Organophosphorus poisoning is a widespread problem facing millions of people around the world yearly according to the WHO [7] as the use of organophosphorus compounds is essential for agricultural purposes and exposure is unavoidable. Besides, these insecticides can cause household toxicity especially in children due to excessive unsafe use or not keeping them away from the children's reach.
In a study conducted in Washington State, Lu et al. [11] analyzed urine samples collected from 62 agricultural and 14 Urban children and found that organophosphorus metabolite levels were 3–6 times greater for agricultural children than for urban children. Moreover, Curwin et al. [12] reported that the estimated daily pesticide doses were higher for farm children than nonfarm children. As acetylcholinesterase is reported to be a specific biomarker of the organophosphorus pesticides exposure, this study was designed to explore and compare the average acetylcholinesterase level in children from both the agricultural and the non-agricultural pediatric groups as an indicator of the prolonged exposure to the organophosphorus pesticides considering that the exposure in the rural areas is higher and in more various ways of exposure, e.g., inhalation, skin contact, and ingestion. Medical history, clinical, and laboratory assessments of the children were performed, and the acetylcholinesterase level, the indicator of the exposure, was correlated to the other investigated hematological parameters.
In the current study, the rural residents showed a significant difference in weight, more visits to the fields, more prevalent unhealthy habits, e.g., eating vegetables without washing and keeping insecticides at home, previous organophosphorus toxicities, and family history of previous organophosphorus toxicities. Recurrent eye, respiratory, cardiac, central nervous system, muscle, gastrointestinal, and urinary were also more common in the rural group.
In accordance with our clinical findings, Rastogi et al. [13] found that the organophosphorus pesticide-related eye symptoms observed in exposed rural children were blurred vision, burning sensation in the eye, lacrimation, and Miosis 4.9%. The prevalence of organophosphorus pesticide-related respiratory symptoms observed in the exposed rural children was 5.7% bronchoconstriction and 3.11% chest pain. Amr et al. [14] found that topical eye changes were significant among the exposed group compared to the control subjects. Miosis, excessive salivation, convulsions, and other symptoms of acute cholinergic stimulation might be caused by organophosphorus pesticides inhibiting acetylcholinesterase. Pesticides may act on the respiratory system through one or more of the following mechanisms: (1) Non-specific irritation. (2) Allergic: pesticide or its solvent act as an antigen.
(3) Inhibition of acetylcholinesterase and build-up of Ach with bronchial cholinergic effects and spasms.
(4) Metabolic or trace element changes (Cu, Zn, Ca, Fe, etc., which are essential for ATP/ cAMP turn-over).
Regarding the cardiac symptoms, Rastogi et al. [13] found that the commonest organophosphorus pesticide-related cardiac symptom was irregular heartbeats in 4% of the exposed children. Amr et al. [14] found that acetylcholinesterase activity below 60% showed significantly more cardiorespiratory problems, in which cardiac symptoms were significant among exposed than control. Moreover, Rasoul et al. [15] found that the participants in the agricultural group had more dizziness (24%), difficulty in concentration (24%), trouble in remembering (24%), feelings of depression (26%), irritability (22.%), numbness (18%), and fatigue (30.0%), compared to the control participants (8%, 8%, 8%, 6%, 10%, 6%, 2%, and 10%, respectively) (p < 0.05). The conversion of thions (P=S) to oxons (P=O) in the body by the activity of liver microsomes, which are more toxic than thions, might be linked to the neurotoxic effects of organophosphorus pesticides. Damage to the afferent fibers of peripheral and central nerves, which is linked to the suppression of neuropathy target esterase, is another probable cause for delayed neurotoxicity. Organophosphate delayed neuropathy is the name given to this delayed condition, which is characterized by weakness, paralysis, and paresthesia in the extremities. The average cholinesterase level in this study was 77.4 ± 15.7 IU in the urban residence and 38 ± 30.2 IU in the rural residence. Leukocytosis was found in the rural residence group, and it was not correlated to the serum cholinesterase level. This coincides with earlier studies performed by Wafa et al. [16] and Hundekari et al. [17] who reported leukocytosis in the exposed group relative to the control. Leucocytosis can be an immune defense mechanism against OP chronic poisoning.
Wongta et al. [18] also found that vegetable growers had lower acetylcholinesterase activity compared with nonfarm workers at p < 0.05. However, other studies doubted the role of acetylcholinesterase as a screening test [9, 10, 19, 20] but these studies did not explain the mechanism of toxicity for the symptoms associated with the prolonged exposure.
In the present study, red blood cell count was decreased with microcytic hypochromic anemia in the exposed group and these alterations were significantly correlated to the serum cholinesterase level. In accordance with these findings, Fareed et al. [21] and Wafaa et al. [16] reported the decreased red blood cells, hematocrit, and hemoglobin with chronic exposure to pesticides. Dalbó et al. [22] found that patients exposed to pesticides show results, with decreases in erythrocyte count and mean corpuscular volume. Erythrocyte count from 5.05 million/mm3 to 4.98 million/mm3 is within the normal range. The mean corpuscular volume from 85.62 mm3 to 82.64 mm3 can suggest a reduced synthesis of hemoglobin in the erythrocytes that resulted in smaller cells. However, the red cell distribution width (RDW) analyzed suggests changes in red blood cells, although not statistically significant. The RDW has been reported as an independent predictor of 30-day mortality in patients with organophosphorus poisoning.
The microcytic hypochromic anemia may result from the inhibition of red blood cells synthesis through the affection of the erythrocyte delta-aminolevulinic acid dehydratase (ALAD enzyme) associated with the organophosphorus exposure as reported by Hernández et al. [23].
In contrary to this finding, Sandra et al. [24], Parron et al. [25], and Fareed et al. [21] reported the erythrocytosis associated with chronic exposure to organophosphorus pesticides.
In the current study, thrombocytopenia was found in the exposure group and it was negatively correlated to the serum cholinesterase level. This comes in line with the reported finding of Sandra et al. [24], and this suggests that the hematotoxicity of the organophosphorus pesticides includes the reduction of synthesis of red blood cells and platelets.
The current findings showed that weight % was significantly decreased in the rural group that showed various recurrent symptoms of exposure as eye, chest, cardiac, central nervous system, muscle, gastrointestinal, and urinary complaints. Unhealthy habits as eating vegetables without cleaning were more common in the rural group. Family history of a previous organophosphorus poisoning was more increased in the rural group even with no past history of poisoning in the exposed child himself suggesting that the fact of Rohitrattanaet al. [26] that acute toxicity can happen upon the unrevealed chronic poisoning. Also, they found significant associations between organophosphorus toxicity and being a member of a farming family (p < 0.001), parentally observed dirt on the body (p = 0.02), being with a parent on the farm (p = 0.02), playing on farms (p = 0.03), and frequency of OP application (p = 0.001).
4.1 Limitation
This study had some limitations; first, the small sample size can affect the results. It would be more appropriate to conduct the study on different areas and a bigger group of children and we did not measure organophosphorus urinary metabolites to assess the exposure; further studies are needed to confirm the results and correlate acetylcholinesterase level with these metabolites.