IPCS INCHEM Home


    ETHIOFENCARB           JMPR 1977

    IDENTITY

    Chemical name

    2-ethylthiomethylphenyl methylcarbamate

    Synonyms

    CronetonR 1 HOX 1901

    Structural formula

    CHEMICAL STRUCTURE 5

    Other information on identity and properties

    Molecular weight:   225

    Specific gravity:   1.147 at 20° C
                                  4°

    Appearance:         colourless crystals (pure a.i.)

    Melting point:      33.4° C (pure a.i.)

    Boiling point:      decomposes

    Vapour pressure:    5 × 10-6 mbar at 20° C

    Solubility (pure):  in water (20° C): approx. 0.19 g/100 g

                        in methylene chloride,)
                        propan-2-ol           ) >60 g/100 g
                        and toluene:          )

                        in ligroin (80-110° C): 1-5 g/100 g

    Formulations:       10% Granular, 10% and 50% emulsifiable
                        concentrates

    Minimum purity:     90%

    Impurities in the technical material

    Detailed information on the impurities in technical ethiofencarb was
    reported to the Meeting.

    EVALUATION FOR ACCEPTABLE DAILY INTAKE

    BIOCHEMICAL ASPECTS

    Absorption, distribution, excretion and biotransformation

    Studies on these points have been conducted with samples of
    ethiofencarb labelled with 14C either in the ring or in the carbonyl
    carbon. These studies have been described in several reports, all
    issued during 1976-77. These experiments have demonstrated that
    regardless of the position labelled the compound is readily absorbed
    by the oral route, and is rapidly eliminated thereafter.

    When administered as a single oral dose to rats, 41% of the
    carbonyl-labelled compound was eliminated in the urine and 7% in the
    faeces (within 72 hr), while 47% was eliminated as 14CO2. When
    similarly administered but in ring-labelled form, 96% was eliminated
    in the urine and 2% in the faeces within 72 hr. The compound,
    therefore, undergoes hydrolysis, producing a phenol and a carbamic
    acid derivative which breaks down further to CO2.

    Maintenance of rats on a diet containing 6.6 ppm of ethiofencarb gave
    similar results with the total excretion (urine plus faeces)
    decreasing to 1% of one day's intake by the third day after return of
    the animals to the normal diet. The major metabolites identified were
    the sulphoxide and sulphone of ethiofencarb and the sulphoxide and
    sulphone of the phenol; the latter two compounds were excreted mainly
    as conjugates, and the parent compound was detected in the urine only
    in trace amounts. Tissue residues detected after either a single oral
    dose of 0.5 mg/kg b w or administration of 6.6 ppm in the diet for one
    week were below 1 mg/kg, and these declined more rapidly after
    administration of the ring-labelled than the carbonyl-labelled
    compound. This suggests that the carbonyl-labelled residues were
    incorporated into normal tissues components, as would be expected (Nye
    et al., 1976).

    Experiments bearing on the metabolism of ethiofencarb by livestock and
    poultry and of some of its plant metabolites by rats, are described in
    the section "Fate of residues", "In animals". Metabolic pathways are
    illustrated in Figure 1.

    Effects on enzymes and other biochemical parameters

    The depression of acetylcholinesterase activity in plasma,
    erythrocytes and brain was investigated in rats and dogs (Kimmerle and
    Eben, 1974).

    Rats were treated with single oral doses of 0, 2.5, 10 and 50 mg/kg
    and 0, 2.5, 10, 40, 125, 210 and 330 mg/kg for females and males
    respectively. The maximum dose-related level of plasma cholinesterase
    activity depression of 60% in females treated with 50 mg/kg and of
    80-100% in males treated with 330 mg/kg was reached about 0.5 to 5 hours
    after administration. Enzyme activity increased again thereafter. Two
    males of the 330 mg/kg group died one hour after treatment.
    Cholinesterase activity depression was lower in erythrocytes and brain
    than in plasma. Maximum depression levels were reached after about 2
    hours in erythrocytes and after about 1 hour in the brain.

    In a 4-week oral study male and female rats received the test compound
    daily at a rate of 0, 5, 10, 20 and 40 mg/kg. Dose-related depression
    of plasma- and erythrocyte acetylcholinesterase activity was found in
    the animals treated with 20 and 40 mg/kg. Male rats showed within 2
    hours after administration of 10 mg/kg bw a depression of
    plasma-cholinesterase of 25% and of erythrocyte-cholinesterase of 15%.

    In male and female rats which were exposed for a period of 3 weeks to
    concentrations of 0, 5.0, 29.7 and 148.4 mg/m3 of air for 6 hours on
    5 consecutive days per week the concentrations of 29.7 mg/m3 and
    above caused depression of the plasma cholinesterase, whereas
    erythrocyte cholinesterase activity was depressed only at the highest
    concentration level.

    Following single oral administration of 5, 10, 25 and 50 mg/kg,
    dose-dependent depression of the cholinesterase activity was found in
    plasma at dose levels of 10 and above. Maximum depression was found
    1 - 2 hours after administration. 3 hours post-administration the
    activity increased again (Kimmerle and Eden, 1974).


    TOXICOLOGICAL STUDIES

    Special study on mutagenicity

    In a dominant-lethal test, groups of 20 NMRI male mice were treated
    with a single oral dose of 0 and 25 mg/kg. The male mice were mated
    with untreated females for 8 consecutive weeks. The acute oral dose of
    25 mg/kg was a sublethal dose causing transient toxicity symptoms such
    as slight somnolence and piloerection. The application did not
    influence the fertility of the male rats. This experiment gave no
    indication of treatment-related pre- and post-implantation losses and
    therefore gave no indication of a mutagenic effect of the test
    substance (Machemer, 1973a).

    Special study on neurotoxicity

    A group of 30 atropinized hens was treated with a single oral LD50
    dose of 870 mg/kg. During the 3-week observation period only one hen
    died. After 3 weeks the survivors were atropinized again and re-dosed
    with 870 mg/kg. Three other animals died 3 weeks after treatment. No

    neurotoxic symptoms wore observed. The histopathological investigation
    of the brain, spinal marrow and Nn. ischiadici gave no indication of
    nerve damage, whereas the positive control animals which had been
    treated with a single oral dose of 375 mg/kg tri-o-cresyl phosphate
    (TOCP) showed evidence of delayed neurotoxicity with respect to
    clinical symptoms as well as histopathology.

    The test compound did not show any neurotoxic effect (Thyseen, 1975a).

    Special study on teratogenicity

    Rats

    Groups of 20 female rats were treated with daily oral doses of 0, 5,
    15 and 40 mg/kg from gestation day 6 to 15. None of the studied dose
    levels had any adverse effect on the dams with respect to their health
    condition and fertility. The embryonic and foetal development was not
    affected by the treatment up to and including the dose level of 15
    mg/kg. Treatment of the dams with 40 mg/kg caused reduction of the
    average foetus weight. Two foetuses of dams treated with 40 mg/kg
    showed multiple malformations, which are considered to be spontaneous
    malformations of the strain. In a repeat experiment these
    malformations could not be verified. Signs of immature skeletal
    development in some foetuses and a higher frequency of slight bone
    alterations of the 40 mg/kg group in comparison with controls were
    found in the repeat experiment.

    Based on these data the test compound was considered not to be
    embryo-toxic or teratogenic (Machemer, 1973b).

    Groups of 10 pregnant rabbits received daily oral doses of 0, 5, 15
    and 40 mg/kg from gestation day 6 through 18. The administration did
    not have any adverse effects on the dose. No significant differences
    between the control group and treated groups with respect to embryonic
    and foetal development could be found. The only malformed foetus
    occurring in the 40 mg/kg group was considered to be a spontaneous
    malformation. Therefore the test-compound at doses up to and including
    40 mg/kg was considered not to have teratogenic effects (Machemer,
    1975).

    Special study on potentiation

    The simultaneous administration of ethiofencarb with either malathion
    or EPN to rats caused no potentiation effects on the acute oral
    toxicity (Thysson, 1975b).

    Simultaneous oral administration of ethiofencarb in combination with
    trichlorfon produced likewise only a less than additive acute toxicity
    (Thyssen and Kimmerle, 1975).

    FIGURE 3

    Acute toxicity

        TABLE 1a, Acute toxicity of ethiofencarb

                                                                                                
    Species         Sex         Route           LD50             References
                                                mg/kg
                                                                                                

    Rat             m           oral            308              Thyssen and Kimmerle, 1975

    Rat             m           oral            411              Kimmerle 1972b

    Rat             f           oral            499              ibid.

    Rat             m           i.p.            41.8             ibid.

    Rat             f           i.p.            41.9             ibid.

    Rat             m           dermal          >1000            ibid.

    Mouse           m           oral            256              ibid.

    Mouse           f           oral            224              ibid.

    Rabbit          m           oral            approx. 225      Kimmerle 1972c

    Rabbit          m           dermal          >8000            Lamb and Matzkanin 1976a

    Rabbit          f           dermal          >8000            ibid.

    Dog             f           oral            >50              Kimmerle 1972b

    Hen                         oral            approx. 1000     ibid.
                                                                                                
    
    The typical symptoms of acetylcholinocaterase inhibition such as
    salivation, muscle tremors, spasms and convulsions preceded death.

    A good antidotal effect was obtained when rats orally treated with
    ethiofencarb received i.p. injection of atropine sulphate (Kimmerle
    1972d).

    Short term studies

    Rat

    Groups of 15 male and 15 female rats were treated orally for 30 days
    at dose levels of 0, 5, 10, 20 and 40 mg/kg. The administration had no

    effects with respect to physical appearance, behaviour, body weight,
    haematological and clinical chemistry test values. No gross
    pathological alterations of tissues were observed and organ weights
    did not significantly differ from those of the control animals.
    Tissues were not examined microscopically (Kimmerle, 1972e).

    In another subacute study 10 male and 10 female rats per dosage group
    were exposed for 6 hours daily on 5 consecutive days per week over a
    3-week period to aerosol concentrations of 0, 29.7 and 148.5 mg/m3
    of air. All these concentrations were tolerated without any adverse
    effect with respect to behaviour, general health condition, body
    weight, haematological and clinical chemistry values.

    The macroscopic examination of the major tissues revealed no
    pathological alteration and organ weights did not differ significantly
    between the control group and the treated groups (Kimmerle, 1972e).

    Groups of 20 male and 20 female rats were fed ethiofencarb at
    concentrations of O, 250, 500 and 1000 ppm for 3 months. Physical
    appearance, behaviour, mortality and food consumption were not
    affected by the diet. The average body weights of male rats fed 500
    and 1000 ppm were higher than the corresponding weights of the control
    animals. Values of urinalyses, haematology and clinical chemistry were
    within the physiological range. Macroscopic and microscopic
    examination of the principal organs revealed no treatment-related
    alterations. The relative liver weights in male rats treated with 1000
    ppm were higher than those of the control animals (Klimmer, 1973).

    Dog

    Groups of 4 male and 4 female dogs were maintained for 3 months on a
    diet containing ethiofencarb at concentrations of 0, 100, 300 and 1000
    ppm. The treatment did not effect physical appearance, behaviour, food
    consumption, body weight, mortality or ophthalmoscopic and
    neurological findings. Parameters of haematology, clinical chemistry
    and urinalyses showed no significant differences between control and
    treated groups. At 1000 ppm an increase of the relative liver weights
    of about 10% was noted in both sexes and an increase of about 40% in
    relative kidney and spleen weights in male animals only. Gross and
    histopathological examination showed no treatment-related alteration
    (Mührmann, 1973).

    Groups of 4 male and 4 female dogs received a diet for a period of 104
    weeks containing ethiofencarb at concentrations of 0, 330, 1000 and
    3000 ppm. The administration of up to and including 1000 ppm did not
    affect the test animals with respect to their physical appearance,
    behaviour, food consumption and ophthalmoscopic findings. The dietary

    level of 3000 ppm caused vomiting immediately after feeding,
    especially in the second half of the study; food consumption was
    retarded and reduced in some female dogs at the 3000 ppm level,
    whereas female dogs at 330 and 1000 ppm made bigger gains in
    comparison with controls. Haematological and urinalyses values
    revealed no pathological alterations. Results of chemistry tests (with
    respect to blood sugar, urea, creatinine, total protein, GOT,
    bilirubin) were within the physiological range. The ALP activities
    showed a 3 -4 fold increase at 3000 ppm and in some dogs of the same
    group an increased level of GPT activity and cholesterol were noted.
    Relative liver weights of the animals of both sexes at 1000 and 3000
    ppm showed a dose-related increase. One dog at the 3000 ppm feeding
    level showed enlargement of the liver. At 3000 ppm the
    histopathological examination of tissues disclosed signs of treatment-
    related alterations in liver such as enlarged hepatocytes, hepatocytes
    nuclei and granular cytoplasmic structures (Hoffmann and Weischer,
    1976).

    Long term studies

    Rat

    Groups of 50 male and 50 female (100 male and 100 female in control
    group) were fed a diet containing ethiofencarb at concentrations of 0,
    330, 1000 and 3000 ppm for 24 months. The treatment did not affect the
    physical appearance, behaviour and mortality of the test animals. The
    values of haematological and clinical chemistry tests (with respect to
    ALP, GOT, GPT, GLDH, bilirubin and proteins in serum), urinalyses and
    kidney function tests were within the physiological ranges. Blood
    sugar values did not differ from the control, whereas a dose-related
    increase of the cholesterol values in treated animals was found,
    especially at 3000 ppm. No gross pathological alterations that could
    be attributable to treatment were seen in rats which died during the
    feeding study or which were sacrificed at the end of the study. Some
    variations in the relative organ weights were found.

    A dose-dependent increase of the relative liver-weight at 1000 and
    3000 ppm was observed. The histopathological examination of tissues
    revealed no treatment-related alterations. The incidence and
    localization of tumours provided no indication for a carcinogenic
    effect of ethiofencarb (Bombard and Löser, 1976).


        TABLE 1b. Acute toxicity of ethiofencarb metabolites

                                                                                                             

    Species                                Sex    Route        LD50             References
                                                               mg/kg
                                                                                                             

    Ethiofencarb-sulfoxide:

    Rat                                     m     oral         200-250          Thyssen 1976
    Rat                                     f     oral         200-250          ibid.
    Rat                                     f     oral         133              Lamb and Matzkanin 1977a

    Ethiofencarb-sulfone:

    Rat                                     m     oral         600-750          Thyssen 1976
    Rat                                     m     oral         468              Lamb and Matzkanin 1977b
    Rat                                     f     oral         approx. 600      Thyssen 1976

    Ethiofencarb-phenol:

    Rat                                     m     oral         approx. 200      Lamb and Matzkanin 1977c
    Rat                                     f     oral         approx. 200      ibid.

    Ethiofencarb-phenol-sulfoxide:

    Rat                                     m     oral         >1000            Lamb and Matzkanin 1977d
    Rat                                     f     oral         >1000            ibid.

    Ethiofencarb-phenol-sulfone:

    Rat                                     m     oral         >1000 <20        Lamb and Matzkanin 1977e
    Rat                                     f     oral         >1000 <20        Ibid.

    TABLE 1b. (Continued)

                                                                                                             

    Species                                Sex    Route        LD50             References
                                                               mg/kg
                                                                                                             
    N-methyl-hydroxy metabolite of ethiofencarb:
    Rat                                     m     oral         >2000            Lamb and Matzkanin 1977f
    Rat                                     f     oral         approx 2000      ibid.

    N-methyl-hydroxy sulfoxide metabolite:

    Rat                                     m     oral         >2000            Lamb and Matzkanin 1977g
    Rat                                     f     oral         >2000            ibid.

    N-methyl-hydroxy-sulfone metabolite

    Rat                                     m     oral         >2000            Lamb and Matzkanin 1977h
    Rat                                     f     oral         >2000            Ibid.
                                                                                                             
    

    Comments

    Ethiofencarb is almost completely absorbed in mammals and it is
    excreted rapidly in the form of metabolites mainly in the urine. The
    major metabolic reactions are demethylation and subsequent hydrolysis
    of the carbamate and oxidations to sulphoxides and sulphones.
    Ethiofencarb inhibits the activity of acetylcholinesterase only
    transiently.

    In a 4-week study daily oral administration of 10 mg/kg to male rats
    led to a maximal depression of 25% of the plasma-cholinesterase and of
    15% of the erythrocyte-cholinesterase after 2 hours. Recovery occurred
    almost completely within 24 hours. This dose level was taken as a
    basis for establishing an acceptable daily intake for humans. The fact
    that at 10 mg/kg marginal effects occurred was taken into account by
    using a safety factor higher than is usual for
    cholinesterase-inhibiting compounds.

    The compound was not mutagenic in a dominant lethal test, nor was it
    teratogenic. No three-generation study was available. However, such a
    study was felt to be important since the depression of the
    cholinesterase activity often manifests itself unfavourably in a
    reduced viability of the pups.

    In a 2-year feeding study in dogs no untoward effects were seen up to
    1000 ppm. A long-term feeding study in rats revealed no more than a
    moderate increase of the relative liver weights at 3000 ppm.

    TOXICOLOGICAL EVALUATION

    Level causing no toxicological effect

         Rat: 10 (mg/kg bw)/day

         Dog: 1000 mg/kg in the diet, equivalent to 25 mg/kg bw

    ESTIMATE OF TEMPORARY ACCEPTABLE DAILY INTAKE FOR HUMANS

         0-0.1 mg/kg bw

    RESIDUES IN FOOD AND THEIR EVALUATION

    USE PATTERN

    Ethiofencarb in a systemic insecticide which has a selective effect
    against aphids. It gives control of numerous aphid species on
    vegetables, fruit crops, field crops and ornamental plants. It
    displays good activity against both susceptible and
    organophosphorusresistant strains. Used as a soil treatment, e.g. by
    the soil drench method or as a granular application, ethiofencarb
    displays long residual activity; when applied to the aerial parts of

    plants it is somewhat less persistent. In trials conducted to date,
    ethiofencarb has shown no phytotoxicity.

    Ethiofencarb is sold or registered in Bulgaria, Chile, Denmark,
    Federal Republic of Germany, Israel, Italy, Portugal, Spain, Sweden,
    Switzerland and Turkey.

    Applications for registration have been filed in a number of other
    countries.

    Pre-harvest treatments

    Ethiofencarb is formulated as an emulsifiable concentrate for spraying
    and as a granular product. Used as a spray, it is applied broadcast at
    the onset of aphid infestation. As a granular formulation, it is
    applied at sowing or planting, mainly in-furrow.

    Details of uses and recommendations for pre-harvest treatments with
    ethiofencarb are given in Table 2.

    Post-harvest treatments

    No treatments recommended.

    Other uses

    Ethiofencarb is also used on ornamental plants.

    RESIDUES RESULTING PROM SUPERVISED TRIALS

    The residue data obtained after the application of ethiofencarb to
    fruit, vegetables and field crops are summarized in Table 3. The data
    originate from trials conducted in the U.S.A., Japan, Great Britain,
    France, the Netherlands and the Federal Republic of Germany.

    The residues were determined by gas-chromatographic methods which
    determine residues of ethiofencarb and the metabolites with an intact
    carbamate group.

    After application by spraying, half-lives of 2 to 18 days were noted
    for the total residue.

    Detailed studies with different formulations using the same active
    ingredient dose produced the following half-lives for the given crops:

              Apple:             13   (5-18) days
              Bush bean:          5   (4-7 ) days
              Head lettuce:       5   (4-6 ) days
              Savoy cabbage:      5   (2-9 ) days

    With crops of which the foliage and edible parts were analyzed
    separately, e.g. potatoes, sugar beet, broad beans and radish, it was

    found that the residues were present mainly in the foliage owing to
    the pronounced systemic mode of action of ethiofencarb, residues were
    found in the analyzed plant samples also after application of the
    granular formulation to the soil. Here, too, there was an accumulation
    of the residues in the leaves, as proved by studies on broad beans and
    sugar beet.

    FATE OF RESIDUES

    General

    The metabolism of ethiofencarb (I) is illustrated in Figure 1. It is
    found to be of the same pattern, with oxidation of the sulphur and
    hydrolysis of the carbamate group, in soil, plants and animals, with
    only quantitative differences. In soil and plants, ethiofencarb
    sulphoxide (II, Figure 1) and ethiofencarb sulphone (III) were the
    main products with an intact carbamate group. In animal metabolism
    studies, phenolic degradation products formed by hydrolysis of the
    carbamate group were also detected. CO2 released from the carbamate
    group by hydrolysis was found to be incorporated into plants.

    In animals

    Studies on ethiofencarb metabolism in rats are described previously
    under "Biochemical aspects". Marshall and Dorough (1976,1977)
    investigated the fate of water-soluble plant metabolites of
    ethiofencarb in rats. Bean plants were stem-injected with either
    ring-14C- or carbonyl-14C-ethiofencarb. After 20 days almost all
    the radiocarbon residue was in the epicotyl leaves. The distribution
    in the unextractable, organic and aqueous fraction was 3.3%, 45.8% and
    40.7% for the ring label and 1.3%, 13.8% and 2.6% for the carbonyl
    label. 14C in the aqueous fractions when orally dosed to rats was
    largely excreted within 36 hours, mainly by routes similar to those of
    the parent compound, viz. in urine (92% of ring and 39% of CO-label)
    and as expired CO2 (30% of CO-label).

    Sorghum plants treated with ring-14 C-ethiofencarb (I) in an
    emulsifiable spray were used as a source of unextractable metabolites
    (Marshall and Dorough, 1977). When these bound residues of I were
    administered to rats, 90.8% of the dose was voided in the faeces and
    16.4% in the urine within 2 days; the bile contained 2.5% of the dose.
    These data demonstrated that bound residues of I were very poorly
    absorbed from the gastrointestinal tract of rats, while the conjugated
    ones were readily absorbed.

    Gronberg at al. (1976) continuously fed I to dairy cows for 28 days at
    50, 150 and 500 PPM in the diet, equivalent to 1.5, 4.5 and 15 mg/kg
    body weight/day. From the residue data obtained it was calculated that
    tissue residues would be less than 0.1 mg/kg I + II + III equivalents
    and milk residues would be less than 0.01 mg/kg for animals on a
    ration containing 90 ppm and 14 ppm of ethiofencarb respectively.

    Residues in milk averaged about 1 mg/kg at the highest feed level.
    Tissue residues are shown in Table 4.

    A lactating cow and a pig were treated with a single oral dose of 0.5
    mg/kg 14C-ring-labelled ethiofencarb (Dorough, 1976h). 24 hours
    after administration 97.8% of the dose had been excreted via the urine
    from the cow and 90% from the pig. Elimination of the radiocarbon in
    the faeces was <1% and 5.1% in cow and pig respectively.

    Tissues of the pig contained no detectable radioactive residues 24
    hours after treatment. Of the bovine tissues only kidney, liver and
    skin contained detectable residues (Table 4) of 0.016, 0.017 and 0.05
    mg/kg ethiofencarb equivalents respectively. Maximum concentrations of
    14C in the blood of the cow, reached 3 hours following
    administration, were 0.3 mg/kg. The milk the peak residue level was
    0.15 mg/kg, reached 4 hours after dosing. About 67% of the milk
    residue consisted of free metabolites, mainly ethiofencarb sulphoxide
    and sulphone.

    11.6% of the urinary metabolites in the cow were in the free form,
    predominantly as phenol sulphoxide and phenol sulphone. Other
    metabolites were eliminated as conjugates. In the pig 40.6% of the
    dose was excreted in free form.

    Eight laying hens were treated with a single oral dose of
    14C-ring-labelled ethiofencarb at a rate of 0.5 mg/kg (Dorough,
    1976). over 80% of the administered radiocarbon was eliminated in the
    excreta after 24 hours and over 90% after 3 days. The highest
    radiocarbon level 8 hours after application was found in kidney at
    0.062 mg/kg. Liver, muscle and blood showed lower residue levels and
    C, fat and heart no residues could be detected (see Table 4). 24 hours
    post-administration no 14C could be detected in the tissues. Eggs
    laid during a 3-day period following the single treatment were free
    from detectable residues.

    In a further study (Dorough,1976i) 10 hens were given
    14C-ring-labelled ethiofencarb as daily treatment for 7 days at a
    rate of 0.5 mg/kg twice a day. 2 days after the start of treatment
    about 60% of the cumulative dose was excreted and after 7 days about
    92%. Tissues of animals sacrificed 3-4 hours after the final dose
    contained 14C-ethiofencarb equivalents ranging from about 0.02 mg/kg
    in fat to 0.32 mg/kg in kidney. 4 days after the termination of
    treatment muscle, skin, kidney and liver contained 0.001, 0.006, 0.007
    and 0.009 mg/kg 14C-ethiofencarb equivalents respectively. In bloody
    brains fat and heart no residues were detectable. Levels of
    radiocarbon in the eggs reached a maximum of 0.06 - 0.07 mg/kg after 7
    days of continuous treatment. In eggs (white and yolk) residues were
    about 0.03 - 0.04 mg/kg after 2 days of treatment, reached a maximum
    of 0.06 - 0.07 mg/kg after 7 days and were below detectable levels 3
    days after treatment was stopped.


        TABLE 2. Use pattern of ethiofencarb

                                                                                                                      

    Crop                     Concentration or            Formulation               Number of       Pre-harvest
                             application rate (a.i.)                               applications    interval(days)
                                                                                                                      

    Vegetables               0.0375-0.05%                E.C.                      2-3             4-7
    (Cucurbitaceae,          foliar spray/overall
    eggplants, peas          application
    brassicas, peppers,      0.075 -0.1 g./linear        GR                        1
    lettuce, tomatoes        metre at sowing/
    Vicia, etc.)             planting

    Cereals                  100-500 g./ha.              E.C.                      1-2             14-21
    (including millet)       foliar spray/overall
                             application

    Potatoes                 500-600 g./ha               E.C.                      2-3             14
                             foliar spray/overall
                             application
                             0.075-0.1 g./linear         GR                        1
                             metre at planting

    Pome and stone fruit,    0.05%                       E.C.                      2-3             7-10
    small (soft) fruit,      foliar spray/overall
    citrus fruit             application

    Beets                    400-500 g./ha               E.C.                      2-4             14
                             foliar spray/overall
                             application

    Tobacco                  0.05-0.075%                 E.C.                      2-3             4-7
                             foliar spray/overall
                             application
                             0.075-0.1 g./linear         GR                        1
                             metre at sowing/
                             planting
                                                                                                                      

    TABLE 3. Residues of ethiofencarb, its sulphoxide and sulphone from supervised trials

                                                                                                                                             

                                     Application         Residues (mg/kg) at interval (days) after last application
    Crop               Country a)    No.    kg/hab)        0           3-4          7-10        14-16       18-21       >21           Ref. c)
                                                                                                                        (number in
                                                                                                                        brackets)
                                                                                                                                             
    Apple              D             2-3    1 EC           0.9-2.2     0.4 -2.0     0.4 -1.3    0.4 -1.6    0.2 -1.4    0.3-1.0       1)
                                                                                                                        (28d:)
                       F             1      0.5 EC         0.6                      0.3 -0.4    0.4                                   1)
                       J             3/5    3-3.5 EC                                                        1.2 - 1.3   0.8-1.2       2)
                                                                                                                        (30d.)

    Apricot            J             2/4    7.5 gEC/tree                                                    0.8 -1.2    1.8-2.1       3)
                                                                                                                        (28d.)

    Artichoke          F             1      0.5-1EC        1.0                      0.4 -4.7    0.2 -3.0    0.2 -1.0                  1)

    Beans
    broad beans        D             2-3    0.3 EC                                                                                    1)
    beans                                                  0.02-0.04                0.02-0.04   0.02-0.03   <0.02
    pods                                                   0.2 -0.43   0.08-0.26    0.05-0.22   0.04-0.11   0.02-0.05
    greens                                                 5.5 -10.1   0.8 -4.6     0.6 - 4.6   0.5 -3.1    0.2 -1.0
    broad beans        D             1      1.5            G                        (55d.)      (89d.)      (111d.)
    beans                                                                                       0.02-0.13   0.02-0.04
    pods                                                                                        0.19-0.42   0.19-0.57
    greens                                                                          14-30       2.2 -6.1    0.17-0.84
    bush}              D             2-3    0.3 EC         0.14-0.68   0.25-0.43    0.03-0.32   0.02-0.19   0.02-0.11   <0.02         1)
                                                                                                                        (28d.)
    beans}             F             1      0.75 EC                                 1.46-2.47   0.77-1.84
                       F             1      2    G                                  0.05        0.05        0.03                      1)

    TABLE 3. (Continued)
                                                                                                                                             
                                     Application         Residues (mg/kg) at interval (days) after last application
    Crop               Country a)    No.    kg/hab)        0           3-4          7-10        14-16       18-21       >21           Ref. c)
                                                                                                                        (number in
                                                                                                                        brackets)
                                                                                                                                             

    Cabbage
    Brussels sprouts   D             3      0.3 EC         0.5 -1.4    0.4 -0.94    0.2 - 0.9                                         1)
    Cauliflower        D             2      0.3 EC         0.3 -0.5    0.1 -0.43    0.05-0.2
                       F             1      0.5 EC                                  0.26        0.11        0.07                      1)
    Chinese cabbage    J             3/5    0.75-2EC                   0.04-2.7     0.04-1.8                0.06-2.4                  4)
                                                                       (5d.)
    Red cabbage        D             2      0.3 EC         0.2 -1.1    0.2 - 0.4    0.05-0.5                                          1)
    Savoy cabbage      D             2      0.3 EC         0.4 -3.1    0.1 - 1.3    0.05-1.3    0.2 - 0.6   0.06-0.4    0.05-0.3      1)
                                                                                    (46d.)      (78d.)      (88d.)      (28d.)

    Savoy cabbage      D             1      1 G                                     0.5 -0.6    0.05        <0.05                     1)
    White cabbage      D             2      0.3 EG         0.2         0.1          <0.05                                             1)
    White cabbage      GB            1      3              G                        0 09                                              1)
    Cherry (see end of table)                                                       (105d.)
    Cucumber           J             3/5    0.75-          0.7 -0.9    0.3 -0.8     0.2 -0.5    0.1 -0.32                             4)
                                            2.5 EC
    Currant
    Blackcurrant       D             2      1 EC           1.1 - 2.8   0.5 - 1.4    0.6 - 1.4
    Red currant        D             2      1 EC           0.5 - 2.9   0.4 - 1.0    0.2 - 0.6                                         1)
    Eggplant           F             1      0.75 EC                                 0.03-0.5    0.02-1.0                              1)
    Lettuce
    (outdoor)          D             2      0.3 EC         4.3 - 10.1  1.3 - 4.4    0.6 - 2.2   0.4 - 0.8   0.2 - 0.6   0.1 - 0.2     1)
                                                                                                                        (28d. )
    (under glass)      D             2      0.3 EC         2.3 - 18.8  2.2 - 10.1   1.6 -6.4    1.5                     0.5 - 0.8     1)
    (under glass)      NL            1      5 G                                                                         (44-67d.)     1)

    Peach              D             1-2    0.75-1EC       1.2 -2.3    1.1 -1.7     0.5 -2.0    0.4 -1.4    0.3 -1.1
    Peach              F             1      0.5 EC         0.3 -0.8                 0.2 -0.3    0.1 -0.2

    Plum (see end of table)

    TABLE 3. (Continued)
                                                                                                                                             
                                     Application         Residues (mg/kg) at interval (days) after last application
    Crop               Country a)    No.    kg/hab)        0           3-4          7-10        14-16       18-21       >21           Ref. c)
                                                                                                                        (number in
                                                                                                                        brackets)
                                                                                                                                             

    Potatoes           D             3      0.4-0.6        0.16-0.23                            0.09-0.25   0.08-0.17   0.02-0.16     1)
                                            EC                                                                          (28d.)
    Potatoes           US            2-6    0.5-2 EC       <0.02-0.06                          <0.02-0.06                             6)
    Potatoes           J             4-5    0.9-1.75                                0.07-0.1    0.04-0.16   0.04                      7)
                                            EC
    Potatoes leaf      J             1      0.7-1.7 EC     38-57       2.2 -4.6     0.3 -1.3    0.2 -0.6                              7)
    Potatoes           D, NL,        1      1.5  G                                                                      <0.02-0.06    1)
                                                                                                                        (91-135d.)

    Radish             J             3/5    1-1.5 EC                                0.10-0.12   0.03-0.14   0.02-0.10
    Radish leaf        J             3/5    1-1.5 EC                                0.1-1.5     0.06-1.2    0.1-0.6                   8)

    Soybean
    Soybean,                         3      0.75-1.5                                0.02-1.04   <0.02-0.18
    green+shell                             EC
    Soybean, bean                    3/5    0.75 EC                                             0.04-0.06               0.02-0.04     9)
                                                                                                                        (44-67d.)


    Wheat                                                                                                                             1)
    grain              D             2      0.4 EC
    straw                                                  9.6 -11.4                1.4 -1.9    <0.02       <0.02                     1)
    grain              F             1      0.5 EC                                              1.2 -1.7    0.06-0.8
    straw                                                                                                               <0.02
                                                                                                                        0.1 -0.32
                                                                                                                       (34.53d.)

    TABLE 3. (Continued)
                                                                                                                                             
                                     Application         Residues (mg/kg) at interval (days) after last application
    Crop               Country a)    No.    kg/hab)        0           3-4          7-10        14-16       18-21       >21           Ref. c)
                                                                                                                        (number in
                                                                                                                        brackets)
                                                                                                                                             
    Sugar beet
    beet               D,GB          2-5    0.25-0.5                   0.04-0.06                0.03        0.02        0.01-0.03     1)
    top (leaf)                                    EC                   3.0 -4.7                 2.0 -2.2    2.7 -4.9    0.12-1.4
                                                                                                                        (31-76d.)
    beet               D, GB         1      1-5-3 G                                                                     0.01-0.08     1)
    top (leaf)                                                                                                          0.05-1.1
                                                                                                                        (124-195d.)
    Tobacco                          3      0.3-0.4        12.5-52     5.4-37       4.5-21      1.3 - 9.3   2.9 - 5.7   1.1 -13
                                                                                                                        (25-28d.)     1)
    air -
    cured              D             1      1.5 G                                                                       4.5 -12.3
                                                                                                                        (54-58d.+
                                                                                                                        132-137d.
                                                                                                                        cured)

    Cherry
    (morello)          D             3      1 EC           1.8 -5.9    0.5 -5.9     1.2 -4.2                                          1)

    Plum               D             3      1 EC           2.4 -3.5    1.3 -3.4     1.3 -2.6                                          1)

                                                                                                                                             

    Trials in a)
    Fed. Rep. Germany = D
    France = F
    Great Britain = GB
    Japan = J
    Netherlands = NL
    United States Amer. = US

    TABLE 3. (Continued)

    b)
    EC = Emulsifiable concentrate
    G = Granular

    References c)
    1) Bayer AG, 1972/77
    2) Nitokuno Inst., 1976
    3) Nitokuno Inst., 1975
    4) Nitokuno Inst., 1975/76
    5) Nitokuno Inst., 1975a
    6) Chemagro Report, 1976
    7) Nitokuno Inst., 1975/76a
    8) Nitokuno Inst., 1976a
    9) Nitokuno Inst., 1976b


    TABLE 4. Ethiofencarb equivalents in various tissues of warm-blooded animals
                                                                                                                                             

                                                    Radioactivity expressed as ethiofencarb (mg/kg) in

    Animal   Application             Time after    Blood   Brain    Fat    Giblet   Heart    Kidney   Liver   Muscle   Skin  Ref.
                                     first
                                     application
                                                                                                                                             

    Rat     0.5 mg/kg Ring- 14C      2.5 h         0.021)                                    0.061)   0.041)  0.031)         Dorough,
            single oral dose                                                                                                1976j

    Rat     0.5 mg/kg N-Methyl-14C   8 h                                                     0.24     0.88                   Hurst and
            single oral dose         24 h                                                    0.19     0.46                   Dorough,
                                                                                                                             1976

    Rat     6.6 ppm/day in diet                    0.24    0.18     0.06                     0.29     1.18    0.10           Nye at al.,
            for 7 days, carbonyl-14C                                                                                         1976

    Cow     0.5 mg/kg Ring-14C       3 h           0.32                                      0.016    0.017            0.05  Dorough,a
            single oral dose         24 h                                                                                    1976h

    Cow     2xdaily 50 PPM in diet                         0.03     0.042)          0.03     0.01     <0.01   0.083)         Gronberg
            for 28 days                                                                                                      et al.,
            2xdaily 150 PPm in diet                        0.27     0.232)          0.29     0.10     0.01    0.853)        1976
            for 28 days 
            2xdaily 500 PPM in diet                        2.17     1.012)          2.53     0.89     0.13    4.313)
            for 28 days 

    Hen     0.5 mg/kg Ring-14C       8 h           0.053   0.028                             0.062    0.035   0.039    0.022 Dorough,
            single oral dose                                                                                                 1976i

            0.5 mg/kg Ring-14C       4 days        0.016   0.001                    0.005    0.016    0.025            0.013
            2xdaily for 7 days       7 days4)      0.099   0.039    0.019           0.072    0.324    0.180   0.069    0.075

    TABLE 4.  (Continued)
                                                                                                                                             

                                                    Radioactivity expressed as ethiofencarb (mg/kg) in

    Animal   Application                Time after  Blood   Brain    Fat    Giblet   Heart    Kidney   Liver   Muscle   Skin  Ref.
                                        first
                                        application
                                                                                                                                             
    Hen    45 ppm in diet for 28 days                               0.03   0.04                               0.05     0.05  Gronberg
           150 ppm in diet for 28 days                              0.07   0.13                               0.08     0.10  and
           450 ppm in diet for 28 days                              0.16   0.41                               0.29     0.24  Dorough,
                                                                                                                             1976
                                                                                                                                             



    1)   The values were derived from graphs

    2)   Mixed omental, renal and subcutaneous fat

    3)   Mixed loin, round, flank

    4)   Higher residues at 7 than at 4 days were due largely to the fact that the 7-day birds were sacrificed 3-4 h
         after last treatment while 4-day birds were sacrificed 8 h after treatment
    

    The major identified metabolites eliminated in the excreta were the
    phenol sulphoxide and sulphone, existing as free metabolites or
    conjugates, the proportion of free metabolites being higher in the
    singly dosed birds. Small amounts of the sulphoxide and sulphone of
    the carbamate were also found in the continuous feeding study only.
    The same sulphoxidation products were found as the principal
    metabolites in eggs, about 50% of the residue being the phenol
    sulphone and about 20% the phenol sulphoxide.

    Poultry were continuously fed with ethiofencarb for 28 days at a
    ration level of 0, 15, 45, 150 and 450 ppm (Gronberg and Dorough,
    1976). The average concentration of ethiofencarb equivalents (Table 4)
    in fat, skins muscle and giblet ranged from 0.03 to 0.05 mg/kg at the
    45 ppm level, from 0.07 to 0.13 mg/kg at the 150 ppm level and from
    0.16 to 0.4 mg/kg at 450 ppm. Average residues in eggs collected at
    days 26, 27 or 28 of treatment were approximately 0.01, 0.04 and 0.1
    mg/kg at the 451 150 and 450 ppm feeding levels respectively. Prom
    these residue data it me concluded that tissue residues would be less
    then 0.1 mg/kg and egg residues less than 0.01 mg/kg for animals on a 
    ration of 100 ppm and 40 ppm respectively.

    After continuous exposure of Channel catfish to 10 µg/1
    14C-ring-labelled ethiofencarb for 28 days, 14C residues accumulated
    to a plateau of about 50-75 mg/kg reached after 4 days. The edible
    parts of the fish contained about 27% of the residues. During the
    withdrawal period about 82% of the accumulated residues were excreted
    wIthin 1 day and about 95% within 4 days (Lamb and Roney, 1976).

    In plants

    Ethiofencarb has good systemic properties and is absorbed in large
    amounts by the plant roots and translocated to the aerial parts
    (Homeyer, 1976).

    Bean seedlings absorbed a total of 34.6% of the available
    14C-ring-labelled ethiofencarb from a solution via the roots in 4
    days, whilst 18.1% was found after application of
    14C-carbonyl-labelled compound. The distribution of radiocarbon in
    the plant after 4 days was: roots 5.1%, stems 9.0%, leaves 16.5%
    (Dorough, 1976 g).

    Dräger (1976a) applied 10% granules of ethiofencarb (I, Figure 1), its
    sulphoxide (II) and its sulphone (III) separately to soil at the time
    of sowing beans. Results are shown in Table 5. Generally, the total
    residue in the green parts was highest after applying Ill and lowest
    after the application of I. The highest residues ware in the green
    parts (leaves and stems) followed by pods and beans; the highest
    levels were found at the first sampling 4 weeks after sowing.


        TABLE 5. Uptake of ethiofencarb (I), its sulphoxide (II) and sulphone (III) by beans

                                                                                                                      

    Interval                                               Total residue (mg/kg) after application of
    after
    application,                          I Granular                II Granular                 III Granular

    weeks
                                                                                                                      

                                     a*       b*       c*      a        b         c         a        b       c
    4                                159      -        -       210      -         -         310      -       -
    6                                61       -        -       135      -         -         204      -       -
    8                                49       -        -       74       -         -         96       -       -
    12                               78       0.95     0.27    25       0.18      <0.1      141      0.20    0.06
                                                                                                                      

    *a: green parts;
    b: pods;
    c: beans
    

    Following foliar application of 14C-carbonyl-labelled and
    14C-ring-labelled I to beans, potatoes and sorghum, it was found that
    14 days after application only 60.7, 29.0 and 45.1% of the insecticide
    had been absorbed from the leaf surfaces of the respective plants
    (Dorough, 1976g).

    Potato and sorghum plants were treated at 0.56 kg/ha with ring-14C-I
    in an E.C. formulation. The plants were treated at 10-day intervals
    5-7 times during the growing season. Radiocarbon residues were much
    lower in potatoes than in sorghum. Total ethiofencarb equivalents
    remained essentially constant in potato peels (0.2 mg/kg) and pulp
    (about 0.15 mg/kg) for 31 days after treatment. In sorghum the highest
    levels of ethiofencarb equivalents were located in the leaves (10-100
    mg/kg) followed by heads (5-25 mg/kg), grain (1-10 mg/kg) and stalks
    (0.05-0.5 mg/kg). Sorghum leaf levels showed an increase from 85 to
    131 mi/kg during the first two weeks but declined to about 94 mg/kg at
    31 days. Levels remained relatively constant in the stalks. Levels in
    the grain appeared constant (6-9 mg/kg) throughout the entire study
    except for the 1 week sample (19 mg/kg). Total radiocarbon in the
    heads tripled from 50 mg/kg at time 0 to 167 mg/kg at 1 week and then
    declined to 90 mg/kg at 31 days (Dorough, 1976f).

    Dräger detected II and Ill in various plant parts after application of
    10% granular 14C-carbonyl-labelled ethiofencarb at planting of beans
    (0.05 g I/1.6 kg soil; 1976a) and potatoes (0.05 g /approx. 20 1 soil;
    1976c). The extractable residues in the roots and green parts of both
    potatoes and beans consisted mainly of II and Ill. 0.21-7.79 mg/kg II
    and 0.14-0.31 mg/kg III were found in the roots of the potatoes
    between days 34 and 96, with 1.39-16.2 mg/kg II and 3.08-8.79 mg/kg
    Ill in the green parts. The bigger increase in the sulphone content of
    the green parts of the potatoes is indicative of an increased
    oxidation of the sulphoxide in the plant system. The two metabolites
    were detected also in the potato tubers and beans but there was too
    little material available for extensive quantitative studies on the
    beans. The potato tubers contained 0.05-0.28 mg/kg II and 0.06-0.14
    mg/kg Ill.

    The unextractable radioactivity in the green parts of the beans was
    less than 1% or the total applied, and accounted for a maximum of 7.7%
    of the radioactivity measured at the sampling times (Drägert 1976a).
    The major portion of the unextractable radioactivity in the potato
    tuber was in the glucose moiety of the starch. Therefore, CO2 formed
    by hydrolysis of the carbamate group was utilized in carbohydrate
    metabolism. The unextractable but water soluble radioactivity in
    rootsy green parts and potato tubers was also considered to be
    incorporated in products of carbohydrate metabolism. For details of
    the distribution of radioactivity in potatoes and beans, see Table 6.


        TABLE 6. 14C-ethiofencarb and metabolites in plants (as % of radioactivity applied or recovered)

                                                                                                                                               

                                             % of activity recovered as 1)
    Plant          Time after   Label and
                   application  Formulation   I     II     III    IV     V    VI    unidentified activity   As% of    As% of       Ref.
                                                                                    % found at indicated    applied   recovered
                                                                                    TLC positions           activity  activity
                                                                                                                                               

    Bean           0 day        14CO+       61.9   29.6    1.6          0.7         origin-0.1;             98.0                   Dorough,
                                                                                    x2 = 4.1                                       1976g
                   3 days       Ring-       10.8   55.9    4.4          6.7  1.9    origin = 11.3; x1=0.5;  94.0
                                                                                    x2 =2.5
                   7 days       14C                49.7   11.4          1.4  0.5    origin=20.2;x1=0.4;     84.6
                                                                                    x2=1.0
                   14 days      EC                 15.6    0.6          1.7  0.6    origin=49.8;x1=0.5      69.1
                                                                                    x2=0.3

    Potato         0 day                    41.3   50.0    1.0                      origin=1.5; x1=1.8;     100.3
                                                                                    x2=4.7
                   3 days                   23.1   48.6    3.3          2.0         origin=5.9; x1=1.8;     91.2
                                                                                    x2=7.9
                   7 days                    7.0   42.2    6.5          2.6  0.4    origin=15.7; x1=1.9;    80.4
                                                                                    x2=4.1
                   14 days                   1.8   38.0    9.6          3.5  0.8    origin=14.0; x1=6.2     77.1
                                                                                    X2=3.2

    Sorghum        0 day                    73.0   22.8    0.9                      origin=0.9; x2=0.9      98.5
                   3 days                   18.1   49.3    1.3          0.8  0.3    origin=5.9; x2=2.3      78.0
                   7 days                    3.2   47.0    4.3          1.3  1.0    origin=10.3; x2=2.0     69.1
                   14 days                   0.3   38.6    6.1          0.7  0.3    origin=23.6; x2=0.5     70.1

    TABLE 6. (Continued)

                                                                                                                                               

                                             % of activity recovered as 1)
    Plant          Time after   Label and
                   application  Formulation   I     II     III    IV     V    VI    unidentified activity   As% of    As% of       Ref.
                                                                                    % found at indicated    applied   recovered
                                                                                    TLC positions           activity  activity
                                                                                                                                               

    Potato
    Peel                        Ring-
    org.           0 day        14C          5.2   10.0    2.7          3.4  2.6    origin=1.3; x1=3.8                29.0         Dorough, 1976f
    -soluble
    water-                      EC                                      1.7  3.3    origin=1.0; x1=2.1                8.1
    soluble
    unhydrolysed                                                                                                      18.1
    by H2O
    unextractable                                                                                                     44.8
                                                                                                                      100.0
                                                                                                                      (102.4)2)

    Potato
    Peel
    org.           31 days      Ring-        3.6    2.7    2.7          8.0  6.3    origin=0.9                        24.2         Dorough, 1976f
    soluble
    water soluble               14C                                                                                   20.9
    unhydrolysed                EC                                                                                    31.0
    by H2O
    extractable                                                                                                       24.1
                                                                                                                      100.0
                                                                                                                      (90.9)2)

    TABLE 6. (Continued)

                                                                                                                                               

                                             % of activity recovered as 1)
    Plant          Time after   Label and
                   application  Formulation   I     II     III    IV     V    VI    unidentified activity   As% of    As% of       Ref.
                                                                                    % found at indicated    applied   recovered
                                                                                    TLC positions           activity  activity
                                                                                                                                               

    Pulp
    org.-soluble   0 day                            3.5                 7.1  5.8    origin=0.3                        16.7
    water-soluble                                                       4.2  5.3    origin=0.5; x1=3.9                14.0
    unhydrolysed                                                                                                      20.7
    by H2O
    unextractable                                                                                                     48.6

                                                                                                                      100.0
                                                                                                                      (100.6)2)


    org.-soluble   31 days                   0.7    2.5    0.6          6.6  2.1    origin=0.2                        12.7
    water-soluble                                                                                                     16.2
    unhydrolysed                                                                                                      38.8
    by H2O
    unextractable                                                                                                     32.3

                                                                                                                      100.0
                                                                                                                      (90.6)2)

    Sorghum
    Leaves
    org.-soluble   0 day        Ring-        1.4   50.5   11.6    0.9   2.1  5.2    origin=1.0; x3=0.5                73.2
    water-soluble                   14C      0.2    0.6                 8.3  4.1    origin=0.2; x2=0.7                14.1
    unhydrolysed                EC                                                                                    5.2
    by H2O
    unextractable                                                                                                     7.5
                                                                                                                      100.0
                                                                                                                      (98.8) 2)

    TABLE 6. (Continued)

                                                                                                                                               

                                             % of activity recovered as 1)
    Plant          Time after   Label and
                   application  Formulation   I     II     III    IV     V    VI    unidentified activity   As% of    As% of       Ref.
                                                                                    % found at indicated    applied   recovered
                                                                                    TLC positions           activity  activity
                                                                                                                                               

    Leaves
    org-soluble    31 days      Ring-        0.4   11.3   15.7          3.1 17.8    origin=0.6; x2=0.4                50.4         Dorough, 1976f
                                    14C                                             x3=0.7; x5=0.4
    water-soluble               EC                 0.6     0.4          4.2  4.9    origin=0.3; x2=0.7                11.1
    unhydrolysed
    by H2O                                                                                                            12.8
    unextractable                                                                                                     25.7
                                                                                                                      100.0
                                                                                                                      (99.4)2)


    Stalks
    org.-soluble   0 day                           56.2   15.6               2.5    origin=1.2                        75.5
    water-soluble                                                           11.4    origin=0.5                        11.9
    unhydrolysed
    by H2O                                                                                                            7.1
    unextractable                                                                                                     5.4
                                                                                                                      99.9
                                                                                                                      (97.0)2)

    Stalks
    org.-soluble   31 days                         14.6   25.5          1.8  3.0    origin=0.6                        45.5
    water-solube                                                            27.8    origin=0.9                        28.7
    unhydrolysed
    by H2O                                                                                                            15.3
    unextractable                                                                                                     10.5
                                                                                                                      100.0
                                                                                                                      (105.4)2)

    TABLE 6. (Continued)
                                                                                                                                               
                                             % of activity recovered as 1)
    Plant          Time after   Label and
                   application  Formulation   I     II     III    IV     V    VI    unidentified activity   As% of    As% of       Ref.
                                                                                    % found at indicated    applied   recovered
                                                                                    TLC positions           activity  activity
                                                                                                                                               
    Heads
    org.-soluble   0 day                     1.7   45.2   14.4    0.9   1.8  5.2    origin=0.6; x2=0.7;
                                                                                    x5=2.1                            72.6
    water-soluble                                   0.4    2.2          3.9  0.4    origin=0.2; x1=0.3;
                                                                                    x2=0.5                            7.9
    unhydrolysed
    by H2O                                                                                                            4.2
    unextractable                                                                                                     15.3
                                                                                                                      100.0
                                                                                                                      (95.9)2)

    Sorghum
    Heads
    org.-soluble   31 days      Ring-        1.6   26.0   27.1    0.4   1.6  9.9    origin=1.0; x2=1.0;               70.6         Dorough, 1976f
                                14C                                                 x5=2.0
    water-soluble               EC           0.3    0.3    0.2          3.3  2.8    origin=0.2; x1=0.2;               7.8
                                                                                    x2=0.5
    unhydrolysed                                                                                                      4.7
    by H2O
    unextractable                                                                                                     16.9
                                                                                                                      100.0
                                                                                                                      (98.7) 2)

    Grain

    org.-soluble   0 day                           51.1    1.7          5.5  2.2    origin=0.8; x2=0.7;
                                                                                    x5=1.8                            63.8
    water-soluble                                                       4.2  5.7    origin=0.9; x2=0.6                11.4
    unhydrolyzed
    by H2O                                                                                                            7.0
    unextractable                                                                                                     17.8
                                                                                                                      100.0
                                                                                                                      (99.2)2)

    TABLE 6. (Continued)
                                                                                                                                               
                                             % of activity recovered as 1)
    Plant          Time after   Label and
                   application  Formulation   I     II     III    IV     V    VI    unidentified activity   As% of    As% of       Ref.
                                                                                    % found at indicated    applied   recovered
                                                                                    TLC positions           activity  activity
                                                                                                                                               

    Grain

    org.-soluble   31 days                         11.2    9.0          1.3  3.7    origin=0.5; x2=0.6;
                                                                                    x5=1.6                            27.9

    water-soluble                                          8.4         14.7  0.8    origin=0.5; x1=0.5;
                                                                                    x2=1.0                            26.1
    unhydrolysed
    by H2O                                                                                                            12.5
    unextractable                                                                                                     33.5
                                                                                                                      100.0
                                                                                                                      (99.3)2)

    Potato                                                                          unextractable by
                                                                                    organic solvents

    Roots          34 days      14-CO       0.044  1.26   0.14                      solid residue
                                                                                    0.10 in aqueous
                                                                                    layers 0.11             1.654                  Dräger, 1976c
                   68 days      Granular    0.055  0.42   0.10                      solid residue
                                                                                    0.27 in aqueous
                                                                                    layers 0.15             0.945
                   96 days      soil               0.04   0.05                      solid residue
                                                                                    0.11; in aqueous
                                                                                    layers 0.07             0.27

    TABLE 6 (Continued)
                                                                                                                                               
                                             % of activity recovered as 1)
    Plant          Time after   Label and
                   application  Formulation   I     II     III    IV     V    VI    unidentified activity   As% of    As% of       Ref.
                                                                                    % found at indicated    applied   recovered
                                                                                    TLC positions           activity  activity
                                                                                                                                               

    Green parts    34 days                         7.15   3.89                      solid residue
                                                                                    1.02 in aqueous
                                                                                    layers 0.94
                   68 days                         10.28  9.03                      solid residue
                                                                                    2.78 in aqueous
                                                                                    layers 3.04             25.12

                   96 days                         4.38   10.18                     solid residue
                                                                                    2.17 in aqueous
                                                                                    layers 3.42             20.15

    Tubers         68 days                  0.00   10.35  0.18                       solid residue
                                                                                     0.973) in aqueous
                                                                                     layers 0.60             2.101

                   96 days                         0.17   0.20                       solid residue 2.393)
                                                                                     in aqueous layers 0.92  3.46
    Bean
    Roots          5 weeks                         0.26   0.07                       unextractable: 0.07     0.40                  Dräger, 1976c
                   10 weeks                        0.15   0.19                       unextractable: 0.13     0.47

    Green parts    5 weeks                         3.53   0.95                       unextractable: 0.27     4.75
                   10 weeks                        3.02   4.27                       unextractable: 0.61     7.90
                                                                                                                                               

    TABLE 6 (Continued)
                                                                                                                                               
    1) Compounds I-VI are identified in Figure 1.
    2) The figures in Parentheses indicate percent of total recovery, based on combustion
    3) Consisting of:
                              68days         96days

    14C-CO2 (CO3-)            0.04           0.39
    14C-Glucose in starch     0.85           1.66
    Non-hydrolyzable          0.08           0.34
                              0.97           2.39
    

    Following foliar and soil application, and stem injection of 14CO-and
    ring-14C- labelled ethiofencarb to beans, potatoes and sorghum,
    Dorough 1976f,g found that in addition to the major metabolites II and
    III, minor amounts of IV, V and VI as well as unidentified metabolites
    had formed. For quantitative data, see Table 6.

    Bean plants were also treated with II and III (14C-ring-labelled),
    After three days, 86.6% of II and 91.7% of III had been converted to
    water-soluble metabolites which were easily degraded by acid
    hydrolysis (Dorough, 1976g).

    In soil

    Studies with 14C-carbonyl-labelled ethiofencarb (granular
    application; Dräger, 1976c 1977a) showed that ethiofencarb was
    oxidized in soil to the corresponding sulphoxide (II) and sulphone
    (III). Details are given in Table 7. After 5 weeks II was the main
    residue but the proportion of III increased with time. Residues of
    ethiofencarb in the first sample taken after 5 weeks were 2 mg/kg in
    one experiment(1976c) and undetectable in another (1976a). The
    unextractable residues amounted to 3-9% of the applied radioactivity.

    Dräger (1977b) also found in laboratory studies with soil 34 clay
    after the application of carbonyl-ethiofencarb (1) residues of 4.4% I,
    68% II and 14% III. The carbamate group was hydrolyzed to CO2 with a
    half-life of about 90 days. After 82 days, 43% of the radioactivity of
    the carbonyl group was identified as gaseous CO2 Of the remaining
    radioactivity left in the soil, II accounted for 1.7%, III for 38.3%,
    and unextractrables for 17%; I could not be detected.

    Ethiofencarb was degraded in the field in different soils with
    half-lives of 20-30 days (Bayer, 1972/77), and in laboratory studies
    with a maximum half-life of 32 days (Nitokuno, 1976d). In other
    studies half-lives of approx. 90 and 130 days were obtained.

    After the application of ethiofencarb 2 kg/ha as an emulsifiable
    concentrate to different types of soil the following maximum residues
    (I + II + III) were found: 8.8 mg/kg 0 days after application), 4.4
    (7), 3.2 (14), 1.1 (30), 0.6 (60), 0.25 (92) and 0.1 (120) (Bayer
    1972/77).

    In greenhouse experiments with 14CO-labelled ethiofencarb granules,
    Dräger calculated a half-life of about 6-7 weeks from the
    radiochemical degradation rate of the total residue in soil planted
    with potatoes (1976c) and a half-life of about 2 weeks in soil planted
    with beans (1976a).

    Half-lives for the degradation of ethiofencarb in soil are presented
    in Table 8.


    
    TABLE 7. Distribution of radioactivity in soil after application of
    14C-carbonyl ethionfencarb

                                                                                                      

    Compound                                            % of initial 14C remaining on day

                                             35         56        70        34         68        96
                                                                                                      
    Ethiofencarb (I)                         n.d.       n.d.      n.d.      2.20       0.22      0.08

    Ethiofencarb sulphoxide (II)             16.72      3.14      1.96      41.79      8.10      0.87

    Ethiofencarb sulphone (III)              4.37       2.94      2.46      8.18       4.81      3.01

    Unextractable                            5.45       9.12      7.49      7.32       5.64      2.60

    Total                                    26.54      15.20     11.91     59.49      18.77     6.56

    References                               Dräger,    1976 a,b,c          Dräger,    1976 a,b,c
                                                                                                      

    

    The soils were planted either with beans (0.05 g I/1.6 kg soil; 
    Dräger, 1976a) or with potatoes T 0.05 g I/approx. 20 1 soil., Dräger,
    1976 c) so that a portion of the radioactivity was absorbed by the
    plants (see "Fate In Plants").

    In laboratory studies to investigate the leaching behaviour of
    ethiofencarb, normal dosages of formulations were applied to soil
    which were eluted to simulate a rainfall of 200 mm in 2-21 days. The
    leachate contained the following percentages of the applied dose as
    total residues of I + II + III: low-humus sand 26.6-62.5%; high-humus
    loamy sand 7.1-19.4%; sandy loam 18.2-74.5%. When II was applied to
    low-humus sand and sandy loam, leachates contained 41% and 57% of the
    dosage respectively. After application of Ill, the corresponding
    figures were 50% and 40% (Bayer, 1972/77).

    Rieck (1976a) found in laboratory studies with ring-labelled
    14C-ethiofencarb (columns: 20 cm high and 10 cm diameter; application
    of water equivalent to 500 m of rainfall) that the products of
    ethiofencarb were not leached as rapidly from the Boils with higher
    organic matter as from in the sandier, lean organic soils. In silty
    clay, 88% of the radiocarbon was found in the upper 8 cm of the
    column. Approximately 1-15% of the radiocarbon was found in the
    leachates, of which at least 80% was II. The only other product found
    in all the leachates was III. The products that remained in soil were
    the same as those in the leachates and were in the same proportion.

    Whereas carbamates were found in the leachate in these laboratory
    experiments with small soil columns, no ethiofencarb and no products
    with an intact carbamate structure were found in leachate samples
    examined over a period of 16 months in leaching studies with an intact
    soil core (10 cm diameter, 130 cm high) taken from the field after
    rainfall typical of practical conditions (755 mm/year) (Dräger,
    1976d).

    Further studies of the leaching characteristics of aged ethiofencarb
    residues under laboratory conditions were carried out by Dräger
    (1977c) and Rieck (1976b) In the studies of Dräger, about 40-50% of
    the applied 14Carbonyl activity was found in the leachate
    irrespective of the soil type. Of this, only part was extractable with
    chloroform. The unextractable portion was considered to be carbonate
    or hydrogen carbonate formed during the experiment by hydrolysis of
    the carbamate group of I (see also "Fate in Water"). The extractable
    portions consisted of II and IlI, in a ratio similar to that of the
    initial aged residues. I was no longer detectable. Rieck (1976b) also
    did not detect I in four different soils after 30 days of aerobic
    aging. The predominant residues were II and III, together with a
    considerable amount of unextractable radioactive residue. In contrast
    to the studies of Dräger (1977c) most of the radiocarbon was found in
    the upper 8 cm of the soil with less than 2% in the leachate.


    Thorton et al. (1976) compared the leaching behaviour of I with that
    of 23 other pesticides. The pesticides were spotted on thin-layer
    plates coated with six different types of soil ranging from
    non-adsorptive sand to fine-textured clay. The plates were developed
    and Rf values were compared. The compounds were grouped into five
    categories ranging from immobile to highly mobile. I was placed in
    class 49 as one of the mobile compounds.

        TABLE 8. Half-lives of ethiofencarb (as total residues
    of parent + sulphoxide + sulphone) in various soils

                                                                                    

                             Soil                                         Half-life
                                                                          (days)
                                                                                    

    Laboratory trials

    Carbon: 1.05%; fines: 30.4%; pH: 5.7 (Laacher Haf)                    90
    Carbon: 0.8% ; fines: 4.2%; pH: 7.0 (low-humus sand)                  96
    Carbon: 0.57%; fines: 19.5%; pH: 5.2 (sandy loam)                     133

    Clay: 14 %; org. matter: 5.85%; pH: 5.7 (sandy loam)                  13
    Clay: 13.6%; org. matter: 0.8%; pH: 7,0; Cation Exchange              32
    Capacity:4-5 me/100g
    (sandy loam)

    Greenhouse trials

    Carbon: 0.1%; fines: 22.1%; pH: 5.8; clay: 9.5%; fine silt: 12.6%     ca.14
    Carbon: 1.08%; fines: 23.2%; pH: 6.1; water cap.: 19-25%              42-49

    Field trials
    Clay 3.8%: silt: 18.3%; pH: 6.6; water cap. 36.1%                     20
    Clay: 13.7% silt: 29.4%; pH: 6.2; water cap. 61.3%                    20

    Carbon: 1.35%; fines: 9.1%; pH: 7.0                                   30
    Carbon: 0.8 %; fines: 15.3% pH: 6.5                                   23

    Clay: 14%; org. matter: 5.85%; pH: 5.7 (sandy loam)                   22
    Clay: 40%; org. matter: 5 %;
    Cation Exchange Capacity 15-18 me/200 g (loam)                        20
                                                                                    

    
    In water

    Ring-labelled 14C-I was incubated under sterile conditions in aqueous
    solutions buffered at pH 3, 6 and 9 at 25, 35 and 45°C. Ethiofencarb
    was shown to be stable for 30 days at PH 3 and 25°C, whereas the
    half-life at pH 9 and 45°C ranged from 0.3 to 0.7 days (Table 9). The
    primary hydrolysis product was IV, Figure 1 (max. 92.6% of the
    radioactivity of the sample) with only small amounts (<10%) of II
    (Kurtz and Gronberg, 1976). The hydrolysis rates of
    carbonyl-14C-labelled I, II and III were determined at pH 9.0, 9.5,
    10.0, 10.5 and 11.0. I was 3-5 times as stable as II or Ill. Again,
    the half-life of all compounds decreased with increasing pH (Table 9)
    (Dorough, 1976 d).

    Studies with 14CO-ethiofencarb showed that it decomposed in water (pH
    6.8) with a half-life of about 8 days, largely by hydrolysis of the
    carbamate group. In contrast to the metabolism in soil and plants, II
    and Ill were very minor products: their sum represented about 10% of
    the total carbamate residue throughout the experiment. After 31 days,
    83% of the original carbonyl carbon could be determined as carbonate
    or carbon dioxide gas, 3.4% was present as I, 0.3% as II and 0.2% as
    III (Dräger, 1976 b, 1977a)

    Photodecomposition

    The photodegradation of ring-14C-or carbonyl-14C-I was studies under
    artificial and natural sunlight on glass plates, silica gel plates,
    soil plates, and in aqueous solution (distilled water or pond water).
    5% or less of I was found after 6 hours irradiation. II was the major
    product: Ill and VI were found as minor constituents (Dorough,1976e).
    For quantitative data, see Table 10.

    The effect of anthraquinone as a photosensitizer was profound when
    applied as a mixture with I on silica gel plates. Although the extent
    of degradation of 1 me essentially unaffected, there was an increase
    in the number of minor photoproducts (those less than 1%) with
    anthraquinone and an increase in the polar material remaining at the
    origin after 7 days of exposure to a sunlamp. Almost no II was
    produced and a compound with a similar Rf to IV was the major product
    (48% after 7 days of exposure). There were also lesser amounts of Ill
    and VI (Dorough, 1976e).

    In storage and processing

    In head lettuce that had been field-sprayed in accordance with good
    agricultural practice, no decline of the total residue was noted after
    one year of storage in a deep freezer at -20°C (Bayer, 1974).



        TABLE 9. Half-lives of ethiofencarb in buffered solutions.

                                                                                                                           

                                                                Half-life of compound
    Conditions                                I                  II                   III               Ref.
                                            (ethiofencarb)     (ethiofenoarb        (ethiofencarb
                                                               sulphoxide)          sulphone)
                                                                                                                           

    pH:  9.0                                6.67 hours         2.03 hours           2.13 hours          Dorough, 1976d
         9.5                                2.67 hours         0.47 hours           0.72 hours
         10.0                               1.17 hours         0.23 hours           0.40 hours
         10.5                               0.43 hours         0.08 hours           0.12 hours
         11.0                               0.09 hours         0.02 hours           0.03 hours

    25 °C:     10 ppm;  pH 3                stable                                                      Kurtz and
                        pH 6                324 days                                                    Gronberg, 1976
                        pH 9                3.5 days
    25 °C;     100 ppm; pH 3                stable
                        pH 6                stable
                        pH 9                2.5 days
    35 °C;     10 ppm;  pH 3                stable
                        pH 6                68 days
                        pH 9                1.5 days
    35 °C;     100 ppm; pH 3                stable
                        pH 6                68 days
                        pH 9                2.0 days
    45 °C;     10 ppm;  pH 3                stable
                        pH 6                22 days
                        pH 9                0.7 days
    45 °C;     100 ppm; pH 3                stable
                        pH 6                20 days
                        pH 9                0.3 days
                                                                                                                           


    TABLE 10A. Photodegradation of 14c-ring labelled ethiofencarb (Dorough, 1976e)

                                                                                                                                      

                             % of applied 14C recovered as indicated Compound1) after indicated time
                                         1 hour                                          3 hours
    Conditions
                        O      I      II     III    IV     V      VI     xn     O      I      II     III    IV     V      VI     xn
                                                                                                                                      

    artifical light,    1.0    51.4   44.9                        3.5    2.3    1.8    16.3   70.3                        4.8    2.9
    TLC plates
    germicidal light,   14.2   6.6    22.7   24.1   0.6           15.6   9.5    20.1   1.3    10.8   23.9   1.0           14.6    10.0
    TLC
    plates
    natural
    light,              0.6    42.1   62.0   0.7                  1.9    0.8    1.2    2.9    91.4   2.2                  2.7    1.2
    TLC plates
    artifical light,    1.6    1.0    84.2   4.3                  7.1    0.9    1.9    1.4    79.1   5.3           1.7    9.0    1.0
    soil plates
    germicidal light,   1.6    1.8    80.1   44.4                 10.4   1.9    1.9    1.4    79.1   5.3           1.7    9.0    1.0
    soil plates
    natural light,      1.4    1.3    80.5   5.9                  9.5    1.5    1.2    1.9    82.7   6.3           0.5    6.6    0.9
    soil plates
    natural light,      1.1    0.5    46.1                 5.1    1.7           2.3    0.6    36.1   7.7                  1.6    
    glass plates
    natural light,      1.9    6.5    78.2   6.5           1.0    4.6    1.6    4.2    2.9    70.1   22.5                 6.5    5.3
    aquous
    solution
                                                                                                                                      

    1) 0 = polar material remaining at origin of TLC plate; I-VI are identified in Figure 1;
       xn = total unidentified radioactivity not remaining at TLC origin.

    TABLE 10B. Photodegradation of 14 c-ring labelled ethiofencarb (Dorough, 1976e)

                                                                                                                                      

                             % of applied 14C recovered as indicated Compound 1) after indicated time
                                   6 hours
    Conditions
                        O      I      II     III    IV     V      VI     xn
                                                                                                                                      
    artifical light,    2.4    5.2    78.6                 6.3    3.5
    TLC plates
    germicidal light,   21.2   4.3    8.8    24.3   1.0          14.0    9.7
    TLC plates
    natural light,      1.4    0.8    90.5   2.7                  2.9    1.2
    TLC plates
    artifical light,    2.1    1.0    83.6   5.9                  5.1    1.6
    soil plates
    germicidal light,   1.9    2.6    76.3   6.5           1.0    9.1    1.3
    soil plates
    natural light,      1.0    1.1    87.8   5.7           0.8    2.6    1.1
    soil plates
    natural light,      4.2    0.3    26.0   13.1          0.9    2.3
    glass plates
    natural light,      5.8    0.4    65.6   11.7          1.8    8.4    3.2
    aquous solution
                                                                                                                                      

    1)  0 = polar material remaining at origin of TLC plate; I-VI are identified in Figure 1;
        xn = total unidentified radioactivity not remaining at TLC origin.


    

    Studies to investigate the stability of the sulphoxide and sulphone
    metabolites in potatoes revealed that the content of both compounds
    remained constant on storage for 11 months at -20°C (Chemagro, 1976b).
    When bovine and poultry tissues, milk and eggs were fortified with
    14C-labelled ethiofencarb and stored under frozen conditions for 7
    months, 84-98% of the residue was found as intact carbamate (Chemagro,
    1976c).

    Poultry rations fortified with ethiofencarb for use in various animal
    feeding studies were stored for 5 weeks at -10°C; no degradation of
    the ethiofencarb was noted (Chemagro, 1975).

    Processing of plant material by baking and boiling results in the
    reduction of ethiofencarb residues. Broad beans which had a residue
    content of 0.13 mg/kg before boiling were found to contain < 0.02 mg
    I + II + III/kg after being boiled for 15 minutes. In the green parts
    (stems and leaves), the residues were reduced by boiling to between 3
    and 7% of the original content of 14-30 mg/kg; 0.4-3.4% of the
    original residue (I + II + III) was found in the water used for
    boiling (Bayer, 1975).

    Raw potatoes fortified with 14C-labelled ethiofencarb (1 mg/kg) were
    processed by pan frying, french frying and baking. Both pan and french
    frying processes reduced the residue (I + II + III) with an average
    loss of 52 and 58%, respectively. Leaching of the residue (2-20%) into
    the frying oils and volatilization were observed. The baking process
    showed a loss of about 2% of the 14C activity. Of the remaining
    activity, ethiofencarb accounted for 66%, ethiofencarb sulphoxide for
    14%, and ethiofencarb phenol for 20% (Chemagro Report, 1976d).

    METHODS OF RESIDUE ANALYSIS

    Residues of ethiofencarb can be determined by gas chromatography using
    a sulphur-specific flame photometric detector. The methods available
    for the analysis of plant samples# animal tissue samples and soil
    samples simultaneously determine metabolites with an intact carbamate
    structure, i.e. ethiofencarb sulphoxide and ethiofencarb sulphone.
    Oxidation with potassium permanganate converts ethiofencarb and
    ethiofencarb sulphoxide to the sulphone. For gas-chromatographic
    determination, the total carbamate residue is derivatized by reaction
    with bix-trimethylsilytrifluoroacetamide to the thermostable, volatile
    2-ethylsulfonylmethylphenyl trimethylsilyl ether.

    For the extraction step, acetone (Dräger, 1974) or methanol/water
    (Morris and Gronberg, 1976; Dorough, 1976a) were used for plant and
    soil samples. Soil samples can also be extracted with a mixture of
    acetonitrile and 0.1 × hydrochloric acid (Morris and Gronberg, 1977)
    or by reflux with a methanol/chloroform mixture (Morris, 1976a).
    Water-containing animal tissues and eggs are extracted with 
    acetonitrile; prior to extraction, fat is dissolved in hexane and
    acetone is added to milk to separate protein (Dorough, 1976b).
    Isolation of the residues from the extracts is achieved by shaking
    with chloroform, and separation of co-extractives is accomplished by
    precipitating with a solution of ammonium chloride/phosphoric acid.

    After oxidation of the residues with potassium permanganate to
    ethiofencarb sulphone, silylation is carried out in acetone or
    benzene.

    With some types of sample, further chromatographic clean-up steps are
    needed before silylation, in order to separate sulphur-containing
    plant co-extractives which interfere with the gas-chromatographic
    determination. With brassica extracts clean-up was by thinlayer
    chromatography and with hop extracts by column chromatography (Dräger,
    1974). In the analysis of animal tissues, eggs and milk, the residue
    was hydrolyzed to the corresponding phenol sulphone before silylation
    in order to increase reproducibility (Dorough, 1976b).

    For the gas-chromatographic determination, columns packed with 5%
    DC-200 on Gaschrom Q (Dräger, 1974) and with -3% OV-1 on Chromosorb W
    (Morris and Gronberg, 1977) have proved suitable. For a confirmatory
    procedure, a column packed with the polar phase Carbowax 20-M on
    Chromosorb W (Morris,1976b) was used. The lower limit of determination
    is generally 0.02-0.05 mg/kg for plant and soil samples. 0.01 mg/kg
    for fat, and 0.005 mg/kg for eggs and milk.

    The methods were shown to be specific in a study in which pesticides
    registered in the U.S.A. for use on potatoes, sorghum, animal tissues,
    milk and eggs were checked for possible interference: none of the 50
    chemicals tested interfered at their maximum registered level
    (Dorough, 1976c).

    NATIONAL TOLERANCES REPORTED TO THE MEETING

    The only tolerances reported to the Meeting were on fruit and
    vegetables in Switzerland, but pre-harvest intervals have been
    specified in several other countries as shown below (Table 11).

    APPRAISAL

    Ethiofencarb is a systemic insecticide used especially against sacking
    insects an vegetables, fruit, field crops and tobacco, It is effective
    against some organophosphorasresistant strains. It is formulated an
    granules and emulsifiable concentrates. The usual dose is 0.3-2 kg
    a.i./ha in spray, or approximately 0.1 g a.i. per linear metre as
    granules at sowing or planting. Ethiofencarb is used in various
    European countries, Chile and Israel.

    In plants and soil ethiofencarb (I) is oxidized to its sulphoxide (II)
    and sulphone (III) which are also hydrolysed. In plants and soil the
    main intact carbamates are II and III. Little or no ethiofencarb is
    usually detectable at harvest. In animals, the corresponding phenols
    and their conjugates are the main metabolites.


        TABLE 11. National tolerances and pre-harvest intervals reported to the Meeting.

                                                                                                         

    Country                  Crop                            Tolerances                  Pre-harvest
                                                             in mg/kg                    interval in
                                                                                         days
                                                                                                         

    Germany                  Beets, sugar beets                                          28
    (FRG)                    Head lettuce                                                4
                             Bush beans, pole beans,
                             broad beans                                                 7
                             Potatoes                                                    14

    Israel                   Peppers                                                     5
                             Potatoes                                                    4
                             Cauliflower, drumhead
                             cabbage                                                     7
                             Apples                                                      7

    Italy                    Vegetables                                                  7
                             Fruit crops                                                 14
                             Beets                                                       30

    Spain                    Fruit crops incl. citrus,
                             winter cereals, maize,
                             potatoes, beets, sugarcane,
                             cotton, oilseed crops                                       21

    Switzerland              Pome, stone and small
                             fruit                           0.2
                             Vegetables excl. spinach        1.0                         14

                             Fruit crops, peas for
                             harvesting dry (dried,
                             threshed)                                                   21
                             Sugar beet, field beans                                     42
                                                                                                         

    

    Half-lives of I + II + III in soil vary between 2 and 12 weeks in the
    field.

    On the basis of feeding a diet containing 50 ppm of I to cows, pigs
    and hens, it can be estimated that residues of I + II + III are
    unlikely to exceed 0.02 mg/kg in their meat or in eggs or milk.

    Boiling broad beans reduced carbamate residues of 0.13 mg/kg to below
    0.02 mg/kg. Cooking the green parts of beans reduced the residues to
    3-7% of the original content of I + II + III (14-30 mg/kg). 0.4-3.4%
    of these residues was found in the water used for boiling. Deep and
    shallow frying of potatoes fortified with 1 mg ethiofencarb/kg
    decreased the total carbamate residue by about 50%. Baking potatoes
    caused no loss of carbamate residues.

    Gas-chromatographic procedures for the determination of residues of I
    + II + III, suitable for regulatory purposes, in various crops, eggs,
    milk and soil have been elaborated.

    RECOMMENDATIONS

    The following temporary maximum residue limits are recommended. They
    refer to the am of ethiofencarb, its sulphoxide and its sulphone,
    expressed as ethiofencarb.

    Commodity                     Limit,    Pre-harvest interval (days)
                                  mg/kg     on which recommendations
                                            are based
                                                                      

    Cherries, lettuce             10        4-7
    Apples, pears, apricots                 4-7
    Artichokes, beans with pod,   4-7
    beet tops,
    sugar beet tops (leaves),               14
    brassicas peaches plums       5         4-7
    Currants (black, red),
    eggplants,                              4-7
    wheat straw                   2         14
    Cucumbers                     1         4
    Potatoes,                               14
    Radishes                      0.5       4
    Beans without pods
    soybeans without pod          0.2       4-7
    Fodder beets,
    sugar beets (roots)           0.1       14
    Raw grain
    (barley, oats, rye, wheat)    0.05      30
    Meat of cattle, pigs
    and poultry, eggs, milk       0.02*
                 

    * At or about the limit of determination

    FURTHER WORK OR INFORMATION

    REQUIRED (by July 1978)

    1. Submission of the results of the reproduction study now in
    progress.

    2. Further residue data from supervised trials on apricots,
    artichokes, various brassicas, cherries, cucumbers (including those
    grown under glass), eggplants, plums, radishes, soybeans.

    DESIRABLE

    1. Further residue data from supervised trials on other crops on which
    ethiofencarb is known to be used.

    REFERENCES

    Bayer, A.G. (1972/77) Ethiofencarb; Pflanzensohutzmittel-Rückstände,
    Dräger, Bayer-Leverkusen, unpublished.

    Bayer, A.G. (1974) Report RA 301; (unpublished).

    Bayer, A.G. (1975) Report RA 655; 20 Nov. 1975.

    Bothard, E. and Löser, E. (1976) HOX 1901 Chronic Toxicity Study on
    Rats. Nov. 30, Rep. No. 6493 from Bayer AG, Inst. f. Tox., unpublished
    report submitted by Bayer AG. Addendum., Histopathological Examination
    by J.P. Finn, Hazleton Laboratories, Inc.

    Chemagro Report (1975) 45 176; 12 Sept, 1975, R & D Dep. of Chemagro,
    Agricult. Div., Mobay Chemical Corp., Kansas City, No. 64 1209 USA.

    Chemagro Report (1976a) Chemagro Agricult. Div.; Groneton; Potatoes
    (Kats; Russet Burbank), Rep. No. 49 735/49 751; 17 Nov. 1976
    (unpublished).

    Chemagro Report (1976b) No. 51 062; 30 Dec. 1976 (unpublished).

    Chemagro Report (1976c) No. 49 896; 27 Dec. 1976.

    Chemagro Report (1976d) No. 46995; 11 Feb. 1976.

    Dorough H.W. (1976a) A Gas Chromatographic Method for the
    Determination of Croneton Residues in Various Animal Tissues, Crops,
    and Soil. CR 49 879, 1.12.1976.

    Dorough H.W. (1976b) A Gas Chromatographic Method for the
    Determination of Croneton Residues in Bovine Tissues and Milk and
    Poultry Tissues and Eggs. CR 49 880; 18.11.1976.

    Dorough H.W. (1976c) An Interference Study for the Residue Method for
    Croneton and Metabolites in Various Crops and Animal Tissuee, Milk and
    Eggs. CR 49 893, 17.12.1976.

    Dorough H.W. (1976d) Rate of Hydrolysis of CRONETON TM GRONETON
    Sulphoxide, and CRONSTON Sulphone in Aqueous Solutions. Chemagro
    Report No. 49 890 (1976).

    Dorough H.W. (1976e) Photodcoomposition of CRONETON TM on Various
    Substrates. Chemagro Report No. 49 891 (1976).

    Dorough H.W. (1976f) The Metabolism and Residue in Potatoes and
    Sorghum Treated Under Field Conditions Using CRONETON
    TM-ring-UL-14C. Chemagro Report No. 49 894 (1976).

    Dorough H.W. (1976g) The Metabolism of CRONETON TM in Plants.
    Chemagro Report No. 49 895 (1976).

    Dorough H.W. (1976h) Metabolism of CRONETON TM in a Lactating
    Holstein Cow and a Male Yorkshire Swine. Chemagro Report No. 49 897
    (unpublished).

    Dorough H.W. (1976i) The Metabolism of CRONETON TM Poultry. Chemagro
    Report No. 49 898 (unpublished).

    Dorough, H.W. (1976j) Correlation of Blood and Tissue Radiocarbon
    Levels Following a Single Oral Dose of CRONETON TM-ring-14C to Rats.
    Chemagro Report No. 49 887 (1976).

    Dräger, G. (1974) Method for gas-chromatographic determination of
    Croneton residues in plants and soil. Pflanzenschutz-Nachrichten Bayer
    91, 144-155 (1974).

    Dräger, G. (1976a) Study to investigate uptake and metabolism of
    Croneton in beans (Vioia faba) after application in granular form.
    Bayer AG, Pflanzensohutz-Anwendungstechnik, unpublished Report RA-79,
    January 19, 1976.

    Dräger, G. (1976b) Studying the Metabolism of Croneton in Water. Bayer
    AG Pflanzenschutz-Anwenclungstcohnik, unpublished Report RA-438v June
    9, 1976.

    Dräger, G. (1976c) Studies on the Metabolism of CRONETON in Potatoes
    and Soil and Identification of Bound Residues in the Potato Tuber.
    Bayer AG, Pflanzenschut Anwendungstechnik, unpublished Report RA-7989
    October 89 1976.

    Dräger, G. (1976d) Untersuchunger zum Versickerungsverhalten von
    CronetonR (Makro-Säulen-Versuch). Bayer AG,
    Pflanzenschutz-Anwenclungeteohnik, unpublished Report RA-961.

    Dräger, G. (1977a) Untersuchung des Metabolismus von Groneton in Boden
    und Wasser. Pflanzenschutz-Nachrichten Bayer 30, 18-27 (1977).

    Dräger, G. (1977b) Weiterer Abbau, von gealterten Croneton-Rückständen
    im Boden unter Laborbedingungen Bayer AG Pflanzenschutz-
    Anwendungsteohnik, unpublished report RA-133, February 16, 1977

    Dräger, G. (1977c) Versickerungsverhplten von gealterten
    Groneton-Rlickstgnden in Boden unter Laborbedingunger, Bayer AG,
    Pflanzenschutz-Anwendungsteohnik, unpublished Report RA-346.

    Gronberg, R.R., Dorough, H.W., (1976) Effect of Feeding CRONTEONTM
    to Poultry. Chemagro Report No. 49 899 (unpublished).

    Gronberg, R.R., Dorough, H.W., Hemken, R.W. (1976) Effect of Feeding
    CRONETONTM to Dairy Cattle. Chemagro Report No. 50 500 (1976)
    (unpublished).

    Hoffmann, K. and Weischer, C.H. (1976) 1901/Chronio Study on Dogs. May
    26, Rep. No. 6120 from Bayer AG, Inst. f. Tox., unpublished report
    submitted by Bayer AG.

    Homeyer, B. (1976) Croneton als wurzelaystemieches Aphizid.
    Ptlanzenschutz-Nachrichten Bayer 29 255-266 (1976).

    Hurst, H., Dorough, H.W. (1976) The Metabolism of CRONETON TM-
    N-methyl-14C in Rats-A Progress Report. Chemagro Report No. 49 886
    (1976).

    Kimmerle, G. (1972b) HOX 1901/Acute Toxicity Studies. July 10, Rep.
    No. 3557 from Bayer AG, Inst. f. Tox., unpublished report submitted by
    Bayer AG.

    Kimmerle, G. (1972c) HOX 1901/Acute orale Toxizität an männlichen
    Kaninchen. Nov. 13, report from from Bayer AG, Inst. f. Tox.,
    unpublished report submitted by Bayer AG.

    Kimmerle, G. (1972d) Antidotal Effect of Atropine. July 10, report
    from Bayer AG, Inst. f. Tox., unpublished report submitted by Bayer
    AG.

    Kimmerle, G. (1972e) HOX 1901/Subacute Toxicity Studies. July 10, Rep.
    No. 3558 from Bayer AG, Inst. f. Tox., unpublished report submitted by
    Bayer AG.

    Kimmerle, G. and Eben, A. (1974) HOX 1901/Effect of Acute and Subacute
    Oral Administration and Subacute Inhalation on Plasma, Erythrocyte and
    Brain Acetylcholinesterase Activity in Rats and Dogs. Aug. 8, Rep. No.
    4843 from Bayer AG, Inst. f. Tox.p unpublished report submitted by
    Bayer AG.

    Klimmer, O.R. (1973) Study Report / Bayer HOX 1901/Subchronic
    Toxicological Studies on Rats. Febr. 27, Rep. No. R 739 from
    Pharmakologisches Instit der Rhein. Friedr.-Wilh.-Univ., Bonn,
    unpublished report submitted by Bayer, AG.

    Kurtz, S.K., Gronberg, R.R. (1976) The Stability of CRONETON TM in
    Aqueous Systems. Chemagro Report No. 50 798 (1976).

    Lamb, D.W., Roncy, D.J. (1976) Accumulation and Persistence of
    Residues in Channel Catfish Exposed to CRONETON-14C. Chemagro Report
    No. 49 128 (unpublished).

    Lamb, D.W. and Matzkanin, G.S. (1977a) The Acute Oral Toxicity of
    CRONETON Sulphoxide. Febr. 18, Rep. No. 51 716 from Mobay Chem. Corp.,
    unpublished report submitted by Bayer AG.

    Lambt D.W. and Matzkanin, G.S. (1977b) The Acute Oral Toxicity of
    CRONETON Sulphone. Febr. 21, Rep. No. 51 717 from Mobay Chem. Corp.,
    unpublished report submitted by Bayer AG.

    Lamb, D.W. and Matzkanin, G.S. (1977c) The Acute Oral Toxicity of
    CRONETON Phenol. Febr. 17, Rep. 51 719 from Mobay Chem. Corp.,
    unpublished report submitted by Bayer AG.

    Lamb, D.W. and Matzkaning G.S. (1977d) The Acute Oral Toxicity of
    CRONETON Phenol Sulphoxide. Febr. 17, Rep. No. 51 718 from Mobay Chem.
    Corp., unpublished report submitted by Bayer AG.

    Lamb, D.W. and Matzkanin, C.S. (1977e) The Acute Oral Toxicity of
    CRONETON Phenol Sulphone. Febr. 17, Rep. No. 57 715 from Mobay Chem.
    Corp., unpublished report submitted by Bayer AG.

    Lamb, D.W. and Matzkanin, C.S. (1977f) The Acute Oral Toxicity of
    CRONETON (Formerly BAY HOX 1901) Metabolite N-Methyl (Hydroxy). April
    26, Rep. No. 52 878 from Mobay Chem. Corp., unpublished report
    submitted by Bayer AG.

    Lamb, D.W. and Matzkanin, C.S. (1977g) Acute Oral Toxicity of CRONETON
    (Formerly BAY HOX 1901) Metabolite N-Methyl (Hydroyy) Sulphoxide.
    April 29, Rep. No. 52 879 from Mobay Chem. Corp., unpublished report
    submitted by Bayer AG.

    Lamb, D.W. and Matzkanin, C.S. (1977h) The Acute Oral Toxicity of
    CRONETON Metabolite N-Methyl (Hydroxy) Sulphone. April 29, Rep. No. 52
    880 from Mobay Chem. Corp., unpublished report submitted by Bayer AG.

    Machemer, L. (1973a) HOX 1901/Dominant Lethal Test on the Male Mouse
    to Test for Mutagenic Effect. Dec. 14, Rep. No. 4339 from Bayer AG,
    Inst. f. Tox., unpublished report submitted by Bayer AG.

    Machemer, L. (1973b) HOX 1901/Studies for Embryotoxic and Teratogenic
    Effects on Rats Following Oral Administration. July 25, Rep. No. 4174
    from Bayer AG, Inst. f. Tox., unpublished report submitted by Bayer
    AG.

    Machemer, L. (1975) HOX 1901/Studies of Embryotoxic and Teratogenic
    Effect on Rabbits Following Oral Administration. July 24, Rep. No.
    5545 from Bayer AG, Inst. f. Tox., unpublished report submitted by
    Bayer AG.

    Marshall, T., Dorough, H.W. (1976) Fate of Water Soluble CRONETON TM
    Plant Metabolites in Rats (Progress Report). Chemagro Report No. 49
    892 (1976).

    Marshall, T.C., Dorough, H.W. (1977) Bioavailability in Rate of Bound
    and Conjugated Plant Carbamate Insecticide Residues. Chemagro Report
    No. 52 737 (1977).

    Morris, R.A. (1976a) Determination of Baygon, Baytex, Bolster,
    Croneton, Dasanit, Di-Syston, Dylox, Guthion, Hinosan, Mesurol, 
    Meyasystox-R, Monitor, Morestan, Nemacur, Systox Residues in Soil. CR
    49 675, 15.9.1976.

    Morris, R.A. (1976b) A Confirmatory Procedure for the Analytical
    Residue Method for Croneton in Potatoes, Plant Forage and Cereal
    Grains. CR 51 0639 30.12.1976.

    Morris, R.A. Gronberg, R.R. (1976) A Gas Chromatographic Method for
    the Determination of Residues of Croneton (Bay BOX 1901) and
    Metabolites in Potatoes, Plant Forage, and Cereal Grains. CR 49 666#
    23.8.1976.

    Morris R.A., Gronberg, R.R. (1977) A Gas Chromatographic Procedure for
    the Determination of Croneton (Bay HOX 1901) in Soil. CR 49 6659
    10.2.1977.

    Mürmann, P. (1973) HOX 1901/Subohronic Toxicity Study on Dogs. June
    28, Rep. No. 4143 from Bayer AG, Inst. f. Tox., (unpublished).

    Nitokuno Inst., (1975a) Report No. 3599 unpublished.

    Nitokuno Inst., (1975b) Reports No. 335 and 336, unpublished.

    Nitokuno Inst., (1975/76a) Reports No. 333, 334 and 390, unpublished.

    Nitokuno Inst., (1975/76b) Reports No. 360-362 and 395-396,
    unpublished.

    Nitokuno Inst., (1976a) Report No. 379, unpublished.

    Nitokuno Inst. (1976b) Reports No. 391-1949 unpublished.

    Nitokuno Inst. (1976c) Reports No. 397-4009 unpublished.

    Nitokuno Inst. (1976d) NIHON TOKUSHU NOYAKU SEIZO K.K. Residual
    Analysis Results of HOX 1901 (ethiofencarb) in Upland Soil. Report No.
    1042 (RA), January, 28, 1976.

    Nye, D.E., Hurst, H.E., Dorough, H.W. (1976) Fate of Croneton
    (2-Ethylthiomethylphenyl N-Methyl-carbamate) in Rats. J. Agric. Food
    Chem. 24, 371-377.

    Rieck, C.E. (1976a) Leaching characteristics of CRONETON TM in
    various soils. Chemagro Report No. 50 783.

    Rieck, C.E. (1976b) Leaching characteristics of CRONETON TM on aged
    soil. Chemagro Report No. 51 028.

    Thorton, J.S., Hurley, J.B. and Obrist, J.J. (1976) Soil thin-layer
    mobility of twenty four pesticides chemicals. Chernagro Report No. 51
    016.

    Thyssen, J. and Kimmerle G. (1975) Präparat 6757/Untersuchungen zur
    Anwendungstoxikologie. Nov. 27, Rep. No. 5751 from Bayer AG, Inst. f.
    Tox., unpublished report submitted by Bayer AG.

    Thyseen, J. (1975a) HOX 1901/Neurotoxicity Studies on Hens. Nov. 18,
    Rep. No. 5735 from Bayer AG, Inst. f. Tox., unpublished report
    submitted by Bayer AG. Appendix: ROX 1901 Neurotoxicity Studies on
    Hens/Histopathological Finding by Prof. Dr. U. Mohr, Med. Hoohsohule
    Hannover.

    Thyssen, J. (1975b) Studies to Investigate Acute Oral Toxicity of HOX
    1901 when Administered Simultaneously with Malathion or EPN, Nov. 18,
    Rep. No. 5732 from Bayer AG, Inst. f. Tox., unpublished report
    submitted by Bayer AG.

    Thyssen, J. (1976) HOX 1901-Metaboliten. Sept. 1, report from Bayer
    AG, Inst. f. Tox., unpublished report submitted by Bayer AG.
    





    See Also:
       Toxicological Abbreviations
       Ethiofencarb (ICSC)
       Ethiofencarb (Pesticide residues in food: 1978 evaluations)
       Ethiofencarb (Pesticide residues in food: 1980 evaluations)
       Ethiofencarb (Pesticide residues in food: 1981 evaluations)
       Ethiofencarb (Pesticide residues in food: 1982 evaluations)
       Ethiofencarb (Pesticide residues in food: 1983 evaluations)