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    Original:  ENGLISH
    Distr.: LIMITED
    Date of issue:  February 1994
                            WHO/FAO DATA SHEET ON PESTICIDES
                                           No. 76

    It must be noted that the issue of a Data Sheet for a particular 
    pesticide does not imply endorsement of the pesticide by WHO or FAO for 
    any particular use, or exclude its use for other purposes not stated. 
    While the information provided is believed to be accurate according to 
    data available at the time when the sheet was compiled, neither WHO nor 
    FAO are responsible for any errors or omissions, or any consequences 
    The issue of this document does not constitute formal
    publication.  It should not be reviewed, abstracted or quoted
    without the agreement of the Food and Agriculture Organization
    of the United Nations or of the World Health Organization.
    Ce document ne constitue pas une publication.  Il ne doit faire
    l'objet d'aucun compte rendu ou résumé ni d'aucune citation
    sans l'autorisation de l'Organisation des Nations Unies pour
    l'Alimentation et l'Agriculture ou de l'Organisation Mondiale
    de la Santé.                                                 

    Primary use:          Insecticide
    Secondary use:        Acaricide
    Chemical group:       Organophosphorus compound
    1.1   COMMON NAME:      bromophos (ISO)
    1.1.1  Identity
          IUPAC chemical name:        O-4-bromo-2,5-dichlorophenyl 
                                        O,O-dimethyl phosphorothioate. 
          CAS chemical name:          O-(4-bromo-2,5-dichlorophenyl) O,O-
                                        dimethyl phosphorothioate. 
          CAS registry number:        2104-96-3
          RTECS number:               TE7175000
          Molecular formula:          C8H8BrCl2O3PS
          Relative molecular mass:    366.0
          Structural formula:   
          Synonyms and tradenames : Bromofos;  BrofeneR;  BropheneR;  
          CELA-1942;  ENT-27162;  NexionR;  Omexan;  OMS-658;  S-1942;  
    1.2   SYNOPSIS:  Bromophos is a broad spectrum, 
          non-cumulative non-systemic organophosphorus insecticide.  It is 
          a cholinesterase inhibitor with contact and stomach action, 
          having slight toxicity to mammals, fish and bees.  Bromophos is 
          listed in the WHO Recommended Classification of Pesticides by 
          Hazard under class III, "Slightly hazardous". 
    1.3.1  Physical characteristics: Bromophos consists of 
          yellowish crystals with a melting point of 53 °C.  It has a 
          boiling point of 140-142 °C.  The technical product is 95% pure. 
    1.3.2  Solubility:  In water, solubility is 40 mg/L 
          at 27 °C and it is soluble in most organic solvents. 
    1.3.3  Stability:  Bromophos is stable in aqueous 
          suspension up to pH 9 but it hydrolyses in a stronger alkaline 
    1.3.4  Vapour pressure:  17 mPa (20 °C).
    1.4.1  Common formulations:  These include emulsifiable 
          concentrates of 250 and 400 g a.i./L; wettable powder, 250 g/kg;  
          dusts, 20-50 g/kg; granules, 50-100 g/kg;  atomising concentrate,
          400 g/L;  dip 200 g/L; and coarse powder, 30 g/kg. 
    1.4.2  Susceptible pests:  Active against  Hemiptera , 
           Diptera , certain  Lepidoptera ,  Coleoptera and other insects. 
    1.4.3  Use pattern:  Used at a concentration of 
          250-1500 g a.i./ha on field, vegetable and fruit crops as well as
          ornamentals and grain storage.  Also used as a sheep dip. 
    1.4.4  Unintended effects:  Bromophos is not 
          recommended for use on cotton or grapes.  Injury has been 
          reported on varieties of cabbage, pears and ornamentals. 
    1.5.1  Common formulation:  See section 1.4.1.
    1.5.2  Pests controlled:  See section 1.4.2.
    1.5.3  Use pattern:  Used in the control of flies and
          mosquitos at 0.5 g/m2. 
    1.5.4  Unintended effects:  None reported.
    1.6   HOUSEHOLD USE:  No recommended usage 
    2.1.1  Absorption:  Bromophos may be absorbed through 
          intact skin as well as by the respiratory and gastrointestinal 
    2.1.2  Mode of action:  Bromophos is an indirect 
          inhibitor of cholinesterase through phosphorylation of the 
          esteratic site of the enzyme.  Accumulation of acetylcholine at 
          nerve synapses and myoneural junctions causes the toxic effects. 
    2.1.3  Excretion products:  Bromophos is excreted 
          rapidly via the urine, the major metabolites found are 
          dichloro-bromophenol and monodesmethyl bromophos.  Extremely low 
          levels of bromoxon may also occur in blood.  Approximately 63% of 
          a 10 mg/kg oral dose of bromophos was excreted in urine and 16% 
          in faeces over a 24 hour period. 
    2.1.4  Toxicity, single dose:
           Oral LD50
              Rat (M,F)           3750 - 6100 mg/kg b.w.
              Rat (M,F)             1600-1730 mg/kg b.w.
              Mouse                 2829-5850 mg/kg b.w.
              Guinea pig                 1500 mg/kg b.w.
              Rabbit                      720 mg/kg b.w.
           Dermal LD50
              Rat (M,F)                  5000 mg/kg b.w.
              Rabbit                     2181 mg/kg b.w. (scarified skin)
           Intraperitoneal LD50
              Rat                   1625-3125 mg/kg b.w.
              Mouse                      1040 mg/kg b.w.
    2.1.5  Toxicity, repeated dose:  Rats given bromophos
          by gavage at doses from 188 to 1250 mg/kg b.w. for 100 days 
          displayed signs of poisoning for approximately one hour after 
          each administration.  Observed compound related adverse effects 
          were:  depression of body weights, depressed food consumption at 
          the high dose level and depression of brain, liver and plasma 
          esterase at all doses. 
    2.1.6  Dietary studies:
          Short term:  Rats were fed bromophos at 0, 1500, 6000 and 10000
          mg/kg/diet for a period of 100 days.  Animals at the 2 higher 
          doses showed a marked decrease in weight gain.  Some minor 
          pathological changes were observed in liver and kidney at the 
          highest dose. 
          Groups of male and female beagle dogs were fed bromophos at 
          levels of 0, 20, 80, 320 and 1280 mg/kg/diet for one year.  
          Reduced body weight and food consumption occurred at 1280 
          mg/kg/diet and females in this group had less frequent oestrus.  
          Plasma cholinesterase inhibition occurred at 80, 320, 1280 
          mg/kg/diet, erythrocyte cholinesterase inhibition occurred at 320 
          and 1280 mg/kg/diet and brain cholinesterase inhibition occurred 
          at 1280 mg/kg/diet. 
          Long term:  Male and female dogs were given bromophos at 11, 44 
          and 87.5 and 175 mg/kg/b.w./day, by gavage for two years.  One 
          dog at 87.5 mg/kg b.w. and three at 175 mg/kg b.w. died after 
          developing respiratory difficulties, hoarseness, salivation, 
          tremors followed by ataxia and then paresis of the hind limbs.  
          Two other dogs at 175 mg/kg b.w. developed the same signs but 
          recovered.  Plasma, erythrocytes, liver and brain cholinesterases 
          were depressed at all doses. 
    2.1.7  Supplementary studies of toxicity:
          Carcinogenicity:   Male and female rats were administered 87.5, 
          175 and 350 mg/kg b.w. of bromophos by gavage for two years.  
          Cholinesterase was inhibited in plasma, erythrocytes, brain and 
          liver at all dose levels.  No tumours were reported to have 
          occurred at any dose level. 
          Albino mice fed bromophos at 0, 85, 350 and 1400 mg/kg/diet for 
          18 months did not reveal any carcinogenic potential.  Erythrocyte 
          and brain cholinesterase inhibition occurred at 350 and 1400 
          Mutagenicity:  No mutagenic activity was seen using  Drosophila 
          melanogaster as a test organism. 
          Neurotoxicity:  In early studies in hens administered bromophos, 
          either as a single oral dose of 10 g/kg b.w./day, or as 1 
          g/kg/day for periods of 12-56 days, incoordination and ataxia 
          associated with demyelination were observed.  These studies were 
          considered unsatisfactory. 
          In later studies hens were given 5.5 g/kg b.w. over a period of 7 
          weeks, or 2 oral doses of 2 g/kg b.w. 3 weeks apart.  No 
          neuropathological changes were observed in the CNS or peripheral 
          In order to reinvestigate the paralysis described in dogs in the 
          2 year feeding study described under Section 2.1.6.  Long term 
          dietary studies, dogs were administered 87.5 and 175 mg/kg 
          b.w./day orally for 270 days.  An extensive neuropathological 
          examination  of the central nervous system, spinal ganglia and 
          peripheral nerves failed to reveal any pathological changes. 
          Teratogenicity:  Female rabbits were administered 25, 50, 100, 
          200 or 400 mg/kg b.w. of bromophos from day 6 to 18 of pregnancy.  
          In no group did the type or number of malformations observed 
          differ from that of the controls. 
          Reproduction:  No effect was seen in a three generation study at 
          5 and 20 mg/kg of bromophos.  At 80 mg/kg, reduced weanling 
          weight and increased stillbirths were seen in F1a generation.  In 
          this study the cholinesterase activity of liver and plasma was 
          significantly depressed in animals receiving five mg/kg/day.  The 
          threshold dose for erythrocyte enzyme inhibition was between 5 
          and 30 mg/kg/day and for brain enzyme between 5 - 30 mg/kg/day 
          for males and 20-80 mg/kg/day for females. 
    2.1.8  Modification of toxicity:  Potentiation of the 
          acute toxicity of bromophos occurred with, bromophos-ethyl, 
          diazinon, dichlorvos, dimethoate, malathion, mevinphos, naled, 
          parathion and carbaryl. 
    2.2   TOXICOLOGY - MAN
    2.2.1  Absorption route:  Bromophos is absorbed through the 
          intact skin as well as by the respiratory and gastrointestinal 
    2.2.2  Dangerous doses:
          Single:  Not known.
          Repeated:  Not known.
    2.2.3  Observations on occupationally exposed 
          workers: A group of workers applied bromophos to house 
          interiors for malaria control, for 4 hours on one day and for 2.5 
          hours on the following day.  No clinical effects were seen in 
          spraymen or villagers. Spraymen plasma cholinesterase activities 
          the day after spraying were 94.9% of the pre-exposure levels.  
          One week after spraying villagers had plasma cholinesterase 
          activities 92% of pre-exposure value rising to 94.4% four weeks 
    2.2.4  Observations on exposure of the general population: 
          See section 2.2.3.
    2.2.5  Observations on volunteers:  The no effect 
          level for bromophos was found to be 0.4 mg/kg b.w./day after a 28 
          day period of administration.  At 0.8 mg/kg/b.w./day, plasma 
          cholinesterase was inhibited. 
    2.2.6  Reported mishaps:  No information available.
    2.3.1      Birds:
        Oral LD50       Chickens      9700 mg/kg 
    2.3.2  Fish:  
          Mosquito fish, at 0.5 - 1.0 mg/L, no mortality. 
        LC50            Guppies          0.5 mg/L 
    2.3.3  Other species:  Slightly toxic to honey bees.
          [For definition of categories see the 'Introduction to Data 
          All available liquid formulations, Category 4.
          All available solid formulations, Category 5.
          Formulations in category 4:  Should be transported in clearly
          labelled, rigid and leakproof containers out of reach of 
          children, away from food and drink.  Storage should be under lock 
          and key and secure from access by children and other unauthorized 
          persons.  Avoid contact with metals other than aluminium and tin. 
          Formulations in category 5:  Should be transported and stored in
          clearly labelled, leakproof containers out of reach of children, 
          away from food and drink.  Avoid contact with metals other than 
          aluminium and tin. 
    3.3   HANDLING
          Formulations in category 4:  Full protective clothing should be
          used by all handling the compound.  Adequate washing facilities 
          should be available at all times during handling and they should 
          be close to the site of handling.  Eating, drinking and smoking 
          should be prohibited during handling and before washing hands and 
          Formulations in category 5:  No facilities other than those needed
          for the handling of any chemical are required. 
          All formulations:  Containers must be decontaminated (for method 
          see paragraph 4.3 of part 4).  Decontaminated containers should 
          not be used for food and drink.  Containers that are not 
          decontaminated should be burned or crushed and buried below 
          topsoil (at least 0.5 m).  Care must be taken to avoid subsequent 
          contamination of water sources.  
          Formulations in category 4:  Pre-employment medical examination for
          workers desirable. Special account should be taken of the 
          workers' ability to comprehend and follow instructions. 
          Formulations in category 5:  Warning of workers to minimize contact
          is essential.
          All formulations:  Pilots and loaders should have special training
          in application methods and recognition of early warning symptoms 
          of poisoning, and they must wear a suitable respirator. Flagmen 
          should wear overalls and a broad brimmed hat and, be well away 
          from the dropping zone. 
    3.7   LABELLING
          Formulations in category 4 - minimum cautionary statement:
                              WARNING - POISON
                       (Skull and cross bones insignia)
          Bromophos is an organophosphorous compound which inhibits 
          cholinesterase.  It is of slight toxicity. Contact with the skin, 
          inhalation of dust or spray, or swallowing may be hazardous.  
          Wear protective gloves, clean protective clothing.  Bathe 
          immediately after work.  Ensure that containers are stored under 
          lock and key.  Empty containers must be disposed of in such a way 
          as to prevent all possibility of accidental contact with them.  
          Keep the material out of reach of children and well away from 
          foodstuffs, animal feed and their containers. 
          In case of contact, immediately remove contaminated clothing and 
          wash the skin thoroughly with soap and water;  for eyes, flush 
          with water for 15 minutes. 
          If poisoning occurs, call a physician.  Atropine sulphate is a 
          pharmacological antidote.  Repeated doses may be necessary.  
          Artificial respiration may also be needed. 
          Formulations in category 5 - minimum cautionary statement:  This
          formulation contains bromophos, it is poisonous if swallowed.  
          Keep the material out of reach of children and well away from 
          food stuffs, animal feed and food containers. 
          Maximum Residue Limits (MRLs) have been recommended by the Joint 
          FAO/WHO Meeting on Pesticide Residues.  In 1977 an Acceptable 
          Daily Intake (ADI) for bromophos was set at 0.04 mg/kg b.w. 
    4.1.1  General: Bromophos is an organophosphorus pesticide 
          of slight mammalian toxicity. It is readily absorbed through the 
          intact skin, from the gastrointestinal tract, and by inhalation 
          of dust or spray mist.  Repeated exposure may have a cumulative 
          effect on acetylcholinesterase activity. 
    4.1.2  Manufacture and formulation - TLV:  Closed 
          systems and forced ventilation may be required to reduce as much 
          as possible the exposure of workers to the chemical. 
    4.1.3  Mixers and applicators:  When opening the 
          container and when mixing, protective impermeable boots, clean 
          overalls, gloves and a suitable respirator should be worn.  
          Mixing, if not mechanical, should always be carried out with a 
          paddle of appropriate length.  When spraying tall crops or during 
          aerial application, a face mask should be worn, as well as an 
          impermeable hood, clothing, boots, and gloves.  The applicator 
          should avoid working in spray mist and avoid contact with the 
          mouth.  Particular care is needed when equipment is being washed 
          after use.  All protective clothing should be washed separately 
          from other laundry immediately after use, including the insides 
          of gloves.  Splashes must be washed immediately from the skin, or 
          eyes with large quantities of water.  Before eating, drinking, or 
          smoking, hands and other exposed skin should be washed. 

    4.1.4  Other associated workers:  Persons exposed to 
          bromophos and associated with its application should wear 
          protective clothing and observe the precautions described above 
          in 4.1.3. under "Mixers and Applicators". 
    4.1.5  Other populations likely to be affected: 
          With good application practice subject to 4.2 below, other 
          persons are not likely to be exposed to hazardous amounts of 
          Unprotected persons should be kept out of tall crops for four 
          days and out of other crops for 24 hours. 
          Residues in containers should be emptied in a diluted form into a 
          deep dry pit (depth >0.5 m) taking care to avoid contamination 
          of ground waters.  The empty container may be decontaminated by 
          rinsing two or three times with water and scrubbing the sides.  
          An additional rinse should be carried out with 5% sodium 
          hydroxide solution which should remain in the container 
          overnight. Impermeable gauntlets should be worn during this work, 
          and a soakage pit should be provided for the rinsings.  
          Decontaminated containers should not be used for food, feed or 
          water storage. Spillage of bromophos and its formulations should 
          be removed by washing with 5% sodium hydroxide solution and then 
          rinsing with large quantities of water. 
    4.4.1  Early symptoms of poisoning:  Early symptoms of 
          poisoning may include excessive sweating, headache, weakness, 
          giddiness, nausea, vomiting, inceased salivation, stomach pains, 
          blurred vision, diarrhoea, slurred speech and muscle twitching. 
          Later there may be shortness of breath, convulsions and coma. 
    4.4.2  Treatment before person is seen by physician, if
    these symptoms appear following exposure:  
          The person should stop work immediately, remove contaminated 
          clothing and wash contaminated skin with soap and water and flush 
          the area with large quantities of water.  If swallowed, and if 
          the person is conscious, vomiting should be induced.  In the 
          event of collapse, artificial respiration should be given bearing 
          in mind that if mouth-to-mouth resuscitation is used, vomit may 
          contain toxic amounts of bromophos. 
    5.1.1  General information:  Bromophos is an
          organophosphorus pesticide of slight mammalian toxicity which is 
          active against a variety of agricultural and public health pests. 
          It is readily absorbed from the gastrointestinal tract, through 
          the intact skin, and by inhalation of dust or spray mist.  It is 
          converted  in vivo to the oxygen analogue of bromophos which 
          inhibits acetylcholinesterase.  It does not accumulate in body 

    5.1.2  Symptoms and signs:  Symptoms of poisoning are 
          due to excessive stimulation by acetylcholine of all cholinergic 
          innervation.  Thus initial symptoms and signs of poisoning may 
          include excessive sweating and salivation, headache, weakness, 
          miosis, dyspnoea, nausea, and diarrhoea, blurred vision and 
          muscle fasciculations.  More severe poisoning leads to 
          respiratory failure due to a combination of bronchorrhea, 
          bronchoconstriction (muscarinic effects), paralysis of 
          respiratory muscles (nicotinic effects) and respiratory centre 
          paralysis (central effects).  Central nervous system effects 
          include, in severe cases, coma and convulsions. 
    5.1.3  Laboratory:  Diagnosis is confirmed by finding 
          inhibition of erythrocyte or whole blood acetylcholinesterase.  
          However, treatment must start immediately and cannot be delayed 
          until confirmation from the laboratory.  This test cannot be used 
          to control the effectiveness of the treatment nor is it of help 
          for prognosis. 
    5.1.4  Treatment:  Patients with respiratory failure 
          must be given artificial ventilation, then diazepam (10 mg 
          intravenously) to control convulsions.  When vital functions are 
          controlled, atropine sulfate is given (initial dose is usually 2 
          mg intravenously) followed by pralidoxime (1000 mg) or toxogonin 
          (250 mg) by slow intravenous infusion. 
          If the pesticide has been ingested, gastric lavage might be 
          needed or vomiting induced.  Protection of airways (intubation) 
          is required if inducing vomiting in unconscious patients. 
          For skin contact, the skin should be washed with soap and large 
          amounts of water.  Precautions should be taken by medical 
          personnel during these decontamination procedures to prevent 
          their own overexposure.  If the compound has entered the eyes, 
          they should be washed with large quantities of saline or water. 
          Atropine treatment might be required for several days after 
          poisoning.  Only clinical assessment determines atropine dose, 
          i.e. evident signs of atropinization (dry mouth, tachycardia, 
          vasodilation, mydriasis) should be maintained.  Total amounts of 
          atropine given to these patients might be extremely high because 
          they are tolerant to the effects of atropine. 
          Caution should be taken when doses of atropine are reduced because 
          reappearance of symptoms might occur, due to redistribution 
          processes in the body.  Cholinesterase reactivators such as 
          pralidoxime and toxogonin are usually only effective during the 
          first few days of poisoning, unless the slow disposal of the 
          chemical within the body suggests that some acetylcholinesterase 
          is newly inhibited.  Indications for the continuing use of 
          reactivators might derive from measurements of erythrocyte 
          cholinesterase before and after treatment with such reactivators. 
    5.1.5  Prognosis:
          Unless brain hypoxia has occurred, full recovery is expected. 
    5.1.6  References to previously reported cases:  
          No information available.
          Any fall of erythrocyte cholinesterase activity to 70% of pre-
          exposure values requires an investigation of working methods and 
          hygiene and more frequent cholinesterase tests.  Symptoms of 
          poisoning may appear when the erythrocyte cholinesterase activity 
          is less than 35% of normal. If erythrocyte cholinesterase 
          activity is less than 50% of normal, the worker must be suspended 
          from all contact with organophosphorus or carbamate pesticides 
          until the level rises above 70% of normal. Pseudocholinesterase 
          activity in the plasma can fall to very low levels without 
          evidence of symptoms. This only indicates undesirable exposure. 

    5.3.1  Detection and assay of compound:
          Thin-layer chromatography and gas liquid chromatography methods 
          have been used to analyze bromophos in technical products and in 
          its formulations.  Analysis of residues in plant and animal 
          tissues is by gas chromatography and flame photometry methods. 
          Weeren RD & Eichler D (1978), Anal Methods Pestic Plant Growth 
          Regul 10: 31-40. 
    5.3.2  Other tests in case of poisoning:  Activity of 
          cholinesterase in the blood provide the most useful diagnosis of 
          Ellman GL et al (1969) Biochem pharmacol 7: 88-95.
          Wilhelm K & Reiner E (1973),  Bull Wld Health Org, 48:  235-238.
          Measurement of urine metabolites such as dialkylthiophosphates 
          may also be determined in order to give an indication of exposure 
          for methods.  See section 5.3.1, Detection and Assay. 
    1.    The Pesticide Manual, A World Compendium (9th edition 1991), 
          Worthing, C.R. and Hance, eds., British Crop Protection Council, 
          20 Bridport Road, Thornton Heath, CR4 7QG, United Kingdom. 
    2.    WHO (1975), 1974 Evaluations of Some Pesticide Residues in Food.  
          WHO Pesticide Residue Series No. 4, 295-333, Geneva, World Health 
    3.    WHO (1994) The WHO Recommended Classification of Pesticides by 
          Hazard and Guidelines to Classification 1994-1995, Geneva, World 
          Health Organization mimeographed document (WHO/PCS/94.2). 
    4.    FAO/WHO (1988) Pesticide Residues in Food - 1987 Evaluations, 
          Part II - Toxicology, FAO Plant Production and Protection Paper 
          86/2, Rome, Food and Agriculture Organization of the United 
    5.    WHO (1986).  Environmental Health Criteria No. 63, 
          Organophosphorus Insecticides:  A General Introduction.  
          UNEP/ILO/WHO Geneva. 
                                             = = = 

See Also:
        Bromophos (PIM 742)