Ziram was originally evaluated in 1965 (toxicology) and 1967 (toxicology and residues) and is included in the dithiocarbamate group of compounds. It was evaluated at the present Meeting within the CCPR periodic review programme.
Ziram is a dithiocarbamate contact fungicide with protective action and is registered for use on fruit, vegetables, tree nuts and ornamentals in many countries. Ziram, applied to dormant fruit trees, is also used to repel hares and rabbits.
The Meeting received information on the metabolism of ziram in goats and apples, methods of residue analysis, the stability of residues in stored analytical samples, approved use patterns, supervised residue trials and the fate of residues during the processing of apples.
Ziram is hydrolysed very quickly at pH 5 (half-life 10.4 minutes) and more slowly at pH 7 (half-life 17.7 hours) and pH 9 (half-life 6.3 days). The major hydrolysis product at pH 5 and 7 is CS2. At pH 9 CS2 was produced, but dimethyldithiocarbamic acid, carbon oxysulphide, isothiocyanic or thiocyanic acid and N,N-dimethylformamide were also identified.
When two lactating goats were dosed for 6 days with [thiocarbonyl-14C]ziram at a rate equivalent to 300 ppm ziram in the feed the levels of 14C in milk increased for the first 2 or 3 days of feeding and then reached a plateau. A large part of the administered 14C was not accounted for (39% and 58%). By analogy with the animal metabolism of thiram losses as CS2 and CO2 in expired air would be expected, but 14C was not measured in the expired air. More of the 14C dose was in the faeces (42% and 61%) than in the urine (3%), tissues (0.93% and 0.78%) or milk (0.28% and 0.51%).
The levels of 14C were higher in the liver than in other tissues and approximately 10% of the 14C in the liver was liberated as CS2 when treated with hot acid. Liberated CS2 was not detected in the other tissues and milk but the total 14C levels were generally too low to expect its detection. The 14C residues in the milk and tissues were not extractable until after protease treatment. The liberated 14C was present in polar water-soluble compounds. Since lactose and casein containing 14C were isolated from milk some 14C had evidently been incorporated into natural products.
Because of the fairly rapid hydrolysis of ziram the parent compound would not be expected to occur in animal tissues, which generally agrees with the findings of the goat metabolism study. Dimethyldithiocarbamic acid, identified as a hydrolysis product of ziram at pH 9, was the major intermediate in the metabolism of thiram. It is probably also a hydrolysis product of ziram at lower pHs, but would disappear too quickly for identification. The presence of dimethyldithiocarbamic acid as a hydrolysis product suggests that the metabolites of ziram are likely to be the same as those of thiram.
When apples and apple leaves on a tree were treated with [thiocarbonyl-14C]ziram the parent compound was detected in washings from the apples and leaves 0, 14 and 28 days after treatment. Residues on the surface disappeared more quickly than incorporated residues. The parent compound was detected in the pulp from apples sampled on the day of treatment, but not at later sampling times. The extractable incorporated 14C was in polar material and was not identified because the reference compounds which had been chosen as possible metabolites did not correspond to the 14C fractions.
Extracts of apple peel and pulp were analysed by a CS2 evolution head-space GLC procedure. CS2-related residues were not detected in the extracts of pulp, but constituted up to 5% of the total 14C residues in the peel. In whole-apples the highest level of CS2-related residue was 0.016 mg/kg as CS2.
Ziram residues are essentially on the surface. Most of the residue which becomes incorporated into tissue no longer contains the CS2 structure. As in animal metabolism, because dimethyldithiocarbamic acid is a hydrolysis product of ziram it is quite likely that the plant metabolites of ziram are the same as those of thiram.
Studies of environmental fate were not provided for review by the FAO Panel, but the Meeting was informed that studies were available and had been supplied to the Environmental Core Assessment Group. They would be supplied for future evaluation by the FAO Panel. The Meeting agreed that the recommended MRLs would be temporary pending the review of data on environmental fate by the FAO panel.
The analytical methods for ziram residues rely on acid hydrolysis to release CS2, which is then measured colorimetrically or by head-space gas chromatography. The methods are the same as those for other dithiocarbamates (see also the monograph on thiram). The methods used in the trials gave satisfactory recoveries and LODs were about 0.05-0.1 mg/kg.
The Meeting received information on the frozen storage stability of ziram residues in apples, peaches, almond kernels and almond hulls.
Ziram in macerated apples fortified at 1 mg/kg and stored at -20°C was stable for the duration of the test (18 weeks).
Ziram in macerated apples and peaches fortified at 2 mg/kg stored at -20±2°C was of marginal stability (about 70% remaining) after 3 months storage and had decreased to approximately half the fortification level after 6 months. Ziram residues were stable in almond kernels and almond hulls at -20±2°C for the intervals tested, 6 months and 3 months respectively.
The Meeting was informed that storage stability studies are in progress on ziram residues in whole peaches, whole apples, almond kernels and almond hulls. Summary data for 12 months storage generally showed adequate stability but the Meeting agreed to await full reports of the studies.
Ziram residues are measured as evolved CS2 by the methods that are used for the other dithiocarbamates. All samples from supervised trials on ziram have been analysed by these methods. The Meeting agreed that ziram should be included in the definition of the dithiocarbamate residues.
For estimates of dietary intake and comparison of calculated intakes with the ADI it is preferable to express the residues as ziram because the ADI is expressed in terms of ziram.
Because the residues in the supervised trials are expressed as CS2 it is convenient to discuss them in this form and convert them to a ziram basis (ziram = CS2 x 2.01) for recommendations for STMRs.
The Meeting received data from supervised residue trials on, apples (Belgium, France, Italy, The Netherlands, Spain, USA), pears (Belgium, France, Italy, The Netherlands, Spain, USA), apricots (USA), cherries (Spain, USA), nectarines (Italy, USA), peaches (France, Italy, Spain, USA), plums (France, Spain), almonds (USA), pecans (USA) and almond hulls (USA).
The residues are expressed as CS2 in the following discussion. In some trials other dithiocarbamates had been used on the crop; if this occurred during the growing season the trials were not considered valid for ziram.
Because the frozen storage stability studies had shown that ziram residues in fruit had decreased to about 70% of the initial level after 3 months freezer storage, trials on fruit were considered invalid where no information was provided on the storage conditions or duration or where the duration of storage was excessive. Residues would be expected to be more stable when samples were stored as whole unchopped fruit, as was demonstrated by the storage stability of thiram on whole plums. The stability of ziram and thiram in frozen storage should be comparable.
In France ziram is registered for use on apples at 2.2 kg ai/ha with a PHI of 14 days. The residues in apples in a trial in Belgium where ziram was used at 2.4 kg ai/ha were 0.58 and 0.61 mg/kg as CS2 14 and 28 days after the final application respectively. In 3 trials in France also close to the registered use pattern dithiocarbamate residues as CS2 were 0.53, 1.4 and 2.4 mg/kg. The residue as CS, was 0.70 mg/kg in an apple trial in The Netherlands which closely followed French GAP.
In Italy ziram is registered for use on apples at 2.3 kg ai/ha (0.23 kg ai/hl) with a PHI of 10 days. In a trial in Italy at 2.4 kg ai/ha the residues was 0.90 mg/kg as CS, 10 days after the final application.
Ziram is registered in Spain for use on pome fruit at a spray concentration of 0.25-0.35 kg ai/hl with a PHI of 7 days. Residues of 3.0 mg/kg as CS, were recorded in apples in a Spanish trial 21 days after application at 0.23 kg ai/ha. Although this residues was obtained from an application approximating GAP and residues appeared to be decreasing quite slowly 21 days is too remote from 7 days to be considered for evaluation.
US GAP on apples permits ziram applications at 5.2-6.8 kg ai/ha with harvest 14 days after the final application. In 8 US trials according to this use pattern residues as CS, in apples were 0.16, 0.97, 0.98, 1.1, 1.4, 1.8, 2.4 and 3.5 mg/kg. In 3 of the trials the residues at 21 days were higher than at 14 days and are therefore included in the evaluation.
In summary, ziram residues as CS, in apples from 14 trials in rank order (median underlined) were 0.16, 0.53, 0.61, 0.70, 0.90, 0.97, 0.98, 1.1, 1.4, 1.4, 1.8, 2.4, 2.4 and 3.5 mg/kg.
GAP for pears in The Netherlands permits the application of 2.3 kg ai/ha (0.15 kg ai/hl) of a WP formulation and harvest 14 days after the last of 4 applications. Trials with WG formulations in Belgium, France and The Netherlands were evaluated according to this use pattern because in this situation residues from the use of WP and WG formulations would be expected to be similar. Ziram residues as CS2 in 1 Belgian trial, 2 French trials and 1 trial in the Netherlands approximating Netherlands GAP were 0.66, 3.8, 1.6 and 0.58 mg/kg. In the French trials residues from longer PHIs were higher and replaced the residue at the GAP PHI.
In Italy ziram is registered for use on pears at 2.3 kg ai/ha (0.23 kg ai/hl) with a PHI of 10 days. In a trial in Italy at 2.8 kg ai/ha the ziram residue was 0.64 mg/kg as CS, 10 days after the final application.
Ziram is registered in Spain for use on pome fruit at a spray concentration of 0.25-0.35 kg ai/hl with a PHI of 7 days. Ziram residues of 1.9, 1.6 and 1.1 mg/kg as CS2 were recorded in pears in 3 sub-plots of a Spanish trial where fruit were harvested 7 days after the final ziram application at a spray concentration of 0.23 kg ai/hl, which is at the lower end of the acceptable range for evaluation purposes.
US GAP on pears allows ziram application at 5.2-6.8 kg ai/ha with a PHI of 5 days in the west and 14 days in the east. Residues as CS2 in 2 US trials according to these 2 use patterns were 0.94 and 2.0 mg/kg. A third US trial could not be evaluated because other dithiocarbamates had been used during the growing period.
In summary, valid results on pears were available from 8 trials with residues as CS2 or 0.58, 0.64, 0.66, 0.94, 1.6, 1.9, 2.0 and 3.8 mg/kg.
The Meeting concluded that the residues in apples and pears appeared to be from similar populations and could be combined to represent pome fruit. Ziram residues as CS, in pome fruit in rank order (median underlined) were 0.16, 0.53, 0.58, 0.61, 0.64, 0.66, 0.70, 0.90, 0.94, 0.97, 0.98, 1.1, 1.4, 1.4, 1.6, 1.8, 1.9, 2.0, 2.4, 2.4, 3.5 and 3.8 mg/kg.
The Meeting estimated a maximum residue level of 5 mg/kg as CS, for dithiocarbamates in pome fruits arising from the use of ziram and noted that this level was consistent with the MRL already established. The Meeting estimated an STMR for ziram on pome fruit of 1.04 mg/kg as CS2, equivalent to 2.1 mg/kg as ziram.
US GAP on apricots permits application of ziram at 6.8 kg ai/ha and harvest of the fruit 30 days after the final application. The maximum ziram residues as CS, with GAP on apricots from 3 US trials at 6.8 kg ai/ha and 1 US trial at 5.1 kg ai/ha were 1.6, 3.7, 4.8 and 5.3 mg/kg.
The stone fruit registration in Spain permits 4 ziram applications at spray concentrations of 0.25-0.35 kg ai/hl with a 7-day PHI. In two Spanish trials on cherries where ziram was applied at 0.23 kg ai/hl and fruit were harvested 7 days after the last of 3 applications the residues as CS, in the three sub-plots of each trial were 0.45, 0.60 and 0.70 mg/kg and 0.55, 0.85 and 0.85 mg/kg.
US GAP for cherries permits ziram application at 3.4-4.3 kg ai/ha with 7- and 14-day PHIs in the west and east respectively. The application rate in the US trials was 5.1 kg ai/ha, but data from 3 trials could not be used because the shortest interval between the final application and harvest was 30 days, which is too remote from the registered 7 days. In the remaining 2 trials the residues as CS2 14 days after the final application were 0.84 and 0.79 mg/kg (replaced for evaluation by residues at 14 days of 1.3 mg/kg).
In summary, the residues as CS, from the 4 valid trials on cherries were 0.70, 0.84, 0.85, and 1.3 mg/kg.
The stone fruit registration in Italy permits ziram applications at 2.4 kg ai/ha (spray concentrations of 0.15-0.20 kg ai/hl) with a 10-day PHI. In an Italian trial on nectarines ziram was applied at 2.4 kg ai/ha. The residues as CS, were 0.27 mg/kg after 10 days and 0.28 mg/kg after 21 days.
The US registration for nectarines permits ziram application at 6.8 kg ai/ha with harvest 14 and 30 days after the final application in the east and west respectively. The residues as CS2 in 2 nectarine trials from the west and 1 from the east according to these use patterns were 0.12, 0.20 and 1.1 mg/kg.
In summary, residues as CS, from the 4 valid trials on nectarines were 0.12, 0.20, 0.28 and 1.1 mg/kg.
In 2 Italian trials on peaches according to GAP the residues as CS, were 1.4 and 0.96 mg/kg after 10 days. In the second trial the residue at 15 days was 1.8 mg/kg and this higher residue was used for evaluation.
Ziram may be applied 3 times at 2.2 kg ai/ha to peaches with harvest 14 days after the final application according to the registration in France. One trial in France and 2 in Spain conformed to this use pattern and the maximum residues as CS2 in each trial were 1.1, 0.94 and 1.8 mg/kg.
US GAP for peaches is the same as for nectarines. The residues as CS2 in 3 peach trials according to the use pattern in the east were 0.43, 2.3 and 5.3 mg/kg. The highest residues as CS, in each of 4 trials according to the use pattern in the west were 0.08, 0.50, 0.72 and 0.77 mg/kg. In one of these trials the residue in a 60-day sample, 0.77 mg/kg, was much higher than the residues in samples from 30 days, 0.03 and 0.05 mg/kg.
In summary, the residues as CS2 from the 12 valid trials on peaches (median underlined) were 0.08, 0.43, 0.50, 0.72, 0.77, 0.94, 1.1, 1.4, 1.8, 1.8, 2.3 and 5.3 mg/kg
In a Spanish trial on plums according to GAP for stone fruit where ziram was applied at 0.23 kg ai/hl and fruit were harvested 8 days and after the final application ziram residues as CS2 in the three sub-plots of the trial were 0.2, <0.2 and 0.2 mg/kg. Residues in plums harvested on day 14 were <0.2, 0.3 and 2.5 mg/kg. The 2.5 mg/kg value seemed inconsistent with the other results, but the analysis had been repeated. A French trial where ziram was applied to plums at a spray concentration of 0.23 kg ai/hl and fruit were harvested 7 days after the final application was evaluated against Spanish GAP. The residues as CS2 in the three sub-plots were 0.45, 0.80 and 1.7 mg/kg. In summary, the residues as CS2 on plums from two valid trials were 1.7 and 2.5 mg/kg.
The use patterns for ziram on the different stone fruits within a country are generally the same and the Meeting concluded that the data from the trials on stone fruits could be combined although the residues on apricots tended to be higher than on the other fruits. The residues from the valid trials were 3.7, 4.8, 5.3 mg/kg on apricots, 0.70, 0.84, 0.85, 1.3 mg/kg on cherries, 0.12, 0.20, 0.28, 1.1 mg/kg on nectarines, 0.08, 0.43, 0.50, 0.72, 0.77, 0.94, 1.1, 1.4, 1.8, 1.8, 2.3, 5.3 mg/kg on peaches and 1.7, 2.5 mg/kg on plums. The residues as CS2 in 26 trials on stone fruit in rank order (median underlined) were 0.08, 0.12, 0.20, 0.28, 0.43, 0.50, 0.70, 0.72, 0.77, 0.84, 0.85, 0.94, 1.1, 1.1, 1.3, 1.4, 1.6. 1.7, 1.8, 1.8, 2.3, 2.5, 3.7, 4.8, 5.3 and 5.3 mg/kg.
The Meeting estimated a maximum residue level of 7 mg/kg (as CS2) for dithiocarbamates in stone fruit arising from the use of ziram and an STMR of 2.2 mg/kg as ziram (1.1 mg/kg as CS2) for ziram in stone fruit.
Ziram is registered for use on almonds in the USA with an application rate of 6.8 kg ai/ha and with the last of 3 applications to be completed by 5 weeks after petal fall. The pre-harvest intervals in the supervised trials were in the range 139-167 days and the conditions were taken to comply with US GAP. In 12 of the 13 trials no residues were detected (0.02 mg/kg as CS2) while in one trial the residue was 0.03 mg/kg. The median residue for the 13 trials was 0.02 mg/kg.
The Meeting estimated a maximum residue level of 0.1* mg/kg CS2 in almonds from the use of ziram. This is a practical LOD which can be achieved by regulatory methods. The Meeting estimated an STMR of 0.04 mg/kg as ziram (0.02 mg/kg as CS2) for ziram in almonds.
The residues as CS2 on the almond hulls from the 13 almond trials in rank order (median underlined) were 1.3, 2.0, 2.8, 3.0, 4.5, 4.6, 5.3, 5.8, 6.1, 6.7, 6.9, 8.8 and 9.3 mg/kg. No information was available on the moisture content of the almond hulls; residue levels in animal feed materials should be expressed on a dry-weight basis.
The Meeting estimated a maximum residue level of 10 mg/kg for dithiocarbamates as CS2 on almond hulls arising from the use of ziram and an STMR of 10.6 mg/kg as ziram (5.3 mg/kg as CS2) for ziram on almond hulls.
Ziram is registered for use on pecans in the USA with an application rate of 6.8 kg ai/ha and a PHI of 55 days. In the 7 trials the interval between the final application and harvest was 51-83 days. In 6 of the 7 trials no residues were detected (0.02 mg/kg as CS2) while in one trial the residue was 0.03 mg/kg. The median residue for the 7 trials was 0.02 mg/kg.
The Meeting estimated a maximum residue level of 0.1* mg/kg CS2 in pecans from applications of ziram, taking into account MRLs recommended by the 1993 JMPR for dithiocarbamates in almonds and peanut at a practical LOD of 0.1* mg/kg, and an STMR of 0.04 mg/kg as ziram (0.02 mg/kg as CS2) for ziram in pecans.
In a processing study on apples sprayed with ziram at an exaggerated rate (34 kg ai/ha) ziram residue levels in the juice were about 10% of those in the apples while the residues in the wet pomace were 1.34 times those in the apples. The levels of ziram in dry pomace were 30-40% higher than in wet pomace which suggests loss of ziram during the drying process because dry pomace is only 20-25% by weight of wet pomace. The processing factors from apples to juice, wet pomace, and dry pomace were 0.097, 1.34 and 1.82 respectively. The process did not include a washing step. Because ziram residues are on the apple surface a commercial process with an initial washing and cleaning step would be expected to reduce the residue.
The supervised trials median residues (STMR-Ps) for the processed apple commodities, calculated from the processing factors and the STMR for pome fruit (2.1 mg/kg) are apple juice 0.204 mg/kg, wet apple pomace 2.81 mg/kg, dry apple pomace 3.82 mg/kg, all expressed as ziram.
Monitoring data for dithiocarbamate residues in commodities in trade are included in the monograph on thiram.
