WORLD HEALTH ORGANIZATION FOOD AND AGRICULTURE
ORGANIZATION
ORGANISATION MONDIALE DE LA SANTE ORGANISATION POUR L'ALIMENTATION
ET L'AGRICULTURE
VBC/PDS/DS/85.61
ORIGINAL: ENGLISH
DATA SHEETS ON PESTICIDES No. 61
DEMETON-S-METHYL
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.
CLASSIFICATION:
Primary use: Insecticide
Secondary use: Acaricide
Chemical group: Organophosphorus compound
1. GENERAL INFORMATION
1.1 COMMON NAME
Demeton-S-methyl (ISO, BSI and JMAF; exception USSR - methyl-
mercaptofos teolovy)
1.1.1 Identity
IUPAC and CAS: S-2-ethylthioethyl O,O-dimethyl
phosphorothiate
CAS Reg. No.: 919-86-8
Molecular formula: C6H15O3PS2 Molecular weight: 230.3
Structural formula:
1.1.2 Synonyms
AzotoxR; Bayer 18436; Bayer 21/116; Bayer 25/154; Campbell's
DsMR; Demeton-S-methyl; Demeton-S-metile; DemetoxR; DuratoxR;
Isometasystox; Isomethylsystox; Metaisoseptox; MetaisosystoxR;
Metasystox iR; Methyl demeton thioester; Methyl isosystox; Methyl
mercaptofos teolovy
1.2 SYNOPSIS
Demeton-S-methyl is a broad spectrum, non-cumulative, systemic
organophosphorus insecticide; a cholinesterase inhibitor with good
contact and limited stomach action; highly toxic to mammals, other
vertebrates and bees. Its toxicity is maintained after metabolism to
the oxygen derivatives, i.e., sulfoxide and sulfone.
1.3 SELECTED PROPERTIES
1.3.1 Physical characteristics
Demeton-S-methyl is a pale yellow oily liquid. It has a boiling
point of 89°C at 0.15 mmhg; a density (d20) of 1.707; and a
4
refractive index (n20 ) of 1.5065.
D
1.3.2 Solubility
In water, 3.3 g/litre at 25°C, it is readily soluble in
conventional organic solvents.
1.3.3 Stability
Demeton-S-methyl has a half-life of 7.6 days in an ethanol-Ph 6
buffer solution (1:4) at 70°C. In aqueous solutions, Ph 1-5, it has
a half-life of 88 days. The shelf-life is quite short yielding the
highly toxic sulfonium compound.
1.3.4 Vapour pressure
4.79 x 10-5 Kpa (3.6 x 10-4 mmhg) at 20°C.
1.4 AGRICULTURE, HORTICULTURE AND FORESTRY
1.4.1 Common formulations
These include emulsifiable concentrates of various
concentrations in the range of 250 g a.i./kg.
1.4.2 Pests controlled
Aphid vectors of vital diseases, whiteflies, leafhoppers,
sawflies, red spider mites and other pests of garden crops, fruit
and hops.
1.4.3 Use pattern
It is recommended for use on alfalfa, almonds, apples,
apricots, barley, beans, blackberries, broccoli, brussel sprouts,
cabbage, cauliflower, celery, clover cotton, dewberries, eggplant,
filberts, gooseberries, grapefruit, grapes, hops, lemons, lettuce,
loganberries, muskmelons, nectarines, otas, oranges, peaches, pears,
peas, pecans, peppers, pineapples, plums, potatoes, raspberries,
sorghum, strawberries, sugar beets, walnuts, wheat, conifers and
ornamentals. It is generally applied at 140-800 g/ha.
1.4.4 Unintended effects
Demeton-S-methyl is phytotoxic to ornamentals, especially
certain chrysanthemum cultivars; it is toxic to bees.
1.5 PUBLIC HEALTH USE
No recommended use.
1.6 HOUSEHOLD USE
No recommended use.
2. TOXICOLOGY AND RISKS
2.1 TOXICOLOGY - MAMMALS
2.1.1 Absorption
Demeton-S-methyl may be absorbed from the gastrointestinal
tract; through the intact skin; and by inhalation of spray mist and
dusts.
2.1.2 Mode of action
Demeton-S-methyl is a direct inhibitor of cholinesterase
through phosphorylation of the esteratic site of the enzyme.
Accumulation of acetylcholine at nerve synapses and myoneural
junctions causes the toxic effects. Demeton-S-methyl and its
oxidation products, the sulfoxide and the sulfone, are equally
toxic. The thiono-isomer is less toxic than the thiolo-isomer.
2.1.3 Excretion products
The metabolism and excretion of demeton-S-methyl have not been
extensively studied in mammals. By extrapolation from the ethyl
homologue demeton, metabolism should involve oxidation of the
thioether to the sulfoxide and, more slowly, to the sulfone by liver
microsomal enzymes. In mice 97% of demeton-S-methyl sulfoxide was
eliminated within 15 hours of dosing (per oral or subcutaneous),
mostly in urine.
2.1.4 Toxicity, single dose of demeton-S-methyl
Oral LD50:
Rat (H, F) 35-83 mg/kg bw; technical material
Guinea-pig (M) 110 mg/kg bw; technical material
Rabbit 20-50 mg/kg bw; technical material
Cat 5-10 mg/kg bw; technical material
Dog 50 mg/kg bw; technical material
Dermal LD50:
Rat 50-100 mg/kg bw; technical material
Cat 10-20 mg/kg bw; technical material
I.P. LD50;
Rat (M, F) 2-10 mg/kg bw; technical material
Rat (M, F) 27.5 mg/kg bw (pure)
Guinea-pig 12.5 mg/kg bw; technical material
I.V. LD50;
Rat (M) 8.4 mg/kg bw; technical material
Rat (M) 17.3 mg/kg bw (pure)
Rat (F) 64.5 mg/kg bw (pure)
Mouse (M) 4.1 mg/kg bw (purity unknown)
Mouse (M) 13.0 mg/kg bw (pure)
Oral LD50:
Rat 676 mg/kg bw
I.V. LD50;
Rat 216 mg/kg bw
Inhalation LC50:
Rat 500 mg/m3/4 hours
2.1.5 Toxicity repeated doses
Oral: Groups of male rats were given doses of 0, 1, 5 or 10
mg/kg bw for up to six months. Increased mortality was observed at
the two highest doses only; no ill-effects were observed at 1
mg/kg/day.
Dermal: No information available on demeton-S-methyl.
Demeton-S-methyl sulfoxide, a metabolite, was administered to
male and female rats for 60 days at dosage levels of 25 or 50 mg/kg
bw. The animals on the highest dose only showed signs of increased
cholinergic activity for the initial two weeks of treatment only. No
other ill-effects were observed.
Oxydemeton, a metabolite, was also administered to male and
female rats, approximately one-fifth of the LD50, five days a week
for three weeks. A slight reduction in body weight and a marked
inhibition of brain cholinesterase activity were observed at the end
of the study. No other ill-effects or changes in tissue histology
could be attributed to oxydemeton treatment.
Inhalation studies: Groups of male and female rats were
exposed to the metabolite demeton-S-methyl sulfone at concentrations
of 0, 0.0068 and 0.017 mg/litre for four hours a day, five days per
week for a period of 10 weeks. Cholinesterase depression was marked
and body weight gain was significantly depressed in all treatment
groups; no other ill-effects were observed.
Cumulation of compound: Demeton-S-methyl does not accumulate
in body tissues.
Cumulation of effect: Dermal and oral studies indicate that
there is none.
2.1.6 Dietary studies
Short-term: Groups of male rats were fed demeton-S-methyl at
dietary levels of 0, 50, 100 or 200 mg/kg. Depression of
cholinesterase activity was observed in all treatment groups;
however, signs of cholinergic toxicity were evident at the highest
dietary level only. Growth rates were depressed from 100 mg/kg
(diet). There were no treatment-related changes in gross or
microscopic anatomy.
Groups of male and female weanling rats were maintained on
diets containing 0, 2, 5, 10 or 20 mg/kg of demeton-S-methyl for
three months. There were no signs of toxicity or laboratory findings
that could be attributed to demeton-S-methyl at 10 mg/kg (diet) or
less.
Long-term: See section on Carcinogenicity.
2.1.7 Supplementary studies of toxicity
Carcinogenicity: Short-term dietary studies in rats have not
shown a carcinogenic potential for demeton-S-methyl. Two-year rat
studies with demeton-S-methyl sulfoxide have also not produced
evidence of carcinogenic activity for that compound at dietary
levels as high as 100 mg/kg. Mammalian mutagenicity and reproductive
studies show no supportive evidence for an oncogenic role.
Mutagenicity: Demeton-S-methyl has shown some mutagenic
potential in non-mammalian systems at 5 mg/plate in an E. coli and
an S. typhimurium plate test and in a Drosophila melanogaster
nondisjunction test. In mammalian systems, however, the sulfoxide
analogue was not mutagenically active in a mouse dominant lethal
assay (5 and 10 mg/kg bw).
Teratogenicity: Pregnant female rabbits were given oral doses
of oxydemetonthalidomide at 0, 0.1 and 0.2 mg/kg bw from days 6 to
18 of gestation; a thalidomide positive control was also carried
out. No clear treatment-related embryotoxic or teratogenic effects
were observed nor were there any ill-effects observed among the
does.
Reproduction: No clear treatment-related adverse effects were
observed in rats in a three-generation study at dosage levels of 10-
50 mg/kg (diet), although cholinesterase depression was produced. At
50 mg/kg (diet) the number of pregnancies and litter size were
significantly reduced.
Neurotoxicity: Demeton-S-methyl sulfone did not produce any
delayed neurotoxic effects at doses up to and including 200 mg/kg
bw.
2.1.8 Modifications of toxicity
No evidence of acute potentiation was observed when oxydemeton-
methyl was given in pairs with 15 other organophosphorus compounds,
at one-half the LD50 dose, to male rats.
2.2 TOXICOLOGY - MAN
2.2.1 Absorption route
Demeton-S-methyl or related compounds may be absorbed from the
gastrointestinal tract; through the intact skin; and by inhalation
of spray mist or dusts.
2.2.2 Dangerous doses
Single: Not known.
Repeated: Not known.
2.2.3 Observations on occupationally exposed workers
Over 700 cases of poisoning are known, including three
fatalities which followed a one-week exposure in an agricultural
spray programme. Lack of good personal hygiene was implicated as a
cause. All others apparently recovered without sequelae, most after
atroprine therapy and/or withdrawal from contact.
2.2.4 Observations on exposure of the general population
A group of teenagers and children living adjacent to a spray
area were found to have depressed cholinesterase levels. The
depression was attributed to air-borne contamination.
2.2.5 Observations on volunteers
The no-effect level for oxydemeton-methyl was found to be 0.05
mg/kg bw after a 60-day period of administration. 0.4 mg/kg bw
caused depression of serum and erythrocyte cholinesterase after
several days but no signs of poisoning. A single application of 1
mg/kg bw was tolerated without affecting cholinesterase activity,
whereas a 2 mg/kg bw single dose inhibited the enzyme.
2.2.6 Reported mishaps
There have been several cases of suspected suicide. A 60-year-
old man drank two liqueur glasses of demeton-S-methyl with two
bottles of beer. Conventional treatment was given in hospital within
two hours though there were no signs of toxicity at that time. In
addition, the patient was treated for chronic illnesses. At 60 hours
numbness developed, followed by diarrhoea at 72 hours and he died of
cardiac failure at 81 hours post-administration. No laboratory
findings were reported. A 65-year-old male ingested 15 ml of a
mixture of demeton-S-methyl (25%) and benzene methyl chloride; there
were no clinical signs of toxicity upon admission to hospital. After
32 hours his condition deteriorated; signs and symptoms were
consistent with anticholinesterase poisoning. Given conventional
treatment, he appeared to be recovering but died nine days later of
a pulmonary embolus.
A farmer drank 90 ml of a 70% a.i. solution of demeton-S-
methyl. Hospitalized within 30 minutes with the usual signs and
symptoms of anticholinesterase poisoning, he responded well to
conventional treatment including gastric lavage, recovering
completely.
A 26-year-old male injected demeton-S-methyl into his upper arm
at a rate of 44.6 mg/kg; surgical drainage released some of the
fluid. The patient survived a protracted illness with conventional
treatment.
2.3 TOXICOLOGY - NON-MAMMALIAN SPECIES
Fish, LC50 (96 hours);1
Cyprinus carpio 40-60 mg/litre
Scardinius erythrothalmis 30-40 mg/litre
Idis 20-40 mg/litre
Carassius duratus 20-40 mg/litre
1 Data supplied by manufacturer.
3. FOR REGULATORY AUTHORITIES - RECOMMENDATIONS ON REGULATION OF
COMPOUND
3.1 RECOMMENDED RESTRICTIONS ON AVAILABILITY
(For definition of categories, see the Introduction to Data
Sheets)
Liquid formulations of 20.0% and over, Category 2
Other liquid formulations, Category 3
There are no solid formulations available.
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 children and other unauthorized persons. No food or
drink should be stored in the same compartment.
3.3 HANDLING
All formulations - Full protective clothing (see section
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 necessary. Workers suffering from hepatic or renal disease
should be excluded from contact. Pre-employment and periodic
cholinesterase tests for workers desirable. Special account should
be taken of the workers' mental ability to comprehend and follow
instructions. Training of workers in techniques to avoid contact
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-S-methyl is an organophosphorus compound which inhibits
cholinesterase. It is highly toxic. 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 and
pralidoxime are specific 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 Pesticide Residues.
4. PREVENTION OF POISONING IN MAN AND EMERGENCY AID
4.1 PRECAUTIONS IN USE
4.1.1 General
Demeton-S-methyl 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.
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, 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 section 4.1.3 under "Mixers and
applicators".
4.1.5 Other populations likely to be affected
With good application practice, subject to section 4.2 below,
other persons are not likely to be exposed to hazardous amounts of
the compound.
4.2 ENTRY OF PERSONS INTO TREATED AREAS
Unprotected persons should be kept out of tall crops for four
days and out of other crops for 24 hours after application.
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 groundwaters. 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 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 pesticide.
5. FOR MEDICAL AND LABORATORY PERSONNEL
5.1 MEDICAL DIAGNOSIS AND TREATMENT IN CASES OF POISONING
5.1.1 General information
Demeton-S-methyl is an organophosphorus pesticide of moderate
mammalian toxicity which is active against a variety of agricultural
and public health pests. It is readily absorbed from the
gastrointestinal tract; through the intact skin; and by inhalation.
It is converted in vivo to the oxygen derivatives which inhibit
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. Neither
method is specific for the compound.
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.
Contraindicated are morphine, barbiturates, phenothiazine,
tranquillizers and central stimulants of all kinds. Pralidoxime and
toxogonin alone are not regarded as effective antidotes in
organophosphorus poisoning. In cases of severe poisoning, when
administered early, pralidoxime may be used to relieve nicotinic
effects.
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
Demeton-S-methyl has been implicated in a number of cases of
pesticide poisoning.
Barr, A.M. (1964) M. J. Aust., 1, 792-796
Tilsner, V. (1966) Vergiftung Argtliche Fosch., 20, 272-273
United Kingdom Ministry of Agriculture, Fisheries and Food
(1969) Report on the use of poisonous substances in agriculture and
on the worker and of the Agriculture Regulations during 1969
Hegazy, M. R. (1965) Br. J. Med., 22, 230-235
Khasanor, V. K. & Li, A. P. (1970) Med. Zh. Uzb., 7, 12-13
Readhead, I. H. (1968) Lancet, 1, 686-688
5.2 SURVEILLANCE TESTS
Normal Action Symptomatic
Test level* level* level*
Plasma cholinesterase 100% 50% variable
Whole blood or erythrocyte
cholinesterase 100% 70% usually 40%
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 demeton-S-methyl in technical products and
in its formulations. Analysis of residues in plant and animal
tissues gas chromatography and flame photometry methods.
Boshoff, P. R. & Pretorium, V. (1979) J. Agric. Food Chem.,
27(3), 626
Brinkman, U. & De Vries, G. (1979) Chromatog., 161(1), 167
CIPAC HANDBOOK (1970) Vol. 1, p. 312
Fysh, R. R. & Jones, L. V. (1980) Forensic Toxicol., Eur.
Meet. Int. Assoc. Forensic Toxicol., pp. 189-203
Hild, J. & Thief, H. P. (1978) Z. Lebensom. Unters. Forsch.,
166(1), 9
Laws, E. Q. & Webley, D. J. (1959) Analyst (London), 84, 28
MacDougal, D. (1964) Anal. Methods Pestic. Plant Growth
Regulators Food Adit., 2, 295 Ramsay, J. D. et al. (1980) J.
Chromatogr., 184(2), 185
Stan, H. J. (1977) Z. Lebensom. Unters. Forsch., 164(3), 153
Start, H. J. et al. (1977) Fresenius 'Z'. Anal. Chem.,
287(4-5), 271
Tietz, H. & Frehse, H. (1960) Hoefchen-Briefe (Eng. Edition),
3, 212
* Expressed as percentage of pre-exposure activity.
Van der Merwe, J. H. & Taylor, W. B. (1977) Pflanzenschutz-
Nachr. (Amer. Edition), 24, 259
Wagner, K. & Thorton, J. S. (1977) Pflanzenschutz-Nachr.,
30(1), 1
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 give an indication of exposure. For methods, see section
5.3.1, "Detection and assay of compound".