WORLD HEALTH ORGANIZATION ORGANISATION MONDIALE DE LA SANTE PESTICIDE DEVELOPMENT AND SAFE USE UNIT DIVISION OF VECTOR BIOLOGY AND CONTROL WHO HEADQUARTERS, GENEVA
VBC/82 .1 ENGLISH ONLY t. - ~---~
J
(l
S
v
r'
I
I !
C(} l
FIELD SURVEYS OF EXPOSURE TO PESTICIDES STANDARD PROTOCOL 1
1.
GENERAL AIM
To examine the exposure of those workers involved in applying pesticides in order to be able to determine: (a) (b) whether the actual exposure constitutes a safe level; what protective measures need to be implemented to ensure safe use.
This can be achieved for a particular pesticide by the following activities: (a) defining accurately the environmental conditions under which the pesticide is applied, the method and rate of application; (b) collecting data on:
This document replaces unpublished document VBC/75.9, Survey of Exposure to Organophosphorus Pesticides in Agriculture. It was reviewed in November 1981 by a workshop organized by the Scientific Committee on Pesticides of the International Association on Occupational Health whose assistance is gratefully acknowledged. The participants were: Dr J. L. Bonsall, F.B.C. Ltd., Hauxton, Cambridge, United Kingdom; Dr J. F. Copplestone, Chief, Pesticide Development and Safe Use, Division of Vector Biology and Control, WHO, Geneva (Chairman); Dr R. Goulding, Chairman of the Scientific Sub-committee, UK Pesticides Safety Precautions Scheme, Ministry of Agriculture, Fisheries & Food, United Kingdom; Dr T. B. Hart, ICI, Plant Protection Division, Fernhurst, West Sussex, United Kingdom; Dr K. W. Jager, Secretary, Scientific Committee on Pesticides, International Association on Occupational Health, Carel van Bylandtlaan ?O, The Hague, The Netherlands; Dr L. H. Machemer, Bayer AG, Institute of Toxicology, ~uppertal, Federal Republic of Germany; Dr H. G. S. van Raalte, Chairman, GIFAP Toxicology Committee, c/o Group Toxicology Division, Shell Internationale Research, Maatschappij B.V., The Hague, The Netherlands; Dr W. F. Tordoir, Group Toxicology Division, Shell Internationale Research, Maatschappij B.V., The Hague, The Netherlands. Unable to attend: Professor L. Rosival, Chairman of the Scientific Committee on Pesticides, Research Institute of Preventive Medicine, Bratislava, Czechoslovakia.
1
VBC/82.1 page 2 (i) (ii) (iii) times of exposure; the quantity of pesticide applied by each man; details of protection used;
(iv) the amount of pesticide coming into contact with the exterior of clothing, beneath clothing, and exposed skin; (v) (vi) quantitative tests of absorption and excretion of parent compound or metabolite details of any effects of exposure.
If the exposure is equivalent to or exceeds a threshold level for safety, then the contributory factors involved (e.g. type of protection provided, personal hygiene, pattern of use) and their relative importance should be determined and appropriate recommendations for safe use should be made.
2.
INDICATIONS FOR CARRYING OUT A FIELD STUDY
Field studies should be carried out whenever the toxic properties of the substance and/or formulation together with the pattern of usage give cause for concern about workers' safety. Considerations in determining this include: (a) the acute dermal toxicity of the formulated proquct when dermal exposure is considered the most significant route of absorption; ' (b) a significant opportunity for inhalational exposure at work of a material which is toxic by the respiratory route; (c) where compounds have been found to cause adverse effects only at very high doses to ascertain that worker exposure will be at low levels, providing a significant safety margin; (d) significant changes in formulation of compound or application procedures.
Studies may need to be repeated if there are changes in use patterns, application techniques .or formula tions which might alter the hazard to workers employed in application. 3.
CHOICE OF SU RVEY SITE AND GROUP
3.1 The spraying operation should be under single administrative control and should last a period appropriate t o the pattern of use and the pharmacokinetics of the pesticide. 3.2 The pesticide should be applied in uniform concentration by uniform means throughout the operation. 3.3 The group studied should consist of four t o 10 workers engaged in the application. If practicable, the occupational groups (mixers, loaders, sprayers, flagmen, etc.) sh ould be considered separately. Ideally, the group should not have been exposed to the pesticide used during the survey or to any o ther pesticide with a similar mode of action during a relevant period preceding the commencement of the ppe ration. 3.4 If it is necessary to select from spraymen , the selection should be on the basis of typical working clothing worn in the area in order that thi s might be standardized as far as possible. If possible, photographs of the men in their working clothing should be taken. If the workers engaged in the application ar e n o t experience d in pesticide application pr oper instructions and training sh ould be given b e for e the study commences.
VBC/82 .1. page 3 3.5 Depending on the parameters measured and the period of the survey a suitable control group applying a blank formulation may be indicated.
4.
SURVEY STAFF
4.1 Staff for the adequate superv1s1on of the operational aspects, including proper application of the pesticide, have not been included as it is assumed that these would be provided for in a planned operation. 4.2 The minimum survey staff consists of a physician-toxicologist and one or two assistants of technician status. 4.3 The physician-toxicologist is responsible for: (a) (b) the general organization of the survey; the keeping of records;
(c) medical supervision of applicators during the operation, including the collection and handling of specimens where necessary; (d) 5. the training of local staff in evaluation techniques.
METHODS Cholinesterase determination Organophosphorus compounds:
5.1
The principal effect of exposure to an organophosphorus compound is depression of cholinesterase. The degree of depression can be estimated in blood by, for example, the methods described by Michel, 1 Ellman, 2 or Voss & Sachsse3 or other similar methods. When field conditions would in~olve an interval be~een collection and analysis exceeding 10-12 hours, then it is necessary, ~ven when the samples are adequately cooled, to use a field kit such as the Tintorneter method.4 Cholinesterase test papers are also available; as they are of lower sensitivity, they are of more use for routine surveillance than for survey work. Tests should be carried out on all personnel included within the study: (a) once on each of three days preceding any exposure to cholinesterase inhibitors; the mean of these three values provides the baseline for the individual against which subsequent values are matched; (b) on working days when spraying has been completed and the sprayrnen have removed their protective clothing and washed or bathed; (c) if a gap of one or more days occurs during the operations, a pre-work test should be carried out on the day that work is resumed;
1 2 3
Michel, H. 0. (1949) J. Lab. clin. Med., 34, 1564. Ellman, G. L. et al. (1961) Biochem. Pharmacal.,
I,
88.
Voss, G. & Sachsse, K. (1970) Toxicol. Appl. Pharmacal.,
J&,
764.
Edson, E. F. (1958) World Crops, 10, 49; Salisbury, United Kingdom.
4
obtainable from the Tintometer Sales Co. Ltd.,
VBC/ 82.1 page 4 (d) when any worker in the survey group complains of symptoms which could be related to pesticide exposure, a cholinesterase determination should be carried out immediately; thereafter cholinesterase should be measured at regular intervals until its recovery is established; (e) if any worker has had an asymptomatic cholinesterase depression which has led to suspension from work, cholinesterase determination should be carried out on succeeding days until it is obvious that its recovery is taking place. Blood should be taken from an uncontaminated area, preferably by the venous route. Capillary blood is usually used in field tests but in the case of direct acting cholinesterase inhibitors great care has to be taken to prevent the contamination from the skin. Venous blood may have to be used. Insecticidal carbamates: Due to the rapid reactivation of cholinesterase when inhibited by insecticidal carbamates, measurement of cholinesterase is not a feasible indicator of impending overexposure. In these surveys, in addition to other tests of exposure, surveillance should be adequate to detect any clinical signs.
5.2
Biological monitoring
5.2.1 Biological monitoring provides a quantitative measure of the absorbed pesticide resulting from exposure via all routes. The objective of biological monitoring is to relate! the level of parent compound or the specific, representative metabolite in biological material to the total uptake. This implies that for this purpose specific and sensitive methods have been developed or should be 1 developed to enable the determination of the above-mentioned substances in biological material. In view of the limitations inherent to field conditions the biological material in which the pesticide or its metabolite is determined is usually blood or urine or both. Since it may not always be possible to carry out the required analysis of the specimens close enough to the location of the field study, means of adequate preservation and despatching should be available.
5.2.2
5.2.3 Time and frequency of sampling and the volume of the_ specimen are dependent on the properties of the compound, the characteristics of the application procedure and the specific conditions of the study. Detailed guidelines cannot be given; however, some general guidance is presented below:
(a) One or more pre-exposure samples must be analysed in order to establish a reliable baseline. (b) During the application period an adequate number of samples should be collected in order to provide a good measure of the total uptake and an indication about possible transient retention. (c) After the application period samplfng should continue long enough to provide data on the elimination pattern.
A list of metabolites and the pesticides with which they are related is shown in Annex 1. This list is not exhaustive and other tests will be developed in the future.
1
VBC/82.1 page 5 (d) The decision to collect either spot samples or 24-hour urine samples in the case of monitoring urinary metabolites will depend on the properties of the pesticide, the level and the rate of absorption and the analytical requirements. A check on the adequacy of the 24-hour urine sampling should be carried out by, for example, measuring the creatinine content of that urine. (e) Safeguards should be taken to avoid contamination of any sample with the parent compound. 5.2.4 The toxicological interpretation of the amounts determined in blood or in urine cannot be made without the knowledge of the pharmacokinetics, preferably in man. 5.3 Assessment of dermal exposure This may be done by one of the two methods described below. 5.3.1 Disposable overalls and gauntlets
•
Each worker, who is to be assessed for dermal exposure, is required to wear a new disposable overall and gauntlets for a minimum period of one hour or more during any one day's spraying. If significant head exposure is likely, then a head pad as described below or a disposable hat should also be used. Care should be taken to ensure that the overall or gauntlets do not become saturated and should this occur a fresh overall and gauntlets must be worn. The exact periods of time and amount of pesticide used during the period that each overall(s)/gauntlets are worn must be accurately recorded.
On completion of each assessment period the overalls and gauntlets should be carefully taken off by an assistant to avoid cross-contamination. Each gauntlet should then be placed in a separate plastic or polythene bag and stored in a place out of direct sunlight and as cool as is practicable, prior to analysis. The overall(s) is (are) immediately sectioned into the following parts: (a) (b) (c) legs - above and below knee; arms - above and below elbow; torso - front and back.
Care should be taken to ensure that the instrument used for sectioning the overall is not contaminated. Decontamination can be carried out by swabbing with cotton wool soaked in an appropriate solvent. Each body part sample is then stored separately under identical conditions as are the gauntlets. All bags should be labelled separately to include the following information: (i) (ii) 5.3.2 the worker's number; number of day of survey - preceded by the letter D.
Exposure pads
Pads are preapred of ~-cellulose, 10 x 10 em, backed with glassine paper or aluminium foil. Aluminium foil alone can be used with oily formulations. Benchkote~ (Whatman) a white abosrbent paper backed with polyethylene, has also been successfully used as an absorbent pad. Prior extraction of pad material is essential to ensure that there will be no in~erference with the analysis of residues of a particular pesticide (see section 7).
VBC/82 .1 page 6
Pads should be fixed with masking tape covering the edges of the pad only, and on clothing with safety pins through the edge of the pad. On each day of application, four spraymen from the survey group should be chosen serially to wear exposure pads for at least one hour (as for overalls) except for the "skin pad" which should be worn the entire day. The attachment of the pads should be checked frequently and corrected if necessary. Pads should be applied as shown below, on clothing (where worn) or on skin. set out for a right-handed man; if the man is left-handed opposites apply. Arm : This is
Upper surface of left forearm held with elbow bent at right-angle across body, midway between elbow and wrist. (1) (2) front of left leg, above ankle; front of left leg, mid thigh. over sternum; on back between shoulder blades.
Leg:
Trunk:
(1)
(2)
Head:
If head not covered, forehead as high as possible to give good adhesion. If head covered, on hat as close as practicable to top of forehead.
In addition, one pad (the "skin pad") is applied to the skin under clothing to the upper abdomen at approximately the same height as the arm pad and below the sternal pad but not shielded by it. On removal at the end of the day, a 5 x 5 em square shduld be cut from the pad. should be taken that the scissors or other cutting instruments are not contaminated. Decontamination can be carried out as described above (5.3.1).
.
Care
The central portion of the pad should be placed either in a bottle containing solvent or in a plastic envelope (see section 7). If a bottle is used, the cap of the bottle should have an aluminium liner inserted, the bottle closed and shaken gently to ensure that the whole pad is wetted with the solvent. The exterior of the envelope or bottle should be labelled clearly with: (i) (ii) the number of the day, preceded by the letter D; the worker's number;
(iii ) th e site of the pad, and whether i t was attached to clothing "C" or skin "S" (e.g. 11 03 6 Thigh C"). In addition, on two da ys during the trial period, a control _ to determine laboratory recovering rate of the pesticide should be carried out. To 5 x 5 em squares cut from exposure pads or overalls, add carefully measuredl 0.05 and 0.1 ml samples of the pesticide concentrate . and di luted spray respectively. These samples are then treated in the same way as those taken from the spraymen. 5.4 Respirators
Since the respiratory route of absorption is no t significant in most s tandard pesticide applications, the measurement of respirato ry exposure need not be carried out in each study. This is based on the fact that respiratory exposure does not usually exceed 1% of the dermal exposure, except po ssibly in the case of gaseous fumigants and exposure in confined spaces, or in cases where respiratory toxicity is very high in relation to percutaneous t oxicity. 1
These samples ne ed to be measured by pipette, using a suction bu l b to draw up the
liquid.
VBC/82.1 page 7 To estimate respiratory exposure, two of the men in each group of four wearing pads for the day should be asked to wear half-face cartridge-type respirators for the whole of the working day. Respirator pads should be fitted each morning on the external side of chemical filter cartridges; these pads are removed at the end of the day and placed entirely in a plastic envelope or bottle, clearly marked as in 5.3.2 above. The man should be carefully instructed on the care of the respirator in order to avoid any contamination at times when it is removed. All respirators should be carefully washed at the end of each working day, after the chemical filter cartridges have been removed. If the men normally wear a surgical or gauge mask, respiratory exposure can be measured This is not as accurate by fixing a pad to the underside of the mask in front of the nose. as the wearing of respirators as set out above. Individual respiratory samplers are also available and may be suitable for use in some studies. 6. RECORDS
6.1
Record of operation details
On the day spraying commences, Form 1 (Annex 2) should be completed. On each day subsequently, the data on the form should be reviewed and any changes recorded by completing a new form with details of the changes only.
6.2
Daily record and diary
Each day, from the day before spraying commences onwards, the daily record Form 2 (Annex 3) should be completed. The diary section of Form 2 should be used for recording any events which are relevant to the survey. Sickness in any man, whether or not he is included in the survey group, should be recorded, together with an account of action taken and result. 6.3 Daily personal record st~rted
Form 3 (Annex 4) should be daily. 7. 7.1
for each man in the survey group and should be entered
LABORATORY PROCESSING OF EXPOSURE AND RESPIRATOR PADS AND OVERALLS Before the survey
•
7.1.1 It is necessary to determine the recovery rate for the pesticide by the method used for its determination. In addition, it is necessary to estimate degradation of the pesticide between the time the exposure pad or overall is removed and the time of processing, and whether this can be reduced by the method of _ transportation. This is done by preparing patches of overall material or pads with known quantities of the pesticide and processing them immediately and after one, two and three weeks. If after three weeks recovery exceeds 75%,the overalls or pads can be transported in plastic envelopes, kept in the dark and as cool as practicable. Otherwise a suitable technique must be tested similarly. If solvents need to be used for transport and storag~ it is more practicable to use exposure pads. 7.1.2 A blank estimation using a sample of overall material or the pad only should be carried out to determine whether it is fe~sible to use an overall or whether prior extraction of pads is needed.
VBC/ 82 .1 page 8 8. CALCULAIIO S AND PRESENTATION OF RESULTS
8.1
Calculation of percentage toxic dose received by each man Dermal exposur Exposed area: (from pads)
8.1.1
This is calculated from the exposure pads, relating th quantity of pesticid in a pad o( known area to the exposed area of th limb or part of the body as modified from Berkow (1931) Amer . J. Surg., £, 315. These are add d to give a total amount expressed in m&/day or per hour . . Read neck area • 1100 c~: Upper
r:~::~ 'b~ :fq~::e~ ~;, h:~2
2
rn • 82 5 cm
Top of shoulders near neck • 300 c~ Back just below neck • 100 caf Forearms • 1200 crrJ. Banda • 800 caf Legs from knees down • 2300 cm2 Upper legs from knees up • 3500 c~ These areas may need adjustment according to area unclothed. Unexpoa d are :
bead pad sternal pad head pad back pad arm pad arm pad or hand wash low r leg pad thigh pad
Add areas of exposed parts and subtract from 18 000 em the dermal contamination unexposed area is calculated from the " sldn pad" underneath the clothing. 8.1 . 2 Dermal exposure (from overalls)
2
o~
the
The potential dermal exposure is found by calculating the quantity of pesticide per section of overall and by adding the quantity of pesticide (in mg) of all sections of the overall covering parts of the body no norm lly covered by working clothes, plus the quantity of pesticide in the head pad (if worn) relating the m&fcm2 to a figure of 1100 c~. If a head pad was not used the total exposure is body exposure + lO t . The total exposure is then related to the time th suit was worn, as follow : total quantity in mg x 60 total t1 e (in 8.1.3 Respiratory exposure If done, this is calculated and 8.1.4 Percentage toxic dos xpressed in m&/day or mg/bour. t
t 1
(
/hour)
per day or hour he m th d of Durham & W ol { 1962
This is Bull. Wld Hl
from these indices adap ed from 75-91 using the ormu1a:
D rmal xposure ms/day or hour) + ( respire ory exposure (m&/day or hour} x 10 70
i f measured
VBC/82.1 page 9 8.2 Comparison of sites
All the results for a particular exposure pad site are grouped together and the mean and standard deviation (SD) are calculated. If any results fall outside the meant (SD x 3), these are excluded and a new calculation made of the mean and SD of those that remain. The purpose of this is to give an idea of the "normal" distribution after those results that represent some unusual contamination have been excluded. The chance of such exclusions being made in error is 1% .
•
i : .. ~ >I
~
!5 ...
TABLE OF PESTICIDES AND TBEIJ. METABOLITES OF USE FOR BIOLOGICAL K>NITOIU!IG Pesticide Aldrin Biological 1118terial Blood
Compound measured dieldrin
Method
Reference l.
2. Azinphos-ethyl Carbaryl Chlorfenvinphos Cypermethrio Blood Urine Urine Urine azinphoa-etbyl 1-naphthol 2,4 dichlorobenzoic acid 2 ,2 -dicbloravinyl-3,
Richardson, A.; IDbinaon, J.; Buab, B~; Daviea, J. M. Arch. Environm. Health (1967) !!• 703-708. Dale, W. E.; Curley, A.; Cueto, C. Life Sciences (1966) 2_, 47-54.
oc oc
Stein,
v.
B.
J. Aaa. Off. Anal. Chem. (1976), 59, 1094
Shafik, M. T. et al. (1971) §., 34 Not published* Not published*
Bull. Enviroaa. Cont ... Toxicol.
3-dimethylcyclopropane-1carboxylic ac i d 2,4-D 1,3-Dichloropropene Dichlorvos Dichlorvos Blood ) urine 2 ,4-D
oc
Rivera, J. B. et al. Not published*
J. Chromatog. (1970) 50, 334
Urine Blood Urine
N-acetyl-S(3-chloroprop-2enyl) cysteine dichlorvos dimethyl phosphoric acid
oc
Analyaen in biolog. Material** Blair, D.; 1186 Roderick, B. R.
D. Reaachler, Verla& 1Jeial11aia
J. A&ric. Food Ch-. ( 1976),
!1.• ~
Dicrotophoe Dieldrin
Urine Blood
dimethyl phoaphoric acid dieldrin
Blair, D. ; Roderick, H. R. Chem. (1976), 17, 1186. 1. 2.
J. Agrtc. Food
Richardson, A. ; R.obinaon , J. ; Juab, B. ; Davies , J. M. Arch. Environm. Health (1967), 14, 703-708. Dale, W. !.; Curley, A. ; Cueto , c. Life Scieocea . (1966). 2_, 47-54.
D:lale t hoate Endrin Fenitrothion Flamprop-ieopropyl
Blood Blood Urine Urine Urine
dimethoate liimetboxon anti-12-hydroxyendrin p-nitrophenol N-benzoyl-N-(3-chloro - 4fluorophenyl)-l-aminopropion! acid M-benzoyl-N-(3-chloro-4-fluorophenyl)-2-aminopropionic acid gr8Dl0xone ion
oc TLC
Martena , M. A. et al. Med. Fac. Landbo,_t, Rijkauniv. Gent (1974), 39, 1279
Baldwin, K. K.;
Hutaon, D. H.
Analyat (191k>), 105, 60-65 D. Hensch l er, Verlag Weinbeia
oc.
PhM
Analysen in biolog. Material** Not published*
Flamprop-methyl Gramoxone
Urine Urine Blood
Not published* CM Calderbank, A.; Yuen, S. H. Analyst (1965), 90, 99
FORM 2.
DAILY RECORD
Day of spraying 1
2
3
4
5
6
7
8
9
10
11
12
13
14
Time spraying commenced Time spraying finished Quantity of pesticide used in daily operation (before dilution) Estimate of area covered Minimum temperature Maximum temperature Relative humidity Rain during spraying period (hours) Rain outside spraying period (hours) Wind force Wind direction in relation to general direction of sprayl 1 DIARY : S = side, B
X
X X
--x-
o c oc
X
X
X
X
=
wind behind, F
= wind
in front, V
=
variable,
Note below any relevant events, sickness of spraymen, accidents to equipment or man, etc.
~ z X
tt1
~-Q__ CX> 1-'N
'tl Ill
tJj
<
w
w.
1-'
VBC/82.1 page 14 ANNEX 4 FORM 3. Name DAILY PERSONAL RECORD Personal No.
Details of exposure to any pesticide during preceding month
Day 1 Type of work 1 Time started work Time finished work Total working hours Amount of pesticide applied or number of pump charges Clothing worn2 Overall Scarf Hat or helmet Boots Shoes Thongs Face mask Gloves Apron Number of times washing during day: hands face Time (minutes) between end of work and bathing changing clothes Smoking (while spraying) Eating or drinking Cholinesterase level: before work after work Haematocrit Urine sample taken Urine volume Blood sample taken Days exposure pads worn Days respirator worn 1 X X X X
2
3
4
5
6
7
8
9
10 11 12 13 14 21
X X
X X X X
X X X X
X
X
X
Material X X X X X X X X X X X X X X X X X X X X X X X X X X X
X X
X X
X X
X X
X X X X
X X X X
X X
X X X X X X X X
X
X
X
X
X
X
X
X
X
X
X
X
X X
X X
X
X
s
spraying; not worn;
M = mixing. W = worn. newlv washed: X worn. not washed since last
2 N