WORLD HEALTH ORGANIZATION FOOD AND AGRICULTURE
ORGANIZATION
ORGANISATION MONDIALE DE LA SANTE ORGANISATION POUR L'ALIMENTATION
ET L'AGRICULTURE
WHO/PCS/DS/94.76
ORIGINAL: ENGLISH
Distr.: LIMITED
DATA SHEETS ON PESTICIDES No. 76
1994
BROMOPHOS
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 therefrom.
The issue of this document does Ce document ne constitue pas une
not constitute formal publication. Il ne doit faire
publication. It should not be l'objet d'aucun compte rendu ou
reviewed, abstracted or quoted résumé ni d'aucune citation sans
without the agreement of the l'autorisation de l'Organisation
Food and Agriculture des Nations Unies pour
Organization of the United l'Alimentation et l'Agriculture
Nations or of the World Health ou de l'Organisation Mondiale de
Organization. la Santé.
CLASSIFICATION:
Primary use: Insecticide
Secondary use: Acaricide
Chemical group: Organophosphorus compound
1.0 GENERAL INFORMATION
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; SHG-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 SELECTED PROPERTIES
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 medium.
1.3.4 Vapour pressure
17 mPa (20 °C).
1.4 AGRICULTURE, HORTICULTURE AND FORESTRY
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 PUBLIC HEALTH USE
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 reported.
2.0 TOXICOLOGY AND RISKS
2.1 TOXICOLOGY - MAMMALS
2.1.1 Absorption
Bromophos may be absorbed through intact skin as well as by the
respiratory and gastrointestinal tracts.
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 garage 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 mg/kg/diet.
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
nerves.
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 Fla 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 tracts.
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 later.
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 TOXICITY TO NON-MAMMALIAN SPECIES
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.
3.0 FOR REGULATORY AUTHORITIES - RECOMMENDATIONS ON REGULATION OF
COMPOUND
3.1 RECOMMENDED RESTRICTIONS ON AVAILABILITY
[For definition of categories see the 'Introduction to Data Sheets'].
All available liquid formulations, Category 4.
All available solid formulations, Category 5.
3.2 TRANSPORT AND STORAGE
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 face.
Formulations in category 5: No facilities other than those
needed for the handling of any chemical are required.
3.4 DISPOSAL AND/OR DECONTAMINATION OF CONTAINERS
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.
3.5 SELECTION, TRAINING AND MEDICAL SUPERVISION OF WORKERS
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.
3.6 ADDITIONAL REGULATIONS RECOMMENDED IF DISTRIBUTED BY AIRCRAFT
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.
3.8 RESIDUES IN FOOD
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.
4.0 PREVENTION OF POISONING IN MAN AND EMERGENCY AID
4.1 PRECAUTIONS IN USE
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
bromophos.
4.2 ENTRY OF PERSONS INTO TREATED AREAS
Unprotected persons should be kept out of tall crops for four
days and out of other crops for 24 hours
4.3 DECONTAMINATION OF SPILLAGE AND CONTAINERS
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 carded 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 EMERGENCY AID
4.4.1 Early symptoms of poisoning
Early symptoms of poisoning may include excessive sweating,
headache, weakness, giddiness, nausea, vomiting, increased
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 beating in mind
that if mouth-to-mouth resuscitation is used, vomit may contain
toxic amounts of bromophos.
5.0 FOR MEDICAL AND LABORATORY PERSONNEL
5.1 MEDICAL DIAGNOSIS AND TREATMENT IN CASES OF POISONING
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 tissues.
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, vomiting
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 ow
overexposure. If the compound has entered the eyes, they should be
washed with large quantifies 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.
5.2 SURVEILLANCE TESTS
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 LABORATORY METHODS
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 poisoning.
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.
REFERENCES
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 Organization.
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
Nations.
5. WHO (1986). Environmental Health Criteria No. 63,
Organophosphorus Insecticides: A General Introduction.
UNEP/ILO/WHO Geneva.