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    WORLD HEALTH ORGANIZATION             FOOD AND AGRICULTURE
                                          ORGANIZATION
    ORGANISATION MONDIALE DE LA SANTE     ORGANISATION POUR L'ALIMENTATION
                                          ET L'AGRICULTURE

                                                  WHO/VBC/DS/87.60 Rev.1

                                                      ORIGINAL: ENGLISH

                                                      Distr.: LIMITED





    DATA SHEETS ON PESTICIDES No. 60

    DEMETON

    Rev. 1




         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

                               Chemical Group: Organophosphorus compound

    1.0  GENERAL INFORMATION

    1.1  COMMON NAME:

         Demeton (ISO, BSI - exception USSR), a mixture of Demeton-O (I)
    and Demeton-S (II)

    1.1.1  Identity:

         IUPAC and CAS No. 1:

         (I)   O,O-diethyl  O-[2-(ethylthio)ethyl] phosphorothioate

         (II)  O,O-diethyl  S-[2-(ethylthio)ethyl] phosphorothioate

         CAS Reg. No.: 8065-48-3 (mixture of isomers)

                       (I)  298-03-3

                       (II) 126-75-0

         Molecular formula: C8H19O3PS2

         Molecular weight: 258.3

         Structural formula:

    CHEMICAL STRUCTURE

    1.1.2  Synonyms

         (Mixture) Bayer 10756R; Demeton; DemoxR; Mercaptophos;
    SystemoxR; SystoxR; (I) Bayer 8169R; Demeton-O; Demeton I;
    Di-SeptonR; E-1059; Ethylthiometon; Thiodemeton;
    Thiolmercaptophos; (II) Demeton-S, Demeton-II, Isodemeton;
    Isosystox; PO-SystoxR: PS-systoxR, Thioldemeton; Thiol-SystoxR

    1.2  SYNOPSIS

         Demeton is a mixture of isomers; a selective, non-cumulative
    organophosphorus pesticide; and a cholinesterase inhibitor with good
    contact and stomach action. The technical product is of extremely
    high acute toxicity to mammals (WHO Hazard Class Ia). Demeton-O is a
    mutagen in bacterial systems. Demeton is a plant systemic with long
    residual action; selectively phytotoxic; and, extremely toxic to
    bees, fish and wildlife.

    1.3  SELECTED PROPERTIES

    1.3.1  Physical characteristics

         The reaction product, a 65:35 mixture of (I) and (II) is a
    colourless oil with a strong sulfurous odour. The technical product
    is a light yellow oil with a mercaptan odour also. Demeton-O has a
    boiling point of 123°C (1 mmHg = 0.13 kPa); a density (d)21 of
                                                             4
    1.119; and, a refractive index (n)18  of 1.4900. Demeton-S has a
                                      D
    boiling point of 128°C (1 mmhg); a density (d)21 of 1.132; and a
                                                  4
    refractive index (n)18  of 1.500.
                        D

    1.3.2  Solubility (room temperature)

         Demeton-O 60 mg/1 water; soluble in most organic solvents

         Demeton-S 2g/1 water, soluble in most organic solvents

    1.3.3  Stability

         Demeton is hydrolyzed by boiling water and strong alkali, but
    it is compatible with most nonalkaline pesticides, except water
    soluble mercury compounds.

    1.3.4  Vapour pressure

         Demeton-O 2.84 x 10-4 mmHg = 38 mPa at 20°C

         Demeton-S 2.6 x 10-4 mmHg = 35 mPa at 20°C

    1.4  AGRICULTURE, HORTICULTURE AND FORESTRY

    1.4.1  Common formulation

         Formulated as a 2.5g/kg and 6.6g/kg emulsifiable concentrate.

    1.4.2  Pests controlled

         Mites, aphids and sap-feeding insects such as whiteflies,
    leafhoppers, thrips and leafminers.

    1.4.3  Use pattern

         Wide range of fruits, vegetables and ornamentals. Applied as
    soildrench or foliage spray. It is generally applied 140 to 800
    g/ha.

    1.4.4  Unintended effects

         Phytotoxic to some ornamentals; toxic to bees.

    1.5  PUBLIC HEALTH USE

         No recommended use.

    1.6  HOUSEHOLD USE

         No recommended use.

    2.0  TOXICOLOGY AND RISKS

    2.1  TOXICOLOGY - MAMMALS

    2.1.1  Absorption route

         Demeton may be absorbed from the gastrointestinal tract,
    through the intact skin, and, by inhalation of spray mist.

    2.1.2  Mode of action

         Demeton is a direct inhibitor of cholinesterase through
    phosphorylation of the esteratic site of the enzyme. Demeton and its
    oxidation products, the sulfoxide and the sulfone are similar in
    their toxicity and anticholinesterase activity. Demeton also
    inhibits the hydrolysis of diethylsuccinate and tributyrin in liver
    and serum.

    2.1.3  Excretion of products

         A major metabolite  O,O-diethylphosphorothiolate (DEPTH)
    results from the direct hydrolysis of demeton-S and from hydrolysis
    of demeton-O followed by isomerization of  O,O-
    diethylphosphorothionate (DETP - another major metabolite).

    2.1.4  Toxicity, single dose of technical material

         Oral LD50:          Rat (M)        6.2  mg/kg b.w

                                 (F)        2.5  mg/kg b.w.

                             Mouse          7.85 mg/kg b.w.

         Dermal LD50:        Rat (M)        14   mg/kg b.w.

                                 (F)        8.2  mg/kg b.w.

                             Rabbit         24   mg/kg b.w.

         I.P. LD50:          Rat            3.0  mg/kg b.w.

                             Mouse          4.0  mg/kg b.w.

                             Rabbit         3.25 mg/kg b.w.

         I. V. LD50:         Rat            1.75 mg/kg b.w.

                             Mouse          3.9  mg/kg b.w.

         Inhalation - Exposure to 18 mg demeton/m3 of air fatal to
    6/6 rats in 50-90 minutes.

    2.1.5  Toxicity, repeated dose

         Inhalation: Two hour exposure/day to 3 mg demeton/m3 of air
    resulted in no illness in rats during first exposure; tremors during
    second exposure; lacrimation and tremors during third exposure and
    death in 10/17 during fourth exposure.  7/19 rats died after seven
    to 12 one hour daily exposures to 3 mg demeton/m3 air.

    2.1.6  Dietary studies

         Short term: Rabbits were fed demeton sprayed greens for 30-100
    days. Ingestion of 1.5 (mg demeton/kg b.w./day reduced
    cholinesterase activity (55% of normal) with 4/6 deaths by 30 days.
    Ingestion of 2.3 mg/kg b.w./day reduced plasma cholinesterase (70%
    of normal) and 3/6 deaths by 30 days. At 0.15 mg/kg b.w./day for 98
    days, no fatalities or reduced cholinesterase levels occurred.
    Symptoms preceding death included respiratory distress, frothing at
    nose and mouth, marked diarrhoea, muscular paralysis, coma and mild
    asphyxial convulsions. Gastric intubation of 0.4, 0.66, 0.9 or 1.89
    mg demeton/kg b.w./day in rats for 90 days caused intoxication
    (hyperexcitability and tremors) at the two higher doses after 21
    days. In a 16 week study, female rats were fed demeton 0 ,10, 20 and
    50 mg/kg diet. Females at the highest dose were severely poisoned
    but recovered after three to four weeks despite continued intake.
    Blood and brain cholinesterase were 7.1 and 8.2% of normal
    respectively. Rats fed 20 mg/kg diet showed levels of brain and
    blood cholinesterase 15% of normal but otherwise appeared
    unaffected. Brain and blood cholinesterase levels were 90% of normal
    at 1 mg/kg diet (0.05 mg/kg b.w./day) in an 11 week study.

         In a 24 week dog study, animals were fed demeton at 0, 1, 2, or
    5 mg/kg diet. Inhibition of erythrocyte cholinesterase was slight at
    5 mg/kg diet (0.149 mg/kg b.w./day); inhibition of plasma
    cholinesterase was marked at 5 mg/kg diet and slight at 2 mg/kg diet
    (0.047 mg/kg b.w./day). A dietary level of 1 mg/kg diet (0.025 mg/kg
    b.w./day) was the no effect level for both enzymes.

         Long term: No information available.

    2.1.7  Supplementary studies of toxicity

         Carcinogenicity: No information available.

         Mutagenicity: Demeton was mutagenic for reverse mutations in
    five strains of  S. typhimurium and one strain of  E. coli;
    mutagenic in relative toxicity assays with DNA repair - proficient
    and - deficient strains of  E. coli and  B. subtilus and in DNA
    synthesis in human fibroblasts; induced sister chromatid exchange in
    a hamster cell line: Induced mitotic recombination, mitotic crossing
    over, gene conversion and reverse mutation in  S. cerevisiae.

         Teratogenicity: Demeton administered to mice between days
    seven and 12 of gestation as single i.p. dose of 7 or 10 mg/kg b.w.
    or as three consecutive doses of 5 mg/kg b.w. was found to be
    embryotoxic (decreased foetal weight and higher mortality) with only
    mild teratogenic potential. A few minor skeletal abnormalities were
    produced at the 5 mg/kg b.w. dose level.

         Reproduction: I.p. injection of pregnant mice (day 14 of
    gestation) at 5 mg/kg 32P-labelled demeton produced heavy labelling
    of placental tissue, foetal muscle and osteogenic mesenchyma within
    20 minutes but only trace activity persisted after three hours.
    Maximum levels in the liver were found between one to two hours.

         Neurotoxicity: Demeton did not induce delayed neurotoxicity
    in hens fed dose levels up to 1600 mg/kg (diet) for 14-20 weeks.

    2.1.8  Modifications of toxicity

         Rats maintained on a protein deficient diet for 28 days after
    weaning were more susceptible than controls to a single dose of
    demeton. Rats given fluoride by stomach tube at 16.8 or 33.6 mg/kg
    b.w./day for three days had increased susceptibility to demeton.
    Demeton does not potentiate the toxicity of other organic phosphorus
    compounds including malathion.

    2.2  TOXICOLOGY - MAN

    2.2.1  Absorption route

         Demeton may be absorbed from the gastrointestinal tract,
    through the intact skin; and, by inhalation of spray mist.

    2.2.2  Dangerous doses

         Single: Not known.

         Repeated: Not known.

    2.2.3  Observations on occupationally exposed workers

         A number of serious poisonings and a few deaths caused by
    demeton have been associated with occupational exposure. Death was
    attributed to demeton in the case of a worker cleaning a plane used
    in application of the pesticide. Severely depressed cholinesterase
    levels of red blood cells and plasma occurred although route of
    exposure was uncertain. Levels up to 6 mg/m3 of demeton in the air
    breathed by agricultural workers resulted in reduced serum
    cholinesterase activity but no clinical symptoms.

    2.2.4  Observations on exposure of the general population

         No information available.

    2.2.5  Observations on volunteers

         The no-effect level for demeton was found to be 0.05 (mg/kg
    b.w.)/day after 25 days of administration. At 0.1 (mg/kg b.w.)/day,
    depressions of 39.8 and 15.9% in plasma and erythrocyte
    cholinesterase activity occurred.

    2.2.6  Reported mishaps

         Transdermal poisoning by demeton was confirmed in a three year-
    old by its high concentration in the clothing. Treatment with
    pralidoxime chloride and atropine sulfate was effective. Plasma
    cholinesterase levels 15 to 41 hours after exposure ranged from 0.24
    - 0.48 IU. Approximate normal values (2.5 IU) were not reached until
    five and one half days after exposure. Metabolites equivalent to
    4.15 mg of demeton were recovered from his urine during the first 24
    hours of hospitalization.

    2.3  TOXICOLOGY - NONMAMMALIAN SPECIES

         Oral LD50           Mallards (M)        7.19 mg/kg b.w.
         of technical
         material:           Pheasants (F)       8.21 mg/kg b.w.

                             Grouse (M + F)      4.76 mg/kg b.w.

                             Chukar (M + F)      15.1 mg/kg b.w.

                             Coturnix (F)        8.48 mg/kg b.w.

                             Pigeon (M + F)      8.48 mg/kg b.w.

                             Sparrow (F)         9.52 mg/kg b.w.

         Other effects: Ducklings hatched from eggs inoculated via the
    yolk sac on day 13 with 10 or 100 µg demeton were hyperexcitable and
    in some cases had leg paralysis and body tremors with intermittent
    convulsions associated with cholinesterase inhibition.

    3.0  FOR REGULATORY AUTHORITIES

    3.1  RECOMMENDED RESTRICTIONS ON AVAILABILITY

         (For definition of categories see the Introduction to Data
    Sheets)

         All available liquid formulations, Category 1

         There are no solid formulations available. WHO Hazard
    Classification of technical product: Class Ia.

    3.2  TRANSPORTATION AND STORAGE

         All formulations - Should be transported and stored in
    clearly labelled impermeable containers under lock and key, secure
    from access by unauthorized persons and children. No food or drink
    should be stored in the same compartment.

    3.3  HANDLING

         All formulations - Full protective clothing with organic
    vapour cartridge respirator (see 4.1.3) should be used by those
    handling the compound. Adequate washing facilities should be
    available at all times during the handling and should be close to
    site of handling. Eating, drinking and smoking should be prohibited
    during handling and before washing after handling.

    3.4  DISPOSAL AND/OR DECONTAMINATION OF CONTAINERS

         All formulations - Containers must be either burned or
    crushed and buried below topsoil. Care must be taken to avoid
    subsequent contamination of water sources. Decontamination of
    containers in order to use them for other purposes should not be
    permitted.

    3.5  SELECTION, TRAINING AND MEDICAL SUPERVISION OF WORKERS

         All formulations - Pre-employment medical examination of
    workers is necessary. Workers suffering from hepatic or renal
    disease should be excluded from contact. Pre-employment and periodic
    cholinesterase tests for workers are desirable. Special account
    should be taken of the workers' mental ability to comprehend and
    follow instructions. Training of workers in techniques to avoid
    contact is essential.

    3.6  ADDITIONAL REGULATIONS RECOMMENDED IF DISTRIBUTED BY AIRCRAFT

         All formulations - Pilots and loaders should have special
    training in application methods and early symptoms of poisoning, and
    must wear a suitable respirator. Use of flagmen not recommended.

    Flagmen, if used, should wear protective clothing and be located
    well away from the dropping zone.

    3.7  LABELLING

         All formulations

                             "DANGER - POISON"

                      (skull and cross bones insignia)

         Demeton is an organophosphorus compound which inhibits
    cholinesterase. It is highly toxic. Contact with the skin,
    inhalation of spray, or swallowing may be fatal. Wear protective
    gloves, clean protective clothing, and a respirator of the organic-
    vapour type when handling this material. 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 sulphate and pralidoxime are
    accepted antidotes, repeated doses may be necessary. Artificial
    respiration also may be needed.

    3.8  RESIDUES IN FOOD

         Maximum residue levels - Maximum residue levels have been
    recommended by the Joint FAO/WHO Meeting on Pesticides in Residues.

    4.0  PREVENTION OF POISONING IN MAN AND EMERGENCY AID

    4.1  PRECAUTIONS IN USE

    4.1.1  General

         Demeton is an organophosphorus pesticide of high toxicity. It
    penetrates the intact skin and is also absorbed by inhalation and
    from the gastrointestinal tract. Repeated exposure may have a
    cumulative effect on cholinesterase levels. Most formulations should
    be handled by trained personnel wearing protective clothing with
    organic vapour cartridge respirator.

    4.1.2  Manufacture and formulation

         TLV - 0.1 mg/m3 skin (TWA), 0.3 mg/m3 (STEL) - 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 hat, clothing, boots and gloves. The applicator should
    avoid working in spray mist and avoid contact with the mouth.
    Particular care is needed when equipment is being washed after use.
    All protective clothing should be washed immediately after use,
    separate from other laundry, 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 and other exposed skin should be washed.

    4.1.4  Other associated workers (including flagmen in aerial
           operations)

         Persons exposed to the compound 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 application practice, subject to 4.2 below, other
    persons are not likely to be exposed to hazardous amounts of the
    compound.

    4.2  ENTRY OF PERSONS INTO TREATED AREA

         Unprotected persons should be kept out of tall crops for four
    days and out of other crops for 24 hours.

    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 or drink.
    Spillage of the compound 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, giddiness, nausea, vomiting, hypersalivation,
    stomach pains, blurred vision, slurred speech lacrimation,
    urination, diarrhoea and muscle twitching. Later there may be
    convulsions and coma.

    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 and wash the affected skin with soap and water, if
    available, and flush the area with large quantities of water. If
    swallowed, and if the person is conscious, vomiting should be
    induced. In the event of collapse, artificial resuscitation is used,
    vomit may contain toxic amounts of pesticide.

    5.0  FOR MEDICAL AND LABORATORY PERSONNEL

    5.1  MEDICAL DIAGNOSIS AND TREATMENT IN CASES OF POISONING

    5.1.1  General information

         Demeton is an organophosphorus pesticide of high mammalian
    toxicity which is active against a variety of agricultural and
    public health pests. It is readily absorbed from the
    gastrointestinal fact; through the intact skin; and, by inhalation.
    It is converted  in vivo to the oxygen analogue which inhibits
    cholinesterase. It does not accumulate in body tissues.

    5.1.2  Symptoms and signs

         Initial symptoms of poisoning may include excessive sweating,
    headache, weakness, giddiness, nausea, hypersalivation, vomiting,
    stomach pains, blurred vision, slurred speech 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 finding is reduction of activity of blood
    cholinesterases. Urinary levels of organic phosphorus containing
    metabolites may also be used as a measure of exposure. Metabolites
    can be identified specifically.

    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 formulations containing petroleum
    distillates gastric lavage should be done using a cuffed
    endotracheal tube to prevent aspiration of the material. For skin
    contact, the skin should be washed with soap and water. If the
    compound has entered the eyes, they should be washed with large
    quantities of 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 by intravenous
    injection and 1000 mg 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 a reactivator. 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. Diazepam may be given to
    control convulsions. The patient's condition including respiration,
    blood pressure, pulse frequency, salivation, and convulsions should
    be carefully observed as a guide to further administration of
    atropine. If the patient is cyanotic, oxygen should be given at the

    same time as atropine sulfate. The airways should be kept free and
    artificial resuscitation should be applied if required, preferably
    by mechanical means. If necessary, intubation should be performed.
    Contraindications are morphine, aminophylline, phenothiazine,
    reserpine, furosemide or ethacrynic acid. Give adrinergic amines
    only if there is a specific indication. Pralidoxime and toxogonin
    alone are not regarded as effective antidotes in organophosphorus
    poisoning.

    5.1.5  Prognosis

         If the acute toxic effect is survived and adequate artificial
    resuscitation has been given if needed, the chances of complete
    recovery are good. However, in very severe cases, particularly if
    artificial resuscitation has been inadequate, prolonged anoxIa may
    give rise to permanent brain damage.

    5.1.6  References of previously reported cases

         Felsenstein, W. C.  et al. (1976) Arch. Environ. Health
              31(5): 266-269

         Hayes, W. J. 1982, Pesticides Studied in Man, Williams &
              Wilkins, Baltimore, MD, p. 390

         Warinner, R. A.  et al. (1977) Arch. Environ. Health 32 (5):
              203-205

    5.2  SURVEILLANCE TESTS

    Test                Normal level*  Action level*  Symptomatic level*

    Plasma cholinesterase    100%           50%             variable

    Whole blood or           100%           70%            usually 40%
    erythrocyte
    cholinesterase

    5.3  LABORATORY METHODS

    5.3.1  Detection and assay of compound

         Bowman, M. C.  et al. (1969), J. Assoc. Off. Anal. Chem.,
              52, p. 157

         CIPAC HANDBOOK (1979), Vol. 1, p. 302

                 

    * Expressed as percentage of pre-exposure values.

         Hild, J. and Their, H. P., (1978), Z. Lebensom Unters
              Forsch., 166(1), p. 9

         MacDougall, D. (1964), Anal. Methods Pestic., Plant
              Growth Regul., Food Addit., 2, p. 451

         MacDougall, D. (1972), Anal. Methods Pestic. Plant Growth
              Regul., 6, p. 483

         Stan, H. J. (1977) Z. Lebensom Unters Forsch., 164(3), p. 153

         Thornton, J. S. and Anderson, C. A. (1968), J. Agric. Food
              Chem., 16, p. 895

    5.3.2  Other tests in case of poisonings

         Levels of cholinesterase in the blood, particularly plasma,
    provide the most useful diagnosis 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:
        Demeton (ICSC)
        Demeton (PIM 759)