WORLD HEALTH ORGANIZATION FOOD AND AGRICULTURE ORGANIZATION ORGANISATION MONDIALE DE LA SANTE ORGANISATION POUR L'ALIMENTATION ET L'AGRICULTURE VBC/DS/78.39 ORIGINAL: ENGLISH DATA SHEETS ON PESTICIDES No. 39 June 1978 NALED 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: Acaricide and fungicide Chemical group: Organophosphorus compound Date issued: June 1978 1. GENERAL INFORMATION 1.1 COMMOM NAME: Naled (ISO) 1.1.1 Identity: 1,2-dibromo-2,2-dichloroethyl dimethyl phosphate 1.1.2 Synonyms: Dibrom RE 4355 Local synonyms: 1.2 SYNOPSIS Naled is an organophosphorus insecticide and acaricide of moderate mammalian toxicity. It is not cumulative in body tissues. 1.3 SELECTED PROPERTIES 1.3.1 Physical characteristics The technical product is a yellow liquid of about 93% purity with a slightly pungent odour, b.p. 110°C at 0.5 mmHg. The pure compound has a m.p. of 26°C. 1.3.2 Solubility Naled is practically insoluble in water, slightly soluble in aliphatic solvents and readily soluble in aromatic solvents. 1.3.3 Stability Stable under anhydrous conditions, but is rapidly hydrolysed in water: 90-100% in 48 hours at room temperature, and by alkali. It is stable in glass containers but in the presence of metals and reducing agents, rapidly loses bromine and reverts to dichlorvos. 1.3.4 Vapour pressure 266 x 10-6 kPa at 20°C. 1.4 AGRICULTURE, HORTICULTURE AND FORESTRY 1.4.1 Common formulations Emulsifiable concentrates 3.6 lb and 7.2 lb per US gal; non-emulsifiable concentrates 12.6 lb per US gal; dusts 4%. 1.4.2 Pests controlled Effective contact and stomach insecticide and acaricide with some fumigant action. Brief residual activity. Recommended against adult mosquitos and flies. 1.4.3 Use pattern On many crop plants and under glass in mushroom houses at 3 g/1000 ft3. 1.4.4 Unintended effects No data available. 1.5 PUBLIC HEALTH PROGRAMME No data available. 1.6 HOUSEHOLD USE No household use. 2. TOXICOLOGY AND RISKS 2.1 TOXICOLOGY - MAMMALS 2.1.1 Absorption route May be absorbed from the gastrointestinal tract, by inhalation and through the intact skin. 2.1.2 Mode of action Naled is a direct cholinesterase inhibitor. 2.1.3 Excretion products Naled is rapidly hydrolysed to give a number of metabolites which include dichlorvos, dichlorobromoacetaldehyde, dimethyl phosphate and certain complex amino-acid conjugate of the degraded product. When 25 mg/kg of 32p naled was given orally to a cow, 9% was recovered in urine and 34% in faeces up to one week after dosing. 2.1.4 Toxicity, single dose Oral: LD50 rat: 430 mg/kg Dermal: LD50 rat: 800 mg/kg LD50 rabbit: 1100 mg/kg 2.1.5 Toxicity, repeated doses: Oral: Rats given 1/10 of the LD50 daily for 9 weeks showed moderate inhibition of blood and brain cholinesterase. Inhalation: No toxic effects were observed in rats and guinea-pigs exposed to vapour at a concentration of 19 µg/l for 6 h per day, 5 days per week for 5 weeks. Cumulation of compound: Naled is not cumulative in body tissues. Cumulation of effect: Repeated exposure to na!ed may have a cumulative effect on cholinesterase levels. 2.1.6 Dietary studies Short-term: Groups of male and female rats were fed levels of 200, 400 and 800 mg technical naled kg diet respectively, for 28 days and at levels of 800, 1600 and 3200 mg/kg diet for the balance of the 94-day test period. Growth patterns among all test animals were comparable to the control group for the first 28 days. Significant growth depressions and reduced food intake was observed among animals fed 1600 and 3200 mg/kg throughout the 29-94 day feeding period. No deaths and two isolated cases of tremor were observed among two females in the 3200 mg/kg diet group. Blood and urine data and clinical blood chemistry data were comparable to those of the control animals. No gross or microscopic pathological changes could be directly correlated to ingestion of technical naled. In another experiment, groups of male and female dogs were administered 0.25, 0.75, 2.5 and 7.5 mg technical naled/kg diet per day for 89 days. No mortalities or untoward signs of intoxication were observed at the dose levels tested. Haematological studies, urine analysis, liver, kidney function tests and microscopic examination did not reveal any significant adverse effects. Plasma cholinesterase activity was slightly inhibited at the 0.25 and 0.75 (mg/kg)/day levels; plasma and erythrocyte cholinesterase activity was reduced in all animals at dietary levels of 2.5 and 7.5 mg naled/kg per day. Long-term: Technical naled was fed over a two-year period to a group of male and female rats at dietary levels of 5, 25 and 100 mg/kg diet and to groups of male and female dogs at graded dose levels of 0.25, 2.5 and 7.5 (mg/kg)/day. No adverse effects were observed in either experiment in the following parameters: body weights and weight gains; food consumption; mortality and intoxication reactions; haematologic and urologic studies; gross and microscopic pathological changes; organ weights and ratios; and rumour incidence. 2.1.7 Supplementary studies of toxicity Carcinogenicity: See 2.1.6 Dietary studies, long-term. Reproduction study and teratogenicity: Administration of 1, 5 and 25 mg technical naled/kg diet to three generations of albino rats had no effect on mating and fertility indices, incidence of pregnancy, parturition and gestation times, lactation indices, offspring and their survival. Mutagenicity: Intraperitoneal injection of male mice with single doses of 15 and 30 mg technical naled/kg body weight, did not cause a dominant lethal effect. No significant differences in mating indices, early resorptions or mutation rates could be attributed to naled administration. Delayed neurotoxicity: No neurotoxicity was observed in hens on high single and repeated doses. 2.1.8 Modification of toxicity: No information available. 2.2 TOXICOLOGY - MAN 2.2.1 Absorption Naled may be absorbed from the gastrointestinal tracts by inhalation and through the intact skin. 2.2.2 Dangerous doses Single: Not known. Repeated: Not known. 2.2.3 Observations of occupationally exposed workers No information available. 2.2.4 Observations on exposure of the general population No information available. 2.2.5 Observations of volunteers No information available. 2.2.6 Reported mishaps Entry into a chrysanthemum field previously sprayed with a combination of naled, captan and dicofol and in which the spray had not dried, has given rise to contact dermatitis. Three of the four cases on subsequent patch testing, gave positive reactions to naled, but not to other pesticides involved. 2.3 TOXICITY TO NON-MAMMALIAN SPECIES 2.3.1 Fish Toxic 2.3.2 Birds Toxic (mallards, sharp tailed grouse, Canada geese, LD50 27-111 mg/kg). 2.3.3 Other species Toxic (mule deer LD50 200 mg/kg). Bees unaffected. 3. FOR REGULATORY AUTHORITIES - RECOMMENDATIONS ON REGULATION OF COMPOUND 3.1 RECOMMENDED RESTRICTIONS ON AVAILABILITY (for definition of categories, see introduction) All formulations above 5%, Category 3 All formulations 5% or less, Category 4 3.2 TRANSPORTATION AND STORAGE All formulations - Should be transported or stored in clearly labelled rigid and leakproof containers under lock and key safe from access by unauthorized persons and children. No food or drink should be stored in the same compartment. 3.3 HANDLING All formulations in Category 3 - Full protective clothing (see 4.1.3 in part 4) should be used for all handling of the compound. Adequate washing facilities should be available at all times during handling and should be close to the site of handling. Eating, drinking and smoking should be prohibited during handling and before washing after handling. All formulations in Category 4 - Protective clothing should be used for those handling the concentrate. Adequate washing facilities should be available at all times during handling and should be close to the site of handling. Eating, drinking and smoking should be prohibited during handling and before washing after handling. 3.4 DISPOSAL AND/OR DECONTAMINATION OF CONTAINER All formulations - Container may be decontaminated (for method, see paragraph 4.3 in part 4). Decontaminated containers should not be used for food and drink. Containers that are not decontaminated should be burned or should be crushed and buried below top-soil. Care must be taken to avoid subsequent contamination of water sources. 3.5 SELECTION, TRAINING AND MEDICAL SUPERVISION OF WORKERS Pre-employment medical examination including cholinesterase test for workers desirable. Workers suffering from active hepatic or renal disease should be excluded from contact. Special account should be taken of the worker's mental ability to comprehend and follow instructions. Training of 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 and must wear a suitable respirator. Flagmen, if used, should wear overalls and be located well away from the dropping zone. 3.7 LABELLING All formulations - Minimum cautionary statement - Naled is an organophosphorus compound which inhibits cholinesterase. It is poisonous if swallowed. If may be absorbed through the skin and by inhalation. Avoid skin contact; wear protective gloves, clean protective clothing and a respirator when handling the material. Wash thoroughly with soap and water after using. Keep the material out of reach of children and well away from foodstuffs, animal feed and their containers. If poisoning occurs call a physician. Atropine and pralidoxime are specific antidotes and artificial respiration may be needed. 3.8 RESIDUES IN FOOD Maximum residue levels have not yet been recommended by the joint FAO/WHO Meeting on Pesticide Residues. 4. PREVENTION OF POISONING IN MAN AND EMERGENCY AID 4.1 PRECAUTIONS IN USE 4.1.1 General Naled is an organophosphorus compound of moderate mammalian toxicity. It is readily absorbed by inhalation, through the intact skin and from the gastrointestinal tract. 4.1.2 Manufacture and formulation T.L.V.: 3 mg/m3 (ACGIH). Closed systems and forced ventilation may be required to reduce as much as possible the exposure of workers to the chemical. 4.1.3 Mixers and applicators When opening the container and when mixing, protective impermeable boots, clean overalls, gloves and respirator should be worn. Mixing, if not mechanical, should always be carried out with a paddle of appropriate length. When spraying tall crops or during aerial application, a face mask should be worn as well as an impermeable hood, clothing, boots and gloves. The applicator should avoid working in spray mist and avoid contact with the mouth or skin. Particular care is needed when equipment is being washed after use. All protective clothing should be washing immediately after use, including the insides of gloves. Splashes must be washed immediately from the skin or eyes with large quantities of water. Before eating, drinking or smoking, hands or other exposed skin should be washed. 4.1.4 Other associated workers (including flagmen in aerial operations) Persons exposed to naled and associated with its application, should wear protective clothing and observe the precautions described above in 4.1.3 under "mixers and applicators". 4.1.5 Other populations likely to be affected With good agricultural and manufacturing practice subject to 4.2 below, other persons should not be exposed to hazardous amounts of naled. 4.2 ENTRY OF PERSONS INTO TREATED AREAS Unprotected persons should be kept out of treated areas for at least one day. 4.3 DECONTAMINATION OF SPILLAGE AND CONTAINERS Residues in containers should be emptied in a diluted form into a deep pit, taking care to avoid ground waters. The empty container 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 the 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 naled 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 of poisoning may include, excessive sweating, headache, weakness, nausea, vomiting, stomach pains, blurred vision, slurred speech, salivation and muscle twitching. Later there may be convulsions, coma, loss of reflexes and loss of sphincter control. 4.4.2 Treatment before person is seen by a physician; if these symptoms appear following exposure The person should stop work immediately, remove contaiminated clothing and wash the affected skin with water and soap, if available, and flush the area with large quantities of water. If swallowed, vomiting should be induced if the person is conscious. In the event of collapse, artificial respiration should be given, bearing in mind that if mouth to mouth respiration is used, vomit may contain toxic amounts of haled. 5. FOR MEDICAL AND LABORATORY PERSONNEL 5.1 MEDICAL DIAGNOSIS AND TREATMENT IN CASES OF POISONING 5.1.1 General information Naled is an organophosphorus insecticide of moderate mammalian toxicity, which also has some fumigant properties. It is readily absorbed through the intact skin, by inhalation and from the gastrointestinal tract. 5.1.2 Symptoms and signs Initial symptoms of poisoning may include excessive sweating, headache, weakness, giddiness, nausea, vomiting, stomach pains, blurred vision, slurred speech, salivation, and muscle twitching. More advanced symptoms of poisoning may be convulsions, coma, loss of reflexes and loss of sphincter control. 5.1.3 Laboratory The most important laboratory finding is reduction in activity of blood cholinesterases. 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. Persons without signs of respiratory insufficiency but with manifest peripheral symptoms should be treated with 2-4 mg of atropine sulfate and 1000-2000 g of pralidoxime chloride or 250 mg of Toxogonin (adult dose) by slow intravenous injection. More atropine may be given as needed. Persons with severe intoxication with respiratory difficulties, convulsions, and unconsciousness, should immediately be given atropine and an oxime. In such severe cases, 4-6 mg of atropine sulfate should be given initially followed by repeated doses of 2 mg at 5-10 minute intervals. The patient's condition including respiration, blood pressure, pulse frequency, and salivation should also be carefully observed as a guide to further administration of atropine. If the patient is cyanotic, artificial respiration should be given simultaneously with atropine sulfate. Contraindicated are morphine, barbiturates, phenothiazine tranquillizers and central stimulants of all kinds. 5.1.5 Prognosis Although there have been no reported cases, if may be assumed that if the acute toxic effect is survived, the chances of complete recovery are good. In very severe cases it is possible that without adequate artificial respiration, prolonged anoxia could give rise to permanent brain damage. 5.1.6 Reference of previous reported cases Edmundson, W. F. (1967) Dermatitis from naled, Arch. Envir. Health, 15, 89-91. 5.2 SURVEILLANCE TESTS Test Normal level* Action level* Symptomatic level* Plasma cholinesterase 100% 50% variable Erythrocyte cholinesterase 100% 70% 40% 5.3 LABORATORY METHODS 5.3.1 Detection and assay of compounds References are given only. Most methods for the estimation of residues of naled require the conversion of naled to dichlorvos by reaction with a sulfydryl compound and estimation by microcolouri-metric gas chromatography, see: Pack, D. E. et al. (1964) Dibrom, 11, 125 Analytical methods for pesticides plant growth regulators and food additives, Vol. II insecticides edited by G. Zweig, Academic Press. Analytical methods for pesticides and plant growth regulators, Vol. VI Gas chromatographic analysis, edited by G. Zweig & J. Sherma, Academic Press, 1972. A method involving flame photometric determination of bromine may also be useful, see: Gutsche, B. et al. (1969) Ueber eine Angwendungsmaeglichkeit der glammen photometrischen Bromanlysen [The suitability of flame photometric bromine analysis] Deut Lebansm-Rundscha, 65(11), 352-355. *Expressed as percentage of pre-exposure activity. 5.3.2 Other tests in cases of poisoning Levels of cholinesterase activity in the blood provide the most useful data in diagnosi of poisoning. Michel, N. O. (1949) J. Lab. Clin. Med., 34, 1564-1568. Ellman, G. L. et al. (1961) Biochem. Pharmacol., 7, 88-95.
See Also: Naled (ICSC) Naled (PIM 555)