ELSEVIER Toxicology91 (1994) 15-27

IOXICOLOGY
Chapter 3

Organophosphorous compounds

Jerry Jeyaratnam and Marco Maroni

3.0 Name of group

Organophosphorous (OP) compounds are a group of insecticides which are also

acutely toxic to mammals. They act by inhibiting the enzyme acetylcholinesterase
(ACHE) in the target species and as such they are termed anticholinesterase insec-
ticides. Organophosphorous esters include a large number of substances chemically
deriving from phosphoric and thiophosphoric acids. A large number of these com-
pounds are not in current use anymore and have been replaced by less toxic insec-
ticides such as pyrethroids or carbamates.
A few OP compounds are used as herbicides (glyphosate, merphos, etc.).
Organophosphorous herbicides are structurally different from the OP insecticides
and their ACHE-inhibiting power is very weak.
In particular, glyphosate (glycerol phosphoric acid), used for nonselective weed
control, is not a significant inhibitor of cholinesterase and is not relevant from the
toxicological point of view. Therefore it will not be discussed in this chapter.

3.1 Mode of action - - toxic effects

OP compounds owe their toxic effect to the inhibition of cholinesterase enzyme

activity in the nervous tissue. There are different types of cholinesterases in the
human body, which differ in their location in tissues, substrate affinity, and
physiological function. The principal ones are ACHE, which besides nervous tissue
is also present in red blood cells, and plasma cholinesterases (PCHE), which are a
group of enzymes present in glial cells, plasma and liver. All the effects induced by
OP compounds in the organism are due to the inhibition of ACHE; PCHE is in-
hibited as well, but with no apparent functional impairment. Acetylcholinesterase,
under normal physiological conditions, performs the breakdown of acetylcholine,
which is the chemical mediator responsible for physiological transmission of nerve
impulses at different sites. In the presence of OP insecticides, acetylcholinesterase is
phosphorylated and is no longer able to break down acetylcholine into choline and

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16 J. Jeyaratnam, M. Maroni / Toxicology 91 (1994) 15-27

acetic acid (Fig. 1). The resulting accumulation of acetylcholine in the parasym-
pathetic nerve synapses (muscarine-like action), the motor end-plate (nicotine-like
action), and in the central nervous system is responsible for all the typical symptoms
occurring after acute poisoning with OP compounds.
Even though all OP compounds have a common mechanism of action, their effec-
tiveness as inhibitors of acetylcholinesterase varies widely. Further, OP compounds
can be classified as direct or indirect inhibitors of acetylcholinesterase. Direct in-
hibitors are effective without any further metabolic modification after absorption
into the body. Indirect inhibitors need to be transformed in the body to be effective.
All thiono OP pesticides, that is those containing a P~-S bond (mainly the
phosphorothioates and phosphorodithioates), are not active inhibitors of ACHE,
but require activation by oxidation of the P = S to the P = O group. The practical
importance of this classification is that direct inhibitors cause symptoms and signs
to appear quickly during or after exposure, providing an early warning; whereas in
the case of indirect inhibitors symptoms and signs appear later and the effects last
longer after-cessation of exposure. The insecticide dichlorvos is an example of a
direct inhibitor while malathion and parathion are indirect inhibitors. Other ex-
amples are reported in the annexed list of OP compounds.

3.2 Signs and symptoms of poisoning in man

For most OP pesticides, dermal exposure and subsequent absorption through in-
tact skin represents the most important route of entry in case of occupational ex-
posure.
The oral route of entry is important in accidental ingestion and ingestion with in-
tent to commit suicide. Occupational accidental ingestion may occur as a result of
poor work practices and lack of personal hygiene.
The respiratory route is generally less important. Inhalation of OP depends on
volatility of the compound, on the type of formulation and on the technique of ap-
plication.
Acute effects appear immediately or shortly after exposure to OP pesticides: with
dermal absorption it usually takes about 2-3 h for symptoms and signs to become
manifest. However, it is possible to observe effects within 1/2-1 h, depending on the
circumstances of the intoxication. A few OP compounds may be retained in the fat
tissue of the body which may result in symptoms to be delayed for up to 24 h.
The symptoms of intoxication can be divided into muscarine-like and nicotine-like
effects, as well as effects on the central nervous system. The muscarine-like effects
include increased sweating, pinpoint pupils, salivation and lachrymation, broncho-
constriction and increased secretion from the bronchial glands, abdominal spasms
with vomiting and diarrhoea, and bradycardia. The nicotine-like effects include
tachycardia and muscular fasciculation or twitching of fine muscles, in more severe
cases of diaphragm and respiratory muscles. The central nervous system manifesta-
tions include headache, slight tiredness, dizziness, anxiety, confusion, convulsions,
depression of the respiratory centre, coma.
 C~..N-~C~"LrO'C = 0 C= 0
I I I
CH= ~ C~
ACETYLCHOLINE ACYLATED ENZYME

D IETHYLPHOSPHORIC
ACID

PARAOXON PHOSPHORYLATED
ENZYME
Fig. 1. Reactions of acetylcholinesterase (ACHE) with inhibitors or substrates. A, Hydrolysis of the
physiological substrate acetylcholine. B, Reaction with paraoxon.
18 J. Jeyaratnam, M. Maroni/Toxicology 91 (1994) 15-27

Onset and intensity of symptoms vary depending on the compound (direct/indirect

inhibitors, see 3.1), and on the route and level of exposure.
The first symptoms are usually nausea, headache, tiredness, giddiness, and blurred
vision - - often described 'as though a veil has fallen over the eyes' - - and pupillary
constriction. Depending on the severity of poisoning these symptoms become worse
with the onset of vomiting, abdominal pain, diarrhoea, sweating and salivation. Pro-
gressive worsening is characterized by muscular twitchings which usually commence
in the tongue and the eyelids, progressing to tremor convulsions and finally
paralysis. There is also bronchoconstriction and bronchial hypersecretion and in the
final stages, paralysis, convulsions, respiratory depression and coma are observed.
In fatal OP poisoning the immediate cause of death is generally asphyxia resulting
from respiratory depression.
The diagnosis of organophosphorous acute poisoning is usually based on the
above clinical picture and on:
(1) a definite history of exposure in the previous 6 - 8 h;
(2) a lowering of the plasma (as an index of exposure) or red blood cell
cholinesterase.
A reasonable correlation exists between red cell and plasma cholinesterase inhibi-
tion and the clinical signs of acute intoxication.
The correlation tends to increase as the rate of inhibition is faster. When inhibition
occurs slowly and repeatedly, as happens on chronic or repeated exposure, the cor-
relation with illness may be low or totally nonexistent. For instance, after continuous
exposure, clinical signs of intoxication may appear only at inhibition of 85-90% of
the pre-exposure A C H E level, as opposed to the 60-70% inhibition level usually
observed after a single exposure. Table 1 summarizes the correlation existing bet-
ween severity and prognosis of acute OP intoxication and the levels of cholinesterase
inhibition determined in peripheral blood.

Table 1
Severity and prognosis of acute OP intoxication at different levels of ACHE inhibition

o/0ACHE Level of Clinical symptoms Prognosis

inhibition poisoning

50-60 Mild Weakness, headache, dizziness, nausea, salivation, Convalescence in

lacrimation, miosis, moderate bronchial spasm 1-3 days

60-90 Moderate Abrupt weakness, visual disturbances, excess Convalescencein

salivation, sweating, vomiting, diarrhoea, 1-2 weeks
bradycardia, hypertonia, tremor of hands and
head, disturbed gait, miosis, pain in the chest,
cyanosis of the mucous membranes

90-100 Severe Abrupt tremor, generalized convulsions, psychic Death from

disturbance, intensive cyanosis, oedema of the respiratory or
lung, coma cardiac failure
 J. Jeyaratnam, M. Maroni / Toxicology 91 (1994) 15-27 19

The great majority of OP compounds are rapidly metabolized and excreted and
subacute or chronic poisoning does not occur. However, since several OP com-
pounds cause slowly reversible inhibition of cholinesterase, accumulation of this ef-
fect can occur. Thus, signs and symptoms resembling those occurring after a single
high dose may be produced by repeated small doses absorbed on prolonged ex-
posure.
Some OP pesticides are able to induce delayed neuropathy in experimental
animals and the structure-activity relationship for this effect has been in part iden-
tified. So far human cases of delayed neuropathy have been reported only as a sequel
to acute poisoning with few compounds, most of which are no longer in use. Cases
of delayed neuropathy occurring after long-term, low-level exposure are so far not
known.
Clinical onset of the 'delayed neuropathy' occurs 1 to 3 weeks after acute ex-
posure. The main symptoms, cramping muscle pain and progressive weakness, begin
in the legs and may eventually involve the arms. Subjective sensory loss is typically
mild or absent. Depression of tendon reflexes and flaccid weakness of the distal limb
muscle are the outstanding signs. Electromyographic examination reveals a pattern
of partial denervation of the affected muscles and electroneurography shows an ap-
preciable delay in terminal motor latencies while maximal motor conduction velocity
is normal or very slightly decreased in most cases. Recovery from the neuropathy
is very slow and functional impairments due to muscular atrophy or involvements
of the lateral columns of spinal cord may last years after the onset of the neuropathy.

3.3 Medical surveillance*

Since symptoms and signs of OP pesticide intoxication are very typical, a primary
function of medical surveillance is to inform workers and all persons likely to come
into contact with these compounds, of early signs and symptoms of poisoning.
Thereafter the workers should be instructed to seek medical attention on the first
recognition of any evidence of poisoning.
A pre-employment medical examination should be carried out before employment
of a subject at a workplace with potential exposure to OP pesticides. The objective
of the examination is to establish a baseline knowledge of the state of health of the
worker and to identify subjects with an increased susceptibility.
Besides recording medical and occupational history, a general physical examina-
tion should be performed, with special emphasis on the condition of skin and
peripheral and central nervous system.
It is recommended to perform liver and kidney function tests and a basic
haematological screen. Baseline values of acetylcholinesterase in red blood cells and
of plasma cholinesterase should also be determined. If this is not possible, baseline
values of whole blood cholinesterase can be determined.

*The programme of medical surveillanceis primarily directedat persons who are regularlyexposedto
pesticideswithin an occupationalsetting(see Section 1.1). Refer to Section2.5 for generalcriteria for the
occupational health surveillanceof pesticide workers.
20 J. Jeyaratnam, M. Maroni/Toxicology 91 (1994) 15-27

The frequency and content of the periodical medical examinations should be

determined by a competent physician, taking into account the exposure patterns and
the health status of the population at risk. A minimum frequency of 6 months to 1
year is suggested.
Apart from the general examination, the periodical examination should be based
on a detailed occupational history with particular reference to the possible occur-
rence of subacute episodes of poisoning and inspection of the skin and evaluation
of peripheral and central nervous system function. Depending on the medical and
work history, and on the results of biological monitoring (see section 3.4) additional
tests may be indicated, such as electromyographic and electroneurographic examina-
tions. The possibility of adverse effects caused by the carrier solvent should also be
considered.
Before returning to work after a significant clinical condition, a similar medical
examination (see above) may be indicated to determine any increased susceptibility
and/or to set a new baseline.

3.4 Biological monitoring

3.4.1 Indicators of effect

Inhibition of red blood cell ACHE activity as well as PCHE activity is highly cor-
related with intensity and duration of OP exposure. Red blood cell ACHE, being
the same molecular target as that responsible for acute OP toxicity in the nervous
system, is an indicator more specific than PCHE. Some OP compounds such as for
example malathion, diazinon and dichlorvos, are earlier inhibitors of PCHE than
ACHE. With these substances serum PCHE determination might be a more sensitive
indicator of exposure than ACHE; however PCHE inhibition may not be associated
with symptoms or signs of toxicity.
After a single OP exposure, serum PCHE activity recovers more quickly than
ACHE activity in red blood cells. After severe intoxication, the reduction of enzyme
lasts up to 30 days in plasma and up to 100 days in erythrocytes, corresponding to
the time of liver PCHE resynthesis and life of the red blood cell.
Coefficients of variation between individuals in cholinesterase activity of the
general population have been determined in the region of 15-25% for the PCHE and
10-18% for erythrocyte ACHE. Corresponding figures for intra-individual variation
are 6 and 3-7%, respectively. The validity of testing cholinesterase activity in
monitoring human OP exposure is limited because of the natural variation of blood
cholinesterase activity in healthy people. The sensitivity of the test can be increased
by adopting individual pre-exposure values as a reference (average of 3 tests). Every
time it is possible, 3 sequential samples should be taken before exposure in order to
establish a normal baseline for each worker. Cholinesterase activities after exposure
have to be compared with the individual baseline values.
Erythrocyte ACHE shows no difference in activity between sexes when the sex-
related difference in red-cell packed volume is taken into consideration. There is no
significant variation with age, with the exception of the less than 6-months-old-
infants who have values lower than adults.
 J. Jeyaratnam, M. Maroni / Toxicology 91 (1994) 15-27 21

Plasma PCHE shows normal values 10-15% greater in males than in females.
Significant correlations have been found between PCHE activity and body mass or
serum cholesterol level. No correlation has been observed between PCHE activity
and age. Repeated seasonal and circadian measurements of ACHE and PCHE in
healthy subjects have not shown any periodical intra-individual variation.
Low values of PCHE not related to OP exposure may be found in liver diseases
(hepatitis, icterus, cirrhosis), uraemia, cancer, heart failure and allergic reactions. In
females, lower values are also measured during menstruation and pregnancy. In-
creased values of PCHE are present in hyperthyroidism and other conditions of high
metabolic rate.
With ACHE, abnormally low values not related to OP exposure have been observ-
ed in subjects affected with leukemias or other neoplasmas. Increased values may be
found in polycythemia and in thalassemia or other congenital blood dyscrasias.
Preferably, sampling of blood should be done within 2 h after exposure. Venipunc-
ture is preferred even though it requires trained personnel (small samples often suf-
fice for the determination of enzyme activity), because capillary blood from a finger
or ear-lobe is nearly always contaminated with the chemical residing on the skin in
occupationally exposed subjects. This should not be underestimated.
Many analytical methods are available for the determinations of ACHE and
PCHE. Most of them yield comparable results, but accuracy and precision vary from
one method to another. Some methods have a sensitivity scale different from others,
so that a given percentage of inhibition of a method may not concur in terms of ab-
solute activity with the same percentage of inhibition measured with a different
technique. Calibration and comparability among different methods should be
established in the same laboratory and among different settings.
A modified version of the Ellman spectrophotometric method to determine
cholinesterase (CHE) activity in plasma or in erythrocytes is described in the WHO
document no. WHO/VBC/84.889 (Plestina, 1984). The method determines CHE ac-
tivity in whole blood and in plasma; red blood cells' CHE activity is derived from
the difference between whole-blood and plasmatic activity. Under field conditions,
whole blood cholinesterase can be measured using a field kit such as the Tintometer
method. Recently paper-test methods have also been developed for screening pur-
poses and field use in agriculture. These methods, though only semiquantitative,
have the advantage of low cost and ease of application.

3.4.2 Indicators of internal dose

For the majority of OP pesticides, the blood or urine concentration of the

substance itself or its metabolites represent an indicator of exposure.
The measurement ofp-nitrophenol in urine to assess the internal dose of parathion
has been among the oldest tests developed. Favoured by the availability of col-
orimetric analytical methods, this test has been widely experimented and has proved
to be successful in evaluating exposure to parathion. Parathion-methyl and EPN are
other pesticides which yield p-nitrophenol in urine. Exposure to fenitrothion may be
surveyed by measuring p-nitrocresol in urine.
22 J. Jeyaratnam, M. Maroni / Toxicology 91 (1994) 15-27

The alternative consists of measuring alkylphosphates in urine. The rationale for

the use of this method resides in the fact that metabolism of most OPs yields
alkylphosphates or alkyl(di)thiophosphates as terminal products. Since these
metabolites are common to several different OPs, this method is not compound-
specific and is only usable to assess exposure to all the parent compounds which may
generate these derivatives.
The various alkylphosphates detectable in urine and the main parent compound
they can originate from, are listed in Table 2.
The measurement of alkylphosphates in urine requires rather sophisticated
analytical methods, based on derivatization of the compounds and separation and
detection by Gas Liquid Chromatography. So far, the measurement of
alkylphosphates has been performed in few studies, mostly for research purposes.
Biological assessment of exposure through urinary metabolite determination may
be a very sensitive method, capable of revealing exposure in a range of doses which
are too low to be detected with ACHE monitoring.
OP metabolites are usually excreted in the urine within a short time and the peak
of emission occurs a few hours after the beginning of exposure. Therefore in occupa-
tional exposure samples collected soon after the end of the work are suitable for
metabolite determination when 24-h urine collection is impractical. When using spot
specimens, creatinine or specific gravity can be determined in order to select and
discard those samples which are too diluted or too concentrated.

3.5 Intervention

Subjects who suffer from skin or liver diseases, neurological disorders and signifi-
cant cardiovascular or respiratory conditions should be very carefully considered
before employment in occupations with exposure to OP compounds. People with
serious liver damage (for instance, chronic alcohol abusers) or with markedly low
cholinesterase level (congenital or acquired) should avoid exposure.

Table 2
Organic phosphates detectable in urine as metabolites of OP pesticides

Metabolite Principal parent compounds

Monomethylphosphate (MMP) Malathion

Dimethylphosphate (DMP)
Diethylphosphate (DEP)
Dimethylthiophosphate (DMTP)
Diethylthiophosphate (DETP)
Dimethyldithiophosphate
(DMDTP)
Diethyldithiophosphate (DEDTP)
Phenylphosphonic acid
Dichlorvos, trichlorfon, mevinphos, malaoxon, dimethoate, fen-
chlorphos
Tetraethylpyrophosphate, paraoxon, demeton-oxon, diazinon-
oxon, dichlofenthion
Fenitrothion, fenchlorphos, malathion, dimethoate
Diazinon, demeton, parathion, fenchlorphos
Malathion, dimethoate, azinphos-methyl
Disulfoton, phorate
Leptophos, EPN
 J. Jeyaratnam, M. Maroni / Toxicology 91 (1994) 15-27 23

The d e v e l o p m e n t o f any e x p o s u r e - r e l a t e d adverse effects or the a p p e a r a n c e o f

clinical c o n d i t i o n s considered i m p o r t a n t in the p r e - e m p l o y m e n t e x a m i n a t i o n should
lead to a careful e v a l u a t i o n before re-exposure. R e a d m i s s i o n at w o r k after m a j o r
illnesses should only be allowed after medical evaluation.
Table 3 shows the relationships between levels o f A C H E inhibitions a n d
biological/clinical effects a n d advised intervention measures established at the
W o r k s h o p on E p i d e m i o l o g i c a l T o x i c o l o g y o f Pesticide E x p o s u r e held in A m s t e r d a m
in 1971, organized by the Scientific C o m m i t t e e on Pesticides o f the I C O H (Zielhuis,
1972). The advice on intervention p r o v i d e d in the table has been confirmed in subse-
quent w o r k s h o p s ( I C O H , 1986).

3.6 First aid advice for lay persons

The p r i m a r y principle o f first aid is to t a k e care o f life-threatening events. In this

context the air w a y should be k e p t clear to m a i n t a i n respiration, p a r t i c u l a r l y when
the patient is unconscious or has vomited. The m o u t h and p h a r y n x should be cleared
and dentures removed. The j a w should be s u p p o r t e d a n d the patient placed in a face
d o w n position with the head d o w n a n d t u r n e d to one side, with the tongue d r a w n

Table 3
Relationships between levels of ACHE inhibitions and biological/clinical effects and advised intervention
measures (Zielhuis, 1972; I.C.O.H., 1986)

Level Significance ACHE inhibi- Measures re-

tion (a) quired

First level (no Values at which no physiological or biochemi- No inhibition No action

effect) cal effects are expected. Values usually found needed
in population without exposure

Second level Values indicative of or compatible with minor 0-30 (1) Medical surveil-
(surveillance) and reversible effects 0-50 (2) lance needed.
Working condi-
tions to be
examined to
avoid exceeding
such a level

Third level Values indicative of or compatible with minor 30-60 (1) Temporary
(effect) damages (initial symptoms, mild alterations of 50-70 (2) removal from
sensitive clinical indexes) exposure and
analysis of
working condi-
tions needed

(a) By definition any 'effect test' cannot evaluate the first level.
(1) Based on individual pre-exposure baseline.
(2) Based on normal reference values.
24 J. Jeyaratnam, M. Maroni / Toxicology 91 (1994) 15-27

forward. The first aid should include, if necessary, mouth-to-nose respiration, car-
diac massage and avoidance of injury in patients with trauma.

Skin contact." Insecticide present on the skin may continue to be absorbed for a
few days. Clothing should be removed if contaminated and con-
taminated areas of the skin washed with soap and water.
Eye contact." Contaminated eyes should be treated by irrigating the eyes with cold
water for at least l0 rain.
Ingestion." Insecticide present in the stomach and intestine may continue to be
absorbed for a few days. Medical attention should be sought im-
mediately whenever uptake has occurred via the oral route.
Inhalation." If inhalation has occurred, remove the victim from the con-
taminated area to fresh air and seek medical attention.

In severe cases the patient should be transported to a hospital for treatment.

3.7 Advice on treatment

To prevent gastrointestinal absorption in unconscious patients who have swallow-

ed OP pesticides, perform stomach lavage with bicarbonate solution and activated
charcoal.
Atropine must be administered as early as possible and could save lives, if given
in time and in adequate dosage. Patients with organophosphate poisoning require
amounts of atropine far in excess of doses usually employed in medical practice. The
therapeutic objective is to achieve atropinisation, as evidenced by dilation of the
pupils, drying of secretions, pulse rate of over 120/rain, and flushing of the skin.
In less severe cases begin with 2 mg atropine i.v. for adults or 0.05 mg atropine/kg
body weight i.v. for children under 12 years of age and repeat administration of the
drug at 15-30-rain intervals. In severe cases a total atropine dose of 20-80 mg in
the first hour may be necessary, with repeated drug administrations at 3-10-rain in-
tervals. When signs of atropinisation appear, the dose and frequency of administra-
tion should be reduced to a schedule that will maintain full atropinisation for at least
24 h. Overdosage with atropine is rarely serious, but underdosage may be fatal in
poisoning with organophosphorous compounds.
In any severe or progressive case of poisoning a cholinesterase reactivator, e.g.
pralidoxime (2PAM), if available, should be administered, preferably within 8 h
after intoxication. An average dose is 1 g for an adult (up to 50 mg/kg for children),
usually given half as a single intramuscular or intravenous injection and the other
half as an intravenous infusion with glucose and/or saline. In severe cases this treat-
ment may be repeated in 1-2 h, then at 10-12-h intervals if needed, but not beyond
24 h, or 48 h at the most. Pralidoxime should be administered very slowly. If respira-
tion is depressed during or after pralidoxime injection, pulmonary ventilation should
be assisted mechanically.
Toxogonin is a more recent cholinesterase reactivator. It can be administered in-
stead of 2PAM at a dose of 250 mg i.m. for adults (4-8 mg/kg for children) and,
if necessary, repeated after I - 2 h.
 J. Jeyaratnam, M. Maroni / Toxicology 91 (1994) 15-27 25

D i a z e p a m should be included in the t h e r a p y o f severe cases a n d whenever convul-

sions appear. Doses o f 5 - 1 0 mg for adults ( 2 - 5 m g for children) can be administered
i.v. or s.c. or per rectum, a n d repeated as required.
Because o f their r e s p i r a t o r y - d e p r e s s a n t effects, m o r p h i n e and similar drugs are
c o n t r a i n d i c a t e d for patients p o i s o n e d with o r g a n o p h o s p h o r o u s c o m p o u n d s .
If p u l m o n a r y o e d e m a develops, a d d i t i o n a l conventional t r e a t m e n t will be re-
quired, including b r o n c h i a l suction a n d toilet, positive- and expiratory-pressure-
ventilation by mechanical means, etc. In any event, the normal, supportive measures
should always be applied, over the a n t i d o t a l treatment.

3.8 Key references

Haynes, J., Meredith, T.D. and Jacobson, D. (Eds), (1994) IPCS/CEC Antidotes Series. Vol. IV. An-
tidotes for Organophosphate poisoning. Cambridge University Press, Cambridge, UK (in press).
International Commission on Occupational Health. (1986) Biological Monitoring of Workers Manu-
facturing, Formulating and Applying Pesticides. Proceedings of the Seventh International Workshop
of the Scientific Committee on Pesticides, Szeged, Hungary, April 15-17. In: E.A.H. van Heemstra-
Lequin, N.J. van Sittert (Eds), Toxicol. Lett. 33.
Jaeger, R.B. (1987) Cholinesterase inhibition as an indication of adverse toxicologic effect. Risk assess-
ment forum EPA, Washington, D.C., June.
Maroni, M. (1986) Organophosphorous pesticides. In: Alessio, (Ed), Biological Indicators for the Assess-
ment of Human Exposure to Industrial Chemicals, Commission of the European Communities (EUR
10704), Berlin, Boni, Roi, pp. 51-72.
Plestina, R. (1984) Prevention, Diagnosis and Treatment of Insecticide Poisoning. WHO/VBC/84.889.
World Health Organization, Geneva.
World Health Organization. (1986) Organophosphorous Insecticides: A General Introduction, No. 63
Environmental Health Criteria. International Programme on Chemical Safety, Geneva.
World Health Organization. (1987) Organophosphorous Pesticides: An Epidemiological Study, No. 22
Environmental Health Series, Copenhagen.
Zielhuis, R.L. (1972) Epidemiological toxicology of pesticide exposure. Report of an international
workshop. Arch. Environ. Health 25, 399-405.

3.9 List of main representative organophosphorous pesticides (compounds marked with

• are indirect inhibitors of ACHE)

ISO name* Class** M a i n use***

Chlorfenvinphos Ia I
• Chlormephos Ia I
• Chlorthiophos Ia I
Dimefox Ia I
• E P N (ESA name) Ia I
Ethoprophos Ia I-S
Fenamiphos Ia N
• Fensulfothion Ia I
• Fonofos la I
Mevinphos Ia I
26 J. Jeyaratnam, M. Maroni / Toxicology 91 (1994) 15-27

ISO name* Class** Main use***

Mephosfolan Ia I
Phosfolan Ia I
• Parathion-methyl Ia I
• Prothoate Ia A,I
Schradan Ia I
• Parathion Ia I
• Demeton-O Ia I
• Disulfoton Ia I
• Phorate Ia I
Phosfamidon Ia I
TEPP Ia A
• Sulfotep Ia I
• Terbufos Ia I-S
• Thionazin Ia N
• Trichloronat Ia I-S

Dichlorvos Ib 1
Crotoxyphos Ib I
Dicrotophos Ib I
Edifenphos Ib F
• Fenthion Ib I,L
• Demeton-S Ib 1
• Azinphos-methyl Ib I
• Azinphos-ethyl Ib 1
Methamidophos Ib 1
Monocrotophos Ib I
Omethoate Ib I
• Pirimiphos-ethyl Ib 1
• Thiometon Ib I
• Triazophos Ib 1
Vamidothion Ib 1

• Fenitrothion II I
• Fenchlorphos II I
• Diazinon II I
• Dimethoate II I
• Phosalone II I
Naled II I
• Quinalphos II I
• Chlorpyrifos II I

Acephate I|I I
• Bromophos III I
 J. Jeyaramam, M. Maroni / Toxicology 91 (1994) 15-27 27

ISO name* Class** Main use***

• Malathion III I
Trichlorphon III I
Glyphosate u.h. H
• Temephos u.h. I,L
Tetrachlorvinphos u.h. I
• Leptophos n.e. I
• Phoxim n.e. I

(*) These pesticides are marketed under variable trade names.

(**) W H O recommended classification by hazard (1992)

(Refer to Chapter 1 for the criteria for classification)

Ia extremely hazardous
Ib = highly hazardous
II = moderately hazardous
III = slightly hazardous
u.h.= unlikely to present acute hazard
n.e. = not evaluated

***) Main use

A = acaricide
AP = aphicide
I = insecticide
L = larvicide
N = nematocide
-S = applied to soil