E:/Biomedica Vol.23 Jul. – Dec. 2007/Bio-1               (A)


              EVALUATION OF SUSPECTED CHRONIC PESTICIDE
          POISONING AMONG RESIDENTS NEAR AGRICULTURE FIELDS

                      1AFTAB    TURABI, 2AHMED DANYAL, 3SAUD HASSAN, 4YUSAF SALAT
                              5MANSOOR   AHMAD, 6M. A. RASHID, 7AFZAL HAQ ASIF
                   1-5,7Department  of Pharmacology, Islamic International Medical College, Rawalpindi
                            2,7 FrontierMedical College, Abbottabad, 3Dow Medical College, and
              4 Sind Medical College, Karachi, 5Research Institute of Pharmaceutical Sciences, Univ. of Karachi
                 6Department of Forensic Medicine and Toxicology, Foundation Medical College, Rawalpindi



     The present study was performed to evaluate the incidence of organophosphorus toxicity among
     agrarian and non agrarian subjects residing near agriculture fields. The location of this study
     was Nawakot village, Multan. From the cotton producing area of Multan, 225 volunteers (far-
     mers) including 103 females and 122 males were selected. Children <12 years of age constitute
     15% of the population. A total of 100 volunteers (non agrarians) from Multan city were taken as
     control. Blood (4 ml) was drawn from the volunteers to test the level of acetylcholine estrase
     (Ach E) in plasma. The blood samples were then analysed at the laboratory of National Poison
     Control Center (NPCC). Organo-phosphate (OP) & carbamates (CM) both act to block Ach E
     hydrolysis, necessary for synaptic response in the CNS. Acute illnesses were seen in 6 (2.67%),
     children (group 1). They had fever and signs of pulmonary infections. Generalised weakness
     was found in 9 males and 13 females. Paraesthesia was found in 11 volunteers of group IV.
     Blood sampling test revealed that 6 volunteers (2.67%) had plasma Ach E below 5300 IU/ml (<
     50% reduction), whereas 4 volunteers had Ach E level between 5300 - 5500 IU/ml (< 45%
     reduction), 81 volunteers fall in group “c”, and 126 individuals had an Ach E reduction of at least
     25% and 8 volunteers had the serum cholinesterase level above 10000 IU/ml. None of volun-
     teers had the value above 11000 IU whereas plasma Ach E level of control population was
     between 11500 - 13500 IU/ml. Medical tests of the level of Ach E in plasma suggest that the over-
     all incidence of poisoning from exposure to OP & CM is quite high, and appears to be consistent
     with the results from other studies in other developing countries.

Indiscriminate use and improper handling of syn-                en poverty, illiteracy and infant mortality are still
thetic pesticides in agriculture have resulted into             major problems. In part, the resistance of policy
serious problems for human health in many deve-                 makers is due to uncertainty about the severity of
loping countries. However, the true extent of the               the problem, its sources, and suitable interventi-
problem is hard to determine for a variety of rea-              ons. Their uncertainty is understandable, since
sons. First, farmers with mild pesticide poisoning              systematic studies of the health effects of pestici-
often do not report because treatment services are              des are scarce. Most existing studies rely on far-
costly, inaccessible, or fear that drawing attention            mers’ self-reported symptoms, as appropriate pa-
to themselves may result in the loss of employ-                 thological tests are costly and relatively difficult for
ment opportunities. Second, health-care profess-                many developing country institutions to admini-
ionals in rural areas often fail to correctly diag-             ster.
nose poisoning, as many of the related symptoms                      To assess the potential health hazards of pesti-
are quite general in nature or mimic other com-                 cides, the NPCC with the technical collaboration of
mon health problems e.g. headaches, dizziness,                  WHO studied the pesticide poisoning among the
vomiting13 (FAO, 2001) etc. At least 20,000 wor-                families of agriculture workers.41,42 The study in-
kers die from exposure every year, the majority in              cludeed clinical examination by doctors from the
developing countries. World Health Organization.                NPCC, along with blood tests for cholinesterase
18,26,30,40                                                     inhibition due to contamination by organophosp-
     Although the health hazards of pesticides are              hate and carbamate. Epidemiological studies have
serious, support from policy makers for remedial                linked carbamates (CM) and organophosphates
measures has been lukewarm in developing count-                 (OP) with foetal death, hormonal changes, DNA
ries. There is a widespread concern about diverting             damage, birth defects, and abnormal sperm and
resources to alternative pest control methods wh-               ova.43 In addition, OP, as a class of insecticides,

Biomedica Vol. 23 (Jul. - Dec. 2007)
EVALUATION OF SUSPECTED CHRONIC PESTICIDE POISONING                                                            77

has been linked with Non-Hodgkin's lymphoma,            population (non-agrarians). They all were healthy
leukaemia, and lung cancer. In children OP have         individuals, who underwent the same protocol of
been linked to aplastic anaemia, the failure of the     clinical examination and blood test (Fig. 1 and 2).
bone marrow to produce blood cells, and leuke-
mia. Children with asthma may have severe reacti-
ons to OP in particular.44
     Human beings have three types of cholineste-
rases: red blood cell (RBC) cholinesterase, called              25%
                                                                                      35%          21-45 yrs
“true cholinesterase”; plasma cholinesterase, call-
ed “pseudocholinesterase”; and brain cholineste-                                                   >45 yrs
rase. RBC cholinesterase is the same enzyme that                                                   12-12 yrs
is found in the nervous system, while plasma cho-                     40%
linesterase is made in the liver. When a cholines-
terase blood test is taken, two types of cholinester-    Fig. 1: Age Groups of volunteers from control
ases can be detected. Physicians find plasma choli-              population
nesterase readings helpful for detecting the early,
acute effects of organophosphate poisoning, while
RBC readings are useful in evaluating long-term,
or chronic, exposure. In this study we only per-
formed the plasma AchE level due to limited reso-
urces.                                                                          35%              12-20 (47)
     Human exposure to cholinesterase-inhibiting               45                                <12 (34)
pesticides can result from inhalation, ingestion, or                                40%          >45 (43)
eye or skin contact during the manufacture, mix-                             25%                 20-45 (101)
ing, or applications of these chemicals. Signs and
symptoms of cholinesterase inhibition from expo-        Fig. 2: Age groups of volunteers from farmer families
sure to CM or OP include the following:
1. Mild cases: tiredness, weakness, dizziness, na-
     usea and blurred vision.                                Using clinical examination results, the team
2. Moderate cases: headache, sweating, tearing,         collected the blood samples for cholinesterase
     drooling, vomiting, tunnel vision, and twitch-     inhibition test. In each case, a 4 ml blood sample
     ing.                                               drawn from the volunteer was used to test the level
3. Severe cases: abdominal cramps, diarrhea,            of AchE in plasma (Serum Butyryl Cholinesterase
     muscular tremors, staggering gait, pinpoint        Kit, Randox Laboratories Ltd. UK). The normal
     pupils, hypotension, slow heartbeat, breathing     value for serum AchE ranges between 5300 –
     difficulty, and possibly death, if not promptly    13300 IU/ml according to the kit used. The blood
     treated by a physician.                            samples were then analysed at the laboratory of
                                                        NPCC. OP and CM act so as to inhibit acetylcho-
SUBJECTS AND METHODS                                    line hydrolysis, a necessary task for synaptic res-
To investigate the health impacts of pesticide use,     ponse in the central nervous system. The presence
structured questionnaires designed by NPCC team         of cholinesterase inhibiting chemicals prevent the
were used to collect information on farming sys-        breakdown of acetylcholine. Acetylcholine can
tems, pesticide use and practices, applicator pre-      then build up, causing a “jam” in the nervous sys-
cautions, and protective measures. The study was        tem. The normal value for serum cholinesterase
carried out to determine the incidence of organo-       according to the kit used in this study ranges bet-
phosphate toxicity in the families of agriculture       ween 5300-13300 IU/ml. Groups have been con-
workers who were not involved directly in agricul-      stituted showing age and cholinesterase levels
ture. Outskirts of Multan city, Nawakot village,        (Fig. 3).
was selected, that is basically, a cotton producing
area. The families of farmers, include children,
young and elderly of both genders. A total of 225       RESULTS
volunteers were evaluated in three days among           Total 225 volunteers were included in the study
which 103 (46%) were females and 122 (54%) were         out of which 122 were males and 103 were females.
males. Children, < than 12 years of age constitutes     Various age groups has been constituted, the lar-
15% of the population. All participants were exam-      gest population size was between 20-45 years
ined by doctors from NPCC. 100 volunteers from          (45%), and the smallest was found in group I (≤ 12
Multan city and its outskirts were taken as control     years) that constitutes 15% of the total (Fig. 1 & 2)


                                                                               Biomedica Vol. 23 (Jul. - Dec. 2007)
78                                                                      AFTAB TURABI, AHMED DANYAL, SAUD HASSAN et al

(Table 1).
     History taking and physi-       140      133
cal examination revealed that
64 volunteers were symptom           120
free that includes 39 males                             103
and 25 females. A total of 133       100                         94
volunteers (55 males and 78
                                           78
females) had complaints of            80
decrease appetite (59.1%),                                                                                    64
abdominal pain in 103                 60 55           54      51
(45.78%), and diarrhoea in                         49
                                                            43
94 volunteers (41.78%). Ac-                                                                             39 25
                                      40
ute illnesses were seen in 6
                                                                                                     22
(2.67%) children (group I),                                                                11
                                      20                                                          13
who had fever and signs of                                               2 6 4      6   56      9
                                                                      4          2
pulmonary infections. Gene-
                                        0
ralised weakness and easy                                Pain Abdomen




                                                                                   Pulmonary




                                                                                                        Numbness




                                                                                                                             Symptom Free
                                              Decrease




                                                                        Diarrhea




                                                                                                Fever




                                                                                                                   Fatigue
                                              Appetite




                                                                                    Infection
fatigability were found in 9
males and 13 females. Peri-
pheral numbness and tingling
were present in 11 volunteers
of group IV (Fig. 3).
     Building upon the initial                            Male            Female           Total
clinical examination, the me-
dical team carried out blood              Fig. 3: Clinical evaluation data for organophosphate exposure
tests for 225 volunteers to ch-
eck for cholinesterase enzyme                                                                 Group D
inhibition from exposure to                                                                   126(56%)
organophosphate and carba-
                                    120
mate pesticides. The results
displayed in graph IV indi-
cate that (2.67%) 6 volunteers      100
had plasma AchE below 5300                                                      Group C
IU/ ml (≤ 50% reduction),                                                       81(36%)
                                     80
whereas 4 volunteers had
AchE level between 5300 and
5500 IU/ml (≤ 45% reduce-            60
tion), 81 volunteers fall in
group “C”, 126 individuals
had an AchE reduction of at          40
least 25%, and 8 volunteers
had the serum cholinesterase         20          Group A
                                                                                                               Group E
                                                                Group B                                        8(3.6%)
level just above 10000 IU/ml.                     6(2.6%)        4(1.8%)
No single individual had the
value above 11000 IU where-           0
                                          <5300IU/ml     5300-5500IU      5500-7500     7500-10000     >10000IU/ml
as plasma AchE level of con-
trol population ranged bet-
ween 11500 – 13500 IU/ml                      Fig. 4: Age groups showing serum cholinesterase
with an average of 12500 IU/
ml.
     We calculated the           Table 1: Age groups of volunteers and control population
correlation of the blo-                     Group I            Group II            Group III          Group IV
od test results against
                                           < 12 Years       12 – 20 Years        21 – 45 Years       > 45 Years
an index of equally we-
ighed symptoms that          Volunteers         34                 47                  101                43
are commonly associa-        Control             0                 25                   35                40


Biomedica Vol. 23 (Jul. - Dec. 2007)
EVALUATION OF SUSPECTED CHRONIC PESTICIDE POISONING                                                              79

ted with poisoning. Our evidence does not lend            pain; lacrimation and irritation of the eyes; dif-
support to the use of self-reported symptoms as           ficulty in seeing; restlessness; difficulty in falling
indicators of actual pesticide poisoning. Given the       asleep; trembling of hands; and irritability.1,24 In
relatively high incidence of poisoning in the sam-        this study acute toxicity was observed in 13.5% ca-
ple, however, our results strongly support regular        ses below 12 years of age.22, 31 Volunteers showed
medical testing for people who are exposed to hig-        59.1% gastrointestinal symptoms referred as loss
hly or moderately toxic organophosphate and/or            of appetite, off and on abdominal pain and diar-
carbamate pesticides.                                     rhoea.38 64 individuals had no symptoms and their
     According to the medical literature, the types       serum cholinesterase levels ranged from 7500 –
and severity of cholinesterase inhibittion sympto-        1100 IU/ml. No individual in the study was direct-
ms depend on the amount of pesticide involved in          ly involved in the farming or spray even then they
the exposure, the toxicity of the pesticide, the rou-     are suffering from sub clinical and delayed effects
te of exposure, and the duration of exposure.12           of pesticide toxicity. The expected source of expo-
                                                          sure observed was the use of empty cans of pesti-
DISCUSSION                                                cide as drinking water reservoir, storage of pestici-
Unintentional poisonings kill an estimated 355000         des in houses and bad hygiene. If we look into ser-
people each year.41,42 Two-thirds of these deaths         um cholinesterase level it was observed that 6 indi-
occur in developing countries, where such poison-         viduals had the value below 5300 IU/ml that mea-
ing is strongly associated with excessive exposure        ns acute exposure whereas rest of them had their
to, and inappropriate use of, toxic chemicals. In         cholinesterase level within range, although none of
many such settings, the toxic chemicals may be            them reached the upper limit. This shows that the
emitted directly into soil, air and water.43              individuals even with cholinesterase levels within
                                                          range were also suffering from sub clinical long-
     There are many pesticides with thousands of
                                                          term exposure to organophosphates.
trade names. Two-thirds of their total use is in
agriculture.42 Chronic pesticide exposure is often a           After literature search and evaluation of our
problem in occupational settings, particularly am-        findings we came to the conclusion that sub clini-
ong poor rural populations, where men, women              cal damage does occur, however longer follow up
and children all work and live in close proximity to      studies are needed. It is suggested that the govern-
fields on which chemicals are applied and stored.         ment in collaboration with pesticide industry sho-
                                                          uld encourage awareness programs for the farmers
     There is a paucity of data on the possible dele-
                                                          that may help in the reduction of pesticide morta-
terious effects of chronic exposure to OPCs in occ-
                                                          lity and morbidity.
upational and/or environmental settings. In gene-
ral, the literature brings out three types of ‘non-            Detailed, long-term studies of occupational or
acute’ OPC poisoning: occupational exposure with          environmental exposures to OPC are needed to
reductions in AchE levels; occupational exposure          distinguish the effects of the active OPC. Subtle
with no reduction in AchE levels; and environmen-         abnormalities on neurological examination, such
tal exposure. However, the relationships between          as impaired two-point discrimination and vibra-
chronic exposure, AchE inhibition and symptoms            tion sensation, have also been reported in workers
do not, as yet, seem to be well established.              chronically exposed to OPCs.4,38 Some report evi-
     Available evidence suggests that there is a pos-     dence of nerve abnormalities during occupational
sibility of adverse effects occurring below OPC           exposure9,36 while others do not.11,23 A recent study
concentrations that are generally considered to be        from Sri Lanka has shown inhibition of AchE enzy-
safe based on measurements of AchE inhibition;            me activity and impairment of sensory and motor
i.e. these effects are not clearly related to the inhi-   nerve conduction due to long-term, low-level exp-
bition of cholinesterases1,27,32,34 Studies on health     osure to OPC.25 Evidence of toxicity was found not
hazards to agricultural workers who handle, store         only among the farmers who directly handled (spr-
and use OPC pesticides have documented a range            ayed) OPCs, but also among those employed in inl-
of non-specific self-reported symptoms that have          and fisheries living within a 25 km radius of the
been attributed to chronic exposure. These inclu-         cultivated land, who were not directly exposed.
de: burning or prickling of the skin; tingling or nu-          Chronic organophosphate-induced neuropsyc-
mbness of hands and face; muscular twitching or           hiatric disorders (COPIND) occur without choline-
cramps in the face, neck, arms and legs; respirat-        rgic symptoms, and although the underlying mec-
ory symptoms, including chest pain, cough, run-           hanisms are not established, they do not seem
ning nose, wheezing, shortness of breath, irritation      dependent on AchE inhibition.6,28,29,34 Clinical fea-
of the throat; excessive sweating; nausea, vomit-         tures reported include: anxiety disorder; depress-
ing, diarrhoea; excessive salivation; abdominal           ion; psychotic symptoms; dysthymic disorder

                                                                                 Biomedica Vol. 23 (Jul. - Dec. 2007)
80                                                            AFTAB TURABI, AHMED DANYAL, SAUD HASSAN et al

(DSM-III-R); problems with short-term memory,            blood tests should be conducted for those who
learning, attention, information processing, eye-        were directly or indirectly exposed to toxic organo-
hand coordination and reaction time; autonomic           phosphate and carbamate pesticides although the-
dysfunction; and extra pyramidal symptoms. 3,32,         re is no definite relationship established yet bet-
34,37 Similar clinical features have also been repor-    ween the signs and symptoms of poisoning and
ted by soldiers suffering from the much-publicised       AChE activity.
Gulf-war Syndrome, which led to the, so far unpro-
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24.   Ohayo-Mitoko et al., 2000 G.J.A. Ohayo-Mitoko, H.           exposure to organophosphates in sheep dip, Lancet
      Kromhout, J.M. Simwa, J.S.M. Boleij and D. Hee-             345 (1995), pp. 1135–1139.
      derik, Self reported symptoms and inhibition of         38. Stokes et al., 1995 L. Stokes, A. Stark, E. Marshall
      acetylcholinesterase activity among Kenyan agricul-         and A. Narang, Neurotoxicity among pesticide ap-
      tural workers, Occup. Environ. Med. 57 (2000), pp.          plicators exposed to organophosphate pesticides,
      195–200.                                                    Occup. Environ. Med. 52 (1995), pp. 648–653.
25.   Peiris-John et al., 2002 R. Peiris-John, D.K. Rub-      39. Thuy et al., 2003 Thuy, A.B., Wangsuphachart, V.,
      eru, A.R. Wickremasinghe, L.A.M. Smit and W. Van            Kaewkurgwal, J., 2003. Cholinesterase Screening
      der Hoek, Effects of occupational exposure to orga-         Test among Organophosphate Exposure of Rice
      nophosphate pesticides on nerve and neuromus-               Farmers in Southern Vietnam. The Book of Abs-
      cular function, J. Occup. Environ. Med. 44 (2002),          tracts, Medical Publishing House, Hanoi, pp. 186–
      pp. 352–357.                                                187.


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40. WHO, 1990 WHO, 1990. Report on Pesticides in                 cia-Nieto and F. Diaz-Barriga, Overview of human
    Agriculture. World Health Organization, Geneva.              health and chemical mixtures: problems facing dev-
41. WHO, 2003 WHO, 2003. World Health Report:                    eloping countries, Environ. Health Perspect. 110
    Shaping the Future. World Health Organization,               (2002), pp. 901–909.
    Geneva.                                                  44. Zahm et al., 1997 S.H. Zahm, M.H. Ward and A.
42. World Health Organization (WHO), 1990. Public                Blair, Pesticides and cancer. In: M. Keifer, Editor,
    Health Impact of Pesticides Used in Agriculture.             Occupational Medicine: State of the Art Reviews.
43. Yáñez et al., 2002 L. Yáñez, D. Ortiz, J. Calderon, L.       Vol. 12: Pesticides, Hanley and Belfus, Inc., Phila-
    Batres, L. Carrizales, J. Meija, L. Martinez, E. Gar-        delphia (1997), pp. 269–289.




Biomedica Vol. 23 (Jul. - Dec. 2007)

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Pesticide Poisoning of Residents Near Farm Fields

  • 1. E:/Biomedica Vol.23 Jul. – Dec. 2007/Bio-1 (A) EVALUATION OF SUSPECTED CHRONIC PESTICIDE POISONING AMONG RESIDENTS NEAR AGRICULTURE FIELDS 1AFTAB TURABI, 2AHMED DANYAL, 3SAUD HASSAN, 4YUSAF SALAT 5MANSOOR AHMAD, 6M. A. RASHID, 7AFZAL HAQ ASIF 1-5,7Department of Pharmacology, Islamic International Medical College, Rawalpindi 2,7 FrontierMedical College, Abbottabad, 3Dow Medical College, and 4 Sind Medical College, Karachi, 5Research Institute of Pharmaceutical Sciences, Univ. of Karachi 6Department of Forensic Medicine and Toxicology, Foundation Medical College, Rawalpindi The present study was performed to evaluate the incidence of organophosphorus toxicity among agrarian and non agrarian subjects residing near agriculture fields. The location of this study was Nawakot village, Multan. From the cotton producing area of Multan, 225 volunteers (far- mers) including 103 females and 122 males were selected. Children <12 years of age constitute 15% of the population. A total of 100 volunteers (non agrarians) from Multan city were taken as control. Blood (4 ml) was drawn from the volunteers to test the level of acetylcholine estrase (Ach E) in plasma. The blood samples were then analysed at the laboratory of National Poison Control Center (NPCC). Organo-phosphate (OP) & carbamates (CM) both act to block Ach E hydrolysis, necessary for synaptic response in the CNS. Acute illnesses were seen in 6 (2.67%), children (group 1). They had fever and signs of pulmonary infections. Generalised weakness was found in 9 males and 13 females. Paraesthesia was found in 11 volunteers of group IV. Blood sampling test revealed that 6 volunteers (2.67%) had plasma Ach E below 5300 IU/ml (< 50% reduction), whereas 4 volunteers had Ach E level between 5300 - 5500 IU/ml (< 45% reduction), 81 volunteers fall in group “c”, and 126 individuals had an Ach E reduction of at least 25% and 8 volunteers had the serum cholinesterase level above 10000 IU/ml. None of volun- teers had the value above 11000 IU whereas plasma Ach E level of control population was between 11500 - 13500 IU/ml. Medical tests of the level of Ach E in plasma suggest that the over- all incidence of poisoning from exposure to OP & CM is quite high, and appears to be consistent with the results from other studies in other developing countries. Indiscriminate use and improper handling of syn- en poverty, illiteracy and infant mortality are still thetic pesticides in agriculture have resulted into major problems. In part, the resistance of policy serious problems for human health in many deve- makers is due to uncertainty about the severity of loping countries. However, the true extent of the the problem, its sources, and suitable interventi- problem is hard to determine for a variety of rea- ons. Their uncertainty is understandable, since sons. First, farmers with mild pesticide poisoning systematic studies of the health effects of pestici- often do not report because treatment services are des are scarce. Most existing studies rely on far- costly, inaccessible, or fear that drawing attention mers’ self-reported symptoms, as appropriate pa- to themselves may result in the loss of employ- thological tests are costly and relatively difficult for ment opportunities. Second, health-care profess- many developing country institutions to admini- ionals in rural areas often fail to correctly diag- ster. nose poisoning, as many of the related symptoms To assess the potential health hazards of pesti- are quite general in nature or mimic other com- cides, the NPCC with the technical collaboration of mon health problems e.g. headaches, dizziness, WHO studied the pesticide poisoning among the vomiting13 (FAO, 2001) etc. At least 20,000 wor- families of agriculture workers.41,42 The study in- kers die from exposure every year, the majority in cludeed clinical examination by doctors from the developing countries. World Health Organization. NPCC, along with blood tests for cholinesterase 18,26,30,40 inhibition due to contamination by organophosp- Although the health hazards of pesticides are hate and carbamate. Epidemiological studies have serious, support from policy makers for remedial linked carbamates (CM) and organophosphates measures has been lukewarm in developing count- (OP) with foetal death, hormonal changes, DNA ries. There is a widespread concern about diverting damage, birth defects, and abnormal sperm and resources to alternative pest control methods wh- ova.43 In addition, OP, as a class of insecticides, Biomedica Vol. 23 (Jul. - Dec. 2007)
  • 2. EVALUATION OF SUSPECTED CHRONIC PESTICIDE POISONING 77 has been linked with Non-Hodgkin's lymphoma, population (non-agrarians). They all were healthy leukaemia, and lung cancer. In children OP have individuals, who underwent the same protocol of been linked to aplastic anaemia, the failure of the clinical examination and blood test (Fig. 1 and 2). bone marrow to produce blood cells, and leuke- mia. Children with asthma may have severe reacti- ons to OP in particular.44 Human beings have three types of cholineste- rases: red blood cell (RBC) cholinesterase, called 25% 35% 21-45 yrs “true cholinesterase”; plasma cholinesterase, call- ed “pseudocholinesterase”; and brain cholineste- >45 yrs rase. RBC cholinesterase is the same enzyme that 12-12 yrs is found in the nervous system, while plasma cho- 40% linesterase is made in the liver. When a cholines- terase blood test is taken, two types of cholinester- Fig. 1: Age Groups of volunteers from control ases can be detected. Physicians find plasma choli- population nesterase readings helpful for detecting the early, acute effects of organophosphate poisoning, while RBC readings are useful in evaluating long-term, or chronic, exposure. In this study we only per- formed the plasma AchE level due to limited reso- urces. 35% 12-20 (47) Human exposure to cholinesterase-inhibiting 45 <12 (34) pesticides can result from inhalation, ingestion, or 40% >45 (43) eye or skin contact during the manufacture, mix- 25% 20-45 (101) ing, or applications of these chemicals. Signs and symptoms of cholinesterase inhibition from expo- Fig. 2: Age groups of volunteers from farmer families sure to CM or OP include the following: 1. Mild cases: tiredness, weakness, dizziness, na- usea and blurred vision. Using clinical examination results, the team 2. Moderate cases: headache, sweating, tearing, collected the blood samples for cholinesterase drooling, vomiting, tunnel vision, and twitch- inhibition test. In each case, a 4 ml blood sample ing. drawn from the volunteer was used to test the level 3. Severe cases: abdominal cramps, diarrhea, of AchE in plasma (Serum Butyryl Cholinesterase muscular tremors, staggering gait, pinpoint Kit, Randox Laboratories Ltd. UK). The normal pupils, hypotension, slow heartbeat, breathing value for serum AchE ranges between 5300 – difficulty, and possibly death, if not promptly 13300 IU/ml according to the kit used. The blood treated by a physician. samples were then analysed at the laboratory of NPCC. OP and CM act so as to inhibit acetylcho- SUBJECTS AND METHODS line hydrolysis, a necessary task for synaptic res- To investigate the health impacts of pesticide use, ponse in the central nervous system. The presence structured questionnaires designed by NPCC team of cholinesterase inhibiting chemicals prevent the were used to collect information on farming sys- breakdown of acetylcholine. Acetylcholine can tems, pesticide use and practices, applicator pre- then build up, causing a “jam” in the nervous sys- cautions, and protective measures. The study was tem. The normal value for serum cholinesterase carried out to determine the incidence of organo- according to the kit used in this study ranges bet- phosphate toxicity in the families of agriculture ween 5300-13300 IU/ml. Groups have been con- workers who were not involved directly in agricul- stituted showing age and cholinesterase levels ture. Outskirts of Multan city, Nawakot village, (Fig. 3). was selected, that is basically, a cotton producing area. The families of farmers, include children, young and elderly of both genders. A total of 225 RESULTS volunteers were evaluated in three days among Total 225 volunteers were included in the study which 103 (46%) were females and 122 (54%) were out of which 122 were males and 103 were females. males. Children, < than 12 years of age constitutes Various age groups has been constituted, the lar- 15% of the population. All participants were exam- gest population size was between 20-45 years ined by doctors from NPCC. 100 volunteers from (45%), and the smallest was found in group I (≤ 12 Multan city and its outskirts were taken as control years) that constitutes 15% of the total (Fig. 1 & 2) Biomedica Vol. 23 (Jul. - Dec. 2007)
  • 3. 78 AFTAB TURABI, AHMED DANYAL, SAUD HASSAN et al (Table 1). History taking and physi- 140 133 cal examination revealed that 64 volunteers were symptom 120 free that includes 39 males 103 and 25 females. A total of 133 100 94 volunteers (55 males and 78 78 females) had complaints of 80 decrease appetite (59.1%), 64 abdominal pain in 103 60 55 54 51 (45.78%), and diarrhoea in 49 43 94 volunteers (41.78%). Ac- 39 25 40 ute illnesses were seen in 6 22 (2.67%) children (group I), 11 20 13 who had fever and signs of 2 6 4 6 56 9 4 2 pulmonary infections. Gene- 0 ralised weakness and easy Pain Abdomen Pulmonary Numbness Symptom Free Decrease Diarrhea Fever Fatigue Appetite Infection fatigability were found in 9 males and 13 females. Peri- pheral numbness and tingling were present in 11 volunteers of group IV (Fig. 3). Building upon the initial Male Female Total clinical examination, the me- dical team carried out blood Fig. 3: Clinical evaluation data for organophosphate exposure tests for 225 volunteers to ch- eck for cholinesterase enzyme Group D inhibition from exposure to 126(56%) organophosphate and carba- 120 mate pesticides. The results displayed in graph IV indi- cate that (2.67%) 6 volunteers 100 had plasma AchE below 5300 Group C IU/ ml (≤ 50% reduction), 81(36%) 80 whereas 4 volunteers had AchE level between 5300 and 5500 IU/ml (≤ 45% reduce- 60 tion), 81 volunteers fall in group “C”, 126 individuals had an AchE reduction of at 40 least 25%, and 8 volunteers had the serum cholinesterase 20 Group A Group E Group B 8(3.6%) level just above 10000 IU/ml. 6(2.6%) 4(1.8%) No single individual had the value above 11000 IU where- 0 <5300IU/ml 5300-5500IU 5500-7500 7500-10000 >10000IU/ml as plasma AchE level of con- trol population ranged bet- ween 11500 – 13500 IU/ml Fig. 4: Age groups showing serum cholinesterase with an average of 12500 IU/ ml. We calculated the Table 1: Age groups of volunteers and control population correlation of the blo- Group I Group II Group III Group IV od test results against < 12 Years 12 – 20 Years 21 – 45 Years > 45 Years an index of equally we- ighed symptoms that Volunteers 34 47 101 43 are commonly associa- Control 0 25 35 40 Biomedica Vol. 23 (Jul. - Dec. 2007)
  • 4. EVALUATION OF SUSPECTED CHRONIC PESTICIDE POISONING 79 ted with poisoning. Our evidence does not lend pain; lacrimation and irritation of the eyes; dif- support to the use of self-reported symptoms as ficulty in seeing; restlessness; difficulty in falling indicators of actual pesticide poisoning. Given the asleep; trembling of hands; and irritability.1,24 In relatively high incidence of poisoning in the sam- this study acute toxicity was observed in 13.5% ca- ple, however, our results strongly support regular ses below 12 years of age.22, 31 Volunteers showed medical testing for people who are exposed to hig- 59.1% gastrointestinal symptoms referred as loss hly or moderately toxic organophosphate and/or of appetite, off and on abdominal pain and diar- carbamate pesticides. rhoea.38 64 individuals had no symptoms and their According to the medical literature, the types serum cholinesterase levels ranged from 7500 – and severity of cholinesterase inhibittion sympto- 1100 IU/ml. No individual in the study was direct- ms depend on the amount of pesticide involved in ly involved in the farming or spray even then they the exposure, the toxicity of the pesticide, the rou- are suffering from sub clinical and delayed effects te of exposure, and the duration of exposure.12 of pesticide toxicity. The expected source of expo- sure observed was the use of empty cans of pesti- DISCUSSION cide as drinking water reservoir, storage of pestici- Unintentional poisonings kill an estimated 355000 des in houses and bad hygiene. If we look into ser- people each year.41,42 Two-thirds of these deaths um cholinesterase level it was observed that 6 indi- occur in developing countries, where such poison- viduals had the value below 5300 IU/ml that mea- ing is strongly associated with excessive exposure ns acute exposure whereas rest of them had their to, and inappropriate use of, toxic chemicals. In cholinesterase level within range, although none of many such settings, the toxic chemicals may be them reached the upper limit. This shows that the emitted directly into soil, air and water.43 individuals even with cholinesterase levels within range were also suffering from sub clinical long- There are many pesticides with thousands of term exposure to organophosphates. trade names. Two-thirds of their total use is in agriculture.42 Chronic pesticide exposure is often a After literature search and evaluation of our problem in occupational settings, particularly am- findings we came to the conclusion that sub clini- ong poor rural populations, where men, women cal damage does occur, however longer follow up and children all work and live in close proximity to studies are needed. It is suggested that the govern- fields on which chemicals are applied and stored. ment in collaboration with pesticide industry sho- uld encourage awareness programs for the farmers There is a paucity of data on the possible dele- that may help in the reduction of pesticide morta- terious effects of chronic exposure to OPCs in occ- lity and morbidity. upational and/or environmental settings. In gene- ral, the literature brings out three types of ‘non- Detailed, long-term studies of occupational or acute’ OPC poisoning: occupational exposure with environmental exposures to OPC are needed to reductions in AchE levels; occupational exposure distinguish the effects of the active OPC. Subtle with no reduction in AchE levels; and environmen- abnormalities on neurological examination, such tal exposure. However, the relationships between as impaired two-point discrimination and vibra- chronic exposure, AchE inhibition and symptoms tion sensation, have also been reported in workers do not, as yet, seem to be well established. chronically exposed to OPCs.4,38 Some report evi- Available evidence suggests that there is a pos- dence of nerve abnormalities during occupational sibility of adverse effects occurring below OPC exposure9,36 while others do not.11,23 A recent study concentrations that are generally considered to be from Sri Lanka has shown inhibition of AchE enzy- safe based on measurements of AchE inhibition; me activity and impairment of sensory and motor i.e. these effects are not clearly related to the inhi- nerve conduction due to long-term, low-level exp- bition of cholinesterases1,27,32,34 Studies on health osure to OPC.25 Evidence of toxicity was found not hazards to agricultural workers who handle, store only among the farmers who directly handled (spr- and use OPC pesticides have documented a range ayed) OPCs, but also among those employed in inl- of non-specific self-reported symptoms that have and fisheries living within a 25 km radius of the been attributed to chronic exposure. These inclu- cultivated land, who were not directly exposed. de: burning or prickling of the skin; tingling or nu- Chronic organophosphate-induced neuropsyc- mbness of hands and face; muscular twitching or hiatric disorders (COPIND) occur without choline- cramps in the face, neck, arms and legs; respirat- rgic symptoms, and although the underlying mec- ory symptoms, including chest pain, cough, run- hanisms are not established, they do not seem ning nose, wheezing, shortness of breath, irritation dependent on AchE inhibition.6,28,29,34 Clinical fea- of the throat; excessive sweating; nausea, vomit- tures reported include: anxiety disorder; depress- ing, diarrhoea; excessive salivation; abdominal ion; psychotic symptoms; dysthymic disorder Biomedica Vol. 23 (Jul. - Dec. 2007)
  • 5. 80 AFTAB TURABI, AHMED DANYAL, SAUD HASSAN et al (DSM-III-R); problems with short-term memory, blood tests should be conducted for those who learning, attention, information processing, eye- were directly or indirectly exposed to toxic organo- hand coordination and reaction time; autonomic phosphate and carbamate pesticides although the- dysfunction; and extra pyramidal symptoms. 3,32, re is no definite relationship established yet bet- 34,37 Similar clinical features have also been repor- ween the signs and symptoms of poisoning and ted by soldiers suffering from the much-publicised AChE activity. Gulf-war Syndrome, which led to the, so far unpro- ven, hypothesis that the illness was caused by chr- REFERENCES onic exposure to chemical agents with similar effe- 1. Ames et al., 1989 R.G. Ames, S.K. Brown, D.C. cts to OPCs.14 Some organophosphates (such as Mengle, E. Kahn, J.W. Stratton and R.J. 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