TOPIC SUMMARY 2PESTICIDE CHEMISTRYKimaya Rajwade Abstract: In this paper, definitions andclassification as well as history of pesticides were looked at. Detailed studyinto carbamate pesticides was done. This included method of carbamatesynthesis, mechanism of toxicity (neurotransmitter inhibition), fate ofcarbamate pesticides after being consumed, some drawbacks and benefits.
WHAT ARE PESTICIDES? According to the EPA, Pesticides are any substance or mixtureof substances meant to destroy, prevent or mitigate any pest. Pesticides canalso be defined as any substance or mixture of substances synthesized for useas plant defoliant, desiccant or regulator ( Environment Protection Agency , 2013).In a broader sense, pesticides are chemical compounds whichare meant to control pest (Environmental Protection Agency, 2007).
There are several types of pesticides available in the markettoday, with various methods of classification present to help determine whichpesticide is to be used for a particular case.Based on target organisms, pesticides can be classified intoinsecticides, herbicides, rodenticide, fungicide, bactericide, piscicide,molluscicide, nematicide, avicide, animal repellant, insect repellant,antibacterial and sanitizer (Randall, Hock, Crow, Hudak-Wise, & Kasai, 2013). On the basis of the chemical composition, pesticides can beclassified into organic and inorganic pesticides. Inorganic pesticides can befurther classified as mineral or non-mineral based pesticides. Organicpesticides are classified into natural organics and synthetic organics.
Naturalorganics can be plant based or animal based. Synthetic organics are furtherclassified into organophosphates, organochlorides and carbamates. Based on the way pesticides function, they are classifiedinto contact toxicants, systemic toxicant, fumigants and chemical repellents. The use of pesticides is not a new phenomenon. Humans havebeen using pesticides to control pests since before 2000 B. C. The first knownpesticide used was sulfur dusting, in the ancient Mesopotamia (this dates backto 4500 years ago) (Rao, Rupela, Rao, & Reddy, 2007).
In the 15th century, poisonous chemicals like lead, arsenic, mercuryetc. were applied on soil to kill insects and rodents. This trend did notchange for a long time. Until the mid-20th century, arsenic basedpesticides were predominantly used in the industry. In the 1950s, Paul Mullerdiscovered that DDT was a very effective pesticide. From this point on,organochlorides started dominating the pesticide industry, and were usedextensively in agriculture and landscape pest control (Ritter, 2009).
However, theharmful effects of DDT and such soon started coming to the forefront, afterRachel Carson’s Silent Springs waspublished. The U. S. has since banned the use of organochlorides (effectivesince 1975), with the pesticide industry making a transition toorganophosphates and carbamates. Due to the ever-growing population, a tremendous pressure onfood supply and agriculture industries has been created.
In such a scenario,pesticide use has become a necessity. There wasn’t much information availableon the consequences of use of pesticides when their use first began, but in thecurrent pesticide industry, efforts are being made to create pesticides that donot harm the ecology in the way previously used pesticides have. Despite of thenegative effects, the use pf pesticides has been profitable for the cropindustry. Every dollar spent on pesticides leads to 4 dollars saved on cropyields (Pimental, Acquay, Biltonen, Rice, & Silva, 1992). CARBAMATESCarbamates are synthetic organic pesticides used to controlpests in agricultural, landscape as well as household environments.
Carbamatesare derived from carbamic acid. The first carbamate to be used as a pesticidewas carbaryl, which was introduced in 1956. To this day, carbaryl is the mostused carbamate in the pesticide industry (Fishel, 2005). Fig:Structure of Carbaryl. Carbamates are effective on a broad spectrum of pests. Threetypes of carbamate pesticides are used in industry. Carbamate ester derivativesare used as insecticides, carbamates with aromatic groups are used as herbicidesand benzimidazoles are used as fungicides (World Health Organization , 1986)The figure above represents a general carbamate compound. TheR and R’ represent two different alkyl groups.
Carbamates are low vapor pressure compounds, which makes themhighly volatile. They are sparingly soluble in water; however, oxidationproducts of carbamates are soluble in water (World Health Organization , 1986)Temik, Fudaran and Sevin are a few commercially usedcarbamates. SYNTHESISVarious methods for the synthesis of carbamates areavailable. Listed below are few such methods. 1) Synthesis by Carbonylimidazolide. In this method, Carbonylimidazolidereacts with a nucleophile to give a carbamate. Urea and thiocarbamate are alsoreleased as byproducts. The initial reaction takes place at 0o Cwith pressure equal to 1.
2 equilibrium. This method of synthesis is economicsince it does not require an inert atmosphere. It also liberates commerciallyuseful byproducts, which can be sold for profit. The three end products of thisreaction are separated by the means of filtration (Padiya, et al., 2012).Fig: (Padiya, et al., 2012) 2) Synthesisby Hydroxamic acid Hydroxamicacids are converted to isocyanates through the Lossen rearrangement in thismethod (in the presence of Carbonyl diimidazole). The reaction takes place atroom temperature, with 3 equilibrium pressure (with a reaction time of about 4hours).
This process is quite mild and simple, with carbon dioxide andimidazole being the only by-products. This method avoids the use of anyhazardous reagents, hence proving to be a green alternative to some of the moretraditional routes for synthesising carbamates (Dubé, et al., 2009). Fig: (Dubé, et al., 2009) 3) OnePot Synthesis from Amides In this process, aliphatic oraromatic amides are converted to methyl and benzyl carbamates respectively, viathe Hofmann rearrangement. High yields are obtained in the presence ofcatalysts such as bromoacetamide and lithium hydroxide/methoxide. It is anefficient, one pot process.
In the presence of Lithium methoxide, reactiontakes place at room temperature for 24-48 hours. In the presence of Lithiumhydroxide, reaction takes place at high pressure (2-9 equilibrium) for ashorter duration of time (Jevti?, Došen-Mi?ovi?, Ivanovi?, & Ivanovi?, 2016). Fig: (Jevti?, Došen-Mi?ovi?, Ivanovi?, & Ivanovi?, 2016) MODE OF ACTIONCarbamates are effective aspesticides due to their ability to inhibit the acetylcholinesterase enzyme(AChE) in the nervous system. AChE acts a catalyst to the hydrolysis of theneurotransmitter acetylcholine (ACh) to choline and acetic acid. (ACh is asynaptic mediator that plays a part in the transmission of nerve impulses ininsects and mammals) (World Health Organization , 1986)”Like organophosphates, carbamatescan inhibit esterases which have serine in their enzymatic centers (known asserine esterases or beta esterases).
This has also been linked to the toxicpotential of carbamates” (World Health Organization , 1986)When a muscle is innervated, a nerveimpulse travels down a neuron to reach nerve endings. ACh is a muscle stimulatingchemical present on the tips of nerve endings which are connected to muscles. Whenthe compound is in this state, muscles contract. When a nerve impulse isregistered by the nerve endings, AChE hydrolyses ACh, which in turn causesmuscles to relax (World Health Organization , 1986)Carbamates inhibit this hydrolysisreaction which means that the muscles are in a stimulated state at all times.This leads to muscle exhaustion and damage. (World Health Organization , 1986).
This inhibition mechanism is lethalto insects and smaller mammals like rodents, but not to greater mammals andhuman beings (the effect of exposure for humans wears off in four hours). Fig: (World Health Organization , 1986) The reaction mechanism of inhibition is given below:Fig : (World Health Organization , 1986) As demonstrated in the figure, the carbamate compound reactswith the enzyme to form a carbamate-enzyme complex. This complex is thenhydrolyzed instead of the acetylcholine compound on the nerve endings, thusinhibiting the muscle relaxation process. FATE OF CARBAMATE PESTICIDES: After being consumed by organisms,carbamates are metabolically biotransformed. The transformation reactions takeplace with the help of enzymes naturally present in animal tissues. Carbamateesters are converted into water soluble compounds with increased polarproperties. The compounds thus formed are excreted via urine and feces.
Theexcreted compounds are usually non-toxic (World Health Organization , 1986).The main method of metabolism ofinsecticidal carbamate esters is through oxidation and is generally associatedwith the mixed-function oxidase (MFO) enzymes, which exist in many tissues.There are various sites on carbamate molecules which lend themselves tooxidation (World Health Organization , 1986).
“Typical oxidative reactions include:(a) hydroxylation of aromatic rings, or epoxidation; (b) O -dealkylation; (c) N-methyl hydroxylation; (d) N -dealkylation; (e) hydroxylation and subsequentoxidation of aliphatic side chains; and (f) thioether oxidation to sulfoxidesand sulfones” (World Health Organization , 1986) Shown in the figure are various siteson a carbamate molecule where oxidation could hypothetically take place. DRAWBACKS OF CARBAMATES. Carbamate compounds, though effectiveas pesticides, do have their own set of drawbacks. Low dosage exposure tocarbamates causes skin irritation, skin sensitization and eye irritation. Itcan also cause headache, nausea and vomiting if exposure dose is high (itshould be noted that, though these symptoms occur, the effect of the pesticidewears off within a matter of a few hours) (World Health Organization , 1986). Studies done on male and female rats showedthat oral exposure to carbaryls lead to decrease in fertility in male rats and embryonicdeaths in female rats.
Exposure to carbaryls also lead to endocrinal systemdefects in tested rats (World Health Organization , 1986).Certain types of commerciallyavailable carbamates (Benomyl, Carbendazim) were found to be potentiallycarcinogenic since their structures are like those of known carcinogens (World Health Organization , 1986).Some carbamate oxidation products(5-hydroxycarbyl, 5-hydroxypropoxur) are known to be toxic, and to exhibit AChreaction inhibiting properties. This increases the toxic potential of thepesticide group (World Health Organization , 1986).
WHY CARBAMATES? Rachel Carson brought to light thevery real threat the environment was faced with due to overuse oforganochloride pesticides, especially DDT. Since then, scientists haveconducted numerous studies to find efficient pesticides which do not take atoll on the environment. Carbamates have proven to fulfill these criteria. Carbamates are not as ecologicallyintrusive as organophosphates and organochlorides. Since 1975, mostorganophosphates and organochlorides are banned in the U.
S., which promoted theuse of carbamate pesticides (McDaniel College, 1998)Carbamate pesticides are morebiodegradable than other classes of pesticides available, which means they canget easily biotransformed into non-threatening compounds in the soil, hence notleaving any toxic residue (in most cases) (McDaniel College, 1998).Even when carbamates are consumed byliving beings (animals and humans), the compounds do not penetrate the centralnervous system. Any damage that is caused by the chemicals is treatable andshort-lived. Hence, carbamates are benign compared to other pesticides (McDaniel College, 1998).