Biological Monitoring of
Workers
Exposed to Organo-phosphorus Pesticides.
Guidance Note MS 17 from the British Health and Safety Executive.
Medical Series 17
First published 1981, revised
1986 Second revision 1987.
INTRODUCTION
1 The term 'pesticide' as used in this Guidance Note. applies to
preparations used to control or destroy living organisms that interfere
with man's agricultural, environmental or amenity requirements.
2 Organo-phosphorus (OP) pesticides include phosphates, phosphites,
phosphonates, phosphoramides, pyrophosphates and their sulphur analogues.
Formulations are usually either liquids or powders which are mixed with
water and applied as sprays, or are directly applied in granule form. a list
of commonly used approved chemicals will be found in the booklet Pesticides
198.
Pesticides approved under the Control of Pesticides Regulations 1986,
published annually by the Ministry of Agriculture, Fisheries and Food,
reference 500.
3 There has been a rapid increase in the production and use of OP pesticides
in recent years, because they are more short-lived in the environment and
in biological systems than the organo-chlorine pesticides which they have
replaced. However, acute and subacute exposure to OP pesticides can
produce harmful effects in man, and repeated exposure at lower doses may
cause insidious cumulative toxicity.
4 Another class of chemicals, the carbamates, are also used as agricultural
pesticides and have similar pharmacological actions to the OP compounds.
Exposure to both groups of chemicals produces similar symptoms of acute
intoxication; the main difference lies in the speed of re-activation of
inhibited enzyme acetylcholinesterase. Recovery of the enzyme from
carbamate inhibition is generally faster than recovery from OP inhibition,
and there is no cumulative action.
5 Within the group of OP and carbamate compounds there is wide
variation in toxicity and not all are cholinesterase inhibitors.
POTENTIAL OCCUPATIONAL SOURCES OF EXPOSURE
6 any job which involves contact with OP pesticides either directly or
indirectly constitutes a potential source of absorption. Those at risk range
from laboratory workers undertaking research on OP pesticides to ambulance
workers who, during the course of their duties, may come into contact with
injured operators or their contaminated clothing.
7 Workers occupationally at risk include those involved with OP pesticides
in:
(a) manufacture and packaging;
(b) transport, storage and distribution;
(c) application and use;
(d) handling used containers e.g. scrap recovery.
ROUTES OF ABSORPTION
8 The most common routes of absorption of OP pesticides are via skin,
respiratory tract and eyes. Under normal conditions of use ingestion is
rare, although small amounts may be swallowed in contaminated saliva.
In agricultural practice, the major route of absorption is via the skin,
with
inhalation being less important. OP formulations based on organic solvents
are liable to penetrate protective clothing unless contamination is washed
off promptly. Contamination of the eyes may produce local effects and
disturbance of vision.
BIOLOGICAL EFFECTS
9 When poisoning with proprietary formulations of OP compounds occurs,
the presence and influence of the solvent should not be forgotten. Local
skin
effects will almost certainly be due to the solvent; in exceptional and
severe cases the presence of an organic solvent may encourage considerably
the development of intoxication symptoms.
10 The toxic effects produced by OP compounds in man are generally
considered to be due to inhibition of the nervous system acetylcholinesterases.
CLINICAL MANIFESTATIONS OF ORGANO-PHOSPHORUS
POISONING
11 The diagnosis of OP poisoning is not easy. Some signs and symptoms
can be clearly defined, whereas others, particularly those of central nervous
system origin, may be variable and not easily detected. Some OPs require
metabolic activation before they inhibit cholinesterase. Active metabolite
may continue to be formed for some time after absorption.
12 Repeated absorption of small doses, as may occur
from contaminated
clothing, has cumulative effects resulting in progressive inhibition of
nervous tissue cholinesterase.
This happens when the repeat exposures occur within the cholinesterase
recovery period. Further small exposure may then precipitate the classical
condition of OP poisoning.
Clinical effects do not generally appear until plasma
cholinesterase activity
has fallen to 30% of normal pre-exposure values.
13 Symptoms of poisoning include:
(a) non-specific symptoms: headache, giddiness, loss of appetite, nausea
and
diarrhoea;
(b) those related to over-reactivity of voluntary muscle, tremors, impaired
co-ordination;
(c) those related to excessive activity of the autonomic nervous system:
miosis (pin-point pupils), blurred vision, excessive salivation and sweating,
increased bronchial gland secretion, bradycardia with decreased cardiac
output and hypotension.
14 Other symptoms include:
(a) urinary incontinence, abdominal pain, vomiting and broncho-constriction
caused by over-activity of smooth muscle;
(b) central nervous system effects:
(i) depression of the respiratory centre
(ii) various non-specific psycho-motor
effects e.g. apprehension, anxiety,
restlessness, irritability, depression, sleep problems such as insomnia and
dreaming, hallucinations, expressive language defects, changes of mood,
lack of concentration, memory impairment, slowed reaction time.
15 The pattern of signs and symptoms as they develop will to some extent
depend upon the route of absorption of the OP compound. Thus, following
inhalation, the earliest effects may be miosis, rhinitis and chest tightness.
Following ingestion, intestinal colic, nausea, vomiting and diarrhoea are
early features. Miosis, rhinitis and chest tightness may not develop after
skin absorption.
16 Death may be caused by respiratory failure due to paralysis of
respiratory muscles aggravated by central depression of the respiratory
centre, bronch-constriction and decreased bronchial secretion.
MEASUREMENT OF CHOLINESTERASE ACTIVITY AS AN INDEX
OF ORGANO-PHOSPHORUS UPTAKE AND EFFECT.
17 Although different OP compounds inhibit neural, erythrocyte and plasma
cholinesterases to varying extents, and with differing time courses, the
measurement of erythrocyte and plasma cholinesterase activity provides
an indication of the uptake of these compounds. Such measurements have
therefore found a place in monitoring workers exposed to OP compounds,
especially in the case of repeated exposures.
18 Erythrocyte and plasma cholinesterases have different substrate
specificities. The erythrocyte acetylcholinesterase has its major activity
towards acetylcholine and acetyl thiocholine, whereas the plasma enzyme
has a broader range with increased activity towards propionyl and butyryl
cholines.
Using acetyl choline as substrate, over 80% of enzyme activity of whole
blood is then provided by the erythrocyte enzyme.
19 There is a series of genetically determined variants of plasma
cholinesterase and these may be associated with increased sensitivity to
the muscle relaxant succinyl choline, used by anaesthetists. Anyone who has
such an abnormal variant may show a low level of plasma cholinesterase
activity even though unexposed to OPs. Although this may make routine
monitoring more difficult, it does not increase sensitivity to OP compounds.
20 Several methods of measuring plasma and erythrocyte cholinesterases are
available, including electrometric and spectrophotometric methods. The units
in which activity is expressed (and the normal range) depend on the method
used.
21 A convenient spectrophotometric way of measuring plasma and erythrocyte
cholinesterase activity is Ellman's method which uses acetyl thiocholine
as
the substrate. One version of this method which has proved useful for
routine screening is the 'Automated discrete kinetic method for erythrocyte
acetyl cholinesterase and plasma cholinesterase' described by P J Lewis,
R K Lowing and D Gompertz in Clinical Chemistry 1981 27 926.
22 Both erythrocyte and plasma cholinesterases have a wide range of values
in normal unexposed individuals, although in any one individual activity
varies
little with time. Interpretation of measurements in exposed subjects is greatly
assisted if pre-exposure levels are available for both enzyme activities.
In the absence of such base-line measurements, true falls in enzyme activity
may remain undetected.
23 In spite of its limitations as an index of functional disorder, the technique
has found considerable practical value as a monitor for exposure to OP
compounds.
BIOLOGICAL MONITORING
24 The success of any system of monitoring designed to detect early toxic
effects depends on:
(a) the availability of adequate pre-exposure information;
(b) whether the procedure is carried out on a regular basis using
appropriate technology, suitably trained staff and with the full co-operation
of employees and management.
25 Regular monitoring should be considered for anything more than occasional
exposure to OP compounds e.g. garden use. An effective programme for
screening workers regularly exposed to OP compounds would include:
(a) pre-exposure measurement of both plasma and erythrocyte enzymes. There
should be a minimum of 60 days without exposure, including maintenance
operations on contaminated plant, before these measurements are made. At
the same time advice can be given on safe methods of use and the recognition
of early signs of poisoning;
(b) regular monitoring of plasma cholinesterase levels in repeatedly exposed
subjects. Every four weeks would be reasonable for most workers. A shorter
interval should be considered for workers potentially heavily exposed, e.g.
contract sprayers, and for those in occupations, e.g. pilots involved in
aerial spraying, where early symptoms such as blurred vision and impaired
co-ordination could present a special hazard to the person affected, other
workers or the general public;
(c) measurement of both enzymes in cases of acute heavy exposure and
investigations of possible incidents. The measurement of erythrocyte as
well as plasma cholinesterases in workers under regular health surveillance
offers little advantage. However, in cases of over-exposure when the base
line measurements are not available, measurements of both enzymes are
desirable.
26 If, during routine monitoring, plasma cholinesterase activity has been
shown top have fallen by more than 30% of pre-exposure levels, the workers
should be medically examined.
The medical officer may then, at his own discretion, taking into account
the
nature of the work involved and the clinical symptoms, recommend that the
worker be suspended from further exposure to OP compounds until considered
fit to resume normal work. The rate of recovery of enzyme activity varies
with
the chemical structure of the OP compound to which the individual has been
exposed.
The return of enzyme activity to pre-exposure level may occasionally take
as
long as 60 days. It is not necessary for pre-exposure cholinesterase levels
to be reached before resumption of normal work. The medical officer should
base his decision on both the clinical evidence and the results of biological
monitoring.
ELECTRO PHYSIOLOGICAL MONITORING
27 Electromyograph (EMG) measurements have been used to screen workers for
occupational over-exposure to OP compounds. Doubts have been expressed as
to
the value of EMG measurements as part of routine monitoring. Such measurements
are more likely to be of use in the clinical evaluation of special cases
of suspected
OP toxicity rather than in routine monitoring.
EMERGENCY TREATMENT
28 If a worker is suspected of having OP poisoning, medical attention should
be sought as soon as possible.
29 Recommended first-aid treatment:
(a) stop the patient working, remove him from the exposure area into
protective cover and keep him at rest.
(b) remove contaminated clothing, taking care to avoid contaminating your
own skin. Wash contaminated skin with plenty of water. Cover the patient
with a clean blanket, rug or coat:
(c) if breathing weakens or ceases, make sure the breathing passages are
clear, remove false teeth or other obstructions from the mouth and apply
mouth to mouth artificial respiration, unless the mouth is contaminated,
when a manual method should be used. If the patient's eyes are affected,
wash them out with clean running water for several minutes. When transporting
the patient to hospital, see that he is in the recovery position to prevent
inhalation of vomit:
(d) remember to tell the hospital and the doctor which chemical the patient
has been using and show them any available leaflet or label regarding the
chemical: or give them a note showing the name copied from the container.
The free leaflet MS(B)7 Poisoning by pesticides published by the Health and
Safety Executive gives details of treatment.
30 A sample of the patient's blood should be taken as soon as possible after
exposure and separated (if possible). The sample should then be stored at
4F8C until the cholinesterase activities can be measured. Plasma cholinesterase
can be measured at most hospitals, but erythrocyte acetyl cholinesterase
analysis requires a specialist laboratory.
31 A medical officer should treat a patient presenting signs of OP poisoning
with Atropine (2 mg. intramuscularly or subcutaneously). If the condition
is
severe, Atropine may be given intravenously. When symptoms are not promptly
relieved, the dose may be repeated every 5 to 10 minutes until the patient
is fully atropinised.
Victims of OP poisoning can tolerate doses of Atropine which are very large
by conventional standards. Pralidoxime mesylate (P2S), available from Poisons
Centres, is a specific antidote but should not be use alone as first-aid
treatment.
A list of hospitals which have facilities for this antidote and treatment
can
be found in the DHSS booklet Pesticide poisoning -notes for the guidance
of medical practitioners. Both Atropine and Pralidoxime are most effective
during the first 24 hours post exposure and an assessment of the need to
continue with Atropine should certainly be made after 24 hours.
The heart rate is a useful guide and a rate of between 70 and 80 beats per
minute should be the target. When muscular activity and convulsions are a
feature, Diazepam by injection will be of considerable value.
NOTIFICATION
32 OP poisoning is a reportable disease under the Reporting of injuries,
Disease and Dangerous Occurrences Regulations 1985 and is also a prescribed
disease under the Industrial Injuries Provisions of the Social Security Act
1975. An HSE agricultural inspector must be informed when an agricultural
worker or a self-employed person is suspected of suffering from OP poisoning
caused by a substance specified in the Poisonous Substances in Agriculture
Regulations 1984.
REFERENCES
1 Ministry of Agriculture, Fisheries and Food, Ref 500 Pesticides 198,
Pesticides approved under the Control of Pesticides Regulations 1986.
HMSO published annually.
2 Ministry of Agriculture, Fisheries and Food, Pesticides Safety Precautions
Scheme 1984. Products cleared for agricultural, food storage, public
hygiene, domestic and related uses in the United Kingdom. HMSO published
annually.
3 Lewis P J, Lowing R K and Gompertz D, Automated discrete kinetic method
for erythrocyte acetyl cholinesterase and plasma cholinesterase. Clinical
Chemistry 1981 27 926.
4 Health and Safety Executive, Poisoning by pesticides. MS(B)7.
5 Department of Health and Social Security, Pesticide poisoning-notes for
the guidance of medical practitioners. 1984 HMSO.
FURTHER INFORMATION
This Guidance Note is produced by the Health and Safety Executive.
Further advice on this or any other publications produced by the Executive
is obtainable from:
Health and Safety Executive
Library and Information Services
Broad Lane
SHEFFIELD S3 7HQ
Telephone: (0742) 752539
Health and Safety Executive
Library and Information Services
St. Hugh's House
Stanley Precinct
Trinity Road
BOOTLE
Merseyside L20 3QY
Telephone: 051-951-4381
Health and Safety Executive
Library and Information Services
Baynards House
1 Chepstow Place
Westbourne Grove
LONDON W2 4TF
Telephone: 01-221-0870
First published 1981, revised 1986 Second revision 1987. ISBN 0 11 883951
9.
For current information see:
~~*~~
Report
on Organophosphate Pesticides
Royal College of Physicians and Psychiatrists
~~*~~
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