R-residue and analytical aspects
RESIDUE AND ANALYTICAL ASPECTS
Dicloran, a fungicide, was first evaluated for toxicology and residues in 1974 and subsequently in 1977. The compound was again evaluated by the Meeting in 1998 for toxicology and residues under the CCPR Periodic Review Programme. The 1998 JMPR changed the ADI from 0-0.03 to 0-0.01 mg/kg body weight and concluded that an acute RfD was unnecessary. It recommended that the definition of the residue for compliance with MRLs and for the estimation of dietary intake should be dicloran and indicated that the residue was fat-soluble. It also estimated revised maximum residue levels for carrot and bulb onion while recommending withdrawal of the existing CXLs for grapes, head lettuce, peach, plums (including prunes), strawberry and tomato. The 33rd CCPR in 2000 decided to retain for four years the MRLs recommended for withdrawal in accordance with the procedures of the Periodic Review Programme pending the submission of additional data on these commodities.
The Meeting received information on residues in rotational crops, an analytical method, use patterns, and residue trials on nectarines, peaches, plums, grapes, strawberries, tomatoes and lettuce.
Rotational crops
When dicloran was applied to loamy sand at a rate equivalent to 3 kg ai/ha, the applied radioactivity remained mainly in the soil. Both the TRR and dicloran were significantly higher in the first growing period than the second and third in all crops. The highest residues were found in leaves or straw of lettuce, sugar beet and wheat but the TRRs decreased sharply after the first growing period. Unchanged dicloran found in plant extracts was less than 10% of the TRR in the first growing period and was at or below the limit of quantification in the second and third periods.
When dicloran was sprayed on the surface of sandy loam soil at a rate of 14.8 kg ai/ha, the average TRR in harvested crops (lettuce, turnip and wheat) was highest in the 120-day rotation and lowest in the 365-day rotation. On average, acetonitrile extracts, methylene chloride extracts and acid and alkaline extracts contained about 20%, 3% and 20% of the TRR respectively. Unextracted fractions contained about 30% of the TRR, which was found to be associated with cell wall components. Dicloran was observed in most samples on days 30, 120 and 365 at generally decreasing levels. The presence of dicloran metabolites was confirmed throughout the course of the study: 4-amino-2,6-dichlorophenol, 4-amino-2,6-dichloroacetanilide, 3,5-dichloro-4-hydroxyacetanilide, 4-amino-3,5-dichloroacetanilide, 2,6-dichloro-4-hydroxyaniline, 2,6-dichloro-4-nitrophenol, 2,6-dichlorophenol and 2,6-dichloroaniline were identified.
In a study of the uptake of dicloran from soil by rotational crops under actual field conditions dicloran was applied at a rate of 4.4 kg ai/ha and lettuce, mustard, radish, wheat and sorghum were planted 30, 120 and 360 days after the application. In most crops dicloran concentrations were below the limit of quantification (<0.05 mg/kg). The highest dicloran concentrations were found in radish roots of the 30-day rotation at 0.278 and 0.243 mg/kg.
Analytical methods
The validity of the method used for the determination of dicloran in milk, eggs and tissues from goats and hens in metabolism studies was checked. Egg white and chicken muscle samples, with and without fortification, were extracted with acetone/water (6:1), and partitioned with hexane/ethyl acetate (9:1). Milk and fat samples were extracted with acetone/water (7:1) followed by extraction of the aqueous layer with hexane and partition into acetonitrile. After a clean-up step including a solid-phase extraction on a diol column, dicloran was eluted with toluene and determined by gas chromatography with an electron capture detector. The recovery from the fortified samples ranged from 93.0 to 106.7%, showing that the method can be satisfactorily used for the determination of dicloran in these samples. However, comparison of the analytical results with those from radio-analysis indicated that while the average recoveries from egg white, chicken muscle and goat fat were above 80%, that from goat milk was 47.8%.
Residues from supervised trials
The Meeting received the results of supervised trials on nectarines, peaches, plums, strawberries and lettuce in Brazil, grapes in Brazil and Mexico and tomatoes in Italy, all conducted after the last evaluation by the 1998 JMPR. The Meeting also considered the results of supervised trials on these crops which had been evaluated by the 1998 JMPR, against GAP reported to the current Meeting.
Nectarines. Three new post-harvest trials were conducted in Brazil in 2001. The conditions (in 0.087-0.089 kg ai/hl dip) were in accordance with GAP in Chile for post-harvest application to nectarines (dip or immersion in 0.09 kg ai/hl). The residues were 2.3, 2.3 and 5.5 mg/kg.
The 1998 JMPR evaluated pre-harvest, post-harvest, and combined pre- and post-harvest trials carried out in the USA in 1968. One pre-harvest trial (PHI 1 day) did not comply with GAP in the USA which requires a PHI of 10 days. The post-harvest trials and combined pre- and post-harvest trials were not in compliance with any GAP.
One Australian post-harvest trial (0.075 kg ai/hl, SC) complied with Chilean post-harvest GAP but only the surface residue was measured and could not be used to estimate a maximum residue level.
Peaches. Two new pre-harvest supervised trials were conducted in Brazil in 2001. The conditions (0.146 kg ai/hl, 3 applications at an interval of 15 days, 1-day PHI) were in accordance with GAP in Argentina (0.15 kg ai/hl, 3 applications, 1-day PHI). The residues were 2.7 and 4.8 mg/kg.
A pre-harvest trial, and post-harvest and combined pre- and post-harvest trials conducted in the USA in 1966, 1988 and 1996 were evaluated by the 1998 JMPR. The pre-harvest trial with a PHI of 4 days was not in compliance with US GAP which requires a PHI of 10 days. Four combined trials in 1988 and 1996 with a post-harvest rate of 0.09 kg ai/hl were in accordance with post-harvest GAP in Argentina (0.09-0.11 kg ai/hl spray or immersion) and in Chile (0.09 kg ai/hl dip or immersion) but in two of these trials the last pre-harvest application was made one day before harvest while US pre-harvest GAP requires 10 days. The residues from two other trials in conformity with US GAP (pre-harvest) and Argentinean and Chilean GAP (post-harvest) were 5.3 and 5.8 mg/kg. Of two combined trials and four post-harvest trials in 1966, a post-harvest trial at an application rate of 0.15 kg ai/hl and another at 0.06 kg ai/hl approximated GAP in Argentina. The residues were 2.1 and 2.5 mg/kg.
Three Australian post-harvest trials (1973) reported only surface residues and could not be used for estimating a maximum residue level, and one pre-harvest (1964) and one post-harvest trial (1966) in Canada did not comply with any GAP.
The residues from post-harvest trials on nectarines and peaches were mutually supportive. The combined residues were 2.1, 2.3, 2.3, 2.5, 2.7, 4.8, 5.3, 5.5 and 5.8 mg/kg. The Meeting therefore estimated a maximum residue level of 7 mg/kg Po and an STMR of 2.7 mg/kg for nectarines and peaches.
Plums. Three new pre-harvest trials were carried out in Brazil in 2001. The conditions (0.146 kg ai/hl, 3 applications at an interval of 15 days, 1-day PHI) were in compliance with pre-harvest GAP in Argentina (0.15 kg ai/hl, 3 applications, 1-day PHI). The residues were <1.0, 1.1 and 1.4 mg/kg.
Four combined and one pre-harvest trial in the USA in 1986 and 1995 were not in accordance with any GAP reported to the current Meeting.
The Meeting concluded that there were too few valid trials to estimate a maximum residue level.
Grapes. Three new trials in Brazil and four in Mexico in 2001 were reported to the Meeting. Although trials were conducted in Brazil (0.256 kg ai/hl, 5 applications with an interval of 1 month, 1-day PHI), no GAP is reported for Brazil and they did not comply with GAP in Argentina (0.19 kg ai/hl, 7-day PHI).
Trials carried out in Sonora and Baja California, Mexico (2.25 kg ai/ha, 3 applications at an interval of 15 days, 1-day PHI) were in accordance with GAP in the USA (1.7-3.9 kg ai/ha for WP or 2.0 kg ai/ha for DP, 1-day PHI; applicable to grapes grown west of the Rocky Mountains only). The residues were 0.36, 0.83, 0.95 and 1.5 mg/kg.
The 1998 JMPR evaluated data from US supervised trials in California in 1967, 1984 and 1995. One trial in 1967 and two trials in 1984 with a WP application at 2.2 kg ai/ha followed by 1-3 dust applications at 2.0 kg ai/ha with 1-day PHI were comparable with US GAP (1.7-3.9 kg ai/ha for WP or 2.0 kg ai/ha for DP, 1-day PHI). The residues were 0.29, 0.62 and 6.0 mg/kg.
One US trial in 1995 with a WP application at 4.5 kg ai/ha and 3-day PHI approximated US GAP. The residue was 1.0 mg/kg
The combined residues from Mexican trials and valid US trials were 0.29, 0.36, 0.62, 0.83, 0.95, 1.0, 1.5 and 6.0 mg/kg. The Meeting estimated a maximum residue level of 7 mg/kg and an STMR of 0.89 mg/kg.
Strawberries. Three new trials were conducted in Brazil in 2001 at a rate of 0.256 kg ai/hl, with 4 (2 trials) or 11 applications (1 trial) and a PHI of 1 day. No GAP for strawberries was reported for Brazil or Argentina.
A number of trials were carried out in the USA in 1963 but no GAP for strawberries was reported for the USA.
The Meeting concluded that there were insufficient data to estimate a maximum residue level.
Tomatoes. Three new trials were conducted in Italy in 2001 at a rate of 0.095 kg ai/hl which complied with GAP in Italy (0.07-0.12 kg ai/hl). The residues at a PHI of 20 days were <0.01, 0.04 and 0.08 mg/kg.
Trials conducted in the USA in 1962 (greenhouse) and in 1963 and 1995 (field) were not in compliance with US GAP (0.84 kg ai/ha, 4 applications, PHI of 10 days). One trial in the UK in 1972 (greenhouse) reported only residues in the surface wash.
The Meeting concluded that there were too few valid trials to estimate a maximum residue level.
Lettuce. Three new pre-harvest trials were conducted in Brazil in 2001. The conditions (0.293 kg ai/hl, 2 applications at an interval of 7 days, 14-day PHI) were in accordance with pre-harvest GAP in Argentina (0.28 kg ai/hl, 10-day PHI). The residues were <0.10, 0.16 and 0.51 mg/kg.
Three field trials and one greenhouse trials were conducted in the USA in 1964 and 1972 respectively. While US GAP requires a PHI of 14 days, samples were taken only up to 4 days or at 25-26 days.
The Meeting concluded that there were too few valid trials to estimate a maximum residue level.
Processing studies
The 1998 JMPR estimated processing factors for grapes to be 1.1 to juice, 1.5 to wet pomace and 0 to sun-dried grapes, so STMR-Ps were calculated to be 0.98 mg/kg for grape juice, 1.3 mg/kg for wet pomace and 0 mg/kg for sun-dried grapes.
DIETARY RISK ASSESSMENT
Long-term intake
The International Estimated Dietary Intakes (IEDIs) were calculated for the five GEMS/Food regional diets using STMRs for 3 commodities estimated by the current Meeting and 2 estimated by the 1998 JMPR, and STMR-Ps for two processed commodities (Annex 3). The ADI allocated by the 1998 JMPR was 0-0.01 mg/kg bw. The calculated IEDIs were 0-30% of the maximum ADI. The Meeting concluded that the intake of residues of dicloran resulting from the uses considered by the 1998 JMPR and the current JMPR was unlikely to present a public health concern.
Short-term intake
The 1998 JMPR agreed that an acute RfD was unnecessary for dicloran. The Meeting therefore concluded that the short-term intake of dicloran residues was unlikely to present a public health concern.
