RESIDUE AND ANALYTICAL ASPECTS
Thiabendazole was evaluated by the Joint Meeting several times from 1970 to 1981, when MRLs were recommended for a number of commodities. The compound was evaluated by the present Meeting under the periodic review programme of the CCPR.
At its 1992 meeting JECFA noted that total residues of thiabendazole and 5-hydroxythiabendazole were below 0.1 mg/kg in all analysed tissues and milk within a few days of withdrawal and therefore adopted the definition of the residue and the MRLs of 0.1 mg/kg recommended by the 1975 JMPR for animal commodities and milk.
Thiabendazole is registered in many countries for use as a post-harvest and pre-harvest fungicide, veterinary drug and human medicine. The major use for plant protection is the post-harvest application.
The disposition of thiabendazole and its metabolites in humans and farm animals has been extensively studied. Many of the studies have also been published in the open literature. The oral administration of thiabendazole to sheep, cattle, goats, dogs and humans resulted in rapid absorption from the gastrointestinal tract. The time to achieve peak plasma levels varied with species and ranged from about 1 hour in dogs to 7 hours in sheep, goats and cattle. In dogs, goats and cattle, approximately 82% of the dose was excreted in the urine and faeces within the first 72 hours after oral administration. In all the species studied, almost all the recovered 14C (97-99.6%) was in the urine and faeces. The hydroxylation of the benzimidazole ring at the 5-position to form 5-hydroxythiabendazole and subsequent conjugation to form the glucuronide and sulfate are the major metabolic steps. A minor metabolic pathway found in faeces and tissues involves loss of the thiazolyl group to form benzimidazole (BNZ). None of these residues are likely to persist in edible tissues in view of their relatively low concentrations and rapid elimination. Although the magnitude and profile of the residues differ slightly among different animal species (rats, lactating goats and laying hens), and samples (tissues, milk, eggs and excreta) the major metabolic steps and metabolites are the same.
Single gelatine capsules, each containing 120 mg of [14C] thiabendazole, were administered daily to lactating goats for 7 consecutive days. Milk was collected twice daily and tissue samples after slaughter on the 8th day, within 24 hours after the final dose. An average of 74% of the administered dose was accounted for at the end of the study in the excreta (urine + faeces), tissues and milk, nearly all of it in the urine (69%) and faeces (28%). In urine, the residues, expressed as thiabendazole, consisted of unconjugated 5-hydroxythiabendazole (-7.9 mg/kg) and its O-sulfate conjugate (~9.5 mg/kg). The residues in the faeces consisted of unconjugated 5-hydroxythiabendazole (2.1 mg/kg), together with lower levels of benzimidazole (~0.4 mg/kg) and unmetabolized thiabendazole (~0.3 mg/kg). About 1% of the dose was found in the tissues. The highest tissue residues were in the liver and consisted of low levels of unmetabolized thiabendazole, unconjugated 5-hydroxythiabendazole and benzimidazole, at maximum concentrations of 0.2, 0.12 and 0.08 mg/kg respectively. Total residues in milk reached a steady state in 3 days and averaged about 1% of the orally administered dose (~1 mg/kg) after the final (7-day) dose. In milk the O-sulfate conjugate of 5-hydroxythiabendazole accounted for about 39% of the 14C (0.4 mg/kg). No other individual residue was detectable (£ 0.5% of the total radioactivity). Fractionation studies indicated that the unidentified residues were mainly products arising from the extensive degradation of thiabendazole followed by incorporation into proteins (20-60%), lipids (12-14%) and polysaccharides (~1%).
Single gelatine capsules, each containing 3.19 mg of [14C] thiabendazole were orally administered daily to laying hens for 10 consecutive days; eggs and excreta were collected twice and once daily respectively. The hens were killed on the 11th day, within 24 hours after the final dose.
An average of 96.6% of the total administered dose was recovered. About 99.6% of this recovered dose was found in the excreta, and consisted of unconjugated (3.4 mg/kg) and conjugated (4.4 mg/kg) 5-hydroxythiabendazole. Cumulatively, the total residues found in the tissues and eggs accounted for about 0.4% or less of the 14C. The total residues in eggs attained a level of about 0.1 mg/kg by day 2 and remained relatively unchanged throughout the next 8 days. The residues in tissues and eggs consisted mainly of unconjugated 5-hydroxythiabendazole, unmetabolized thiabendazole and benzimidazole at maximum concentrations, in the kidneys, of 0.4, 0.11 and 0.12 mg/kg respectively. The proposed metabolic pathway in poultry is the same as in goats.
Neither thiabendazole nor its related residues are likely to persist in milk, eggs or edible tissues because of their relatively low concentrations and rapid elimination.
The fate of [phenyl-14C] thiabendazole was studied in actively growing wheat (2-3 tiller stage), soya beans (late flowering to early pod set) and sugar beet treated at maximum recommended rates (0.8, 0.68 and 2.015 kg ai/ha respectively). Residues were characterized after a combination of solvent (MeOH, MeOH/H2O) and hydrolytic (KOH/MeOH) extractions, by reversed-phase HPLC and electron-impact GC-MS analyses. The same pattern of metabolites was seen in all three crops.
The total residues were about 0.12 mg/kg in wheat grain, 22 mg/kg in the straw, and 67.5 mg/kg in the foliage. Neither thiabendazole nor any individual metabolite was detectable in grain (£ 0.05 mg/kg). The major individual residue found in the shoots was thiabendazole and the highest level, 65.6 mg/kg, was detected in early foliage. In all wheat tissues examined, only low proportions of the applied thiabendazole were converted to benzimidazole, which was subsequently conjugated with sugars. The benzimidazole could be released from the conjugate(s) by treatment with glucosidase. Benzimidazole was detected only in shoot tissues (<0.05 mg/kg in forage and 7.49 mg/kg in straw), either free or as the sugar conjugate(s). The highest level of unextractable residues was found in immature wheat forage (5.77 mg/kg), constituting about 14% of the total radioactive residue. The unextractable residues were distributed in very small amounts throughout several fractions of natural products, all of which were individually at or below the limit of detection (0.05 mg/kg). These results are consistent with findings in residue trials on wheat, including seed dressing and foliar treatments at or higher than the recommended rates with unlabelled thiabendazole, in which no residue (<0.05
mg/kg) was detectable in the grain at harvest. Since thiabendazole was present at higher levels than benzimidazole in growing wheat plants, the expected levels of benzimidazole in grain will also be undetectable (i.e. <0.05 mg/kg).
The aerial parts of actively growing soya bean crops were sprayed twice, at a 14-day interval, with [14C] thiabendazole at a total rate of about 0.68 kg ai/ha. Immature samples (foliage and forage) were taken at intervals of 2 h and 27 days after treatment and mature samples were harvested and separated into grain and straw about 78 days after the first spray. The extractable residues were characterized by both reversed-phase HPLC and GC-MS. The total residues in the seed (~0.9 mg/kg) were less than 10% of those in the straw (~10 mg/kg). At day 27, thiabendazole was the single major residue (59% or 15.12 mg/kg) found in the shoots and benzimidazole-related compounds were present in smaller amounts (1.4% or 0.36 mg/kg). Benzimidazole was released from the conjugate(s) by glucosidase treatment. Thiabendazole (42.9% of the TRR) was the only individual residue detected (³ 0.05 mg/kg) in the grain.
The foliage of actively growing sugar beet plants was sprayed five times, at 14-day intervals, with [14C] thiabendazole at a total application rate of about 2.02 kg ai/ha. Immature top and root samples were taken about 2 h after the first and last treatments. About 90 days after the first treatment (35 days after the fifth and final spray) mature samples were harvested and separated into tops and roots. The residues were characterized by HPLC. At day 56 the organo-extractable residue in the roots was about 90% thiabendazole, amounting to 55.8% of the TRR. In the mature roots the total residues (~0.40 mg/kg) were about 4% of those in the tops (~10 mg/kg). The main component was the parent thiabendazole, at about 0.10 mg/kg; no other individual component was detectable (<0.05 mg/kg). A level of 2.7 mg/kg of thiabendazole was present in mature tops, where benzimidazole (1.4 mg/kg) was also present.
The distribution of the residues in wheat, soya beans and sugar beet is consistent with other results showing the predominantly axoplasmic movement of thiabendazole which results in measurable levels of thiabendazole residues in shoot tissues such as leaves and straw, and relatively less in storage tissues (grains and roots). It can be concluded that the profile and distribution of residues of thiabendazole in three representative actively growing crops (small grain, legume and root crops), following foliar applications, are the same.
The uptake, distribution and metabolism of thiabendazole by seed potatoes were studied under post-harvest storage conditions. Potatoes were briefly immersed in solutions of [14C] thiabendazole at concentrations of 50, 100, 200 and 500 mg/kg and pH levels of 2-9. Skin and tissue sections were subsequently analysed. Potato tubers sorbed thiabendazole from aqueous solutions rapidly (within 5 minutes) at all pH levels. Thiabendazole penetrated only about 2 mm into the tubers in 2 weeks and a little more after 12 weeks, most of it (~96%) remaining on the outer skin. Even after 120 days of post-harvest storage, the only radioactive component detected was thiabendazole, accounting for over 80% of the applied 14C. These results are supported by several additional studies indicating that thiabendazole does not penetrate into the fleshy tissues and does not undergo metabolic transformation. Benzimidazole was not detected (<0.05 mg/kg).
The uptake, distribution and residual fate of [14C] thiabendazole under typical post-harvest storage conditions were also examined in Valencia oranges. Virtually all (~95%) of the radioactivity was sorbed by the peel and none penetrated into the inner pulp. Radiometric assays of the orange samples over the 28-day storage period demonstrated that practically all (~95%) of the radioactivity was due to thiabendazole itself although the conditions, at 21°C, were favourable for metabolism.
The post-harvest treatment studies on oranges, potatoes and pears gave similar results, showing sorption of thiabendazole by the outer surface of storage tissues without penetration into the fleshy interior.
The uptake of soil residues was studied in three representative crops: wheat (small grain), turnips (root) and lettuce (leafy vegetable). Three sandy loam plots were sprayed with [14C] thiabendazole once, or twice two weeks apart, at a total application rate of 2.15 kg ai/ha representing the worst case that might occur in practice. The crops were harvested at maturity. After 137, 223 and 398 days, the extractable residues in the soil amounted to 75.3, 88.6, and 78.1% of the TRR respectively and thiabendazole accounted for 69.6, 86.9 and 63.2% of the TRR at these times. The residues were present in the upper 0-15 cm of the soil; no significant residues were found at 15-30 cm. The major components of the residues in the crops were thiabendazole (0.08-0.23 mg/kg in mature lettuce, 0.08-0.11 mg/kg in turnip roots, 0.63-1.0 mg/kg in turnip tops, <0.05-0.09 mg/kg in wheat grain, 2.61-10.25 mg/kg in wheat straw) and benzimidazole (0.03 mg/kg in mature lettuce, <0.05 mg/kg in turnip roots, 0.05-0.43 in turnip tops, <0.05 mg/kg in wheat grain, and 0.8-2.5 mg/kg in wheat straw), with the benzimidazole both free and as sugar conjugate(s). Lower levels of 5-hydroxythiabendazole (maximum 25-30% of the thiabendazole) were also observed in immature lettuce and wheat forage. Since 5-hydroxythiabendazole is a degradation product in soil, but not a plant metabolite, it is reasonable to conclude that it was produced in the soil and subsequently taken up by the crops. In addition to thiabendazole, benzimidazole, 5-hydroxythiabendazole and the unextractable residues, other radioactive components were also observed in the HPLC radio-chromatograms of various crop extracts, but all of them individually at levels below 0.05 mg/kg. The results demonstrate that the profile and distribution of thiabendazole residues in three representative crops (leafy vegetables, small grains and root crops) planted in treated soil are the same, but the composition of the residue is different from that in actively growing crops following foliar applications.
The fate of thiabendazole in microbially active sandy loam soil was studied under aerobic conditions at 25 ± 1°C. Thiabendazole was degraded with an aerobic half-life of about 737 days. The products consisted of low levels of benzimidazole (<2.5%) and 5-hydroxythiabendazole (<0.5%). Unextractable radiocarbon increased slowly during the study from 1.24% at day 0 to 20.2% at day 120. This increase is consistent with the strong binding of thiabendazole to soil. Volatile material, 96% of which was 14CO2, also increased slowly, attaining its highest level after 12 months and accounting for 5.8% of the applied radioactivity. These results indicate that thiabendazole is fairly stable in soil but will eventually be mineralized under aerobic conditions to CO2. Practically no degradation was observed under anaerobic conditions.
Thiabendazole was found to be photolytically stable on the surface of soil, with a calculated half-life of 933 days. Recoveries of 14C from irradiated and unirradiated soil samples averaged about 98 and 104% respectively, and 90-100% of the radioactivity was due to thiabendazole; no other residue was found.
The adsorption of thiabendazole to soil was studied with silt loam, clay, sandy loam and sand. The results (KOC values ranged from 1,104 to 22,467) indicate that thiabendazole is bound very tightly to soil. Similarly, the desorption of thiabendazole from these soils was also low, with KOC values from about 1,336 to 18,325. Column leaching studies with the parent compound and residues aged on soil surfaces indicated that about 98% of the applied radioactivity remained in the top 2.5 cm of the column. On the basis of the high KOC values and the column leaching studies, thiabendazole is considered to be immobile in soil.
[14C] Thiabendazole was shown to be degraded rapidly in water when exposed to artificial sunlight, with a half-life of approximately 29 hours. The degradation resulted in the formation of benzimidazole-2-carboxamide (~10%), a polar fraction (8.6%) and relatively low levels (~6%) of benzimidazole. A minor degradation product, with HPLC retention properties consistent with a carboxybenzimidazole, was also present in trace amounts.
Analytical methods for determining residues from supervised trials have been validated with all the crops reported in this review. Validated methods are also available for analysing animal tissues and milk, as well as soil and water. The recoveries in food commodities were above 70% and the typical limits of detection and determination were 0.01-0.05 mg/kg and 0.05-0.1 mg/kg respectively.
Thiabendazole, free and conjugated 5-hydroxythiabendazole, and benzimidazole were found to be stable during frozen storage in crops for periods of 12 to 28 months, and in animal commodities for at least 2 months.
Definition of the residue
The studies carried out with labelled thiabendazole and related studies with the unlabelled material show that the only individual detectable residue (³ 0.05 mg/kg) in edible crop commodities is likely to be the parent thiabendazole.
The animal metabolism and transfer studies indicate that thiabendazole and 5-hydroxythiabendazole are the major residue components in meat and eggs, while the sulfate conjugate, which was determined in all reported studies, is the major component in milk. The parent thiabendazole occurred at much lower concentrations in all commodities.
The Meeting concluded that the following definitions of the residue are appropriate.
For compliance with MRLs
For plant products: thiabendazole.
For animal products: sum of thiabendazole and 5-hydroxythiabendazole.
For estimations of dietary intake
For plant products: thiabendazole.
For animal products: sum of thiabendazole, 5-hydroxythiabendazole and its sulfate conjugate.
Post-harvest trials were conducted in the USA and Spain from 1990 to 1994 on oranges, lemons, grapefruit and tangerines. Ten trials were carried out on oranges in Spain with single post-harvest drench applications at 66 g ai/hl and 110 g ai/hl, and eight in the USA on citrus fruit with initial dip applications at 100 g ai/hl, followed by mist applications in wax with 350 or 500 g ai/hl at rates of 8.4 or 12 g ai/t fruit, much higher than the rates of 0.8-5.5 g ai/t specified on the labels. Residues of thiabendazole on unwashed whole fruit from the US trials in rank order were 1.2, 1.8, 2.9, 3.0. 3.8. 3.9, 4.8 and 5.4 mg/kg. The Spanish trials were reported in a summarized form which did not contain essential details and could not be used to estimate maximum residue levels.
Since there were no residue data from treatments according to GAP, the Meeting recommended the withdrawal of the existing CXL of 10 mg/kg.
Post-harvest residue trials were conducted in the USA (10) and Spain (5) in 1990-1991 on apples and pears. In the US trials, initial dip applications at 60 g ai/hl were followed by mist applications at 200 g ai/hl in wax (about twice the GAP concentration). The US labels provided do not include application in wax for pome fruits, however, in contrast to citrus fruits for which application in wax is specified. The residues on apples and pears (*) in the US trials were 0.89, 1.1* 3.0, 3.2, 3.2, 3.4, 3.4, 3.4, 3.7* and 5.1* mg/kg whole fruit. The trials in Spain were at 110 g ai/hl, the maximum GAP concentration, but were reported in a summarized form which did not contain essential details and they could not be used for the estimation of maximum residue levels.
Pre-harvest foliar applications on apples at four times the Japanese GAP rate gave rise to residues in the range 0.08-0.52 mg/kg.
As the trials were not according to national GAP, the Meeting recommended the withdrawal of the existing CXLs for apples and pears.
Pre-harvest residue trials on strawberries in Mexico, where there is no GAP, and Spain in 1989-1992 were with ground foliar applications of SC and WP formulations. In Mexico four applications were made 7 days apart, at rates of 0.50-2.0 kg ai/ha. In Spain a single application was carried out at 1.2 kg ai/ha (approx. 1.3 times GAP). The residues from the Spanish trials were 0.33 and 1.6 mg/kg at 3 days PHI. The data were insufficient to estimate a maximum residue level.
Residues following the post-harvest treatment of bananas were determined in a number of trials in Hawaii, Honduras and Guadeloupe. Residues in 10-20 replicate samples taken from individual treated lots indicated that the treatments were fairly uniform. The highest residues of the parent thiabendazole in each trial with 0.04 kg ai/hl in rank order were 0.79, 0.88, 1.0, 1.2, 1.4, 1.6, 1.7, 1.8, 2.3 and 3.3 mg/kg. Benzimidazole residues could not be detected in any samples. The dip treatments in Hawaii and Guadeloupe gave higher residues than the spray applications in Honduras. The pulp of ripened bananas from four trials contained average residues in the range 0.011-0.021 mg/kg which amounted to 1.3-2.9% of the residues measured in whole green bananas. The highest residues in individual samples from each trial in rank order were 0.016, 0.028, 0.029 and 0.031 mg/kg.
Since the use patterns (20-40 g ai/100 l) for post-harvest applications are very similar in a number of countries, the Meeting estimated a maximum residue level of 5 mg/kg for banana to replace the current CXL (3 mg/kg) and an STMR level of 0.029 mg/kg for banana pulp.
No information was provided on residues in onions. The Meeting therefore recommended the withdrawal of the CXL for bulb onions.
Four pre-harvest residue trials were conducted on tomatoes grown under plastic in Spain in 1990-1991 with ground spray foliar applications of SC and WP formulations. Two trials in 1990 were with two applications 7 days apart, at 0.50 kg ai/ha, and two trials in 1991 were with single applications at 3.1 kg ai/ha (approximately 3 times the GAP rate). The data were insufficient to estimate a maximum residue level and the Meeting recommended the withdrawal of the CXL for tomatoes.
Single dip or spray applications of SC and SL formulations of thiabendazole were used on chicory roots. Twenty trials were conducted with flowable SC and 20-S formulations at 67-630 g ai/hl. The chicory leaves, hearts and roots were all analysed for thiabendazole residues. Residues in the edible witloof chicory sprouts did not exceed 0.05 mg/kg even when the roots were treated at a sixfold rate.
The Meeting estimated a maximum residue level, at or about the limit of determination, of 0.05 mg/kg, and an STMR level of 0.05 mg/kg for witloof chicory (sprouts).
Post-harvest residue trials were conducted on potatoes. In seven trials in the UK whole potatoes were treated with a single spray mist application of a flowable formulation at 30-80 g ai/tonne. Potatoes in the US trials were subjected to an initial seed treatment at 2400 g ai/hl (approximately twice the GAP concentration) before cutting and planting, followed by an application of thiabendazole at 6.2 g ai/t (1.1 times the GAP rate) immediately after harvest and before storage, and a similar application about 30 days later. The residues of thiabendazole on unwashed potatoes from both sets of trials in rank order were 1.9, 2.0, 2.2, 2.4, 2.6, 4.2, 5.4, 5.5, 7.3 and 11 mg/kg.
The Meeting estimated a maximum residue level of 15 mg/kg and an STMR of 3.4 mg/kg for potato (adhering soil may be removed by rinsing or gentle brushing, to conform to the commodity to which Codex MRLs apply).
Pre-harvest residue trials on sugar beet were reported from Spain. One or two ground sprays were applied at 480 g ai/ha after development of 4-8 leaves. The residues of thiabendazole were <0.01 mg/kg in all 16 root samples taken from 0 to 91 days after the last application. The leaves and tops contained residues up to 0.41 mg/kg after 59-65 days. Since no GAP or processing studies were reported, the Meeting could not estimate maximum residue levels for sugar beet, sugar beet leaves or tops, molasses or dry pulp, and consequently recommended the withdrawal of the CXLs.
Mushrooms were treated with four applications of an aqueous solution by irrigation at 54-108 g ai/100 m2 or by direct spray at 9.5-19 g ai/hl. Applications were made after pinning or after the first harvest break and then after the second, third and fourth breaks according to US label instructions. The maximum residues of thiabendazole on mushrooms collected 12 hours after the last application were 1.9, 2.2, 2.4, 2.5, 3.1, 3.2, 3.9, 3.9, 6.0, 6.1, 7.3, 8.0, 9.6, 12 and 13 mg/kg for irrigation and 21, 27, 30, 31, 36, 41 and 52 mg/kg for spray applications. The residues of benzimidazole were <0.01 mg/kg in all samples.
In four residue trials in Japan a WP formulation was applied once to the bed medium at a rate of 0.120 g ai/kg. The residues of thiabendazole were £ 0.25 mg/kg.
The Meeting evaluated the residues from direct spray applications according to US GAP and estimated a maximum residue level of 60 mg/kg and an STMR of 31 mg/kg for mushrooms.
In fourteen pre-harvest trials on wheat a single ground or aerial spray was applied at 620 g ai/ha (US GAP) after development of 2 to 3 tillers but before the first node, and the wheat was grown to harvest. The residues of thiabendazole and benzimidazole were <0.05 mg/kg in all 14 grain samples. The thiabendazole residues in the straw in rank order were <0.05 (11), 0.07, 0.11 and 0.13 mg/kg.
The Meeting noted that wheat readily takes up thiabendazole residues from soil (<0.05-0.09 mg/kg in wheat grain and 2.61-10.25 mg/kg in wheat straw grown in soil treated at 2.15 kg/ha). Although the pre-harvest use is limited and the application rates (up to 1 kg/ha except onion and garlic 1.4 kg ai/ha) are relatively low, the Meeting concluded that further field-scale rotational crop studies would be required before the pre-harvest use of the compound could be recommended and accordingly recommended the withdrawal of the CXL for cereal grains.
Animal transfer studies were conducted with poultry and cows. Ten groups of chickens (25 per group, males and females) were treated continuously for 7 weeks with thiabendazole at levels corresponding to 2, 20, 200 and 2000 ppm in the feed. Four males and 4 females at each treatment level were killed within four hours after the last dose and the liver, kidney, fat and muscle analysed for thiabendazole and 5-hydroxythiabendazole, as were eggs from the three highest treatment levels. The sum of thiabendazole and 5-hydroxythiabendazole, including its conjugate released by acid hydrolysis, was 0.02-0.028 mg/kg in fat (taken from different parts of the birds), 0.017-0.023 mg/kg in a 1:1 mixture of breast and leg meat, and 0.06-0.08 mg/kg in liver at the 20 mg/kg feed level (the expected level based on a poultry diet of 70% corn grain, 20% potatoes and waste and 10% wheat grain). At the same feeding level the average residues were 0.023-0.05 mg/kg in egg yolk and 0.007-0.023 mg/kg in egg white.
The Meeting noted the 3.4 mg/kg STMR for potatoes and the processing factor of 17 for processing potatoes to dry potato peel, and concluded that the 20 mg/kg feeding level appropriately covered the residues likely to occur in poultry feed. The Meeting estimated maximum residue and STMR levels of 0.05 mg/kg for poultry meat and 0.1 mg/kg for eggs.
Dairy cattle were treated once daily by capsule for 28 days with thiabendazole at levels corresponding to 25, 75 and 250 ppm in the feed. Milk samples were collected from all cows on days -1, 1, 2, 4, 7, 14, 21, 28, 29, 35, 42 and 56. Tissues and organs from two of the three cows in each treatment group were collected on day 29, and the remaining cow from each group was slaughtered on day 57. All the samples were analysed for thiabendazole and 5-hydroxythiabendazole. The residues in the milk reached plateaus two days after treatment of 0.014 mg/kg thiabendazole and 0.012 mg/kg 5-hydroxythiabendazole in the 25 ppm group and 0.017 mg/kg thiabendazole and 0.11 mg/kg 5-hydroxythiabendazole in the 250 ppm group, but these levels were less than 0.01 mg/kg higher than the control value at the 25 ppm feeding level, and below the limit of determination of the analytical procedure (0.05 mg/kg). The total residues of thiabendazole plus 5-hydroxythiabendazole in the cows of the 25 ppm group were <0.05 mg/kg in the milk and tissues except a single value of 0.05 mg/kg in kidney. At the 250 ppm level the residues were highest in kidney (0.024-0.03 mg/kg thiabendazole, 0.33-0.55 mg/kg 5-hydroxythiabendazole) and liver (0.056-0.08 thiabendazole, 0.12-0.16 mg/kg 5-hydroxythiabendazole), with much lower residues in the muscle and fat (0.014-0.017 mg/kg thiabendazole, 0.004-0.01 mg/kg 5-hydroxythiabendazole). No difference was observed between the thiabendazole residues in various meat tissues. The residues decreased rapidly to control levels when the animals were returned to a thiabendazole-free diet. The level of 25 ppm is a likely maximum rate, based on a diet of 50% maize grain, 25% apple pomace and 25% potato waste.
On the basis of the likely maximum residues in feed items the Meeting estimated maximum residue levels of 0.05 mg/kg for cattle meat and milk and 0.1 mg/kg for cattle edible offal, and STMRs of 0.05 mg/kg for all three commodities.
The metabolism study in goats at a level corresponding to approximately 20 ppm in the feed indicated much higher total residues of 1.1 mg/kg in milk (0.4 mg/kg 5-hydroxythiabendazole), 4.8 mg/kg in liver, 1.4 mg/kg in kidney and 0.1 mg/kg in meat. The Meeting concluded that further feeding studies would be required to estimate maximum residue levels in the meat, milk and edible offals of other animals, and recommended the withdrawal of the CXLs for milks and the meat and edible offals of goats, horses and sheep.
The effect of cold storage was studied with apples and potatoes after post-harvest treatment. The residues decreased during the first 24 hours but then remained relatively constant for 5 to 6 months.
The effects of processing were studied with post-harvest-treated apples, oranges and potatoes. Apples were treated with a post-harvest dip at 60 g ai/hl followed by a spray mist application in wax at 8.4 g ai/t approximately 30 days after cold storage. Whole fruits were processed into juice, wet pomace and dried pomace. The study could not be used to estimate processing factors, because a wax treatment is not specified on the label and the residues on whole unwashed apples were lower than on washed fruit, which cast doubt on the reliability of the results. Properly planned and executed processing studies representing typical industrial processes would be required before maximum residue levels could be estimated.
Oranges and grapefruit were treated with a post-harvest dip at 12 g ai/t followed by a spray mist application of thiabendazole in wax at 500 g ai/hl. The whole, washed fruits were processed into various fractions. The processing factors were 0.05 for juice and 8 for dried pomace.
The effect of home-processing on residues of thiabendazole in home-made marmalade was studied in the UK in 1993. The processing factors for home-made marmalade prepared in a preserving pan and in a microwave oven were 0.32 and 0.37 respectively.
Since no maximum residue level or STMR could be estimated for citrus fruits, no STMR-P levels could be estimated.
The effect of washing on the thiabendazole residues in potatoes was studied in several trials. The reduction of residues depended mainly on the time which elapsed between treatment and washing, and probably on the efficiency of washing which was not quantified. The processing (i.e. washing) factors calculated from the experiments in rank order were 0.05, 0.09, 0.11, 0.11, 0.12, 0.14, 0.16, 0.16, 0.17, 0.26 and 0.34 with a median of 0.15 and a mean of 0.13. Peeling removed a further substantial proportion of the residues in washed potatoes. The Meeting noted that residues are transferred from the peel to the peeled potatoes during peeling as potatoes peeled before washing contained average residues of 1.54 mg/kg and after washing 0.08 mg/kg. During industrial processing potatoes are always washed before peeling, and in a kitchen operation either before or after peeling or both. The Meeting therefore concluded that it is more appropriate to estimate the effect of peeling washed potatoes. The average ratio of the residue in pulp to that in washed potatoes was 0.045.
Since washing reduced the residues in raw potatoes by an average factor of 0.13 the Meeting estimated STMR-P levels of 0.44 mg/kg (3.4 x 0.13) for washed potatoes, and 0.02 mg/kg (0.44 x 0.045) for washed and peeled potatoes.
In processing trials in the USA seed potatoes were dipped in an aqueous suspension of thiabendazole containing 2400 g ai/hl before cutting and planting followed by a spray application to the daughter tubers at 6.2 g ai/t immediately after harvest and before cold storage, followed by a second application of 6.2 g ai/t approximately 30 days later. The processing of the potatoes involved washing, abrasive peeling, washing, slicing, washing, frying in vegetable oil at 178-182 °C, de-oiling, and salting.
The effect of microwave and oven cooking on the residues of thiabendazole in or on potatoes was studied in the UK in 1990. Potatoes were treated post-harvest with a single application at 40 g ai/t. The tubers were stored for 182 days and the raw peel, raw pulp and unpeeled raw potatoes subjected to microwave and oven cooking.
In four trials on the effects of washing, boiling, baking and crisping in the UK in 1976 potatoes were treated post-harvest with single applications at 40 and 80 g ai/t. The tubers were stored for 4 and 21 days after treatment before processing.
The processing factors founs in the US and UK trials were 1.13, 1.16, 1.2 (2) and 1.34, mean 1.2, for baked whole potatoes; 0.044, 0.055 and 0.073, mean 0.06, for potato chips; 0.03 for potato flakes and 17 for dried potato peel.
Since baking and frying do not change the residue content substantially, baked potatoes may be consumed with or without peel, and cooked or fried potatoes may be prepared in widely varying ways, the Meeting recommended the use of STMR-Ps for washed potato (0.44 mg/kg) and washed and peeled potato (0.02 mg/kg) for the assessment of dietary intake.
