CARBENDAZIM JMPR 1976 Explanation This pesticide was evaluated by the 1973 Joint Meeting (FAO/WHO, 1974b). The data were not considered adequate for the estimation of an acceptable daily intake for man and the following studies were required. (1) Long term studies to investigate chronic toxicity and carcinogenicity. (2) Reproduction and teratogenicity studies. (3) Metabolism and distribution studies in several species. (4) Elucidation of the effect in the liver of female rats and dogs. These studies have not been provided, and further evaluation for the estimation of an acceptable daily intake was not possible. Some further information on the occurrence and fate of residues and on methods of analysis which has become available since the 1973 Meeting is evaluated in this monograph addendum. RESIDUES IN FOOD AND THEIR EVALUATION RESIDUES RESULTING FROM SUPERVISED TRIALS New residue data derived from supervised trials with fruits, vegetables and individual industrial crops have been presented from various sources. Most of the residues fall within the ranges described in the earlier monograph (FAO/WHO, 1974b), and the data therefore give further support to the guideline levels already recorded. Lettuce Special mention should be made of the data on carbendazim applications to lettuce grown during the winter season in greenhouses (Netherlands, 1976). The residue data presented in Table 1 indicate that up to 2 months may be required before carbendazim residues fall below 5 mg/kg when application is at the rate of 4 kg/ha. This situation was dealt with in greater detail by the 1975 Meeting in the evaluation of benomyl (FAO/WHO, 1976b) and on the basis of the information then available the guideline level of 5 mg/kg for benomyl, calculated as carbendazim, was recorded. Unless carbendazim can be applied at lower dosage rates and the usual trimming prior to marketing is effective in removing the bulk of the residue, the level of 5 mg/kg would not be adequate to cover residues resulting from the direct application of carbendazim, even with a very long pre-harvest interval. The Meeting considered that it could not record a limit high enough to cover residues of the order indicated in Table 1. It was agreed that the guideline level of 5 mg/kg recorded by the 1975 Meeting for benomyl in lettuce and applying to total residues of benomyl, carbendazim and 2-aminobenzimidazole, expressed as carbendazim, should be retained. Animal feedstuffs New information on carbendazim residues in wheat (Netherlands, 1976) and peanuts (Snelson, 1976) are summarized in Table 2. This supplements earlier data and confirms the previous guideline level of 0.1 mg/kg (at or about limit of determination) for raw cereals. Amendments, however should be made to include peanut hulls and hay and wheat straw for animal feeding purposes. FATE OF RESIDUES In plants and soil There is a continued interest in the behaviour of carbendazim and other benzimidazole fungicides in general plant metabolism. Rouchaud and co-workers (1974) confirmed the rapid uptake and translocation of carbendazim following the application of either carbendazim or benomyl) into the leaves of melon plants. Leroux & Gredt (1975) from work with maize plants, suggest that carbendazim is taken up in its non-ionic form, and they show that the maximum absorption is at the base rather than the apex of the roots. In the studies of Rouchaud et al. (1974) 7 metabolites were identified from non-radioactive benomyl, namely: carbendazim, 2-aminobenzimidazole, benzimidazole, o-aminobenzonitrile, aniline and B-glycosidic conjugates of carbendazim and of 2-aminobenzimidazole. The presence and rate of degradation of carbendazim in soils were investigated by van Wambeke & van Assche (1976) in a well designed 4-factor experiment to study the effects of soil composition, microbiological activity, moisture content and temperature. All of these greatly affect the degradation and their influence is illustrated by the findings that only 0.1% of the applied dosage of carbendazim was recovered after 126 days in a humid. organic soil kept at 23°C, while about 60% was recovered from a dry sandy soil, which was steam sterilized and kept at 10°C for the same period. Carbendazim is ionized by both acids and bases, and this affects its behaviour in soils. Aharonson & Kafkafi (1975a) have shown that acidity increases the absorption of carbendazim to soil particles and thereby hinders leaching. These authors also confirm the increased rate of degradation of carbendazim by increased humidity of the soil. TABLE 1. Carbendazim residues on greenhouse (winter) lettuce, Netherlands Treatment Dosage Time after Residues, mg/kg, last application, mean (range) days Exp. 1 Exp. 2 Spraying 4 kg/ha 11 - 31 (25-36) (W.P. 47%) 20 - 19.5 (11-24) 27 - 10 (9-11.5) 32/34 17.9 (13-28) 6.5 (1.8-11.5) 41 8.2 (5-12) - 53 6.5 (4-8.5) - 62 0.9 (0.5-1.2) - TABLE 2. Carbendazim residues in wheat and peanuts Country Application Days after Residues, mg/kg and last Crop Rate, treatment Straw/ kg/ha No. Kernels hay Hulls Netherlands 0.15 2 52 <0.1 <0.1 3 50-51 <0.1-<0.1 <0.1-<0.1 0.24 1 48-120 <0.1-<0.1 <0.1-<0.1 3 50-51 <0.1-<0.1 <0.1-<0.1 0.3 2 15-54 <0.1 0.15 0.5 1 54 - <0.1 Australia 0.3 5 28 <0.1 2.0 <0.2 Peanuts TABLE 3. Residues of carbendazim (including benomyl) in imported samples (Sweden)o) Crop Number of samples containing .....mg/kg+) 0.1 0.1-0.5 0.6-2.0 2.1-5.0 Apples 101 18 6 2 Grapes 2 Oranges 32 1 1 Peaches 5 Pears 6 Potatoes 18 Strawberries 15 3 3 Total 213 samples o) = February 1973 - July 1975 +) = Calculated as benomyl Residues in food in commerce or at consumption Earlier reports from Belgium and the Netherlands on market sample surveys for benzimidazole fungicides have been described in a previous monograph on benomyl (FAO/WHO, 1976b) they are of equal interest in connection with carbendazim. A Further survey has now been reported from Sweden, covering a total of 213 samples of imported fruit (Table 3). This survey gave broadly similar results, indicating that quantifiable residues of carbendazim may be found in about 25% of imported apples and strawberries at the time of marketing. Significant residues were also found in two of 34 samples of oranges. METHODS OF RESIDUE ANALYSIS As in the case of other benzimidazole fungicides (FAO/WHO, 1976b), the greatest interest recently has been concerned with two problems, namely the efficiency of extraction from crops and soils and the selective determination of benzimidazole compounds, especially by means of high speed or high-performance liquid chromatography. In addition, a recent report on the gas-liquid chromatography of carbendazim after trifluoroacetyl derivatization has been published (Rouchaud and Decallonne, 1974). Valuable reviews have been published on these subjects by Austin et al. (1975), Baker & Hoodless (1974), Gorbach (1976), Watkins (1976) and others. For the final determination of carbendazim, UV-spectrophotometry still seems to be the preferred method of measurement. This method when combined with partition clean-up offers an adequate sensitivity for most routine purposes (Gorbach, 1976). In the recently published methods based on high speed liquid chromatography (Maeda & Tsuji, 1976) and gas liquid chromatography (Rouchaud & Decallonne, 1974) the limit of detection is given as 0.02 mg/kg. NATIONAL TOLERANCES REPORTED TO THE MEETING Table 4 lists national tolerances reported to the Meeting. They are additional to those reported previously with the exception of the Netherlands tolerance "Grain (raw) 0.1 mg/kg" which replaces the earlier provisional tolerance "Raw cereals 0.5 ppm". TABLE 4. National tolerances reported to the Meeting Tolerance, Country Crop mg/kg Netherlands Citrus 3.5 Grain (raw) 0.1 Potatoes 0.05 New Zealand Fruits 5 Vegetables 2 Cereals 1 APPRAISAL This compound was evaluated by the 1973 Joint Meeting and guideline levels for a number of commodities were recommended. Since then new data have become available, partly in response to earlier requests and partly as supplementary information which supports the earlier recommendations. Data have been presented from supervised trials on carbendazim treatments of greenhouse lettuce grown during the winter season. The rate of decline of residues was so slow that even 50 days after treatment the mean residue was above the guideline level of 5 mg/kg previously recorded for benomyl but applying to total residues of benomyl, carbendazim and 2-aminobenzimidazole. The Meeting considered that it could not record a guideline level high enough to cover residues resulting from such a use of carbendazim. In view of the earlier evaluation of data on carbendazim and other benzimidazole fungicides, it confirmed the guideline level of 5 mg/kg for benomyl. On the basis of new information, recommendations can be made for guideline levels in certain peanut products and in straw of wheat. In the course of general studies on the fate of benzimidazole fungicides, a rapid uptake and translocation of carbendazim residues into plants has been confirmed. The behaviour and degradation of carbendazim residues in soils has been further described. In response to the request of the 1973 Meeting, information on market sample surveys made in Belgium, the Netherlands and Sweden has been presented to this and to the 1975 meeting. The data indicate that residues of benzimidazole fungicides, presumably including carbendazim, may be present in up to about 25% of a number of fruits. vegetables and berries. Residues in positive samples were generally low and only in occasional samples approached guideline levels. Spectrophotometric, gas chromatographic and high-performance liquid-chromatographic methods are now available for the determination of carbendazim in various commodities. A full validation of methods for regulatory purposes still seems to be lacking. EVALUATION The following guideline levels, additional to those of 1973, are recorded. Commodity Guideline level, mg/kg Peanut 0.1 Peanut hull 0.2 Peanut hay, wheat straw 2 FURTHER WORK OR INFORMATION Required (before an acceptable daily intake can be estimated and maximum residue limits can be recommended) 1. Long-term studies to investigate chronic toxicity and carcinogenicity. 2. Reproduction and teratogenicity studies. 3. Metabolism and distribution studies in several animal species. 4. Elucidation of the effect on the liver in female rats and dogs. 5. Information on the nature and level of residues in meat, milk and eggs after feeding animals on crops or feedstuffs treated with carbendazim. Desirable 1. Further studies to define the apparent "high-level" effects on male reproductive organs. 2. Validation of methods of residue analysis for regulatory purposes. REFERENCES Aagren, O. Residue data and other information on Benomyl and 1976 carbendazim submitted by the Swedish Codex Secretariat. Letter no. 308/76 of July, 30. Aharonson, N. & Kafkafi, U. Adsorption of Benzimidazole 1975a fungicides on montmorillonite and kaolinite clay surfaces. J. agr. Fd Chem. 23, 434-437. Aharonson, N. & Kafkafi, U. Adsorption, mobility and persistence of 1975b thiabendazole and methyl-2-benzimidazole-carbamate in soils. J. agr. Fd Chem. 23, 720-724. Austin, D.J., Briggs, G.G. & Lord, K.A. Problems in the assay 1975 of residues of carbendazim and its precursors. Proc. 8th Brit. Insec. Fung. Conf., Brighton, November. Baker, P.B. and Hoodless, R.A. Analytical methods for the detection 1974 and determination of residues of systemic fungicides. Pestic. Sci., 5: 465-472. FAO/WHO. 1973 Evaluations of some pesticide residues in Food. 1974 FAO/AGP/1973/M/9/1. WHO Pesticide Residues Series, No. 3. Gorbach, S. Review on the residue analysis of the systemic 1976 fungicides benomyl, carbendazim, thiophanate, thiophanatemethyl and thiabendazole. Paper presented to the International Union of Pure and Applied Chemistry (IUPAC). 36 pages. Analytical Laboratory, Hoechst, Germany. Leroux, P. & Gredt, M. Absorption of methylbenzimidazole- 1975 2-yl-carbamate (carbendazim) by corn roots. Pestic. Biochem. Physiol. 5, 507-514. Maeda, M. & Tsuji, A. Determination of benomyl and 2 1976 (4-thiazolyl) benzimidazole in plant tissues by high-performance liquid chromatography using fluorometric detection. J. Chromat. 120, 449-455. Netherlands. Carbendazim residue data submitted by the Nation 1976 al Codex Committee of the Netherlands. Staatstoezicht op de Volksgezondheid, September 28. New Zealand. Information received from the National Codex 1976 Committee of New Zealand. Rouchaud, J.P. & Decallonne, J.R. A gas chromatographic method 1974 for the analysis of MBC in plants and soil. J. agr. Fd Chem. 22, 259. Rouchaud, J.P., Decallonne, J.R. & Meyer, J.A. Metabolic Fate of 1974 methyl-2-benzimidazole carbamate in melon plants. Phytopathology, 64, 1513-1517. Snelson, J.T. Australian Residue data submitted through the 1976 National Codex Committee of Australia. Van Wambeke, E. & van Assche, C. The importance of some factors 1976 involved with the persistence of carbendazim (MBC) in soil. Report presented at the 28th International Symposium on Crop Protection in Gent, May 4, 1976. Watkins, D.A.M. Benzimidazole Pesticides: Analysis and 1976 Transformations. Pestic. Sci. 7, 184-192.
See Also: Toxicological Abbreviations Carbendazim (EHC 149, 1993) Carbendazim (HSG 82, 1993) Carbendazim (ICSC) Carbendazim (WHO Pesticide Residues Series 3) Carbendazim (Pesticide residues in food: 1977 evaluations) Carbendazim (Pesticide residues in food: 1978 evaluations) Carbendazim (Pesticide residues in food: 1983 evaluations) Carbendazim (Pesticide residues in food: 1985 evaluations Part II Toxicology) Carbendazim (Pesticide residues in food: 1995 evaluations Part II Toxicological & Environmental) Carbendazim (Pesticide residues in food: 1995 evaluations Part II Toxicological & Environmental) Carbendazim (JMPR Evaluations 2005 Part II Toxicological)