WORLD HEALTH ORGANIZATION FOOD AND AGRICULTURE
ORGANIZATION
ORGANISATION MONDIALE DE LA SANTE ORGANISATION POUR L'ALIMENTATION
ET L'AGRICULTURE
VBC/DS/77.30
ORIGINAL: ENGLISH
DATA SHEETS ON PESTICIDES No. 30
FENITROTHION
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.
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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
Date issued:
1. GENERAL INFORMATION
1.1 COMMON NAME: Fenitrothion (ISO)
Identity: O,O-dimethyl O-(3-methyl-4-nitrophenyl) phosphorothioate
Synonyms: OMS-43, sumithion, folithion, accothion, novathion,
agrothion
Local synonyms:
1.2 SYNOPSIS
An organophosphorus insecticide and selective acaricide of moderate
mammalian toxicity.
1.3 SELECTED PROPERTIES
1.3.1 Physical characteristics
Brownish yellow liquid of b.p. 145°C at 0.4 mm Hg (0.53 mbar) with
decomposition.
1.3.2 Solubility
Practically insoluble in water but soluble in most organic solvents;
low solubility in aliphatic hydrocarbons.
1.3.3 Stability
It is hydrolysed by alkali and its half-life in 0.01 N NaOH at 30°C
is 272 minutes. It readily isomerizes on distillation. Completely
stable for two years at 20-25°C.
1.3.4 Vapour pressure
(volatility) low, 6 x 10-6 mm Hg at 20°C, or 8 x 10-6 mbar at
20°C.
1.4 AGRICULTURE, HORTICULTURE AND FORESTRY
1.4.1 Common formulations
Emulsifiable concentrates 50%; dusts 2, 3 and 5%; wettable powders
40% and 50%; granules 3% and 5%, baits, ULV.
1.4.2 Susceptible pests
Aphids, weevils, sandfly, raspberry beetle, tortrix, midges, moths,
thrips, ermine moth, leatherjackets, leaf hoppers, rice borers, and
budworms.
1.4.3 Use pattern
Used on cotton and rice at up to 2 kg/ha; used on vegetables at up
to 1.25 kg/ha; used on cereals at up to 1.0 kg/ha; used in forestry
and on cocoa at up to 0.5 kg/ha; coffee, spray concentration 0.1%;
top fruit, spray concentration 0.1%; ornamentals, spray
concentration 0.1%; sugar cane, spray concentration 0.075; tea,
spray concentration 0.05%.
1.4.4 Unintended effects
Should not be used on flowering crops. Phytotoxicity is possible on
brassicae and orchard fruit - should not be applied directly to
grains. Livestock may be affected if given access to treated areas
within one week of application.
1.5 PUBLIC HEALTH
Successfully tested on residual insecticide for control of malaria
vectors, as a 5% suspension of water dispersible powder. This is
applied on the surfaces indoors at 2 g/m2 at a three-monthly
interval. Also used as ULV application from ground or air, technical
insecticide being applied at the rate of 250-500 ml/ha for the
control of vital epidemics transmitted by Aedes aegypti or Culex
sp. It has also been used as a mosquito larvicide at dosage rates
varying from 224 to 336 g/ha.
1.6 HOUSEHOLD USE
No known use.
2. TOXICOLOGY AND RISKS
2.1 TOXICOLOGY - MAMMALS
2.1.1 Absorption route
Absorbed from the gastrointestinal tract as well as by the intact
skin and by inhalation.
2.1.2 Mode of action
An organophosphorus cholinesterase inhibitor.
2.1.3 Excretion
Converted to the oxygen analogue. Metabolites include
3-methyl-4-nitrophenol and 3-carboxy-4-nitrophenol. Up to nine
metabolites have been isolated. Excretion is mainly in the urine
90-95% and up to 10% in the faeces.
2.1.4 Toxicity, single dose
Oral LD50 rat (M) 504 mg/kg
Dermal LD50 rat (M & F) 3500 mg/kg
Most susceptible species, cat (M) oral LD50 142 mg/kg
2.1.5 Toxicity, repeated doses
Oral: No fatalities occurred among male rats dosed for 28 days at
13 mg/kg/day, however, erythrocyte cholinesterase activity was
reduced and recovery took 30 days after cessation of dosing. Twenty
male rats dosed orally six days a week for two months at 10 and
11 mg/kg, showed some deterioration of general condition and weight
loss during the first weeks. However, haematology and urinalysis
during the experiment and histological examination at its
termination, did not reveal any abnormalities.
Dogs of both sexes were dosed orally by capsule at 2.9 or 40 mg/kg
for 98 days. Body weights, blood biochemistry, cholinesterase levels
and haemograms were checked at intervals. No effect was found at
2 mg/kg. At 9 mg/kg there was a slight reduction of whole blood,
plasma and erythrocyte cholinesterase activities, after 60 days, and
at 40 mg/kg a moderate reduction after 29 days. At 40 mg/kg, marked
cholinergic symptoms were observed.
Inhalation: Groups of six male and female rats, Sprague Dawley
strain, were exposed to fenitrothion mist during two hours per day
for five consecutive days. The aerial concentration of fenitrothion
in the chamber was approximately 62, 15 and 8 mg/m3. Plasma,
erythrocyte and brain cholinesterase activities of the rats exposed
to 7 mg/m3 of fenitrothion for five days showed no reduction as
compared with the control, while at the dose of 15 mg/m3 of
fenitrothion plasma cholinesterase activity was reduced
approximately by 30-50%. At 62 mg/m3 erythrocyte cholinesterases
were inhibited by 50% or more. Brain cholinesterase activity was not
affected at the lower dosages and only by exposure to 62 mg/m3 of
fenitrothion was it reduced to about 50% of the control.
In another trial, groups of 16 male and 16 female rats and 15 each
of male and female mice, were exposed to 1 and 0.2% fenitrothion
mist for two hours, six days per week for four weeks; plasma and
erythrocyte cholinesterase recovered within seven days after
termination of the exposure to 0.2% fenitrothion, and at the higher
dosage (1%) both cholinesterases were still 10-20% below the control
values after 14 days. None of the rats died during four weeks of
exposure, and there were no adverse effects on weight gain,
haematology, clinical biochemistry, organ weight and histopathology.
Similar results were obtained with mice.
Cumulation of compound: Does not accumulate in body tissues to any
significant extent.
Cumulation of effect: Repeated exposure may produce cumulative
inhibitory effect on cholinesterase. Acute effects are prolonged and
recovery of erythrocyte cholinesterase activity after severe
inhibition may take up to 30 days.
2.1.6 Dietary studies
Short-term: Groups of male rats (16 or 17 in number), were fed 0,
32, 63, 125, 250, and 500 ppm of fenitrothion in the diet for 90
days. All the animals fed 500 ppm showed clinical symptoms of
anticholinesterase poisoning and there were minimal symptoms in four
animals in the 250 ppm group. In the 500 ppm group, the average
weight of testes and brain were increased in comparison with those
of the control group. Cholinesterase activity of plasma,
erythrocyte, brain cortex, liver and kidneys showed a dose-dependent
reduction, the lowest being in the brain. The cholinesterase
activity in the 32 and 63 ppm groups generally recovered after 60
days of dosing to a level within the normal limits, the best
recovery being in the plasma, kidney and brain, less in the
erythrocyte and the liver.
Long-term: Fenitrothion was fed to groups of male and female
beagle dogs at concentrations ranging from 5 to 200 ppm for periods
of one to two years. In the first trial, groups of dogs (six males
and six females per group) were fed fenitrothion for two years at
doses of 30, 100 or 200 ppm in the diet. No measurable deviations
from the control were found in the treated groups with respect to
growth, food consumption, behavioural reactions, mortality
haematology and clinical blood chemistry values, urinary analysis,
organ weights and their ratio to body weight and gross and
microscopic pathological examinations. At 30 ppm, erythrocyte
cholinesterase activity was unaltered but plasma cholinesterase was
reduced throughout the two-year experiment. Brain cholinesterase
activity was not affected at the highest dose level.
Additional sub-acute feeding study was carried out to check blood
cholinesterase activity at the doses of 5 and 10 ppm for one year.
Five out of eight beagles exposed to 5 ppm of fenitrothion showed
slight reduction of plasma enzyme activity for the first three
months, but the activity recovered thereafter. Brain cholinesterase
was normal. The "no effect" level of fenitrothion for cholinesterase
activity was determined to be 5 ppm. Several studies on long-term
oral toxicity of fenitrothion, including carcinogenicity study have
been carried out in rats. It was found that fenitrothion fed at
concentrations from 2.5 to 150 ppm for periods ranging from six
months to two years produced no measurable deviation from the normal
with respect to the parameters investigated except cholinesterase
activity. Fenitrothion fed to rats at a concentration of 5 ppm was
determined as the "no effect" level with regard to cholinesterase
activity.
2.1.7 Supplementary studies of toxicity
Carcinogenicity: See 2.1.6, dietary studies, long-term.
Reproduction study: Fenitrothion was administered in the diet to
albino rats at dosage levels of 10, 30 and 150 ppm through weaning
of the first (F1A litters) filial generation and 10, 30 and
100 ppm thereafter. Body weight reduction occurred due to the
feeding of 150 ppm fenitrothion to the P1 generation animals and
100 ppm fenitrothion to the P2 generation animals. Lactation index
was significantly depressed for all the filial generations at the
highest dietary levels of fenitrothion. At these levels, weaning
body weights of both sexes of the F1A, males of the F1B, and
both sexes of the F2A generations were significantly lower than
the respective control values. The organs of representative
weanlings sacrificed from control and test groups showed no gross
compound-related changes at any of the test levels. No microscopic
evidence of compound-related histomorphologic alterations were
present in sections of thyroid, liver, kidney, stomach and small
intestine taken from male and female F3B weanlings which received
the highest level (100 ppm) of fenitrothion.
Teratogenicity: Technical fenitrothion was administered to
pregnant albino rabbits at daily rates of 0.3 mg/kg and 1.0 mg/kg of
body weight during early gestation. No adverse effects on body
weight gain were noted which could be attributed to fenitrothion. No
deaths or unusual reactions were noted among females. Foetal
mortality was not affected by the treatment with fenitrothion, nor
were any external and skeletal abnormalities observed among the
foetuses.
Delayed neurotoxicity: Tests in hens at 250, 400 and 500 mg/kg
have not revealed any paralysis or associated nerve damage. In rats
fed 10 mg/kg/day for six months, fine structure of neuromuscular
junctions was unchanged.
2.1.8 Modification of toxicity
In potentiation studies among several organophosphorus compounds
tested in combination with fenitrothion, only phosphamidon has shown
positive effects in both male and female rats, as evidenced by
increased mortality.
2.2 TOXICOLOGY - MAN
2.2.1 Absorption
Absorbed from the gastrointestinal tract as well as by inhalation
and by the intact skin.
2.2.2 Dangerous doses
Single: Not known.
Repeated: Not known.
2.2.3 Observations of occupationally exposed workers
Fenitrothion is applied as a residual indoor spray for adult
mosquito control. When supervision, including cholinesterase
monitoring, has been adequate, there have been no cases of poisoning
during residual indoor spraying. Only in a few instances has it been
necessary to remove individuals from spraying due to symptomless
reduction of whole blood cholinesterase activity, usually observed
towards the end of six to eight weeks spraying cycles. No cases of
poisoning occurred.
2.2.4 Observations on exposure of the general population
In a malaria control trial in northern Nigeria involving 10 000 and
16 500 people, whole blood cholinesterase levels were unaffected in
299 villagers representative of this population, tested 5-30 days
after their houses had been sprayed. This represents a higher
exposure than encountered by its proper agricultural use.
Fenitrothion has been used in agriculture for a number of years
without any cases of poisoning being reported.
2.2.5 Observations of volunteers
Single dose: Twenty-four volunteers were given a single oral dose
of from 2.5 to 20 mg of fenitrothion. In one case there was some
reduction of plasma cholinesterase activity, six and 24 hours after
receiving the largest dose. The excretion of the metabolite
3-methyl-4-nitrophenol in urine was maximal at 12 hours and almost
complete at 24 hours.
Repeated: Five individuals were given four daily doses of 2.5 and
5 mg fenitrothion. Metabolites appeared in the urine at 0-12 hours
after administration. After the third and fourth doses there was a
tendency towards a rise in erythrocyte cholinesterase levels. No
cholinesterase inhibition was seen in the plasma.
2.2.6 Reported mishaps
Accidental poisoning has occurred but no large-scale mishaps have
been reported.
2.3 TOXICITY TO NON-MAMMALIAN SPECIES
2.3.1 Fish
Toxic (4.4 ppm/h for carp; 1.0 ppm/h for trout).
2.3.2 Birds
Moderately toxic (LD50 523 mg/kg for chickens; for wild birds:
mallard duck 1190 mg/kg, pheasant 55.6 mg/kg).
2.3.3 Other species
Toxic to bees and livestock, game and wild animals.
3. FOR REGULATORY AUTHORITIES - RECOMMENDATIONS ON REGULATION OF
COMPOUND
3.1 RECOMMENDED RESTRICTIONS ON AVAILABILITY
(for definition of categories, see introduction)
All formulations 10% or above, Category 4
Formulations below 10%) Category 5
3.2 TRANSPORTATION AND STORAGE
All formulations in Category, 4: Should be transported or stored
in clearly labelled, rigid and leakproof containers. No food or
drink should be transported in the same compartment. Storage should
be under lock and key and secure from access by unauthorized persons
and children.
Formulations in Category 5: Should be transported in clearly
labelled, leakproof containers, out of reach of children and away
from food and drink.
3.3 HANDLING
All formulations in Category 4: Full protective clothing should be
used by all those handling the compound. Adequate washing facilities
should be available at all times during handling and should be close
to the site of handling. Eating, drinking and smoking should be
prohibited during handling and before washing after handling. Some
liquid formulations contain flammable volatile solvents.
Formulations in Category 5: No facilities other than those needed
for handling of any chemical need be required.
3.4 DISPOSAL AND/OR DECONTAMINATION OF CONTAINERS
All formulations: Containers may be decontaminated (for method see
para. 4.3). Decontaminated containers should not be used for food or
drink. Containers that are not decontaminated should be burned or
should be crushed and buried below topsoil. Care must be taken to
avoid subsequent contamination of water sources.
3.5 SELECTION, TRAINING AND MEDICAL SUPERVISION OF WORKERS
All formulations in Category 4: Pre-employment medical examination
of workers desirable. Workers suffering from active hepatic or renal
disease should be excluded from contact. Special account should be
taken of the workers' mental ability to comprehend and follow
instructions. Training of workers in techniques to avoid contact
essential. Pre-employment and routine cholinesterase test for
workers is desirable.
Formulations in Category 5: Warning of workers to minimize contact
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 symptoms of
poisoning. Use of flagmen not recommended. Flagmen if used should
wear protective clothing and be located well away from the dropping
zone.
3.7 LABELLING
All formulations in Category 4: Fenitrothion is an
organophosphorus compound that inhibits cholinesterase. It is
poisonous if swallowed or inhaled. It may be absorbed through the
skin. Avoid skin contact; wear hand protection, clean protective
clothing, and, if in poorly ventilated area, a respirator when
handling the material. Wash thoroughly with soap and water after
using. Keep out of reach of children and well away from foodstuffs,
animal feed and their containers. If poisoning occurs, call a
physician. Atropine and pralidoxime are specific antidotes and
artificial respiration may be needed.
Formulations in Category 5: Fenitrothion is a toxic substance. It
is poisonous if swallowed. It may be absorbed through the skin or
inhaled as dust or mists. Avoid skin contact, wear protective gloves
and clean protective clothing while using this material. Wash
thoroughly with soap and water after using. Keep the material out of
reach of children and well away from foodstuffs, animal feed and
their containers.
3.8 RESIDUES IN FOOD
Maximum residue limits for fenitrothion have been recommended by the
Joint FAO/WHO Meeting on Pesticide Residues.
4. PREVENTION OF POISONING IN MAN AND EMERGENCY AID
4.1 PRECAUTIONS IN USE
Fenitrothion is an organophosphorus insecticide of moderate
toxicity. It can be absorbed by mouth, by inhalation of the dust and
through the intact skin. Most formulations should be handled by
trained personnel wearing protective clothing.
4.1.1 Manufacture and formulation
TLV: No information. Although volatility is low, vapour and dust
should be controlled preferably by mechanical means. Protective
equipment for the skin and respiratory protection is usually
necessary.
4.1.2 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 mist and avoid contact with the mouth.
Particular care is needed when equipment is being washed after use.
All protective clothing should be washed immediately after use,
including the inside 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.
4.1.3 Other associated workers (including flagmen in aerial
operations)
Persons exposed to fenitrothion and associated with its application
should observe the precautions described in 4.1.3 under "mixers and
applicators".
4.1.4 Other populations likely to be affected
With good agricultural practice, subject to 4.2 below, other
populations should not be exposed to hazardous amounts of
fenitrothion.
4.2 ENTRY OF PERSONS INTO TREATED AREAS
Unprotected persons 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. In additional rinse should be carried out with
5% sodium hydroxide solution which should remain in the container
overnight. Impermeable gloves 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
fenitrothion 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, and vomiting, stomach pains, joint and muscle
pains, slurred speech, blurred vision and constricted pupils.
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. 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 fenitrothion.
5. FOR MEDICAL AND LABORATORY PERSONNEL
5.1 MEDICAL DIAGNOSIS AND TREATMENT OF CASES OF POISONING
5.1.1 General information
An organophosphorus pesticide of moderate toxicity which is absorbed
through the intact skin as well as by inhalation and from the
gastrointestinal tract. It is converted in vivo to the oxygen
analogue (fenitrothion) which is an active cholinesterase inhibitor.
Prolonged and continuous exposure to low amounts may inhibit blood
cholinesterase to hazard levels.
5.1.2 Symptoms and signs
Initial symptoms of poisoning may include excessive sweating,
headache, weakness, giddiness, nausea, vomiting, stomach pains,
muscle and joint pains, blurred vision, slurred speech, muscle
twitching and hypersalivation. More advanced symptoms of poisoning
may include coma, cyanosis, loss of sphincter control and loss of
reflexes.
5.1.3 Laboratory
The most important laboratory finding is reduction in activity of
blood cholinesterases.
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.
Persons without signs of respiratory inefficiency but with manifest
peripheral symptoms should be treated with 2-4 mg of atropine
sulfate and 1000-2000 mg of pralidoxime chloride or 250 mg of
toxogonin (adult dose) by slow intravenous injection. More atropine
may be given as needed. Persons with severe intoxication with
respiratory difficulties, convulsions and unconsciousness should
immediately be given atropine and a reactivator; in such severe
cases 4-6 mg of atropine sulfate should be given initially followed
by repeated doses of 2 mg at 5-10 minute intervals. The patient's
condition, including respiration, blood pressure, pulse frequency,
salivation and convulsions should be carefully observed as a guide
to further administration of atropine. If the patient is cyanotic,
artificial respiration should be administered at the same time as
atropine sulfate. The airways should be kept free and artificial
respiration should be applied, if required, preferably by mechanical
means. If necessary, intubation should be performed.
Contraindications are morphine, barbiturates, phenothiazine,
tranquillizers, and central stimulants of all kinds.
5.1.5 Prognosis
If the acute toxic effects are survived and these may be prolonged,
and adequate artificial respiration has been given, the chances of
complete recovery are good. However, in very severe cases,
particularly if artificial respiration has been inadequate,
prolonged hypoxia may give rise to permanent brain damage.
5.1.6 References of previously reported cases
No clear-cut poisoning cases. However, the following references may
be helpful:
Matsushima, S. (1972) Baioteku, 3(4), 258
Tshikawa, T. (1972) Baioteku, 3(4), 263
5.2 SURVEILLANCE TESTS
Test Normal level* Action level* Symptomatic level
Plasma cholinesterase 100% 50% Variable
Erythrocyte cholinesterase 100% 70% Usually 40%
*Expressed as percentage of pre-exposure activity.
5.3 LABORATORY METHODS
5.3.1 Detection and assay of compound
It is unlikely that unchanged fenitrothion will be detectable in
human tissues after exposure. Determination of levels of blood
cholinesterase and urinary 3-methyl-4-nitrophenol (see 5.3.2 below)
should be used in cases of suspected poisoning.
Residues may be determined by hydrolysis to 3-methyl-4-nitrophenol
which is measured at 400 mu by difference in absorbency in acid and
alkaline solution or by gas liquid chromatography; see Möllhoff
(1968). For an intra-red method, see Delves & Williams (1966).
The most sensitive methods for fenitrothion utilize gas
chromatography with either a plasma-photometric detector (Bowman &
Beroza, 1969) or a thermionic detector (Miyamoto et al., 1967);
detection limits are usually 0.01-0.001 ppm.
5.3.2 Other tests in cases of poisoning
Levels of cholinesterase in the blood provide the most useful
diagnosis of poisoning; for methods of estimation see: Michel (1949)
and Stubbs (1960) for electrometric method, Ellman et al. (1961) for
spectrophotometric method and Edson (1958) for tintometric method.