WORLD HEALTH ORGANIZATION FOOD AND AGRICULTURE
ORGANIZATION
ORGANISATION MONDIALE DE LA SANTE ORGANISATION POUR L'ALIMENTATION
ET L'AGRICULTURE
VBC/DS/77.25
ORIGINAL: ENGLISH
DATA SHEETS ON PESTICIDES No. 25
DECEMBER 1976
PROPOXUR
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.
Part 1 - General information
CLASSIFICATION:
Primary use: Insecticide
Secondary uses: acaricide
Chemical group: carbamate
Data sheet No. 25
Date issued: December 1976
1.1 COMMON NAME - PROPOXUR
Identity: 2-isopropoxyphenyl N-methylcarbamate
Synonyms: Local synonyms:
BAYGON
BAY 9010 Baygon
BAY 39007
UNDEN
OMS 33
ARPROCARB
1.2 SYNOPSIS
A carbamate insecticide of moderate mammalian toxicity which is
rapidly metabolized and does not accumulate in tissues.
1.3 SELECTED PROPERTIES
1.3.1 Physical characteristics
A white crystalline powder with a faint characteristic odour and a
melting point of 86-91.5°C (technical a.i.).
1.3.2 Solubility:
Its solubility in water is 0.2% at 20°C; it is soluble in polar
organic solvents, but only slightly soluble in non-polar organic
solvents.
1.3.3 Stability:
It is unstable in highly alkaline media with a half-life at pH 10 at
20°C of 40 minutes.
1.3.4 Vapour pressure (Volatility):
(Volatility) 10-2 mm Hg at 120°C.
1.4 AGRICULTURE, HORTICULTURE AND FORESTRY
1.4.1 Common formulations
Wettable powders 50%; dusts 2%, granules, oils, emulsifiable
concentrates 200 g/litre, pressurized sprays, smokes, baits of
different concentrations.
1.4.2 Pest controlled
Jassids, bugs, aphids, flies, mosquitos, cockroaches, ants,
millepedes and other household pests.
1.4.3 Use pattern
Used on pome and stone fruit, currants, grapes, vegetables, hops,
cotton, cocoa, rice, sugar cane, ornamentals and forest crops.
1.4.4 Unintended effects
May have a slight fruit thinning effect if applied to orchard fruit
shortly before blossom. It should not be sprayed any earlier than
three weeks after petal fall.
1.5 PUBLIC HEALTH
Used in hospitals, factories and stables at a concentration of 0.5%
active matter against ants, flies, fleas, cockroaches, woodlice,
mosquitos, bedbugs and ticks.
1.6 HOUSEHOLD USE
Used for household control of flies, ants, aphids, mosquitos,
cockroaches and millepedes.
Part 2 - Toxicology and risks
2.1 TOXICOLOGY - MAMMALS
2.1.1 Absorption route
Can be absorbed by inhalation, from the gastrointestinal tract and
to a lesser extent, through the intact skin.
2.1.2 Mode of action
Inhibition of cholinesterase which is relatively rapidly reversible.
2.1.3 Excretion products
The major metabolites appear to be O-hydroxyphenyl N-methylcarbamate
and 2-isopropoxyphenol; the latter appears in the urine as the
glucuronide. The urine is probably the main route of excretion for
this compound.
Toxicity, single dose
Oral: LD50 Rats (M) 116.0 mg/kg
LD50 Rats (F) 95.0 mg/kg
Dermal:
LD50 Rats (M & F) > 2400 mg/kg
(at this dose, 2 out of 10 rata died in both sex groups)
2.1.5 Toxicity, repeated doses
Oral: Male rats were dosed daily for 30 days at 5 mg/kg and for 15
days at 10 and 20 mg/kg. No effect was observed at 5 mg/kg. At 10
and 20 mg/kg, fasciculations were observed immediately after dosing
for the first 4-5 days, but after day 5, rats tolerated these doses
with no observable signs of distress.
Inhalation: Female rats and mice were exposed for 1 hour to
different concentrations of aerosols, particle size 1-3 µ. A
concentration of 210 mg/m3 killed half the rats but none of the
mice. At the lowest concentration tested, 168 mg/m3, 3 out of 10
rats died. Both rats and mice showed acute cholinergic signs 10-15
minutes after exposure began.
Cumulation of compound: Propoxur is not cumulative in body
tissues.
Cumulation of effect:
Rats injected intramuscularly six days a week for two weeks at
2 mg/kg/day (approx. 1/20 LD50), showed no cumulative effect as
measured by plasma cholinesterase levels. (See also 2.1.5 and
2.2.3.)
2.1.6 Dietary stucies
Short-term: Male and female rats were fed propoxur in their diet
at 250, 500, 1000 and 2000 ppm for 16 weeks. At 1000 and 2000 ppm,
food intake and body-weight were decreased in females but not in
males. Cholinesterase activity was reduced in whole blood at dietary
levels of over 500 ppm. At termination of the experiment,
cholinesterase activity was markedly reduced in plasma, whole blood
and brain at 1000 and 2000 ppm. Liver function and haematological
tests were normal. Some necrosis and bile duct proliferation was
observed in the liver.
Long-term: In a two-year feeding study a dietary concentration of
250 ppm had no ill effect on male and female rats. At 750 ppm, the
liver weight of the female rats was increased; otherwise there were
no adverse effects.
2.1.7 Supplementary studies of toxicity
Carcinogenicity: 30 mice were injected subcutaneously with
propoxur from birth to 38 weeks of age. The total dose of propoxur
given over this period was 9.6 mg per mouse. Urethane, which is a
known carcinogen, was given to the second group of 30 rats as a
positive control using the same dosing regime. The mice were then
observed for the remainder of their life span, and at death
post-mortem examination was performed. Incidence of tumours was
6.25% in the group receiving only the dosing vehicle, 6.77. for
those receiving propoxur and 45% for those receiving urethane. It
was concluded that propoxur had no carcinogenic effect in mice.
Teratogenicity: Rats were dosed on days 6, 8 and 11 of gestation
with 8.3, 25 and 50 mg/kg of propoxur. The two higher doses produced
obvious signs of maternal toxicity. No teratogenic effect was
observed, though the highest dose caused a slight reduction in mean
foetal weight.
Mutagenicity: No information available.
2.1.8 Modification of toxicity:
No information.
2.2 TOXICOLOGY - MAN
2.2.1 Absorption
Propoxur can be absorbed by inhalation and from the gastrointestinal
tract, and to a lesser extent through the intact skin.
2.2.2 Dangerous doses
Single: A single oral dose of 1.5 mg/g caused blurred vision,
sweating and vomiting and a reduction in cholinesterase activity to
27% of the pre-dosing level. (see 2.2.5)
Repeated: (see 2.2.5)
2.2.3 Observations of occupationally exposed workers
In malaria spraymen exposed to propoxur, occasional short lasting
symptoms of overexposure have been observed. These included nausea,
headache, sweating and weakness. These symptoms were enough to make
a sprayman stop work with a consequent rapid recovery. Where safety
precautions have been meticulously observed, there have been no
recorded illnesses attributable to propoxur exposure.
2.2.4 Observations on exposure of the general population
Some mild reactions to propoxur were reported among the residents of
the sprayed houses, and these were almost always associated usually
by entering the houses during or immediately after spraying or by
sweeping the floors with an insufficient amount of water.
2.2.5 Observations of volunteers
Volunteers took doses of 0.75 mg/kg or 1.0 mg/kg, split up into five
doses at half-hour intervals. Reduction in erythrocyte
cholinesterase activity of about 60% normal activity was observed.
Three hours later, erythrocyte cholinesterase levels had returned to
normal. No symptoms were observed. A single dose of 0.36 mg/kg
caused stomach discomfort, sweating and redness of the face. A dose
of 1.5 mg/kg caused reduction in erythrocyte cholinesterase activity
to 27% of pre-exposure level, associated with vomiting, sweating and
blurred vision. These symptoms lasted for one hour.
2.2.6 Reported mishaps
Occupational poisoning of a person by propoxur with a fatal outcome
has not been reported. See 2.2.3 for mild symptoms of overexposure
to propoxur.
2.3 TOXICITY TO NON-MAMMALIAN SPECIES
2.3.1 Fish
Toxic (Trout 6 ppm/48 hrs - carp 20 ppm/48 hrs).
2.3.2 Birds
Toxic to wild birds.
2.3.3 Other species
Toxic to bees, livestock, game and wild animals.
Part 3 - For regulatory authorities
RECOMMENDATIONS ON REGULATION OF COMPOUND
3.1 RECOMMENDED RESTRICTIONS ON AVAILABILITY
(For definition of categories, see introductory note)
Liquid formulations over 50% Category 3, and over 5% Category 4
Solid formulations over 20% Category all other formulations
Category 5
3.2 TRANSPORTATION AND STORAGE
Formulations in Categories 3 and 4
Should be transported or stored in clearly labelled rigid and
leakproof containers and away from containers of food and drink.
Storage should be under lock and key and secure from access by
unauthorized persons and children.
Formulations in Category 5
Should be transported or stored in clearly labelled, leakproof
containers out of reach of children away from food and drink.
3.3 HANDLING
Formulations in Categories 3 and 4
Protective clothing (see part 4) should be provided for those
handling concentrates. Adequate washing facilities should be
available close at hand. Eating, drinking and smoking should be
prohibited during handling and before washing after handling.
Formulations in Category 5
No special facilities other than those for handling of any chemical
need be required.
3.4 DISPOSAL AND/OR DECONTAMINATION OF CONTAINER
If not decontaminated, container must either be burned or crushed
and buried below top-soil. Care must be taken to avoid subsequent
contamination of water sources. Container may be decontaminated (for
method see paragraph 4.3 on part 4). Decontaminated containers
should not be used for food and drink.
3.5 SELECTION, TRAINING AND MEDICAL SUPERVISION OF WORKERS
Formulations in Categories 3 and 4
Pre-employment medical examination for workers desirable. Workers
suffering from active hepatic or renal disease should be excluded
from contact. Pre-employment and periodic cholinesterase tests for
workers desirable. Training of workers in techniques to avoid
contact essential.
Formulations in Category 5
Warning of workers to minimize contact essential.
3.6 ADDITIONAL REGULATIONS RECOMMENDED IF DISTRIBUTED BY AIRCRAFT
All formulations
Pilot and leaders should have special training in application
methods and early symptoms of poisoning. Flagmen, if used, should
wear overalls and be located well away from the dropping zone.
3.7 LABELLING
Formulations in Categories 3 and 4
Minimum cautionary statement
"Propoxur is a carbamate compound that inhibits cholinesterase. It
is poisonous if swallowed or inhaled. Keep the material out of reach
of children and well away from foodstuffs, animal feed and their
containers. If poisoning occurs call a physician. Atropine is a
specific antidote and artificial respiration may be needed."
Formulations in Category 5
Minimum cautionary statement
"This formulation contains propoxur, a carbamate insecticide which
inhibits cholinesterase. It is poisonous if swallowed. Keep the
material out of the reach of children and well away from foodstuffs,
animal feed and their containers. If poisoning occurs, call a
physician. Atropine is a specific antidote and artificial
respiration may be needed."
3.8 RESIDUES IN FOOD
Maximum residue levels have been recommended by the Joint FAO/WHO
Meeting on Pesticide Residues.
Part 4 - Prevention of poisoning in man and emergency aid
4.1 PRECAUTIONS IN USE
4.1.1 General
Propoxur is a carbamate insecticide of moderate toxicity which is
quickly metabolized and therefore acts only as an acute poison. It
can be absorbed by inhalation of the dust and also to some extent
through the intact skin. It is important that concentrated
formulations be washed immediately from the skin and eyes.
4.1.2 Manufacture and formulation
T.L.V.
No information.
Although volatility is low, vapour and dusts should be controlled
preferably by mechanical means. Protective equipment for the skin
and respiratory protection is usually necessary.
4.1.3 Mixers and applicators
When opening the container and when mixing, care should be taken to
avoid contact with the mouth and eyes. If necessary a facial visor
and gloves should be worn. Mixing, if not mechanical should always
be carried out with a paddle of appropriate length. The applicator
should avoid working in spray mists and avoid contact with the
mouth. 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 (including flagmen in aerial
operations)
Persons exposed to propoxur and associated with its application
should observe the precautions described in 4.1.3 under "mixers and
applicators."
4.1.5 Other populations likely to be affected
With correct use in agriculture and public health, the general
population should not be exposed to hazardous amounts of propoxur.
4.2 ENTRY OF PERSONS INTO TREATED AREAS
The general population should be kept out of treated areas for at
least one day.
4.3 DECONTAMINATION OF SPILLAGE AND CONTAINERS
Residues in containers should be emptied in a diluted form into a
deep pit taking care to avoid 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 a 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 and drink.
Spillage of propoxur 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 may include excessive sweating, headache, weakness,
giddiness, nausea, vomiting, stomach pains, salivation, tightness of
the chest, blurred vision, slurred speech and muscle twitching.
4.4.2 Treatment before person is seen by a physician, if these
symptoms appear following exposure
The person should stop work immediately remove contaminated
clothing, wash the affected skin with soap and water if available,
and flush the area with large quantities of water. If swallowed,
vomiting should be induced if the person is conscious.
Part 5 - for medical and laboratory personnel
5.1 MEDICAL DIAGNOSIS AND TREATMENT IN CASES OF POISONING
5.1.1 General information
Propoxur is a carbamate insecticide of moderate toxicity. It is
absorbed from the gastrointestinal tract and by inhalation, and only
to a limited extent through the intact skin. Its mode of action is
by reversibly inhibiting acetyl cholinesterase. Erythrocyte
cholinesterase is more inhibited than plasma cholinesterase.
Symptoms of poisoning are short lasting and in case of occupational
overexposure occur without a delay and at doses well below the fatal
dose. Because of its rapid metabolism and excretion it does not
accumulate in the tissues.
5.1.2 Symptoms and signs
Symptoms of poisoning include excessive sweating, headache, chest
tightness, weakness, giddiness, nausea, vomiting, stomach pains,
salivation, blurred vision, slurred speech and muscle twitching.
Paresthesia and mild skin reactions have also been reported.
5.1.3 Laboratory
Because propoxur is a reversible inhibitor of cholinesterase,
measurements of cholinesterase activity should be made by a method
which minimizes the reactivation of inhibited enzyme. Erythrocyte
cholinesterase determination is more informative than measuring
either plasma or whole blood cholinesterase, but the enzyme will
only be inhibited for a short time (few hours) after exposure. The
presence of phenol metabolites of propoxur in urine is also
indicative of exposure.
5.1.4 Treatment
If the pesticide has been ingested, unless the patient is vomiting,
rapid gastric lavage should be performed using 5% sodium
bicarbonate, if available. For skin contact, the skin should be
washed with soap and water. If the compound has entered the eyes
they should be washed with isotonic saline or water. Since the
symptoms of poisoning with propoxur are of short duration, atropine
treatment is usually not necessary by the time the patient reaches a
place where this antidote is available. Where there are manifest
symptoms 1-2 mg of atropine sulfate (adult dose) may be given
intramuscularly or even intravenously and repeated as necessary.
Care should be taken to avoid over-dosage of atropine, especially
when treating children. In extreme cases, if the patient is
unconscious or is in respiratory distress, oxygen may be required.
Contraindications are oximes such as pralidoxime, barbiturate and
central stimulants of all kinds.
5.1.5 Prognosis
If the acute toxic effect is survived, the chances of complete
recovery are very good.
5.1.6 References of previously reported cases
Mild symptoms of overexposure among malaria spraymen and residents
of sprayed houses have been reported: Wright, J. W. et al. (1969)
Bull Wld Hlth Org., 40, 67. See also "Safe Use of Pesticides"
(1973), Wld Hlth Org. techn. Rep. Ser., No. 513, pp 17-18.
5.2 SURVEILLANCE TESTS
Due to the rapid reactivation of inhibited enzyme, determination of
blood cholinesterase levels is of little if any practical value in
determining when workers should be withdrawn to prevent
overexposure. Minor complaints, such as headache and nausea, cause
the worker to stop work and thus prevent further exposure. The
worker quickly recovers, particularly if he washes the contaminated
skin.
5.3 LABORATORY METHODS
5.3.1 Detection and assay of compound
Because of its rapid metabolism, it is unlikely that measurable
amounts of propoxur will be found in human tissues. A gas
chromatographic method is described for analysis of propoxur and its
metabolites in animal tissues and milk, see Stanly (1972).
Estimation of excreted phenol in urine, derived from propoxur, by
both colorimetric and chromatographic methods is described by Dawson
et al. (1964).
Other methods for determining residues include a spectrophotometric
method (Gils, 1970) and a method of chromatographic analysis using
dansyl chloride as a fluorigenic agent (Frei et al., 1972).
5.3.2 Other tests in cases of poisoning
Cholinesterase levels in blood are unreliable as a routine test to
detect poisoning by propoxur. However, shortly after absorption,
inhibition of erythrocyte cholinesterase may be demonstrated by an
appropriate method. See Ellman, G. L. et al. (1961).
References
Dawson, J. A. et al. (1964) Bull Wld Hlth Org., 30, 127-134
Ellman, G. L. et al. (1961) Biochem. Pharmacol., 7, 88-95
Frei, R. W. & Lawrence, J. F. (1972) Chromatography, 67, (1),
87-95
Gils, W. F. (1970) Analyst, 95 (1126), 88-90
Stanley, C. W. (1972) J. Agr. Chem., 20 (6), 1269-1273