK OR INFORMATION
Data on residues occurring in commerce and/or at consumption (from 1994 Meeting).