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    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

    Structural Formula

    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:
       Toxicological Abbreviations
       Naled (ICSC)