WHO/FOOD ADD./70.38



    Issued jointly by FAO and WHO

    The content of this document is the result of the deliberations of the
    Joint Meeting of the FAO Working Party of Experts and the WHO Expert
    Group on Pesticide Residues, which met in Rome, 8 - 15 December 1969.



    Rome, 1970



    Chemical name

    S-[2-(ethylthio)ethyl] dimethyl phosphorothiclothionate


    S-[2-(ethylthio)ethyl] 0,0-dimethyl phosphorodithioate, Ecatin(R),
    Intration (Czechoslovakia)

    Structural formula

             CH3O  S
                 \ "

    Other relevant chemical properties

    Properties of thiometon - boiling point 110°C/0.1 mm; d4 1.209;
    colourless oil with characteristic odour; soluble in most organic
    solvents, less soluble in petroleum ether, 200 mg/l at 25°C in water;
    stable in apolar solvents, unstable pure or under alkaline conditions.

    Formulations - 20 and 25 percent by weight emulsifiable concentrates
    and 2 percent by weight dust. Stability of formulations with full
    activity in at least two years when stored below 40°C.



    Absorption, distribution and excretion

    No information is available on the metabolism of thiometon in animals.
    Oxidative metabolites have been found in plants treated with thiometon
    (Jucker, 1958). See also the section entitled "RESIDUES IN FOOD AND

    Effect on enzymes and other biochemical parameters

    The anti-cholinesterase properties of thiometon have been demonstrated
    from in vitro experiments with guinea-pig serum cholinesterase.
    Concentrations of 10-4 molar and 10-3 molar of the pure compound gave
    inhibitions of 54 percent and 85 percent respectively (Klotzsche,

    A single oral dose of 125 mg/kg body-weight of thiometon was
    administered to adult and seven week old chickens. Symptoms of
    poisoning appeared after three hours in all birds and death followed
    within eight hours. There was almost complete depletion of
    cholinesterase when the first signs of poisoning appeared. A
    significant increase in ascorbic acid and glucose concentration in the
    blood as well as a decrease in adrenal cholesterol and liver glycogen
    also occurred (Madejski and Juszkiewicz, 1966).

    Two groups, each comprising 16 egg-laying hens, were given a single
    dose of 0 or 250 mg/kg of thiometon by gavage. Symptoms of poisoning
    in the test group appeared after three to four hours followed by death
    after approximately seven hours. At the terminal stage the treated
    birds displayed complete inhibition of cholinesterase activity in red
    cells, plasma and liver, and a highly significant decrease of
    cholinesterase, activity in brain, heart and adrenals associated with
    increasing sinus bradycardia. Increase in blood ascorbic acid and
    glucose occurred with no significant changes in the blood cholesterol
    level. Distinct electrocardiographic changes were recorded in the
    poisoned birds (Juszkiewicz and Rakalska, 1968).

    Special studies on neurotoxicity

    Two groups, each of four chickens, were given 35 mg/kg body-weight of
    thiometon by intramuscular injection. One of the groups was protected
    against acute anti-cholinesterase poisoning with atropine and
    pralidoxime. The unprotected chickens died, while the protected group,
    and a further group given atropine and pralidoxime alone, did not
    develop any signs of neurotoxicity during an observation period of 29
    days. A positive control group given triorthocresylphosphate displayed
    definite signs of paralysis (Sandoz, 1968a).

    Special studies on potentiation

    Groups of male and female rats were given thiometon by stomach tube in
    combination with the following organophosphorus compounds: diazinon,
    dimethoate, formothion, malathion, parathion and phosphamidon. There
    was no indication of potentiation except possibly in the female rats
    given the thiometon-parathion combination, and in this case, the
    effect if any, was extremely slight (Klotzsche, 1967).

    Special studies on reproduction

    After six months of administering thiometon in the 12-month experiment
    in rats, described under "Short-term studies", 10 male and 10 female
    animals from each dose-level and from the control group were mated and
    the off-spring observed for 30 days. The number of pairs producing
    off-spring were five (controls), seven (1 mg/kg), three (2 mg/kg), one
    (6 mg/kg), and two (18 mg/kg). Based upon these limited numbers of
    animals it was concluded that there was no difference between the
    controls and the groups given 1 and 2 mg/kg of thiometon as regards
    litter size and development of the young animals over 30 days (Sandoz,

    Groups of rats (15 males and 15 females) were administered by stomach
    tube 1 mg/kg body-weight of thiometon daily through three generations.
    The second litter from each generation served as parents to establish
    the next generation. In the F2b generation a dose-level of 2 mg/kg
    body-weight was administered as well as the 1 mg/kg level. It is
    claimed that no adverse effects on the parents or on their progeny
    were found with respect to growth, mortality, pathology and
    reproduction performances (Sandoz, 1968a; Thomann and Klotzsche,

    Special studies on teratogenicity

    Groups of 10 female rabbits were given 1 and 5 mg/kg body-weight of
    thiometon by stomach tube from days 6 to 18 of pregnancy. Several
    groups served as controls. After sacrifice on day 29 of pregnancy the
    foetuses were recovered by Caesarean section and no difference was
    found between the treated groups and the four control groups examined
    with respect to the number of implantations, live and dead foetuses,
    embryonic and foetal deaths, resorptions and the number of
    malformations. There were also no appreciable differences between the
    foetal and placental weights in the control and test groups (Sandoz,
    1968a; Thomann and Klotzsche, 1969).

    Acute toxicity

                                LD50 mg/kg
    Animal            Route     body-weight            References

    Mouse (mixed)     oral      65                     Sandoz, 1968b

    Rat (M)           oral      225 (pure compound)    Klotzsche, 1958

    Rat (M)           oral      100-120                Sandoz, 1968b

    Rat (F)           oral      120-125                Sandoz, 1968b

    Rat (M)           i.v.      27.5                   Sandoz, 1968b

    Rat (F)           i.v.      35.5                   Sandoz, 1968b

    Guinea pig        oral      261                    Sandoz, 1968b

    Rabbit (M)        oral      95                     Sandoz, 1968b

    Rabbit (M)        i.v.      22                     Sandoz, 1968b

    Cat               oral      36                     Sandoz, 1968b

    Except where otherwise stated the LD50 values were obtained from the
    formulated product Ekatin 25 percent and are reported on an active
    ingredient basis.

    The animals displayed the same symptoms as in poisoning with other
    organophosphorus compounds. The symptoms started with tremors, later
    convulsions, the formation of red lachrymal fluid and difficulties in
    breathing. The onset of symptoms were usually delayed for 60-90
    minutes after oral administration (Sandoz, 1968a).

    Short-term studies


    Groups of dogs (two males and one female) were initially treated
    orally with 0, 1, 2, 10 and 50 mg/kg body-weight of thiometon in
    gelatine capsules for six months for an unspecified number of days per
    week. All dogs in the 50 mg/kg group died within one week. In the 10
    mg/kg group, one animal died and the dose was decreased to 5 mg/kg for
    the two remaining dogs. Food consumption, body-weight, haematology,
    urinalysis and blood enzymes were comparable in the 1, 2 and 5 mg/kg
    groups and in the control group. Serum cholinesterase activity was
    slightly, but not definitely, lower in the test animals, while the red
    cell cholinesterase activity was markedly lower from the second week
    onward when compared to the controls. Brain cholinesterase measured in
    the cerebellum of the sacrificed animals showed no inhibition in the 1
    mg/kg group, a definite inhibition in the 2 mg/kg group and a marked
    inhibition in the 5 mg/kg group. No specific pathological changes
    attributable to thiometon were found by histological examination of
    all the dogs in the experiment (Sandoz, 1968a, Sandoz, 1969).


    Groups of rats each containing 25 males and 25 females were given
    daily doses by stomach tube of 0, 2, 6 and 18 mg/kg body-weight of
    thiometon for 12 months. Food intake, haematology, (limited number of
    animals) urinalysis and biochemical serum enzyme tests were comparable
    in the test and control groups. Females from all experimental groups
    showed the same weight gain as the controls, while the male rats given
    6 mg/kg showed a slight and with 18 mg/kg a marked decrease in weight
    gain. Serum and red blood cell cholinesterase determined in animals
    after monthly interim sacrifices showed fluctuating values both in the
    experimental and control groups. Both serum and red cell
    cholinesterase displayed a distinct depression in the 2 mg/kg, 6 mg/kg
    and 18 mg/kg groups. In the rats given 1 mg/kg there was a possible
    depression of serum cholinesterase and a definite depression of the
    red cell cholinesterase activity. Upon examination of 10 animals of
    each sex from each group, the average organ and body-weights were
    comparable in experimental and control groups and no changes in
    gross- or histopathology attributable to thiometon were found (Sandoz,
    1968a; Sandoz, 1969).

    Groups, each initially containing five male rats, were given oral
    doses of 5, 10, 15 and 20 mg/kg body-weight of thiometon for three
    months. All the animals showed mild to severe symptoms of poisoning.
    In the surviving five rats (four from the 5 mg/kg and one from the 10
    mg/kg group) the symptoms disappeared after 10 weeks of receiving
    thiometon and histological examination did not reveal specific
    pathological changes. These animals were sacrificed after 13 weeks
    (Sandoz, 1968a; Klotzsche, 1958).

    Groups of rats (five males and five females) were given 0, 0.08, 0.8
    and 8 mg/l of thiometon in their drinking water for six months.
    Water-intake, weight-gain, haematology and urinalysis were comparable
    in experimental and control groups. Other groups, containing five male
    rats, were treated with thiometon six times a week for six months with
    doses of 0, 0.0008, 0.008 and 0.8 mg/kg of body-weight using a stomach
    tube. In the rats given 0.008 and 0.08 mg/kg an effect on conditional
    reflexes and slight, but not definite, changes in haematology and
    urinalysis were apparent (Cabejszek et al., 1967).

    Long-term studies

    No Information available.


    No information on metabolic studies in animals and no observations in
    man are available. No long-term studies have been reported, the
    12-month study in the rat not being of sufficient duration for
    consideration as a long-term study, and the experiment in dogs was of
    only six months' duration. In these short-term studies, the lowest
    dose tested, namely 1 mg/kg, displayed marked inhibition of
    erythrocyte cholinesterase activity and slight depression of serum
    cholinesterase in two species of animal. Therefore, a no-effect level
    could not be established. Inadequate information is available on the
    composition of the technical product. For these reasons it is not
    possible to establish an acceptable daily intake for man at this time.



    Thiometon is a phosphorus-containing systemic insecticide and
    acaricide with activities as a contact and stomach poison. It has no
    ovicidal action. It is applied as an emulsifiable concentrate or dust
    to control aphids, red spider mites and saw flies on a wide variety of
    crops including cereals, cotton, sugarbeets, oil crops, forage, fruit,
    field crops, vegetables, coffee, tea, and tobacco. Protection when
    properly applied lasts 10-20 days depending on season, crop, and
    susceptibility of the pests. The standard concentration for high
    volume spray application is 0.1%. In low-volume applications thiometon
    per unit area or per tree remains the same. Amounts sprayed are 100 to
    600 g/ha. The usual methods of application are used; under certain

    conditions when rapid uptake or translocation is possible the
    formulated insecticide may be applied as a drench.

    Formulations of thiometon can be combined with most fungicides
    excluding alkaline ones. However, separate applications are

    The insecticide has been used in agricultural areas in Europe, South
    America, Africa, Asia, and Australia. Thiometon and its formulations
    have been registered in over 50 countries. Waiting periods after
    treatment are two weeks in Great Britain, three weeks in Australia,
    four weeks in Belgium, Denmark, Netherlands, Sweden, and Switzerland,
    and five weeks in Austria. Waiting periods before harvest more aptly
    depend on individual circumstances.

    Pre-harvest treatments

    Rate of spraying the insecticide on vegetables, bananas, cotton,
    coffee, tea, citrus, and sugarbeets is 0.025 percent and on stone
    fruits and vines 0.025-0.04 percent. On beets, cereals, and potatoes
    125-250 g/ha is applied. Application on beets and potatoes is repeated
    in 10-14 days to prevent virus infection. A 0.05 percent drench is
    also used on vegetables and hops.

    Post-harvest treatments


    Other uses

    Used on ornamentals, tobacco, and some other plants where sucking
    insects are a problem.


    Maximum residues following treatment of various crops are given in
    Table I. Residues after normal application generally decrease to less
    than 1 ppm after 10 days and, depending upon the crop and
    environmental factors (rainfall, temperature), disappear in two to
    four weeks.
        TABLE I
    Maximum residues found after treating various crops

                         Dosage             Pre-harvest         Maximum residue at end
    Crop                 % Conc. or g/ha    interval, days*     of interval, ppm*

    Apple                0.04%              21, 120             0.09, n.d.

    Bean                 0.02%              7, 14, 21           0.05, 0.25, 0.15

    TABLE I (cont'd)
    Maximum residues found after treating various crops

                         Dosage             Pre-harvest         Maximum residue at end
    Crop                 % Conc. or g/ha    interval, days*     of interval, ppm*

    Bean                 0.025%             1, 7, 14            0.6, 0.15, <0.1

    Cabbage              300-800g           106                 n.d.

    Carrots              0.25%              126                 n.d.

    Grapes               0.02%              21, 67              0.5, 0.1

    Lettuce              0.02%              3, 9, 14            5, 0.5, 0.1

    Olives               - **               7, 21               1.0, 0.70***

    Olive Oil            - **               7, 21               0.4, 0.10***

    Orange Fruit Pulp    0.0375%            45                  n.d.

    Orange Peel          0.0375%            45                  0.9***

    Orange Jam           0.0375%            (45)                n.d.

    Peach Fruit          0.03%              7, 21, 28           0.11, 0.12, 0.12

    Peanuts              100g               7                   0.15

    Peers                0.02%              33, 49              0.3, <0.05

    Plums                0.02%              10, 31              n.d., n.d.

    Potatoes             200g               36                  n.d.

    Potatoes             250-700g           89, 100             n.d., n.d.

    Sugarbeet            200g               43                  n.d.

    Tea, Green           0.025%             4, 7, 10            0.2, 0.2, 0.1

    Tomato               0.025%             7, 14, 21           n.d., n.d., 0.05

    TABLE I (cont'd)
    Maximum residues found after treating various crops

                         Dosage             Pre-harvest         Maximum residue at end
    Crop                 % Conc. or g/ha    interval, days*     of interval, ppm*

    Wine                 0.02%              (97)                n.d.

    *    When more than one interval is given, the residue values at each interval are in
         respective order. n.d. - none detected. Residues are sum of sulfone and sulfoxide
         of thiometon with but few exceptions.
    **   Amount applied not given (Gandolfo et al., 1966)
    ***  Data insufficient for setting tolerance.

    According to Sandoz (1969) thiometon is rapidly converted to
    metabolites and in a short time cannot be found in pure form. The
    following oxidation products are formed in the living plant:


    The major metabolites which impart the insecticidal action of
    thiometon are said to be the sulfoxide and sulfone of thiometon.
    According to Sandoz (1969) the sulfoxide and sulfone of
    demeton-S-methyl occur in very small amounts and therefore have much
    less significance; despite inclusion in some of the analyses, they are
    usually not detected. All metabolites are gradually inactivated by
    hydrolysis and after 10-14 days are usually gone.

    Data on mammalian metabolism was not provided.


    No information is available on residues in commerce or at the time of
    consumption. Residues in crops are said to be rapidly degraded by high
    temperature, especially by cooking.


    The early residue analyses utilized paper chromatography and more
    recent ones paper and thin-layer chromatography. These procedures
    require a thorough cleanup, some are only semi-quantitative, and they
    have limited sensitivity and specificity. With paper chromatography
    recovery is 85-95 percent for thiometon sulfoxide and 70-80 percent
    for thiometon sulfone; limit of detection is 0.03-0.05 and 0.06-0.09
    ppm, respectively (Faderl 1962; Sandoz, 1969). Thin-layer
    chromatography was slightly less sensitive.

    In line with today's improved technology a gas chromatographic method
    would be the method of choice in terms of accuracy, recovery,
    sensitivity, and specificity. Askew et al. (1969) and Ruzicka and
    co-workers (1967) utilized the Varian-Aerograph version of the
    thermionic detector to analyze compounds related to thiometon, but
    reported that oxydemeton-methyl was not detected by gas chromatography
    under their conditions. (Oxydemeton-methyl is a metabolite of
    thiometon). Bowman et al. (1969) showed that oxydemeton-methyl and its
    sulfone may be analyzed by the same flame-photometric gas
    chromatographic procedure used for disulfoton (ethyl analogue of
    thiometon). By utilizing a temperature of 165°C, they avoid the
    decomposition encountered at higher temperatures, and they condition
    the analytical column to the extract and compounds being analyzed.
    Their method may be adaptable for analysis of residues of thiometon.
    Sensitivities are in the order of 0.01 to 0.04 ppm. Specificity in
    excellent and virtually no cleanup is needed except for oily crops for
    which a simple hexaneacetonitrile portion should suffice.

    Another alternative is to oxidize the residues to the sulfone before
    gas chromatography. Procedures to accomplish this analysis or that of
    related compounds (disulfoton, phorate, and fenthion) have been
    described (Bowman and Beroza, 1969). By their procedure oxidation with
    m-chloroperbenzoic acid converts all of the metabolites to the
    oxygen analogue sulfone for analysis as a single compound. Recoveries
    usually were 80-100 percent. The 1968 FAO/WHO report indicates that
    oxydemeton-methyl (FAO/WHO, 1969; p. 225), may be oxidized to its
    sulfone for analysis by gas chromatography. Recoveries were 74-117
    percent for levels between 0.1 and 0.4 ppm. This procedure utilizes
    potassium permanganate and if applied to thiometon should produce two
    sulfones, one of thiometon and the other of demeton-S-methyl.
    Oxidation of the residues to a single compound would probably be the
    preferred practical procedure for regulatory purposes and might be
    made part of a general scheme for detecting organophosphorus


    Only the Netherlands and Switzerland have a definite tolerance for
    thiometon. It is 0.5 ppm.


    Thiometon is a systemic organophosphorus insecticide and acaricide
    that acts by contact and as a stomach poison. It in used to control
    plant lice, mites, and sawflies on a wide variety of crops.
    Applications by spray or dust (ingredients of product undefined) range
    from 0.1 to 0.6 kg/ha and protection usually lasts 10-20 days.
    Pre-harvest intervals are two to four weeks. Residue data from
    experimental trials in a number of countries are available.

    Thiometon itself is rapidly changed to its sulfoxide which is the
    principal residue along with the sulfone. The oxygen analogue
    sulfoxide and sulfone are said not to occur as residues to any great
    extent. Inspection of residues from related compounds (disulfoton,
    phorate, fenthion) indicate that the sulfoxides and sulfones of the
    oxons are occasionally found in significant amounts. Accordingly
    residue analyses for thiometon, its sulfoxide, and sulfone will
    suffice when experimental trials indicate that the corresponding
    oxygen analogues do not form in significant amounts.

    Metabolism studies on animals have not been reported, and residues in
    meat and milk have not been determined although parts of plants
    treated with thiometon are likely to be used as animal feed. It is not
    expected that residues of thiometon will appear in milk or meat since
    such residues have not been found after feeding similar compounds such
    as oxydemeton-methyl or disulfoton to dairy cows.

    The most suitable method for analysis is gas chromatography with a
    thermionic or flame-photometric detector. Such a method is likely to
    be more accurate, more sensitive (ca. 0.01 ppm), and more specific
    than methods currently in use. Evaluation of such a method for
    regulatory purposes is suggested.

    No data on residues in commerce or in studies of diets have been


    The data were insufficient for recommendations to be made.


    REQUIRED (before an acceptable daily intake or tolerances can
    be established)

    1. Long-term studies in animals.

    2. Cholinesterase inhibition studies to establish a no-effect level.

    3. Information on the content of the technical product and assurance
       of standard composition.

    4. Data on residue levels in way agricultural commodities moving in
       commerce and in total diet studies.

    5. Data on rate of disappearance during storage, processing and

    6. Information on composition of technical products, including

    7. Data on animal metabolism and residues in meat and milk of animals
       consuming agricultural products treated in accordance with good
       agricultural practice.


    1. Adequate information on metabolism.

    2. Investigation on cholinesterase inhibition in man.

    3. A gas chromatographic method for analysis of residues of thiometon
       and its metabolites suitable for regulatory purposes.


    Askew, J., Ruzicka, J.R. and Wheals, B.B. (1969) A general method for 
    the determination of organophosphorus pesticide residues in river
    waters and effluents by gas, thin layer and gel chromatography.
    Analyst 94, 275-83

    Bowman, M.C. and Beroza, M. (1969) A rapid gas chromatographic method 
    for determining residues of the insecticides fenthion, disulfoton,
    and phorate in corn, milk, grass and feces. J. Ass. Offic. Anal.
    Chem. 52, 1231-7

    Bowman, M.C., Beroza, M. and Gentry, C.R. (1969) GLC determination of
    residues of disulfoton, oxydemetonmethyl and their metabolites in
    tobacco plants. J. Ass. Offic. Anal. Chem. 52, 157-62

    Cabejszek, I., Rybak, K. and Szulinski, S. (1967) Effects in 
    warm-blood animals of thiometon (2-ethylthioethyl-O,O-dimethyl
    phosphorodithioate) in drinking water (Translated title) Roczn.
    Zak. Kig. (Warsz.), 18:257-65

    Faderl, N. (1962) Methode zur Bestimmung von Mikromengen organischer
    Phosphorinsektizide. Lebensm. Hyg. 53, 154-75

    FAO/WHO. (1969) 1968 evaluations of none pesticide residues in food. 
    FAO/PL: 1968/M/9/1; WHO/Food Add. 69.35

    Gandolfo, N., Camoni, I., D'Antonio, C., Leoni, V., Ramelli, G.C. and
    Sampaolo, A. (1966) Determination of O,O-dimethyl S-ethylmercaptoethyl
    phosphorodithioate (thiometon) and its metabolites in olives and
    olive oil. Atti simp. Int. Agrochim. 6, 224-33. (Chem. Abstr. 67,
    98979g (1967)

    Jucker, O. (1958) Thiometon, Verhalten in der Pflanze, Bestimmung von
    Spritzrücksänden. Mitt. Lebensmitt. Hyg., 49:299-322

    Juszkiewicz, T. and Rakalska, Z. (1968) Biochemical and 
    electrocardiographic changes in the course of an acute experimental 
    poisoning of hens with O,O-dimethyl-S-ethylmercaptoethyl 
    dithiophosphate. (Translated title) Pol. Arch. weteryu., 11:494-506

    Klotzsche, C. (1958) Thiometon, ein neuer systemischer
    Phosphorsäureester. Mitt. Lebensmitt. Hyg., 49:72-77

    Klotzsche, C. (1967) Toxicological investigations on the 
    potentiation effect of Ekatin (Thiometon). Unpub. Rept. from the 
    Department of Occupational Hygiene, prepared and submitted by Sandoz

    Madejski, Z. and Juszkiewicz, T. (1966) Effects of Ekatin poisoning on 
    some biochemical indices in chickens (Translated title) Pol. Arch.
    weteryn., 10:93-101

    Ruzicka, J., Thomson, J. and Wheals, B.B. (1967) The 
    gas-chromatographic examination of organophosphorus pesticides and
    their oxidation products. J. Chromatogr. 30, 92-9

    Sandoz. (1968a) Thiometon. An organophosphorus systemic insecticide. 
    Unpub. Rept. on animal toxicology submitted by Sandoz Ltd., Basle

    Sandoz. (1968b) Thiometon, Unpub. Rept. prepared and submitted by 
    Sandoz Ltd., Basle

    Sandoz. (1969) Ekatin R. Systemisches Insektizid und Akarisid. 
    Unpub. Rept. prepared and submitted by Sandoz Ltd., Basle Ref. AGRO 
    SLK No.E-3681

    Thomann, G. and Klotzsche, C. Untitled. Unpub. information submitted
    by Sandoz Ltd., Basle

    See Also:
       Toxicological Abbreviations
       Thiometon (ICSC)
       Thiometon (WHO Pesticide Residues Series 3)
       Thiometon (Pesticide residues in food: 1976 evaluations)
       Thiometon (Pesticide residues in food: 1979 evaluations)