PESTICIDES AND HERBICIDES.

Food Additives.

Airborne and Solvent borne toxins.

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What are pesticides ?

• substance or group of substances intended for destroying, preventing or controlling pests.

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What are pests?

• Unwanted organisms, interferes with food production, human health, and peace and quietness of environment and causes economic harm.
• Pests include bacteria, fungi, insects, weeds, rodents etc.

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• By their nature, Pesticides create some risk of harm to humans, animals or the environment.

Ideal Pesticide

• Kills target pests
• Non-persistent, short lived.
• No adverse effects on other organisms.
• No genetic resistance
• Less costly than economic losses.

Types of pesticides

• Rodenticides
• Bactericides
• Fungicides
• Herbicides
• Insecticides

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Pesticide ingredients

Active ingredients

• An active ingredient is one that prevents, destroys, repels or mitigates pest.
• By law, the active ingredient must be identified by name on the label together with its percentage by weight.

Inert ingredients

• An inert ingredient is simply any ingredient in the product that is not intended to affect a target pest.e.g Isopropyl alcohol.
• The law does not require inert ingredients to be identified by name and percentage on the label, but the total percentage of such ingredients must be declared.

Chemistry and mode of action of insecticides

• Compounds affecting voltage-dependent sodium channels
• Pyrethroids
• The pyrethroids insecticides are typically esters of chrysanthemic acid having a high degree of lipophilicity (fat solubility).
• Type 1
• Pyrethrins
• Alletrin
• Tetrametrin
• Permetrin
• Tefluthrin
• Type 11
• Fenvalerate
• Fluvalinate

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Typical signs of intoxication by pyrethroids

• Hyperexcitability
• Convulsions
• Whole body tremor
• Ataxia
• Incoordination
• Choreoathetosis (sinuous writhing)
• Salivation
• Paraesthesia
• Tingling or burning sensation.

Mechanism of action

• Intoxication results from their potent effects on nerve impulse generation within both the central and peripheral nervous system.
• The nerve impulse or action potential consists of a transient depolarization (positive wave) whose upstroke is driven by an influx of sodium ions, followed by a down stroke from the efflux of potassium ions.

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• Compounds affecting the neuro-muscular function.

Veratrum alkaloids

• Veratridine
• Cevadine

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Mechanism of action

• Ditto

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• Acetylcholine mimics
• Nicotine
• Imidacloprid

Mechanism of action

• Nicotine and Imidacloprid mimic the action of acetylcholine.

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• After acetylcholine is released by the presynaptic cells, it binds to the postsynaptic nicotinic acetylcholine receptor and activates an intrinsic cation channel.

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• This results in a depolarization of the postsynaptic cell due an influx of sodium and calcium ions.

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• The synaptic action of Ach is terminated by the enzyme acetylcholinesterase which rapidly hydrolyzes the ester linkage in acetylcholine.

• Nicotine and Imidacloprid also activate the nicotinic acetylcholine receptor, but do so persistently since they are insensitive to the action of acetylcholinesterase.

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• This persistent activation leads to an overstimulation of cholinergic synapses and results in hyperexcitation, convulsions, paralysis and death of the insect or mammal.

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• Compounds/pesticides as acetylcholinesterase inhibitors.
• The organophosphorus pesticides (OPs )
• Phosphates
• Phosphonates
• Phosphorothionates
• Phosphorodithioates.
• Phosphoramidothioates
• Acephate. Azinophos-ethyl. Bromophos. Coumaphos. Dichlorvos.

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Mechanism of action

• The primary target site for the OPs is the enzyme acetylcholinesterase.

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• The OPs react with a serine hydroxyl group within the enzyme active site, phosphorylating this hydroxyl group and yielding a hydroxylated “ leaving group”.

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• This process inactivates the enzyme and also blocks the degradation of the neurotransmitter acetylcholine.

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• The synaptic concentrations of Ach then build up and hyperexcitation of the CNS occurs.

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Signs of intoxication

• Restlessness
• Hyperexcitability
• Tremor
• Convulsions
• Paralysis

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Management of OPs poisoning

• Atropine
• Midazolam or diazepam
• Glycopyrollate
• This is a quaternary ammonium antimuscarinic agent with peripheral effects similar to atropine.
• Pralidoxime (PAM, 2- pyridine aldoxime methylchloride )
• This is cholinesterase reactivator which reverses the nicotinic effects as well as some of the central nervous system effects of OPs poisoning.
• WHO advices the use of 30mg/kg within 15mins and a maintenance dose of 10mg/kg for 7days.
• Obidoxime

FOOD ADDITIVES

Definition

• Food additives fall into two broad categories :
• Those that prevent food spoilage (e.g. Preservatives)
• Those added to enhance the appearance, flavor or texture of food.

Preservatives

• Many chemicals have been used in the preservation of food for many years.
• Techniques include :
• Salting of meat, fish and vegetables
• Curing of bacon and ham
• Smoking of meat and fish and vegetables
• Making jellies, Jams and prickles etc

• These are traditional chemical preservatives including smoke,salt,sugars ,vinegars and spices.

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• Sulphur dioxide is the commonest preservative in use and owes its action to yielding sulphorus acid in solution.

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• Thiamine is rapidly destroyed by sulphites and pork sauges which contain sulphites as preservative contain much less thiamine than the original pork.

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• Sulphites promote the retention of vitamin C, their presence in fruit juice and pulp is advantageous, apart from their preservative qualities.
• All preservatives mentioned above prevent food spoilage caused by microorganisms and do so by destroying or preventing the growth of microorganisms and in some cases reducing attacks.

• Food spoilage may also be brought about by chemical action as when fats and foods containing fats go rancid.
• Rancidity is due to the oxidation of the fats and the addition of antioxidants would prevent oxidative changes.

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Additives for enhancing Appearance, Flavor and Texture

• The appearance, taste and smell of a food (the organoleptic quality) rather than its nutritive value, determine the appeal of food.
• The appearance and smell stimulate the flow of digestive juices and so aid digestion.
• Flavoring agents e.g. dried herbs
• Flavor enhancers e.g. Monosodium Glutamate (MSG …. Aji no moto)
• Allergy to MSG
• MSG has the tendency to make one thirsty.

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• Ribonucleotides have been isolated from microorganisms and are added to processed meat and fish products.
• Only small quantities are required as their flavor enhancing property is very great, about 10 times that of MSG.

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Sweetening Agents

• Sugar
• Obesity, dental decay, coronary disease, high energy value.
• Saccharin
• Low energy value, artificial sweetener
• 300 -500x sweeter than sucrose with an unpleasant bitter after taste.
• Cyclamates
• 1/10^th as sweet as saccharin
• Sorbitol
• Made from glucose.
• Slowly absorbed, so used in diabetic foods with caution.

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Emulsifying agents and Stabilizers

• Eggs, Starches ( natural emulsifiers)
• GMS ( Glyceryl monostearate)
• Used in margarine, ice cream etc to maintain a smoother and softer texture.
• To delay staling process in bread making.

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Anti caking substance, Humectants

• These absorb moisture and so reduce the effect of humidity and inert gas (nitrogen) used in packaging to minimize oxidation.

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Food enrichment

• Foods may be fortified or enriched using some nutrients.
• Niacin, thiamine, iron, calcium.
• Vitamin A and D (margarine)
• Vitamins in baby foods etc.

ANTIDOTES

• Atropine -------------- Neostigmine, physiostigmine
• Benzodiazepine ----- Flumazenil
• Cupper -------------- Penicillamine
• Cyanide -------------- Sodium thiosulphate
• Heparin -------------- Protamine sulphate
• Mercury --------------- Dimercapol
• Methanol -------------- Ethanol
• Mushroom ------------- Atropine
• Organophosphates --- Atropine,pralidoxime
• Oral anticoagulants --- Vitamin K.
• Paracetamol ----------- N- acetyl cysteine

Mechanism of methanol toxicity.

• The discovery of methanol’s metabolic pathway has led to the proper mgt of methanol poisoning.
• Methanol is oxidized by alcohol dehydrogenase to formaldehyde and the formaldehyde is oxidized by formaldehyde dehydrogenase to formic acid.

How does methanol poisoning occur?

• Accidental ingestion
• Suicide attempt
• Extensive skin exposure
• Breathing in fumes

Symptoms of methanol poisoning

• Drowsiness
• Reduced level of consciousness (cns depression)
• Blindness
• Inability to coordinate muscle movement
• Metabolic acidosis which is manifested by low serum bicarbonate level.
• The anion gap is increased secondary to high lactate and ketone levels
• This is due to formic acid accumulation.

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Why is ethanol given for methanol poisoning?

• Ethanol is a preferred substrate for alcohol dehydrogenase
• Fomepizole is an inhibitor of alcohol dehydrogenase.
• Bicarbonate to neutralize formic acid
• Hemodialysis to get alcohol out of the blood.
• Folate and Thiamine.

Note

• Methanol and ethylene glycol is associated with an acute inebriation followed by an asymptomatic period lasting 24 to 36hrs.
• Abdominal pain caused by pancreatitis,seizures,blindness and coma may develop.

How does acetaminophen cause toxicity in overdose .

Mechanism of acetaminophen toxicity.

• In cases of pcm overdose, the sulphate and the glucuronide pathways become saturated and more pcm is shunted to the cytochrome P450 system to produce NAPBQI…….. N-acetyl-p-benzoquinonimine.
• As a result, hepatocellular supplies of glutathione become depleted as the demand for glutathione is higher than its generation.
• This overwhelms the way the liver functions.

What is MOA of N-acetyl-cysteine?(Antidote).

• NAC is a precursor of glutathione.
• NAC increases the concentration of glutathione available for the conjugation of NAPBQI.
• NAC also enhances sulphate conjugation of unmetabolized pcm, functions as an anti-inflammatory and antioxidant and has positive inotropic effects.

Cyanide toxicity

• Inhalation of fire smoke
• Ingestion of some vitamin supplements e.g vit B17 (amygdalin)HCN
• Food e.g cassava root.

Symptoms of toxicity

• Hypothermia
• Tachycardia
• Fixed dilated pupils
• Spontaneous breathing
• Diabetes
• Elevated plasma lactate

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• Altered level of consciousness
• Hypotension

Antidotes (cyanokit)

• Hydroxocobalamin
• Sodium thiosulfate

MOA OF ANTIDOTES

• Sodium thiosulfate is considered an ineffective antidote for acute cyanide toxicity……. Why?
• Because it has poor intracellular penetration
• Slow onset of effect
• A short half life
• Limited volume of distribution

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• it is used in conjunction with other rapid acting antidotes.
• Sodium thiosulfate acts as a sulfur donor to detoxify cyanide by forming a thiocyanate by the enzyme rhodanese.
• Hydroxocobalamin has a rapid onset of action and has immediate diffusion into the different tissue compartments when administered intravenously.
• Hydroxocobalamin binds cyanide and forms the non-toxic cyanocobalamin, which is renally excreted.
• Therefore there is synergistic action of sodium thiosulfate and hydroxocobolamin.

NOTE

• Hydroxocobalamin and sodium thiosulfate can be combined safely.
• The only limitation is that sodium thiosulfate and hydroxocobalamin may not be mixed in the same vial because this induces the formation of inefficient thiosulfactocobolamin.