WORLD HEALTH ORGANIZATION FOOD AND AGRICULTURE
ORGANIZATION
ORGANISATION MONDIALE DE LA SANTE ORGANISATION POUR L'ALIMENTATION
ET L'AGRICULTURE
WHO/VBC/DS/87.60 Rev.1
ORIGINAL: ENGLISH
Distr.: LIMITED
DATA SHEETS ON PESTICIDES No. 60
DEMETON
Rev. 1
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
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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
1.0 GENERAL INFORMATION
1.1 COMMON NAME:
Demeton (ISO, BSI - exception USSR), a mixture of Demeton-O (I)
and Demeton-S (II)
1.1.1 Identity:
IUPAC and CAS No. 1:
(I) O,O-diethyl O-[2-(ethylthio)ethyl] phosphorothioate
(II) O,O-diethyl S-[2-(ethylthio)ethyl] phosphorothioate
CAS Reg. No.: 8065-48-3 (mixture of isomers)
(I) 298-03-3
(II) 126-75-0
Molecular formula: C8H19O3PS2
Molecular weight: 258.3
Structural formula:
1.1.2 Synonyms
(Mixture) Bayer 10756R; Demeton; DemoxR; Mercaptophos;
SystemoxR; SystoxR; (I) Bayer 8169R; Demeton-O; Demeton I;
Di-SeptonR; E-1059; Ethylthiometon; Thiodemeton;
Thiolmercaptophos; (II) Demeton-S, Demeton-II, Isodemeton;
Isosystox; PO-SystoxR: PS-systoxR, Thioldemeton; Thiol-SystoxR
1.2 SYNOPSIS
Demeton is a mixture of isomers; a selective, non-cumulative
organophosphorus pesticide; and a cholinesterase inhibitor with good
contact and stomach action. The technical product is of extremely
high acute toxicity to mammals (WHO Hazard Class Ia). Demeton-O is a
mutagen in bacterial systems. Demeton is a plant systemic with long
residual action; selectively phytotoxic; and, extremely toxic to
bees, fish and wildlife.
1.3 SELECTED PROPERTIES
1.3.1 Physical characteristics
The reaction product, a 65:35 mixture of (I) and (II) is a
colourless oil with a strong sulfurous odour. The technical product
is a light yellow oil with a mercaptan odour also. Demeton-O has a
boiling point of 123°C (1 mmHg = 0.13 kPa); a density (d)21 of
4
1.119; and, a refractive index (n)18 of 1.4900. Demeton-S has a
D
boiling point of 128°C (1 mmhg); a density (d)21 of 1.132; and a
4
refractive index (n)18 of 1.500.
D
1.3.2 Solubility (room temperature)
Demeton-O 60 mg/1 water; soluble in most organic solvents
Demeton-S 2g/1 water, soluble in most organic solvents
1.3.3 Stability
Demeton is hydrolyzed by boiling water and strong alkali, but
it is compatible with most nonalkaline pesticides, except water
soluble mercury compounds.
1.3.4 Vapour pressure
Demeton-O 2.84 x 10-4 mmHg = 38 mPa at 20°C
Demeton-S 2.6 x 10-4 mmHg = 35 mPa at 20°C
1.4 AGRICULTURE, HORTICULTURE AND FORESTRY
1.4.1 Common formulation
Formulated as a 2.5g/kg and 6.6g/kg emulsifiable concentrate.
1.4.2 Pests controlled
Mites, aphids and sap-feeding insects such as whiteflies,
leafhoppers, thrips and leafminers.
1.4.3 Use pattern
Wide range of fruits, vegetables and ornamentals. Applied as
soildrench or foliage spray. It is generally applied 140 to 800
g/ha.
1.4.4 Unintended effects
Phytotoxic to some ornamentals; toxic to bees.
1.5 PUBLIC HEALTH USE
No recommended use.
1.6 HOUSEHOLD USE
No recommended use.
2.0 TOXICOLOGY AND RISKS
2.1 TOXICOLOGY - MAMMALS
2.1.1 Absorption route
Demeton may be absorbed from the gastrointestinal tract,
through the intact skin, and, by inhalation of spray mist.
2.1.2 Mode of action
Demeton is a direct inhibitor of cholinesterase through
phosphorylation of the esteratic site of the enzyme. Demeton and its
oxidation products, the sulfoxide and the sulfone are similar in
their toxicity and anticholinesterase activity. Demeton also
inhibits the hydrolysis of diethylsuccinate and tributyrin in liver
and serum.
2.1.3 Excretion of products
A major metabolite O,O-diethylphosphorothiolate (DEPTH)
results from the direct hydrolysis of demeton-S and from hydrolysis
of demeton-O followed by isomerization of O,O-
diethylphosphorothionate (DETP - another major metabolite).
2.1.4 Toxicity, single dose of technical material
Oral LD50: Rat (M) 6.2 mg/kg b.w
(F) 2.5 mg/kg b.w.
Mouse 7.85 mg/kg b.w.
Dermal LD50: Rat (M) 14 mg/kg b.w.
(F) 8.2 mg/kg b.w.
Rabbit 24 mg/kg b.w.
I.P. LD50: Rat 3.0 mg/kg b.w.
Mouse 4.0 mg/kg b.w.
Rabbit 3.25 mg/kg b.w.
I. V. LD50: Rat 1.75 mg/kg b.w.
Mouse 3.9 mg/kg b.w.
Inhalation - Exposure to 18 mg demeton/m3 of air fatal to
6/6 rats in 50-90 minutes.
2.1.5 Toxicity, repeated dose
Inhalation: Two hour exposure/day to 3 mg demeton/m3 of air
resulted in no illness in rats during first exposure; tremors during
second exposure; lacrimation and tremors during third exposure and
death in 10/17 during fourth exposure. 7/19 rats died after seven
to 12 one hour daily exposures to 3 mg demeton/m3 air.
2.1.6 Dietary studies
Short term: Rabbits were fed demeton sprayed greens for 30-100
days. Ingestion of 1.5 (mg demeton/kg b.w./day reduced
cholinesterase activity (55% of normal) with 4/6 deaths by 30 days.
Ingestion of 2.3 mg/kg b.w./day reduced plasma cholinesterase (70%
of normal) and 3/6 deaths by 30 days. At 0.15 mg/kg b.w./day for 98
days, no fatalities or reduced cholinesterase levels occurred.
Symptoms preceding death included respiratory distress, frothing at
nose and mouth, marked diarrhoea, muscular paralysis, coma and mild
asphyxial convulsions. Gastric intubation of 0.4, 0.66, 0.9 or 1.89
mg demeton/kg b.w./day in rats for 90 days caused intoxication
(hyperexcitability and tremors) at the two higher doses after 21
days. In a 16 week study, female rats were fed demeton 0 ,10, 20 and
50 mg/kg diet. Females at the highest dose were severely poisoned
but recovered after three to four weeks despite continued intake.
Blood and brain cholinesterase were 7.1 and 8.2% of normal
respectively. Rats fed 20 mg/kg diet showed levels of brain and
blood cholinesterase 15% of normal but otherwise appeared
unaffected. Brain and blood cholinesterase levels were 90% of normal
at 1 mg/kg diet (0.05 mg/kg b.w./day) in an 11 week study.
In a 24 week dog study, animals were fed demeton at 0, 1, 2, or
5 mg/kg diet. Inhibition of erythrocyte cholinesterase was slight at
5 mg/kg diet (0.149 mg/kg b.w./day); inhibition of plasma
cholinesterase was marked at 5 mg/kg diet and slight at 2 mg/kg diet
(0.047 mg/kg b.w./day). A dietary level of 1 mg/kg diet (0.025 mg/kg
b.w./day) was the no effect level for both enzymes.
Long term: No information available.
2.1.7 Supplementary studies of toxicity
Carcinogenicity: No information available.
Mutagenicity: Demeton was mutagenic for reverse mutations in
five strains of S. typhimurium and one strain of E. coli;
mutagenic in relative toxicity assays with DNA repair - proficient
and - deficient strains of E. coli and B. subtilus and in DNA
synthesis in human fibroblasts; induced sister chromatid exchange in
a hamster cell line: Induced mitotic recombination, mitotic crossing
over, gene conversion and reverse mutation in S. cerevisiae.
Teratogenicity: Demeton administered to mice between days
seven and 12 of gestation as single i.p. dose of 7 or 10 mg/kg b.w.
or as three consecutive doses of 5 mg/kg b.w. was found to be
embryotoxic (decreased foetal weight and higher mortality) with only
mild teratogenic potential. A few minor skeletal abnormalities were
produced at the 5 mg/kg b.w. dose level.
Reproduction: I.p. injection of pregnant mice (day 14 of
gestation) at 5 mg/kg 32P-labelled demeton produced heavy labelling
of placental tissue, foetal muscle and osteogenic mesenchyma within
20 minutes but only trace activity persisted after three hours.
Maximum levels in the liver were found between one to two hours.
Neurotoxicity: Demeton did not induce delayed neurotoxicity
in hens fed dose levels up to 1600 mg/kg (diet) for 14-20 weeks.
2.1.8 Modifications of toxicity
Rats maintained on a protein deficient diet for 28 days after
weaning were more susceptible than controls to a single dose of
demeton. Rats given fluoride by stomach tube at 16.8 or 33.6 mg/kg
b.w./day for three days had increased susceptibility to demeton.
Demeton does not potentiate the toxicity of other organic phosphorus
compounds including malathion.
2.2 TOXICOLOGY - MAN
2.2.1 Absorption route
Demeton may be absorbed from the gastrointestinal tract,
through the intact skin; and, by inhalation of spray mist.
2.2.2 Dangerous doses
Single: Not known.
Repeated: Not known.
2.2.3 Observations on occupationally exposed workers
A number of serious poisonings and a few deaths caused by
demeton have been associated with occupational exposure. Death was
attributed to demeton in the case of a worker cleaning a plane used
in application of the pesticide. Severely depressed cholinesterase
levels of red blood cells and plasma occurred although route of
exposure was uncertain. Levels up to 6 mg/m3 of demeton in the air
breathed by agricultural workers resulted in reduced serum
cholinesterase activity but no clinical symptoms.
2.2.4 Observations on exposure of the general population
No information available.
2.2.5 Observations on volunteers
The no-effect level for demeton was found to be 0.05 (mg/kg
b.w.)/day after 25 days of administration. At 0.1 (mg/kg b.w.)/day,
depressions of 39.8 and 15.9% in plasma and erythrocyte
cholinesterase activity occurred.
2.2.6 Reported mishaps
Transdermal poisoning by demeton was confirmed in a three year-
old by its high concentration in the clothing. Treatment with
pralidoxime chloride and atropine sulfate was effective. Plasma
cholinesterase levels 15 to 41 hours after exposure ranged from 0.24
- 0.48 IU. Approximate normal values (2.5 IU) were not reached until
five and one half days after exposure. Metabolites equivalent to
4.15 mg of demeton were recovered from his urine during the first 24
hours of hospitalization.
2.3 TOXICOLOGY - NONMAMMALIAN SPECIES
Oral LD50 Mallards (M) 7.19 mg/kg b.w.
of technical
material: Pheasants (F) 8.21 mg/kg b.w.
Grouse (M + F) 4.76 mg/kg b.w.
Chukar (M + F) 15.1 mg/kg b.w.
Coturnix (F) 8.48 mg/kg b.w.
Pigeon (M + F) 8.48 mg/kg b.w.
Sparrow (F) 9.52 mg/kg b.w.
Other effects: Ducklings hatched from eggs inoculated via the
yolk sac on day 13 with 10 or 100 µg demeton were hyperexcitable and
in some cases had leg paralysis and body tremors with intermittent
convulsions associated with cholinesterase inhibition.
3.0 FOR REGULATORY AUTHORITIES
3.1 RECOMMENDED RESTRICTIONS ON AVAILABILITY
(For definition of categories see the Introduction to Data Sheets)
All available liquid formulations, Category 1
There are no solid formulations available. WHO Hazard
Classification of technical product: Class Ia.
3.2 TRANSPORTATION AND STORAGE
All formulations - Should be transported and stored in
clearly labelled impermeable containers under lock and key, secure
from access by unauthorized persons and children. No food or drink
should be stored in the same compartment.
3.3 HANDLING
All formulations - Full protective clothing with organic
vapour cartridge respirator (see 4.1.3) should be used by those
handling the compound. Adequate washing facilities should be
available at all times during the handling and should be close to
site of handling. Eating, drinking and smoking should be prohibited
during handling and before washing after handling.
3.4 DISPOSAL AND/OR DECONTAMINATION OF CONTAINERS
All formulations - Containers must be either burned or
crushed and buried below topsoil. 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 medical examination of
workers is necessary. Workers suffering from hepatic or renal
disease should be excluded from contact. Pre-employment and periodic
cholinesterase tests for workers are desirable. Special account
should be taken of the workers' mental 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
All formulations - Pilots and loaders should have special
training in application methods and early symptoms of poisoning, and
must wear a suitable respirator. 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
"DANGER - POISON"
(skull and cross bones insignia)
Demeton is an organophosphorus compound which inhibits
cholinesterase. It is highly toxic. Contact with the skin,
inhalation of 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 sulphate and pralidoxime are
accepted antidotes, repeated doses may be necessary. Artificial
respiration also may be needed.
3.8 RESIDUES IN FOOD
Maximum residue levels - Maximum residue levels have been
recommended by the Joint FAO/WHO Meeting on Pesticides in Residues.
4.0 PREVENTION OF POISONING IN MAN AND EMERGENCY AID
4.1 PRECAUTIONS IN USE
4.1.1 General
Demeton is an organophosphorus pesticide of high toxicity. It
penetrates the intact skin and is also absorbed by inhalation and
from the gastrointestinal tract. Repeated exposure may have a
cumulative effect on cholinesterase levels. Most formulations should
be handled by trained personnel wearing protective clothing with
organic vapour cartridge respirator.
4.1.2 Manufacture and formulation
TLV - 0.1 mg/m3 skin (TWA), 0.3 mg/m3 (STEL) - ACGIH.
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 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 hat, 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 immediately after use,
separate from other laundry, 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 (including flagmen in aerial
operations)
Persons exposed to the compound 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 the
compound.
4.2 ENTRY OF PERSONS INTO TREATED AREA
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 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 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 or drink.
Spillage of the compound 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, hypersalivation,
stomach pains, blurred vision, slurred speech lacrimation,
urination, diarrhoea and muscle twitching. Later there may be
convulsions and coma.
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 and wash the affected skin with soap and water, if
available, 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 resuscitation is used,
vomit may contain toxic amounts of pesticide.
5.0 FOR MEDICAL AND LABORATORY PERSONNEL
5.1 MEDICAL DIAGNOSIS AND TREATMENT IN CASES OF POISONING
5.1.1 General information
Demeton is an organophosphorus pesticide of high mammalian
toxicity which is active against a variety of agricultural and
public health pests. It is readily absorbed from the
gastrointestinal fact; through the intact skin; and, by inhalation.
It is converted in vivo to the oxygen analogue which inhibits
cholinesterase. It does not accumulate in body tissues.
5.1.2 Symptoms and signs
Initial symptoms of poisoning may include excessive sweating,
headache, weakness, giddiness, nausea, hypersalivation, vomiting,
stomach pains, blurred vision, slurred speech and muscle twitching.
More advanced symptoms of poisoning may be convulsions, coma, loss
of reflexes and loss of sphincter control.
5.1.3 Laboratory
The most important finding is reduction of activity of blood
cholinesterases. Urinary levels of organic phosphorus containing
metabolites may also be used as a measure of exposure. Metabolites
can be identified specifically.
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 formulations containing petroleum
distillates gastric lavage should be done using a cuffed
endotracheal tube to prevent aspiration of the material. For skin
contact, the skin should be washed with soap and water. If the
compound has entered the eyes, they should be washed with large
quantities of isotonic saline or water. Persons without signs of
respiratory insufficiency but with manifest peripheral symptoms
should be treated with 2-4 mg of atropine sulfate by intravenous
injection and 1000 mg 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. Diazepam may be given to
control convulsions. 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, oxygen should be given at the
same time as atropine sulfate. The airways should be kept free and
artificial resuscitation should be applied if required, preferably
by mechanical means. If necessary, intubation should be performed.
Contraindications are morphine, aminophylline, phenothiazine,
reserpine, furosemide or ethacrynic acid. Give adrinergic amines
only if there is a specific indication. Pralidoxime and toxogonin
alone are not regarded as effective antidotes in organophosphorus
poisoning.
5.1.5 Prognosis
If the acute toxic effect is survived and adequate artificial
resuscitation has been given if needed, the chances of complete
recovery are good. However, in very severe cases, particularly if
artificial resuscitation has been inadequate, prolonged anoxIa may
give rise to permanent brain damage.
5.1.6 References of previously reported cases
Felsenstein, W. C. et al. (1976) Arch. Environ. Health
31(5): 266-269
Hayes, W. J. 1982, Pesticides Studied in Man, Williams &
Wilkins, Baltimore, MD, p. 390
Warinner, R. A. et al. (1977) Arch. Environ. Health 32 (5):
203-205
5.2 SURVEILLANCE TESTS
Test Normal level* Action level* Symptomatic level*
Plasma cholinesterase 100% 50% variable
Whole blood or 100% 70% usually 40%
erythrocyte
cholinesterase
5.3 LABORATORY METHODS
5.3.1 Detection and assay of compound
Bowman, M. C. et al. (1969), J. Assoc. Off. Anal. Chem.,
52, p. 157
CIPAC HANDBOOK (1979), Vol. 1, p. 302
* Expressed as percentage of pre-exposure values.
Hild, J. and Their, H. P., (1978), Z. Lebensom Unters
Forsch., 166(1), p. 9
MacDougall, D. (1964), Anal. Methods Pestic., Plant
Growth Regul., Food Addit., 2, p. 451
MacDougall, D. (1972), Anal. Methods Pestic. Plant Growth
Regul., 6, p. 483
Stan, H. J. (1977) Z. Lebensom Unters Forsch., 164(3), p. 153
Thornton, J. S. and Anderson, C. A. (1968), J. Agric. Food
Chem., 16, p. 895
5.3.2 Other tests in case of poisonings
Levels of cholinesterase in the blood, particularly plasma,
provide the most useful diagnosis of poisoning.
Michel, N. O. (1949), J. Lab. Clin. Med., 34:1564-1568
Ellman, G. L. et al. (1961), Biochem. Pharmacol., 7:88-95