BROMOPHOS              JMPR 1972


    Chemical name



         Nexion(R), S 1942, SHG-1942, bromofos.

    Structural formula


    Other information on identity and properties

    Molecular weight: 366.0

    State: white crystals

    Melting point: 53°C

    Boiling point: 140-142°C at 10-2 torr.

    Vapour pressure: 1.3 x 10-4 mm Hg at 20°C

    Solubility:    soluble in most organic solvents, e.g., toluene,
                   carbon tetrachloride, diethyl ether. Slightly
                   soluble in low molecular weight alcohols. Water
                   solubility - 40 ppm at 27°C.


    Stable in aqueous suspension. Hydrolyzes in distinct alkaline medium.

    Purity of technical material:

    O-dimethyl-phosphorothioate: approx. 95.0%; 
    approx. 3.0%;
    approx. 1.0%;
    approx. 1.0% (chlorine position not defined).



    Absorption, distribution and excretion

    Studies on rats with 32P and 3H-labelled bromophos showed it is well
    absorbed from the gastrointestinal tract. In the first 12 hours
    following oral, intravenous or intraperitoneal administration, large
    quantities of radioactivity were found in the stomach, intestine,
    liver and kidneys, but after 24 hours the majority was found in urine
    and faeces. Bromophos showed no tendency to accumulate in any organ.
    The maximum blood level was found 7 hours after oral administration,
    and the biological half life in rats was 14 hours. Approximately 96%
    of the activity of a 10 mg/kg dose of 3H-bromophos was excreted in
    urine and 1% in faeces during 24 hours following oral administration.
    Excretion was complete in 96 hours, a total of 2% of activity
    appearing in the faeces. In the same period, administration of
    32P-bromophos resulted in the excretion of 63% of activity in urine
    and 16% in faeces. During 8 hours following intraduodenal
    administration of 5 mg/kg of 3H-bromophos, 25% of the activity was
    excreted in bile in rats. Since only 1% of 32P-bromophos was excreted
    in the same period, the biliary excretion was probably mainly
    dichlorobromophenol or its metabolites. Biliary excreted 3H is
    probably re-absorbed since only 2% of an oral dose was found in
    faeces. The relatively high 32P content in faeces may result from
    metabolism of bromophos in the intestine (Stiasni et al., 1967).


    Five urine metabolites were found after administration of
    32P-bromophos whereas three were found after administration of
    3H-bromophos. Analysis showed that the metabolites were phosphate,
    dimethylthionophosphate, monodesmethyl-bromophos and
    dichlorobromophenol. Two metabolites were unidentified. Bromophos
    itself, its O-analogue bromoxon and monodesmethyl-bromoxon were not
    found in urine (Stiasni et al., 1967).

    Effect on enzymes and other biochemical parameters

    Bromophos inhibits cholinesterase activity in rats and dogs, the
    no-effect level when administered over a 100-day period being 0.63
    mg/kg/day in rats and 1.5 mg/kg/day in dogs (Kinkel and Seume, 1963;
    Kinkel et al., 1965; Kinkel and Dirks, 1966; Boehringer, 1968;
    Leuschner et al., 1967). When a single oral dose of 800 or 1200
    mg/kg was given to horses, plasma cholinesterase was inhibited even
    after 16 days, although partial reactivation was found (Paton, 1965).


    Special studies on the metabolites

    Several metabolites were found during investigations on rats and dogs
    and on examination of metabolism of bromophos in plants. The most
    important of these have been examined. A summary of acute oral
    toxicities of bromophos metabolites is given in Table 1.

    Short-term toxicity of metabolites

    Groups of 10 male and 10 female rats were fed for 5 weeks on control
    diet or diet providing 25, 100 or 400 mg/kg/day bromoxon, 250, 500 or
    1000 mg/kg/day desmethyl-bromoxon or 250, 500 or 1000 mg/kg/day of
    2,5-dichloro-4-bromophenol. At the highest dosage levels with each
    metabolite the growth of animals was significantly inhibited. Plasma
    and RBC cholinesterases were inhibited by bromoxon at 25 mg/kg
    (maximum inhibition), and the plasma enzyme by desmethyl-bromoxon at
    500 mg/kg. No enzyme inhibition occurred with dichloro-4-bromophenol.
    The results of other investigations were normal; histopathological
    studies were not carried out (Leuschner, 1968)

    Groups of 10 male and 10 female rats were fed on diets providing 0,
    125, 250 and 500 mg/kg/day of desmethyl-bromophos for 5 weeks. At 500
    mg/kg, plasma cholinesterase was minimally inhibited. The weights of
    liver and pituitary were above normal in male animals and histological
    examination showed minimal centrilobular fatty infiltration of the
    liver, the latter finding was considered to be reversible. Body weight
    and food intake were reduced at the 500 mg/kg level. No abnormalities
    were found at lower dosage levels (Leuschner et al., 1969).

    Special studies on neurotoxicity

    Six adult hens were administered 10 g/kg body-weight of bromophos
    together with atropine and 2-PAM. Ataxia and incoordination were
    present in all birds for several days, and three died. Histological
    examination was said to reveal severe demyelination in all birds
    (Byewater, 1966).


    TABLE 1

    Acute oral toxicities of bromophos metabolites


    Compound                                                   Animal      LD50             Reference
                                                                       (mg/kg body-weight)

    Bromoxon                                                    Mouse       2 100            Muacevic, 1965
    Monodesmethyl-bromophos                                     Rat         1 900-4 600      Muacevic, 1965
                                                                Mouse       1 800            1966
    Desmethyl-bromophos                                         Mouse       1 085            Muacevic, 1968
    (triethylamine salt)
    Desmethyl-bromoxon                                          Mouse       2 150            Muacevic, 1965
    O,O-dimethyl-O-(5,6-dichloro-4-bromophenyl)-thiophosphoric  Mouse       2 850            Muacevic, 1965
    acid ester
    O,O-dimethyl-O-(4,6-dichloro-2-bromophenyl)-thiophosphoric  Mouse       about 2 000      Muacevic, 1965
    acid ester
    O,O-dimethyl-O-(2,4-dichloro-6-bromophenyl)-thiophosphoric  Mouse       >6 000           Muacevic, 1965
    acid ester
    O,O-dimethyl-thiophosphoric acid                            Mouse       4 700            Muacevic, 1965
    2,5-dichloro-4-bromophenol                                  Mouse       1 100-1 900      Muacevic, 1965
                                                                Rat         3 200-3 550      1966

    Ten adult hens each received orally 1 g bromophos/kg/day until signs
    of paralysis developed (between 12 and 56 days), at which time each
    was examined for histological changes in the brain and spinal cord.
    These were reported to consist of degeneration of ganglia cells and
    demyelination (Kinkel and Hubner, 1966), but the suitability of the
    material for accurate pathological interpretation was challenged
    (Glees, 1966).

    Two adult hens were each given 5.5 g/kg of bromophos in divided doses
    over a period of 7 weeks. A 300 mg/kg dose produced transient
    excitability and diarrhoea and the 4th of 5 and 4th of 8 consecutive
    doses of 400 mg/kg day given at a 3-week interval caused an unsteady
    gait and diarrhoea which persisted each time for 6-9 days after
    administration. The hens completely recovered following this
    treatment, indicating the lack of delayed neurotoxic effect (Barnes,
    1966). Ten adult hens received two oral doses of 2 g/kg of bromophos
    at 3-week intervals. A neuropathological examination carried out after
    a 3-week observation period revealed no degenerative processes in the
    CNS or peripheral nerves (Muacevic and Glees, 1967).

    Groups of 10 adult hens were administered 0, 12.5 or 125 mg/kg of
    bromophos/day in their food for 4 weeks. Clinically apparent
    neurological signs were reversible when treatment ceased and a
    neuropathological examination of 2 birds of each group showed no CNS
    changes (Muacevic and Glees, 1968).

    In order to investigate the occurrence of paralysis in dogs
    administered bromophos for 2 years, and the finding on
    neuropathological examination of localized ganglion cell degeneration
    and other lesions in the CNS (Kinkel et al., 1965), an experiment
    was carried out in which two groups of 3 male and 3 female dogs were
    administered 0 and 87.5 mg/kg and 6 male and 6 female dogs 175 mg/kg
    body-weight/day of bromophos orally in capsules for periods up to 270
    days. One dog on 175 mg/kg had a single epileptiform fit and another
    was killed after 62 doses because it was cachectic. An extensive
    neuropathological examination of the central nervous system, spinal
    ganglia and peripheral nerves failed to reveal any neuropathological
    changes (Boehringer, 1968).

    Special studies on pharmacology

    Bromophos inhibits cholinesterase activity indirectly through its
    metabolite bromoxon. No antidote effect was found with atropine
    sulphate and aldoximes when rats and mice were administered high doses
    of bromophos orally or intraperitoneally. The lack of effect was
    probably due to the toxic effect of the high doses of solvent which
    had to be used to administer the bromophos. However, cholinesterase
    inhibition was diminished in mice by atropine and Toxogonin (Muacevic,
    1965). Inhibition of brain cholinesterase in bromophos treated rats
    could be prevented by intravenous injection of several reactivators
    (Muacevic, 1968). Administration of atropine and 2-PAM stopped

    development of signs of poisoning when 0.02-0.2 g/kg body-weight of
    bromophos was administered to chickens. At 0.5 and 1.0 g/kg dosage
    levels the development of signs of poisoning were delayed (Kinkel,

    Special studies on reproduction

    Groups of 20 male and 20 female rats were fed on diets providing 0, 5,
    20 and 80 mg bromophos/kg/day. These formed the parent generation of a
    standard three generation study (F.D.A. advisory committee, 1970). The
    80 mg/kg dosage level produced no clinical signs of poisoning but the
    rate of body-weight gain was depressed in all generations,
    particularly in males. The fertility and size and weight of litters
    was unaffected, but the number of stillbirths in this group was high.
    The survival rate of young was also reduced except in the first litter
    and the parent generation. Animals consuming 5 or 20 mg/kg
    bromophos/day were no different from control animals. No runts or
    malformations were observed at any dosage or in any generation, and
    the behaviour, appearance, food intake, results of haematological
    investigations and adult survival were also unaffected. In this study
    the cholinesterase activity of plasma and liver was significantly
    depressed in animals receiving 5 mg/kg/day. The threshold dosage level
    for RBC enzyme inhibition was between 5 and 30 mg/kg and for brain
    enzyme between 5 and 20 mg/kg in males and 20 and 80 mg/kg in females
    (Leuschner et al., 1967).

    Special studies on teratogenicity

    Five groups of 10 pregnant female rabbits were administered by gavage
    25, 50, 100, 200 or 400 mg/kg body-weight of bromophos each day
    between day 6 and 18 of pregnancy. Forty animals acted as controls.
    Foetuses were removed and examined on day 30 of pregnancy. Twenty five
    mg bromophos/kg/day orally had no untoward effect on foetuses or
    parent animals. At higher dosage levels the parent animals became
    debilitated and developed limb flaccidity and diarrhea, and the number
    of fully-grown, live foetuses was reduced. In no group did the type or
    number of malformations observed differ from that of the controls
    (Leuschner and Leuschner, 1966a).

    Acute toxicity

    Studies on the acute toxicity of bromophos in several animal species
    are summarized in Table 2.

    TABLE 2  Acute toxicity of bromophos in animals

    Animal         Route     LD50              References

    Mouse          oral      3 311 - 5 900     Muacevic, 1963; 1964;
                                               1965; 1967;
                                               Worth et al., 1967

    Mouse          i.p.      1 000 - 4 900     Oettel, 1963; Muacevic,

    Rat            oral      3 750 - 8 000     Kinkel et al., 1966;
                                               Oettel, 1963; Muacevic,

    Rat            i.p.      3 125             Kinkel and Sann, 1964.

    Guinea pig     oral      >6 000            Muacevic, 1967

    Rabbit         oral      720               Muacevic, 1964

    Fowl           oral      9 700             Kinkel, 1964a

    Dog            oral      >625              Worth et al., 1967

    Potentiation of the acute toxicity of bromophos occurred with
    bromophos-ethyl, diazinon, dichlorvos, dimethoate, malathion,
    mevinphos, naleb, parathion and carbaryl. DDT, heptachlor and lindane
    possessed strong antagonistic activity to the acute effects of
    bromophos (Kinkel, 1964b; Muacevic 1964, 1965, 1966, 1967, 1968).

    Short-term studies


    Four groups of 6 male and 6 female rats received diets providing 0,
    0.65, 1.25 and 2.5 mg bromophos per kg body-weight/day for 100 days.
    The cholinesterase activity in RBC was not significantly affected at
    any dosage level. Plasma enzyme was inhibited at the 1.25 mg/kg level,
    but not at the lower level, and it returned to normal in two weeks
    after the treatment was stopped. The behaviour, growth, food intake
    and macroscopic appearance of organs were normal (Leuschner and
    Leuschner, 1966b).

    Four groups of 16 male rats received by gastric tube daily doses of 0,
    188, 750 and 1 250 mg bromophos/kg body-weight/day for 100 days. The
    rate of body-weight gain was reduced in all test groups while food
    intake was lower only at the highest level. Animals in the 750 and
    1 250 mg/kg groups became restless for an hour or so after treatment
    but the degree of restlessness did not increase during the test.
    Brain, liver and plasma cholinesterase were inhibited at all dosage
    levels. Hydropic swelling of the hepatic cells was seen at all dosage
    levels; this effect was dose related. In the 1 250 mg/kg group hyaline
    droplets were seen in tubular cells and protein within the tubules of
    the kidneys. Urine analysis and the bromosulphophthalein retention
    test yielded negative results. Haematological findings and the
    macroscopic appearance of internal organs were normal (Kinkel and
    Seume, 1963).


    Three groups of 2 male and 2 female beagle dogs received diets
    providing 0.75, 1.5 and 3.0 mg bromophos/kg/day for 100 days. The
    control group consisted of one male and one female. No or only slight
    inhibition of the plasma and RBC cholinesterase activities (never
    exceeding 36%) was observed at the three dosage levels; an inhibition
    of 20% was suggested as no-effect level in this experiment.
    Erythrocyte cholinesterase was more susceptible to inhibition than
    plasma cholinesterase. In one dog exposed to the lowest dosage level,
    35% inhibition of the RBC cholinesterase was observed, but this was
    reduced to 20% when tested seven weeks later. Neither the brain nor
    the liver cholinesterase was found to be inhibited when examined
    (Kinkel and Dirks, 1966).

    Six groups of 3 male and 3 female mongrel dogs aged 1-3 years and
    weighing between 3.9 and 10.3 kg were administered 0, 11, 43.8, 87.5
    and 175 mg bromophos/kg body-weight by gastric tube on every working
    day for 2 years. Treatment at the 87.5 and 175 mg/kg levels made the
    animals restless for some time after dosage. One animal on each of the
    43.8 and 175 mg/kg levels died after suffering bites, and one on 87.5
    and 3 on 175 mg/kg died after developing respiratory difficulties,
    hoarseness, salivation and tremors followed by ataxia and then paresis
    of the hind limbs. Two dogs of the 175 mg/kg group developed the same
    signs but recovered, one after being taken off treatment and the other
    while administration of bromophos continued. Histological examination
    of the animals which died on the two highest dosage levels showed foci
    of ganglion cell degeneration in the spinal cord; this involved only
    small numbers of cells in the ganglia. In addition, spermatogenesis
    was impaired with proliferation of Leydig's cells in 2 males of the
    175 mg/kg group. Degeneration of the CNS in animals which did not die
    during the test was insignificant or non-existent. Plasma, RBC, liver
    and brain cholinesterase activities were depressed at all dosage
    levels in this test. The food intake, growth, sexual cycle, urinary
    ascorbic acid excretion and the results of haematological, liver
    function and urine tests were similar in test and control groups. The

    relative organ weights and results of macroscopic and microscopic
    examination of organs were normal in the 11 and 43.8 mg/kg groups
    (Kinkel et al., 1965).
    In a nine month study (See special studies on 
    neurotoxicity) groups of mongrel dogs weighing 6-20 kg were
    administered 0, 87.5 or 175 mg bromophos/kg body-weight 
    daily in capsules for 270 days. Body-weight and food intake were
    reduced in accordance with the dose given. Although 2/6 bitches on
    175 mg/kg/day were at no time on heat, histological examination of
    the ovaries and uterus revealed no pathological findings.
    Histological examination showed seminiferous tubule degeneration in
    3 dogs receiving 175 mg/kg/day. Prostatic hypertrophy was also more
    evident in test animals. The death of one dog of the high level group
    was not regarded as being due to bromophos consumption. Erythrocyte
    and plasma cholinesterase were inhibited in both test groups. The
    results of haematological tests, serum analysis and urine analysis
    were all normal (Boehringer, 1968).

    Long-term studies


    Groups of 6-month-old rats were administered 0, 87.5, 175 and 350 mg
    bromophos/kg body-weight by gavage each working day for 2 years. The
    groups consisted of 25 male and 25 female animals, but 3, 5, 5 and 17
    animals were included in the test after the start in the 0, 87.5, 175
    and 350 mg/kg dosage groups, respectively. After 8, 10, 12, 15, 18 and
    21 months, two animals, one of each sex, were killed for
    histopathological examination. The rate of body-weight gain was
    depressed at the highest dosage level, and in this group proteinuria
    was more evident than in controls; in addition, the number of
    erythrocytes in the urinary sediment was increased but the kidneys
    were histologically normal.

    Cholinesterase was inhibited in the plasma, RBC, brain and liver by
    all treatment levels. Survival was poor, with only 5, 4, 2 and 5 males
    and 9, 6, 7 and 8 females of the 0, 87.5, 175 and 350 mg/kg groups,
    respectively, surviving for 100 weeks. The behaviour of all test
    groups was normal as were the results of haematological and liver
    function tests. Urinary ascorbic acid excretion was unaltered by
    bromophos administration. The weights of 8 organs and the results of
    macroscopic and microscopic examinations revealed no lesion which
    could be attributed to treatment. No tumours were reported to have
    occurred in control or test groups (Kinkel et al., 1965).


    Workers exposed to bromophos during production and formulation for two
    years showed no change in RBC cholinesterase levels as estimated at
    monthly intervals (Boehringer, 1966). Eight subjects were engaged in
    spraying bromophos for 6´ hours over a period of 2 days, and 5 sprayed
    for 4 hours a day on 14 days during a 22-day period in trials at the
    WHO Insecticide Testing Unit, Lagos. Protective clothing was worn. No
    clinical symptoms occurred, but plasma cholinesterase levels were
    slightly depressed, the lowest being 75% of the pre-exposure level.
    Levels returned to normal after one month (WHO, 1967).


    Bromophos is rapidly absorbed, metabolized and excreted, mainly in the
    urine. The compound potentiates the activity of several
    organo-phosphates and carbamates, but its acute effects are
    antagonized by some chlorinated hydrocarbons. The data on
    neurotoxicity are contradictory and hence unsatisfactory. However, the
    studies said to give positive results were poor, and the Meeting felt
    that the compound was unlikely to cause neuropathy.

    A reproduction study in rats showed no effect at 20 mg/kg/day.
    Increased stillbirths and decreased pup weight were evident at 80

    Short-term studies in rat showed no effects on plasma cholinesterase
    at 0.63 mg/kg/day. Somewhat higher doses caused erythrocyte
    cholinesterase depression. At much higher doses brain cholinesterase
    depression occurred. Hydropic swelling of hepatic cells at 188
    mg/kg/day and hyaline droplets in tubular cells and protein in kidney
    tubules at 1 250 mg/kg/day were observed.

    Short-term studies in dog indicated no effect on plasma cholinesterase
    at 1.5 mg/kg/day. At 175 mg/kg/day impaired spermatogenesis was

    A long-term study in rat did not reveal any tumours, but survival was
    poor at termination of the study.

    Although the studies were considered poor by present day standards,
    the Meeting decided that data were adequate to permit establishment of
    a temporary ADI.


    Level causing no toxicological effects

         Rat: 0.63 mg/kg body-weight/day

         Dog: 1.5 mg/kg body-weight/day


         0 - 0.006 mg/kg body-weight



    Bromophos is an insecticide with contact and stomach action. It is
    effective against a broad spectrum of chewing and sucking insects and
    possesses a very low mammalian toxicity. It can be used as an
    emulsifiable concentrate, ULV concentrate, wettable powder, granular
    or dust formulation, seed dressing, aerosol formulation and fog
    solution. It is compatible with other insecticides and fungicides.
    Bromophos is of moderate toxicity to bees and should not be sprayed on
    flowering crops during the flight of bees.

    Bromophos has been used in the majority of European countries as well
    as Algeria, Canada, Kuwait, Mexico, New Zealand, Nicaragua, Pakistan,
    South Africa, Syria and Venezuela.

    Pre-harvest treatments

    Bromophos is used on various crops, mainly fruit and vegetables, for
    control of a large number of important sucking and chewing insect
    pests, such as vegetable root maggots, aphids, sawflies, fruit flies,
    codling moths, mangold fly and beetles.

    According to the single crop and the main pest species occurring, the
    recommended concentrations of spray wash are given between 0.02% and
    0.1% a.i.; the application rates range from 0.4 kg to 1.5 kg a.i./ha.

    Bromophos is suitable for the treatment of a number of crops, except
    for certain susceptible varieties of grape, pear, melon, cucumber,
    lettuce and cabbage, mainly as frequent short interval treatments. Use
    in glasshouses is not recommended.

    The withholding periods range from 1 day to 21 days, depending on
    local conditions and crop.

    Post-harvest treatments

    Bromophos is registered and recommended for storage pest control in
    Mexico, South Africa, Spain and the United Kingdom and is currently
    being introduced into other European and overseas countries.

    Application of between 6 ppm and 12 ppm is recommended for grain
    protection against various species of weevil and beetle causing damage
    to stored products.

    Other uses

    Bromophos is used for the indoor and outdoor control of pests of
    hygienic importance. As it shows a good effect against larval as well
    as against adult stages and as it has a very low mammalian toxicity,
    bromophos has proved to be an effective and safe compound for public
    health operations. Furthermore, this material is recommended in the
    veterinary field against chicken mites and other ectoparasites on
    domestic animals and is highly effective against blowflies on sheep.


    Residue data are available from supervised trials on a variety of
    fruits, vegetables, field crops and stored wheat (Boehringer,
    1965-1971). Summaries of much of this information, and additional data
    as well, have been published recently (Eichler, 1971). Table 3
    presents a summary of available data, together with relevant
    information on rates of application, number of applications and
    pre-harvest interval.

    In one reported trial, stored wheat that had been treated with
    bromophos at 3 rates was milled into flour and the flour baked into
    bread (Boehringer, 1965-1971). Analysis at each step gave the results
    shown in Table 4.

    Thus, less than 10% of the original amount of pesticide applied to
    wheat is carried through to the final product, bread.

    Data are also available on residues resulting from supervised trials
    in animals.

    Four lambs were dipped in 0.5% bromophos weekly for 9 weeks. Omental
    biopsies were performed up to 22 days after the final dipping and the
    fat samples analyzed by microcoulometric gas chromatography. Residues
    of bromophos ranged from 5-14 ppm on day 1 to 0.07-0.43 ppm on day 22.
    Bromoxon and 2,5-dichloro-4-bromophenol were not determined (Clark
    et al., 1966).

        TABLE 3 Bromophos residues on several crops


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

    Cauliflower         0.06    g/m2        1             0               4.901
                                                          7               0.041
                                                          14              <0.021

    Broccoli            0.05    g/plant     1             62              <0.10

    Kidney beans        0.06    g/m2        1             0               0.62-1.50
                                                          7               0.26-0.56

    Cucumbers           0.04    g/m2        1             0               0.15-0.45
                                                          7               0.03-0.05

    Garden lettuce      0.015   g/m2        1             4               1.9-2.6
                        0.025   g/m2        1             4               0.34-0.60
                                                          7               0.09-0.26

    Lambs lettuce       0.025   g/m2        1             7               0.94-1.17

    Kohlrabi            0.04    g/m2        1             7               <0.02
                        0.06    g/plant     1             30              0.04

    Leek                0.8     kg/ha       1             0               2.76-2.80
                                                          14              1.27-1.43

    Carrots             0.25    g/m2        2             38              2.90-3.55
                        0.2     g/m2        2             45              0.89-1.03
                                                          80              0.58-0.59

    Peas                0.04    g/m2        1             7               <0.03

    Radish              0.25    g/m2        1             16              1.03-1.32
                                                          21              0.12-0.23

    Celery              120     g/ha        4             75              <0.05 (stalks)
                                                                          0.32-0.55 (leaves)

    Spinach             0.04    g/m2        1             1               5.48-7.85
                                                          7               0.25-0.67
                                                          14              <0.03-0.16

    TABLE 3 (Cont'd.)


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

    Red cabbage         0.05    g/m2        1             7               <0.08

    White cabbage       0.05    g/m2        1             7               <0.06-0.10

    Savoy cabbage       0.06    g/m2        1             1               1.18-2.70
                                                          7               0.57-1.00
                                                          14              0.03-0.42

    Onions              0.1     g/m2        1             123             <0.02

    Maize               2.0     kg/ha       1             75              <0.17

    Sugar beets         0.06    g/m2        1             14              <0.15-0.22 (beet)
                                                                          1.1-1.9 (leaves)

    Wheat               114     g/ha        1             14              0.17
                        228     g/ha        2             45              <0.02

    Rape                228     g/ha        1             49              0.09 (seed)
                                                                          0.17 (oil)

    Apples              2.0     g/tree      1             0               1.10-1.20
                                                          4               1.49-1.70
                                                          7               0.51-1.30
                                                          14              0.48-0.61

    Pears               1.25    g/tree      1             8               0.59-0.77

    Yellow plums        0.62    g/tree      1             7               0.512

    Cherries            2.5     g/tree      1             1               1.103
                                                          7               0.363

    Peaches             0.38    g/tree      1             7               0.03-0.13
                                                          14              <0.03-0.25

    Blackcurrants       0.25    g/shrub     1             7               0.13-0.36

    Redcurrants         0.25    g/shrub     1             7               0.64-0.74
                        0.8     kg/ha       1             0               0.56-0.61
                                                          7               0.11-0.13

    TABLE 3 (Cont'd.)


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

    Blackberries        0.25    g/shrub     1             7               0.14-0.19

    Strawberries        0.8     kg/ha       1             0               0.61-0.64
                                                          7               0.11-0.12

    Gooseberries        0.8     kg/ha       1             0               0.20-0.25
                                                          7               0.06-0.07
                        0.25    g/shrub     1             7               0.40-0.43

    Olives              4.5     g/tree      1             10              2.58-2.92

    Olive oil           4.5     g/tree      1             10              3.00-3.15

    Stored wheat        0.012   g/kg        1             0               8.0
                                                          122             5.6
                                                          365             5.3

    1 average of 4 analyses; raw data not available.
    2 average of 9 analyses; raw data not available.
    3 average of 6 analyses; raw data not available.

    TABLE 4  Bromophos residues in wheat and wheat products


    Rate of        Post-treatment            Residues (ppm)
    application    interval (days)    Wheat      Flour        Bread

    6 ppm          270                1.32       1.20         0.38-0.41

    12 ppm         270                3.00       2.65-2.90    0.78-0.87

    25 ppm         880                4.57       3.98-4.25    1.14-1.16


    Milk from ten cows was analyzed for residues after stall spraying at
    0.5 g/m2 of wall surface. Five cows were present during the spraying
    and five were removed. Milk from the latter cows did not contain
    measurable amounts of bromophos (<0.02 ppm). Milk from the five cows
    left in the stalls during treatment had residues of 0.032-0.042 ppm on
    post-treatment day 1; 0.031-0.045 ppm on day 2; 0.026-0.034 ppm on day
    3; and <0.020 on day 5 (Boehringer, 1965-1971).


    General comments

    The metabolism or degradation of bromophos appears to be similar in
    plants and animals, with the exception that hardly any bromoxon is
    found in animals whereas low levels of bromoxon are likely to be
    encountered in plant material. This is summarized in Figure 1.

    FIGURE 1

    In animals

    The absorption, distribution and excretion of 32P and 3H-labelled
    bromophos administered to rats by various routes are discussed in the
    preceding section on BIOCHEMICAL ASPECTS.

    The decomposition of 32P-labelled bromophos following cutaneous
    application to lactating cows (20 mg/kg in alcohol or paraffin oil)
    was studied by Dedek and Schwarz (1969). No bromoxon was detected in
    blood or milk by thin-layer chromatography. Concentrations of 0.4 to
    0.7 ppm of desmethyl-bromophos and traces of bromophos were present.

    The two methyl groups of bromophos appear to be simultaneously split
    off by mild alkaline hydrolysis and by the action of a
    glutathione-dependent liver enzyme (Stenersen, 1969a, 1969b).

    In plants

    In studies on tomato plants using 32O and 3H-labelled bromophos, it
    was found that it does not act systemically but penetrates from the
    surface into the interior of the leaf and also from a nutrient
    solution into the root. In addition to unchanged bromophos,
    dichlorobromophenol was found as a main metabolite (13% of the total
    dose applied after 7 days) and small amounts of bromoxon,
    monodesmethyl-bromophos, dimethyl thionophosphate and inorganic
    phosphate were detected (Stiasni et al., 1969).

    The metabolism of bromophos-32P was studied in wheat-, carrot-, and
    onion-seedlings and by soil microorganisms (Stenerson, 1969). The main
    finding was that bisdesmethyl-bromophos had been produced in several
    of the experiments, but no desmethyl-bromophos was detectable.
    However, the identification of bisdesmethyl-bromophos was not certain.

    In soil

    Bromophos E.C. was applied one time at 0.5 g a.i./m2 to high moorland
    soil (acid, high organic), Ingelheim sand and clay soil. Zero to 20
    cm-deep samples were taken periodically for 26 weeks and analysed for
    bromophos and dichloro-bromophenol residues, with the results shown in
    table 5.

        TABLE 5 Bromophos residues in soil


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

    High moorland       0                   13.102              0.30
    soil                1                   9.00                0.26
                        3                   8.18                1.14
                        6                   6.95                0.57
                        9                   2.15                1.72
                        13                  0.75                0.53
                        26                  0.58                0.93

    Sandy soil          0                   1.433               0.65
                        1                   0.64                0.53
                        3                   0.20                0.20
                        6                   0.13                0.10
                        9                   <0.02               0.10
                        13                  <0.02               0.10
                        26                  <0.02               0.10

    Clay soil           0                   1.544               0.59
                        1                   0.81                0.29
                        3                   0.20                0.21
                        6                   0.09                <0.10
                        9                   <0.02               <0.10
                        13                  <0.02               <0.10
                        26                  <0.02               <0.10

    1  Values calculated as dry substance from the measured moisture

    2  Y = 1.006-0.056 log X;     r = 0.9188

    3  Y = 0.047-0.187 log X;     r = 0.9777

    4  Y = 0.095-0.201 log X;     r = 0.9890
    Degradation of bromophos is clearly much more rapid in sandy and clay
    soils. When the sandy soil was treated once at the same rate with
    bromophos granules, the residues (corrected for moisture in sample)
    fell from 5.98 ppm at week 0 to <0.02 at week 26. Although initial
    residues were higher than for E.C., no measurable residue remained
    after 26 weeks (Boehringer, 1965-1971). The generally rapid
    degradation in soil was further indicated by trials in Germany with 3%

    coarse dust and 5% granular applied one time at 2, 4, or 8 kg/ha which
    gave residues of 0.03-0.16 ppm after 92 days (Boehringer, 1965-1971)
    and by elaborate tests in the United States using a range of
    application rates, numbers of applications, sampling intervals and
    soils in diverse geographic and climatic areas. There was no
    appreciable build-up of residues or leaching down through soil to any
    extent observed for either bromophos or dichlorobromophenol (Tepe,

    In storage and processing

    Bromophos was applied to stored wheat grains at 10 ppm and the
    decomposition studied over a 10-week period. Although only traces of
    dimethylphosphorothionate were found, indicating that
    desmethyl-bromophos is the main phosphatase degradation product, large
    amounts of monomethyl-phosphorothionate were detected. Bromoxon was
    found only during the first 20 days in amounts up to 10 percent of the
    original bromophos level. Degradation of bromophos proceeded rapidly
    for about 7 days, then stopped for about 3 weeks due to the
    accumulation of desmethyl-bromophos, which inhibits phosphatase
    hydrolysis. After the desmethyl-bromophos had been degraded, bromophos
    degradation resumed. The level of free dichlorobromophenol did not
    increase significantly until degradation of desmethyl-bromophos was
    well underway, suggesting the formation of the phenol from the
    desmethyl or oxon compounds. When bromophos was applied to autoclaved
    grains, only dimethyl-phosphorothionate and dichloro-bromophenol were
    produced (Rowlands, 1966a).

    Oxidation of bromophos to bromoxon occurred in the seed coats and
    germs of wheat grains. Hydrolytic activity was found in the germ and
    endosperm (Rowlands, 1966b).


    Many general and specific chemical, biochemical and biological methods
    of analysis have been developed for residues of bromophos. These have
    recently been reviewed and summarized by Eichler (1971) and will not
    be elaborated here. An excellent method has been developed by Leber
    and Deckers (1968). It utilizes gas chromatography with a phosphorus
    detector and can estimate quantities down to the range of 0.001 to
    0.01 ppm with a 100-g sample. The method also includes procedures for
    determining bromoxon either by colorimetry or by gas chromatography
    with a sensitivity of 0.03 to 0.05 ppm. Thin-layer chromatographic
    procedures are also given for identifying residues.

    Since bromophos is among the pesticides listed as detectable by the
    multi-residue gas chromatographic procedure of Abbott et al. (1970),
    that method is the most suitable for regulatory use. The method of
    Leber and Deckers (1968) would be suitable for confirmation of the
    identity of residues.


    Some examples of tolerances in various countries were reported to the
    Joint Meeting and are listed in Table 6.

    TABLE 6  Examples of national tolerances reported to the Meeting


    Country                Commodity                            Tolerance

    Canada                 Apple                                1.5

    Germany, Federal       Berries, pome fruit, leaf
    Republic               vegetables, cabbage                  1.5

                           Stone fruit, legumes,                0.6
                           root vegetables

                           Field corn                           0.2

    Hungary                                                     2

    Netherlands                                                 0.5
                           Carrots                              1.5

    Germany, Democratic    Fruit, vegetables (except
    Republic               onions and potatoes)                 11

                           Animal fat, vegetable oil,
                           potatoes, onions, meat, fish,
                           eggs, milk, grain, baby foods        0

    South Africa           Stored maize                         8

    1  not more than 0.1 ppm oxon.


    Bromophos is a non-systemic halogen-containing organophosphorus
    insecticide used on a wide variety of crops and animals to control
    biting and sucking insects. It is also used to protect stored
    products, as a seed protection agent for grain crops and as a vector
    control agent in public health.

    Supervised experiments with foliar, row or surface treatments on
    fruits and vegetables have shown bromophos to have a generally low
    persistence. However, the comparative rate of residue decline is
    highly dependent on many factors, such as botanical species,
    morphological structure, weather formulation, and method and time of
    treatment. The lipophilic nature of the compound causes it to
    penetrate the cuticular wax of certain crops (for example - apples and
    pears) which delays release and degradation. This property makes it
    necessary for tolerance recommendations to be made on an individual
    commodity basis rather than on broad crop categories.

    On the basis of a single trial in which four lambs were dipped in 0.5%
    bromophos weekly for 9 weeks, it would appear that the compound did
    not accumulate excessively in the fat and was eliminated fairly
    rapidly after treatment ceased, dropping from about 10 ppm on day 1 to
    about 2 ppm on day 8 and to about 0.2 ppm after 22 days. Milk cows
    exposed to bromophos during stall treatment had low levels in the milk
    (0.045 ppm maximum) which fell below the limit of detection (0.20 ppm)
    after five days.

    The metabolite of bromophos most likely to be found in plants and soil
    is 2,5-dichloro-4-bromophenol. Small amounts of bromoxon and
    monodesmethyl-bromophos were also found in tomato plants according to
    one report, whereas different studies on wheat, carrot and onion
    seedlings indicated the production of bisdesmethylbromophos but not
    desmethyl-bromophos. The identity of the bisdesmethyl-bromophos was
    not certain. In animals, bromophos is excreted rapidly via the urine
    and the major metabolites found are dichloro-bromophenol and
    monodesmethyl-bromophos. Extremely low levels of bromoxon may also
    occur in blood.

    Available multi-residue gas chromatographic procedures are suitable
    for application for regulatory purpose and are recommended.

    Although bromophos is recommended for use against ectoparasites of
    animals and poultry, there was no data available on residues likely to
    occur in meat (except sheep) or eggs and no recommendations for
    tolerances could be made for these commodities.



    The following temporary tolerances are based on residues likely to be
    found at harvest following currently recommended use patterns. For the
    majority of fruits and vegetables, the recommended pre-harvest
    interval is 7 days. In the case of whole milk, the practical residue
    limit is at or about the limit of determination. The temporary
    tolerances are expressed on bromophos.


    Olives, olive oil                                 5

    Apples, lamb's lettuce, leeks,
    radishes                                          2

    Carrots, celery, French beans, pears,
    plums, red currants, savoy cabbage,
    spinach                                           1

    Blackberries, blackcurrants,
    cherries, lettuce, gooseberries,
    peaches, strawberries, sugarbeets
    (roots), fat of meat of sheep                     0.5

    Wheat, rapeseed, rapeseed oil                     0.2

    Broccoli, cauliflower, cucumbers,
    red cabbage, cabbage, kohlrabi,
    onions, peas                                      0.1

    Milk (whole)                                      0.02*

    * at or about the limit of determination


    The temporary tolerance for wheat is based on residues likely to be
    found at harvest.


    REQUIRED (by 30 June 1977)

    1.   A study in dogs using animals of similar weight, age and origin
         in control and test groups, with particular attention to renal
         function and testicular pathology. The dosage levels should be
         set to demonstrate the no-effect level.

    2.   An adequate study to assess the carcinogenic potential of

    REQUIRED (before tolerances can be recommended)

    1.   Residue data from supervised trials for meat of domestic animals
         other than sheep, paultry, eggs, any fruit or vegetables not

    2.   Further information on good agricultural practices for use on
         stored grain and the effects of moisture and temperature on
         residues in stored grain.


    A study to determine dose levels causing no carboxylesterase
    (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, 1966-1977.
    III. Organophosphorous pesticides residues in the total diet. Pestic.
    Sci., 1: 10-13.

    Barnes, J.M. (1966) Mammalian toxicity report. WHO insecticide
    evaluation and testing programme, stage I. (unpublished)

    Boehringer, C.H. Sohn. (1965-1971) Residue investigation reports.

    Boehringer, C.H. Sohn. (1966) Produktion und Formulierung von
    Bromophos bei Laboratories Fher Spanien. Report dated 25/3/66.

    Boehringer, C.H. Sohn. (1968) Chronic oral toxicity tests on dogs
    using the compound bromophos. (unpublished)

    Byewater, J. (1966) Report by Biological Laboratories to Agricola
    Chemicals Ltd. (unpublished)

    Clark, D.E., Younger, R.L. and Ayala, C.H. (1966) Toxicosis and
    residues in bromophos-dipped sheep. J. Agr. Fd. Chem., 14(6): 608-609.

    Dedek, W. and Schwarz, H. (1969) Zum verhalten des mindertoxischen
    Insektizids 32P-bromophos nach cutaner Applikation am Rind. Z.
    Naturf., 24B: 744-747.

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

    El-Sebae, A.H. and El-Sayed, A.M.K. (1969) Persistence of malathion
    and bromophos on bean and clover crops. Z. für angew. Entomol., 63:

    Engst, von R., Knoll, R. and Ackermann, H. (1969) Zur
    Rückstandsproblematik von Pflanzenschutz und
    Schödlingsbekämpfungsmitteln (PSM) in der Kleinstkinderernährung.
    Dtsch. Gesundheitsw., 24: 1744.

    Food and Drug Administration. (1970) Advisory committee on protocols
    for safety evaluations: Panel on reproduction report on reproduction
    studies in the safety evaluation of food additives and pesticide
    residues. Toxicology and Applied Pharmacology, 16: 264-296.

    Glees, P. (1966) Neuropathological report to C.H. Boehringer Sohn.

    Kinkel, H.J. (1964a) Ermittlung der akuten peroralen Toxizität und
    Untersuchungen über die Neurotoxizität des Präparates Bromophos (CELA
    S 1942 = O,O-dimethyl-O-2,5-dichlor-bromophenylthionophosphat)
    an Hühnern. Report Battelle Institut. (unpublished)

    Kinkel, H.J. (1964b) Prüfung des Potenzierungseffektes: Bromophos-EPN.
    Report Battelle Institut. (unpublished)

    Kinkel, H.J. and Dirks, E. (1966) Investigations on the cholinesterase
    activity in dogs after oral application of bromophos. Report Battelle
    Institut. (unpublished)

    Kinkel, H.J. and Hübner, K.H. (1966) Histopathologische Untersuchungen
    an Hirn und Rückenmark bei Hühnern nach oraler Applikation von
    Bromophos. Report Battelle Institut. (unpublished)

    Kinkel, H.J., Hübner, K.H., Königsman, G. and Dirks, E. (1965) Chronic
    oral toxicity assay of bromophos
    (O,O-dimethyl-O-(2,5-dichloro-4-bromophenyl)-thionophosphate) on
    dogs and rats. Report Battelle Institut. (unpublished)

    Kinkel, H.J., Muacevic, G., Sehring, R. and Bodenstein, G. (1966) Zur
    Toxikologie von Bromophos. Archiv. für Toxikologie, 22: 36-57.

    Kinkel, H.J. and Sann, E. (1964) Ermittlung der akuten
    intraperitonealen Toxizität und Untersuchungen über die Hemmürkung des
    Präparates Bromophos (CELA S 1942) auf die Erythrozyten-Cholinesterase
    bei der Ratte. Report Battelle Institut. (unpublished)

    Kinkel, H.J. and Seume, F.W. (1963) Investigations on the toxicity of
    O,O-dimethyl-O-2,5-dichloro-4-bromo-phenyl-thionophosphate (S
    1942). Report Battelle Institut. (unpublished)

    Leber, G. (1967) Ruckstandsbestimmung von bromophos in fettarmen
    pflanzlichen material. Internal reports RU 2,22/02/10-8/22/67 and
    12/20/67 C.H. Boehringer Sohn.

    Leber, G. (1968) Ruckstandsbestimmung von bromophos in tierischem
    material. Internal Report RU 2,22/14/80-3/28/68. C.H. Boehringer Sohn.

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

    Leuschner, F. (1968) Uber die subakute Toxizität von 3
    Bromophos-metaboliten bei peroraler Verabreichung an Wister-Ratten.
    Report C.H. Boehringer Sohn. (unpublished)

    Leuschner, F. and Leuschner, A. (1966a) Untersuchungen über die
    Wirkung von Bromophos auf den Foetus und das trächtige weibliche
    Kaninchen bei peroraler Applikation. Report C.H. Boehringer Sohn.

    Leuschner, F. and Leuschner, A. (1966b) Untersuchüngen über die
    Einwirkung von Bromophos auf die Acetyl-cholinesterase bei
    Wistar-Ratten. Report C.H. Boehringer Sohn. (unpublished)

    Leuschner, F., Leuschner, A. and Pöppe, E. (1967) Chronischer
    Reproduktionsversuch über 3 Generationen an Wistar-Ratten bei
    fortdauernder Verabreichung von Bromophos. Report C.H. Boehringer
    Sohn. (unpublished)

    Leuschner, F., Leuschner, A., Schwerdtfeger, W. and Otto, H. (1969)
    Über die subakute Toxizität von Desmethylbromophos bei peroraler
    Verabreichung an Sprague-Dawley Ratten. Report C.H. Boehringer Sohn.

    Muacevic, G. (1963) Reports C.H. Boehringer Sohn. (unpublished)

    Muacevic, G. (1964) Reports C.H. Boehringer Sohn. (unpublished

    Muacevic, G. (1965) Reaktivierungsversuche bei Bromophos. Report C.H.
    Boehringer Sohn. (unpublished)

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

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

    Muacevic, G. (1968) Die Reaktivierbarkeit der Cholinesterase durch
    verschiedene Aldoxime nach Applikation von Bromophos im Rattengehirn
    (in vivo-Versuche). Report C.H. Boehringer Sohn. (unpublished)

    Muacevic, G. and Glees, P. (1967) Report on bromophos (1942) fowl
    trial. C.H. Boehringer Sohn. (unpublished)

    Muacevic, G. and Glees, P. (1968) Bericht über die Prüfung von
    Bromophos an Hühnern. Report C.H. Boehringer Sohn. (unpublished)

    Oettel, H. (1963) Report to C.H. Boehringer Sohn. Gewerbehyg.
    Pharmakol. Institut der BASF. (unpublished)

    Paton, I.M. (1965) Necropsy parasite recovery data controlled test.
    Report Jensen-Salsbery Laboratories. (unpublished)

    Rowlands, D.G. (1966a) The activation and detoxification of three
    organic phosphorothionate insecticides applied to stored wheat grains.
    J. stored Prod. Res., 2: 105-116.

    Rowlands, D.G. (1966b) The metabolism of bromophos in stored wheat
    grains. J. stored Prod. Res., 2: 1-12.

    Rygg, T. and Somme, L. (1967) Rester av fosformidler i gulrot. Norsk
    Landbruk, 13: 14.

    Stenersen, J. (1969a) Degradation of 32P-bromophos by micro-organisms
    and seedlings. Bull. Environ. Contam. Toxicol., 4: 104-112.

    Stenersen, J. (1969b) Demethylation of the insecticide bromophos by a
    glutathione-dependent liver enzyme and by alkaline buffers. J. Econ.
    Entomol., 62(5): 1043-1045.

    Stiasni, M., Rehbinder, D. and Deckers, W. (1967) Absorption,
    distribution, and metabolism of
    (bromophos) in the rat. J. Agr. Fd. Chem., 15: 474-478.

    Stiasni, M., Deckers, W., Schmidt, R. and Simon, H. (1969)
    Translocation, penetration and metabolism of O-(4-bromo-2,5-
    dichlorophenyl)-O,O-dimethylphosphorothioate (bromophos) in tomato
    plants. J. Agr. Fd. Chem., 17(5): 1017-1020.

    Tepe, J.B. (1968) Data from soil persistence and degradation study.
    Eli Lilly and Company, communication to CELA G.m.b.H.

    World Health Organization. (1967) Safe use of pesticides in public
    health. Sixteenth report of the WHO expert committee on insecticides.
    World Health Organization Technical Report Series No. 356.

    Worth, H.M., Kehr, C.C. and Gibson, W.R. (1967) Effect of a single
    dose of bromophos. Report Eli Lilly and Co. (unpublished)

    See Also:
       Toxicological Abbreviations
       Bromophos (WHO Pesticide Residues Series 5)
       Bromophos (Pesticide residues in food: 1977 evaluations)
       Bromophos (Pesticide residues in food: 1982 evaluations)
       Bromophos (Pesticide residues in food: 1984 evaluations)