WORLD HEALTH ORGANIZATION FOOD AND AGRICULTURE ORGANIZATION
ORGANISATION MONDIALE DE LA SANTE ORGANISATION POUR L'ALIMENTATION
ET L'AGRICULTURE
WHO/VBC/DS/87.74
ORIGINAL: ENGLISH
Distr.: LIMITED
DATA SHEET ON PESTICIDES No. 74
PHOSPHAMIDON
CLASSIFICATION:
Primary Use: Insecticide
Secondary Use: Acaricide
Chemical Group: Organophosphorus compound
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.
1.0 GENERAL INFORMATION
1.1 COMMON NAME: Phosphamidon (ISO, BSI and ANSI)
1.1.1 Identity:
IUPAC: 2-chloro-2-diethylcarbamoyl-1-methylvinyl dimethyl
phosphate
CAS: 2-chloro-3-(diethylamino)-1-methyl-3-oxo-1-propenyl
dimethyl phosphate
CAS Reg. No.: 297-99-4 (trans-isomer), 23783-98-4
(cis-isomer), 13171-21-6 (mixture)
Molecular formula: C10H19ClNO5P
Molecular weight: 299.70
Structural formula:
1.1.2 Synonyms: Phosphamidone; Famfos; DimecronR; DixonR; C-570;
Ciba-570; ENT 25,515; ML-97; Or-1,911
1.2 SYNOPSIS: Phosphamidon is a noncumulative systemic
organophosphorous pesticide with a broad spectrum of activity: It
is a cholinesterase inhibitor with rapid contact and stomach
action. The technical product is very highly toxic to mammals and
is listed in WHO Hazard Class Ia.
1.3 SELECTED PROPERTIES
1.3.1 Physical characteristics - Phosphamidon is a pale yellow to
colorless oily liquid with a faint odour. It has a boiling point
of 162°C at 1.5 mmHg; a density (d)254 of 1.2132 and a refractive
index (n)20D of 1.4721. Phosphamidon exists as a mixture of 70%
cis-isomer and 30% trans-isomer and is corrosive to iron,
tinplate and aluminium.
1.3.2 Solubility - Phosphamidon is miscible with water. It is soluble
in aromatic hydrocarbons but insoluble in non-polar aliphatic
hydrocarbons.
1.3.3 Stability - It is stable in neutral and acid media but is
hydrolyzed by alkali; halflife at 23°C is 13.8 days at pH 7 and
2.2 days at pH 10. Phosphamidon decomposes above 160°C.
1.3.4 Vapour pressure - 2.5 x 10-5 mmHg.
1.4 AGRICULTURE, HORTICULTURE AND FORESTRY
1.4.1 Common formulations - Available as 20-100% soluble concentrates
(from 200 to 1000 g a.i./l in 2-propanol), as 0.5g/kg granules
and in U.L.V. formulations. The granules are in WHO Hazard Class
II (moderately hazardous).
1.4.2 Pests controlled - These include sap-feeding insects, sugar cane
and rice stemborers and rice leaf beetles.
1.4.3 Use pattern - Phosphamidon is used on citrus and cotton crops,
deciduous fruit and nut crops at rates of 300-600 g a.i./ha for
sap-feeding insects and 500-1000 g a.i./ha for other pests.
1.4.4 Unintended effects - Phosphamidon is highly toxic to bees. It is
non-phytotoxic except to some cherry and sorghum varieties.
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 - Phosphamidon may be readily absorbed from the
gastrointestinal tract, through the intact skin and by inhalation
of spray mists and dusts.
2.1.2 Mode of action - Phosphamidon is a cholinesterase inhibitor. An
impurity in the technical product, gamma-chlorphosphamidon,
inhibits mammalian cholinesterases 10 to 20 times more than pure
phosphamidon.
2.1.3 Excretion products - Metabolism and excretion is rapid in
mammals. After ip injection of 32P-labelled phosphamidon to
rats, 60% of the dose was recovered in 24 hours. In rats and
goats, oxidative metabolism yielded mostly desethyl phosphamidon,
phosphamidon amide and deschloro-phosphamidon. However over 90%
of radioactivity in the urine was in the form of nontoxic
unextractable polar metabolites.
2.1.4 Toxicity, single dose -
Oral LD50:
Rat 17 mg/kg b.w.
Mouse 10 mg/kg b.w.
6.5 mg/kg b.w. (cis-isomer)
220 mg/kg b.w. (trans-isomer)
Dog 50 mg/kg b.w.
Rabbit 32 mg/kg b.w.
Onset of poisoning is extremely rapid. Clinical signs include
hypersalivation, lacrimation, miosis, dyspnea, vomiting,
ataxia, convulsions, tetany and opisthotonos.
Dermal LD50:
Rat 374 mg/kg b.w.
Inhalation LC50:
Rat 102 mg/m3/4h (head only exposure)
Rat 135 mg/m3/4h (whole body exposure)
Rat 160 mg/m3/4h
Mouse 33 mg/m3/4h
Guinea pig 1300 mg/m3/4h
I.P. LD50:
Rat 9.2 mg/kg b.w.
Mouse 5.8 mg/kg b.w.
I. V. LD50:
Mouse 6 mg/kg b.w.
Most susceptible species - No appreciable species variability
has been found among the animals tested.
2.1.5 Toxicity, repeated doses -
Oral: Male rats (5/group) were administered 2.5, 5.0 or 10 mg/kg
b.w./day of 83% phosphamidon by stomach tube. All rats at 5 and
10 mg/kg b.w./day died after 1-33 days. Similarly all rats given
daily oral doses of 5 and 10 mg/kg b.w. of 20% phosphamidon in
isopropanol died within 41 days. One of five rats at 2.5 mg/kg
b.w./day died during a ten-week period.
Rats were dosed daily by stomach tube with 0.3 or 3.0 mg/kg b.w.
phosphamidon in propylene glycol. At 3 mg/kg b.w. serum
cholinesterase activity was reduced by 14% and brain
cholinesterase was reduced by 12.5% after one dose. After seven
and 14 days treatment, the inhibition was 42.5 and 37% in serum
and 55 and 67.5% in brain respectively. In rats left undosed for
a further seven days, brain cholinesterase activity remained
inhibited at 47.5%. The no-effect level was reported to be 0.3
mg/kg b.w./day.
Daily oral doses of phosphamidon of 1.08 mg (approximately 68
mg/kg b.w.) in adult female rabbits for 30 days did not reveal
any significant clinical symptoms of toxicity. Higher levels of
2.16 mg of phosphamidon (approximately 1.35 mg/kg b.w.) resulted
in overt toxicity in a 15 day treatment period. Treated animals
showed morphological changes in liver, kidney, adrenal and brain,
and haemoglobin and erythrocyte levels increased. Cholinesterase
activity was inhibited in erythrocytes and brain by 72.05 and
84.15% respectively.
Daily oral doses of phosphamidon in rabbits resulted in one of
three animals dying at 3.5 mg/kg b.w. (in 21 days), two of three
animals dying at 7 mg/kg b.w. (in eight days), and total
mortality of five animals at 15 mg/kg b.w. within seven days.
Dermal: Rabbits dosed with 0.1, 0.25 or 0.5 ml/kg b.w. of a 12%
solution of phosphamidon for six weeks showed erythema and oedema
in increasing incidence, thought to be solvent related. Other
toxic signs included hyperpnoea, hypersalivation, tremor and
ataxia at the two highest dose levels. Inhibition of blood and
brain cholinesterases was significant in males and females at
0.25 ml/kg level with the exception of brain cholinesterase
activity in females which appeared unaffected at 0.25 ml/kg
level. No effect level: 0.1 ml/kg (0.019- mg a.i./kg b.w.).
Inhalation: Wistar rats exposed to a continuous flow of air
containing 0.05 or 0.5 mg/m3 of phosphamidon for four hours
daily, five times a week, for 42 days suffered a temporary
inhibition of erythrocyte cholinesterase. No effect on
mortality, behaviour, haematology, clinical chemistry or
pathology was observed.
Intravenous: In a 14 day experiment, rabbits survived dally
injections of 3 mg/kg b.w. phosphamidon whereas 2/3 mortality was
observed at 7.5 mg/kg b.w.
2.1.6 Dietary studies -
Short term: Dogs fed phosphamidon at 0, 0.05, 0.1, or 2.5 mg/kg
b.w./day in capsule form for three months did not show any ill
effects except in the highest dose group. Decreases in body
weight gain, in food consumption in females, in haematology
parameters, as well as an increase in GTP in males and
inhibitions of blood and brain cholinesterases for both sexes
occurred at the highest dose level. No other findings were
noted.
No effect level: 0.1 mg/kg/b.w./day.
Long term: Two year feeding studies: No effect levels:
Rat 1.25 mg/kg b.w./day
Dog 0.1 mg/kg b.w./day
A 5 mg/kg b.w./day dose in rats caused significant weight
depression while moderate clinical symptoms, attributable to
cholinesterase inhibition, occurred at a dose level of 2.5 mg/kg
b.w./day in dogs.
2.1.7 Supplementary studies of toxicity -
Carcinogenicity: When Osborne-Mendel rats were fed dietary levels
of 80 or 160 mg/kg diet phosphamidon was found to give equivocal
results. In B6C3F1 mice fed similar dietary levels of
phosphamidon, no evidence of carcinogenicity was indicated.
Teratogenicity: No information available.
Reproduction: No information available.
Mutagenicity: Phosphamidon has been shown to demonstrate
clastogenic effects in in vivo tests with bone marrow cells of
rats and mice. It has also been shown to be capable of inducing
genetic damage in in vitro human lymphocyte studies and in vivo
host mediated assays and micronuclei tests. Phosphamidon was not
mutagenic in metabolically activated or non-activated systems of
mouse lymphoma cells (L5178Y/TK+/-), or Salmonella typhimurium.
Phosphamidon was mutagenic only in metabolically activated
systems of Saccharomyces cerevisiae D7, exerted slight
clastogenic activity in a Chinese hamster-nucleus anomoly test at
levels over 5 mg/kg but was not mutagenic in sister chromatid
exchange assays using Chinese hamster bone marrow cells (10
mg/kg). No DNA damage was induced in systems utilizing rat
hepatocytes and human fibroblasts.
Neurotoxicity: No published information available.
2.1.8 Modifications of toxicity - The cis-isomers of phosphamidon and
its desethyl metabolite were found to be approximately 40 times
more toxic than the trans-isomers. N-deethylation of phosphamidon
increases its toxicity.
In acute studies, no potentiation occurred between equal
quantities of phosphamidon and other organophosphorus
insecticides (dimethoate, endothion, ethion, malathion,
mevinphos, oxydemeton-methyl, and parathion.
2.2 TOXICOLOGY - MAN
2.2.1 Absorption - Phosphamidon may be absorbed from the
gastrointestinal tract, through the intact skin and by inhalation
of spray mists and dusts.
2.2.2 Dangerous doses -
Single: Phosphamidon has been given a toxicity rating of 5
(Gosselin), the probable oral lethal dose is 5-50 mg/kg b.w.
Temporary acceptable daily intake for man: 0-0.001 mg/kg b.w.
Repeated: No information available.
2.2.3 Observations on occupationally exposed workers - Two operators
were completely drenched with 50% phosphamidon and six others
were splashed. Following a thorough wash, symptoms of gastric
pains, headache and burning sensation in the eyes were reported
with uneventful recovery.
2.2.4 Observations on exposure of the general public - No information
available.
2.2.5 Observations on volunteers - Thirty two people (10-70 years old)
remained in paddy fields during and one hour after ULV
phosphamidon aerially sprayed at 550 g/ha. The unprotected
volunteers, exposed to twice the recommended rate of compound,
experienced conjunctival irritation. Plasma cholinesterase
levels were depressed 0-25% in 19 people, 26-50% in 19 other
people and over 50% in two people with complete recovery in nine
days. Erythrocyte cholinesterase was not affected.
[Editors note: Inhibition of plasma cholinesterase is an accepted
sign of exposure as in this case intoxication is related to
inhibition of erythrocyte cholinesterase.]
2.2.6 Mishaps - In one suicidal poisoning, an apneic and cyanotic 18-
year-old girl survived six days before severe bilateral
bronchopneumonia caused her death. Autopsy revealed brain and
liver injury but investigators concluded that anoxia may have
been a factor in tissue injury.
A 10 year-old boy ingested between 60 and 120 mg/kg b.w. of 20%
phosphamidon. Recovery was rapid following the use of an emetic.
2.3 TOXICOLOGY - NON-MAMMALIAN SPECIES
2.3.1 Fish - Low toxicity to fish.
LC50: (24 hr) Fathead minnows 4.8 mg/l
Rainbow trout 4.4 mg/l
LC50: (96 hr) Rainbow trout 3.2-20 mg/l
(technical
product) Crucian carp 600 mg/l
Channel catfish 360 mg/l
Bluegill 150 mg/l
Guppy 54 mg/l
2.3.2 Birds -
Acute Oral LD50:
Mallard duck (F) 3.81 mg/kg b.w. 80% in water
Mallard duck (F) 3.05 mg/kg b.w. 80% in isopropanol
Chukar partridge (M,F) 9.07 mg/kg b.w. 80% in isopropanol
Pigeon (M,F) 2-3 mg/kg b.w. 80% in isopropanol
Mourning dove (M,F) 2-4 mg/kg b.w. 80% in isopropanoglycol
Whitewing dove (M,F) 26 mg/kg b.w. 85% in isopropanol
Acute Dermal LD50:
Mallard duck (F) 26 mg/kg b.w. 85% in propylene
Eight Day Feeding Study LD50:
Technical Product:
Wildbirds (five species) 3.16-5.62 mg/kg
Other species 2.1-14.0 mg/kg
Pheasant 0.8 mg/kg
Eight Day Feeding Study LC50:
Peking Ducks 918.0 mg/l
Japanese Quails 1612.0 mg/l
Dietary Studies:
In a 100 day study, 50% mortality in young and adult birds was
observed at dietary levels of 1-100 and 10-200 mg/kg
respectively. Treatment of chick embryos with phosphamidon (1
mg per egg) resulted in growth retardation and malformations in
the head, and neck regions. Limb buds and eyes were also
adversely affected. Complete agenesis was seen in some organs
such as eyes at higher doses (2 and 20 mg per egg).
2.3.3 Other species - Phosphamidon is highly toxic to bees.
3.0 FOR REGULATORY AUTHORITIES - RECOMMENDATIONS ON REGULATION OF
COMPOUND
3.1 RECOMMENDED RESTRICTIONS ON AVAILABILITY
(For definitions of categories, see the Introduction to Data Sheets)
All formulations 85% and over are placed in Category 1
All other available formulations are placed in Category 2
3.2 TRANSPORTATION AND STORAGE -
Formulations in category 1 and 2: 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
secure from access by unauthorized persons and children.
3.3 HANDLING
Formulations in category 1 and 2: Full protective clothing (see
part 4) should be used by all those handling the compound.
Adequate washing facilities should be available close at hand.
Eating, drinking and smoking should be prohibited during
handling and before washing after handling.
3.4 DISPOSAL AND/OR DECONTAMINATION OF CONTAINER - Container must be
either burned or crushed and buried below topsoil. Care must be
taken to avoid subsequent contamination of water sources.
Container may be decontaminated (for method see paragraph 4.3 of
Part 4) but should not be used for food or drink.
3.5 SELECTION, TRAINING AND MEDICAL SUPERVISION OF WORKERS -
Formulations in category 1 and 2: Pre-employment and periodic
medical examination for workers desirable. Workers suffering from
active hepatic or renal diseases should be excluded from
contact. Pre-employment and cholinesterase tests for workers are
desirable except for those handling only 0.5g/kg granules.
Special account should be taken of 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 -
All formulations: Pilot and loaders should have special training
in application methods and early symptoms of poisoning. Flagmen,
if used, should wear overalls and a broad brimmed hat and, be
located well away from the dropping zone.
3.7 LABELLING -
All formulations, minimum cautionary statement:
"DANGER - POISON"
(skull and cross bones insignia)
Phosphamidon is an organophosphorous compound which inhibits
cholinesterase. It is of very high toxicity. Contact with the
skin, inhalation of dust or spray, or swallowing may cause illness
or be fatal. Wear protective gloves, and clean protective
clothing, 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 and oximes are accepted antidotes; repeated doses may be
necessary. Artificial respiration also may be needed.
3.8 RESIDUES IN FOOD - Maximum residue levels have been recommended by
the Joint FAO/WHO Meeting on Pesticide Residues.
4.0 PREVENTION OF POISONING IN MAN AND EMERGENCY AID
4.1 PRECAUTIONS IN USE
4.1.1 General - Phosphamidon is an organophosphorous pesticide of
extremely high 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 cholinesterase levels. Most formulations
should be handled by trained personnel wearing protective
clothing.
4.1.2 Manufacture and formulation - TLV - No information. 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, and gloves
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 applicqror 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 (including flagmen in aerial operations)
Persons exposed to phosphamidon 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 phosphamidon.
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 at
least 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.
The container should then be filled with water and allowed to
stand 24 hours. Empty and repeat three times. Decontaminated
containers should not be used for food, feed or drinking water.
Spillage of phosphamidon and its formulations should be removed by
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 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 should be given, bearing in mind that if
mouth-to-mouth resuscitation is used, vomit may contain toxic
amounts of phosphamidon.
5.0 FOR MEDICAL AND LABORATORY PERSONNEL
5.1 MEDICAL DIAGNOSIS AND TREATMENT IN CASES OF POISONING
5.1.1 General information - Phosphamidon is an organophosphorous
pesticide of extremely high mammalian toxicity which is active
against a variety of agricultural 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 analogues of phosphamidon which also 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 whole blood or erythrocyte cholinesterase. Urinary levels of
organic phosphorus containing metabolites may also be used as a
measure of exposure. Neither method is specific for phosphamidon.
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 large quantities of
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 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, barbiturates, phenothiazine, tranquillizers (except
Diazepam) and central stimulants of all kinds. Pralidoxime and
toxogonin alone are not regarded as effective antidotes in
phosphamidon 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 - Phosphamidon has been
implicated in several cases of pesticide poisoning, see Gitelson,
S. et al., (1965) Br. J. Ind..Med., 22 236-239.
5.2 SURVEILLANCE TESTS
Test Normal Action Symptomatic
level* level* level*
Plasma cholinesterase 100% 50% variable
Whole blood or erythrocyte 100% 70% usually 40%
cholinesterase
* Expressed as percentage of pre-exposure values
5.3 LABORATORY METHODS
5.3.1 Detection and assay of compound - Thin-layer chromatography and
gas-liquid chromatography methods have been used to analyse
phosphamidon in technical products and in its formulations.
Analysis of residues in plant and animal tissues - gas
chromatography and flame photometry methods.
5.3.2 Other tests in case of poisoning - 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.
Measurement of urine metabolites may also be determined in order
to given indication of exposure for methods. See section 5.3.1,
Detection and Assay.