WORLD HEALTH ORGANIZATION FOOD AND AGRICULTURE
ORGANISATION MONDIALE DE LA SANTE ORGANISATION POUR L'ALIMENTATION
Date of issue: February 1994
WHO/FAO DATA SHEET ON PESTICIDES No. 92
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.
Primary use: Nematicide
Secondary use: Insecticide
Chemical group: Organophosphorus compound
1.0 GENERAL INFORMATION
1.1 COMMON NAME: fenamiphos (E-ISO); phénamiphos (F-ISO)
IUPAC name: ethyl 4-methylthio-m-tolyl
CAS name: ethyl 3-methyl-4-(methylthio)phenyl (1-
CAS registry number: 22224-92-6
RTECS number: TB3675000
Molecular formula: C13H22NO3PS
Relative molecular mass: 303.4
Synonyms or trade names: Bay 68138; NemacurR; Nemacur PR.
1.2 SYNOPSIS: Fenamiphos, an organophosphorus
nematicide, is extremely toxic to mammals. The technical product is
listed in the WHO Recommended Classification of Pesticides by Hazard
under class Ia, Extremely hazardous. Readily absorbed through
foliage and roots of plants, it has a fairly long-acting systemic
activity in plants. Residues are generally moderately well adsorbed
on soil, reducing the amount of leaching through soil into ground
waters. No indications of toxicity other than through inhibition of
acetylcholinesterase activity are reported in the limited amount of
published data available.
1.3 SELECTED PROPERTIES
1.3.1 Physical characteristics: The technical product is
a tan, waxy solid with a melting point around 46 °C. Pure fenamiphos
is a white crystalline product with a melting point of 49.3 °C. The
technical material has a minimum purity of 87%. Fenamiphos is not
1.3.2 Solubility: In water at 20 °C, 700 mg/L.
Slightly soluble in most organic solvents.
1.3.3 Stability: Hydrolysed by strong acids and
alkalis. No degradation in propanol/water (1:1) at 40 °C, pH 7,
after 50 days.
1.3.4 Vapour pressure: 0.12 mPa (20 °C)
1.4 AGRICULTURE, HORTICULTURE AND FORESTRY
1.4.1 Common formulations: Granular 5-15%, emulsifiable
concentrate 40%, 250 g/L EW. In combination with carbofuran,
disulfuron, isofenphos or fensulfothion in granule and emulsifiable
1.4.2 Susceptible pests: Effective against ecto- and
endo-parasitic, free-living, cyst-forming and root-knot nematodes.
May also control mites, aphids, thrips, fleahoppers and mealy bugs.
1.4.3 Use pattern: Used as a soil treatment, with or
without incorporation, as a root dip, as a seed treatment or as a
foliar application. Fenamiphos is readily absorbed through roots
and leaves to give a systemic nematicidal action. Controls nematodes
in a wide variety of field, vegetable and fruit crops; good water
solubility makes it particularly useful in wet or heavy soils.
1.4.4 Unintended effects: Toxic to fish. Some
phytotoxicity has been reported following foliage application to
alfalfa, squash, tomatoes, and some ornamentals.
1.5 PUBLIC HEALTH USE:
No recommended usage reported.
1.6 HOUSEHOLD USE: No recommended usage reported.
2.0 TOXICOLOGY AND RISKS
2.1 TOXICOLOGY - MAMMALS
2.1.1 Absorption route: Femamiphos may be absorbed from
the gastrointestinal tract; by inhalation or through intact skin.
2.1.2 Mode of action: Direct inhibition of
cholinesterases. The sulfoxide and sulfone metabolites are more
potent inhibitors than fenamiphos itself.
2.1.3 Excretion products: Fenamiphos is extensively
metabolized by the rat to sulfoxides and sulfones, N and O
dealkylation products and conjugates. Excretion of a 2 mg/kg b.w.
radio-labelled oral dose was predominantly via the urine and expired
air and was essentially complete within 15 hours.
2.1.4 Toxicity, single dose:
Rat (M & F) 2.3 - 19.4 mg/kg b.w.
Mouse (M) 22.7 mg/kg b.w.
Mouse (F) 8.3 mg/kg b.w.
Rabbit 5.0 mg/kg b.w.
Rabbit (M) 10 - 17.5 mg/kg b.w.
Guinea pig (M) 56 - 100 mg/kg b.w.
Dog (M) ca. 10 mg/kg b.w.
Cat (M) ca. 10 mg/kg b.w.
Rat (M) 73 - 500 mg/kg b.w.
Rat (F) 84 - 154 mg/kg b.w.
Rabbit 178 - 225 mg/kg b.w.
1 hour Rat 110 - 175 mg/m3
4 hour Rat 91 - 100 mg/m3
Rat (M & F) 3.0 - 4.9 mg/kg b.w.
Mouse (M & F) 3.4 mg/kg b.w.
Guinea pig (M) 17.3 mg/kg b.w.
Primary irritation: Application of 0.25 ml of a liquid formulation
(equivalent to 0.085 mg a.i.) to intact or abraded rabbit skin did
not cause primary irritation. Instillation of the same formulation
into the conjunctival sac of rabbits caused irritation at 0.034 mg
2.1.5 Toxicity, repeated dose: Oral or
intraperitoneal administration of 1.7 or 1.5 mg/kg b.w./day
respectively, five days/week for sixty days, was not lethal to male
rats, and no evidence of cumulative toxicological effects was
observed. Female rats survived daily intraperitoneal administration
of 1 mg/kg for sixty days while 40% of those administered 2 mg/kg did
not survive. All rats died at 3 mg/kg.
No effects on growth, haematology, clinical chemistry, gross or
microscopic pathology were observed in rats exposed to aerosol
concentrations of up to 3.5 mg/m3 for three weeks. Plasma
cholinesterase activity was depressed at 3.5 mg/m3 but no effect
was observed on erythrocyte and brain cholinesterase.
Dermal application 0.5, 2.5 or 10 mg/kg b.w. to rabbits for three
weeks caused no adverse effects other than a slightly decreased
plasma cholinesterase activity at 2.5 mg/kg b.w. and above.
Cumulation of effect: Fenamiphos does not accumulate in body
tissues but cumulation of effects was demonstrated during exposure.
Plasma and erythrocyte cholinesterase activity remain inhibited but
clinical symptoms such as behavioural changes and tremors appear
only during the early period of exposure.
2.1.6 Dietary studies:
Short term: Administration of 0, 4, 8, 16 or 32 mg/kg/diet to rats
for three months caused a slight increase in absolute liver weights
in males at the two highest concentrations. Relative liver weights
were unaltered, however, and no abnormal histopathology of this, or
any other organ, was observed. Evidence of cholinergic stimulation
was apparent in both sexes at 32 mg/kg/diet but was only observed for
the first two months of the study. Plasma cholinesterase activity
was depressed at 8 mg/kg/diet and above. A no-effect-level (NOEL)
based upon plasma cholinesterase was found to be 4 mg/kg/diet.
Groups of beagle dogs were fed fenamiphos in the diet at 0, 2, 6 and
18 mg/kg/diet for three months. Administration of 18 mg/kg/diet to
male and female dogs caused behavioral abnormalities, evidenced by
signs of cholinergic stimulation and a decreased growth rate in the
females. At 2 mg/kg/diet plasma cholinesterase activity was
marginally decreased in both sexes while erythrocyte cholinesterase
activity was unaffected at this dose. The NOEL for dogs was
considered to be 2 mg/kg/diet.
In a two year feeding study in dogs at concentrations of 0, 0.5, 1.0,
2.0, 5.0 and 10.0 mg/kg/diet no adverse effects other than inhibition
of blood cholinesterase were observed. The NOEL for plasma
cholinesterase was 1 mg/kg/diet.
Long term: Signs of cholinergic stimulation were observed in
Wistar rats receiving 30 mg/kg/diet (maximum dose tested) but were
apparent only for the first six weeks of the two year study.
Inhibition of plasma cholinesterase was observed at concentrations
above 3 mg/kg/diet. Increased absolute and relative thyroid weights
were observed in females receiving 30 mg/kg/diet, but goitre, tumours
or other abnormal histopathological findings were absent. No adverse
effects were observed on growth, mortality, haematologic or clinical
chemistry evaluations, or in histopathologic examinations. A NOEL
was set at 3 mg/kg/diet (equivalent to 0.17, to 0.23 mg/kg b.w./day)
on the basis of plasma cholinesterase inhibition.
Groups of male and female Fischer 344 rats were fed diet containing
mean effective concentrations of 0, 1.7, 7.8 and 37 mg/kg/diet
(equivalent to 0, 0.1, 0.5 and 2.5 to 3.4 mg/kg b.w./day) of
technical fenamiphos (89.3% pure) for two years. Erythrocyte
cholinesterase activity was significantly inhibited in both sexes at
all dose levels (approximately 6%, 30% and 70% at 1.7, 7.8 and 37
mg/kg/diet respectively). Brain cholinesterase activity was also
significantly decreased in high dose males at termination and in both
sexes after one year of treatment only. No treatment-related
neoplastic lesions were observed.
2.1.7 Supplementary studies of toxicity:
Carcinogenicity: No evidence of carcinogenicity was observed in
two two-year chronic/carcinogenicity studies in rats (see Long term
above) or in mice fed fenamiphos for 18 months at 25 and 50
Rats: Pregnant female FB30 rats were orally administered (gavage)
fenamiphos (92.5%) at doses of 0, 0.3, 1.0 and 3.0 mg/kg b.w. day
from day 6 to day 15 of gestation.
Cholinergic signs were observed in 18 out of 25 dams receiving 3
mg/kg b.w./day. No signs of toxicity were observed at 0.3 and 1.0
It was concluded that fenamiphos at doses up to and including 3.0
mg/kg b.w./day was not embryotoxic or teratogenic in FB30 rats.
Rabbits: Pregnant female Chinchilla rabbits were orally
administered (gavage) fenamiphos (91% pure) at doses of 0, 0.1, 0.5
and 2.5 mg/kg b.w./day from day 6 through day 18 post coitum.
Maternal toxicity including death was observed at 5 mg/kg b.w./day.
Based on the maternal toxicity observed at the high dose level, the
NOEL for the females was 0.5 mg/kg b.w./day. Fenamiphos was not
considered to be embryotoxic or teratogenic to Chinchilla rabbits.
Reproduction: No adverse effects on reproduction were observed in
a three-generation study in rats receiving fenamiphos at 0, 3, 10 and
30 mg/kg of diet.
Mutagenicity: Fenamiphos showed no mutagenic activity in a
micronucleus test, in the Ames test and in Escherichia coli . In a
dominant lethal test in mice, fenamiphos did not induce alterations
in male germinal cells.
Neurotoxicity: No evidence of delayed neurotoxicity was observed in
hens following a single gavage dose of 5.0 mg/kg b.w. (LD50) or
thirty days dietary administration of 1, 3, 10 or 30 mg/kg/diet.
2.1.8 Modification of toxicity: No potentiation
occurred when fenamiphos in combination with disulfoton was
administered to male rats.
2.2 TOXICOLOGY - MAN
2.2.1 Absorption route: Fenamiphos may be absorbed from
the gastrointestinal tract, from the lungs and through intact skin.
2.2.2 Dangerous doses:
No published information available.
2.2.3 Observations on occupationally exposed workers:
No published information available.
2.2.4 Observations on exposure of the general population:
No published information available. With good agricultural practice
the general public should not be exposed to hazardous amounts of
2.2.5 Observations on volunteers:
No published information available.
2.2.6 Reported mishaps:
No published information available.
2.3 TOXICITY TO NON-MAMMALIAN SPECIES
2.3.1 Fish: Toxic to fish
LC50 (96 hour)
Rainbow trout 0.07 - 0.11 mg/L
Goldfish 3.2 mg/L
Bluegill sunfish 0.01 - 0.017 mg/L
Mallard duck (M) 1.7 mg/kg b.w.
Mallard duck 0.9 - 1.2 mg/kg b.w.
Bobwhite quail 0.7 - 1.6 mg/kg b.w.
Mallard duck (M) 2.3 mg/kg b.w.
Mallard duck 316 mg/kg/diet
Japanese quail 59 mg/kg/diet
Bobwhite quail 38 mg/kg/diet
Reproduction: In a 19 week dietary study with mallard ducks,
fertility, egg fragility and brain cholinesterase activity were not
affected at the highest dose tested (16 mg/kg/diet) while egg
production and hatchling survival were reduced. The NOEL was
reported to be 8 mg/kg/diet.
2.3.3 Other species: No published information
available. As an organophosphate with insecticidal activity,
toxicity to bees would be anticipated.
3.0 FOR REGULATORY AUTHORITIES - RECOMMENDATIONS OF COMPOUND
3.1 RECOMMENDED RESTRICTIONS ON AVAILABILITY
[For definition of categories see the 'Introduction to data sheets'].
Solid formulations > 30% and liquid formulations > 7.5%:
All other formulations: Category 3
3.2 TRANSPORTATION AND STORAGE
All formulations: Should be transported in clearly labelled,
leakproof containers, away from food and drink. Storage should be
under lock and key and secure from access by children and other
All formulations: Protective clothing (see part 4) should be worn
for the handling of all formulations. Adequate washing facilities
should be available in the immediate area. Eating, drinking and
smoking should be prohibited during handling and before washing after
3.4 DISPOSAL AND/OR DECONTAMINATION OF CONTAINERS
All formulations: Whenever possible containers should be either
returned to the supplier, or safely disposed of in an approved
manner. Care must be taken to avoid subsequent contamination of
water sources. Decontamination of containers in order to use them
for other purposes should not be permitted.
3.5 SELECTION, TRAINING AND MEDICAL SUPERVISION OF WORKERS
All formulations: Pre-employment and periodic medical examination
of workers is necessary and should include blood cholinesterase
tests. Special account should be taken of the workers' ability to
comprehend and follow instructions. Training of workers in
techniques to avoid contact is essential.
3.6 ADDITIONAL REGULATIONS RECOMMENDED IF DISTRIBUTED BY AIRCRAFT
No recommended aerial usage reported.
DANGER - POISON
(Skull and cross bones insignia)
Fenamiphos is an organophosphorus compound which inhibits
cholinesterase enzymes. It is of very high toxicity. Contact with
the skin, inhalation of dust or spray, or swallowing may be fatal.
Wear protective gloves, clean protective clothing, and a respirator
of the organic-vapour type when handling this material. 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 sulfate is a pharmacological
antidote. Artificial respiration may be needed.
3.8 RESIDUES IN FOOD
Maximum Residue Levels (MRLs) have been recommended by the FAO/WHO
Joint Meeting on Pesticide Residues (JMPR). The Acceptable Daily
Intake (ADI) has been estimated by the JMPR at 0 - 0.0005 mg/kg b.w.
4.0 PREVENTION OF POISONING IN MAN AND EMERGENCY AID
4.1 PRECAUTIONS IN USE
4.1.1 General: Fenamiphos is an organophosphorus pesticide
of high toxicity. It is readily absorbed through intact skin from
the gastrointestinal tracts and by inhalation. Repeated exposure may
have a cumulative effect on cholinesterase activity. Fenamiphos
formulations should only be handled by trained personnel wearing
protective clothing. Its use is severely restricted in several
4.1.2 Manufacture and formulation: TLV - 0.1 mg/m3.
This time-weighted average value has been determined from risks
associated with skin exposure and subsequent dermal absorption.
Dust and aerosol formation must be controlled, preferably by
mechanical means. Protective clothing (see 4.1.3) and respiratory
equipment is necessary to reduce dermal and inhalation exposures.
4.1.3 Mixers and applicators: When opening the
container and when mixing, protective impermeable boots, clean
overalls, neoprene gloves and 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 neoprene 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 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
fenamiphos 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 agricultural practice and subject to section 4.2 and 4.3
below, other populations should not be exposed to hazardous amounts
4.2 ENTRY OF PERSONS INTO TREATED AREAS
Unprotected persons should be kept out of treated areas for at least
4.3 SAFE DISPOSAL OF CONTAINERS AND SPILLAGE
Residues in containers should be kept to a minimum and emptied in a
diluted form into a deep dry pit (depth over 0.5 m), taking care to
avoid contamination of ground waters. The empty containers should be
disposed of in an approved manner. If not returned to the producer
re-use of containers should not be permitted for any purpose.
Spillage of liquid fenamiphos formulations should be covered with
absorbent material. This material or spillage of dry residues should
be collected and burned or buried as described above. Residues
should be removed by scrubbing with detergent and then rinsing with
large quantities of water.
Impermeable gauntlets and protective overalls should be used for all
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,
diarrhoea, blurred vision, 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. Artificial respiration should
be given when necessary bearing in mind that if mouth-to-mouth
resuscitation is used, vomit may contain toxic amounts of pesticide.
Call a physician immediately or organize immediate transport to a
physician or hospital.
5.0 FOR MEDICAL AND LABORATORY PERSONNEL
5.1 MEDICAL DIAGNOSIS AND TREATMENT IN CASES OF POISONING
5.1.1 General information: Fenamiphos is an
organophosphorus pesticide of high mammalian toxicity. It is readily
absorbed through intact skin and by inhalation. It acts by direct
inhibition of acetylcholinesterase affecting nerve transmission.
5.1.2 Symptoms and signs: Poisoning is 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). The
latter includes, 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
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.
Unless brain hypoxia has occurred, full recovery is expected.
5.1.6 References to previously reported cases:
No published information available.
5.2 SURVEILLANCE TESTS
Any fall in erythrocyte cholinesterase activity to 70% of the pre-
exposure value, 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 pre-exposure value. 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 the pre-exposure value.
Pseudocholinesterase activity in the plasma can fall to very low
levels without evidence of symptoms. This only indicates undesirable
5.3 LABORATORY METHODS
5.3.1 Detection and assay of compound:
A specific gas-chromatographic procedure for the determination of
residues of fenamiphos and sulfoxide and sulfone is available. Some
basic references are listed as follows:
Luke MA, Froberg JE, Doose GM, Masumoto HT (1981), J Assoc Off Anal
Chem 64(5): 1187-1195.
Peterson D, Winterlin W (1986), J Agric Food Chem, 34(2): 153-156.
Thornton JS, (1971), J Agric Food Chem 19: 890-893.
5.3.2 Other tests in case of poisoning: Activity of
cholinesterase in the blood or plasma 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.
1. 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.
2. 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.
3. WHO (1975), 1974 Evaluations of Some Pesticide Residues in Food. WHO
Pesticide Residue Series No. 4, 295-333, Geneva, World Health
4. WHO (1986), Environmental Health Criteria No. 63, Organophosphorus
Insecticides: A General Introduction. UNEP/ILO/WHO Geneva.
5. 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).
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