4-(4-chlorophenyl)-2-phenyl-2-(1H-1,2,4-triazol-1-ylmethyl)butyronitrile
Fenbuconazole is a triazole fungicide intended for use as an agricultural and horticultural fungicide spray for the control of leaf spot, yellow and brown rust, powdery mildew and net blotch on wheat and barley and apple scab, pear scab and apple powdery mildew on apples and pears. It was considered for the first time by the present Meeting.
TOXICOLOGY
Fenbuconazole is rapidly absorbed and eliminated, mainly in the faeces through significant biliary excretion; there was no evidence of significant retention in tissues. The compound was also extensively metabolized with phase I oxidation or hydroxylation at a number of sites in the molecule, followed by phase II sulphate and glucuronide conjugation (predominantly glucuronidation). Dermal absorption of fenbuconazole (technical material and a formulation) constituted 2-13% of the administered dose over 24 h, the absorption over 10 h being <5%.
Fenbuconazole was of low acute toxicity when administered orally (LD50 > 2000 mg/kg bw), dermally (LD50 > 5000 mg/kg bw), or by inhalation (LC50 > 2.1 mg/litre air). It was not irritating to the skin or eyes and was not a sensitizer in a Buehler test, but was a weak sensitizer in a maximization test. WHO has not yet classified fenbuconazole for acute toxicity.
After dietary administration, hepatomegaly with associated effects on clinical chemistry, such as changes in cholesterol and triglyceride levels and increases in the serum activity of hepatic enzymes, were seen in mice, rats, and dogs. In a 13-week study of toxicity in mice with dietary levels of 0, 20, 60, 180, or 540 ppm the NOAEL was 60 ppm (equal to 11 mg/kg bw per day) on the basis of hepatic effects at higher doses. In a three-month study of toxicity in rats with dietary levels of 0, 20, 80, 400, or 1600 ppm the NOAEL was 20 ppm (equal to 1.3 mg/kg bw per day) on the basis of hepatic effects and hypertrophy of the thyroid gland follicular cells at higher doses. In a 13-week study of toxicity in dogs with dietary levels of 0, 30, 100, 400, or 1600 ppm the NOAEL was 100 ppm (equal to 3.3 mg/kg bw per day). In a one-year study in dogs with dietary levels of 0, 15, 150, or 1200 ppm the NOAEL was 150 ppm (equal to 5.2 mg/kg bw per day). The NOAELs in the studies in dogs were based on decreased body-weight gain and increased incidence of hepatic hypertrophy with associated effects on clinical chemistry at higher doses.
In a 78-week study of toxicity and carcinogenicity in mice, with dietary levels of 0, 10, 200, or 650 ppm in males and 0, 10, 650, or 1300 ppm in females, there was clear evidence of treatment-related hepatomegaly, with dose-related hepatocytic hypertrophy and vacuolation and limited evidence of treatment-related hyperplasia and tumorigenicity in the liver at the highest dose. The NOAEL was 10 ppm (equal to 1.3 mg/kg bw per day). In a two-year study in rats with dietary levels of 0, 8, 80, or 800 ppm, the predominant effects were hepatocytic hypertrophy, thyroid follicular-cell hypertrophy and an increase in thyroid follicular-cell adenomas; in addition thyroid carcinomas were seen at the high dose. The NOAEL was 80 ppm, equal to 3 mg/kg bw per day.
The aetiology of the hepatic and thyroidal effects in rats was further investigated in a 4-13-week study which illustrated the biological feedback mechanism in rats: hepatomegaly leading to increased metabolism and excretion of thyroxine, increased levels of thyroid stimulating hormone and thyroid hypertrophy/hyperplasia. The effects seen after four weeks in this study were reversible. In studies designed to investigate the hepatotoxicity of fenbuconazole, hepatic effects were seen in rats and mice that were similar to those induced by phenobarbital. Increased cytochrome P450 activity (CYP2B form) was observed, with hepatocellular hypertrophy and proliferation. The NOAEL in mice after treatment for 13 weeks was 60 ppm (equal to 14 mg/kg bw per day).
Fenbuconazole was adequately tested for genotoxicity in vitro and in vivo. The Meeting concluded that fenbuconazole is not genotoxic.
Fenbuconazole was not teratogenic in either rats (at doses of 0, 30, 75, or 150 mg/kg bw per day) or rabbits (at doses of 0, 10, 30, or 60 mg/kg bw per day) but fetotoxicity was seen in both studies with an NOAEL of 30 mg/kg bw per day. The NOAELs for maternal toxicity were 30 mg/kg bw per day in rats and 10 mg/kg bw per day in rabbits. No effects on reproductive parameters were seen in a multigeneration study in rats at dietary levels of 0, 8, 80, or 800 ppm, but fetotoxicity was again seen at high doses together with maternal toxicity. The NOAEL was 80 ppm, equal to 5.8 mg/kg bw per day.
An ADI of 0-0.03 mg/kg bw was allocated, on the basis of the NOAEL of 3 mg/kg bw per day in the two-year study in rats using a safety factor of 100. The Meeting noted that the NOAEL in the 13-week study in rats and in the 78-week study in mice was 1.3 mg/kg bw per day, but it concluded that this figure should not be used to derive the ADI. The NOAEL from the 13-week study in rats was not considered to be relevant in the light of the results of the larger, two-year study. The Meeting concluded that the overall NOAEL in mice was 14 mg/kg bw per day. This figure was taken from the 13-week study which included detailed investigations of hepatotoxicity. Hepatotoxicity was the critical effect in the long-term study in mice and the NOAEL in the 13-week study was lower than the lowest dose causing hepatotoxicity in the long-term study.
A toxicological monograph was prepared summarizing the data that were reviewed at the present meeting.
TOXICOLOGICAL EVALUATION
Levels that cause no toxic effect
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Mouse: |
60 ppm, equal to 14 mg/kg bw per day (13-week study of hepatotoxicity) |
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10 ppm, equal to 1.3 mg/kg bw per day (78-week study of toxicity) |
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Rat: |
20 ppm, equal to 1.3 mg/kg bw per day (13-week study of toxicity) |
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80 ppm, equal to 3.0 mg/kg bw per day (two-year study of toxicity) |
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30 mg/kg bw per day (maternal toxicity in a study of developmental toxicity) |
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80 ppm, equal to 5.8 mg/kg bw per day (two-generation study of reproductive toxicity) |
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Rabbit: |
10 mg/kg bw per day (maternal toxicity in a study of developmental toxicity) |
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Dog: |
150 ppm, equal to 5.2 mg/kg bw per day (one-year study of toxicity) |
Estimate of acceptable daily intake for humans
0-0.03 mg/kg bw
Studies that would provide information useful for the continued evaluation of the compound
Observations in humans
Toxicological criteria for setting guidance values for dietary and non-dietary exposure to fenbuconazole
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Human exposure |
Relevant route, study type, species |
Results, remarks |
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Short-term |
Oral toxicity, rat |
LD50 > 2000 mg/kg bw |
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Dermal toxicity, rat |
LD50 > 5000 mg/kg bw |
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Inhalation toxicity, rat |
LC50 > 2.1 mg/l |
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Dermal irritation, rabbit |
Not irritating |
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Ocular irritation, rabbit |
Not irritating |
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Dermal sensitization, guinea pig |
Not sensitizing in Buehler test, weakly sensitizing in maximization test |
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Medium-term |
Repeated oral, 1 -year, toxicity, dog |
NOAEL = 5.2 mg/kg bw per day: hepatic effects |
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Repeated dermal, 4 weeks, toxicity, rat |
NOAEL = 1000 mg/kg bw per day (highest dose tested) |
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Repeated oral, reproductive toxicity, rat |
NOAEL = 5.8 mg/kg bw per day: maternal and fetal toxicity |
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Repeated oral, developmental toxicity, rabbit |
NOAEL =10 mg/kg bw per day: maternal toxicity |
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Long term |
Repeated oral, 2 years, toxicity and carcinogenicity, rat |
NOAEL = 3 mg/kg bw per day: hepatic and thyroid effects |
RESIDUE AND ANALYTICAL ASPECTS
Fenbuconazole is a white solid with low solubility in water and low vapour pressure. It has a log Pow of 3.22 and is reasonably soluble in fat. It is a triazole fungicide formulated mainly as an EC or an EW.
Fenbuconazole was rapidly absorbed and eliminated, mainly in the faeces with significant biliary excretion, in rats; there was no evidence of any retention in the tissues. The compound was also extensively metabolized with oxidation and hydroxylation at a number of sites in the molecule, followed by conjugation to form sulfates and glucuronides, mainly the latter.
Metabolism and distribution were investigated in lactating goats and chickens. In goats dosed at levels equivalent to 1, 10 and 100 ppm in the feed, less than 0.5% of the TRR remained in the milk and less than 1.6% in the tissues. Two major metabolites were identified in the milk as 1,2,4-triazole (0.24 mg/kg fenbuconazole equivalents at the highest dose) and triazolylalanine (TA, 0.15 mg/kg at the highest dose), with very low levels of the parent compound. At the highest dose, the levels of the TRR in the liver, kidney, muscle and fat were 12.4, 0.97, 0.22 and 0.11 mg/kg respectively. In the liver five major components were identified: the parent compound (0.95 mg/kg), 4-(4-chlorophenyl)-2-hydroxymethyl-2-(phenyl)butanenitrile (RH-7968, 0.95 mg/kg), the glucuronide of the 4-hydroxy derivative (1.23 mg/kg), the triazole (1.79 mg/kg) and TA (4.95 mg/kg). A further phenol metabolite was present in the kidney.
When chickens were dosed with the equivalent of 100 ppm in the feed, less than 0.7% of the TRR was found in the eggs and less than 0.8% in the tissues (0.04% in the lean meat, 0.01% in the fat, 0.02% in the liver and 0.02% in the kidneys). Three major components were identified in the eggs: the parent (0.89 mg/kg), two isomeric lactones (0.29 mg/kg) and the triazole (0.54 mg/kg). In the liver the glucuronide (3.69 mg/kg) and the triazole (1.25 mg/kg) were the major metabolites. In the fat the parent was the major component (0.43 mg/kg) with several low-level metabolites identified.
Plant metabolism was studied in peaches, wheat and peanuts. Metabolism occurs by oxidation at the benzylic carbon adjacent to the chlorophenyl ring.
In the wheat study, phenyl- and triazole-labelled [14C] fenbuconazole were foliar-applied at a rate of 2 x 0.4 kg ai/ha. At harvest the total 14C residues (expressed as fenbuconazole equivalent) were 0.04-0.44 mg/kg in the grain and 9.8-10.6 mg/kg in the straw. The predominant components in the grain were TA and triazolylacetic acid (TAA) which were present at levels of 0.25 and 0.11 mg/kg respectively. The parent compound was present in the grain, but at less than 0.01 mg/kg. In the straw fenbuconazole was the main component at levels of 8.8-11.8 mg/kg. Three other components were identified in the straw as the lactones found in chickens (1.1-1.4 mg/kg), a ketone (the 4-oxo derivative, 0.59-0.62 mg/kg) and a glucoside conjugate of the 4-(4-chloro-3-hydroxyphenyl) analogue (0.43 mg/kg).
In the peach study, phenyl- and triazole-labelled [14C] fenbuconazole were foliar-applied five times, at a rate of 0.2 kg ai/ha. At harvest the total 14C residues in the peaches expressed as fenbuconazole equivalent were 0.08-0.12 mg/kg. TA and fenbuconazole predominated, at levels of 0.06 and 0.02-0.04 mg/kg respectively. The lactones and TAA were also identified, plus 5 unknowns which were not individually above 0.01 mg/kg.
In the third study, peanuts were treated four times with phenyl- and triazole-labelled [14C] fenbuconazole at a rate of 0.57 kg ai/ha. The major component in both the vine and the shells was fenbuconazole (48 and 34% respectively), with TA, the glucoside conjugate, and the ketone the main remaining components. In the nut no fenbuconazole was present and 92% of the residue was TA.
In a study of metabolism and distribution in rotational crops, wheat, turnips and collards were planted in soil which had been treated bare with either phenyl- or triazole-labelled fenbuconazole at the exaggerated rate of 8.96 kg ai/ha. At harvest TA and TAA were by far the predominant components of the TRR in the crops. In a further study, phenyl-labelled fenbuconazole was applied to soil at 3 x 0.07 or 4 x 0.28 kg ai/ha and lettuce, radishes, sorghum, carrots or barley were planted 35-260 days after treatment. The total residues in all crop samples at harvest were £ 0.04 mg/kg.
The lactones and ketone formed in plants were identified in the rat metabolism studies; TA and TAA were not identified in rats but are common metabolites of all triazoles. In several of the residue trials the levels of the lactones and ketone were determined but were generally at low concentrations compared with fenbuconazole.
Fenbuconazole was found to be persistent in soil, although degradation varied greatly, with half-lives of 38-367 days in the laboratory and 28-425 days (DT90 >1 year) in the field. The compound was immobile in column leaching studies and showed KOC values of 2185-9042. Neither photolysis nor hydrolysis of fenbuconazole occurred in aqueous media, and in sediment/water systems it partitioned rapidly into the sediment where it persisted.
Several methods of analysis were reported for various commodities, most of them by GLC with NP detection. Most of the methods also allow determination of metabolites (e.g. the lactones) and have limits of determination of 0.01-0.05 mg/kg with recoveries of about 80%. The Meeting agreed that 0.05 mg/kg was an appropriate practical limit of determination of parent fenbuconazole in most commodities for routine monitoring and the enforcement of MRLs.
Residues of fenbuconazole and the lactones, the ketone in plant products and the 2-hydroxymethyl derivative in animal products were stable in apples, wheat grain and straw stored at -10°C and products of animal origin stored at -4°C for at least 18 months and 2-4 months respectively. Residues of fenbuconazole and the lactones (and the ketone in some commodities) were also stable when stored at -10°C for 54 months in peaches and pecans, 12 months in almonds, and about 31 months in hen and cow muscle. There was some decrease in total fenbuconazole residues in some cereal fractions that had been stored for about 56 months.
The Meeting agreed that the residue should be defined as fenbuconazole both for compliance with MRLs and the estimation of dietary intake.
The Meeting concluded that although the solubility of the residue in fat was intermediate the enforcement of MRLs could best be carried out on a whole-product basis; this conclusion is supported by the data on animal metabolism. Accordingly the Meeting agreed not to describe the residue as fat-soluble.
Supervised trials
In listing the residue results, values at or above 0.1 mg/kg have been given to two significant figures and those below 0.1 mg/kg to one significant figure.
Grapefruit and oranges. The only reported GAP was pending in the USA where the maximum application rate for both commodities is 0.28 kg ai/ha with a PHI of 0 days. Residues of fenbuconazole from trials on grapefruit complying with this GAP were 0.02, 0.10, 0.12, 0.13, 0.16, 0.16, 0.19, 0.34 and 0.49 mg/kg in the whole fruit and <0.01 (5) and 0.02 mg/kg in the pulp.
The residues in oranges were 0.18 (2), 0.19 (2), 0.28, 0.30, 0.34, 0.44 and 0.52 mg/kg in the whole fruit and <0.01 (4) and 0.01 mg/kg in the pulp. Because GAP was only pending the Meeting was unable to estimate a maximum residue level for either fruit.
Pome fruit. GAP for apples was reported for France, Israel, Italy, Portugal, South Africa, Turkey and the UK and for pears for Greece, Israel, Italy, Portugal, South Africa and the UK, and was reported to be pending for apples in the USA and Greece and for pears in France. The maximum application concentrations are 0.002-0.004 kg ai/hl except in the UK and the USA where the application rates were reported as 0.068 and 0.14 kg ai/ha respectively. PHIs were either 14 or 28 days.
Residues of fenbuconazole in apples from trials complying with the pending US GAP were 0.01, 0.02, 0.04, 0.05 (2), 0.06 (2), 0.07 (2), 0.08, 0.09 (2), 0.12 (4), 0.13 (2), 0.15, 0.16 (2), 0.17, 0.18, 0.20 (2), 0.27 and 0.28 mg/kg. Many of the results from these trials had been corrected for the average recovery. Because the GAP was pending the Meeting could not use these results to estimate a maximum residue level.
Residues of fenbuconazole in apples from trials according to UK GAP were <0.02, 0.02 (3), 0.03 (3), 0.04 (2), 0.05 and 0.06 mg/kg, those from trials complying with Southern European GAP (France, Greece, Italy and Portugal) were <0.005, <0.01, 0.01, 0.02 and 0.03 mg/kg, and the residues in pears from trials complying with Southern European GAP were 0.01 (2), 0.02 (2), 0.05 and 0.06 mg/kg.
The residues from the trials on apples and pears according to GAP appear to be from similar data populations. The combined residues were <0.005, <0.01, 0.02, 0.01 (3), 0.02 (6), 0.03 (4), 0.04 (2), 0.05 (2) and 0.06 (2) mg/kg. The Meeting estimated a maximum residue level of 0.1 mg/kg and an STMR of 0.025 mg/kg for fenbuconazole in pome fruit.
Cherries. GAP was reported only for the USA. The maximum application is 0.105 kg ai/ha with a PHI of 0 days.
The residues in the trials complying with the maximum US GAP were 0.20, 0.21, 0.31, 0.33, 0.34, 0.36 (2), 0.42 and 0.51 mg/kg. Four other trials with an exaggerated application rate (33% higher than GAP) showed residues of 0.43, 0.47, 0.53 and 0.55 mg/kg at day 0. In addition, trials at the maximum US application rate with residues of 0.01, 0.12, 0.22, 0.25, 0.43 and 0.47 mg/kg at a PHI of 7 days were considered to be within the range of GAP. All of the above residues at day 0 had been corrected for average recoveries. Some of the trial samples were stored frozen for 3.5 to 4 years before analysis. Since the data on the storage stability of fenbuconazole residues in peaches indicated that they were stable up to 54 months the Meeting agreed to use these results, but emphasized that the storage of trial samples for long periods before analysis was undesirable.
The Meeting agreed that an STMR should be estimated from the residues on day 0, including those from the exaggerated rate: 0.20, 0.21, 0.31, 0.33, 0.34, 0.36 (2), 0.42, 0.43, 0.47, 0.51, 0.53 and 0.55 mg/kg. The Meeting estimated a maximum residue level of 1 mg/kg and an STMR of 0.36 mg/kg for fenbuconazole in cherries.
Apricots and peaches. GAP for apricots was reported for Israel and the USA, and pending GAP for France. The maximum application rates are 0.0025 kg ai/hl in Israel, 0.0075 kg ai/hl in France, and 0.105 kg ai/ha in the USA, with PHIs of 0-14 days.
The residues in the trials on apricots considered to comply with US GAP were 0.12, 0.16, 0.21, 0.25 and 0.27 mg/kg. All of these results had been corrected for average recoveries and referred to the residue in the fruit without stone. The trials complying with the pending French GAP with the highest application rate (0.0075 kg ai/hl) gave residues of 0.06, 0.17, 0.26, 0.21 and 0.33 mg/kg. Some of these were in the fruit without stone.
GAP for peaches was reported for Israel and the USA, and pending GAP for France and South Africa. The maximum application rates are 0.002-0.005 kg ai/hl or 0.105 kg ai/ha, with PHIs ranging from 0 to 14 or 60 days: the pending French GAP was originally reported by the company as having a 60-day PHI, but the Meeting was informed that the PHI would be 3 days. Based on a 3-day PHI the residues in trials complying with the pending French GAP were 0.07 (3), 0.09, 0.10 (2), 0.11, 0.13 and 0.21 mg/kg. Some of these results were for the fruit without stone. The residues in the trials considered to comply with US GAP were 0.19, 0.25 (2), 0.28, 0.37, 0.46 and 0.51 mg/kg, corrected for average recoveries, in the fruit without stone.
The Meeting agreed that the US residues in apricots and peaches were mutually supportive and could be combined, giving residues in rank order of 0.12, 0.16, 0.19, 0.21, 0.25 (3), 0.27, 0.28, 0.37, 0.46 and 0.51 mg/kg. The Meeting noted that these results had been corrected for recovery and that the residues were in the fruit without stone, and estimated maximum residue levels of 0.5 mg/kg and STMRs of 0.25 mg/kg for fenbuconazole in peaches and apricots.
Plums (including prunes). GAP was originally reported for Israel and the USA, with pending GAP for France, but the Meeting was informed that the US GAP was actually pending. The maximum application rates are 0.002-0.0075 kg ai/hl in Israel and France and 0.105 kg ai/ha in the USA. PHIs are 0-14 days.
The residues in trials considered to comply with the pending French GAP were 0.05, 0.06, 0.07, 0.16, 0.20, 0.23, 0.27, 0.30, 0.36 and 0.38 mg/kg, and those in the trials complying with the pending US GAP were <0.01, 0.01, 0.02, 0.03 (2), 0.04 (2), 0.06 and 0.07 mg/kg. Three further residues were reported in dried prunes: 0.08, 0.14 and 0.16 mg/kg. All of the US results had been corrected for average recoveries and the residue was in the fruit without stone. As both the French and US GAP is pending, the Meeting could not estimate a maximum residue level.
Grapes. GAP was reported for France, Israel, Italy, Portugal, Spain and Turkey, and pending GAP for Greece. The maximum application rates are 0.002-0.0075 kg ai/hl or 0.03-0.04 kg ai/ha, with PHIs of 7-28 days.
The residues in the trials considered to comply with Italian and pending Greek GAP were 0.04 (2), 0.05 (2) and 0.17 mg/kg and those in the trials complying with French and Spanish GAP were 0.02, 0.05, 0.10, 0.12, 0.16, 0.2, 0.3 (3), 0.35, 0.4 (2) and 0.5 mg/kg. Since the French product labels specified a rate of 0.03-0.0375 kg ai/ha, the Meeting agreed that it was not appropriate to use four German trials in which the application rates were 0.056-0.075 kg ai/ha in the evaluation.
The Meeting estimated a maximum residue level of 1 mg/kg and an STMR of 0.3 mg/kg for fenbuconazole in grapes, based on the trials complying with French and Spanish GAP. Although the highest residue in the trials was only 0.5 mg/kg, the Meeting noted that there were several residues close to 0.5 mg/kg and that the median residue was relatively high.
Strawberries. GAP was reported for Israel. The maximum application rate is 0.075 kg ai/ha with a PHI of 14 days.
Only one trial was considered to comply with Israeli GAP, with a residue of 0.17 mg/kg. Although additional data were available from Spain, the climatic and agricultural practices were not considered to be comparable to those in Israel and these data have not been used in the evaluation. There were therefore insufficient data to estimate a maximum residue level.
Bananas. GAP was reported for Columbia, Costa Rica, Ecuador, Guatemala, Honduras, Mexico, Panama, Venezuela, Philippines and the USA. GAP in all of these countries was the same with a maximum application rate of 0.105 kg ai/ha and a PHI of 0 days.
The residues in the trials with bagged fruit considered to comply with GAP were <0.01 (4) and 0.01 mg/kg in pulp, <0.01 (4) and 0.03 mg/kg in peel, and <0.01 (3) mg/kg in whole fruit. Those in the trials with unbagged fruit which complied with GAP were 0.01 and 0.02 mg/kg in pulp, 0.09 mg/kg in peel, and <0.01 (3), 0.01 and 0.02 mg/kg in whole fruit. The Meeting estimated a maximum residue level of 0.05 mg/kg and an STMR of 0.01 mg/kg for bananas. Although only 6 trials were reported for bagged bananas, the Meeting considered that there were sufficient data to estimate a maximum residue level since all the residues were well below the practical limit of determination of 0.05 mg/kg.
Melons (except watermelons). GAP for melons was reported for France, Israel, Italy, Portugal and Turkey, and pending GAP for Spain and Morocco. The maximum application rates are 0.0375-0.2 kg ai/ha or 0.005-0.01 kg ai/hl. PHIs are 3-7 days. The Meeting was informed that the PHI in France was 7 days and not the 3 days reported in the original company submission.
The residues in trials considered to comply with Italian GAP were <0.005, 0.009, 0.02 and 0.05 mg/kg, and those in the trials complying with French GAP with a 7-day PHI were 0.02, 0.02 (2), 0.03, 0.07, 0.09, 0.1 and 0.13 mg/kg. The residues all appear to be within the same population and can be combined, giving <0.005, 0.009, <0.02, 0.02 (3), 0.03, 0.05, 0.07, 0.09, 0.1 and 0.13 mg/kg. The Meeting estimated a maximum residue level of 0.2 mg/kg and an STMR of 0.025 mg/kg for melons.
Watermelons. GAP was reported for Israel, Italy, Portugal, Spain and Turkey, and pending GAP for Morocco. The maximum application rates are 0.0375-0.2 kg ai/ha or 0.005 -0.01 kg ai/hl, with PHIs of 3 or 7 days. There is no French GAP for watermelons.
Only one trial was considered to comply with Italian GAP, with a residue of <0.005 mg/kg. There were insufficient data to estimate a maximum residue level.
Cucumbers. GAP was reported for Israel, Spain and Turkey, and pending GAP for France and Morocco. The maximum application rates are 0.0375-0.1 kg ai/ha or 0.005-0.01 kg ai/hl, with PHIs of 3 or 7 days.
One Spanish and two Italian field trials, all with residues of 0.02 mg/kg, and five indoor trials in Spain and Greece with residues of <0.01, 0.02, 0.03 (2) and 0.11 mg/kg were considered to comply with Spanish GAP. One trial in Israel complied with Israeli indoor GAP with a residue of 0.1 mg/kg.
The Meeting concluded that the residues in all the trials according to GAP were in a single population and agreed to combine them to give <0.01, 0.02 (4), 0.03 (2), 0.1 and 0.11 mg/kg. The Meeting estimated a maximum residue level of 0.2 mg/kg and an STMR of 0.02 mg/kg for cucumbers.
Summer squash (courgettes, zucchini). GAP was reported for Israel, Spain and Turkey, and pending GAP for France and Morocco. The maximum application rates are 0.0375-0.2 kg ai/ha or 0.005-0.01 kg ai/hl with PHIs of 3 or 7 days.
The residues in trials considered to comply with the pending French GAP were <0.02, 0.03, 0.03 and 0.08 mg/kg; the trial with the residue of 0.03 mg/kg also complied with Turkish GAP. The residues from trials complying with the pending Moroccan GAP were <0.02, 0.03, 0.04, 0.04. 0.06 and 0.08 mg/kg. Because French and Moroccan GAP is pending the Meeting could not use the results to estimate a maximum residue level.
The outdoor trials considered to comply with Spanish GAP showed residues of <0.01 (2), 0.01, <0.02 (3) and 0.02 mg/kg. Some of these trials were also considered to comply with Israeli GAP. The Meeting estimated a maximum residue level of 0.05 mg/kg and an STMR of 0.02 mg/kg for summer squash, based on Spanish GAP.
Tomatoes. GAP for Israel was reported as 0.0075 kg ai/hl (glasshouse) and 0.05 kg ai/ha (field) with PHIs of 7 days in both cases. Pending GAP for Morocco is 0.01 kg ai/hl with a PHI of 3 days for both field and glasshouse applications.
The residues in trials considered to comply with the pending Moroccan GAP were 0.02, 0.03 (2), 0.05 (2), 0.08, 0.10, 0.13, 0.14, 0.16, 0.18, 0.31 and 0.38 mg/kg, but as the GAP was pending the Meeting could not use them to estimate a maximum residue level.
The residues in trials which complied with Israeli glasshouse GAP were 0.08, 0.19 and 0.21 mg/kg and in those complying with the field GAP 0.02 and 0.02 (2) mg/kg.
The Meeting agreed that the Israeli glasshouse use appeared to lead to higher residues than the field use. Since only three trials were available for each of these uses, the Meeting concluded that there were insufficient data to estimate a maximum residue level.
Peppers. GAP was reported for Israel (field use only), and pending GAP for Morocco. The maximum application rates are 0.0075 and 0.01 kg ai/hl, with PHIs of 7 and 3 days respectively.
The residues in field trials which complied with the pending Moroccan GAP were 0.02 and 0.10 mg/kg and in glasshouse trials 0.18, 0.20, 0.29, 0.38 and 0.41 mg/kg. The glasshouse use appeared to lead to higher residues, but as the GAP was pending the Meeting could not use the results to estimate a maximum residue level.
Two trials in Italy and Spain complied with Israeli GAP, but the Meeting agreed that the climatic conditions and agricultural practices in Italy and Spain could not be equated with those in Israel. There was therefore no basis on which the Meeting could estimate a maximum residue level.
Egg plant. GAP was reported only for Morocco, and only one residue trial was reported which complied with it. There were insufficient data to estimate a maximum residue level.
Sugar beet. GAP was reported for Italy and pending GAP for the USA. The maximum application rates are 0.1 and 0.14 kg ai/ha with PHIs of 14 days.
The residues in the trials which complied with US GAP were <0.01, 0.02 (3), 0.03 (3), 0.04, (4), 0.06, 0.07 (2), 0.08, 0.09 and 0.20 mg/kg in the roots and 0.51, 0.55, 0.80, 0.85, 0.95, 1.0, 1.2, 1.2, 1.4, 2.6 (2), 3.1, 4.2, 4.5, 5.0 and 8.9 mg/kg in the tops. As the GAP was pending the Meeting could not estimate a maximum residue level from these trials.
Only two trials complied with Italian GAP, with residues in the roots of 0.02 and 0.03 mg/kg. There were insufficient data to estimate a maximum residue level.
Wheat. GAP was reported for Belgium, France, Germany, Israel, Morocco, Portugal, South Africa and the UK, and pending GAP for the USA. The maximum application rates are 0.07-0.125 kg ai/ha with PHIs of 35-90 days or expressed as "before beginning of flowering growth stage 59".
The residues in trials which complied with the pending US GAP were 0.005, 0.007, <0.01 (17), 0.01 (3), 0.02 (3) mg/kg in the grain and <0.05 (2), 0.08, 0.10, 0.11, 0.12, 0.23, 0.27, 0.28, 0.41, 0.45, 0.57, 0.58, 0.70, 0.75, 0.76, 0.77, 0.80, 1.4 (2), 1.6, 1.9, 2.4, 3.0 and 4.5 mg/kg in the straw. A number of other US trials complied with the pending GAP, but the samples were stored for 3.5-4 years before analysis. Since data on storage stability indicated that fenbuconazole residues were stable in wheat for at least 36 months the Meeting agreed to regard these results as valid, but emphasized that the storage of trial samples for long periods before analysis was undesirable. As the GAP was pending however the results could not be used to estimate a maximum residue level.
The residues in trials which complied with German GAP were 0.02 (9) and 0.06 mg/kg in the grain and 0.14, 0.17, 0.27, 0.41, 0.51, 0.61, 0.84, 0.91, 1.0, 1.3 and 2.5 mg/kg in the straw.
The residues in trials which complied with Portuguese GAP were 0.01 (3) and <0.02 (3) mg/kg in the grain. The straw was not analysed.
The residues in trials which complied with UK GAP were <0.02 (5), <0.02* (7) and 0.06* mg/kg in the grain and 0.11*, 0.17*, 0.39*, 0.75*, 0.79, 0.85, 0.89*, 0.95*, 1.05* and 1.26* mg/kg in the straw. The residues marked with an asterisk were from trials which also complied with German GAP.
The Meeting agreed that the residues in the trials according to German, UK and Portuguese GAP appeared to be from the same population of data and could be combined to give <0.01 (3), <0.02 (17) and 0.06 mg/kg in the grain and 0.14, 0.17, 0.27, 0.41, 0.51, 0.61, 0.79, 0.84, 0.85, 0.91, 1.0, 1.3 and 2.5 mg/kg in the straw. The Meeting estimated maximum residue levels of 0.1 mg/kg for wheat grain and 3 mg/kg for straw, and STMRs of 0.02 mg/kg for grain and 0.79 mg/kg for straw.
Barley. GAP was reported for France, Germany, South Africa and the UK. The maximum application rates are 0.072-0.125 kg ai/ha with PHIs of 35-45 days or expressed as "before beginning of flowering growth stage 59".
The residues in trials which complied with German GAP were <0.02, 0.03 (5), 0.04, 0.05, 0.08, 0.09 and 0.14 mg/kg in the grain, and 0.21, 0.25, 0.28, 0.35, 0.55, 0.56, 0.68, 1.2, 1.7, 1.9 and 2.1 (2) mg/kg in the straw. Those from trials complying with UK GAP were <0.02 (2), <0.02*, 0.02*, 0.03 (3), 0.03* (2), 0.04 and 0.04* (3) mg/kg in the grain and 0.17*, 0.27*, 0.44*, 0.55, 0.55*, 0.67, 1.13*, 1.2, 1.8, 2.1*, 2.07*, 2.2 and 2.4 mg/kg in the straw. The residues marked with an asterisk were from trials which also complied with German GAP.
The Meeting agreed that the results of the UK and German trials could be combined to give 0.02 (3), 0.03 (8), 0.04 (2), 0.05, 0.08, 0.09 and 0.14 mg/kg in the grain and 0.21, 0.25, 0.28, 0.35, 0.55 (2). 0.56, 0.67, 0.68, 1.2 (2), 1.7, 1.8, 1.9, 2.1 (2), 2.2 and 2.4 mg/kg in the straw. The Meeting estimated maximum residue levels of 0.2 mg/kg for barley grain and 3 mg/kg for straw, and STMRs of 0.03 mg/kg for grain an 0.94 mg/kg for straw.
Maize. GAP was reported to be pending in France, with an application rate of 0.075 kg ai/ha and a PHI of 45 days.
The residues in trials which complied with the pending French GAP were <0.02 (5) mg/kg in maize ears and 0.10, 0.12, 0.15, 0.21, 0.26 (2) and 0.27 mg/kg in the fodder. As the GAP was pending the Meeting could not estimate a maximum residue level.
Rye. GAP was reported for Germany, with an application rate of 0.075 kg ai/ha and a PHI of 35 days.
The residues in trials which complied with German GAP were 0.02 and 0.03 mg/kg in the grain, and 0.49 and 1.4 mg/kg in the straw. The Meeting concluded that the residues in wheat grain, resulting from similar GAP, could be used to support those in rye and estimated a maximum residue level of 0.1 mg/kg and an STMR of 0.02 mg/kg for rye grain.
Triticale. Two trials were reported, but there was no information on GAP.
Almonds. GAP was reported for Israel and pending GAP for the USA, with application rates of 0.004 kg ai/hl and 0.105 kg ai/ha and PHIs of 160 and 14 days.
The residues in trials which complied with the pending US GAP were <0.01 (5) in the kernels and 0.13, 0.45, 0.51 and 0.77 mg/kg in the hulls. As the GAP was pending the Meeting could not estimate a maximum residue level or an STMR for almonds or almond hulls.
Pecans. GAP was reported for the USA, with an application rate of 0.14 kg ai/ha and a PHI of 28 days.
The residues in ten trials which complied with US GAP were all <0.01 mg/kg in pecan kernels. The Meeting estimated a maximum residue level of 0.05* mg/kg and an STMR of 0.01 mg/kg for pecans.
Oilseed. GAP for sunflowers was reported only for France. The application rate is either 0.060 or 0.075 kg ai/ha depending on the product, with a PHI of 80 days.
The residues in the seed in trials on sunflowers which complied with French GAP were <0.01 and <0.02 (5) mg/kg. Residues in two further trials with a shorter PHI (34 days) were all <0.02 mg/kg. The Meeting estimated a maximum residue level of 0.05* mg/kg and an STMR of 0.02 mg/kg for sunflower seed.
GAP for rape was also reported only for France, with an application rate of 0.060 kg ai/ha and a PHI of 30 days or 0.075 kg ai/ha and a PHI of 45 days.
The residues in two trials on rape which complied with French GAP were both <0.05 mg/kg. In two other trials with longer PHIs the residues were also <0.05 mg/kg. The Meeting took into account the data on sunflower seed in which no measurable residues were found and estimated a maximum residue level of 0.05* mg/kg and an STMR of 0.05 mg/kg for rape seed.
Animal products. Animal transfer studies were carried out on dairy cattle and hens. Cattle dosed at a level equivalent to 6.5 ppm in the feed, showed total fenbuconazole residues of 0.01 mg/kg in one sample of muscle and up to 0.09 mg/kg in 3 samples of liver. No quantifiable residues were found in the milk, fat or kidney. At a dose level equivalent to 19.5 ppm in the feed the only residues were 0.02 mg/kg in one sample of milk and 0.1-0.2 mg/kg in three samples of liver.
In hens dosed at the equivalent of 0.12, 0.34 or 1.13 ppm in the feed, all the residues in eggs and tissues were below the limit of determination.
The highest residues in fodder crops from trials which complied with GAP were 4.5 mg/kg in wheat straw, 2.1 mg/kg in barley straw, 1.4 mg/kg in rye straw, 0.8 mg/kg in almond hulls and <0.05 mg/kg in rape seed.
Assuming maximum incorporation rates of straw (the feed item with the most significant residues) of 20 and 50% for dairy and beef cattle respectively, the maximum feed intakes will be approximately 1 ppm and 2.5 ppm in the diet. Residues would be expected to be below a limit of determination of 0.05* mg/kg in all cattle products except liver. The Meeting estimated maximum residue levels of 0.05* mg/kg for cattle meat, cattle fat, cattle milk and cattle kidney and 0.05 mg/kg for cattle liver. The Meeting agreed that the STMR should be zero for those cattle commodities in which no measurable residues were found at the equivalent of 6.5 ppm or 19.5 ppm in the diet in the cow feeding studies. Accordingly, the Meeting estimated STMRs of 0.01 mg/kg for cattle meat, milk and liver and 0 mg/kg for cattle kidney and fat.
In poultry, the highest residues would arise from barley grain in which residues were <0.02-0.14 mg/kg. Since cereal grains can constitute up to 70% of the diet the maximum feed intakes will be approximately 0.1 ppm in the diet. The Meeting estimated a maximum residue level of 0.05* mg/kg for poultry fats, poultry meat, edible offal of poultry, and eggs. The Meeting agreed that the STMR should be zero for those poultry commodities in which no measurable residues were found at the equivalent of 1.13 ppm in the diet in the poultry feeding studies. Accordingly, the Meeting estimated an STMR of 0 mg/kg for poultry fats, meat, edible offals, and eggs.
The Meeting agreed not to estimate STMR-Ps for the processed products of apples, peaches or sugar beet since only single samples had been processed on a laboratory scale and the initial residues were low. The Meeting estimated STMR-Ps for wine and grape juice of 0.018 mg/kg (0.3 x 0.06) and 0.03 mg/kg (0.3 x 0.1) respectively. The Meeting also estimated STMR-Ps for bread, flour and bran of 0.0092 mg/kg (0.02 x 0.46), 0.005 mg/kg (0.02 x 0.25) and 0.052 mg/kg (0.02 x 2.6) respectively.
No monitoring data were provided but national MRLs were reported for the USA and several European countries.
Before MRLs can be recommended for the commodities for which GAP is pending confirmation that each proposed GAP has been registered will be required, together with copies of the product labels.
FURTHER WORK OR INFORMATION
Desirable
1. The method of analysis used for the determination of fenbuconazole in soil and water in the studies of environmental fate.2. Data on residues in food in commerce or at consumption (i.e. monitoring or total diet data).
