Agricultural Science Research Journals Vol. 2(9), pp. 512- 522, September 2012 Available online at http://www.resjournals.com/ARJ ISSN-L:2026-6073 ©2012 International Research Journals Review Organophosphate pesticides: A general review *M. Kazemi1, A. M. Tahmasbi1, R. Valizadeh1, A. A. Naserian1 and A. Soni2 1 Department of Animal Science, Excellence Center for Animal Science, Faculty of Agriculture, Ferdowsi University of Mashhad, P. O. Box 91775-1163, Mashhad, Islamic Republic of Iran. 2 Plant Protection Company of Pars Taravat. *Corresponding Author’s Email: [email protected] Abstract Pesticides are chemicals to control a variety of pests that can damage crops and livestock and reduce farm productivity. Organophosphate (OP) compounds are a group of pesticides that includes some of the most toxic chemicals used in agriculture. OP toxicity is due to the ability of these compounds to inhibit an enzyme, acetyl cholinesterase at cholinergic junctions of the nervous system. This review will deal with the history and composition, its uses and role in pollution, metabolism of OPs, health impacts, and clinical manifestations of its toxicity, diagnostic methods and treatment. We suggest that in future, the ministry of agriculture of developing countries especially Iran, should concentrate on the optimization and monitoring of usage of OP compounds as pesticides and furthermore, encouraging the farmers to use natural pesticides and organic agriculture rather than chemical pesticides. Also animal feeds and Milk may serve as a vector for the transmission of substances of extrinsic origin which can be potentially toxic to the consumer. These toxins may originate in cow's milk from the ingestion of plants known to contain toxic substances or feeds contaminated with OP pesticides. In this article, OP pesticide pollution in livestock feed, its excretion from animal and general data about OP pesticides are reviewed. Key words: pesticide, organophosphate, acetyl cholinesterase, agriculture. INTRODUCTION Many Iranian farmers have become reliant on toxic pesticides and their excessive use leads to dangerously high exposure levels for farm workers and consumers in fruits, vegetables, nuts and field crops. OP compounds are used as pesticides, herbicides, and chemical gases used World War (Bowls et al., 2003). OPs constitute a heterogeneous category of chemicals specifically designed for the control of pests, weeds or plant diseases. Their application is still the most effective and accepted means for the protection of plants, and has contributed significantly to enhanced agricultural productivity and crop yields (Bolognesi, 2003). The consumption of OP pesticides in developing country especially in Iran for pest control in agriculture is increasing, for example Iran is the largest producer of pistachios in the world and farmers apply chemicals in pistachio orchards to pest control. About 13 different pests and diseases have been found to attack pistachios. Farmers currently apply 20 different chemicals in pistachio orchards, including OP pesticides (such as phosalone, diazinon and malathion) (Aghasi et al., 2010). Also animal feeds are routinely subjected to contamination from diverse sources, including environmental pollution and activities of insects and microbes. Animal feeds may also contain endogenous toxins arising principally from spraying pesticides against pests. Although residual of OP pesticides are often considered separately, because of their different origins. Thus, particular compounds such as OP pesticides may exert anti-nutritional effects or reduce reproductive performance in farm animals. Furthermore, the combined effects may be the result of additive or synergistic interactions between the environment and animals. The extent and impact of these interactions in practical Kazemi et al. 513 Figure 1. General chemical composition of organophosphate pesticides livestock feeding remain to be quantified. Feed contaminant with pesticides especially OPs occur on a global scale but there are distinct geographical differences in the relative impact of individual compounds. The term "feed" is generally used in its widest context to include compound blends of straight ingredients as well as forages. With such a broad perspective, it is necessary and more instructive to introduce some focus. So the common use of pesticides in public health and agricultural schedules has caused severe environmental pollution and potential health hazards including severe acute and chronic cases of human and animal poisonings (Moghadamnia and Abdollahi, 2002). So we developed a search strategy to find publications about OP poisoning and its management using the key phrases causes of OP compounds, diagnosis, management of OP poisoning and drugs under clinical trials and also this article discuss about the contaminant with OP pesticides that pose significant risks to farm livestock. History and composition OP compounds were first developed by Schrader shortly before and during the Second World War. They were first used as an agricultural insecticide and later as potential chemical warfare agents (Taylor, 1996). In the late 1990 and 2000 years, with the advent of increased awareness of terrorism, nerve agents have gained prominence as weapons of mass destruction. In these compounds, the OPs are a group of both synthetic and biogenic OP compounds, characterized by the presence of the binding covalent, carbon to phosphorus (C-P) bond. In OPs, this carbon to phosphorus bond replaces one of the four carbon-to-oxygen-to-phosphorus bonds of the more common phosphate ester (Wanner and Metcalf, 1992). While the vast majority of phosphorus-containing organic compounds contain the phosphate ester bond, both synthetic and naturally occurring phosphonates are still of importance (Blackburn, 1981). The direct C-P linkage is chemically and thermally inert, with the result, most of organophosphonate compounds are resistant to chemical hydrolysis, thermal decomposition and photolysis compared with analogous compounds containing the more reactive N-P, S-P or O-P linkages (Figure 1). The letter R represents either ethyl or methyl (Figure 2). The insecticides with a double bonded sulfur are OP in the liver. Phosphonate contains an alkyl(R-) in place of one alkoxy group (RO-). X is called leaving group and is the principal metabolite for a specific identification. The use of organophosphate pesticides: pollution and toxicity The projected household demands for food until 2020 show that, between 1995 and 2020 years, the demand for food grains is likely to be doubled, for vegetables more than 2.5 times and for fruits 5 times. Thus, increase in the consumption of pesticides is likely to be at least two to three times more in years to come (Kanekar et al., 2004). The most important effects of the synthetic pesticides, especially OP pesticides are water and soil pollutions, as well as the contamination of vegetables, fruits, milk, food products and other living organisms (Denistrop, 2000; Ahmad, 2001; Erin et al., 2001). Pollution of the water in the river and depleting its resources can put the lives of many people in danger (Chimwanza et al., 2006). A wide range of organic compounds may occur in feedstuffs, including OP pesticides. Pesticides that may contaminate feeds originate from most of the major groups, including organ chlorine, OP and pyrethroid compounds (Van Barneveld, 1999). OP pesticides are examples of agriculture pollutants that may contaminate feed of livestock, particularly herbage. Cows grazing pastures that are sprayed with OP produce milk with higher pesticide content than cows grazing in unsprayed pastures. Moreover, it has also been reported that the ground water, surface water and drinking water are contaminated with pesticide (Raju et al., 1982; Hallberg, 1989). Diazinon levels in the Babol Rud River on the Caspian coast of 4.1 parts per billion (ppb) were recorded, with diazinon, ethion and methyl parathion pesticides the commonest pesticide contaminants in this river (Nasehi, 1999). Another study determined the level of diazinon as 9.5 ppb in the Shirud River (Vaez, 2000). To put these figures in perspective, the UK Environment Agency set their environmental quality standard for annual average 514 Agric. Sci. Res. J. Figure 2: Chemical structures of some OP compounds. Figure 2. Chemical structures of some OP compounds. exposure for diazinon in freshwater at 0.01 ppb, to protect aquatic life (EA, 1999). In Karaj, 40 km west of Tehran, more than 200 people were hospitalized following consumption of pesticide-contaminated cucumber in May 2002, while total poisoning cases were suspected to be even higher. Malathion was earlier reported as the commonest residue in cucumber obtained from wholesale markets in Tehran (Farshad et al., 2001). Number of OP pesticides is countless, so we discuss about some OP pesticides herein. Metabolism in animals is characterized by rapid elimination of phosalone and its metabolites in the urine and feces. Although in most tissues most of the residue has not been identified, the available data indicate oxidation of phosalone to its oxygen analogue, cleavage of phosalone to yield O, Odiethyl dithiophosphoric acid and of the oxon to the corresponding thiolic acid, and of both phosalone and its oxon to 2-oxo-3-mercaptomethyl-6hlorobenzoxazole (Demoras and Fournel, 1968). The transformation of phosalone in rats has been described (Demoras and Fournel, 1968; Demoras and Laurent, 1980; Smith et al., 1988). Phosalone was reported to be oxidized in the rat to its oxon and both of these converted to the putative intermediate thiol, with the phosphorus portion of phosalone forming diethyldithiophosphoric acid and that of the oxon forming diethylthiophosphoric acid. The thiol is presumably subsequently transformed sequentially into the sulphide, sulphoxide and sulphone. In one disposition study 926 mg of radioactive phosalone uniformly labelled in the aromatic ring was administered via a fistula directly into the rumen of a 530 kg lactating Holstein cow whose daily dietary ration was approximately 8.2 kg. Urine and feces samples were collected over a 100-hour period, and the cow was milked in the morning and evening each day after feeding (Craine, 1974). The total recovery of radioactive carbon from the experiment was 100.1%, with urine containing 93.7%, feces 6.1% and milk 0.3%. The lack of radioactive C02 in the urine suggested that no degradation of the benzene ring had occurred. The solubility and stability of phosalone in water at pH 5, 7 and 9 have been investigated, So the solubility of phosalone was determined by suspending 50 g phosalone in 500 mL water, stirring, heating to 50°C and cooling to 20°C or agitating 1 g/100 mL water with ultra-sound. Phosalone in dichloromethane extracts of the filtered solutions by GLC Kazemi et al. was determined. The solubility was estimated to be about 1.7 mg/kg at 20°C (Laurent and Buys, 1975). Little degradation (<10%) was observed during 28 d at pH 5.0 or 7 at 20°C. At pH 9.0 degradation was more pronounced, giving a half-life of about 9 d. Phosalone is a compound of moderate toxicity (Hayes and Laws, 1990; Hayes, 1982). The acute oral lethal dose (LD50) values ranged between 82-205 mg/kg for male rats; and between 90-170 mg/kg for female rats (EPA, 1987). The acute dermal LD50 values for rats ranged between 350 mg/kg and 390 mg/kg (EPA, 1987). The acute percutaneous LD50 for rats is 1,500 mg/kg (Worthing, 1987). Phosalone rates of 700 g/ha were not found to be hazardous to honeybees, provided they were not actively foraging at the time of spraying (Worthing, 1987). Pesticides, one of which was phosalone, applied to host eggs at field rates in the laboratory were highly toxic to Trichogramma brasiliensis released on the eggs, causing 84-100% mortality in 24 h. However, percentage parasitism after 4 d was higher with phosalone (36-73%) than with other pesticides studied, and emergence from treated host eggs did not appear to be affected. Phosalone had little or no effect on adults or cocoons of Apanteles plutellae (Elzen, 1989). Soil acts as filter, buffer and degradation potentials with respect to storage of pollutant with the help of soil organic carbon (Burauel and Bassmann, 2005). It is recognized that the soil is also a potential pathway of pesticide transport to contaminate water, air, plants, food and ultimately in the human via, runoff and subsurface drainage; interflow and leaching; and the transfer of mineral nutrients and pesticides from soils into the plants and animals that constitute the human food chain (Abrahams, 2002). Pesticides which are very persistent in soil slowly break down and result in source of contamination (Stephenson and Solomon, 1993). The sources of contamination are closely related to anthropogenic pollution, such as domestic and industrial discharges, agricultural chemical applications and soil erosion due to deforestation (Bhattacharya et al., 2003). Effects of pesticides have been reported in milk, feed, cottonseed, different fruits, vegetables and fish meal at different intervals (Hussain et al., 2002; Munshi et al., 2004; Saqib et al., 2005). Lloyd and Matthysse (1971) were unable to detect diazinon in milk of dairy cows after feeding diazinon with a protein supplement. Szerletics et al. (2000) reported low amounts (<0.025–1 mg/kg) in milk the first day after treatment of cattle and sheep with diazinon. Diazinon thus can occur in animal products after exposures, but excretion occurs quite rapidly within a few days. Health impacts by organophosphate pesticides Concerns have been raised about the increasing levels of cancer incidence and possible links with high levels of pesticide exposure. Each year 500 people are recorded 515 as dying from cancer in Golestan province (Iran), 350 from stomach and 150 from throat cancer. The main crop in this province is cotton. The investigation also revealed that the incidence of cancer among people in the belt between Ramsar and Behshahr in Mazandaran province was 70% higher than in other parts of the Caspian coast and this area suffers 30% more cancer cases than elsewhere in the Iran (IDNH, 2002). Among pesticides, OP is responsible for more than 50% of total poisoning cases (Abdollahi et al., 1997). In addition, OP has been used as harmful nerve gases (Morgan et al., 1980). Oxidative stress is another mechanism for toxicity of pesticides resulting in cell death (necrosis and apoptosis) and changes in metabolic and vital functions of the cells that leads to cancer types (Abdollahi et al., 2004). Many studies reviewed by the Ontario College show positive associations between solid tumors and pesticide exposure, including kidney cancer. Children are constantly exposed to low levels of pesticides in their food and environment, an elevated risk of kidney cancer was associated with paternal pesticide exposure through agriculture. It has also been reported that the chronic exposure to pesticides leads to kidney failure (Abdollahi et al., 2004). Pesticide metabolism Presently, there are more of 900 pesticides and more of 600 active pesticide ingredients on the market (Hall et al., 2001). Millions of ton of pesticides are applied annually; however, less than 5% of these products are estimated to reach the target organism, with the remainder being deposited on the soil and nontarget organisms, as well as moving into the atmosphere and water (Pimental and Levitan, 1986). The metabolic fate of pesticides is dependent on abiotic factors (temperature, moisture, soil pH, etc.), microbial community or plant species (or both), pesticide characteristics (hydrophilicity, pKa/b and etc.), and biological and chemical reactions (Figure 3). Abiotic degradation is due to chemical and physical transformations of the pesticide by processes such as photolysis, hydrolysis, oxidation, reduction, and rearrangements. Further, pesticides may be biologically unavailable because of compartmentalization, which occurs as result of pesticide adsorption to soil and soil colloids without altering the chemical structure of the original molecule. However, enzymatic transformation, which is mainly the result of biotic processes mediated by plants and microorganisms, is by far the major route of detoxification. Metabolism of pesticides may involve a three-phase process (Shimabukuro, 1985; Hatzios, 1991). In phase I metabolism, the initial properties of a parent compound are transformed through oxidation, reduction, or hydrolysis to produce a more water-soluble and less toxic product than the parent. The second phase involves conjugation of a pesticide or pesticide metabolite 516 Agric. Sci. Res. J. Figure 3. Schematic metabolism pesticides in body(Barr and Needham, 2002). to a sugar, amino acid, or glutathione, which increases further, the water solubility and reduces toxicity compared with the parent pesticide. Phase II metabolites have little or no phytotoxicity and may be stored in cellular organelles. The third phase involves conversion of Phase II metabolites into secondary conjugates, which are also nontoxic (Hatzios, 1991). In leafy spurge (Euphorbia esula L.), examples of Phase III metabolism are the conjugation of the N-glycoside metabolite of picloram with malonate and the formation of a gentibioside from the picloram glucose ester metabolite (Frear et al., 1989). McKellar et al. (1976) fed chlorpyrifos to dairy cattle for 2 weeks. The parent compound and two (oxidized and hydroxylated) metabolites were found at low levels in milk and cream (fat) and the concentrations of all three compounds decreased rapidly after cessation of administration. Johnson et al. (1974) obtained similar results. Hsu et al. (1995) recovered a maximum of 0.14% of intake via the eggs and depletion of residues from the body was rapid. Researcher had shown that pesticides have series deleterious effects on the rumen fluid (Cook, 1969). Cook (1957) was perhaps the first to suggest that rumen liquor played an active role in hydrolyzing OPs, particularly parathion. Additional evidence by Cook (1957) indicated that metabolism of parathion by rumen microorganisms accounted for its apparent lack of toxicity to cattle. Certain OP pesticides were shown by Williams et al. (1963) to stimulate gas production In vitro by rumen holotrich protozoa, whereas these compounds had no appreciable effect when rumen bacteria served as the inoculums source. Kutches et al. (1970) reported toxaphene were ineffectual in causing a depression of In vitro dry matter disappearance at the 100, 250, and 500 µcg per ml of culture environment(consist of rumen fluid). Mechanism of action OP pesticides avidly bind to acetyl cholinesterase (AChE) molecules and share a similar chemical structure (Figure 4). This leads to accumulation of acetylcholine and subsequent over-activation of cholinergic receptors at the neuromuscular junctions and in the autonomic and central nervous systems (Paudyal, 2008). The rate and degree of AChE inhibition differs according to the structure of the OP compounds and the nature of their metabolite. After the initial formation of AChE-OP complex, two reactions are happened: at the first reaction, Spontaneous reactivation of the enzyme may occur at a slow pace, much slower than the enzyme Kazemi et al. 517 Figure 4. Schematic inhibitory of AChE by organophosphate pesticides(Paudyal, 2008) inhibition and requiring hours to days to occur. The rate of this regenerative process solely depends on the type of OP compound: spontaneous reactivation half life that it last 0.7 h for dimethyl and 31 h for diethyl compounds. In general, AChE-dimethyl OP complex spontaneously reactivate in less than one day whereas AChE-diethyl OP complex may take several days and reinhibition of the newly activated enzyme can occur significantly in such situation. The spontaneous reactivation can be hastened by adding nucleophilic reagents like oximes, liberating more active enzymes. These agents thereby act as an antidote in OP poisoning (Eddleston et al, 2002). At the second step, with time, the AChE enzyme-OP complex loses one alkyl group making it no longer responsive to reactivating agents. This progressive time dependent process known as ageing. The rate of ageing depends on various factors like pH, temperature, and type of OP compound; dimethyls OPs have ageing half life of 3.7 h whereas it is 33 h for diethyl OP (Worek et al., 1997; Worek et al., 1999). The slower the spontaneous reactivation, the greater the quantity of inactive AChE available for ageing. Oximes, by catalyzing the regeneration of active AChE from enzyme-OP complex, reduce the quantity of inactive AChE available for ageing. Since ageing occurs more rapidly with dimethyl OPs, oximes are hypothetically useful before 12 h in such poisoning. However, in diethyl OP intoxication they may be useful for many days (Worek et al., 1997; Worek et al., 1999). Alternatives pesticides to reduce the organophosphate Several methods either independent or in conjunction have been used for the removal of these pesticides including chemical oxidation with ozone, photo degradation (Zertal et al., 2005), combined ozone and UV irradiation (Malato et al., 1999), fenton degradation (Watts, 1996), biological degradation (Chen et al., 2009), ozonation (Hua et al., 2006), membrane filtration (Hofman et al., 1997) and adsorption (Daneshvar et al., 518 Agric. Sci. Res. J. 2007). Among various cleanup technologies, the adsorption on activated carbon (AC) is one of the wellestablished and effective techniques (Hind et al., 1999). AC adsorbents are now widely employed for product purification and wastewater treatment, because of their exceptionally large surface areas, well-developed internal pore structure as well as their surface reactivity attributed to the existence of a wide spectrum of oxygen containing surface groups (Yin et al., 2007; Adhoum and Monser, 2002). Being mechanically robust and highly hydrophobic, molecules with large hydrophobic groups can be strongly adsorbed onto carbon surface. The main drawback of adsorption methods is their environmentally incomplete character because they only transfer but not degrade pollutants. In this case, the used adsorbent becomes a hazardous material demanding further treatment subsequently. Nevertheless, some interesting options based on the application of advanced oxidation methods, are under development and may constitute in the near future an efficient solution to degrade the adsorbed contaminants and regenerate the activated carbon on site and in situ (Okawa et al., 2007). Several works (Moreno Castilla, 2004; Boehm, 1994) emphasized the key role of surface chemistry in adsorption of organic solutes from aqueous phase and concluded that adsorptive properties of AC are mainly determined by its chemical composition. It is well known that adsorption behavior is influenced by surface oxygen complex content, which determines the charge of the surface, its hydrophobicity and the electronic density of the graphene layers. To increase the concentration of surface oxygen groups a wide range of oxidizing or/and acid agents such as HNO3, H2O2, HClO4, (NH4)2S2O8, O3 have been successfully applied (Santiago et al., 2005; Canizares et al., 2006). The introduction of acid surface groups was always accompanied by an important destruction of the basic sites excepting for (NH4)2SO4 and H2O2. Possibly, H2O2 was capable to introduce some recognized basic groups as quinones, chromenes or pyrones due to its rather soft oxidation strength. In contrast, surface oxides can be reduced by treatment with alkaline or reductants solutions, e.g., NH3, NaOH, NaHSO3, etc. (Przepiorski, 2006; Alcanaz-Monge and Illan-Gomez, 2008). In general, several research groups have recorded significant decrease in the adsorption of organic compounds such as dodecanoic acid, methyl isoborneol and phenol upon increasing the oxygen content of the carbon adsorbent (mainly by surface oxidation)(Pendleton et al., 1997; Terzyk, 2003). It is well known that ozone was effectively applied to drinking water treatment and wastewater treatment for its powerful oxidization potential (Wu et al., 2005). In animal especially ruminant, there are three general types of antidotes for poisons. First, a mechanical antidote is one that binds a poison in the gut and prevents absorption of the poison. Second, a chemical antidote stimulates the body such that the poison is metabolized and detoxified at a faster rate. Third, a physiologic antidote counteracts the toxic effects of the poison. An example of a mechanical antidote is the so-called "Universal Antidote" which consists of 2 parts charcoal, 1 part magnesium oxide and 1 part tannic acid. Charcoal is an adsorbent, tannic acid is a precipitant for alkaloids, and magnesium oxide is both an adsorbent and an antacid. The barbiturate phenobarbital is an example of a chemical antidote. Phenobarbital very markedly increases the rate of metabolism of drugs and poisons such as zoxazolamine and Warfarin by the liver (Burns, 1969). Examples of physiologic antidotes are atropine and phenobarbital. Atropine is an antidote for poisons such as parathion that interfere with AChE. Phenobarbital can act both as a chemical antidote and a physiologic antidote. Physiologic antidotes are routinely used in veterinary and human medicine but mechanical and chemical antidotes are not used as extensively. A comprehensive review of the literature on the use of activated carbon as an emergency antidote for treatment of ingested poisons was presented in 1963 by Holt and Peter. In this study, authors demonstrated that activated carbon is an excellent adsorbent for many poisons. Toxicological procedure The degree of absorption depends on the contact time with the skin, the lipophilicity of the agent involved and the presence of solvents, for example xylene, and emulsifiers in the formulation which can facilitate absorption. For powders, the finer the powder the more rapid and complete is skin absorption. Other important factors include volatility of the pesticide (e.g. dichlorvos is much more volatile than malathion), the permeability of clothing, the extent of coverage of the body surface and personal hygiene. The rate of absorption also varies with the skin region affected. For example, parathion is absorbed more readily through scrotal skin, maxillae and skin of the head and neck than it is through the skin of the hands and arms. It is probable that traumatized skin or the presence of dermatitis allows greater absorption of OP compounds. In one study, the mean amount of liquid parathion absorbed dermally was only 1.23% of the measured potential dermal exposure (Durham et al., 1972). Following absorption, OP compounds accumulate rapidly in fat, liver, kidneys and salivary glands. The phosphorothioates (P=S), for example diazonin, parathion, and bromophos, are more lipophilic than phosphates (P=O), for example dichlorvos, and are therefore stored extensively in fat which may account for the prolonged intoxication and clinical relapse after apparent recovery which has been observed in poisoning from these OP insecticides. OP compounds generally are lipophilic and therefore cross the blood / brain barrier in most cases (Vale, 1998). Phosphates (P=O) are biologically active as AChE inhibitors, whereas Kazemi et al. phosphorothioates (P=S) need bioactivation to their phosphate analogues (oxon) to become biologically active. As a consequence, the features of intoxication after exposure to phosphorothioates (P=S) are delayed unless aerial oxidation has occurred already to generate traces of oxon. OP compounds other than phosphates (P=O) are metabolically activated to their corresponding oxon by oxidation desulfuration mediated by cytochrome P450 isoforms, by flavincontaining mono-oxygenase enzymes, by N-oxidation and by S-oxidation. The oxons which inhibit AChE can be deactivated by hydrolases, such as the carboxylases and by A-esterases, for example paraoxonase (Vale, 1998). Elimination of metabolites occurs mostly in urine with lesser amounts in feces and expired air. Some OPs, for example dichlorvos which is not stored in fat to any great extent, may be eliminated in hours whereas the inhibitory oxon of chlorpyrifos or dementon-S-methyl may persist for days because of their extensive storage in fat (Vale, 1998). Sign and symptom of poising with OP pesticides Symptoms of acute OP poisoning develop during or after exposure, within minutes to hours, depending on the method of application. Exposure due to inhalation results in the fastest appearance of toxic symptoms, followed by the gastrointestinal route and finally the dermal route. Some of the most commonly reported early symptoms include, in possible order of occurrence: headache, nausea, dizziness, hyper secretion (swearing and salivation), muscle twitching, weakness, and tremors, in coordination, paralysis and starvation (Rickett et al., 1986; Petras, 1981). Diagnostic Strategies The diagnosis of poisoning by AChE inhibitors is confirmed by demonstrating reduced levels of AChE activity in plasma (serum) and erythrocytes. Unfortunately, many hospital laboratories do not have the in-house capability to determine cholinesterase levels. Most patients with a significant, acute exposure demonstrate sharply reduced to absent plasma cholinesterase levels within a few hours of exposure. Any patient who has a full-blown cholinergic syndrome should be treated empirically without waiting for laboratory confirmation of decreased cholinesterase activity. Known or suspected exposure to AChE inhibitors should be confirmed by ordering both plasma and erythrocyte (RBC) AChE levels. In acute exposures, the plasma AChE levels fall first, with decreases in RBC AChE levels lagging behind. Patients with chronic exposures may demonstrate only reduced RBC AChE activity, and their normal plasma AChE levels may impart a false sense of security. The true reflection of depressed AChE activity is 519 found in the RBC activity, and even a very mild acute exposure may result in severe clinical poisoning in these individuals. Red blood cell AChE levels recover at a rate of 1% per day in untreated patients and take about 6 to 12 weeks to normalize, whereas plasma cholinesterase levels may recover in 4 to 6 weeks. Other ancillary studies should be geared toward the evaluation of pulmonary, cardiovascular, and renal function, and fluid and electrolyte balance (Tafuri and Roerts, 1987; Gagandeep and Khurana, 2009; Worek et al., 2005). Treatment The initial objective should be the establishment of an airway and adequate ventilation because the patient with acute OP poisoning commonly presents with respiratory distress secondary to excessive oropharyngeal secretions, bronchospasm, respiratory muscle paralysis and, rarely, acute respiratory distress syndrome and pulmonary edema. Airway management in these cases consists of suctioning the copious oropharyngeal secretions and vomitus, if present. Endotracheal intubation and mechanical ventilation often are required. It is essential to improve tissue oxygenation as much as possible prior to administration of atropine in order to minimize the risk of ventricular fibrillation. After stabilization of the airway, IV atropine sulfate should be administered. Atropine acts as a physiologic antidote in anticholinesterase intoxication by competitively blocking the action of acetylcholine at muscarinic receptors, thus ameliorating the excessive parasympathetic stimulation caused by AChE inactivation. Repeated doses of atropine should be administered until signs of atropinization (mydriasis, tachycardia, flushing, xerostomia, anhydrosis, etc) appear (Haddad and Winchester, 1983; Namba et al., 1971). When cows become contaminated with organ phosphorus pesticides such as phosalone it is recommended that the following steps be taken: firstly check feed, water and insecticide sprays to determine the source of contamination. Then discontinue use of contaminating materials. Secondly in cases of acute pesticide poisoning cows should be drenched with 2 to 2.5 kg of activated carbon. The drench can be slurry made of 2 to 3 parts water and 1 part activated carbon. Thirdly if cows are in convulsions, the veterinarian may also treat them with intravenous injections of phenobarbital or some other barbiturate. When intravenous injections cease, phenobarbital should be fed at a rate of 10 mg per kg of body weight per day. This amounts to about 5 g (one tablespoon) daily. Treatment should be continued for 6 weeks or until milk tests show that the pesticides are below tolerance levels. Phenobarbital can be added to the grain ration. Milk should not be marketed until 7 d after phenobarbital feeding has stopped. Fourthly activated carbon should be fed at the rate of 1 kg per head daily for a 550 kg cow. 520 Agric. Sci. Res. J. The carbon can be fed successfully by mixing either with silage or grain. Also some dairy cooperatives add activated carbon to the concentrate at a level of 10% and then pellet the mixture. When both activated carbon and phenobarbital are fed, some phenobarbital may be trapped in the gut by activated carbon. It is probably best to feed phenobarbital about 2 h before feeding activated carbon. The level of Phenobarbital administered no doubt could be reduced if the drug was given by intramuscular injections (Cook, 1969). Conclusion OP pesticides have become increasingly popular for agricultural, industrial, livestock husbandry and home use and represent a significant potential health risk for human and livestock. At now and especially in the future, the ministry of agriculture of developing countries especially Iran, should concentrate on the optimization and monitoring of usage of OP pesticides and furthermore encouraging the farmers to use natural pesticides rather than chemical pesticides. Also the farmers must be aware to methods of dealing with OP pesticides in Iran for preventing from undesirables problems, for example it is possible to accelerate removal of OP pesticides from livestock feed and environment according to various methods. No doubt, more effective and less harmful pesticides in agriculture and animal husbandry sections or organic agriculture must be developed in Iran. There is considerable scope for promoting organic farming, although no certification system exists yet for organic products for local or export markets in Iran. On the basis of the author’s studies, 70-80% of current pesticide use in most crops is unnecessary, demonstrating the huge potential for pesticide reduction in Iran. With further support from the government, society, institutions and public education, farmers can make huge advances to protect human health and the environment and to improve their income. Acknowledgement The authors would like to thank Dr. Abdolmansour Tahmasbi and prof. Reza Valizadeh for their helps during the preparation of this manuscript. Reference Abdollahi M, Jalali N, Sabzevari O, Hoseini R, Ghanea T (1997). A retrospective study of poisoning in Tehran. J. Toxicol. Clin. Toxicol. 35, 387–393. 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