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- 1. JIMMA UNIVERSITY INSTITUTE OFHEALTH SCIENCE SCHOOL OF MEDICAL LABOTATORY SCIENCE Toxicology and Therapeutic Drug Monitoring Course Assignment On Toxic Effect of Pesticides By: Hindiya Abdurahman and :Reshad Nuredin
- 2. Out line ofpresentation Objectives Introduction Toxicological classification of pesticides Insecticides Herbicides Rodenticides Fungicides Summary References
- 3. Objectives At the endsof this presentation students should be able to; Define pesticides and its application Discuss toxicological classification of pesticides Explain mechanism of toxicity of different classes of pesticides Discuss different types of bio pesticides List toxicity level of pesticides
- 4. Introduction • A pesticideis a substance or mixture of substances intended for preventing, destroying, repelling, or lessening the damage of any pest. • The Chinese used arsenic to control insects, the early Romans used common salt to control weeds and sulfur to control insects. • In the 1800s, pyrethrin was found to have insecticidal properties. • The roots of certain Derris species were used by the Chinese and by South American natives as a fish poison.
- 5. Cont… • However, itwas not until the 1900s that the compounds we identify today as having pesticidal properties came into being. • Petroleum oils, distilled from crude mineral oils, were introduced in the 1920s to control scale insects and red spider mites. • The 1940s saw the introduction of the chlorinated hydrocarbon insecticides such as DDT and the phenoxy acid herbicides such as 2,4 - D). • Triazine herbicides, such as atrazine, introduced in the late 1950s, dominated the world herbicide market for years.
- 6. Cont… • Synthetic pyrethrinsor pyrethroid insecticides (e.g., resmethrin) became and continue to be widely used insecticides due to their low toxicity, enhanced persistence compared to the pyrethrins, and low application rates.
- 7. TOXICOLOGICAL CLASSIFICATION OFPESTICIDES • Pesticide is a common term that characterizes several classes of insecticides, herbicides, fungicides, rodenticides, wood preservatives, garden chemicals and household disinfectants that are used to either to kill or protect from pests. • These pesticides differ in their physical, chemical and identical properties from one class to other. • Therefore, it is worthy to classify them based their properties and study under their respective groups. • They are categorized into various classes depending on the needs.
- 8. Cont… • Presently, thereare three most popular method of pesticides classification suggested by Drum. • These three popular methods of pesticides classes comprises: (i) classification based on the mode of entry (ii) classification based on pesticide function and the pest organism they kill (iii) classification based on the chemical composition of the pesticide.
- 9. Classification Based onMode of Entry Systemic pesticides • Systemic pesticides are pesticides which are absorbed by plants or animals and transfer to untreated tissues. • Systemic herbicide moves through the plant and can reach to untreated areas of leaves, stems or roots. • They can effectively penetrate in the plant tissues and move through plant vascular system to kill specific pests. • Examples of systemic pesticides include 2,4- Dichlorophenoxyacetic acid (2, 4-D) and glyphosate.
- 10. Cont… Non-systemic (Contact) pesticides •The non-systemic pesticides are also called contact pesticides as it acts on target pests when they come in contact. • Pesticides must come into physical contact with the pest to be effective. • These pesticides do not necessarily penetrate the plant tissues and consequently not transported through the plant vascular system. • Examples of contact pesticides are paraquat and diquat dibromide.
- 11. Cont… Stomach poisoning andstomach toxicants • Stomach poisoning pesticide enters the pest’s body through their mouth and digestive system and causes death by poisoning. • Stomach poisons are acquired during feeding of pests, when they ingest the insecticide applied in the leaves and other parts of the plant. • These insecticides kill the vector by destroying the midgut (or stomach) of the larvae • Example: Malathion.
- 12. Cont… Fumigants • Fumigants aresuch pesticides which acts or may kill the target pests by producing vapor. • These pesticides form poisonous gases when applied. • These pesticides in vapor form enter the body of pests via their tracheal system (respiratory) through spiracles and causes death by poisoning. • Fumigants are used to remove stored product pests from fruits, vegetables and grains.
- 13. Classification Based onPesticide Function and Pest Organism They Kill • pesticides are classified based on target pest’s organism and pesticides are given specific names to reflect their activity. • The group names of these pesticides arise from the Latin word cide (meaning kill or killer) that are used as suffix after corresponding name of pests they kill. • Not necessarily, all pesticides end with word-cide.
- 14. Table: Pesticide classificationby target pests Type of pests Target pests/Function Example Insecticides Kill insects and other arthropods Aldicarb Fungicides Kill fungi (including blights, mildews, molds, and rusts) Azoxystrobin Bactericides Kill bacteria or acts against bacteria Copper complexes Herbicides Kill weeds Atrazine Rodenticides Control mice and other rodents Warfarin Acaricides Kill mites Bifenazate Repellents Repel pests by its taste or smell Methiocarb Molluscicides Inhibit or kill mollusc’s i.e. snail’s usually disturbing growth of plants or crops Metaldehyde
- 15. Insecticides • Insecticides playa most relevant role in the control of insect pests. • Most of the chemical insecticides in use today are neurotoxicants, and act by poisoning the nervous systems of the target organisms. • Thus, insecticides are mostly not species-selective with regard to targets of toxicity, and mammals, including humans, are highly sensitive to their toxicity. • As a class, insecticides have higher acute toxicity toward nontarget species compared to other pesticides.
- 16. Fig. : Classificationof insecticides
- 17. Cont… Organochlorine • Organochlorines pesticides(also known as chlorinated hydrocarbons) are organic compounds attached with five or more chlorine atoms. • Most of them were widely used as insecticides for the control of a wide range of insects. • Most common examples of these pesticides includes: DDT, lindane, endosulfan, Aldrin, diel Drin and chlordane.
- 18. Cont… Mechanisms of Action •Organochlorine compound chemicals act on the nervous system to produce adverse effects. • This class of chemicals is thought to act by the interference with cation exchange across the nerve cell membranes resulting in hyperactivity of the nerves. • Benzene hexachloride compounds (BHCs) (lindane and related compounds) are examples of isomers that produce different effects on the nervous system. • he γ isomer, also referred to as lindane, causes severe convulsions with rapid onset,
- 19. Cont… Health Effects ofOrganochlorine Insecticides • The principal adverse effect associated with over-exposure to organochlorine insecticides is nervous system hyperactivity. • Early symptoms seen in chlorinated insecticide intoxications, such as with DDT, include • hyperesthesia’s and paresthesias of the face and limbs • Dizziness • nausea and vomiting • tremor, and mental disturbances • Myoclonic movement and convulsions are sometimes seen in severe cases of poisoning.
- 20. Cont… Organophosphates • Organophosphate pesticidesare considered to be one of the broad spectrum pesticides which control wide range of pests due to their multiple functions. • Organophosphorus insecticides are more toxic to vertebrates and invertebrates as cholinesterase inhibitors leading to a permanent overlay of acetylcholine neurotransmitter across a synapse. • These pesticides are also biodegradable, cause minimum environmental pollution and are slow pest resistance. • Some of the widely used organophosphorus insecticides include parathion, malathion and diaznon.
- 21. Cont… Signs and Symptomsof Toxicity and Mechanism of Action OP • The primary target for OPs is AChE. • Inhibition of AChE by OPs causes accumulation of acetylcholine at cholinergic synapses, with overstimulation of cholinergic receptors of the muscarinic and nicotinic type. • As these receptors are localized in most organs of the body, a “cholinergic syndrome” ensues, which includes • increased sweating and salivation, profound bronchial secretion, bronchoconstriction, miosis, increased gastrointestinal motility, diarrhea, tremors, muscular twitching, and various central nervous system effects.
- 22. Cont… Treatment of Poisoning •Upon OP poisoning, prompt treatment is essential. • In case of dermal exposure, contaminated clothing should be removed, and the skin washed with alkaline soap. • Atropine represents the cornerstone of the treatment for OP poisoning. • Oximes, such as pralidoxime (2-PAM) are also used in the therapy of OP poisoning.
- 23. Cont… Carbamates • Structurally, Carbamatesare similar to organophosphates. • However, they differ in their origin. Organophosphates are derivatives of phosphoric acid, while carbamates derived from carbamic acid. • The mechanism of toxicity of carbamates is analogous to that of OPs, in that they inhibit AChE. • However, inhibition is transient and rapidly reversible, because there is rapid reactivation of the carbamylated enzyme in the presence of water.
- 24. Cont… • The signand symptoms of carbamate poisoning are the same as observed following intoxication with OPs, and include • miosis, • urination, • diarrhea, • salivation, • muscle fasciculation, and CNS effects. • However, differently from OPs, acute intoxication by carbamates is generally resolved within a few hours. • Some of the widely used insecticides under this group include carbaryl, carbofuran, propoxur and aminocarb.
- 25. Herbicides • Herbicides controlweeds and are the most widely used class of pesticides. • This class of pesticide can be applied to crops using many strategies to eliminate or reduce weed populations. • These include: • preplant incorporation • preemergent applications and • post emergent applications.
- 26. Cont… Chlorophenoxy • 2,4-dichlorophenoxy aceticacid (2,4-D) and 2,4,5- trichlorophenoxy acetic acid (2,4,5-T) are the most commonly recognized Chlorophenoxy herbicides. • Some of the commonly used chlorophenoxy herbicides include Banvel (dicamba), Weedone (2,4-D), and Basagran M (MCPA). Figure: 2,4-Dichlorophenoxyacetic acid (2,4-D).
- 27. Cont… • The primaryroutes of exposure to chlorophenoxy herbicides are dermal and inhalation. • Chlorophenoxy compounds act by uncoupling oxidative phosphorylation and decreasing oxygen consumption in tissue. • Large intentional overdoses with chlorophenoxy acids have resulted in symptoms of coma, metabolic acidosis, myotonia, mucous membrane irritation, and myalgias
- 28. Cont… Bipyridyl Compounds-Paraquat andDiquat Paraquat (1,1′-dimethyl-4,4′-dipyridylium) and diquat (1,1′- ethylene-2,2′- bipyridylium) are bipyridylium herbicides. Paraquat poisoning can lead to multiorgan toxicity. Sufficient dermal exposure to paraquat can also cause dermal irritation, blistering, and ulceration. Its proposed mechanism of action leading to pulmonary fibrosis is that by which free radicals are generated leading to lipid peroxidation.
- 29. Cont… • Diquat causesless dermal irritation and injury than does paraquat. • diquat has an effect on the central nervous system, whereas paraquat does not. • The mechanism of action of diquat is thought to be similar to that of paraquat, involving the production of superoxide radicals that cause lipid membrane destruction.
- 30. Cont… Glyphosate • Glyphosate isa widely used herbicide that interferes with amino acid metabolism in plants. • In animals it is thought to act as a weak uncoupler of oxidative phosphorylation. • Glyphosate is moderately absorbed through the gastrointestinal tract. • Various signs and symptoms include gastro-intestinal irritation and damage, as well as dysfunction in several organ systems (e.g., lung, liver, kidney, CNS, and cardiovascular system).
- 31. FUNGICIDES Pentachlorophenol • Pentachlorophenol isreadily absorbed via the skin, lung, and gastrointestinal tract. • Pentachlorophenol and its biotransformation products are excreted primarily via the kidneys. • The biochemical mechanism of action of pentachlorophenol is through an increase in oxidative metabolism from the uncoupling of oxidative phosphorylation. • In fatal cases of poisoning from pentachlorophenol, body temperatures as high as (almost) 41.8 °C (107.4 °F) have been reported.
- 32. Cont… Dithiocarbamates • Dithiocarbamates area group of fungicides that have been widely used since the 1940s to control about 400 fungal pathogens in a variety of crops. • The dithiocarbamates have low acute toxicity by the oral, dermal, and respiratory route. • These compounds are metabolized to a common metabolite, ethylenethiourea (ETU), which is responsible for the effects of dithiocarbamates on the thyroid.
- 33. Cont… • ETU producedthyroid tumors in rats and mice. • That result from the inhibition of the synthesis of the thyroid hormones thyroxine (T4) and triiodothyronine (T3) . • This leads to elevated serum levels of thyroid stimulating hormone (TSH). • There is also some evidence that dithiocarbamates may cause neurotoxicity by mechanisms not involving ETU.
- 34. RODENTICIDES Anticoagulants This classof rodenticides works by depression of the vitamin K synthesis of the blood clotting factors II (prothrombin), VII, IX, and X. Warfarin is a commonly used coumarin rodenticide that causes its toxic effects by inhibiting the formation of prothrombin and the inhibition of vitamin K–dependent factors in the body. Other anticoagulant rodenticides include coumafuryl, brodifacoum, difenacoum, and prolin.
- 35. Cont… Signs and symptomsof intoxication with warfarin include: • epistaxis, • hemoptysis • bleeding gums • gastrointestinal tract and • genitourinary tract hemorrhage
- 36. Cont… Sodium Fluoroacetate • Thiscompound is easily absorbed via ingestion as well as through inhalation and dermal routes. • The toxicity of sodium fluoroacetate is due to the reaction of three molecules of fluoroacetate which form fluorocitrate in the liver. • Fluorocitrate adversely affects cellular respiration through disruption of the tricarboxylic acid cycle (inhibiting the enzyme cis-aconitase). • It is thought that the accumulation of citrate in tissues also accounts for some of the acute toxicity associated with this compound
- 37. Cont… • The targetorgans of sodium fluoroacetate are the heart (seen as arrhythmias leading to ventricular fibrillation) and the brain (manifested as convulsions and spasms) • A specific antidote to sodium fluoroacetate intoxication does not exist. • Treatment consists of decontamination and supportive therapy, including gastric lavage and catharsis.
- 38. Classification based onsources of origin • Pesticide is a chemical or biological substance that aims to destroy the pests or prevent the damage caused by pests. • Based on sources of origin, pesticide may be classified into chemical pesticide and bio-pesticides. • The main benefits of using biological pesticides are host specificity. • Whereas chemical pesticides are usually of wide range which affects large group of non-target organisms.
- 39. Cont… Bio-pesticides • Bio-pesticides groupof pesticides derived from natural materials such as animal, plant and microorganism (bacteria, viruses, fungi, and nematodes). They are classified into three groups. • Microbial pesticides • Plant incorporated protectants • Biochemical pesticides
- 40. Cont… Microbial pesticides • Theactive ingredient in microbial pesticides is microorganism such as bacterium, fungus or protozoan. • These pesticides kill insects either by toxins released by microbial organisms, or by infection by the organisms. • Two most common pesticides that fit within this group include: • The bacterial toxin produced by Bacillus thuringiensis (Bti) • the live bacteria, Bacillus sphaericus (Bs).
- 41. Cont… Plant incorporated protectants •These groups of pesticides are produced by plants naturally. • the gene necessary for production of pesticide is introduced into the plant through genetic engineering. • Hence, the pesticide then produced by such plant and the genetic material introduced are together defined as plant incorporated protectants (PIPs).
- 42. Cont… Biochemical pesticides • Biochemicalpesticides which include natural materials that have nontoxic mechanisms to control pests. • Examples of Biochemical pesticides are insect sex pheromones (act by interfering in mating), a range of aromatic plant extracts (work by attracting insect pests into traps).
- 43. Based on toxicityof pesticides • Depending on the health risk associated with pesticides and toxic behavior of pesticides. • The World Health Organization (WHO) classified them into four categories. • WHO conducted an experiment on rats and other laboratory animals by administering a dose of pesticide orally and dermally? They then estimated the median lethal dose (LD50) that produces death in 50% of exposed animals to reach this conclusion.
- 44. Table: WHO classificationsof pesticides based on toxicity WHO class Toxicity level LD50 for the rat (mg/kg body weight) Examples Oral Dermal Class Ia Extremely hazardous <5 <50 Parathion, Dieldrin Class Ib Highly hazardous 5–50 50–200 Eldrin, Dichlorvos Class II Moderately hazardous 50–2000 200–2000 DDT, Chlordane Class III Slightly hazardous >2000 >2000 Malathion Class IV Unlikely to present acute hazard in normal use >5000 Carbetamide, Cycloprothrin
- 45. SUMMARY • Several groupsof pesticides have been classified based on numerous criteria. • Most popular basis of pesticides classification are the nature of target pests kill and, • chemical composition and characteristics of pesticides, mode of entry and mode of action or the way a pesticide destroys or controls the target pest. • Pesticides with similar structures have similar characteristics and usually have a similar mode of action. • Most pesticide active ingredients are either inorganic or organic pesticides
- 46. Cont… • Pesticides havealso been classified according to how or when they work. • It is seen that the in appropriate application of pesticide may adversely affect all levels of biological organization and every component of the environment. • The effects can be global or local, temporary or permanent, or short-lived (acute) or long-term (chronic). • The most serious effects involve destruction of non-target pest organism
- 47. References 1. Ernest H.Modern Toxicology. Fourth edition, John Wiley & Sons, Inc.,2010:55-66. 2. Casarett and Doull´s Toxicology, The basic science of poisons, seventh edition. McGraw-Hill,2008:883-922. 3.William PL., James Rc., Roberts Sm. Principles of Toxicology, Environmental and Industrial Applications, Second edition. John Wiley & Sons, Inc.,2000:345-363. 4.Yadav, I.C., Devi, N.L. Pesticides Classification and Its Impact on Human and Environment. Environmental Science and Engineering.2017,6(2):140-158. 5.Giliomee, J.H. Pesticides: Environmental Management in South Africa,2014:746-764