Organophosphates

PESTICIDES

1. ORGANOPHOSPHATES PRESENTATION BY DENNIS K MANGOMA

2. Organophosphates Organophosphorus (OP) compounds are usually esters, amides or thiol derivatives of phosphoric acid . They decompose within days to weeks after application. They break down to phosphoric acid, alcohols, and thiols. Organophosphorus compounds are metabolized quickly by animals – no bioaccumulation. They tend to be more acutely toxic than organochlorines. They form a large family (> 50 000 compounds) of chemical agents with biological properties that have important, and sometimes unique, applications for the benefit of mankind. A large group of chemicals used for protecting crops, livestock, human health and as warfare agents. They are also been used as plasticizers, stabilizers in lubricating and hydraulic oils, flame retardants, and gasoline additives.

3. some pesticides in this group are extremely toxic e.g. disulfoton and parathion, while others are relatively safe e.g. malathion. Some are rapidly degrading e.g. dichlorvos and mevinphos, while others are extremely persistent e.g. parathion, azinphos methyl. Some are systemic e.g. dimethoate, disulfoton, demeton-S-methyl, monocrotophos, and methamidophos while others are contact e.g. dichlorvos, and mevinphos. Some have a fumigant action e.g. dichlorvos. Can be foliar or soil- applied, or can be used as a seed dressing e.g. chlorpyriphos and disulfoton.

4. PRACTICAL USES OF ORGANOPHOSPHATES CROP PEST CHEMICAL Apple, pear aphid Dichlorvos, dimethoate, fenitrothion Avocados Thrips, soft brown scale Malathion Banana Aphids, thrips, red spider mites Malathion Beans, potato Aphids     Looper caterpillar Malathion, disulfoton, mevinphos, dimethoate   dichlorvos Cirtus Mealybug, Mediterranean fruit fly Malathion Maize Aphids, maize stalk borer Trichlorfon, demeton-S-methyl Tomato Heliothis bollworm aphids Mevinphos Malathion, demeton-S- methyl Onion thrips Malathion

5. Organophosphates On the basis of structural characteristics they are divided into at least 13 types : phosphates, phosphonates , phosphinates , phosphorothioates (S=), phosphonothioates (S=), phosphorothioates (S substituted), phosphonothioates (S substituted), phosphorodithioates , phosphorotrithioates , phosphoramidothioates . The first OPs were synthesised in the 19th century and used widely in the 1930s. The German chemist Gerhard Schrader synthesised many commercial OPs of which parathion is still used as a common pesticide. At the beginning of the Second World War the development of OP substances switched to highly toxic compounds employed as nerve warfare agents, e.g. sarin , soman and tabun .

6. Organophosphates X is the “leaving group,” that is displaced when the OP phosphorylates acetylcholinesterase (AChE), and is the most sensitive to hydrolysis. R1 and R2 are most commonly alkoxy groups (i.e., OCH3 or OC2H5). other chemical substitutes are also possible; either an oxygen or a sulfur are also attached to the phosphorus with a double bond.

7. There are commonly three types of organophosphates : A) B) C) tend to be the most volatile break down the fastest more stable than type A break down into type A some insects absorb type B and C better than type A generally, but not always less toxic than type A

8. Organophosphates type A highly toxic – LD 50 = 25mg/kg used in fly strips and flea collars due to its volatility type B extremely toxic – LD 50 = 3mg/kg non-specific – can easily kill birds and fish and bees may be responsible for more human deaths than any other pesticide still used in developing countries type C slightly toxic – LD 50 = 985mg/kg widely used agriculturally and domestically used to spray communities to reduce mosquitoes and other pests malathion

9. OPs as Pesticides Most widely used pesticides for insects control. First organophosphate insecticide was Tetraethylpyrophosphate (TEPP), and it was approved in Germany in 1994. It was marketed as substitute for Nicotine to control Aphids. Because of its high mammalian toxicity and rapid hydrolysis in water, TEPP was replaced by other OP insecticides. Parathion was another widely used insecticide due to its stability in aqueous solutions and its broad range of insecticidal activity. However, its high mammalian toxicity through all routes of exposure led to the development of less hazardous compounds. Malathion in particular, has low mammalian toxicity because mammals possess certain enzymes, the carboxylesterases, that readily hydrolyze the carboxyester link, detoxifying the compound.

10. Organophosphates Two examples of OP pesticides are methyl-parathion with a bonded S atom and methyl-paraoxon with a bonded O atom. . The structure of toxic OP warfare agents: (a) tabun, (b) soman, (c) sarin.

11. Organophosphates A single droplet of Sarin , if inhaled or in contact with the skin, can be absorbed into the bloodstream and paralyze the nervous system, leading to respiratory failure and immediate death.

12. MECHANISM OF TOXICITY The toxicity of OPs depends on their chemical structure, metabolism in target organism, concentration (i.e. dose), mode of application, degree of decomposition, mode of entering organisms, etc. The best described OPs toxic effects are the neurological symptoms following acute poisoning as a consequence of the primary target (AcHE). Acute organophosphorus poisoning occurs after dermal, respiratory, or oral exposure to either low volatility pesticides or high volatility nerve agents (e.g., sarin, tabun). Acetylcholinesterase inhibition by organophosphorus pesticides or organophosphate nerve agents can cause acute parasympathetic system dysfunction, muscle weakness, seizures, coma, and respiratory failure.

13. Organophosphates Residues linger on fruits and vegetables. The degree of absorption depends on the contact time with the skin, the lipophilicity of the agent involved and the presence of solvents. The rate of absorption also varies with the skin region affected. For example, parathion is absorbed more readily through scrotal skin, axillae and skin of the head and neck than it is through the skin of the hands and arms. Following absorption, OP compounds accumulate rapidly in fat, liver, kidneys and salivary glands.

14. Organophosphates Organophosphates interfere with cholinesterase activity. Cholinesterase is an enzyme that breaks down acetylcholine. Acetylcholine is an important neurotransmitter. High levels of acetylcholine cause convulsions, irregular heartbeat, and death. Organophosphates thus act as irreversible cholinesterase inhibitors because the organophosphate-cholinesterase bond is not spontaneously reversible without pharmacological intervention. Most poisoning occurs through acute exposure of people applying the insecticides.

15. Organophosphates

16. Organophosphates The inhibition of cholinesterase activity leads to the accumulation of acetylcholine at synapses, causing overstimulation and subsequent disruption of transmission in both the central and peripheral nervous systems. Chronic occupational exposure to OPs has been linked to increased risk for cancer development such as non-Hodgkin lymphoma and some types of leukaemia.

17. Organophosphates Direct immunotoxic effects of OPs can be due to: 1. inhibition of serine hydrolases (complement system) or esterases (lymphocyte and monocyte membranes) in the immune system; 2. oxidative damage of immune system organs; 3. changes in signal transduction pathways that control proliferation and immune cell differentiation.

18. Adverse and Environmental Effects   These pesticides result in acute toxic reactions. If the victim is removed from exposure, recovery is very rapid. There are usually no after effects provided renewed exposure is avoided. Very mild exposure to organophosphates causes headache, and common cold. When acute poisoning is severe, the following symptoms occur: cold sweating, salivation, nausea, bronchoconstriction, tightness of chest, decreased blood pressure and eye pupil constriction. Chronic effects of poisoning include: impaired reasoning capacity, embryo-deforming effects (teratogenic), chromosome abnormalities (mutagenic) and carcinogenic effects. Organophosphates in birds cause behavioral changes: decreased nest attentiveness and death of chicks. They are also harmful to fish.

19. Adverse and Environmental Effects OP are polar, so are not stored body fat. They are readily excreted in urine. They are fast-acting, and are effective against both larva and adults. they are non-selective. avoid applying sub lethal doses as this encourages the development of resistance.  

20. Organophosphates Organophosphates are found in pesticides and nerve gas. Due to their particularly sinister properties, many countries have banned the use of organophosphates in agriculture. Organophosphates poisonings are becoming less common for paramedics, but hold a very high level of mortality and are dangerous for all persons involved.