T- toxicological evaluation; R-residue and analytical aspects
** Evaluated within the Periodic Review Programme of the Codex Committee on Pesticide Residues
TOXICOLOGY
Dimethoate is an organophosphate ester, and virtually all its toxic effects are due to the inhibition of acetylcholinesterase activity. Dimethoate was evaluated for toxicological effects by JMPR in 1963, 1965, 1967, 1984, 1987, and 1996. An ADI of 0-0.002 mg/kg bw was established in 1996 on the basis of the apparent NOAEL of 1.2 mg/kg bw per day for reproductive performance in a study of reproductive toxicity in rats and applying a safety factor of 500. Although a safety factor of 100 would normally be used in deriving an ADI from a study of this type, the Meeting was concerned about the possibility that reproductive performance might have been affected at 1.2 mg/kg bw per day in this study and therefore used a higher-than-normal safety factor. No data were available to assess whether the effects on reproductive performance were secondary to the inhibition of cholinesterase activity. The 1996 JMPR concluded that it was not appropriate to establish the ADI on the basis of results of studies of volunteers, since the crucial end-point (reproductive performance) had not been assessed in humans. The present review was undertaken to consider the need for establishing an acute RfD and to evaluate new studies submitted by the sponsor.
The LD50 of dimethoate when administered orally was about 314-600 mg/kg bw in rats and 150 mg/kg bw in mice.
Acute neurotoxicity was studied in rats given dimethoate by gavage at a single dose of 0, 2, 20 or 200 mg/kg bw after preliminary studies had shown that peak effects for clinical signs occur at about 2 h post-dosing. Abnormal clinical signs and effects on functional observational battery (FOB) parameters were seen at the highest dose, mainly on the first 2 days after treatment and were reversed by day 7. The NOAEL was 2 mg/kg bw, on the basis of the absence of pupil response at 20 mg/kg bw and above. Cholinesterase activity was not analysed in this study.
In a study of acute neurotoxicity in rats given dimethoate in the diet at single doses of 0, 1, 2, 3 or 15 mg/kg bw, no clinical signs and no effects on FOB parameters were observed. A statistically significant inhibition of cholinesterase activity in erythrocytes of males (29%) and in the brain cortex of females (11%) was observed at 3 mg/kg bw and above.
In a special study designed to assess effects on cholinesterase activity, pre-weaning rats (aged 11 days) and young adult rats (aged 7-8 weeks) received dimethoate by gavage at single doses of 0, 0.1, 0.5 or 3 mg/kg bw. There was no difference in susceptibility between pre-weaning and young adult rats. A statistically significant inhibition of brain cholinesterase activity in pre-weaning rats (17-18%) and in young adult rats (12-14%) and of erythrocyte cholinesterase activity in pre-weaning and young adult female rats (26-27%) was observed at 3 mg/kg bw.
The Meeting concluded that the overall NOAEL for acute effects on cholinesterase activity was 2 mg/kg bw.
The Meeting also considered a number of studies in human volunteers which indicated that single or repeated oral doses of dimethoate of up to 0.2 mg/kg bw did not induce clinical effects nor inhibit cholinesterase activity in the blood. It was concluded that these studies were not conducted according to current standards (no details on study design, e.g. age and sex of individual volunteers, were given and no raw data were provided). Therefore, the Meeting considered that the studies in humans were only supportive for setting the acute RfD.
The Meeting also reviewed new studies that were not relevant to the establishment of an acute RfD. In a study of neurotoxicity, rats received dimethoate in the diet at concentrations of 0, 1, 50 or 125 ppm for 91-94 days. The NOAEL for systemic toxicity and neurotoxicity was 1 ppm (equal to 0.06 mg/kg bw per day), on the basis of inhibition of erythrocyte cholinesterase activity (34-49%) and small faeces at 50 ppm (equal to 3.22 mg/kg bw per day) and above.
In a special study designed to assess effects on the activity of cholinesterase, pregnant rats, pre-weaning rats and young adult rats received dimethoate by gavage at repeated doses of 0, 0.1, 0.5 or 3 mg/kg bw per day. The NOAEL was 0.1 mg/kg bw per day, on the basis of a consistent, statistically significant inhibition of brain cholinesterase activity (10-13%) in pregnant, pre-weaning and young adult rats and of erythrocyte cholinesterase activity (23%) in pre-weaning female pups at 0.5 mg/kg bw per day and above.
In a study of developmental neurotoxicity, pregnant rats received dimethoate by gavage at doses of 0, 0.1, 0.5 or 3 mg/kg bw per day from day 6 of gestation to post-natal day 10, and their offspring received the same doses by gavage from post-natal day 11 to post-natal day 21. The NOAEL for functional development of the nervous system and systemic toxicity in the offspring was 0.5 mg/kg bw per day, on the basis of developmental delay observed for some functional parameters and increased pup mortality at a dose of 3 mg/kg bw per day. The Meeting considered these effects to be of no relevance for setting the acute RfD, since they would not be expected to occur after a single exposure and concluded that the new studies supported the current ADI of 0.002 mg/kg bw.
Toxicological evaluation
After considering the previous evaluations of dimethoate and the new data submitted, the Meeting established an acute RfD of 0.02 mg/kg bw on the basis of the overall NOAEL of 2 mg/kg bw for cholinesterase inhibition in studies in rats, and a safety factor of 100. This acute RfD was supported by the NOAEL of about 0.2 mg/kg bw per day in studies in volunteers receiving single or repeated doses, which were evaluated by the 1996 JMPR.
The Meeting recognized that it may be possible to refine this acute RfD based on further characterization of the effects caused by dimethoate.
An addendum to the toxicological monograph was prepared.
Estimate of acute reference dose
0.02 mg/kg bw
Studies that would provide information useful for continued evaluation of the compound
- Further observations in humans
- The two-generation study of reproductive toxicity (available in abbreviated form at the 2003 Meeting)
RESIDUE AND ANALYTICAL ASPECTS
Dimethoate is a systemic insecticide typically applied as an emulsifiable concentrate (EC) at a rate of 0.2-0.9 kg ai/ha. The latest evaluation of dimethoate residues was in 1998 within the CCPR Periodic Review Programme and the toxicology was reviewed in 1996 when an ADI of 0-0.002 mg/kg bw was allocated for the sum of dimethoate and omethoate expressed as dimethoate.
The 1998 JMPR recommended the definition of the residue to be dimethoate for compliance with MRLs and the sum of dimethoate and omethoate, each considered separately, for the estimation of dietary intake.
The manufacturers reported information on physical and chemical properties, plant metabolism and toxicity of metabolites, environmental fate in water-sediment systems, stability of residues in stored analytical samples, use patterns, residues resulting from supervised trials on crops, fate of residues in storage and processing, residues in food in commerce or at consumption and national MRLs. Information on national GAP was provided by the governments of Thailand, The Netherlands, Germany, Brazil, Poland and Australia.
The Meeting considered the new information and reviewed the residue data, taking into account the revised use patterns. Where sufficient residue data reflecting the changed use conditions were available new MRLs were recommended. However the previously estimated maximum residue levels were not changed if the GAP on which they depended was still in effect.
Plant metabolism
Two new plant metabolism studies with [14C]dimethoate on potatoes and wheat were evaluated.
After two spray applications of [14C]dimethoate to potatoes at a mean rate of 340 g/ha per application with 14 days between applications, significant residues were present in foliage decreasing from 12.3 mg/kg as dimethoate after the second application (day 0) to 1.3 mg/kg at day 14 and slightly increasing to 3.5 mg/kg fresh weight at day 28 as moisture loss from the crop caused concentration of the residue. 14C residues in tubers remained constant throughout the study and ranged from 0.19 to 0.30 mg dimethoate equivalent/kg.
After two spray applications of [14C]dimethoate to wheat at 710 g/ha and 420 g/ha with 41 days between applications, significant residues were present in all plant parts. Levels of radioactivity were highest in those parts of the plant directly exposed to the spray, representing up to 29.7 mg/kg dimethoate equivalents in the whole plant immediately after the first application. Concentrations of radioactivity in ears and the remainder of the plant represented 22.7 mg/kg and 16.1 mg/kg respectively, immediately after the second application. At the early harvest (day 62) the concentration of radioactivity in straw had decreased to 6.4 mg/kg dimethoate equivalents although levels in hulls represented 23.3 mg/kg. In grain, which was not directly exposed to the spray, the total radioactivity represented 2.3 mg/kg. The levels increased slightly at the normal harvest (day 73), as a result of drying of the crop, and were 4.3 mg/kg, 33.7 mg/kg and 7.8 mg/kg in grain, hulls and straw respectively.
A similar metabolic profile was found in potato and wheat plants:
Oxidation to yield omethoate (metabolite II)
O- and N-demethylation of omethoate to yield O-demethyl N-demethyl omethoate (XXIII)
Hydrolysis at the amide bond to give dimethoate carboxylic acid (III) and subsequent degradation to give O,O-dimethyl dithiophosphoric acid (XV).
Demethylation and rearrangement to yield O-demethyl dimethoate (X) or O-demethyl isodimethoate (XII).
Demethylation of omethoate to give O-demethyl omethoate (XI) and subsequent hydrolysis of the amide bond to give O-demethyl omethoate carboxylic acid (XX).
No dimethoate or omethoate was detected in the edible parts of potatoes or wheat (i.e. tubers or grain) at any time, indicating that translocation of dimethoate or omethoate did not take place to a significant extent. The plant metabolites of omethoate (III, XI, XII, XX) were found to be toxicologically insignificant.
Methods of analysis
The method used for white cabbage and lettuce involves extraction with ethyl acetate and clean-up of the extract by gel permeation chromatography. Quantification of both dimethoate and omethoate was carried out by gas chromatography with a flame photometric detector in the phosphorus mode or mass selective detection. The LOQ was 0.01 mg/kg.
Whole fruit, peel and pulp except lemons of citrus fruits were analysed by extraction with acetone, followed by partitioning into dichloromethane. The extract was treated with activated charcoal and final clean-up was by column chromatography with activated silica gel. Quantification was by GC with an FPD in the phosphorus mode with an LOQ of 0.01 mg/kg.
Lemon homogenates were extracted with dichloromethane. The solvent was changed to hexane and dimethoate and omethoate were partitioned into water. The aqueous extract was analysed by LC-MS providing an LOQ of 0.01 mg/kg. This method was also applied to olives with the same LOQ. Olive oil was extracted with acetonitrile after dissolution in hexane.
Cherry homogenate was extracted into dichloromethane and, after removal of water with anhydrous sodium sulfate, cleaned up with activated charcoal. Quantification of dimethoate and omethoate was by GC with an FPD in the phosphorus mode with an LOQ of 0.01 mg/kg.
Apples, artichokes, celery, cherries, lettuce, tomatoes, wheat (grain, green plants and straw), sugar beet, (tops and roots), asparagus and melons (peel and pulp) were analysed using dichloromethane for extraction, followed by clean-up by liquid/liquid partition with hexane. Dimethoate and omethoate were partitioned into water for quantification by liquid chromatography with mass spectrometric detection (LOQ 0.01 mg/kg) for all samples. A small modification using an ENVI-Carb Bondelut cartridge pre-wetted with dichloromethane and a double aliquot of the extract (20 ml, equivalent to 2 g of sample) was validated and the limit of quantification was decreased to 0.001 mg/kg in wheat grain.
Methods were validated for the determination of dimethoate and omethoate residues in milk, eggs and animal tissues, where the LOQ was 0.001 mg/kg for milk and eggs and 0.01 mg/kg for tissues.
In a multi-residue method ethyl acetate is used to extract plant samples and extraction is followed by a GPC clean-up. Quantification is by GC with an NPD.
In the DFG S19 multi-residue method acetone was used for extraction, its volume adjusted according to the water content of the sample to achieve an acetone to water ratio of 2:1 during extraction. To separate excess water the extract was saturated with sodium chloride and partitioned with dichloromethane. The clean-up was by GPC with cyclohexane-ethyl acetate elution. Quantification of dimethoate and omethoate was by GC with an NPD.
A modified DFG S19 method used GC with an atomic emission detector for determination, with an internal standard added before extraction (2 µg aldrin dissolved in toluene). Extraction was with acetone. After saturation with sodium chloride and dilution with dichloromethane clean-up was by GPC with cyclohexane/ethyl acetate as eluent. The residue was dissolved in 200 µl toluene before analysis.
Another multi-residue method for olives, oranges, lettuce and wheat grain consisted in extraction with ethyl acetate followed by clean-up by gel permeation chromatography. Olive oil was extracted with acetonitrile after dissolution in hexane. Extracts were analysed by GC with an FPD on a DB-17 column. Quantificatation was by comparison with matrix-matched external standards. Confirmation was by GC with an FPD on a 30 m DB 1701 column.
Stability of residues in stored analytical samples
Dimethoate and omethoate in cherries were stable up to 6 months during storage at -18°C. The government of Australia reported stability of dimethoate and omethoate in mangoes stored for 3 months at -10oC.
Results of supervised trials on crops
The toxicological evaluation of omethoate, the major plant metabolite of dimethoate, revealed that it is about 10 times as toxic as dimethoate. Since consumers are exposed to both dimethoate and omethoate residues at the time of consumption, the difference in toxicity was taken into account (1998 JMPR residue evaluations, p. 510) by multiplying the omethoate residues by a factor of 10 for calculation of the sum of the residues. The total toxicologically significant residues, calculated in this way, were used for the estimation of dietary exposure. The present meeting followed the same practice. In the case of undetectable residues, the concentration of omethoate residues was calculated by taking into account the average ratio of dimethoate to omethoate in the edible portions of the crop at the specified pre-harvest interval. The sum (CT) of dimethoate (CD) and omethoate (CO) residues reported for the specific commodities was calculated as CT = CD + (10 x CO). The HRs and STMRs were estimated on the basis of the calculated CT values.
Citrus fruits (oranges, mandarins/clementines and lemons). Dimethoate EC is registered for use on citrus in Spain, Italy, Greece, Brazil, Thailand and Morocco. The highest application rate according to GAP in southern Europe is 0.06 kg ai/hl. The application rate in Thailand is 0.3 to 0.6 kg ai/ha (0.02-0.04 kg ai/hl) and in Brazil 0.04 kg ai/hl. The PHIs are 3 days in Thailand and Brazil and 20-21 days in Spain, Italy and Greece. The number of applications is not specified in any country.
Eight supervised trials were conducted on oranges and eight on mandarins and clementines in Spain, Italy and Greece using dimethoate EC 400 g/l at application rates between 2.05 and 2.22 kg ai/ha (0.06 g ai/hl) applied three times as a foliar spray. In 1999 two lemon trials were reported from Italy and Greece where Dimethoate EC 400 g/l was applied three times at a rate of 2.08-2.16 kg ai/ha (0.06 kg ai/hl).
Dimethoate residues in whole orange fruit in southern Europe in trials complying with Greek or Spanish GAP in rank order were 0.29, 0.37, 0.41, 0.65, 0.77, 0.83, 0.85 and 1.50 mg/kg. The omethoate residues were <0.01, 0.02, 0.03 (2), 0.04 (2) and 0.05 (2) mg/kg. The residue concentrations in the orange pulp were <0.01 (2), 0.01, 0.02 (3), 0.03, 0.07 mg/kg for dimethoate and 0.002, <0.01(2), 0.01, 0.02, 0.03(2), 0.08 for omethoate. The average ratio of dimethoate to omethoate was 2.63.
Dimethoate residues in whole mandarins or clementines based on Greek or Spanish GAP in rank order were 0.35, 0.37, 0.52, 1.04, 1.17, 1.34, 1.48 and 3.10 mg/kg. The omethoate residues were 0.06, 0.08 (5) and 0.13 (2) mg/kg. The residues in the edible portions of the samples were <0.01 (2), 0.01 (2), 0.02 (3) and 0.07 mg/kg for dimethoate and <0.01, 0.02, 0.04, 0.05 (3), 0.11 and 0.13 mg/kg for omethoate. The average ratio of dimethoate to omethoate was 0.53.
Residues in whole lemon fruit at a 21-day PHI were 0.76 and 1.10 mg/kg dimethoate and 0.07 and 0.11 mg/kg omethoate. The residues in the edible portions were 0.05 and 0.19 mg/kg dimethoate and 0.05 and 0.06 mg/kg omethoate.
In supervised trials according to GAP in Brazil in 2002 dimethoate EC 400 g/l was sprayed 3 times on oranges at 0.8-1.60 kg ai/ha (0.04-0.08 kg ai/hl) with 3 days PHI. The LOQs were 0.02 mg/kg for dimethoate and 0.30 mg/kg for omethoate. The dimethoate residues in whole fruit were 0.15, 0.20 and 0.48 mg/kg. Residues of omethoate were <0.30 mg/kg in all trials.
In four supervised trials in Thailand in 2001 and 2002 dimethoate EC 400 g/l was sprayed on pomelos 4 times at 0.60 kg ai/ha (0.04 kg ai/hl). The residue results were reported only for dimethoate (LOQ 0.01 mg/kg). The trials complied with Thai GAP. The residues on whole fruit at 3 days PHI were 0.02, 0.06, 0.11 and 0.21 mg/kg.
The dimethoate residues from GAP applications in whole oranges, mandarins/clementines, lemons and pomelos were in the same range and can be combined for estimating a maximum residue level. They are in rank order 0.15, 0.2, 0.29, 0.35, 0.37 (2), 0.41, 0.48, 0.52, 0.65, 0.76, 0.77, 0.83, 0.85, 1.04, 1.1, 1.17, 1.34, 1.48, 1.50 and 3.1 mg/kg.
The dimethoate equivalents of the sum of dimethoate and omethoate residues in the citrus pulp (excluding the Brazilian trials) in rank order are 0.03, 0.049, 0.059, 0.11, 0.16, 0.20, 0.2, 0.22, 0.22, 0.32, 0.33, 0.41, 0.41, 0.45, 0.68, 0.81, 1.12, 1.37 mg/kg.
The Meeting estimated a maximum residue level of 5 mg/kg for citrus fruits, and an HR of 1.4 mg/kg and STMR of 0.27 mg/kg for the edible portion of citrus fruits. For the purpose of estimating STMR-Ps for processed commodities, the STMRs are 0.76 mg/kg for dimethoate and 0.035 mg/kg for omethoate.
Cherries. Four residue trials were conducted in southern Europe between 1999 and 2001. Cherries were sprayed once with dimethoate EC 400 g/l at a rate between 0.74 and 0.78 kg ai/ha (0.05 kg ai/hl). GAP in Austria, Belgium, Germany, Italy, Portugal and Spain specifies application rates between 0.02 and 0.04 kg ai/hl except in Spain (0.04-0.06 kg ai/hl) and a PHI of 20-21 days in Austria, Germany and Italy, and 14 days in Belgium, Portugal and Spain. The maximum number of applications is 3 in Germany (with 8-14 days intervals) but is not specified in other countries. Thus, the residue trials complied with GAP in Spain and represent the worst-case situation.
The residues in cherries from southern European trials, evaluated with respect to Spanish GAP, in rank order were 0.12, 0.18, 0.21 and 0.33 mg/kg dimethoate, 0.05, 0.12(2) and 0.17 mg/kg omethoate.
The dimethoate equivalents of the sum of dimethoate and omethoate residues in cherries were 0.68, 1.32, 1.53 and 1.91 mg/kg.
The Meeting recommended an MRL of 2 mg/kg, confirming the existing CXL.
Mangoes. In Australia 5 supervised trials were conducted in 2001 and 2002 on mangoes with dimethoate EC 400 g/l as 3 foliar sprays, 3 foliar sprays plus one dip application, and one dip application only. Application rates were 0.03 kg ai/hl for foliar and 0.04 kg ai/hl for dip applications. Post-harvest treatment of mango fruits by dipping in dimethoate solution for one minute is compulsory whether mangoes had previously received a dimethoate foliar application or not. The residue trials complied with GAP in Australia. The residues were determined separately as dimethoate and omethoate in the peel and pulp, then calculated as dimethoate (sum of dimethoate and omethoate) in the whole fruit, allowing for the weight of the stone. The limit of reporting was 0.02 mg/kg for both dimethoate and omethoate.
Dimethoate residues in whole mango fruit from the Australian trials at a PHI of 3 days for the pre-harvest application and 0 days for the post-harvest application in rank order were 0.18, 0.25, 0.26, 0.34 and 0.43 mg/kg for dimethoate and 0.02 (2), 0.03, 0.05 and 0.06 mg/kg for omethoate.
The average ratio of dimethoate to omethoate was 2.5. The dimethoate equivalents of the sum of dimethoate and omethoate residues in mango pulp were 0.12, 0.15, 0.36, 0.39 and 0.68 mg/kg.
The Meeting estimated a maximum residue level of 1 mg/kg Po for mango, and an HR of 0.68 mg/kg and STMR of 0.36 mg/kg for the edible portion of mangoes.
Olives. Nine trials were conducted in Spain, Italy and Greece from 1999 to 2001. Dimethoate EC 400 g/l was applied four times to olives at application rates of 0.42-0.45 kg ai/ha (0.06 kg ai/hl; water volume 700 l/ha) and 0.71-0.76 kg ai/ha (0.06 kg ai/hl; water volume 1200 l/ha). Dimethoate EC 400 g/l is registered for foliar application to olives in Greece at the rate of 0.03 kg ai/hl repeated at 20-day intervals and a PHI of 20 days for high volume sprays and 15 days for LV and ULV sprays (ULV from air only). In Italy the rate is 0.028-0.56 kg ai/hl with up to 3 applications and 28 days PHI, in Portugal 0.03-0.06 kg ai/hl with one or two sprays and 21-42 days PHI, in Spain 0.04-0.06 kg ai/hl with 60 days PHI and in Morocco 0.04-0.06 kg ai/hl. The highest GAP application rate in southern Europe is 0.06 kg ai/hl which matches the rates in the residue trials.
The dimethoate residues in olives at 28 days PHI in rank order were <0.01 (2), 0.01, 0.03, 0.04, 0.13, 0.15, 0.21 and 0.34 mg/kg. The omethoate residues were 0.06 (2), 0.07, 0.20, 0.22, 0.26, 0.33, 0.40 and 0.44 mg/kg.
The average ratio of dimethoate to omethoate was 0.4. The dimethoate equivalents of the sum of the dimethoate and omethoate residues in olives were 0.61, 0.61, 0.73, 2.01, 2.24, 2.75, 3.31, 4.01 and 4.34 mg/kg.
The Meeting estimated a maximum residue level of 0.5 mg/kg for fresh olives, and an STMR of 2.24 mg/kg and an HR of 4.3 mg/kg for the estimation of dietary intake. For the purpose of estimating the STMR-Ps for processed commodities the STMRs are 0.04 mg/kg for dimethoate and 0.22 mg/kg for omethoate.
Cauliflower. A set of 8 trials, conducted in the UK in 1996 and 1997, was described in the 1998 JMPR evaluation. Dimethoate EC 400 g/l was sprayed at 0.4 kg ai/ha (0.067 kg ai/hl) six times per year, the last application at growth stage BBCH 43-49.
Dimethoate EC 400 g/l is registered for use on cauliflower in Denmark, Germany, The Netherlands, Poland, the UK and Spain. Rates of application range between 0.2 and 0.4 kg ai/hl with PHIs of 14-42 days and 1-6 applications. Six of the trials were evaluated against UK GAP. Dimethoate residue levels at 21 days in rank order were <0.01 (4), 0.02 and 0.11 mg/kg and the omethoate residues were <0.01 (6) mg/kg.
The average ratio of dimethoate to omethoate was 6.5. The dimethoate equivalents of the sum of dimethoate and omethoate residues were 0.025 (4), 0.035 and 0.13 mg/kg.
Noting that the critical GAP in the UK has been changed from a PHI of 7 days to 21 days, the Meeting estimated a maximum residue level of 0.2 mg/kg for cauliflower to replace the existing draft MRL of 0.5 mg/kg, and an STMR of 0.025 mg/kg and HR of 0.13 mg/kg.
Brussels sprouts. Eight trials in the UK in 1996 and 1997 were described in the 1998 JMPR evaluation. According to UK GAP dimethoate EC 400 g/l may be applied 6 times at the rate of 0.4 kg ai/ha (0.067 kg ai/hl), the last application at growth stage BBCH 43-49, with a PHI of 14 days. Dimethoate EC (400-404 g/l) is registered for use in Germany (0.24-0.36 kg ai/ha twice with a PHI of 14 days), The Netherlands (0.20 kg ai/ha, once or twice and PHI 21 days), and Spain (0.04-0.06 kg ai/hl and PHI 21 days). The GAP of the UK has the highest application rate in northern Europe and represents the worst-case situation.
The residues in Brussels sprouts at 14 days PHI in rank order were dimethoate 0.03 (2), 0.04, 0.06, 0.10 (2) and 0.11 (2) mg/kg and omethoate <0.01 (2), 0.02, 0.03 (2), 0.04, 0.07 and 0.11 mg/kg. The average ratio of dimethoate to omethoate was 2.98. The dimethoate equivalents of the sum of dimethoate and omethoate residues in Brussels sprouts were 0.064, 0.14, 0.23, 0.34, 0.36, 0.50, 0.81, 1.20 mg/kg.
Noting that the critical GAP in the UK has been changed from a PHI of 7 days to 21 days, and that the residues from other trials were <0.1 mg/kg, the Meeting estimated a maximum residue level of 0.2 mg/kg for Brussels sprouts to replace the existing draft MRL of 1 mg/kg, and an STMR of 0.35 mg/kg and HR of 1.2 mg/kg,
Head cabbages. Eight residue trials were conducted outdoors in the UK in 1996 and 1997 (evaluated by the 1998 JMPR) and one trial in Poland in 1996 (only dimethoate residues were reported). GAP was reported from Denmark, Finland, Germany, The Netherlands, Norway, Sweden, Spain and Poland but not from the UK. 0.4 kg ai/ha (0.067 kg ai/hl) was applied six times in the UK trials which were evaluated against German GAP. The residues of dimethoate at 14 days PHI in rank order were 0.01, 0.04, 0.06, 0.11, 0.34, 0.67, 0.71 and 0.99 mg/kg and of omethoate 0.01, 0.02 (2), 0.07, 0.25, 0.35, 0.46 and 0.64 mg/kg.
The average ratio of dimethoate to omethoate was 2.47. The dimethoate equivalents of the sum of dimethoate and omethoate residues in cabbage were 0.05, 0.09, 0.12, 0.39, 1.55, 1.71, 1.72 and 3.26 mg/kg.
The Meeting confirmed its previous recommendation (2 mg/kg, now a CXL) for head cabbages (excluding Savoy cabbage). The Meeting estimated an STMR of 0.97 mg/kg and an HR of 3.26 mg/kg.
Sweet peppers. Seven supervised trials were conducted in 2001 and 2002 in Australia. Dimethoate EC 400 g/l was applied by post-harvest dipping at 0.04 kg ai/hl or as a pre-harvest foliar treatment at 0.3 kg ai/ha with 7 days PHI followed by post-harvest application at 0.04 kg ai/hl. The residues were determined in the whole fruit. The limits of reporting were 0.02 mg/kg for dimethoate and 0.02-0.04 mg/kg for omethoate. The trials complied with Australian GAP.
The residues of dimethoate after foliar application at a 7-day PHI were 0.03 (2) and 0.14 mg/kg. Since the residues after foliar and post-harvest application were 0.23, 1.71 and 1.75 mg/kg, it was concluded that the contribution of foliar application to the residues after post-harvest application was negligible and residues from all post-harvest trials could be used for evaluation.
The dimethoate residues after post-harvest (with or without foliar) application were 0.23, 0.27, 1.26, 1.46, 1.5, 1.56, 1.71, 1.75, 1.8 and 2.95 mg/kg. Omethoate residues were 0.19 (2) and not detected.
The average ratio of dimethoate to omethoate was 39. The dimethoate equivalents of the sum of dimethoate and omethoate residues were 0.24, 0.28, 1.27, 1.51, 1.57, 1.72, 1.76, 2.96, 3.36 and 3.7 mg/kg.
The Meeting estimated a maximum residue level of 5 mg/kg, an STMR of 1.64 mg/kg and an HR of 3.7 mg/kg for sweet peppers. The maximum residue level is recommended to replace the existing CXL of 1 mg/kg for peppers.
Melons. Eight residue trials were conducted in Italy, Spain and Greece in 2000 and 2001. No information on GAP for dimethoate use on melons, pumpkins or watermelons was available. The Meeting could not estimate a maximum residue level, STMR or HR.
Tomatoes. Eight supervised trials in 2000 and 2001 were reported from Spain and Italy. Tomatoes were treated twice at 0.614-0.653 kg ai/ha (0.1 kg ai/hl). GAP in Germany on tomatoes in glasshouses is 0.24 to 0.48 kg ai/ha with three applications and 3 days PHI, and in Ireland 0.034 kg ai/hl by foliar application and 7 days PHI. Brazil requires 0.04 kg ai/hl foliar application and 14 days PHI. GAP in Italy is 0.028 to 0.040 kg ai/hl and 21 days PHI. The supervised trials in Italy and Spain did not comply with the corresponding GAP, and the results could not be evaluated. The Meeting recommended withdrawal of the draft MRL of 2 mg/kg.
Head lettuce. Nine residue trials were conducted in Spain, Italy and Greece in 2000 and 2001. Lettuce was sprayed outdoors once at 0.41-0.42 kg ai/ha (0.04 kg ai/hl). GAP in Spain is 0.04-0.06 kg ai/hl LV with 14 days PHI, in Greece 0.03-0.05 kg ai/hl and 20 days PHI and in Italy 0.028-0.040 kg ai/hl and 14 days PHI. The number of sprays is not specified. The trials were evaluated against GAP in Italy.
The residues of dimethoate at 14 days PHI in rank order were <0.002 (3), <0.01 (3), 0.03, 0.07 and 0.11 mg/kg and of omethoate <0.01 (5), 0.01, 0.02, 0.04 and 0.06 mg/kg.
In northern Europe residue trials on lettuce were conducted in 1996 and 1997. Lettuce was sprayed outdoors at a rate of 0.34 kg ai/ha (0.17 kg ai/hl) six times. GAP in Denmark is 0.30-0.32 kg ai/ha (number of application not specified) with a 21-day PHI, in the UK 0.34 kg ai/ha 6 times with a 14-day PHI, in Germany 0.24-0.36 kg ai/ha twice or 0.40 kg ai/ha once with a 21-day PHI, in Ireland 0.34 kg ai/ha repeated as necessary with a 7-day PHI and in The Netherlands 0.20 kg ai/ha 1 or 2 times with a 21-day PHI. Thus, the trials complied with UK GAP and represent the worst-case situation.
The residues of dimethoate at 14 days PHI in ranked order were 0.01, 0.02 (3), 0.04, 0.07 (2) and 0.11 mg/kg and of omethoate <0.01 (5), 0.02 and 0.03 (2) mg/kg.
The residues from southern and northern Europe seem to be from the same population and may be evaluated together, giving residues at 14 days in ranked order of <0.002 (3), <0.01 (3), 0.01, 0.02 (3), 0.03, 0.04, 0.07 (3) and 0.11 (2) mg/kg for dimethoate, and <0.01 (10), 0.01, 0.02 (2), 0.03 (2), 0.04 and 0.06 for omethoate.
Eleven residue trials were conducted in glasshouses in the UK in 1996 and 1998. Dimethoate EC 400 g/l was applied once at 0.34 kg ai/ha (0.17 kg ai/hl) with a PHI of 28 days. GAP for glasshouse use was reported from Ireland (0.34 kg ai/ha, repeated as necessary, 28-day PHI). The supervised trials complied with Irish GAP.
The residues in ranked order were <0.01, 0.01 (2), 0.02 (2), 0.06, 0.16, 0.17, 1.1 (2) and 2.2 mg/kg for dimethoate and <0.01 (4), 0.01, 0.03 (2), 0.04, 0.17, 0.20 and 0.29 mg/kg for omethoate.
Since the indoor use resulted in higher residues the glasshouse trials were used for estimation of a maximum residue level, an STMR and an HR.
The average ratio of dimethoate to omethoate was 11. The dimethoate equivalents of the sum of dimethoate and omethoate residues in indoor lettuce were 0.03 (4), 0.11, 0.31, 0.31, 0.41, 1.71, 2.01 and 2.70 mg/kg.
The Meeting estimated a maximum residue level of 3 mg/kg for head lettuce, recommended to replace the draft MRL of 0.5 mg/kg, and an STMR of 0.31 mg/kg and HR of 2.7 mg/kg.
Sugar beet. Eight trials were conducted in 2000 and 2001 in southern Europe (including 2 decline trials and 2 at-harvest trials in Spain, and 2 decline curve trials and 2 at harvest trials in Italy). Rates of 0.62-0.64 kg ai/ha (0.06 kg ai/hl) were applied twice with a 30-day PHI. Dimethoate EC 400 g/l is registered for use on sugar beet in many countries (Finland, Germany, Greece, Italy, The Netherlands, Poland, Spain, Sweden, the UK and Ireland), with GAP in Italy 0.02-0.04 kg ai/hl, 30 days PHI, Spain 0.04-0.06 kg ai/hl, 60 days PHI and Greece 0.03-0.05 kg ai/hl, 14 days PHI. In one trial in Spain the residue of dimethoate in sugar beet leaves or tops was 0.13 mg/kg at 14 days. The residues of dimethoate at 30 days in sugar beet leaves or tops in rank order were <0.002 (7) and <0.01 mg/kg, and of omethoate <0.01 (4), 0.02 (2), 0.03 and 0.04 mg/kg. No residues of dimethoate or omethoate (<0.01 mg/kg) were found in sugar beet root at PHIs of 30-60 days.
Six residue trials conducted in 1994 and 1995 in Germany, the UK and The Netherlands are described in the 1998 JMPR evaluations. No residues were detected in sugar beet roots. In addition, 2 new trials were conducted in 2001 in the UK and Germany. The first application was 0.08-0.09 kg ai/ha (0.02-0.09 kg ai/hl) and the second at BBCH 38-39 0.41-0.42 kg ai/ha (0.02-0.09 kg ai/hl) with PHIs of 29-30 days. Residues in roots were undetectable (<0.002 mg/kg, LOQ 0.01 mg/kg).
The results of the recent supervised trials evaluated by the present Meeting confirm the recommendations (0.05 mg/kg for root and 0.1 mg/kg for leaves or tops) made by the 1998 JMPR.
Globe artichokes. Four trials were conducted in Italy and Spain in 2000 and 2001. Dimethoate EC 400 g/l was applied three times to artichokes at 0.42-0.43 kg ai/ha (0.04 kg ai/hl) with a PHI of 28 days. The only GAP for dimethoate in Italy is 0.06 kg ai/hl and a PHI of 20 days. Thus, the residue trials approximated GAP in Italy. The residues in the trials at 28 days PHI in ranked order were <0.01, 0.02 (2) and 0.04 mg/kg for dimethoate, and <0.01 (3) and 0.02 mg/kg for omethoate.
The average ratio of dimethoate to omethoate was 5.0, on the basis of the LOD values.
The dimethoate equivalents of the sum of dimethoate and omethoate residues in artichokes were 0.1 (3) and 0.2 mg/kg.
The Meeting estimated a maximum residue of 0.05 mg/kg, an STMR of 0.1 mg/kg and an HR 0.2 mg/kg for globe artichokes.
Asparagus. Six residue trials at rates of 0.41-0.43 kg ai/h (0.04 kg ai/hl) applied twice, the second application at fern stage, were conducted in Spain and Italy in 2000, 2001 and 2002. GAP in Italy is 0.028-0.04 kg ai/hl with a PHI of 14 days and in Greece is 0.03-0.05 kg ai/hl (3 applications). The trials were evaluated against GAP in Italy.
The residues of dimethoate and omethoate were below the limit of detection (<0.002 mg/kg) except in one sample, where 0.01 mg/kg dimethoate was found.
Since the trials in compliance with US GAP evaluated by the 1998 JMPR indicated higher residues, the results of the new trials did not affect the previously estimated maximum residue level.
Celery. Four residue trials were conducted in Italy and Spain in 2000 and 2001. Celery was sprayed with dimethoate EC 400 g/l twice at 0.49-0.51 kg ai/ha (0.05 kg ai/hl). The highest GAP application rate in southern Europe is 0.04 kg ai/hl with PHI 20-21 days (Italy). Thus, the residue trials complied with GAP. The residues were <0.002, 0.07, 0.09 and 0.28 mg/kg for dimethoate, and <0.01, 0.02 and 0.04(2) mg/kg for omethoate.
The average ratio of dimethoate to omethoate was 4.42. The dimethoate equivalents of the sum of dimethoate and omethoate residues in celery were 0.03, 0.2 and 0.4 (2) mg/kg.
The Meeting estimated a maximum residue level of 0.5 mg/kg, an STMR of 0.2 mg/kg and an HR 0.4 mg/kg for celery.
Wheat grain. Eight residue trials were conducted in Italy and Spain in 2000 and 2001. Wheat was sprayed once at 0.40-0.44 kg ai/ha (0.10 kg ai/hl). GAP in Italy is 0.020-0.028 kg ai/hl, PHI 28 days and in Portugal 0.04 kg ai/hl, PHI 14 days.
Only one grain sample from day 14 was analysed. The residues in grain at 28 days were <0.001, <0.01 (4), 0.007, 0.014 and 0.024 mg/kg of dimethoate, and <0.001 (2), 0.002 (2) and <0.01 (4) mg/kg of omethoate.
Seven residue trials were conducted in Germany and the UK in 2001 and 2002. Dimethoate was applied at 0.71-0.77 kg ai/ha (0.35 kg ai/hl) at the first application and 0.35-0.39 kg ai/ha (0.18 kg ai/hl) at the second. The highest GAP application rate in northern Europe is 0.68 kg ai/ha in Germany, Ireland and the UK at the first application and 0.34 kg ai/ha at the second. The PHI in Germany is 21 days. The trials were evaluated against German GAP.
Residues in wheat grain at 28 days (2 trials at 42 days) in ranked order were <0.001 (5) and 0.001 (2) mg/kg of dimethoate, and <0.001 (5), 0.001 and 0.002 mg/kg of omethoate.
In 1998 the critical GAP was from the UK, allowing 4 applications and a PHI of 14 days. Current GAP permits one application before 31 March. The high residues in 1998 derived from the UK trials according to UK GAP at that time, should therefore be excluded from the current evaluation.
The average ratio of dimethoate to omethoate was 9.5. The dimethoate equivalents of the sum of dimethoate and omethoate residues in wheat grain were 0.021 (13), 0.029 and 0.049 mg/kg.
The Meeting estimated a maximum residue level of 0.05 mg/kg for wheat to replace the estimate of 0.2 mg/kg, an STMR of 0.021 mg/kg and an HR of 0.05 mg/kg.
Wheat straw. The residues in wheat straw from the above trials in southern Europe at a 28-day PHI were <0.01, 0.03 (2), 0.10, 0.11, 0.16, 0.37 and 0.45 mg/kg of dimethoate, and <0.01 (4), 0.01, 0.02, 0.07 and 0.08 mg/kg of omethoate.
The residues in wheat straw from northern Europe at PHI 28 days (or at earliest commercial harvest) in ranked order were <0.002 (3), <0.01 (2), 0.02, 0.05 and 0.07 mg/kg of dimethoate, and <0.002 (5), <0.01 (3) mg/kg of omethoate.
The average ratio of dimethoate to omethoate was 7.06. The adjusted sum of dimethoate and omethoate residues in wheat straw were 0.002, 0.006 (2), 0.01, 0.02, 0.05 (2) and 0.07 mg/kg (fresh weight).
Allowing for the standard 88% dry matter for wheat straw (FAO Manual, p. 149), the Meeting estimated a maximum residue level of 1 mg/kg for wheat straw to replace the draft MRL of 10 mg/kg and an STMR of 0.017 mg/kg for wheat straw.
Fate of residues during processing
Processing studies were reported on olives, cabbages and wheat. The STMR-P values of dimethoate and omethoate were calculated from their STMRs in the raw agricultural commodities and the corresponding processing factors, and then the combined STMR-P was calculated from the individual
STMR-P values taking into account the multiplying factor of 10 for omethoate.
In studies on processing olives treated with dimethoate 0.39-3.01 mg/kg in the RAC yielded 0.17-1.26 mg/kg dimethoate in crude olive oil. The results are in line with the studies reported in the 1984 evaluation.
Processing studies on oranges treated with dimethoate were evaluated in 1998 (Residue Evaluations, p. 490). The estimated processing factors were used to estimate the STMR-P values from the STMRs for citrus fruits (dimethoate 0.76, omethoate 0.?? mg/kg) estimated by the present Meeting.
The estimated processing factors and STMR-Ps for orange juice, dry orange pulp, processed olive products and wheat products are summarized below.
|
Processed commodity |
Processing factor |
STMR of RAC, mg/kg |
STMR-P1, mg/kg |
||
|
Dimethoate |
Omethoate |
Dimethoate |
Omethoate |
||
|
Orange juice |
0.14 2 |
0.212 |
0.76 |
0.035 |
0.49 |
|
Orange pulp, dry |
2.1 2 |
1.72 |
0.76 |
0.035 |
1.7 3 |
|
Olive oil, raw |
0.43 |
0.019 |
0.04 |
0.22 |
0.059 |
|
Olive oil, refined |
0.016 |
0.019 |
0.04 |
0.22 |
0.042 |
|
Olive, processed |
0.21 |
0.12 |
0.04 |
0.22 |
0.43 |
|
Wheat wholemeal 2 |
0.19 |
0.1 |
0.09 |
0.01 |
0.027 |
|
White wheat flour |
0.079 |
0.071 |
0.09 |
0.01 |
0.014 |
1 Based on sum of dimethoate and 10 times omethoate (except dry orange pulp)
2 Based on processing factors reported by 1998 JMPR
3 Based on sum of dimethoate and omethoate
The outer leaves of cabbages contained most of the residues (0.19 mg/kg compared with 0.05 mg/kg in whole cabbage) which are removed as part of kitchen processing. Both dimethoate and omethoate were decomposed during cooking.
Residues in animal commodities
On the basis of the metabolism studies, the 1998 JMPR concluded that it was unlikely that residues would occur in animal commodities and did not calculate the animal burden. Consequently the animal burden was not calculated by the present Meeting and MRLs for animal commodities are recommended to be maintained.
DIETARY RISK ASSESSMENT
The toxicological evaluation of omethoate revealed that it is about 10 times as toxic as dimethoate. Since consumers are exposed to both dimethoate and omethoate residues present at the time of consumption, the difference in toxicity was taken into account by multiplying the omethoate residues with a factor of 10 for calculation of the sum of residues. The total toxicologically significant residues, calculated in this way, were used for the estimation of dietary exposure. The sum (CT) of dimethoate (CD) and omethoate (CO) residues was calculated as CT = CD + (10 x CO). The HR and STMRs were estimated from the calculated CT values.
Long-term intake
The International Estimated Dietary Intakes (IEDIs) were calculated for the five GEMS/Food regional diets using STMRs for 12 commodities and STMR-Ps for orange juice, processed olives, virgin olive oil, wheat flour and wheat wholemeal. The IEDI was 150% of the ADI (0-0.002 mg/kg bw) for the European diet. IEDIs for the other four regional diets were in the range of 10-90% of the ADI (Annex 3).
The information provided to the JMPR precludes an estimate that the dietary intake would be below the ADI.
Short-term intake
The International Estimated Short-Term Intakes (IESTIs) were calculated for commodities for which maximum residue levels or STMR(P)s were estimated by the current Meeting. An acute reference dose of 0.02 mg/kg bw was established by the 2003 JMPR. The results are shown in Annex 4.
The IESTI represented 0-320% of the acute RfD for the general population and 1-760% of the acute RfD for children. The values 320 and 130% represent the estimated short-term intakes for head cabbages and head lettuce, head respectively for the general population. The values 760, 200 and 140% represent the estimated short-term intake for head cabbages, head lettuce and sweet peppers respectively for children. The information provided to the JMPR precludes an estimate that the dietary intakes calculated for these 3 commodities would be below the acute reference dose. The Meeting concluded that the short-term intake of residues of dimethoate and omethoate from uses of dimethoate on commodities, other than these three, that have been considered by the JMPR is unlikely to present a public health concern.
The Meeting noted that the acute RfD could be refined upon re-evaluation of the whole toxicological profile of dimethoate.
