WORLD HEALTH ORGANIZATION FOOD AND AGRICULTURE ORGANIZATION ORGANISATION MONDIALE DE LA SANTE ORGANISATION POUR L'ALIMENTATION ET L'AGRICULTURE VBC/DS/82.52 Rev.1 ORIGINAL: ENGLISH DATA SHEETS ON PESTICIDES No. 52 BENDIOCARB It must be noted that the issue of a Data Sheet for a particular pesticide does not imply endorsement of the pesticide by WHO or FAO for any particular use, or exclude its use for other purposes not stated. While the information provided is believed to be accurate according to data available at the time when the sheet was compiled, neither WHO nor FAO are responsible for any errors or omissions, or any consequences therefrom. The issue of this document does Ce document ne constitue pas une not constitute formal publication. Il ne doit faire publication. It should not be l'objet d'aucun compte rendu ou reviewed, abstracted or quoted résumé ni d'aucune citation sans without the agreement of the l'autorisation de l'Organisation Food and Agriculture des Nations Unies pour Organization of the United l'Alimentation et l'Agriculture Nations or of the World Health ou de l'Organisation Mondiale de Organization. la Santé. CLASSIFICATION: Primary use: Insecticide Secondary use: Molluscicide, Nematicide Chemical group: Carbamate Date issued: 1. GENERAL INFORMATION 1.1 COMMON NAME: Bendiocarb (BSI, ISO) 1.1.1 Identity: IUPAC: 2,3-isopropylidene-dioxyphenyl methyl carbamate No. 1: Carbamic acid, methyl, 2,3-(dimethylmethylenedioxy) phenyl ester Reg. No.: 22781-23-3 Molecular formula: C11H13NO4 Molecular weight: 223.25 Structural formula: 1.1.2 Synonyms: Ent-27695; FicamR; GarvoxR; MultamatR; NC 6897; Niomil 3GR; OMS 1394; SeedoxR; TatooR; TurcamR 1.2 SYNOPSIS: Bendiocarb is a broad spectrum, carbamate pesticide; a fast acting anti-cholinesterase agent with effective contact and stomach action. It does not emit toxic vapours at normal working temperatures. Moderately toxic to mammals, it is rapidly metabolized with immediate loss of toxicity. Bendiocarb is a weak plant systemic with excellent residual and knockdown properties. 1.3 SELECTED PROPERTIES 1.3.1 Physical properties The pure compound is a white crystalline solid with a melting point of 132°C. Bendiocarb is an odourless and non-corrosive compound. 1.3.2 Solubility (25°C) 0.04 g/1 water 0.35 g/1 hexane 0.30 g/1 kerosine 10.0 g/1 trichloroethylene 10.0 g/1 O-xylene 40.0 g/1 benzene 40.0 g/1 ethanol 200.0 g/1 acetone 200.0 g/1 chloroform 200.0 g/1 dichloromethane 200.0 g/1 dioxane 300.0 g/1 glycerol 1.3.3 Stability Formulated material (80%) is stable at temperatures below 40°C. In aqueous solution at 25°C the half-life is 48 days at ph 5; 81 hours at ph 7; and 45 minutes at ph 9. Under ph 5 bendiocarb slowly degrades to pyrogallol and acetone. On non-absorptive surfaces and at low humidity it resists oxidation. It undergoes photo-oxidation in direct sunlight. 1.3.4 Vapour pressure 0.667 x 10-6 kPa (5 x 10-6 mmHg) at 25°C. 1.4 AGRICULTURE, HORTICULTURE AND FORESTRY 1.4.1 Common formulations Wettable powders (800, 500 and 200 g a.i./kg); granules for soil and turf treatment (30, 50 and 100 g a.i./kg); dust (10 g a.i./kg); suspension concentrate (500 g a.i./1) for spray or seed treatments; suspension in oil for ULV application (250 g a.i./1; residual sprays, paint on and granular preparations with bait. 1.4.2 Susceptible pests Bendiocarb is effective against a wide range of soil, foliar and stored product pests and ectoparasites of domestic animals. The pests controlled include insects and other arthropods. 1.4.3 Use pattern Bendiocarb may be applied as a soil treatment (300-2000 g a.i./ha); as a seed treatment (1-10 g a.i./kg); as a residual spray (100-1000 g a.i./ha); and, as a ULV spray (50-500 g a.i.,/ha). 1.4.4 Unintended effects Bendiocarb is toxic to some beneficial organisms such as bees and predators of plant pests. 1.5 PUBLIC HEALTH PROGRAMMES 1.5.1 Common formulations See paragraph 1.4.1 above. 1.5.2 Pests mainly controlled Bendiocarb is effective against a wide range of nuisance and disease vector pests; ants, bed bugs, mosquitos, cockroaches, domestic flies, fleas, lice (with ovicidal effects), millipedes, scorpions, spiders, wasps, and other arthropods, molluscs and nematodes. (Some carbamate-resistant cockroach strains may be resistant to bendiocarb on a very limited scale.) 1.5.3 Use pattern The 80% WP should be applied by professional applicators, it should not be directly applied to humans or food stuffs. It may be used safely in houses, public buildings (restaurants, hotels, hospitals and schools); in industrial buildings; and in aircraft and other craft. Provided the manufacturer's instructions are followed and high pressure sprays are avoided, there is little risk of contaminating people, food, or food utensils. 1.6 HOUSEHOLD USE Bendiocarb is available in less concentrated formulations suitable for home use as in section 1.5 above, and in aerosols, ready-to-use liquids, dusts, etc. 2. TOXICOLOGY AND RISKS 2.1 TOXICOLOGY - MAMMALS 2.1.1 Absorption route Bendiocarb may be absorbed from the gastrointestinal tract or to a limited extent through the intact skin. Low vapour pressure makes inhalation unlikely except from airborne spray mist. 2.1.2 Mode of action Bendiocarb acts through inhibition of cholinesterase activity which is rapidly reversible, the half-life of the inhibited enzyme is approximately 30 minutes. 2.1.3 Excretion products Bendiocarb is readily conjugated and metabolized by liver microsome enzymes, it is rapidly excreted, mainly as sulfate and beta-glucuronide conjugates of the phenol derivative. 2.1.4 Toxicity, single dose Oral LD50: Rat (M) 40-156 mg/kg b.w. (unformulated compound) 143-179 mg/kg b.w. (80% a.i. water dispersable powder) Dermal LD50: Rat (M), > 566 mg/kg b.w. (unformulated compound) > 1000 mg/kg b.w. (80% a.i. liquid formulation) 2.1.5 Toxicity, repeated doses Oral: There was no evidence of any treatment-related effect in hamsters fed diets containing up to 500 ppm bendiocarb for at least 30 days. This information was supplied by the manufacturing company. Dermal: In a 21-day dermal toxicity study in rats treated with a 40% aqueous suspension of the 80% wettable powder formulation at up to 800 mg a.i./kg, no macroscopic pathology or histological evidence of dermal irritation was detected and no treatment-related mortality occurred. This information was supplied by the manufacturing company. Inhalation: No signs of toxicity nor cholinesterase inhibition were observed in cats exposed for 33 days in a room treated with bendiocarb (200 mg/m2). Cumulation of compound: Bendiocarb is non-cumulative in mammalian tissues. Cumulation of effect: No evidence of cumulative toxicity was found in rat and dog 90-day dietary studies. 2.1.6 Dietary studies Short-term: See 2.1.5 above. No lasting signs of toxicity were reported in the above-mentioned 90-day studies. Long-term: Two-year feeding studies with bendiocarb in rats and dogs indicate that the principal treatment-related effects resulted from inhibition of cholinesterase activity. In the dog comprehensive histopathological examination showed no abnormality associated with the treatment and a no-effect level of 20 ppm (0.6- 0.7 (mg/kg b.w.)/day) was established. In the rat the no-effect level was 10 ppm (0.34-0.42 (mg/kg b.w.)/day). (See also 2.1.7 below.) This information was supplied by the manufacturing company. 2.1.7 Supplementary studies of toxicity:1 Carcinogenicity: In a two-year chronic oral and carcinogenicity study in rats dietary levels of up to 200 ppm were without effects on the tumour profile. A carcinogenicity study in mice at levels of up to 1250 ppm indicated no treatment-related histopathological alterations in any tissues. Teratogenicity: Bendiocarb was not found to be teratogenic in either the rat or the rabbit. Mutagenicity: No evidence of mutagenic potential was found in a mitotic non-disjunction study on Aspergillus nidulous nor in two microbial assay studies using Bacillus subtilis and Salmonella typhimurium strains. In a dominant lethal study in rats there was no indication that bendiocarb produced any dominant lethal mutations in the male germ cells.1 Reproduction: Various reproduction studies indicated that bendiocarb has no adverse effects upon fertility or reproductive function. This information was supplied by the manufacturing company. Neurotoxicity: Bendiocarb shows no irreversible or delayed neurotoxic effects.1 1 This information was supplied by the manufacturing company. Other: Technical bendiocarb and its commercial formulations are not skin irritants. Contamination of the eye with technical or formulated bendiocarb may cause temporary miosis and no more than mild, temporary irritation.1 2.1.8 Modification of toxicity No published information available. 2.2 TOXICOLOGY - MAN 2.2.1 Absorption The dermal route is the main route of absorption, and inhalation of dust or fine spray mist may also be possible routes. 2.2.2 Dangerous doses The threshold dose for blood cholinesterase inhibition and mild symptoms lies between 0.15 and 0.20 mg a.i./kg, for the oral route, the latter dosage having been rapidly followed by mild vertigo, nausea and sweating. Regression of these effects was advanced 0.5 hours after dosing and complete within 4 hours. Repeated ingestion of 0.1 mg a.i./kg at hourly intervals was without symptoms. This information was supplied by the manufacturing company. 2.2.3 Observations on occupationally exposed workers The safety of bendiocarb when used as a residual mosquito adulticide has been evaluated in both Iran and Indonesia - the latter trial being undertaken in conjunction with the WHO Vector Biology and Control Research Unit. Both studies were organized along the lines of a WMO expanded Stage V evaluation programme. Very few spraymen reported any adverse effects and where such effects were reported the symptoms were both mild and transient. No complaints were made by the villagers. This information was supplied by the manufacturing company. 2.2.4 Observations on exposure of the general public No information available. The public should not be exposed to hazardous amounts of bendiocarb due to its poor persistence in plant and animal tissues and provided proper treatment precautions are followed. 1 This information was supplied by the manufacturing company. 2.2.5 Observations on volunteers Oral administration of bendiocarb to human volunteers showed that man and the rat are equisensitive to the pesticide. The onset of signs of cholinesterase inhibition and the recovery from the toxic effects were both very rapid. 2.2.6 Reported mishaps No cases of bronchospasm due to inhalation of bendiocarb have been reported, nor has any other specific localized response to bendiocarb contamination. There have been no confirmed cases of dermal irritancy, allergic response or hypersensitivity of any type due to bendiocarb or its formulations during development and commercial use. Three cases of deliberate poisoning by ingestion are known, two were fatal. One accidental poisoning by ingestion, possibly from a contaminated drinking-mug, occurred during a spray programme in Indonesia in 1981. This information was supplied by the manufacturing company. 2.3 TOXICITY - NON-MAMMALIAN SPECIES 2.3.1 Fish Bendiocarb is toxic to fish. The range of LC50 for several species is 0.7-1.76 mg a.i./1. 2.3.2 Birds Bendiocarb is toxic to birds, it does not affect the reproductive performance of avian species. This information was supplied by the manufacturing company. Oral LD50: Mallard duck, 3.1 mg a.i./kg b.w. Bobwhite quail, 19.0 mg a.i./kg b.w. Japanese quail, 16.0 mg a.i./kg b.w. Domestic hen, 137.0 mg a.i./kg b.w. 2.3.3 Other species Bendiocarb is very toxic to bees. 3. FOR REGULATORY AUTHORITIES - RECOMMENDATIONS ON REGULATION OF COMPOUND 3.1 COMMENDED RESTRICTIONS ON AVAILABILITY (For definition of categories, see the Introduction to Data Sheets) - All available liquid formulations are in Category 3. Solid formulations over 10%, Category 3 Other solid formulations, Category 4 3.2 TRANSPORTATION AND STORAGE Formulations in Categories 3 and 4: Should be transported or stored in clearly labelled rigid and leakproof containers and away from containers of food and drink. Storage should be under lock and key and secure from access by unauthorized persons and children. 3.3 HANDLING Formulations in Categories 3 and 4: Protective clothing (see part 4) should be provided for those handling concentrates. Adequate washing facilities should be available close at hand. Eating, drinking and smoking should be prohibited during handling and before washing after handling. 3.4 DISPOSAL AND/OR DECONTAMINATION OF CONTAINER Container must be either burned or crushed and buried below topsoil. Care must be taken to avoid subsequent contamination of water sources. Containers may be decontaminated (for method see paragraph 4.3 in part 4). Decontaminated containers should not be used for food and drink. 3.5 SELECTION, TRAINING AND MEDICAL SUPERVISION OF WORKERS Formulations in Categories 3 and 4: Pre-employment medical examination for workers desirable. Workers suffering from active hepatic or renal disease should be excluded from contact. Training for workers in techniques to avoid contact essential. 3.6 ADDITIONAL REGULATIONS RECOMMENDED IF DISTRIBUTED BY AIRCRAFT All formulations - Pilot and loaders should have special training in application methods and early symptoms of poisoning. Flagmen, if used, should wear overalls and be located well away from the dropping zone. 3.7 LABELLING Formulations in Categories 3 and 4 - Minimum cautionary statement - "WARNING - POISON" (skull and cross-bones insignia). Bendiocarb is a carbamate compound which inhibits cholinesterase. It is of moderate toxicity. Avoid contact with the skin, inhalation of dust or spray, or swallowing. Wear gloves, and clean protective clothing, when handling this material, and a respirator when handling concentrates. Bathe immediately after work. Ensure that containers are stored under lock and key. Empty containers must be disposed of in such a way as to prevent all possibility of accidental contact with them. Keep the material out of reach of children and well away from foodstuffs, animal feed and their containers. In case of contact, immediately remove contaminated clothing and wash the skin thoroughly with soap and water; for eyes, flush with water for 15 minutes. If poisoning occurs, call a physician. Atropine is a specific antidote, repeated doses may be necessary. Artificial respiration also may be needed. 3.8 RESIDUES IN FOOD Maximum residue levels - Maximum residue levels have not yet been recommended by the Joint FAO/WHO Meeting on Pesticide Residues (it is on the 1982 agenda). 4. PREVENTION OF POISONING IN MAN AND EMERGENCY AID 4.1 PRECAUTIONS IN USE 4.1.1 General Bendiocarb is a carbamate insecticide of moderate toxicity which is quickly metabolized and therefore acts only as an acute poison. It can be absorbed by inhalation of dust and also to some extent through the intact skin. It is important that concentrated formulations be washed immediately from the skin and eyes. 4.1.2 Manufacture and formulation T.L.V., 0.2 mg/m3; STEL, 0.6 mg/m3. Formulation should not be attempted without advice from the manufacturer. Although volatility is low, vapour and dusts should be controlled preferably by mechanical means. Protective equipment for the skin and respiratory protection is usually necessary. 4.1.3 Mixers and applicators When opening the container and when mixing, care should be taken to avoid contact with the mouth and eyes. If necessary a facial visor and gloves should be worn. Mixing, if not mechanical, should always be carried out with a paddle of appropriate length. The applicator should avoid working in spray mists and avoid contact with mouth. Splashes must be washed immediately from the skin or eyes with large quantities of water. Before eating, drinking or smoking, hands and other exposed skin should be washed. 4.1.4 Other associated workers (including flagmen in aerial operations) Persons exposed to bendiocarb and associated with its application should observe the precautions described in 4.1.3 under "Mixers and applicators". 4.1.5 Other populations likely to be affected With correct use in agriculture and public health, the general population should not be exposed to hazardous amounts of bendiocarb. 4.2 ENTRY OF PERSONS INTO TREATED AREAS Unprotected persons should be kept out of treated areas until the spray solution is dry. 4.3 DECONTAMINATION OF SPILLAGE AND CONTAINERS Residues in containers should be emptied in diluted form into a deep pit taking care to avoid ground waters. The empty containers may be decontaminated by rinsing two or three times with water and scrubbing the sides. An additional rinse should be carried out with 5% sodium hydroxide solution which should remain in a container overnight. Impermeable gauntlets should be worn during this work and a soakage pit should be provided for the rinsings. Decontaminated containers should not be used for food and drink. Spillage of bendiocarb and its formulations should be removed by washing with 5% sodium hydroxide solution and then rinsing with large quantities of water. 4.4 EMERGENCY AID 4.4.1 Early symptoms of poisoning Early symptoms may include excessive sweating, headache, weakness, giddiness, nausea, vomiting, stomach pains, salivation, tightness of the chest, blurred vision, slurred speech and muscle twitching. 4.4.2 Treatment before person is seen by a physician if these symptoms appear following exposure The person should stop work immediately, remove contaminated clothing, wash the affected skin with soap and water. If swallowed, vomiting should be induced if the person is conscious. 5. FOR MEDICAL AND LABORATORY PERSONNEL 5.1 MEDICAL DIAGNOSIS AND TREATMENT IN CASES OF POISONING 5.1.1 General information Bendiocarb is a carbamate insecticide of moderate toxicity. It is absorbed from the gastrointestinal tract and by inhalation, and only to a limited extent through the intact skin. Its mode of action is by reversibly inhibiting acetyl cholinesterase. Erythrocyte cholinesterase is more inhibited than plasma cholinesterase. Symptoms of poisoning are short lasting and in the case of occupational overexposure occur without delay and at doses well below the fatal dose. Because of its rapid metabolism and excretion it does not accumulate in the tissues. 5.1.2 Symptoms and signs Symptoms of poisoning include excessive sweating, headache, chest tightness, giddiness, nausea, vomiting, stomach pains, salivation, blurred vision, slurred speech and muscle twitching. 5.1.3 Laboratory Because bendiocarb is a reversible inhibitor of cholinesterase, measurements of cholinesterase activity should be made by a method which minimizes the reactivation of inhibited enzyme. Erythrocyte cholinesterase determination is more informative than measuring either plasma or whole blood cholinesterase, but the enzyme will only be inhibited for a short time (few hours) after exposure. The presence of metabolites of bendiocarb in urine is also indicative of exposure. 5.1.4 Treatment If the pesticide has been ingested, unless the patient is vomiting, rapid gastric lavage should be performed using 5% sodium bicarbonate, if available. For skin contact, the skin should be washed with soap and water. If the compound has entered the eyes they should be washed with isotonic saline or water. Since the symptoms of poisoning with bendiocarb are of short duration atropine treatment is usually not necessary by the time the patient reaches a place where this antidote is available. Where there are manifest symptoms, 1-2 mg of atropine sulfate (adult dose) may be given intramuscularly or even intravenously and repeated as necessary. Care should be taken to avoid overdosage of atropine, especially when treating children. In extreme cases, if the patient is unconscious or is in respiratory distress, oxygen may be required. Provide patient support as required, including: suction of secretions, maintenance of airways, i.v. fluids p.r.n. and bladder catheterization. Pralidoxime has been shown to be ineffective in bendiocarb poisoning. 5.1.5 Prognosis If the acute toxic effect is survived, the chances of complete recovery are very good. 5.1.6 References of previously reported cases No information 5.2 SURVEILLANCE TESTS Due to the rapid reactivation of inhibited enzyme, determination of blood cholinesterase level is of no value in determining when workers should be withdrawn to prevent overexposure. Minor complaints, such as headache and nausea, cause the worker to stop work and thus prevent further exposure. The worker quickly recovers, particularly if appropriate decontamination procedures are followed. 5.3 LABORATORY METHODS 5.3.1 Detection and assay of compound and residues Whiteoak, R. J. et al. (1978) Anal. Methods Pestic. Plant Growth Regul., 10, 3-17. Behner, J. M. et al. (1980) J. Assoc. Off. Anal. Chem., 43(1), 47-48. 5.3.2 Other tests in cases of poisoning Cholinesterase levels in blood are unreliable as a routine test to detect poisoning by bendiocarb. However, shortly after absorption, inhibition of erythrocyte cholinesterase may be demonstrated by an appropriate method. In plasma: Ellman, G. L. et al. (1961) Biochem. Pharmacol., 7, 88-95. In whole blood: Fleischer, J. et al. (1956) Arch. Indust. Hyg., 14, 510; Wilhelm, K. et al. (1973), Bull. Wld Hlth Org., 48, 235-238. Note: This data sheet was drafted in the Bureau of Chemical Standards, Environmental Health Directorate, Health and Welfare, Canada, and subsequently underwent medical, scientific, and industrial review.