BROMOPHOS-ETHYL             JMPR 1972


    Chemical name



    Nexagan(R), S-2225, SHG-2225, ethyl bromophos, bromophosethyl

    Structural formula


    Other information on identity and properties

         Molecular weight: 394.0

         State: yellow fluid

         Density: d20 = 1.53

         Boiling point: 122-123°C at 10-3 torr.

         Vapour pressure: 4.6 x 10-5 mm Hg at 30°C

         Solubility:    at room temperature miscible with most organic
                        solvents; practically insoluble in water.

         Stability:     stable in aqueous suspension. Saponification only
                        occurs in distinct alkaline medium.

         Purity of technical material:      

    approx. 95.0%;
    approx. 3.0%;
    approx. 1.0%;
    approx. 1.0% (chlorine position not defined)



    Absorption, distribution and excretion

    Studies using bromophos-ethyl labelled with 3H in the benzene ring
    demonstrated that, in the rat, the substance is absorbed following
    oral administration but accumulation generally or in specific organs
    does not occur. Apart from the G.I. tract, only the liver, kidney,
    spleen and brain showed any substantial activity after 4 hours, and
    this declined sharply in 24 hours. Almost total excretion of activity
    occurred within 4 days following 5 daily oral doses of approximately 8
    mg/kg. The distribution pattern was essentially the same after
    intraperitoneal injection, but excretion was slower due to its slow
    release from peritoneal and mesenteric fat.

    Following a single 8 mg/kg oral dose of 3H-labelled bromophos-ethyl,
    40% of the activity appeared in urine and 60% in faeces. When
    administered intraperitoneally or subcutaneously, the major portion
    also occurred in faeces. Radioactivity was detected in bile 40 minutes
    after administration into the duodenum of 3H-labelled material and
    40% was excreted by this route in 9 hours. The identity of the
    substance in bile has not been established (Boehringer, 1967).


    No bromophos-ethyl, the oxidation product bromoxon-ethyl or
    desethyl-bromophos-ethyl, which would be formed by cleavage of the
    C2H5-O-P bond, were found in the urine or faeces of rats after oral
    dosage. The metabolite dichloro-bromophenol and its conjugates were
    identified in urine and faeces and accounted for 85-90% of
    administered product, showing that the principal metabolic route
    involved cleavage of the phenyl-O-P bond (Boehringer, 1967).

    Effects on enzymes and other biochemical parameters

    A single dose of 42 mg/kg of bromophos-ethyl to rats caused maximum
    inhibition of cholinesterase in plasma and RBC after 8 and 2 hours
    respectively. Values showing less than 20% inhibition occurred after
    16 and 48 hours respectively (Muacevic, 1968). A single dose of 15
    mg/kg to sheep inhibited RBC cholinesterase after 24 hours. A normal
    level was found 24 hours later. A dose of 10 mg/kg was without effect
    (Terblanche, 1966). In short-term (Muacevic, 1966; Leuschner, 1966,
    1967) and long-term studies (Leuschner et al., 1969a, 1969b) in rats
    and in short-term studies in dogs (Leuschner, 1966, 1967; Leuschner
    et al., 1968) and cattle (Vuuren, 1964; Muacevic, 1966), inhibition
    of plasma, RBC, brain and liver cholinesterase was noted. In general,
    plasma cholinesterase was the most sensitive of the enzymes.


    Special studies on neurotoxicity

    Bromophos-ethyl, 600 mg/kg (the assumed LD50) was administered orally
    to 10 one-year-old hens; they were treated with atropine and
    toxogonin. No neurological abnormalities were seen in the 6-week
    observation period (Muacevic, 1968).

    Three groups of 10 one-year-old hens were administered orally 0, 1.25,
    or 2.5 mg/kg/day of bromophos-ethyl on 6 days a week for one month.
    Only one bird at the top dosage level showed general weakness;
    neuropathological examination revealed no changes in this or other
    birds examined (Muacevic, 1968).

    Special studies on pharmacology

    Atropine sulphate and toxigonin were shown to protect rats and mice
    from a lethal dose of bromophos-ethyl. Norscopolamine also protected,
    but salicylaldoxime showed no positive effect (Muacevic, 1967; 1968).

    Special studies on reproduction

    Groups of 20 male and 20 female rats were fed on diets providing 0,
    1.25, 3.0 and 7.2 mg/kg/day approximately of bromophos-ethyl. Three
    generations were examined, the parent F1 and F2 generation each
    producing two litters, and mating taking place between week 9 and 15
    and between week 21 and 16. No abnormalities were seen in the
    behaviour, appearance, body-weight, haematological indices, or in
    organs during pathological examinations in adult animals. No effect on
    reproduction was found in the two lower dosage groups, but in the 7.2
    mg/kg group, which showed significant inhibition of liver, brain and
    plasma cholinesterase, the fertility rate and litter size were
    decreased and the number of stillbirths increased. The young also
    tended to have a lower body-weight than controls. However no runts or
    animals with congenital malformations were discovered (Leuschner
    et al., 1969b).

    Special studies on teratogenicity

    Groups of 20 pregnant female rats were administered 0, 0.03, 1.7, 3.5,
    7.0 or 14.0 mg/kg body-weight/day of bromophos-ethyl by gastric
    intubation from day 6 to 15 of gestation. Animals were killed at day
    20 and uteri and foetuses examined. No significant differences from
    controls were found in the number of foetuses or reabsorption sites or
    in foetus weights. No malformations, runts or dead foetuses were found
    in any of the treated groups (Leuschner, 1967).

    Acute toxicity

    The acute toxicity of technical bromophos-ethyl has been studied in
    various animal species. A summary of the results of these studies is
    given in Table 1.

    TABLE 1 Acute toxicity of technical bromophos-ethyl in animals


    Animal     Route     LD50             References

    Mouse      oral      210-550          Barnes, 1968; Muacevic, 1964,

    Rat        oral      52-127           Barnes, 1968; Muacevic, 1964,
                                          1966; Leuschner, 1966, 1967

    Rabbit     oral      28               Muacevic, 1970

    Rabbit     dermal    100-600          Bradford, 1967; Muacevic, 1967

    Dog        oral      335(approx.)     Muacevic, 1970

    Quail      oral      200              Muacevic, 1970

    Hen        oral      600(approx.)     Muacevic, 1969

    Potentiation of acute toxicity

    Potentiation of the acute toxicity of bromophos-ethyl has been
    demonstrated to occur in the rat with bromophos, chlorfenvinphos,
    coumaphos, malathion, mevinphos and parathion-methyl, and in the mouse
    with chlorfenvinphos, diazinon, dimethoate, ethion and malathion.
    Slight potentiation with parathion was found in both species
    (Muacevic, 1966, 1967, 1968).

    Short-term studies


    Groups of 6 male and 6 female rats were fed for 4 weeks on diets
    providing 0, 1 and 10 mg/kg/day of bromophos-ethyl. No significant
    changes in behaviour, growth rate, food intake or macroscopic
    appearance of organs could be observed (Leuschner, 1966).

    Groups of 16 male rats were administered daily by gavage 0, 1, 5, 20
    or 60 mg/kg body-weight of bromophos-ethyl suspension. The highest
    dose was discontinued after 2 days since 9 animals had died. In the
    remaining groups no abnormalities in behaviour, food consumption,
    growth rate, haematological indices or liver function were found. No
    pathological changes in organs were found at autopsy, and the livers,
    kidneys and lungs were microscopically normal (Boehringer, 1964).

    Groups of 42 male and 42 female rats were administered diets providing
    0, 0.78, 1.25, 3.0 and 7.2 mg/kg body-weight of bromophos-ethyl/day.
    During the 16-week period of administration no abnormalities in
    behaviour, body-weight, food consumption or blood counts were
    detected. Necropsy of 5 animals of each group revealed no macroscopic
    abnormalities attributable to treatment. Dosage levels of 1.25 mg/kg
    upwards caused a marked increase in the quantities of ascorbic and
    dehydroascorbic acids excreted in the urine (Leuschner, 1967).


    Three groups of 2 male and 2 female mongrel dogs were administered
    daily in capsules 0, 1.6 or 12.5 mg/kg body-weight of bromophos-ethyl
    for 2 weeks. The highest dose level was increased to 25 mg/kg for a
    further week, and during this period these animals became quiescent,
    lost weight and developed diarrhoea. The composition of urine and
    blood counts were normal in all animals. The two lower dosage levels
    were without untoward effect (Leuschner, 1966).

    Four groups of 2 male and 2 female beagle dogs received daily capsules
    containing 0, 0.52, 1.25 or 3.0 mg bromophos-ethyl for 16 weeks. No
    abnormalities in behaviour, food consumption, body-weight,
    haematological indices, the activity of serum enzymes, chemical
    constituents of blood or urine constituents were found in treated
    animals. No pathological changes were found in the eye, and organ
    weight changes did not occur. The 1.25 mg/kg group excreted an
    increased amount of ascorbic and dehydroascorbic acids in their urine
    and three times the normal amount was excreted by the 3.0 mg/kg group.
    The adrenal was the only organ in which changes occurred which could
    be attributed to treatment. Narrowing of the fascicular zone and
    dispersal of the glomerulose zone, the cells showing a high lipoid
    content, and fibrous dispersal of the capsule were described, the
    degree of change being most marked in the 3.0 mg/kg group (Leuschner,

    Six groups of beagle dogs were administered each day, in capsules,
    sugar (control), coumaphos or bromophos-ethyl as follows: sugar, 1 g;
    coumaphos, 3.0 mg/kg; bromophos-ethyl, 0.26 mg/kg and 0.39 mg/kg (3
    male and 3 female dogs), 1.25 mg/kg (5 males and 5 females), 3.0 mg/kg
    (6 males and 6 females). The administration continued for 18 weeks
    after which a number of animals of each group received no treatment
    for four weeks. Depression of plasma cholinesterase activity occurred
    at the 1.25 mg/kg dosage level, but no definite decrease in enzyme
    activity occurred at any dosage level in the RBC, brain or adrenal
    gland. Caumaphos, however, inhibited RBC and brain enzyme at the 3.0
    mg/kg/day level. Four weeks after treatment ceased all cholinesterase
    levels had returned to normal. Urinary ascorbic and dehydroascorbic
    acids were increased slightly in the 0.39 mg/kg group and the increase
    was marked with higher dosage levels of bromophos-ethyl and with
    coumaphos. The values also returned to normal when administration
    ceased. Histological examination showed that in bromophos-ethyl
    treated animals only the 3.0 mg/kg group showed a moderate broadening
    of the fasciculate zone of the adrenal and a relative increase in
    eosinophilic staining in the frontal lobe of the pituitary. The
    appearance of the adrenals and pituitary were normal after treatment
    had ceased for four weeks (Leuschner et al., 1968).

    Five groups of 4 male and 4 female beagle dogs were fed for 2 years on
    diets containing 0, 10, 20, 30 and 120 ppm bromophos-ethyl. No
    influence was seen on behaviour, food intake or growth of treated
    animals. Analysis of blood for chemical constituents, including
    cortisol, and of urine failed to demonstrate abnormalities. All serum
    enzymes, except cholinesterase, were of normal activity. The weight
    and macro- and microscopic appearance of organs, including the adrenal
    and pituitary glands and bone marrow, were normal when animals were
    killed during and at the end of the test. The dosage threshold at
    which inhibition of cholinesterase occurred was considered to be
    between 10 and 20 ppm for plasma enzyme and above 120 ppm for RBC and
    brain enzymes. Urine ascorbic and dehydroascorbic acid levels were
    increased in the 30 and 120 ppm groups. Excretion was maximum at
    between 6 and 9 months, and then it decreased. No untoward effects
    could be detected in the 10 ppm group (Leuschner et al., 1971).


    Groups of 2 male and 2 female rabbits were administered 0, 2.5, 12.5
    and 62.5 mg/kg/day of bromophos-ethyl on scarified or intact skin in
    the form of an ointment for 6 hours each day for 21 days. They were
    observed for a further 14 days before necropsy. One male of the
    highest dosage group died and body-weight gain was retarded in the two
    highest groups. Varying degrees of liver necrosis, myocardial scarring
    and renal changes were found at the highest dosage level but not at
    lower levels (Stötzer et al., 1970).

    Long-term studies


    Groups of 42 male and 42 female rats, each weighing from 166 to 214 g,
    were fed diets providing 0.78, 1.25, 3.0 or 7.2 mg/kg body-weight/day
    of bromophos-ethyl for 2 years. The threshold levels for a 20%
    inhibition of activity lay between 0.78 and 1.25 mg/kg for plasma and
    3.0 and 7.2 mg/kg for erythrocyte, brain and liver cholinesterase.
    Urinary ascorbic and dehydroascorbic acid excretion was elevated at
    all dosage levels; a 78% increase was seen at the 0.78 mg/kg level.
    With increasing age, the amounts excreted became less marked but were
    still significantly high at 2 years in the 3.0 and 7.2 mg/kg groups.
    The mean body-weights of rats of both sexes on 3.0 and 7.2 mg/kg
    bromophos-ethyl were slightly elevated above that of the controls
    throughout much of the test. Urine analysis showed that the incidence
    of occurrence of erythrocytes, protein, ketone bodies and white blood
    cells was reduced in the 3.0 and 7.2 mg/kg groups compared with
    controls. No significant differences from controls were seen with
    regard to behaviour, survival, food intake, and the results of
    haematological investigations or with regard to gross or microscopic
    changes in organs or tumour incidence and type (Leuschner et al.,


    Bromophos-ethyl is absorbed from the gastro-intestinal tract and
    excreted in urine and faeces principally as dichloro-bromophenol and
    its conjugates. Accumulation does not occur following oral ingestion.
    Bromophos-ethyl inhibits cholinesterase, the plasma enzyme being the
    most sensitive. Acute potentiation was observed in combination with
    several other organo-phosphates in rats and mice. In 2-year studies in
    dogs and rats the no-effect levels for plasma cholinesterase
    inhibition were 0.4 and 0.78 mg/kg body-weight/day, respectively.
    Bromophos-ethyl does not cause delayed neurological injury. Studies in
    rats did not indicate ill effects on reproduction or teratogenic

    In studies in rats and dogs urinary excretion of ascorbic and
    dehydroascorbic acids was increased. The no-effect level in dogs was
    0.26 mg/kg/day. A no-effect level was not demonstrated for rats.
    Investigations to find the cause of the increase were not reported.
    The long-term study in rats showed that, at the dosage levels
    employed, bromophos-ethyl had no carcinogenic activity.


    Level causing no toxicological effects

         Dog: 0.26 mg/kg body-weight


         0 - 0.003 mg/kg body-weight



    Bromophos-ethyl is an organo-phosphorus insecticide and acaricide with
    a broad spectrum of activity and moderate mammalian toxicity. It acts
    as a contact and stomach poison. It is available as an emulsifiable
    concentrate, ULV concentrate, wettable powder, granular or dust
    formulation as well as dip formulations. Bromophos-ethyl is compatible
    with insecticides and fungicides.

    This substance is of moderate toxicity to bees and should not be
    sprayed on flowering crops during the flight of bees.

    Bromophos-ethyl has been used in Argentina, Australia, Austria,
    Belgium, Brazil, Colombia, the Federal Republic of Germany, the
    Netherlands, New Zealand, Nicaragua, Pakistan, South Africa and

    Pre-harvest treatments

    Bromophos-ethyl is applied on various crops, mainly fruits, field
    crops, vegetables, cereals, maize, rice, cotton and tobacco, and is
    effective against a large number of chewing and sucking insect pests,
    especially caterpillars, vegetable root maggots, fruit flies, bean
    fly, aphids and beetles.

    Depending on the different crops and the main pest species present the
    recommended concentrations of spray wash vary between 0.02% and 0.1%
    a.i. and the rates of application between 0.2 and 1.2 kg a.i./ha. The
    majority of crops are tolerant to normal rates of the insecticide.
    Occasionally slight damage was noticed, in particular in connection
    with high dosages.

    The withholding periods range from 14 to 28 days, depending on the
    local conditions and crop.

    Other uses

    Bromophos-ethyl is used in the sector of animal health and tick
    control. The compound is active against ticks, including strains of
    the genus Boophilus which are resistant to chlorinated hydrocarbons
    and other phosphorus preparations, as well as against blowflies, lice
    and other ectoparasites. It also controls mosquitoes, mosquito larvae
    and ants, revealing a remarkable residual effect. Bromophos-ethyl is
    used particularly as a mosquito larvicide.


    Residue data are available from supervised trials on a variety of
    fruits, vegetables and field crops (Boehringer, 1971-1972). Summaries
    of much of this information have recently been published (Eichler
    1971). The following tables 2 and 3 present a summary of available
    data along with relevant information on rates of application, number
    of applications and preharvest interval.

    In trials in the Netherlands (Anonymous, 1970), bromophos-ethyl was
    applied to carrots at 6 kg a.i./ha either by soil surface treatment
    with granules prior to seeding or by foliar treatment with wettable
    powder or emulsifiable concentrate 81 and 89 days after planting. The
    residues obtained are shown in table 4.

    Distribution of residues in 1-year-old beef cattle was determined in
    Germany (Boehringer, 1966) after spraying to runoff 1 or 4 times with
    bromophos-ethyl emulsion (0.05% a.i.). The results are summarized in
    table 5.

    In later trials (Boehringer, 1968), 6 cows were sprayed three times at
    5-day intervals (14 days is more usual) with 0.1% a.i. emulsion (twice
    the concentration generally used). Table 6 summarizes these results.

    Two experimental trials on residues in beef cattle were conducted in
    Australia. In the first of these, two groups of 9 cattle were sprayed
    with bromophos-ethyl at a concentration of 0.05% (Snelson, 1968).
    Group 1 was treated once and Group 2 had three treatments at 5-day
    intervals. Residues were determined in heart, kidney, omental and
    subcutaneous fat with the results shown in Table 7.

    The highest residues were in samples of heart and kidney fat. In the
    second trial, six steers were sprayed each with 2 gallons of 0.05%
    bromophos-ethyl and samples were taken for analysis at 4, 7 and 21
    days after exposure (Harvey, 1968). Residues were distributed as shown
    in Table 8.

    Dipping leads to higher uptake and significantly higher residues in
    fat than does spraying with the same concentration of bromophos-ethyl.
    In a series of dipping trials under the direction of the Board of Tick
    Control in Australia, 12 cattle were dipped once in 0.05%
    bromophos-ethyl emulsion and groups of four were slaughtered 1, 4 and
    8 days post treatment and 12 cattle were dipped three times at
    intervals of 5 days in the same bath and groups of four were
    slaughtered, as before, 1, 4 and 8 days after the third dipping
    (Snelson, 1972). Results are given in Table 9.

    Further trials showed that the uptake varied considerably depending on
    the condition of the animals (fat versus thin), length of hair and
    time of year. It was demonstrated that the half-life of
    bromophos-ethyl residues in internal fat of cattle is 10 to 12 days.

        Table 2  Bromophos-ethyl residues in fruit1

    Crop           Application       Days between last treatment and harvest
                   No.  Rate a.i.    0      1      2      3      4      5      7      8      10     14     15     21     22     28     30

    Apple          1    1.8                                      2.20          1.40                 1.95          1.35
                   1    0.9          1.25          0.7           1.03          1.20                 0.76          0.55
                   1    0.9          0.58                                      0.36                 0.33          0.30          0.28
                   1    1.8                                      1.17                 1.13                 0.81          1.23
                   5    1.2                 3.45                                             2.65                 2.05                 1.95
                   6    1.5                 4.90                                             3.70                 2.50                 2.30

    Pear           1    0.36         0.59                                      0.32                 0.32          0.26          0.15

    Peach          1    0.5                                                    0.38                 0.39

    Yellow plum    1    0.9                                                    1.40                 0.81

    Plum           1    1.8                                      2.08          1.14                 1.35          1.11
                   3    1.8          2.28                                      1.24                 0.73          0.51
                   1    0.54         0.36                                      0.34                 0.14          0.13          0.12

    Sweet Cherry   1    1.8          0.87                        0.45          0.27                 0.07          0.03
                   1    1.8                                      0.21          0.17                 0.09
                   1    1.8          0.89                        0.27          0.16                 0.14          0.03

    Strawberry     1    2882                                                   0.36                 0.07

    Gooseberry     1    0.36                0.33          0.52          0.26   0.31                 0.30

    Red-currant    1    3602                                                   1.18                 0.95

    Black-currant  1    0.36                                                   0.78                 0.12

    1  residue figures given in ppm
    2  g/ha

        Table 3a  Bromophos-ethyl residues in vegetables and field crops1
    Crop           Application          Days between last treatment and harvest
                   No.  Rate      0     1     3     4     5     7     14    21    28    30    
                      (g/ha a.i.)

     lettuce       1    108                         0.31        0.28  0.18
                   1    216       2.35        1.09        1.03  0.37  0.16  0.10
                   1    108                         1.05        0.45  0.09
                   1    108                         0.31        0.28  0.18

    Spinach        1    216                                     2.72  1.60  0.42  0.03        
                   1    216                         6.84        4.42  2.22
                   1    288             8.32  6.66        3.26  2.78  0.44

    Carrot         2    0.182                                                                 
                   1    0.103                                                                 
                   2    0.182                                                                 
                   1    0.183                                                                 
    Cauliflower    2    28.84                                                           <0.02

    Kohlrabi       2    324                                                                   

    White cabbage  1    360                                     <0.08 <0.08
                   1    216       0.20        0.16        0.07  0.04  0.02  <0.02

    sprouts        3    540                                                 0.57        0.51

    Sugar beet     1    144                                                                   

    Onion          2    0.23                                                                  
                   2    0.23                                                                  
                   2    0.23                                                                  

    tuber          3    160                                                 0.19-

    leaf           3    160                                                 2.67-

    Rape seed      1    216                                                                   

    Rape oil       1    216                                                                   

    Horsebean      1    600                                                       <0.02

    Kidney bean    2    324       0.18                          0.07  0.03  0.02  <0.02
    1 residue figures given in ppm.  2 g/m (2x).   3 g/m.   4 mg/plant.

    Table 3b Bromophos-ethyl residues in vegetables and field crops1
    Crop           Application          Days between last treatment and harvest
                   No.  Rate      31    35    42    49    54    56    62    64    66    71    107
                       (g/ha a.i.

    lettuce        1    108       
                   1    216       
                   1    108       
                   1    108       

    Spinach        1    216             0.02
                   1    216       
                   1    288       

    Carrot         2    0.182                             1.21
                   1    0.103                                   0.40
                   2    0.182                                               1.53
                   1    0.183                 1.42
    Cauliflower    2    28.84     

    Kohlrabi       2    324       0.05

    cabbage        1    360       
                   1    216       

    sprouts        3    540       

    Sugar beet     1    144                                                                   <0.02

    Onion          2    0.23                                                            <0.02
                   2    0.23                                                      <0.02
                   2    0.23                                          <0.02

    tuber          3    160       

    leaf           3    160       

    Rape seed      1    216                         0.08

    Rape oil       1    216                         0.33

    Horsebean      1    600       

    Kidney bean    2    324       
    1 residue figures given in ppm.   2 g/m (2x).   3 g/m.   4 mg/plant.
    TABLE 4  Bromophos-ethyl residues in carrots


    Crop      Method of       Rate of        Time between      Residues
              application     application    last treatment    (ppm)
                              (kg/ha/a.i.)   and harvest

    Carrots   soil surface       6              3              0.22 - 0.24

              soil surface       6              3              0.17 - 0.77

              foliar spray       6              2              0.49 - 1.5

              foliar spray       6              2              0.84 - 1.6

        TABLE 5  Distribution of bromophos-ethyl residues in cattle tissue, 1966


             Treatment      Sample interval               Residues (ppm)1
    Animal   (0.05%         (days after        Back       Leg
              a.i.)         last treatment)    muscle     muscle     Brain      Kidney     Liver      Fat

    12       1 spray        1                  0.77       0.90       0.76       <0.13      <0.14      n.d.

    2        4 sprays       3                  n.d.       <0.18NS    n.d.       n.d.       <0.15NS    n.d.

    3        4 sprays       1                  <0.18NS    n.d.       n.d.       n.d.       n.d.       0.67*

    4        4 sprays       11                 n.d.       n.d.       n.d.       n.d.       n.d.       <0.20NS

    5        Control        --                  -- 0.056 --          0.049      0.052      0.053      0.076

    1  n.d. = not detected;  NS = not statistically significant;  * = statistically significant.

    2  High probability that samples were contaminated during taking and handling; data not usable.
        TABLE 6  Distribution of bromophos-ethyl residues in cattle tissue, 1968


              Sample interval                         Residues (ppm)1,2
    Animal    (days after         Fillet    Roasting  Kidney    Liver     Kidney    Subcutaneous
              last treatment)               beef                          fat       fat

    924       1                   0.015     0.015     0.010     <0.005    0.132     0.056

    621       1                   0.017     0.006     0.006     <0.005    0.193     0.065

    110       3                   0.010     0.008     0.007     <0.005    0.236     n.a.

    102       3                   0.007     0.007     0.010     <0.005    0.219     n.a.

    605       7                   <0.005    <0.005    <0.005    <0.005    0.218     n.a.

    228       7                   <0.005    0.010     <0.005    <0.005    0.183     n.a.

    1  n.a. = not analyzed.

    2  Determination by gas chromatography, mean of three determinations.

    Bromophos-ethyl residues in milk from three dairy cows each sprayed
    with two gallons of 0.05% active ingredient are shown in Table 10
    (Snelson, 1968).

    Dipping of dairy cows likewise gives rise to significant residues in
    milk which are all transferred to the butterfat. The level of residues
    in the milk of dipped cows was only slightly higher than those
    reported in Table 10 (Snelson, 1972). The residue level reached a peak
    on the first and second days after dipping and thereafter declined
    rapidly, with a half-life calculated to be between 1-2 and 1-4 days.

    TABLE 7  Bromophos-ethyl residues in fat of beef cattle, trial 1


    Post-treatment day       Group 1,                 Group 2,
                             1 treatment (ppm)        3 treatments (ppm)

    1                        0.08 - 2.9               0.3 - 2.6
    4                        0.1 - 2.0                0.1 - 1.6
    8                        Nil - 0.7                Nil - 0.6

    TABLE 8  Bromophos-ethyl residues in fat of steers, trial 2


    Interval between                   Residues (ppm)
    treatment and      Liver    Kidney    Muscle     Omental    Perirenal
    sampling (days)                                  fat        fat

    4                  <0.05    <0.05     <0.05      0.82       0.63
                       <0.05    <0.05     <0.05      0.62       0.36

    7                  <0.05    <0.05     <0.05      0.70       0.63
                       <0.05    <0.05     <0.05      0.21       0.45

    21                 <0.05    <0.05     <0.05      0.24       0.31
                       <0.05    <0.05     <0.05      0.40       0.29

    TABLE 9  Bromophos-ethyl residues in cattle after dipping


    between                       Residues bromophos-ethyl (ppm)
    last dipping          dipped once                 dipped 3 times
    and slaughter   Internal      Subcutaneous    Internal      Subcutaneous
    (days)            fat            fat            fat            fat

    1               0.15 - 0.23   0.13 - 0.26     1.47 - 3.36   1.2 - 2.32

    4               0.21 - 0.37   0.15 - 0.27     1.38 - 1.83   0.5 - 2.05

    8               0.36 - 0.87   0.23 - 0.50     2.04 - 2.48   0.78 - 2.56

    TABLE 10  Bromophos-ethyl residues in milk


                     Time after         Residues (ppm)
    Treatment        treatment    in butterfat      in milk

    Nexagan 0.05%    5            0.03              0.002
    application)     21           1.01              0.072

                     29           0.71,0.67,0.42    0.038,0.026,0.017

                     45           1.17,0.48,0.60    0.060,0.028,0.026

                     53           0.79,0.60,0.47    0.042,0.028,0.021

                     69           0.47              0.017

                     77           0.63              0.038

                     93           0.25              0.016

                     10 days      0.02              0.001

    In trials in Germany (Boehringer, 1968), three cows were each sprayed
    with 5 liters of 0.05%. a.i. suspension and milk samples were taken
    during the following four days. A second treatment was performed seven
    days later without sampling. A third treatment followed 14 days after
    the start of the trial, and subsequent milkings were analyzed for a
    total time of 21 days. Maximum residues (0.098, 0.077, 0.089 ppm) were
    found about 24 hours after treatment, decreasing within about four
    days below the limit of determination (<0.02 ppm). There was no
    accumulation of residues after the third treatment.


    General comments

    By analogy with bromophos, the major metabolites of bromophos-ethyl
    would be expected to be 2,5-dichloro-4-bromophenol, bromoxon-ethyl,
    and desethyl bromophos-ethyl (see Figure 1 of preceding bromophos
    monograph). The major points of difference appear to be that no
    desethyl-bromophos-ethyl is found after oral administration to rats
    and that somewhat higher ratios of bromoxon-ethyl to bromophos-ethyl
    is found in plants, especially lettuce (Eichler, 1971).

    In animals

    The metabolism and excretion of 3H-labelled bromophos-ethyl in the
    rat was studied by Stiasni (1967). No specific organic accumulation
    occurred following oral and parenteral administration. Quantitative
    excretion occurred between 8 and 12 days. Neither unchanged
    bromophos-ethyl nor bromoxon-ethyl could be found in the excrements
    following oral administration. Desethyl-bromophos-ethyl was also
    missing among the metabolites. The only metabolites identified were
    dichloro-bromophenol and its conjugates.

    In plants

    No tests have been carried out with radioactively labelled
    bromophos-ethyl in plants. However, in connection with supervised
    trials for determining residues in fruits and vegetables,
    bromoxon-ethyl residues were determined in apples, Brussels sprouts
    and lettuce (Eichler, 1971). In apples, the bromoxon-ethyl residues
    never exceeded 0.005 ppm (<1% of bromophos-ethyl residue). In
    Brussels sprouts, the highest bromoxon-ethyl residue found was 0.026
    ppm (5% of bromophos-ethyl residue). In lettuce, after several
    sprayings, bromoxon-ethyl residues reached a maximum of 0.07 ppm (6.4%
    of bromophos-ethyl residue) in three days. The highest ratio found was
    8.8% (0.014 ppm) after 14 days.

    In soil

    Bromophos-ethyl E.C. was applied one time at 0.5 g a.i./m2 to high
    moorland soil (acid, high organic content), Ingelheim sand and clay
    soil. Zero to 20 cm-deep samples were taken periodically for 26 weeks
    and analyzed with the results shown in Table 11 (Eichler, 1970).

    In comparison with bromophos, bromophos-ethyl degrades somewhat more
    slowly in soil; however, neither compound shows any significant

    In storage and processing

    Leber and Deckers (1968) examined the effects on residues in beef
    under storage at +4° and -18°C and after cooking (roasting). No
    significant decrease in residues was observed in meat, kidney and
    kidney fat after a 7-day storage period at +4°C or after a 30-day
    storage period at -18°C. Neither 15 minutes of frying of 100 g steaks
    nor one hour of boiling of 100 g of beef in 200 ml of water resulted
    in any significant decrease in residues of bromophos-ethyl.

    Evidence of residues in food in commerce or at consumption

    In connection with a tick eradication program in Australia, perirenal
    fat from 17 cattle known to have been dipped in 0.05% Nexagan on 27
    occasions over a period of 14 months was analyzed for residues
    (Harvey, 1968). Three samples had residues between 0.5 and 1.0 ppm,
    five between 1.0 and 1.5 ppm, seven between 1.5 and 2.0 ppm and two
    samples had 2.18 and 2.68 ppm, respectively.

    TABLE 11  Bromophos-ethyl residues in soil


                                                   Residues (ppm)1
    Type of             Post-treatment                          Dichloro-
    soil                time (weeks)        Bromophos-ethyl     bromophenol

    High moorland       0                   13.302              <0.10
                        1                   6.26                <0.10
                        3                   4.95                0.54
                        6                   3.92                <0.10
                        9                   3.29                0.60
                        13                  3.44                1.30
                        26                  1.25                <0.10

    Sandy               0                   2.343               <0.10
                        1                   1.40                <0.10
                        3                   0.64                0.13
                        6                   0.40                <0.10
                        9                   0.16                <0.10
                        13                  0.12                <0.10
                        26                  <0.02               <0.10

    Clay                0                   2.764               <0.10
                        1                   2.16                <0.10
                        3                   0.44                0.17
                        6                   0.32                <0.10
                        9                   0.26                <0.10
                        13                  0.14                <0.10
                        26                  <0.02               <0.10

    1  Values calculated as dry substance from the measured moisture

    2  Y = 0.844-0.032 log X;     r = 0.9173

    3  Y = 0.128-0.076 log X;     r = 0.9721

    4  Y = 0.175-0.076 log X;     r = 0.9544

    Samples of internal fat taken from animals, with unknown treatment
    history, being slaughtered in the cattle tick zone in Australia during
    1971/72 revealed some to contain bromophos-ethyl residues. Of 1 055
    samples examined, 52 contained bromophos-ethyl, mostly below 0.5 ppm,
    the highest being 0.8 ppm (Snelson, 1972). During the same period 589
    samples of butter and cheese were examined for organo-phosphorus
    residues. Only three samples were found to contain bromophos-ethyl
    residues, all at 0.1 ppm.


    Many general and specific chemical, biochemical and biological methods
    of analysis have been developed for residues of bromophos-ethyl. These
    have recently been reviewed and summarized by Eichler (1971). A method
    has been developed by Leber and Deckers (1968) for all crops and
    animal tissues. It utilizes gas chromatography with a phosphorus
    specific detector and can estimate quantities down to the range of
    0.001 to 0.01 ppm with a 100 g sample. The method includes procedures
    for determining bromoxon-ethyl either by colorimetry or by gas
    chromatography with a sensitivity of 0.03 to 0.05 ppm. Confirmation of
    residues can be accomplished by the thin-layer chromatographic
    techniques suggested in the method.

    Bromophos-ethyl is among the pesticides listed as being detectable by
    the multi-residue gas chromatographic procedure of Abbott et al.
    (1970), and that method is the most suitable for regulatory use. The
    method of Leber and Deckers would be suitable for confirmation of the
    identity of residues.


    Examples of national tolerances of bromophos-ethyl residues are
    reported in Table 12.

    TABLE 12  Examples of national tolerances as reported to meeting


    Country             Commodity                          Tolerance

    Australia           Fat of meat of cattle
                        and sheep                          3 ppm

                        Milk and milk products
                        (fat basis)                        1 ppm

    The Netherlands     Fruit and vegetables               0.4 ppm


    Bromophos-ethyl is a non-systemic halogen-containing organo-phosphorus
    insecticide and acaricide used on fruit, vegetables, field crops,
    cereals, maize, rice, cotton and tobacco. It is also used extensively
    in tick control, for other ectoparasites of domestic animals and as a
    mosquito larvicide.

    Supervised trials with foliar treatments on fruits and vegetables have
    shown that bromophos-ethyl is somewhat more persistent than bromophos
    and requires a pre-harvest interval about twice as long. The rate of
    residue decline is highly dependent on many factors, especially
    botanical species and morphological structure, which require that
    tolerance recommendations be made on an individual commodity basis
    rather than on broad crop categories.

    Groups of beef cattle were sprayed at recommended rates one or more
    times in trials in several countries. Highest residues were found in
    omental, heart and perirenal fat, ranging in one trial from 0.1 to 2.0
    ppm at four days post-treatment.

    Spray treatment of dairy cows at recommended rates resulted in a
    residue maximum of 1.17 ppm in butterfat at 45 hours post-treatment.
    This fell to 0.02 ppm in butterfat after ten days. There was no
    accumulation of milk residues from the multiple treatments.

    The metabolites of bromophos-ethyl most likely to be found are
    2,5-dichloro-4-bromophenol and bromoxon-ethyl. Only
    dichloro-bromophenol and its conjugates were found in the excrement of
    rats after oral administration of labelled bromophos-ethyl. The
    dichloro-bromophenol also appears to be the only soil metabolite.
    Although no studies have been conducted with the labelled compound in
    plants, supervised field trials have shown small amounts of
    bromoxon-ethyl residues in apples, Brussels sprouts and lettuce (up to
    0.07 ppm in the latter case).

    Available multi-residue gas chromatographic procedures are suitable
    for use for regulatory purposes and are recommended.

    Although bromophos-ethyl is recommended for cereals, maize, cotton,
    rice and in animal health, there were no data available for these
    commodities except fat of meat of cattle and milk. Therefore, no
    recommendations could be made for tolerances on these commodities.



    The following temporary tolerances are recommended for


    Apples, carrots, fat of meat of cattle,
    plums, pears, spinach                             2

    Brussels sprouts, redcurrants                     1

    Celeriac, gooseberries, peaches,
    rape seed oil, cherries (sweet)                   0.5

    Blackcurrants, lettuce                            0.2

    Rape seed, strawberries, cabbage                  0.1

    Kohlrabi, French beans                            0.05

    Cauliflower, beans (without pods),
    onions, sugarbeets, milk (whole)                  0.02*

    * at or about the limit of determination.


    REQUIRED (by 30 June 1975)

    Further studies evaluating the significance of urinary excretion of
    ascorbic and dehydroascorbic acids and its relevance to man.

    REQUIRED (before tolerances can be recommended)

    Residue data from supervised trials on maize, rice and other cereals,
    cotton, domestic animals, other than cattle, and milk products.


    A study to determine dose levels causing no carboxyl-esterase
    (aliesterase) activity depression.


    Abbott, D.C., Crisp, S., Tarrant, K.R. and Tatton, J. O'G. (1970)
    Pesticide residues in the total diet in England and Wales, 1966-1967.
    III. Organo-phosphorus pesticide residues in the total diet. Pestic.
    Sci. 1: 10-13.

    Anonymous. (1970) Utrecht report, project CvF/PD4.2.(2.2.03).

    Barnes, J.M. (1968) WHO insecticide evaluation and testing programme.
    Stage I - mammalian toxicity report. Medical Research Council,
    Carshalton. (unpublished).

    Battelle Institute. (1964) Toxicity tests with the substance S2225 in
    rats, guinea pigs and rabbits. (unpublished)

    Boehringer. (1966) Residue trials and examination of cholinesterase
    activity after spraying with bromophos-ethyl on cattle. Report C.H.
    Boehringer Sohn.

    Boehringer. (1967) Investigations concerning absorption, distribution,
    excretion and metabolism of bromophos-ethyl-3H in rats. Report C.H.
    Boehringer Sohn. (unpublished)

    Boehringer. (1968) Determination of residues of bromophos-ethyl in
    cattle. Report C.H. Boehringer Sohn.

    Boehringer. (1971-1972) Residue investigation reports, C.H. Boehringer

    Bradford, H.A. (1967) Acute dermal toxicity - bromophos-ethyl
    (compound 70625). Report Eli Lilly and Company. (unpublished)

    Eichler, D. (1971) Bromophos and bromophos-ethyl residues. Residue
    Reviews, 41: 65-112.

    Eichler, D. (1970) Report C.H. Boehringer Sohn "Uber den Abban von
    Bromophos und Bromophos-ethyl in verschiedenen Böden".

    Harvey, J.M. (1968) Bromophos-ethyl residues in meat products.
    Communication with C.H. Boehringer Sohn.

    Leber G. and Deckers, W. (1968) Determination of residues of bromophos
    and bromophos-ethyl. Proc. Brit. Insecticide Fungicide Conf.,
    Brighton, Eng. 4: 570.

    Leuschner, F. (1966) Reports C.H. Boehringer Sohn. (unpublished)

    Leuschner, F. (1967) Reports C.H. Boehringer Sohn. (unpublished)

    Leuschner, F., Leuschner, A., Schwerdtfeger, W., Pliess, G. and
    Standinger, H.J. (1968) About the short-term toxicity studies on
    bromophos-ethyl - charge 1487 - in Beagle dogs (with special attention
    to the toxicology of the adrenal gland). Report C.H. Boehringer Sohn.

    Leuschner, F., Leuschner, A., Schwerdtfeger, W., Pliess, G. and
    Dontenwill, W. (1969a) About the chronic toxicity of bromophos-ethyl
    in Wistar rats following oral application. Report C.H. Boehringer
    Sohn. (unpublished)

    Leuschner, F., Leuschner, A., Schwerdtfeger, W. and Otto, H. (1969b)
    About the chronic tolerance of bromophos-ethyl in the reproduction
    test over three generations of Wistar rats. Report C.H. Boehringer
    Sohn. (unpublished)

    Leuschner, F., Leuschner, A., Standinger, H.J., Schwerdtfeger, W. and
    Dontenwill, W. (1971) Two years oral toxicity study in Beagle dogs
    with bromophos-ethyl. Report C.H. Boehringer Sohn. (unpublished)

    Muacevic, G. (1964) Report on Shg 2225. Report C.H. Boehringer Sohn.

    Muacevic, G. (1966) Reports C.H. Boehringer Sohn. (unpublished)

    Muacevic, G. (1967) Reports C.H. Boehringer Sohn. (unpublished)

    Muacevic, G. (1968) Reports C.H. Boehringer Sohn. (unpublished)

    Muacevic, G. (1969) Reports C.H. Boehringer Sohn. (unpublished)

    Muacevic, G. (1970) Reports C.H. Boehringer Sohn. (unpublished)

    Snelson, J.T. (1968) Bromophos-ethyl residues in milk. Communication
    with C.H. Boehringer Sohn.

    Snelson, J.T. (1967 - 1968) Residue studies - bromophos-ethyl.
    Communications with C.H. Boehringer Sohn.

    Snelson, J.T. (1972) Results from experimental investigations and
    residue surveys with bromophos-ethyl following dipping in Australia.
    Report to Joint Meeting.

    Stiasni, M. (1967) Data from C.H. Boehringer Sohn. (unpublished)

    Stötzer, H., Herbst, M., Baumgartner, R. and Guęnard, J. (1970)
    Subacute dermal toxicity of the substance bromophos-ethyl in rabbits
    (New Zealand White). Report C.H. Boehringer Sohn. (unpublished)

    Terblanche. (1966) Toxicity of bromophos-ethyl. Department of
    Agricultural Technical Services, Onderstepoort, South Africa.

    Vuuren, P.J.J. (1964) Whale-blood cholinesterase levels in cattle
    sprayed at weekly intervals with S2225 (CELA). Agricura Laboratoria
    Ltd., Silverton, South Africa. (unpublished)

    See Also:
       Toxicological Abbreviations
       Bromophos-ethyl (WHO Pesticide Residues Series 5)
       Bromophos-ethyl (Pesticide residues in food: 1977 evaluations)