DISULFOTON         JMPR 1975


         Disulfoton was evaluated by the Joint Meeting in 1973 (FAO/WHO,
    1974). In the light of data then available tolerances for vegetables,
    cereals (except rice) and some other food and feed crops were
    recommended. Further work or information was required on the
    occurrence of residues in meat, milk and eggs after feeding animals
    with disulfoton in order to recommend residue limits in food of animal
    origin. In addition, information on residues in food moving in
    commerce was mentioned as desirable. None of this information has been

         Revised national tolerances and pre-harvest intervals as well as
    studies an the fate of residues in rats have become available and are
    summarized in the following monograph addendum.

         Disulfoton is a member of the demeton family of insecticides.
    Disulfoton was reviewed by the 1973 Joint Meeting.  the basis of
    studies available at the time primarily short-term studies, a
    temporary Acceptable Daily Intake for man was estimated to be 0-0.001
    mg/kg (FAO/WHO, 1974). At that time it was understood that long-term
    feeding studies in rats and dogs had been initiated but were not
    complete. Further, it was required that kinetic studies on absorption,
    distribution metabolism and excretion be performed in mammals and an
    evaluation be made of liver damage observed in short-term studies with
    disulfoton sulfoxide. In addition, data was requested on residues in
    meat, milk and eggs after feeding animals on crops or foodstuffs
    treated with disulfoton in order to determine residue limits in foods
    of animal origin. Portions of these requirements have been met and the
    new work has been summarized in the following monograph addendum.




         Disulfoton, 14C-labelled in the O-ethyl position was orally
    administered to 2 male rats at a dose of 1.2 mg/kg and to 2 female
    rats a dose of 0.2 mg/kg. Urine, faeces and expired air were monitored
    over a 10 day interval. The major quantity of 14C-activity was
    observed in urine with males excreting 14C faster than females. In
    males and females respectively, after 10 days; 14C radioactivity was
    found in urine at 84 and 79%, faeces at 6 and 8% and as 14CO2 at 9
    and 9%. Total recovery of the administered dose was noted within 96
    hours of dosing. The excretion rate was different in males and females
    with males excreting one-half the dose in 4-6 hours while females
    excreted one-half the dose in 30-32 hours. Peak levels in tissues and
    blood were reached at about 6 hours. The liver of females contained
    higher (4-fold) relative tissue level than males. These differences

    might be related to the differences in dosage levels or to the greater
    susceptibility of females to acute toxicity of disulfoton.

         Urinary metabolites were characterized predominantly as water
    soluble component diethyl phosphate and diethyl thiophosphate. Organic
    soluble components (<3% of the dose) was characterized as the oxygen
    analogue sulfoxide, disulfoton sulfoxide, disulfoton oxygen analogue
    sulfone and an unknown in the following proportions (56:3:31:10).
    Similar metabolites were observed as small residues in tissue,
    predominantly liver. There was no sex differentiation with respect to
    metabolism. A distinct sex difference with respect to excretion was,
    however, observed (Puhl and Fredrickson, 1975).

    Effects on enzymes and other biochemical parameters

         Using cell culture techniques to examine cytotoxicity and
    susceptibility or changes in cells to infections by virus or to
    destruction by toxin, Gablicks and Friedman (1969) reviewed and
    reported on the increased susceptibility or sensitivity of cell
    cultures exposed to disulfoton. Cytotoxicity was observed with
    disulfoton in both change liver cells and in Hela cells. The effect of
    RNA, DNA and protein in Hela cells was examined (Litterst, et al.,
    1969). At 60 ppm growth was inhibited 50%. At 10 ppm nucleic acid
    synthesis was unaffected while protein systhesis was increased. Other
    studies have demonstrated the dose related inhibitory effect of
    disulfoton on growth of cells in culture. Huang (1973) observed that
    chromosomes were not damaged by disulfoton and the inhibited cell
    growth was readily resumed on removal of disulfoton. Cells in culture
    exposed to disulfoton showed greater sensitivity to polio virus but
    not to diphtheria toxin. Polio virus-treated cells exposed to
    disulfoton were more susceptible than the virus treated cells not
    exposed (Gablicks and Friedman, 1969). Following short-term
    administration of disulfoton to mice at higher levels (1/2 LD50) for
    10 days, a reduced barbiturate sleeping time and increased oxidation
    rate was noted in liver preparations and disulfoton was found to
    induce hepatic enzymes (Stevens, et al., 1972). Clark and Stavinoha
    (1969; 1971) also suggested changes in permeabilities of nervous
    tissue following 60 days dietary treatment in the rat (50 ppm) and
    mice (150 ppm). McPhillips et al. (1969) examined the effect of
    disulfoton on the physiological response of rats and confirmed
    previous findings on the reduction of sensitivity to cholinergic drugs
    by disulfoton. In addition the atrium of disulfoton-treated rats also
    developed reduced sensitivity to carbacol. These workers showed that
    subsensitivity induced by disulfoton did not occur in all tissues and
    cholinesterase inhibition did not relate to subsensitivity (Foley and
    McPhillips, 1972, 1973; McPhillips, 1969; McPhillips and Dar, 1967).
    The full significance of these interactions has not been defined.


         Adult rats and mice pretreated with phenobarbital to induce liver
    microsomal oxidizing enzymes were found to tolerate higher acute doses
    than untreated animals.


                                  LD50 (mg/kg)
         Species                  PB-Treated     Untreated

         Rats                     17.0           2.1

         Mice                     16.3           6.7

         (DuBois and Kinoshita, 1968)

         Administration of disulfoton at high levels (up to 1/2 LD50
    values) resulted in increased elimination of catecholamines rat urine.
    Increased adrenaline and noradrenaline levels in urine were observed
    soon after treatment and the levels returned to normal more rapidly
    than cholinesterase activity (Brzezinski and Ludwicki, 1973). In
    addition, a metabolite of adrenaline and noradrenaline (4-hydroxy,
    3-methoxymandelic acid) was found to have increased in rats poisoned
    with disulfoton (Wysocka-Paruszewska, 1970). It was suggested that the
    excretion of the mandelic acid derivative might be related to the
    toxic action of disulfoton (Wysocka-Paruszewska, 1971).


    Special studies on behaviour

         In an extensive series of papers Clark and coworkers (Clark, et
    al, 1971; Clark and Pearson, 1973) examined the effect of disulfoton
    on rodent behaviour. After 8 weeks of exposure to disulfoton in the
    diet at 150-200 ppm, mice were examined for behaviour changes. Treated
    mice were different from control mice with respect to a head insertion
    test. With rats, again a significant difference was observed in
    behaviour testing when disulfoton was administered in the diet,
    Treated rats made fewer errors and had shorter running times than
    controls. No differences in 3 treated groups (10, 25 and 50 ppm) were
    noted with respect to learning but each was greater than controls.

    Special studies on the metabolites


         Groups of rats (5 males and 5 females/group) were exposed to
    cigarette smoke for 1 hour/day 5 days/week for 3 weeks. The cigarette
    tobacco had been treated with disulfoton sulfoxide, demeton-S sulfone
    and MocapR in two different mixture concentrations. The first
    mixture contained 2.25 mg disulfoton sulfoxide, 1.75 mg demeton-S
    sulfone and 0.02 mg MocapR/kg tobacco. The second mixture contained
    11.25 mg, 8.75 mg and 0.1 mg of each respectively. Utilizing a
    reverse-puff smoking machine, cigarettes made from the treated tobacco
    were burned and the smoke introduced to an exposure chamber. No
    analyses of the chamber were made to confirm the presence of residues
    although smoke concentration was determined. No adverse effects of

    this programme were noted with respect to behaviour, growth,
    hematology, clinical chemistry and urinalysis. Gross and microscopic
    analysis of tissues and organs indicated no unusual pathology.
    Cholinesterase activity of plasma, RBC and brain measured at 21 days
    was not significantly depressed. A slightly depressed cholinesterase
    value of RBC in both males and females was not significantly different
    from controls but was dose dependent suggesting that an enzyme
    inhibitor or its precursor inhibitor did actually get to the animals
    in the smoke stream (Brewer, 1975).


         Groups of Angus steers and heifers were orally treated with a
    mixture of metabolites of disulfoton for periods up to 42 days. The
    mixture ratio was 60:40 disulfoton metabolites to demeton-S
    metabolites with the ratio of each Isomer being 1:2. Five groups of
    equal numbers of males and females were administered doses of 0,
    0.045, 0.09 0.18 and 0.36 mg/kg daily. The 0.36 mg/kg group (2 of each
    sex) were treated for 28 days; the 0.18 mg/kg group (2 of each sex)
    the 0.09 mg/kg group (3 of each sex) and the other two groups (3 of
    each sex) were treated for 42 days.

         In the two highest groups (0.36 and 0.18 mg/kg), signs of
    poisoning were evident and two animals of the high level died.
    Cholinesterase (whole blood) activity was measured weekly over the 7
    week treatment for 12 weeks after the treatment ended. Depression was
    noted in cholinesterase activity at levels of 0.09 mg/kg and above.
    Cholinesterase activity slowly recovered to normal in the surviving
    animals (generally within 3 weeks of the end of treatment). A
    no-effect level for this mixture in cattle was 0.045 mg/kg (Crawford
    and Anderson, 1974b).


         Mixed breed male and female sheep were orally treated with a
    mixture of metabolites of disulfoton as described above under
    "Cattle". Groups of sheep (2 males and 2 females per group) were
    administered the mixture at dose levels of 0, 0.045 and 0.09 mg/kg
    daily. One female of the 0.09 mg/kg dosed group died. Behaviour and
    body weight were not affected. Slight cholinesterase depression was
    noted in the upper level treatment group over the course of the study
    (Crawford and Anderson, 1974 b).

    Short-term studies


         Groups of beagle dogs (4 males and 4 females/group) were fed
    disulfoton in the diet for two years at dosage levels of 0, 5, 1.0
    ppm. A fourth group was fed 2.0 ppm from weeks 1 to 69; 5.0 ppm from
    weeks 70 to 72; 8.0 ppm from 72 to 104. There was no compound related
    mortality noted during the course of the study. Behaviour and growth
    were normal at all dose levels.

         Ophthalmological examinations, clinical chemistry, haematology
    and urinalyses were normal over this time period. Plasma and RBC
    cholinesterase were examined periodically over the course of the study
    and at the conclusion brain cholinesterase activity was determined. No
    depression was noted in plasma, RBC or brain cholinesterase activity
    in the 1.0 ppm group of males and females. At 2.0 ppm and above
    depression was noted in plasma and RBC. This depression was
    accentuated at the time of increased dosing and was evident at the
    conclusion of the study in brain cholinesterase depression (at 8.0
    ppm). At the conclusion of the study gross and microscopic examination
    of tissues and organs revealed no abnormalities. A no-effect level in
    this study is 1.0 ppm in the diet (0.0266 mg/kg body weight) (Hoffmann
    and Weischer, 1975).



         Species            Sex    Route    LD50 (mg/kg)    References


         Rat                F      Oral        2.0          Crawford &
                            M      Oral        >2.0        Anderson, 1974a          

    Disulfoton Sulfoxide

         Rat                F      Oral        1.7                 "
                            M      Oral        >1.7                "

    Disulfoton Sulfone

         Rat                F      Oral        1.24                "
                            M      Oral        >1.24               "

    Demeton-S (isosystox)

         Rat                F      Oral        1.17                "
                            M      Oral        >1.17               "

    Demeton-S Sulfoxide

         Rat                F      Oral        1.24                "
                            M      Oral        >1.24               "


         Rat                F      Oral        1.10                "
                            M      Oral        >1.10               "

    Long-term studies


         Groups of rats (60 males and 60 females/group) were fed
    disulfoton in the diet for two years at dose levels of 0, 0.5 (from
    weeks 0-80), 1.0, 2.0 and 5.0 (from weeks 80 to 104) ppm. Food
    consumption behaviour and growth were normal. Haematology, clinical
    chemistry and urinalysis parameter were unaffected. Plasma, RBC and
    brain cholinesterase inhibition were evident at the higher dose
    levels. In males, a slight blood cholinesterase depression (15%) was
    noted at 2 ppm while in females this slight depression (12%) was seen
    at 1 ppm. The reduction in enzyme activity was dose dependent and
    significant (>20%) above the 2 ppm level. Brain cholinesterase was
    depressed in a dose dependent manner with significant depression
    (>20%) observed at 5 ppm in males and at 2 ppm and above in females.
    Liver esterase activity was slightly affected at the highest level
    only. Gross and microscopic analysis showed no differences from
    controls. No changes in liver epithelial cells were mentioned. A no
    effect level in this study was 1.0 ppm (Klotzsche, 1975).


         Disulfoton is rapidly absorbed and excreted primarily in urine.
    The metabolic scheme reviewed and reported by the 1973 Meeting has
    been further supported by new studies. Toxicological studies of
    combinations of metabolites administered to animals directly, as with
    cattle and sheep or via inhalation as with a rat cigarette smoke
    study, confirm approximately the no-effect level in rat and dog.

         These studies suggest that toxicological studies of the
    combinations are similar to studies of the parent material confirming
    the conclusion of rapid metabolism in animals of disulfoton to active
    antesterase metabolites. In cell culture, protein synthesis is
    reversibly inhibited at 10 ppm and disulfoton is cytotoxic at 60 ppm.

         Results of two year studies, particularly the long-term toxicity
    studies and the metabolic data, confirm the previously suggested ADI
    for man.


    Level causing no significant toxicological effect in animals

         Rat: 1 ppm in the diet equivalent to 0.05 mg/kg bw

         Dog: 1 ppm in the diet equivalent to 0.025 mg/kg bw

    Estimate of acceptable daily intake for man

         0-0.002 mg/kg bw



    In animals

         Feeding studies were carried out in rats using
    diethyl-1-14C-labelled disulfoton. A single dose of 1.2 mg/kg (male)
    and of 0.2 mg/kg (female) was administered directly into the stomach
    (Puhl and Fredrickson, 1975). Each of the doses corresponded to 10% of
    the LD50 value (FAO/WHO, 1974). The animals were allowed food and
    water ad libitum throughout the experiments. 14C was distributed as
    shown in Table 1.

    TABLE 1. Recovery (%) of total 14C from rats dosed with disulfoton


                                 % of administered 14C found in

                          Urine               Faeces        Expired CO2
    Period after                                                        
    (hrs)            male    female       male   female     male   female

    0 - 4            41.6    6.2          -      Na

    4 - 8            19.3    5.0          1.6    Na

    8 - 12           6.0     12.4         1.3    Na

    12 - 24          6.9     19.9         1.6    2.6        6.9b   3.2b

    24 - 48          5.6     17.8         0.9    2.5        0.8    1.6

    48 - 72          2.2     7.0          0.4    1.4        0.6    1.2

    72 - 144         2.0     7.7          0.3    1.2        0.7    1.9

    144 - 240        0.7     2.9                 0.2        0.2    1.3

    Totals           84.3    78.9         6.1    7.8        9.2    9.2

    Combined recovery:  Urine + faeces + CO2,    male      = 99.6%
                                                 female    = 95.9%

    a No faeces excreted.
    b The first sample was for the period 0-24 hrs.

         Tissues and blood were analysed for 14C (disulfoton equivalents)
    at various time intervals. Peak levels occurred after about six hours
    in both male and female rats. Residues in liver were highest, reaching
    a peak of about 3.6 mg/kg for male and 2.3 mg/kg for female rate. The
    relative magnitude of peak residues in other samples (male-female)
    fell in the order kidney (1.4-0.8), plasma (0.8-0.15), fat
    (0.45-0.08), whole blood (0.39-0.01), skin (0.3-0.05), muscle
    (0.13-0.01) and brain (0.08-0.01). Ten days after administration, the
    residue ranges were as follows. Liver (0.154-0.119), kidney
    (0.051-0.026), heart (0.016-0.004), fat (0.090-0.009), muscle
    (0.012-0.002), brain (0.015-0.006), skin (0.037-0.006) and blood
    (0.007-0.002). It should be borne in mind that the dose for female
    rats was only one-sixth of the dose for male rats.

         Excretory pathways were similar for males and females but the
    rate of excretion appeared to be slower for females. Diethyl phosphate
    (DEP) and diethyl phosphorothionate (DEPT) comprised 93% of the 14C
    while minor urinary metabolites included demeton-S sulfone (POSO2)
    and disulfoton sulfoxide (PSSO). Depending upon the sex of the animals
    and the time after administration 19-48% of the total 14C in the
    livers was water-soluble and 0.3-3.4% was soluble in chloroform. The
    respective data for kidneys were 39-78% and 0.5-5.6%.
    Chloroform-soluble oxidation products in liver and urine were POSO,
    PSSO and POSO2. Non-extractable residues in liver may be
    diethylphosphorylated protein.

    FIGURE 1

    TABLE 2.  National tolerances reported to the Meeting
              (Changes and additions since last evaluation)


                                                         Tolerance     interval
    Country               Commodity                      (mg/kg)       (days)

    Argentina      Lettuce, peanuts, potatoes,              0.75
                   cabbage, cauliflower, spinach,
                   tomatoes, pecans, barley,
                   rice, maize (fodder),

                   Sugarcane, coffee, maize                 0.3
                   Sugar beet (roots)                       0.5

                   Wheat                                    0.2

                   Sugar beet (leaves)                      2.0

                   Alfalfa and clover (hay)                 12.0

                   Carrots                                  0

                   Alfalfa (fresh), rye, wheat,             5.0
                   oats, barley (fodder), clover
                   (fresh)  peanuts (fodder)

    Canada         Broccoli, cabbage                        0.75

                   Beans (dry, lima, snap),                 0.5
                   Brussels sprouts, cauliflower,
                   lettuce, peas, spinach,

                   Potatoes                                 0.2

                   Barley (grain), coffee, corn             N.R.
                   (grain) (incl. field corn,
                   sweet corn [kernels plus cob
                   with husk removed] & popcorn),
                   cottonseed, eggplant, oats
                   (grain), peanuts, peppers,
                   pineapple, rice (grain), sugar
                   beets, wheat (grain)

    TABLE 2. (continued)


                                                         Tolerance     interval
    Country               Commodity                      (mg/kg)       (days)

    Federal        Potatoes                              0.2
    Republic of
    Germany        Cereals                               0.1
                   disulfoton-sulfone, demeton, 
                   demeton-sulfone: calculated 
                   together as disulfoton)

    Hungary        General                               0.2              56

    Japan          Rice, fruit, vegetables               0.1
                   beans, potatoes

                   Rice                                                   50

                   Citrus fruit                                           30

                   Eggplants, tomatoes                                    21

                   Soybeans, azukibeans, garden                           60
                   pea, kidney bean, broad bean

    Netherlands    Potatoes                                 0.01

                   All other crops                          0

    New Zealand    Potatoes                                               91

    Switzerland    Lettuce                                  0.2

                   Vegetables, field crops                                42

    TABLE 2. (continued)


                                                         Tolerance     interval
    Country               Commodity                      (mg/kg)       (days)

    United States  Alfalfa (hay), clover (hay)              12.0
    of America
                   Alfalfa (fresh), barley (green           5.0
                   fodder, straw), beans (vines),
                   clover (fresh), corn forage &
                   fodder (incl. field corn,
                   sweet corn and popcorn), oats
                   (green fodder, straw), peanuts
                   (hay), peas (vines), pineapple
                   (foliage), rice (straw),
                   sorghum fodder & forage, sugar
                   beets (pulp, feed additive),
                   wheat (green fodder, straw)

                   Sugar beets (tops)                       2.0

                   Barley (grain), beans (lima              0.75
                   dry, snap), broccoli,
                   Brussels sprouts, cabbage,
                   cauliflower, cottonseed,
                   lettuce, oats (grain),
                   peanuts, pecans, peas,
                   pineapple, potatoes, rice
                   (grain), sorghum (grain),
                   spinach, tomatoes

                   Hops, sugar beets                        0.5

                   Coffee corn grain (incl. field           0.3
                   corn, sweet corn [kernels plus
                   cob with husk removed] & popcorn),
                   sugar-cane (raw), wheat

                   Soybean forage & hay                     0.25

                   Peppers, soybeans                        0.1

    Yugoslavia     General                                  0

                   Field crops                                            60


         Disulfoton was evaluated at the 1973 Joint Meeting (FAO/WHO
    1974). Reviewing the data then available the Meeting required
    information on the occurrence of residues in meat, milk and eggs after
    feeding animals with disulfoton in order to recommend maximum residue
    limits in food of animal origin. In addition, information on residues
    in food moving in commerce was mentioned as desirable. None of this
    information has been received.

         Revised national tolerances and pre-harvest intervals as well as
    studies on the fate of residues in rats have become available.
    Fourty-eight and 72 hours after oral application of a single dose of
    diethyl-l-14C-labelled disulfoton (0.2 mg/kg female rat and 1.2 mg/kg
    male rat) 71% and 81% respectively of the administered 14C was
    excreted in the urine and faeces and expired as carbon dioxide by the
    females. The corresponding figures for males were 93% and 96%. Ten
    days after dosing, 96% (female) and 100% (male) of the 14C had been
    excreted. Diethyl phosphate and diethyl phosphorothionate were
    identified as major metabolites. Peak levels of 14C in tissues
    occurred about 6 hours after dosing, reaching maximum levels
    (disulfoton equivalents) of 3.6 mg/kg in liver, 1.4 mg/kg in kidney,
    0.45 mg/kg in fat, 0.3 mg/kg in skin, 0.13 mg/kg in muscle and 0.08
    mg/kg in brain. Ten days after administration maximum residues in
    tissues and blood ranged from <0.01 to 0.15 mg/kg. A maximum of 3.4%
    of the residues in liver were chloroform-soluble metabolites
    (demeton-S sulfoxide, disulfoton sulfoxide and demeton-S sulfone).

         Since demeton-S sulfoxide and demeton-S sulfone are metabolites
    of disulfoton as well as of demeton, it is difficult or impossible to
    determine which parent compound is responsible for residues of them.
    Further explanation is given in the Appraisal of demeton (see this
    Meeting Report).

         For residue analysis, oxidation of the residues and determination
    of demeton sulfone and disulfoton sulfone by the GLC method previously
    described (FAO/WHO, 1974) should be suitable for regulatory purposes.


         New recommendations (alfalfa [hay], clover [hay], maize) together
    with previous recommendations as set out-below refer to the total
    residue of disulfoton, disulfoton sulfoxide, disulfoton sulfone,
    demeton, demeton sulfoxide and demeton sulfone calculated and
    expressed as disulfoton.


         Commodity                                         Residue Limit

         Alfalfa (hay), clover (hay)                       10

         Forage crops (green) 5

         Vegetables including beans, broccoli,
         Brussels sprouts, cabbage, cauliflower,
         celery, lettuce, maize, potatoes, peanut
         shells, peas (inc. pods), rice (in husk),
         spinach, sugar beets (roots), tomatoes            0.5

         Raw grain (except rice and maize)                 0.2

         Coffee beans, pecans, peanuts (kernels),
         pineapple, soybeans                               0.1



         1.   Residue data from supervised trials for commodities not
              mentioned above, but included in national tolerance lists.

         2.   Results from studies now in progress (expected in the spring
              of 1976) on residues in meat, milk and eggs after feeding
              animals on fodder treated with disulfoton in order to
              determine residue limits in food of animal origin.

         3.   Information on residues in food moving in commerce.


    Brewer, W. E. (1975) 21-day subacute inhalation toxicity study with
    di-syston sulfoxide, di-syston oxygen Analog, sulfone and mocap in
    rat. Unpublished report from Industrial Biotest Laboratories submitted
    to the World Health Organization by Bayer AG.

    Brzezinski, J. and Ludwicki, K. (1973) The interrelationship of the
    changes of acetylcholinesterase and catecholamines, blood and urine
    levels in rats poisoned with di-syston. Pol. Pharmacol Pharm. 25:

    Clark, G. and Stavinoha, W. B. (1969) Alterations in liver RNA induced
    by atropine and disulfoton. Tox. Appl. Pharmacol. 14: 376-79.

    Clark, G. and Stavinoha, W. B. (1971) A permeability change in CNS
    tissue in chronic poisoning with Disulfoton. Life Sci. 10: 421-23.

    Clark, G., Koester, A.G. and Pearson, D. W. (1971) Exploratory
    behaviour in chronic Disulfoton poisoning in mice. Psychapharmacologia
    (Berl.) 20: 169-71.

    Clark, G. and Pearson, D. W. (1973) Learning in chronic disulfoton
    poisoning. J. Gen. Psychol. 89: 305-11.

    Crawford, C. R. and Anderson, R. H. (1974a) The acute oral toxicity of
    several Di-Syston metabolites to female and male rats. Unpublished
    Report from Mobay Chemical Corporation submitted to the World Health
    Organization by Bayer AG.

    Crawford, C. R. and Anderson, R. H. (1974b) Subacute oral toxicity of
    a mixture of four Di-Syston metabolites to cattle and sheep.
    Unpublished Report from Mobay Chemical Corporation. Submitted to the
    World Health Organization by Bayer AG.

    DuBois, K. P. and Kinoshita, F. K. (1968) Influence of induction of
    hepatic microsomal enzymes by phenobarbital on toxicity of organic
    phosphate insecticides. Proc. Soc. Exper. Biol. Med. 129: 699-702.

    Echobichon, D. J. and Kalow, W. (1963) Action of organophosphorus
    compounds upon esterases of human liver. Can. J. Biochem. Physiol. 41:

    Foley, D. J. and McPhillips, J. J. (1972) Relationship between
    cholinesterase activity and sensitivity to cholinergic drugs in the
    rat ileum. Tox. Appl. Pharmacol. 22: 286-87.

    Foley, D. J. and McPhillips, J. J. (1973) Response of the rat ileum
    uterus and vas deferens to carbacol and acetyl choline following
    repeated daily administration of a cholinesterase inhibitor. Brit. J.
    Pharmacol. 48: 418-25.

    Gablicks, J. and Friedman, L. (1969) Effects of insecticides on
    mammalian cells and virus infections. Ann. N.Y. Acad. Sci. 160: Art.
    1: 254-71.

    Hoffmann, K. and Weischer, C. H. (1975) S-276. (Disulfoton) Chronic
    toxicity study on dogs (two year feeding experiments). Unpublished
    report from the Institute for Toxicology submitted to the World Health
    Organization by Bayer AG.

    Huang, C.C. (1973) Effect on growth but not chromosomes of the
    mammalian cells treatment with three organophosphorus insecticides.
    Proc. Soc. Exp. Biol. Med. 142: 36-40.

    Klotzsche, C. (1975) Disulfoton. 2-year Feeding Study in Rats.
    Unpublished report from Agrochemical Research Department. Submitted to
    the World Health Organization by Sandoz Ltd.

    Litterst, C. L., Lichtenstein, E. P. and Kajiwara, K. (1969) Effects
    of insecticides on growth of Hela cells. J. Agr. Food Chem. 17:

    McPhillips, J. J. (1969) Altered sensitivity to drugs following
    repeated injections of a cholinesterase inhibitor to rats. Toxicol.
    Appl. Pharmacol. 14: 67-73.

    McPhillips, J. J. and Dar, M. S. (1967) Resistance to the effect of
    Carbacol on the cardiovascular system and on the isolated ileum of
    rats after subacute administration of an organophosphorus
    cholinesterase inhibitor. J. Pharmacol. Exp. Therap. 156: 507-13.

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    See Also:
       Toxicological Abbreviations
       Disulfoton (ICSC)
       Disulfoton (WHO Pesticide Residues Series 3)
       Disulfoton (Pesticide residues in food: 1978 evaluations)
       Disulfoton (Pesticide residues in food: 1979 evaluations)
       Disulfoton (Pesticide residues in food: 1981 evaluations)
       Disulfoton (Pesticide residues in food: 1984 evaluations)
       Disulfoton (Pesticide residues in food: 1991 evaluations Part II Toxicology)