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    ETHION                           JMPR 1972

    Explanation

    Ethion was evaluated by the Joint Meeting in 1968 (FAO/WHO, 1969), and
    residues in meat (FAO/WHO, 1970) and tea (FAO/WHO, 1971) were
    re-evaluated by subsequent meetings. Since the previous evaluation
    additional information has become available on toxicology of this
    compound, and new experimental work on residues in food has been
    reported.

    EVALUATION FOR ACCEPTABLE DAILY INTAKE

    BIOCHEMICAL ASPECTS

    Absorption, distribution and excretion

    When 14C-methylene labelled ethion was administered orally to rats,
    88% of the 14C was excreted in the urine in four days; the remainder
    was found in the faeces and in respiratory CO2 to the extent of 3.7
    and 3.4%, respectively. No metabolite identification was attempted in
    this experiment, and 78% of the dose was excreted in the urine within
    the first 24 hours (Brandav et al., 1971).

    Effect on enzymes of the oxygen analogues of ethion

    The in vitro inhibitory effects of the oxygen analogues of ethion
    that might possibly occur in foods have been measured in human plasma
    and erythrocyte cholinesterase. The I50 values showed that both
    ethion monooxon and ethion dioxon were more active than ethion, with
    the dioxon being the most active, as shown in Table 1 (Greco et al.,
    1970).

    TABLE 1

    Anticholinesterase activity of ethion and its oxygen analogues

    Compound                 Plasma I50 (M)         RBC I50 (M)

    Ethion                   6.95 × 10-8            3.29 × 10-6

    Ethion monooxon          1.15 × 10-9            6.1  × 10-8

    Ethion dioxon            5.76 × 10-10           3.0  × 10-9

    TOXICOLOGICAL STUDIES

    Special studies on mutagenicity

    A dominant lethal test was carried out in albino mice. Groups of 12
    male mice were each treated with a single intraperitoneal injection of
    50 and 100 mg/kg. A third group of 12 male mice were each injected
    with 300 mg/kg of ethyl methanesulfonate to act as positive control.
    The males were mated with untreated females on a weekly schedule for
    six consecutive weeks. The mutation rates for the ethion treated
    animals did not differ from the controls. The mutation rates with
    positive control animals were significantly increased. Measurements
    were made for implantations, resorptions and number of embryos. In
    addition, ethion did not reduce the ability of males to mate
    successfully (Arnold et al., 1972).

    Special studies on neurotoxicity

    No demyelination was noted in six adult hens treated orally with acute
    median lethal dose (4 290 mg/kg) of ethion technical. The dose level
    was at the LD50. TOCP administered at 500 mg/kg was used as a
    positive control. Measurements included histopathological examination
    of the brain, spinal cord and sciatic nerve (Fletcher et al., 1972).

    Special studies on teratogenicity

    One group of 18 female rats was dosed with ethion at 1.5 mg/kg/day,
    and a second group of 16 female rats received 3.0 mg/kg/day on days 6
    to 15 of gestation. Measurements were made for maternal body-weight,
    maternal mortality, implantation sites, resorption sites, viable
    foetuses, foetal external abnormalities, foetal skeletal development
    and foetal internal development. No teratogenic effects were noted in
    the offspring of these female rats (Haley et al., 1972).

    Acute toxicity

    LD50 of ethion in female rats was found to be 24.4 mg/kg (Kretchmar
    et al., 1971).

    The acute oral LD50 of the oxygen analogues were measured in albino
    rats and found to be 35.1 mg/kg for the monooxon and 12.8 mg/kg for
    the dioxon (Mastri et al., 1970).

    Long-term studies

    Rat

    Four groups, each containing 50 male and 50 female rats, were fed
    ethion at dietary levels of 0, 2, 6 and 20 ppm for two years. Slight
    depression of RBC, plasma and brain cholinesterase activities were
    noted in female rats fed 20 ppm throughout the investigation. Male
    rats fed 20 ppm and all rats fed 2 and 6 ppm exhibited no significant
    inhibition of cholinesterase activity during the study. Results
    obtained during the investigation disclosed no changes which could be
    attributed to the ingestion of ethion in body-weight gains, food
    consumption, blood chemistry, urine analyses, organ weights and ratios
    and gross and microscopic pathologic studies. Erythrocyte and plasma
    cholinesterase activities were determined at ´, 1, 1´, 2, 3, 6, 12, 18
    and 24 months and brain cholinesterase activity after 1, 2, 3 and 24
    months of feeding (Smith et al., 1972).

    Dog

    Four groups of 4 male and 4 female dogs, were fed ethion at dietary
    levels of 0, 2, 6 and 20 ppm for two years. Animals fed 6 and 20 ppm
    displayed depression of plasma cholinesterase activity, which was
    noted through the first 26 weeks of test in the animals receiving 6
    ppm and for the entire 104 weeks in the animals receiving 20 ppm. No
    significant depression was noted in RBC or brain cholinesterase
    activity at the 6 and 20 ppm levels. Animals fed 2 ppm displayed no
    significant depression of plasma, RBC or brain cholinesterase activity
    at any time. Body-weights, food consumption, behavioural reactions,
    mortality, haematologic studies, blood chemistry studies and
    histopathologic studies all gave normal results. Plasma and RBC
    cholinesterase determinations were made on all animals at 0, 2, 4, 6,
    9, 13, 26, 78 and 104 weeks of testing. Brain cholinesterase
    determinations were made on each animal immediately after sacrifice at
    the end of the study (Hartke et al., 1972).

    OBSERVATIONS IN MAN

    Ethion was administered to a group of six male volunteers at levels of
    0, 0.05, 0.075, 0.1 and 0.15 mg/kg/day for a period of three weeks at
    each dose level, with the exception of the highest one which was given
    for three days only. The control group consisted of four individuals.
    The material was administered in divided doses in gelatin capsules as
    solution in corn oil three times a day. Plasma and RBC cholinesterase
    activities were determined five times during two weeks of the pretest
    period and three weeks of the test period. No statistically
    significant depression in RBC cholinesterase was noted. A
    statistically significant depression in plasma cholinesterase of 21%
    and 29% was noted at dose level of 0.1 and 0.15 mg/kg/day,
    respectively. Plasma cholinesterase activity at the highest dose level
    returned to pretest values in seven days. The 0.075 mg/kg/day level
    was considered borderline, with the mean inhibition being about 15%.

    The 0.05 mg/kg/day dose was a definite no-effect level. No adverse
    effects were noted in any of the other parameters studied, which
    included haemoglobin concentration, haematocrit, RBC count, total
    differential leukocyte counts, blood pressure, pulse rate, pupil size,
    light reflex, eye accommodation, chest sound, muscle tone, knee jerk
    and tongue and finger tremor (Palazzolo et al., 1970; 1971).

    COMMENT

    The toxicological data available at the 1968 Meeting were supplemented
    by new information on ethion excretion, acute short and long-term
    toxicity, neurotoxicity, mutagenicity, teratogenicity and
    cholinesterase inhibition. Information was provided on the effects on
    human volunteers.

    Following oral administration of 14C-ethion-methylene to rats, most
    of the radioactivity was found in the urine. Results of a dominant
    lethal test in mice, a teratogenicity test in rats and a neurotoxicity
    test in hens were negative.

    Two-year feeding studies in rats and dogs indicated plasma, RBC and
    brain cholinesterase inhibition at 20 ppm in rats and plasma
    cholinesterase inhibition at 6 ppm and above in dogs. Exposure of
    humans for three weeks indicated a no-effect level on plasma
    cholinesterase at 0.05 mg/kg/day.

    TOXICOLOGICAL EVALUATION

    Level causing no toxicological effect

         Rat:      6 ppm in the diet, equivalent to 0.3 mg/kg
                   body-weight/day.

         Dog:      2 ppm in the diet, equivalent to 0.05 mg/kg
                   body-weight/day.

         Man:      0.05 mg/kg/day.

    ESTIMATE OF ACCEPTABLE DAILY INTAKE FOR MAN

         0 - 0.005 mg/kg body-weight

    RESIDUES IN FOOD AND THEIR EVALUATION

    USE PATTERN

    Ethion preparations have been registered for use in cattle dips and
    sprays in the following countries: Australia, Argentina, Brail,
    Colombia, Costa Rica, Cuba, Mexico, Paraguay, Rhodesia, South Africa
    Uruguay and Venezuela.

    Ethion is approved for application to apples, pears and citrus (often
    to other crops as well) at a maximum rate of 2.5 kg/ha in the
    following countries: Australia, Argentina, Colombia, Iran, Israel,
    Italy, Japan, Mexico, New Zealand, Peru, Spain, Uruguay, U.S.A.,
    Venezuela.

    Additionally, ethion is used extensively on cotton in U.S.A., Pakistan
    and probably in several other countries. An important field of use
    occurs in Ceylon, India and Indonesia where tea is treated at the rate
    of 600 g/ha three times per year. It is not practicable to specify an
    interval between application and harvest, but normally two weeks would
    elapse.

    In Australia, in addition to use on cattle for the control of cattle
    ticks, ethion is registered for the control of specific pests of
    apples, peaches, nectarines, peers, plums, prunes, cherries, almonds
    and quinces where a dormant spray in oil emulsion is applied, and
    passionfruit, grapes, citrus, figs, avocados and onions, where a
    foliage spray in oil emulsion is used.

    In U.S.A. ethion is registered for the uses shown in Table 2, at the
    rates and with the withholding periods indicated.


    TABLE 2  Use of ethion in the United States

                                                                            

    Use                 Rate          Applications     Withholding
                        (kg/ha)       (no.)            period (days)
                                                                            

    Almonds             2.5           -                30

    Apples              5.0           4                60
                                      2                40
                        2.5           4                40
                                      2                20

    Apricots            3.0           1                dormant

    Beans               0.5           -                2
                        1.5           1                10

    Cherries            3.0           1                dormant

    Chestnuts           2.5           2                before husks split

    Corn                1.0           1                50

    Cotton              1.6                            not after bolls open

    TABLE 2  (Cont'd.)

                                                                            

    Use                 Rate          Applications     Withholding
                        (kg/ha)       (no.)            period (days)
                                                                            

    Cucumbers           0.5           -                no time limitation

    Eggplant            0.5           -                no time limitation

    Filberts            2.5           2                before nuts visible

    Garlic              2.0           1                at planting

    Grapes              1.25          -                60
                                      2                30
                        2.2           1                30
                        1.2 (dust)    2                15

    Grapefruit          7.5           -                no time limitation
                        10.0          -                30

    Lemons              7.5           1                21

    Limes               7.5           1                21

    Melons              1.6           -                no time limitation

    Nectarines          1.5           -                dormant

    Onions              2.0           1                at planting

    Oranges             7.5           -                no time limitation
                        10.0          -                30

    Peaches             1.75          2                30
                        5.0           3                60

    Pears               2.7           2                35

    Pecans              2.5           2                not after husks split
                        1.0           3                21

    Pimentos            0.5           -                no time limitation

    Plums and           2.5           2                45
    prunes              1.75          3                21

    TABLE 2  (Cont'd.)

                                                                            

    Use                 Rate          Applications     Withholding
                        (kg/ha)       (no.)            period (days)
                                                                            

    Sorghum             0.5           3                30

    Strawberries        1.0           -                2

    Squash              0.5           -                no time limitation

    Tangelos and        7.5           -                no time limitation
    tangerines

    Tomatoes            0.5(spray     -                2
                        0.8(dust)     -                2

    Walnuts             2.0           -                dormant
                        2.5           2                before husks split
                                                                            


    RESIDUES RESULTING FROM SUPERVISED TRIALS

    In citrus fruit

    Oranges from Florida receiving three foliar sprays of ethion
    emulsifiable concentrate were analysed to determine if ethion residues
    would conform to the 1 ppm tolerance proposed by the Joint Meeting
    when treated according to standard practice for Florida (Niagara,
    1971b).

    Hamlin oranges sampled on the same day after a 1 kg/ha treatment
    yielded maximum ethion and ethion monooxon residues of 0.34 ppm and
    0.015 ppm, respectively. Valencia oranges sampled on the same day
    after a 2.4 lb a.i./acre treatment yielded maximum ethion and ethion
    monooxon residues of 0.60 ppm and 0.060 ppm respectively. No ethion
    dioxon residues were found in either study by a method capable of
    determining 0.025 ppm of dioxon.

    The data indicate that ethion residues would be less than the proposed
    1 ppm tolerance when the emulsifiable formulation is used.

    The orange trees had been treated in summer, autumn and spring at
    intervals of 3 - 6 months.

    Residue studies involving two formulations of ethion were conducted on
    Valencia oranges grown in California (Niagara, 1972a). Application
    rates conformed to registered use patterns in U.S.A. The object of
    these experiments was to determine whether it was possible to comply
    with the tolerance of 1 ppm recommended in 1968 within the time
    interval which would be practicable under normal conditions of
    agriculture.

    Single applications of ethion wettable powder and ethion emulsifiable
    concentrate, each at the rate of 5.0 and 7.5 kg/ha, were made to
    mature Valencia oranges.

    Samples were collected from the wettable powder treated plots at
    intervals of 0, 7 and 14 days after treatment. Average zero day
    residues of 0.75 ppm were found in the 5 kg/ha plot, these residues
    diminished to 0.26 ppm on day 14. In the case of the 7.5 kg/ha
    treatment, initial average residues of 1.50 ppm diminished to 0.63 in
    the same period. Ethion monooxon was found only in the 7- and 14-day
    samples and comprised 16%-17% of the total residue. Ethion dioxon was
    not detected.

    Sampling of the plots treated with emulsifiable concentrate was
    conducted over a 21 day period. Average initial residues of 1.38 ppm
    diminished to 0.63 ppm in the case of the 5 kg/ha treatment. Samples
    from the 7.5 kg/ha application rate showed residues of 1.49 ppm and
    0.65 ppm at day 0 and 21, respectively. Ethion dioxon and ethion
    monooxon were not detected on these samples.

    The time required to bring about a 50% reduction in the residue levels
    varied from 14 to 21 days, but it appeared that, having reached a
    level of 0.5 ppm, the rate of dissipation decreased sharply. In view
    of the fact that some citrus varieties, including Valencias, must be
    sprayed when both mature and immature fruit are on the trees, residues
    above 1.0 ppm may sometimes occur.

    In pome fruit

    Harvest samples of ethion treated apples and pears were analysed for
    the presence of ethion dioxon, ethion monooxon and ethion residues
    (Niagara, 1972b). In all cases, the chemical was applied as the 25%
    wettable powder in accordance with registered use patterns.

    The two apple studies (in California and Washington) showed combined
    oxygen analogue residues which comprised 10-20% of the total residue.
    However, the total residue did not exceed 1 ppm on any of the samples.

    The pear study conducted in Washington showed a maximum residue of
    2.76 ppm, 20% of which was combined dioxon and monooxon. In contrast,
    the California pear study (which involved only one application)
    yielded a maximum residue of 1.21 ppm; of this total, 10% was present
    as the combined oxons.

    In a submission to the U.S. Food and Drug Administration, Niagara
    (1962) showed that the application of ethion wettable powder to pears
    at the rate of 5 kg/ha and 8 kg/ha seven days before harvest gave rise
    to residues of 1.6 ppm (1.08 - 2.2) and 2.5 ppm (2.2 - 2.8) ethion on
    the fresh fruit. When this fruit was dried experimentally, the dried
    fruit contained from 1.12 to 4.8 ppm ethion, but it was shown that
    normal commercial drying would have a more pronounced effect on
    concentrating the residues.

    In stone fruit

    Harvest samples of plum and prune from a maximum ethion treatment
    programme were analysed for the presence of ethion dioxon, ethion
    monooxon and ethion residues (Niagara, 1972c). Both crops had received
    three applications at the registered rate of 1.75 kg/ha as the
    wettable powder and were sampled at an interval of 21 days after the
    final treatment. Total residues did not exceed 0.5 ppm on either fruit
    at this interval. However, the combined oxygen analogues contributed
    approximately 25% of the total residue. Apricots and cherries analysed
    at harvest following previous winter and spring treatment with 0.025%
    and 0.05% solutions in petroleum oil showed no detectable residues by
    a method capable of determining 0.05 ppm (Niagara, 1972d).

    Results of trials carried out by Niagara (1962) and submitted to the
    U.S. Food and Drug Administration show that there is relatively little
    loss of ethion residues in nine days elapsing between application to
    mature fruit, and harvesting of ripe fruit. Following application of
    two sprays three weeks apart (as is typical for the control of
    oriental fruit moth, the total being 4 kg ethion/ha) peaches were
    picked immediately after the second spray and again nine days later.
    The fruit collected immediately after spraying were found to have a
    mean residue of 2.6 ppm (2.4 - 2.8) while those which had remained on
    the trees for nine days still had 1.3 ppm (1.27 - 1.34).

    Peaches from the above trial were subjected to a simulation of the
    normal drying process involving exposure to sulphur dioxide and then
    sun drying for 13 days. The first pickings after drying contained 8.8
    ppm (8.6 - 9.0) while the second still had 4.2 ppm (3.2 - 5.1) after
    drying. This represents a loss of only 15 - 37% of the theoretical
    residue when allowance is made for the loss of moisture. It was
    considered that under drying conditions more in keeping with normal
    practice the loss would have been considerably less.

    In the same submission results are given of trials on fresh and dried
    apricots. Immediately following application of 1.3 kg ethion/ha,
    apricots were found to have 2.8 ppm ethion (2.5 - 3.1). In other
    trials nearby, fruit picked 12 and 14 days after the application of
    the same rate of the same formulation contained 0.65 (0.58 - 0.72) ppm
    and 1.42 (1.16 - 1.77) ppm ethion. Fruit from each of these trials was
    subjected to a normal treatment with SO2 and then sun dried for 14
    days. The residues ranged from 1.2 to 4.7 (average 3.0) ppm ethion.
    The loss of ethion on drying ranged from 31 to 80%.

    In grapes, raisins and grape by-products

    In order to determine the level of residues in grapes following normal
    treatment, the loss between application and harvest and the subsequent
    loss in drying grapes (for raisins and muscats) Niagara (1972e) found
    that though there was a loss of more than 50% in the seven days
    following application the rate of loss thereafter declined, as is
    shown in Table 3.

    Grapes from experiments 4 - 7 were dried in the sun for 35 days and
    the dried muscatels were again analysed. The residue levels in the
    dried fruit ranged from 1.25 - 10.4 ppm. Allowing for the loss of
    water from the fruit, this represented a loss of from 70 - 91% of the
    amount of ethion originally present.

    Samples of ethion treated grapes, raisins, raisin stems and grape
    pomace were analysed for the presence of ethion dioxon, ethion
    monooxon and ethion residues (Niagara 1972e).

    In one location, ethion wettable powder and ethion emulsifiable
    concentrate were applied to separate lots at the maximum registered
    rate and frequency, i.e., 1.25 kg/ha; two applications, the last 32
    days before harvest. Total residues averaged 1.3 ppm on harvest
    samples of the grapes treated with wettable powder, and 0.4 ppm on the
    samples treated with emulsifiable concentrate. When the grapes were
    field dried to raisins, total residues averaged 0.47 ppm with no
    significant difference between the two formulations. Residues on the
    raisin stems were in the range of 0.8 - 0.9 ppm with the combined
    oxygen analogues contributing 45 - 50% of the total residue.

    A similar schedule was used at a second location, but in this case
    only the emulsifiable concentrate was applied. Total residues on the
    fresh grapes at harvest (32 days after the final treatment) averaged
    0.95 ppm (range 0.93 - 0.95). Dry pomace prepared from this fruit in
    the laboratory showed an average total residue of 6.2 ppm with only 2
    ppm present as the oxygen analogue. Raisins obtained from this study
    contained an average total residue of 1.1 ppm (range 1.07 - 1.16).
    Residues on the corresponding stem samples averaged 2.9 ppm of which
    30 - 35% was present as the combined oxygen analogues.

    During the experiment, samples of the wet pomace were fortified with
    ethion, ethion dioxon and ethion monooxon. Subsequent analysis of the
    dried samples showed the following losses had occurred: dioxon 92%,
    monooxon 75% and ethion 67%. These results show the more rapid
    degradation of the dioxon.

    Cucumbers and squash

    In order to demonstrate the level of residues in cucumbers and squash
    following approved use of ethion sprays, Niagara (1962) treated
    cucumbers from two to seven times with from 1.0 to 3.5 kg/ha of ethion
    as wettable powder and as emulsion. The results are summarized in
    Table 4.


    
    TABLE 3  Ethion residues on grape

                                                                                                             

                                 Rate       Residue when sampled x days after application (ppm)
    Location         Variety     ethion
                                 (kg/ha)    0         7           14         21         28         35
                                                                                                             

    Fredonia, N.Y.               2.25       4.8-5.8   2.1-3.0     1.1-1.7    0.9-1.2    0.7-0.9    0.6-1.0

    Fredonia, N.Y.               0.75       10.1      3.4         2.4        2.2        1.9

    Modesto, Cal.    Seedless    1.4        0.65      0.63        0.33       0.12

    Clovis, Cal.     Muscat      5.4                  3.3-4.0

    Biola, Cal.      Muscat      5.4                  4.9-5.8

    Clovis, Cal.     Muscat      5.4                  2.5-3.8

    Biola, Cal.      Muscat      5.4                  6.3-6.7
                                                                                                             

    

    
    TABLE 4  Ethion residues on cucumbers and squash

                                                                                       

    Total ethion     Application       Residues found x days after application (ppm)
    applied          (no.)
    (kg/ha)                            0           5           8           11
                                                                                       

    3.0              6                 0.12        0.09        0.01        0.04

    3.5              7                 0.12        0.09        0.01        0.0

    1.0              2                 -           -           -           0.0

    1.5              3                 0.05        0.02        0.02        0.04
                                                                                       
    

    Cottonseed

    In support of a petition to the U.S. Environmental Protection Agency,
    Niagara (1971a) showed from several trials that the application of
    ethion (several formulations) at the approved rate (1.6 kg/ha), and at
    double rate prior to the opening of bolls, produced residues in the
    ginned seed ranging from non-detectable to 0.25 ppm. The residues
    found were thought to be the maximum likely to occur, to be present on
    the lint only and probably to be due to contamination and/or
    inefficient ginning. The location of the residues in lint was
    confirmed, and it was shown that the acid delinting process removed
    all detectable residues from the cottonseed. Further studies showed
    that any ethion residues present on the seed were mainly in the lint,
    less in hulls and only 4% in the crude cottonseed oil. The maximum
    level of ethion found in crude cottonseed oil was 0.33 ppm.

    Maize (grain, forage and fodder)

    Niagara (1971d) carried out trials in three different regions of
    U.S.A. following the application of ethion emulsifiable concentrate at
    the rate of 1 kg/ha to maize. Samples of forage collected 0, 7, 14 and
    21 days after application contained 20.2 ppm, 5.7 ppm, 3.2 ppm and 1.9
    ppm ethion (total ethion and oxons), respectively. Ethion comprised
    95% of the residues at day 0 and 70 - 80% at day 21. Maximum ethion
    monooxon residues of 0.71 ppm were detected at day 0, and these
    declined to 0.27 ppm at day 21. Maximum ethion dioxon residues of 0.30
    ppm were detected at day 7 and 14, after application. There were wide
    variations in the residue levels between different samples from
    different sites. The maximum level of ethion likely to be found in
    maize forage following approved use would be 15 ppm.

    In separate studies for the same petition Niagara (1971d) showed that
    the application of 1 kg ethion/ha to maize 50 days before harvest
    produced minimum residues in the maize grain. No residues exceeding
    the limit of determination were found.

    In nuts

    Chestnuts, filberts, pecans and walnuts were treated with 0.05% ethion
    in petroleum oil emulsions during the dormant season and again twice
    with ethion wettable powder at the rate of 1.5 - 2.5 kg/ha during the
    growing period, but before the husk split. Analysis of the kernels of
    nuts from six trials showed no detectable residues by a method capable
    of determining 0.05 ppm ethion or metabolites (Niagara, 1972d).

    In dairy cattle

    An indication of the levels of ethion residue found in milk from
    individual cows or an individual herd is shown by a trial conducted by
    the New South Wales Department of Agriculture (Watts, 1969). Four
    dairy cows were dipped once in 0.068% ethion emulsion (slightly less
    than the recommended 0.075% dip). Milk samples were collected,
    pre-dipping and over a period of 12 days post dipping, with the
    results shown in Table 5.

    TABLE 5  Ethion residues in milk after dipping of dairy cattle1
                                                                      

    Samples collected        Mean ethion level        Range ethion
                             (ppm)                    (ppm)
                                                                      

    Pre-dip                  nil                      nil

    5 h post-dip             3.36                     2.66 - 4.10

    1 d post-dip             1.95                     1.70 - 2.14

    2 d post-dip             1.37                     1.14 - 1.58

    3 d post-dip             0.77                     0.56 - 0.84

    4 d post-dip             0.66                     0.50 - 0.81

    5 d post-dip             0.52                     0.49 - 0.56

    6 d post-dip             0.44                     0.39 - 0.58

    10 d post-dip            0.06                     0 - 0.25

    12 d post-dip            0.02                     0 - 0.06
                                                                      

    1  Expressed as ppm in butterfat
    FATE OF RESIDUES

    In animals

    Studies were conducted to determine the effect and fate of ethion in
    the ration of cows in order to gauge whether animals grazing treated
    orchards or fed pomace from treated citrus, grapes or apples or
    cottonseed meal would excrete residues in milk or retain residues in
    meat, fat or meat by-products (Niagara, 1971c).

    Groups of four mature Holstein cows were fed ethion at 5, 10 and 20
    ppm in their daily feed ration for 30 consecutive days. Milk samples
    were collected periodically during the feeding period. At the end of
    the 30-day test feeding period, three cows from each group were
    sacrificed and tissue samples taken.

    A 30-day recovery period followed during which the remaining cows were
    not fed ethion in their daily feed ration. Milk samples were collected
    at weekly intervals. At the end of the recovery period, the cows were
    sacrificed and tissue samples taken.

    Milk samples from the 5 and 20 ppm ethion feeding levels and tissue
    samples (muscle, kidney, liver and fat) from all three feeding levels
    were analysed. Ethion was the only residue detected in any of the milk
    or tissue samples.

    Analysis of milk from the 5 ppm ethion feeding level yielded maximum
    ethion residues of 0.009 ppm at day 8. Milk from the 20 ppm ethion
    feeding level yielded maximum ethion residues of 0.034 ppm at day 4.
    No ethion residues were detected in any of the recovery period milk
    samples.

    It is notable that no oxygen analogues of ethion occurred in any of
    the milk, meat or fat samples. The fat of animals was the only tissue
    to contain significant residues. This study supplements the previous
    study done with radioactive ethion (FAO/WHO, 1969).

    White Leghorn hens were fed ethion at 10 ppm as a portion of their
    daily feed ration for nine consecutive weeks (Niagara, 1969). Egg
    samples were collected from day 54 of ethion feeding through day 60.
    At the end of the nine week test feeding period, one half of the
    chickens were sacrificed and tissue samples taken.

    A four-week recovery period followed during which the remaining
    chickens were not fed ethion in their daily feed ration. Egg samples
    were collected periodically. At the end of the recovery period the
    remaining chickens were sacrificed and tissue samples taken.

    No ethion residues approaching the method sensitivity of 0.01 ppm were
    detected in any of the egg or tissue samples analysed following the
    feeding and recovery periods. Although the analytical method was not
    the newer version that measures extremely low levels of the oxygen
    analogues, no residues would be expected since there were no traces of
    ethion.

    In plants

    An improved analytical method for the measurement of oxidized forms of
    ethion (ethion monooxon and ethion dioxon) has been developed since
    the 1968 review (FAO/WHO, 1969). Apples, pears, plums, prunes, grapes
    and oranges have been treated with ethion formulations at the maximum
    allowable rate to determine the magnitude of the oxidized forms by
    this newer method (Niagara, 1972b,c,d,e). These data are summarized in
    Table 6.


    TABLE 6  Ethion residues in various crops

                                                                             

    Crop         Pre-harvest     Total residue-ethion    Residue present as
                 interval        + oxons (ppm)           oxygen analogue
                 (days)                                  (% of total)
                                                                             

    Apples       20 - 28         0.71 - 0.75             13 - 16

    Pears        20 - 23         1.2  - 2.6              15 - 18

    Plums        21              0.40                    25

    Prunes       21              0.25                    22

    Grapea       30 - 32         0.35 - 1.8              0 - 15

    Oranges      0               1.50                    0

    Oranges      7               0.92                    16

                 14              0.62                    18
                                                                             


    Residues of oxygen analogues resulted only from treatments with
    wettable powders. No oxygen compounds were detected from emulsifiable
    concentrate treatments.

    In storage and processing

    Simulated commercial processing of ginned cottonseed (Niagara, 1970)
    showed that 64% of the residue present on cottonseed from useful
    application of ethion was contained on the lint. The bulk of the
    remainder was present on the hulls (29%). Transfer to the oil was only
    4%.

    This represented a level of 0.33 ppm on the cottonseed oil when the
    total on the ginned seed was 0.84 ppm.

    Evidence of residues in food, in commerce or at consumption

    Duggan et al. (1971), in a report on residues in food in the United
    States from July 1963 to June 1969, reported that ethion was found in
    0.3 to 1.7% of composite samples, with an average daily intake below
    0.003 mg/day. The only samples reported containing residues were large
    and small fruits. The incidence was 11.9% in the case of large fruits
    and 5% in the case of small fruits.

    Corneliussen (1970) reported on a total diet study for the period of
    June 1968 through April 1969. Ethion occurred on six of the 30 fruit
    composites. This was the only category in which ethion residues were
    found. The maximum value was 0.27 ppm. Processing of the fruits
    reduced the residues by 42%. Details of the processing procedure were
    not given.

    The New South Wales Department of Agriculture (Watts, 1972) reported
    results of a critical survey of 1 063 samples of butter produced in
    1971 within the cattle tick quarantine areas and analysed by the Board
    of Tick Control. The residues were found only during the period when a
    compulsory dipping program was being undertaken, i.e., from September
    until March. Of the samples, 54% were reported to contain ethion
    residues ranging from 0.01 to 0.62 ppm. A similar pattern was reported
    for 1970 although, due to less intensive dipping, the number of
    samples with residues was then only 39% of the total analysed. During
    this period, 286 000 head of cattle were being dipped in ethion
    emulsion every 17 - 21 days.

    In a survey of 879 butter samples collected in 1971 from regions where
    cattle tick is endemic, the Australian Department of Primary Industry
    (Snelson, 1972) reported that 17.4% of the samples contained ethion
    residues at levels ranging from 0.05 to 0.5 ppm.

    METHODS OF RESIDUE ANALYSIS

    A gas chromatographic method utilizing a flame photometric detector
    specific for phosphorus has been developed for the analysis of ethion
    residues (Niagara, 1972b). Ethion and the two oxygen analogues can be
    determined simultaneously in the same sample. A limit of determination
    as low as 0.005,ppm has been achieved. The key factor in achieving
    this improvement was the elimination of charcoal absorbents in cleanup
    steps. This method has not been published.

    The EPA multi-residue procedure determines ethion but will not
    determine the oxygen analogues. There are two points in the
    multi-residue procedure where these substances are lost: firstly in
    the hexane/acetonitrite partition where the oxygen analogues do not
    partition quantitatively into the hexane; secondly the oxygen
    analogues are not eluted from the cleanup column with the solvents
    used to isolate the organophosphate materials.

    The multi-detection methods published in the EPA Analytical Manual
    Vol. 1 have been used successfully for the determination of ethion
    residues in many substrates and are recommended for regulatory
    purposes even though not determining oxygen analogues.

    NATIONAL TOLERANCES

    Since the review in 1968 (FAO/WHO, 1969d) the tolerances shown in
    Table 7 have been established for ethion residues.

    TABLE 7

    Examples of national tolerances reported to the meeting

                                                           ppm

    U.S.A.         Maize, forage and fodder                14

                   Cottonseed                              0.5

                   Milk fat (reflecting negligible
                   residues in whole milk)                 0.5

                   Eggs                                    0.2

                   Meat, fat and meat by-products
                   of goats, pigs, horses, poultry
                   and sheep                               0.2

                   Maize grain, apricots, cherries,
                   chestnuts, filberts, pecans and
                   walnuts (kernel)                        0.1

    Australia      Fruit and vegetables                    1

                   Fat of meat of cattle                   2.5

                   Meat of cattle                          0.75

    APPRAISAL

    Ethion is a non-systemic organo-phosphorus insecticide and acaracide
    introduced in 1956 and widely used, especially as an acaracide and
    scale control agent, for many fruit crops, tea and some vegetables,
    often in combination with petroleum oils. It is also used for dipping
    cattle against cattle ticks in many countries.

    Since the review in 1968 (FAO/WHO, 1969), improved methods of analysis
    have enabled studies to be made of the fate of ethion residues on a
    number of fruits. Foliar applications of wettable powder formulations
    can give rise to small amounts of ethion monooxon and ethion dioxon,
    but the amount is usually less than 20% of the total residue. The
    oxygen analogues do not occur when emulsifiable formulations are used.

    Studies made following the feeding of dairy cattle with ethion,
    simulating feeding of contaminated or treated fodder, show that small
    amounts of ethion, but no oxygen analogues, are to be found in milk
    and fatty tissues. Poultry, on the other hand, do not have residues
    either in body fat or eggs when receiving rations containing small
    amounts of ethion.

    Ethion residues have only been found infrequently at low levels in
    composites of the average diet examined in the U.S.A. Butter samples
    taken from areas where cattle must be dipped to control cattle ticks
    show that ethion residues occur frequently at significant levels.

    Analytical procedures suitable for regulatory purposes are available.
    These are capable of determining the oxygen analogues as well as the
    parent compound.

    RECOMMENDATIONS

    The previously recommended temporary tolerances are amended and are no
    longer classified as temporary. The following residue limits are based
    on residues likely to be found at harvest, or in the case of fat of
    meat from cattle, dairy produce and tea, also at the retail level,
    following currently approved use patterns.

    The residue levels are unlikely to decline significantly during
    storage but, except in fat of meat and dairy produce, processing or
    cooking will largely destroy any residues prior to consumption.

    PRACTICAL RESIDUE LIMITS

                                                           ppm

         Apples, grapes, lemons, limes, oranges            2

         Plums, prunes, strawberries                       2

         Nectarines, peaches, pears                        1

         Apricots, cherries                                0.1*

         Melons, tomatoes, beans                           2

         Cucumbers, squash                                 0.5

         Eggplant, garlic, onions                          1

         Pimentos, peppers                                 1

         Cottonseed                                        0.5

         Maize (grain)                                     0.05*

         Almonds, chestnuts, filberts,
         pecans, walnuts (shelled)                         0.1*

         Fat of meat of cattle                             2.5

         Edible offal of cattle                            0.75

         Fat of meat of goats, horses, pigs,
         poultry and sheep                                 0.2*

         Edible offal of goats, horses, pigs,
         poultry and sheep                                 0.2*

         Milk and milk products (fat basis)                0.5

         Eggs                                              0.2*

         Tea (dry manufactured)                            7

         * at or about the limit of determination

    Remarks

    Residues of ethion and its oxygen analogues should each be determined
    and the sum expressed as ethion.

    FURTHER WORK OR INFORMATION

    DESIRABLE

    Determination of the metabolic fate in animals.

    REFERENCES

    Arnold, D., Kennedy, G. and Keplinger, M.L. (1972) Report NCT 461.99,
    Industrial Bio-Test Laboratories, Inc. Mutagenic study with ethion in
    albino mice. (unpublished)

    Brandav, E.G., Knaak, J.B. and McCarthy, J.F. (1971) Excretion of
    ethion-methylene-14C by the rat. Report M2819 Niagara Chemical
    Division, FMC Corporation. (unpublished)

    Corneliussen, P.E. (1970) Pesticide residues in total diet samples
    (V). Pest. Mon. J., 4(3): 89 - 105.

    Duggan, R.E., Lipscomb, G.Q., Cox, E.L., Heatwole, R.E. and Kling,
    R.C. (1971) Pesticide residue levels in foods in the United States
    from 1963 - 1969. Pest. Mon. J., 5(2): 73 - 212.

    FAO/WHO. (1969) 1968 evaluations of some pesticide residues in food.
    FAO/PL:1968/M/9/1; WHO/Food Add./69.35.

    FAO/WHO. (1970) 1969 evaluations of some pesticide residues in food.
    FAO/PL/1969/M/17/1; WHO/Food Add./70.38.

    FAO/WHO. (1971) 1970 evaluations of some pesticide residues in food.
    FAO/AGP: 1970/M/12/1; WHO/Food Add./71.42

    Fletcher, D., Jenkins, D.H. and Keplinger, M.L. (1972) Report NCT
    646.22 Industrial Bio-Test Laboratories, Inc. Neurotoxicity study with
    ethion technical in adult hens. (unpublished)

    Greco, R.A., Keplinger, M.L. and Fancher, O.E. (1970) The in vitro
    inhibitory effects of ethion, ethion monooxon and ethiondioxon on
    human plasma and erythrocyte cholinesterase activity. Report NCT
    402.21 Industrial Bio-Test Laboratories, Inc. (unpublished)

    Haley, S., Plank, B.J. and Wright, P.L. (1972) Teratogenic study with
    ethion technical in albino rats. Report NCT 463.42 Industrial Bio-Test
    Laboratories, Inc. (unpublished)

    Hartke, K., Wright, P.L. and Keplinger, M.L. (1972) Two-year chronic
    oral toxicity study with ethion technical in beagle dogs. Report NCT
    386.32 Industrial Bio-Test Laboratories, Inc. (unpublished)

    Kretchmar, B., Mastri, C. and Keplinger, M.L. (1971) Acute oral
    toxicity study with ethion technical in female albino rats. Report NCT
    422.01 Industrial Bio-Test Laboratories, Inc. (unpublished)

    Mastri, C., Keplinger, M.L. and Fancher, O.E. (1970) Acute oral
    toxicity studies with ethion dioxon and ethion monooxon in albino
    rats. Report NCT 404.01 Industrial Bio-Test Laboratories, Inc.
    (unpublished)

    Niagara. (1962) Pesticide Petition No. 351 to U.S. Food and Drug
    Administration, Niagara Chemicals Division, FMC Corporation.

    Niagara. (1969) Determination of ethion residues in eggs and poultry
    tissues. Report M2548 filed with FAO. Niagara Chemicals Division, FMC
    Corporation. (unpublished)

    Niagara. (1970) Ethion residues on cottonseed; process study. Report
    R-1156 filed with FAO. Niagara Chemicals Division, FMC Corporation.
    (unpublished)

    Niagara. (1971a) Pesticide Petition OF0920 to U.S. Environmental
    Protection Agency. Niagara Chemicals Division, FMC Corporation.

    Niagara. (1971b) Determination of ethion, ethion monooxon and ethion
    dioxon residues in or on oranges. Report M-3035 filed with FAO.
    Niagara Chemicals Division, FMC Corporation  (unpublished)

    Niagara. (1971c) Residue determination of ethion and its oxygen
    analogues in milk and cow tissue. Report M-2808 filed with FAO.
    Niagara Chemicals Division, FMC Corporation. (unpublished)

    Niagara. (1971d) Pesticide Petition 1F1104 to U.S. Environmental
    Protection Agency. Niagara Chemicals Division, FMC Corporation.

    Niagara. (1972a) Ethion residues in or on Valencia oranges. Report
    R-1207 filed with FAO. Niagara Chemicals Division, FMC Corporation.
    (unpublished)

    Niagara. (1972b) Ethion residues in or on apples and pears. Report
    R-1187 filed with FAO. Niagara Chemicals Division, FMC Corporation.
    (unpublished)

    Niagara. (1972c) Ethion residues in or on plums and prunes. Report
    R-1188 filed with FAO. Niagara Chemicals Division, FMC Corporation.
    (unpublished)

    Niagara. (1972d) Pesticide Petition No. OF0918 to U.S. Environmental
    Protection Agency. Niagara Chemicals Division, FMC Corporation.

    Niagara. (1972e) Ethion residues in or on grapes, raisins and grape
    by-products. Report R-1196 filed with FAO. Niagara Chemicals Division,
    FMC Corporation. (unpublished)

    Palazzolo, R.J., Fancher, O.E. and Calandra, J.C. (1970) A study on
    the effects of ethion on plasma and erythrocyte cholinesterase
    activity in human subjects during subacute administration. Report NCT
    380-21 Industrial Bio-Test Laboratories, Inc. (unpublished)

    Palazzolo, R.J., Fancher, O.E. and Calandra, J.C. (1971)
    Cholinesterase inhibition studies in man with ethion. Society of
    Toxicology Meetings, 5 - 9 March 1972. Paper No. 29.

    Smith, P.S., Wright, P.L. and Keplinger, M.L. (1972) Two-year chronic
    oral toxicity study with ethion technical in albino rats. Report NCT
    385.32 Industrial Bio-Test Laboratories, Inc. (unpublished)

    Snelson, J.T. (1972) Results of residue surveys in Australia. Report
    filed with FAO. Department of Primary Industry, Canberra, Australia.

    Watts, R.M. (1969) Report of dipping trials with ethion. New South
    Wales Department of Agriculture.

    Watts, R.M. (1972) Analysis of butter by Board of Tick Control. Report
    to Co-ordinating Committee on Pesticides, Canberra, Australia.
    


    See Also:
       Toxicological Abbreviations
       Ethion (ICSC)
       Ethion (FAO/PL:1968/M/9/1)
       Ethion (FAO/PL:1969/M/17/1)
       Ethion (AGP:1970/M/12/1)
       Ethion (WHO Pesticide Residues Series 5)
       Ethion (Pesticide residues in food: 1982 evaluations)
       Ethion (Pesticide residues in food: 1983 evaluations)
       Ethion (Pesticide residues in food: 1986 evaluations Part II Toxicology)
       Ethion (Pesticide residues in food: 1990 evaluations Toxicology)