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    FENSULFOTHION                              JMPR 1972

    IDENTITY

    Chemical name

         O,O-diethyl-O-[4-(methylsulfinyl)] phosphorothioate.

    Synonyms

         O,O-diethyl-O-[4-(methylsulfinyl)] monothiophosphate.

         Dasanit(R), Terracur(R), Bay 25144.

    Structural formula

    CHEMICAL STRUCTURE 1


    Other information on identity and properties

         Physical state:     yellow-brown liquid

         Molecular weight:   308.35

         Boiling point:      138 - 141°C at 0.01 mm Hg

         Volatility:         <0.01 mg/cu meter (20°C)

         Specific gravity:   D 20 = 1.202
                               4

         Refractive index:   n 25 = 1.54
                               D
         Solubility:         in water, at 20°C, 1200 ppm soluble in most
                             organic solvents except aliphatics

         Stability:          stable under normal conditions of storage and
                             use

         Hydrolysis rate:    half-life at 81°C and pH 2.5 - 6, 120 hours

         Formulations used:  granular 3, 5, 10 and 15%; liquid (EC) 720
                             g/l

         Purity of           fensulfothion 94-96; O,O-diethyl-
         technical           O[4(methylthio)-phenyl] phosphorothioate
         material:           1-3; O,O-diethyl-O-4(methylsulfonyl)-
                             phenyl] phosphorothioate 0.2 - 0.6;
                             4-(methylsulfinyl) phenol 0.8 - 1.0; water
                             0.3 - 0.8 (all figures in % w)

    EVALUATION FOR ACCEPTABLE DAILY INTAKE

    BIOCHEMICAL ASPECTS

    Absorption, distribution and excretion

    Following oral administration to rats fensulfothion is rapidly
    absorbed, distributed and excreted. Following oral doses of 0.7 to 1.5
    mg/kg, tissue residues reached maximum values within 8 hours and
    residues were rapidly excreted within 24 hours, primarily in the
    urine. Female rats appear to excrete the acutely administered dose
    somewhat slower than males. These differences may account for the
    greater susceptibility of females when administered acutely toxic
    doses (Everett, 1968).

    Biotransformation

    The metabolic route is largely through oxidative and/or hydrolytic
    pathways. In female rats, the formation of the oxygen analogue and its
    sulfone followed by P-O-ethyl dealkylation is a significant pathway.
    In male rats hydrolytic and/or oxidative cleavage of the
    phosphorothionate of the sulfoxide or the sulfone is the more
    prevalent route of detoxication. Although the presence of the
    metabolite 4-methylthiophenol was detected in certain biological
    systems, this reductive pathway is believed to be minor.

    Fensulfothion, applied to plant stems or to roots in a water
    dispersion, was absorbed slowly into the plant and converted to the
    phosphate analogue and to the sulfone. After 9 days the sulfone
    phosphate analogue was detected (Katague and Anderson, 1967; Benjamini
    et al., 1959a). In air, slow oxidation to the sulfone and
    isomerization of the phosphorothiolate was shown to occur (Benjamini
    et al., 1959b). This conversion has not been demonstrated in mammals
    with fensulfothion. A summary of the significant features of the
    metabolic pathway of fensulfothion is shown in Figure 1.

    Effect on enzymes and other biochemical parameters

    Fensulfothion, like other organophosphorothionate esters, is a weak
    cholinesterase inhibitor which, after being converted to the
    corresponding phosphate ester of fensulfothion is from 500 to 2 000
    times more active in inhibiting cholinesterase.

    Following intraperitoneal administration of fensulfothion (0.9 mg/kg)
    to rats, inhibition of cholinesterase was maximal within one hour.
    Reversal of inhibition became evident within 6 hours and was
    progressive for 5 days, at which time activity returned to near normal
    values (Dubois & Kinoshita, 1964).

    As with several other compounds of a similar structural nature,
    cholinesterase activity in females is more sensitive to in vivo
    anti-cholinesterase activity. This is possibly a result of a
    difference in enzyme sensitivity or a sex difference in the rate of
    metabolism. No other biochemical parameters appear to be affected by
    fensulfothion.

    TOXICOLOGICAL STUDIES

    Special studies on metabolites

    Acute toxicity of fensulfothion metabolites and related products in
    rats is shown in Table 1.

    Special studies on mutagenicity

    A dominant lethal test using groups of male mice (12 mice/group) was
    conducted by treating the animals with fensulfothion by
    intraperitoneal injection with 0, 0.5 and 1.0 mg/kg. For 6 consecutive
    weeks treated males were placed in a cage with 3 untreated females per
    week. The females were sacrificed at mid-pregnancy and examined for
    reproduction defects; i.e., implantation sites, resorption sites and
    live embryos. There were no significant differences between the test
    and controls on any parameter examined. Fensulfothion does not affect
    the mutation rate as evidenced by the mouse dominant lethal test
    (Industrial Biotest Laboratory, 1971b).

    FIGURE 1

    TABLE 1  Acute toxicity of fensulfothion metabolites and related
             products in rats
                                                                             
                                            LD50
                                           (mg/kg)              I501
                                             ip
    Name                  Formula       M            F          (M)
                                                                             
    Sulfide-P(S)          R-S-CH3                    2.52       3×10-4
                                        5.5          1.53       5.4×10-4

                            O
    Sulfoxide P(S)          "
    (fensulfothion)       R-S-CH3                    1.5        3×10-4
                                        4.5          1.2        2.5×10-5

                            O
    Sulfone P(S)            "
                          R-S-CH3                    1.6        5.1×10-7*
                            "
                            O
                                        3.7          1.4        8.6×10 -5

    Sulfide P(O)          R1-S-CH3                   2.0        1.6×10 -7
                                        1.8          1.5        4.9×10 -7

                             O
                             "
    Sulfoxide P(O)        R1-S-CH3                   1.2        1.6×10 -7
                                        1.8          1.4        5.3×10 -8

                             O
                             "
    Sulfone P(O)          R1-S-CH3                   0.9        4.8×10 -9
                             "
                             O
                                                                             
    CHEMICAL STRUCTURE 2
                                                                             

    1  Rat brain cholinesterase, molar concentration inducing
         50% inhibitions.

    2  Dubois & Kinoshita, 1964
    3  Dubois & Jackson, 1967

    *  This extremely low value is probably due to contamination with the
       P(O) analogue.

    Special studies on neurotoxicity

    Chickens were administered fensulfothion orally or by intraperitoneal
    injection at dosage levels ranging from 0.005 to 0.05 gm/kg (the birds
    were administered atropine and 2-PAM prior to fensulfothion). The hens
    that survived the acute signs of poisoning did not show weakness or
    ataxia. At the dosage levels tested fensulfothion does not induce a
    delayed neurotoxic response, as seen with TOCP (Kimmerle, 1965b).

    Chickens were fed fensulfothion in the diet at levels of 0, 1, 5, 20
    and 100 ppm for 30 days. One day after treatment ended and again 30
    days later hens were sacrificed and nerve tissue examined
    histologically. Histological examination showed no evidence of
    demyelination. The 100 ppm level caused death of half of the animals
    and the survivors showed clinical signs of poisoning. Cholinesterase
    inhibition in blood was depressed after 30 days of feeding but was
    recovered after 4 weeks. There were no clinical or pathological signs
    of delayed neurological disruption, as evidenced with TOCP (Kimmerle,
    1965a; Grundmann, 1965).

    Special studies on potentiation

    Fensulfothion was administered intraperitoneally by simultaneous
    administration of ´ LD50 doses to female rats in combination with 17
    other anticholinesterase pesticides. There was no evidence of greater
    than additive acute effects. This potentiation study was carried out
    with parathion, malathion, EPN, phosdrin, ethion, fenchlorphos,
    methylparathion, azinphos-methyl, chlorobenzilate, dithianon,
    carbaryl, coumaphos, disulfoton, demeton, trithion, schradan, diazinon
    (Dubois and Kinoshita, 1963).

    Special studies on reproduction

    Groups of mice (24 females and 6 males/group fed 0, 1, 5 and 20 ppm
    and 40 females and 10 males/group for the first breeding and 24
    females and 6 males for the second breeding fed 0, 2 and 4 ppm) were
    fed fensulfothion and subjected to a standard 3-generation, 2-litter/
    generation, reproduction study. The level of 20 ppm was lethal and was
    discarded. At 5 ppm female mice of the Fo generation had an increased
    mortality prior to mating. The survivors showed no effects of 5 ppm in
    the diet on reproduction, gestation or lactation indices. A slight
    reduction in lactation index was seen at 5 ppm in the F3b pups
    surviving to weaning. Gross and microscopic examination of tissues of
    the F3b groups showed no changes attributable to the inclusion of
    fensulfothion in the diet. The effects of fensulfothion in the diet at
    20 and 5 ppm, although these levels are toxic to mice, do not reflect
    a hazard to reproduction (Doull et al., 1967).

    Special studies on teratogenicity

    Pregnant rabbits (9-11 rabbits/group) were administered fensulfothion
    orally at dosage levels of 0.05 and 0.1 mg/kg per day on days to 16 of
    gestation. On day 29 all animals were sacrificed and the young removed
    by caesarean section. Fensulfothion did not affect pregnancy or fetal
    mortality as indicated by the number of resorption sites, abortions or
    dead fetuses. There was no evidence of abnormal fetal development from
    gross observation or from examination of skeletal structure at 0.05
    mg/kg/day. At 0.01 mg/kg/day there was a slight nonsignificant
    increase in minor skeletal abnormalities. Fensulfothion is not
    teratogenic to the rabbit (Industrial Biotest Laboratory, 1971a).

    Acute toxicity

    Acute toxicity of fensulfothion has been studied in several animal
    species, a summary of results is given in Table 2.


    TABLE 2  Acute toxicity of fensulfothion in animals

                                                                             

    Species     Sex    Route        LD50          Reference
                                    (mg/kg)
                                                                             

    Rat         M      oral         3.96-10.5     Dubois & Kinoshita, 1964
                                                  Kimerle, 1965c
                                                  Gaines, 1969
                                                  Solly & Harrison, 1971a

                       ip           5.5           Dabois & Kinoshita, 1964
                                                  Spencer, 1968

                F      oral         1-8-2.3       Dubois & Kinoshita, 1964
                                                  Kimmerle, 1965c
                                                  Gaines, 1969
                                                  Solly & Harrison, 1971a

                F      ip           0.9-1.5       Dubois & Kinoshita, 1964
                                                  Spencer, 1968

                M      dermal       14-30         Dubois & Kinoshita, 1964
                                                  Kimmerle, 1965c
                                                  Gaines, 1969

    Rat         F      dermal       3.5-13        Dubois & Kinoshita, 1964
                                                  Kimmerle, 1965c
                                                  Gaines, 1969

    TABLE 2  (Cont'd.)

                                                                             

    Species     Sex    Route        LD50          Reference
                                    (mg/kg)
                                                                             

                M      inhalation   0.113 mg/l    Kimmerle, 1966
                                    (1 h)

                                    0.030 mg/l
                                    (4 h)

    Mouse       M      ip           10.5          Dubois & Kinoshita, 1964

                F      ip           7.0           Ibid.

    Guinea      M      oral         9.0           Ibid.
    Pig

                M      ip           5.4           Ibid.

    Sheep       F      oral         3.4           Solly Harrison, 1971a

    Chick       M      oral         0.99          Sherman & Ross, 1961

    Chicken     p      oral & ip    2.5-5.0       Kimmerle, 1965b
                                                                             


    Signs of poisoning following acute intoxication are typical of other
    organophosphate esters capable of inducing cholinergic signs of
    poisoning. Signs of poisoning occur rapidly and animals return to
    normal within 24 hours (Dubois & Kinoshita, 1964).

    The administration of atropine (100 mg/kg) 10 minutes before
    intraperitoneal administration of fensulfothion increased the LD50
    from 1.5 to 2.0 mg/kg. Intraperitonal injection of PAM (100 mg/kg)
    immediately after fensulfothion raised the LD50 to 6 mg/kg. Treatment
    with both agents resulted in an LD50 of 7 mg/kg (Dubois & Kinoshita,
    1964). Following oral administration of fensulfothion, atropine and
    combinations of atropine and PAM or atropine and BH-6 were shown to
    increase the LD50 values (Kimmerle, 1966). Atropine in combination
    with reactivators of cholinesterase are effective antidotal agents for
    the acute toxic effects of fensulfothion.

    Short-term studies

    Rat

    Groups of female rats (5/group) were administered fensulfothion by
    intraperitoneal injection daily for 60 days at dosage levels of 0,
    0.25, 0.50 and 0.75 mg/kg. Mortality occurred at the highest dose with
    5 of 5 rats dead within one week. At 0.5 mg/kg/day, 4 of the 5 rats
    survived the treatment. All rats showed significantly reduced growth
    rates and reduced brain, serum and submaxillary gland cholinesterase
    activity (Dubois & Kinoshita, 1964).

    Groups of female rats (25 rats/group) were fed fensulfothion for 8
    weeks at dosage levels of 0, 0.5, 1 and 2 ppm. RBC cholinesterase
    inhibition was observed at 2 ppm while plasma and brain levels were
    unaffected. No cholinesterase depression was observed at lower dose
    levels. Mortality, growth, hematology and clinical chemistry
    parameters were normal (Root et al., 1969).

    Dog

    Groups of dogs (2 males and 2 females/group) were fed fensulfothion in
    the diet at levels of 0, 1, 2, 5 and 10 ppm for 12 weeks. Other groups
    fed at levels of 5 and 10 ppm displayed cholinergic signs of poisoning
    and were removed from the study. Inhibition of cholinesterase was
    observed in serum and RBC at 2 ppm and above. At 5 ppm and 10 ppm
    signs of cholinergic poisoning and weight loss were observed (Root
    et al., 1964).

    Groups of dogs (2 males and 2 females/group) were fed fensulfothion in
    the diet at levels of 0, 1, 2 and 5 ppm for 2 years. Severe weight
    loss and reduced food consumption accompanied by signs of cholinergic
    poisoning were evident in the early weeks of the study at 5 ppm. After
    the second month, food consumption increased and lost body weight was
    regained. Slight cholinergic signs at 2 ppm were also observed at the
    beginning of the study. Reduction of serum and RBC cholinesterase was
    evident at 5 ppm throughout the study. Slight reduction was observed
    at 2 ppm with no effects noted at 1 ppm. No mortality was incurred as
    a result of feeding fensulfothion, and hematology and gross and
    histopathologic examination of tissues and organs were normal (Doull
    et al., 1966a).

    Long-term studies

    Rat

    Groups of rats (24 male and 27 female/group) were fed fensulfothion in
    the diet for 17 months at dietary levels of 0, 1, 5 and 20 ppm.
    Mortality of males was increased at 5 and 20 ppm. Growth of males and
    females was slightly impaired at 20 ppm. Cholinesterase depression was
    observed to be dose dependent in serum (19%), RBC (21%), submaxillary
    gland (18%) and brain (24%) in females at 1 ppm and above and in males

    at 5 ppm and above. No effects were observed on gross and histological
    examination of organs and tissues (Doull et al., 1966b).

    COMMENT

    Fensulfothion is acutely very toxic to mammals. The compound is
    metabolized similarly in animals and plants to substances of greater
    toxicity by oxidation of both the enolic leaving group and the
    phosphorothionate moiety. No effects on reproduction in rats,
    neurotoxicity in hens, mutagenicity or teratogenicity at low levels in
    rodents, or potentiation with other organophosphate compounds have
    been observed.

    A no-effect level in long-term studies in rats has not been
    established. In a 17-month study cholinesterase depression at 1 ppm in
    plasma, RBC and brain was observed. By plotting effect versus dose, a
    theoretical no-effect level of 0.5 ppm (0.025 mg/kg/day) may be
    estimated. Somatic effects were not noted up to levels of about five
    times this dose. In a 2-year study in dogs, no adverse effects at 1
    ppm were observed.

    No data are reported on the effects of fensulfothion in man.

    TOXICOLOGICAL EVALUATION

    Level causing no toxicological effect

         Dog: 1.0 ppm in the diet, equivalent to 0.025 mg/kg/day

    ESTIMATE OF ACCEPTABLE DAILY INTAKE FOR MAN

         0 - 0.0003 mg/kg body-weight

    RESIDUES IN FOOD AND THEIR EVALUATION

    USE PATTERN

    Fensulfothion is a systemic organo-phosphorous nematicide and
    insecticide, which is used against soil nematodes (free living, root
    knot and cyst forming nematodes) and a broad spectrum of soil borne
    insects in field crops, vegetables and fruit. It is also used against
    nematodes in turf grasses, in flowers and in ornamentals. In most
    cultures the material is applied before planting or sowing or at
    planting; in some cultures fensulfothion is applied in the soil in
    established cultures.

    Fensulfothion is used a.o. in Canada, Germany, Japan, New Zealand and
    the Philippines.

    Pre-harvest treatments

    Table 3 summarizes the recommendations in accordance with good
    agricultural practice, including rates and methods of application
    (applications to soil at or near sowing or planting time; broadcast
    application or band treatment).


    
    TABLE 3  Officially recommended and registered uses of fensulfothion

                                                                                                                                      

    Country and Crop              Pest                     Dosage
                                                           (a.i.)                 Application time           Restrictions
                                                                                  or pre-harvest
                                                                                  interval
                                                                                                                                      

    Canada1
      Brassicas                                            15 g/100 m row         at planting or
      (broccoli,                                           max. 2.5 kg/ha         shortly after
      Brussels sprouts,                                                           planting
      cabbage, cauliflower,
      rutabagas, turnips)

      Maize                       corn root worm           6-12 g/100 m row       at planting                Do not feed or ensile
                                                           (=0.5-1 kg/ha)                                    treated forage

      Potatoes                    Colorado beetle          5.0 kg/ha              pre-plant                  broadcast
                                  wireworms                                       100 days interval

                                  tuber flea beetle
                                  larvae

                                  Ctenicera spp.

    Cuba, Ecuador
      Banana                                               3-4.5 g/tree           established tree

    Germany (W)2
      Sugarbeet                   beetfly                  1.25-2.5 kg/ha         at sowing
                                  (Pegomya hyoscyami)
                                  centipedes

    Philippines
      Rice (paddy)
      in flooded fields                                    1 kg/ha                15 days after              broadcast
                                                                                  planting

    TABLE 3  (Cont'd.)

                                                                                                                                      

    Country and Crop              Pest                     Dosage
                                                           (a.i.)                 Application time           Restrictions
                                                                                  or pre-harvest
                                                                                  interval
                                                                                                                                      

                                                           2 kg/ha (2x)           45 and 75 days             broadcast, granular
                                                                                  after planting             application to paddy
                                                                                                             water

    U.S.A.3
      Field corn                  corn root worm           0.5.1 kg/ha            at planting
                                                           40 inch row spacing    at planting

      Popcorn

      Sweet corn                                           12 g/100 m row         at planting

      Onions                      onion maggot             1 kg/ha                in furrow at               Do not apply to green
      (dry bulb)                                                                  planting                   bunch onion.


      Peanuts                     nematodes                2-4 kg/ha              band, at planting          Do not feed vines and
                                                                                  and/or at peggig           hay to livestock.

                                  southern corn
                                  rootworm                 2-4 g/100 m row                                   Do not apply more than
                                                                                                             7 kg/ha in one year

      Pineapple                   nematodes                50 kg/ha                                          broadcast
                                  nematodes                50 kg/ha (drench)      pre-plant

      Potatoes                                             2-5.0 kg/ha            pre-plant                  broadcast of granules

      Sugarbeet                                            1-2 kg/ha              at sowing

                                                           15 g/100 m row         at sowing
    TABLE 3  (Cont'd.)

                                                                                                                                      

    Country and Crop              Pest                     Dosage
                                                           (a.i.)                 Application time           Restrictions
                                                                                  or pre-harvest
                                                                                  interval
                                                                                                                                      

      Sugarcane                   nematodes                2-5 kg/ha              at planting                band (40-45 cm)

      Tobacco                     wireworms,               2-10 kg/ha             pre-plant                  broadcast
                                  nematodes

      Tomatoes                    nematodes                3.2-6.4 kg/ha          pre-plant                  band
                                                           10-20 kg/ha                                       broadcast
                                                                                                                                      

    1  Canada Dept. of Agriculture Plant products Division, Production & Marketing Branch
       Use Claim for pesticides registered under the Pest Control Products Act May, 1971 & Jan. 1972, No. 834-128.

    2  Pflanzenschutamittel-Verzeichnis, 23 Auflage, April 1972, Biologischen Bundesanstalt für Land - und
       Forstwirtschaft Braunschweig.

    3  USDA summary of Registered Agricultural Pesticide Chemical uses III D 22 5-31-69; 8-14-70, 3-24-72.
    

    Post-harvest treatments

    Fensulfothion is not recommended for post-harvest treatments.

    RESIDUES RESULTING FROM SUPERVISED TRIALS

    Residue data are available from supervised trials carried out in
    different countries on food crops grown under various conditions. In
    most cases dosage rates were applied in accordance with label
    instructions. However, in some experiments higher dosages were also
    included. Data from these trials are summarized in table 4.

        TABLE 4  Residues in crops treated with fensulfothion

                                                                                                 

    Crop                Rate of application        No. of          Pre-harvest     Net Residue
                        (a.i.)                     applications    interval        (ppm)
                                                                   (days)
                                                                                                 

    bananas             3.0 - 4.5 g/tree           1               1 - 90          <0.01 - 0.02

    corn                1.2 - 3.2 kg/ha            2               21 - 67         <0.05
                        0.18 - 0.27 g/row    )
                        plus 1.1 - 1.7 kg/ha )     2 + 1           29 - 31         <0.01

    cotton seed         0.55 - 0.82 g/m row        1               157 - 206       <0.01

    onions              0.05 - 0.23 g/m row        1               80 - 191        <0.05

    pineapple           60 - 200 kg/ha (drench)    1               561 - 973       <0.01

    potatoes            7 - 8 kg/ha                1               102 - 150       <0.05

    rutabagas           1.1 - 2.7 kg/ha            2 - 6           19 - 84         <0.01 - 0.05

    soybeans            0.18 - 0.27 g/m row        1               71 - 119        <0.01

    sugar beets         2 - 4 kg/ha                1               177 - 182       <0.01 - 0.10
                        0.12 - 2 g/m               1-3             58 - 196        <0.03

    sugar cane          6 - 8 kg/ha (40 cm band)   1               228 - 343       <0.01 - 0.02

    sweet potatoes      6.7 - 11.8 kg/ha           1               101 - 189       <0.01 - 0.05

    tobacco             2 - 16 kg/ha               1               53 - 159        0.1 - 10.5

    tomatoes            20 - 30 kg/ha              1               34 - 121        <0.05
                                                                                                 
    
    The residues in these trials were predominantly determined by GLC 
    utilizing thermionic detection. Included in the analysis are total
    toxic (cholinesterinase inhibiting) metabolites. Samples were taken at
    harvest and immediately frozen until analysis. Bananas were stored
    several days at room temperature before freezing.

    In a ryegrass/white clover mixture the residue decreased from 90 ppm
    (dry weight) immediately after application to 20 ppm after 13 days and
    12, 4 and 1 ppm after 27, 55 and 90 days, respectively (Brewerton,
    1971). Similar figures are given by Solly (1968) from grassland in New
    Zealand.

    FATE OF RESIDUES

    General comments

    The breakdown of fensulfothion in plants and animals seem identical
    since the same metabolites have been identified in both.

    In animals and animal products

    In milk from cows grazing in pasture containing mainly residues of
    fensulfothion sulfone, the oxygen analogue sulfone was detected. An
    oxidative pathway in the ruminant appears most likely. Milk from dairy
    cattle grazing for 10 days on pasture with an initial residue of 41
    ppm fensulfothion contained 0.02 ppm oxygen analogue sulfone on the
    third day, which decreased to 0.01 ppm on the 10th day (Solly
    et al., 1971c).

    Omental fat of sheep grazing for six days in pasture containing 43 ppm
    initial residue of fensulfothion, showed a residue of 0.003 ppm,
    although the erythrocyte cholinesterase depression was approximately
    80% (Solly et al., 1971b).

    In plants

    The systemic action of fensulfothion was first demonstrated after
    topical application stems of cotton plants (Benjamini et al.,
    1959b). Katague and Anderson (1967) studied the fate of fensulfothion
    after stem injection in cotton with 32P fensulfothion. They
    identified the following metabolites by TLC with authentic standards:
    O,O diethyl-O-[4-(methyl sulfinyl) phenyl)] phosphate (= oxygen
    analogue) and O,O diethyl-[-4-(methylsulfonyl) phenyl]
    phosphorothionate (sulfone).

    After root uptake traces of O,O-diethyl-O-[-4 methyl sulfonyl
    phenyl] phosphate (oxygen analogue sulfone) were found. The S-ethyl
    analogue was not detected in either study.

    After stem injection of 32P fensulfothion in maize, beans and cotton
    the S-ethyl analogue could not be detected, but the previously
    mentioned three metabolites were found (Everett and Gronberg, 1967).

    Thornton (1967) analysed maize fodder from field samples by GLC for
    fensulfothion and its metabolites. The interval for harvest was 40-121
    days. The percent distribution of fensulfothion and metabolites was:
    fensulfothion: 0-38% (average 16%), sulfone: 0-34% (average 12%),
    oxygen analogue: 14-68% (average 45%), oxygen analogue sulfone: 8-49%
    (average 27%).

    Thornton (1968) showed the presence of 4-methylsulfonyl phenol in
    maize fodder, but none in the maize kernels and cobs. Solly and
    Harrison (1971a) found the sulfone as a major metabolite in pasture
    grass, with only traces of the oxygen analogue and the oxygen analogue
    sulfone. The same main metabolites were found in cured tobacco (Olson,
    1972).

    In soil

    In soil the breakdown of fensulfothion and metabolites is rather
    rapid. Duffy (1968) found experimentally that one half of the
    fensulfothion in soil was degraded in 14 days. In other tests, in
    which fensulfothion was incorporated in the top six inches of soil,
    residues were determined over a period of one year. The time required
    to decrease the residue to one half of the initial concentration was
    generally less than 30 days; in another test it was slightly longer
    than 180 days (Chemagro, 1968).

    In storage and processing (cooking)

    Thornton (1971) treated cotton seed oil fortified with 5 ppm
    fensulfothion and the oxygen analogue with a laboratory steam
    stripping similar to the process used commercially. The oil was heated
    to 230 - 240°C and steam was passed through it for 3 hours. Analysis
    of the processed oil showed that 48% of fensulfothion and 75% of the
    oxygen analogue was swept away or degraded. The steam was scrubbed
    with chloroform; 5 - 10% of the original 5 ppm were trapped and
    identified as unchanged fensulfothion or oxygen analogue.

    Katague (1968) simulated the refining of raw sugar beets to
    concentrated syrup after fortifying the beets with 32P fensulfothion
    and unlabelled metabolites. In the concentrated syrup the loss of
    residue was 96 - 100% for fensulfothion, sulfone, oxygen analogue and
    oxygen analogue sulfone. It was determined that the maximum total
    concentration expected in the wet pulp would be no more than 5.5% of
    the concentration in the raw beet.

    In fresh harvested rutabagas stored 20 - 25 days at 4°C the total
    residue of fensulfothion and metabolites decreased 50 - 92%. Cooking
    reduced the residues by 48 - 68%. From these figures it may be
    concluded that rutabagas, treated at recommended rates and stored for
    a few weeks and then cooked, would contain no detectable residues.

    Studies have been carried out to determine the extent of carry over of
    residues in the tobacco smoke. Olson (1965) found 1.6% of
    fensulfothion added to the tobacco in the smoke. After fortification
    of cigarette tobacco with fensulfothion and subsequent analysis of the
    solvent used for scrubbing the smoke, 7.9% recovery of unchanged
    fensulfothion was shown in the smoke (Katague, 1966).

    Olson (1968) fortified separate samples with fensulfothion and
    metabolites. Recoveries in the smoke were 3.5, 3.0, 2.4 and 1.4%
    respectively of fensulfothion, sulfone, oxygen analogue and oxygen
    analogue sulfone.

    During frozen storage of onions, potatoes and turnips, residues were
    stable for 770 days, in cowpea vines for at least 98 days (Chemagro,
    1967, 1965).

    Evidence of residues in food in commerce or at consumption

         No data available.

    METHODS OF RESIDUE ANALYSIS

    Gas chromatographic methods for analysis of fensulfothion and
    metabolites are the methods of choice for residue analysis of various
    crops, animal tissue and milk. GLC methods utilizing a KCl thermionic
    detector proved to be particularly suitable for regulatory purposes.

    Methods have been developed and adapted for analysis of maize,
    peanuts, vegetables, forage crops and oil crops (Katague and Olson,
    1969; Olson, 1970). The course of the analysis may be summarized as
    extraction of the crop with acetone followed by partitioning with
    chloroform.

    The dry residue from the extract is oxidized with m-chloroperbenzoic
    acid, which converts fensulfothion, sulfone and oxygen analogue to
    oxygen analogue sulfone. This is further purified by solvent
    partitioning and injected into the gas chromatograph. Residues of
    fensulfothion and its three metabolites are measured as a single peak
    as oxygen analogue sulfone. The method is specific for fensulfothion
    and its metabolites. Twenty-three insecticides and metabolites
    containing phosphorus were shown not to interfere (Olson, 1971).

    Limit of detection of the method is 0.05 ppm or lower for
    fensultothion and metabolites. Recoveries in various crop samples, in
    cattle and in milk, ranged respectively from 71 - 86%, 102 - 109% and
    96 - 116%.

    GLC methods have been developed for the determination of individual
    metabolites (Williams et al., 1971; Bowman and Hill, 1971). These
    methods are less suitable for regulatory purposes than the method
    described above.

    Multidetection GLC methods for determining residues of
    organo-phosphorous compounds in various crop samples were investigated
    by the U.S. Food and Drug Administration. Fensulfothion and its three
    metabolites were included in the study.

    Watts et al. (1969) described a new charcoal liquid chromatography
    procedure for improved clean-up of 60 organo-phosphorous compounds
    including fensulfothion. Bowman and Beroza (1971) determined retention
    times for 146 organo-phosphorous or sulphur compounds, including
    fensulfothion, using a column packed with Dexsil 300
    (polycarborane-siloxane) on HCl washed chromosorb W. The column can
    be purged at temperatures up to 400°C.

    Gas chromatic methods for determination of fensulfothion and
    metabolites in soil have been developed (Olson, 1968; Katague, 1966).

    NATIONAL TOLERANCES

    Examples of national tolerances of fensulfothion residues are reported
    in Table 5.

    APPRAISAL

    Fensulfothion is a systemic organophosphorous nematicide and
    insecticide which is used on a considerable scale in various countries
    on a relatively wide range of crops. Main uses are as soil treatment,
    either broadcast or band treatment, or as a drench, against soil borne
    nematodes (free living, root knot and cyst forming nematodes) and a
    considerable range of soil borne insects.

    Technical fensulfothion contains 94-96% of the pure compound. The
    impurities in the technical material are known. The main components
    are: O,O-diethyl-O-[4-(methylthio)-phenyl]-phosphorothioate
    (1-3%) and 4-(methylsulfinyl)-phenol (0.8-1.0%).

    Fensulfothion is marketed in different formulations, i.e. granular 3,
    5, 10 and 15% and emulsifiable liquid (720 g/l).

    The concentration/rates of application vary depending on pest, crop
    and method of application; "normal" application rates are 1-5 kg a.i.
    per ha.

    TABLE 5  Examples of national tolerances reported to the Meeting1

                                                                             

    Country        Commodity                                       Tolerance
                                                                   (ppm)
                                                                             

    U.S.A.         peanut hulls                                    5

                   maize forage and fodder of field corn,
                   pop corn and sweet corn                         1

                   maize grain, including field corn and
                   pop corn (kernels); fresh maize
                   (including sweet corn), kernels plus
                   cobs, with husks removed; onions,
                   (dry); potatoes; rutabagas (roots) and
                   tomatoes                                        0.1

                   peanuts (shelled); pineapple, pineapple
                   forage, sugar beets (roots and tops)            0.05

                   bananas (whole); sugarcane; meat, fat and
                   meat by-products of cattle, goats and sheep     0.02

    Canada         Brassicas (broccoli, Brussels sprouts,
                   cabbage, cauliflower); rutabagas;
                   turnips, potatoes; maize                        no residue

    Germany,       No official tolerances established.
    Federal        For the following crops tolerances
    Republic       are being considered:

                   sugarbeet.

    New Zealand    all food crops                                  0.1
                                                                             

    1  Fensulfothion and cholinesterase inhibiting metabolites in or on the
       commodities.


    The residue data available were obtained from different countries and
    regions with different climatic and soil conditions. The residue data
    presented for fensulfothion included the three metabolites, sulfone,
    oxygen analogue and oxygen analogue sulfone, and are with a few
    exceptions representative for those likely to occur in conditions of
    good agricultural practice.

    Information is available on the fate of fensulfothion residues in
    soil, in plants and to a lesser extent in animal products after
    feeding animals on treated pasture or with treated crops.

    Approved uses on peanuts and pineapple give rise to residues in peanut
    kernels and in pineapple not exceeding 0.05 ppm (the proposed
    tolerances). Hulls of peanuts and pineapple forage from such treated
    crops will not contain residues in excess of 5 ppm and 0.05 ppm,
    respectively. Likewise, the residue in sugarcane will not exceed 0.02
    ppm. A soil application of fensulfothion in maize (including pop corn
    and sweet corn), giving rise to residues in the kernels not exceeding
    the proposed tolerance of 0.1 ppm, will result in residues in the
    forage of 1 ppm or lower. Feeding of the materials mentioned in this
    paragraph as a part of the ration for cattle or sheep will not give
    rise to residues in meat or milk above the limit of determination
    (i.e. 0.01 ppm).

    Residues which may occur in food either from plant or animal origin,
    after observing the recommended directions of use and the recommended
    harvest intervals, consist largely of the oxygen analogue and the
    oxygen analogue sulfone and to a smaller extent the parent chemical
    and the sulfone. The breakdown products mentioned above could be
    identified in radio-labelled studies and confirmed with other relevant
    methods of analysis, e.g. TLC.

    The breakdown of fensulfothion in plants and animals follows an
    identical pattern; the same metabolites have been identified in both.

    Information is available on the rate of decrease of the residue of
    fensulfothion and metabolites in some crops and commodities during
    storage and processing, including household cooking. In addition,
    information on the extent of carryover of residues in tobacco smoke
    from residues initially applied on tobacco was presented.

    Little information is available on fensulfothion residues in food in
    commerce.

    Gas chromatographic procedures are available for specific
    determination of fensulfothion and its main metabolites, or all
    compounds combined and measure as a single peak as the oxygen analogue
    sulfone. These methods are suitable for regulatory purposes as
    required. Recommendations are given for the most appropriate
    extraction and clean up procedures in food products of plant and
    animal origin. The limit of determination is 0.05 ppm for all crops
    and animal tissue and 0.01 ppm for milk.

    RECOMMENDATIONS

    TOLERANCES

    The following tolerances are recommended for fensulfothion, including
    the metabolites (oxygen analogue, oxygen analogue sulfone and
    sulfone).

                                                           ppm

         Maize grain, including kernels of field
         corn and pop corn, onions, potatoes,
         rutabagas (roots), tomatoes                       0.1

         Peanuts (shelled), pineapple, sugarbeet           0.05

         Bananas (whole fruit)                             0.02

         Fat of meat and edible offal of cattle,
         goats and sheep                                   0.02

    FURTHER WORK OR INFORMATION

    DESIRABLE

    1. Teratogenicity studies at higher dosage levels.

    2. Studies on human exposure.

    REFERENCES

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    See Also:
       Toxicological Abbreviations
       Fensulfothion (ICSC)
       Fensulfothion (PDS)
       Fensulfothion (Pesticide residues in food: 1982 evaluations)
       Fensulfothion (Pesticide residues in food: 1983 evaluations)