Agricultural Chemicals & Pesticides

Introduction

• Agricultural chemicals (pesticides) are used in crop protection, insect pest control, and food preservation.
• Massive and uncontrolled use of agricultural chemicals can lead to acute or chronic poisoning in humans, domestic animals, and wildlife, resulting in widespread ecological adverse effects.

Pesticides

• Herbicides and insecticides (organophosphates and carbamates) are used worldwide in agriculture, industry, homes, and gardens.
• Small animals can be poisoned by these insecticides through malicious activity or accidental exposure.
• Livestock can ingest insecticides in freshly sprayed crops or contaminated feed.
• Rodenticides (warfarin) and fumigants (aluminum phosphide) are common causes of malicious/suicide poisonings due to their easy availability.

Classes of Pesticides

• Insecticides, fumigants, herbicides, rodenticides, nematicides, acaricides, algicides, bird repellents, and mammal repellents are all classes of pesticides
• Insecticides include:
  • Organochlorine (OC)
  • Organophosphorus (OP)
  • Carbamate (CM)
  • Pyrethrins and pyrethroids
  • Formamidines, nicotinoids
  • Natural products (rotenone and nicotine)
• Fumigants include:
  • Inorganic (aluminum phosphide, hydrogen cyanide, carbon disulfide, sulfur dioxide)
  • Organic (methyl bromide, ethylene dibromide, dibromochloropropane)
• Fungicides include:
  • Inorganic (sulfur, metals)
  • Organic (organomercurial, chlorophenols, phthalimides, etc.)
• Herbicides include:
  • Inorganic (arsenicals, chlorates)
  • Organic (chlorophenoxy and its derivatives, dinitrophenols, bipyridyls, ureas)
• A Rodenticide is warfarin

Toxicity of Insecticides

• Insecticides are substances intended to prevent, destroy, repel, or mitigate insects.
• These chemicals pose health risks to non-target species.
• Each exposure, even small doses, can result in compound absorption and storage.
• Repeated short exposures to insecticides may result in intoxication due to cumulative effects.

Organophosphate and Carbamate Insecticides MOA

• Organophosphate (OP) and carbamate (CM) insecticides share a mode of toxicological action
• OPs and CMs inhibit the ChE enzyme within the nervous tissue and at the NMJs
• These block the site where the neurotransmitter acetylcholine attaches to the enzyme AChE.
• Action sites: synapses in the nervous tissue and neuromuscular junctions, and in RBCs
• Blood/RBC-AChE activity during an early exposure period can indicate the degree of exposure.

Organophosphate and Carbamate Toxicity Differences

• "R" denotes a variety of groups that attach to the basic structure
• "P = S" of organophosphorus compounds can be substituted for “P = O”
• “RL” of organophosphates may attach via an “O” to “P”
• OPs have a higher toxicity and longer duration of action and are more common in CNS
• The primary manifestations of acute ChE inhibitor toxicity are those of cholinergic hyperactivity.

Clinical Signs of Toxicity

• Variation in clinical signs depends upon the OP or CM compound and route of exposure.
• This condition may lead to paralysis
• Central effects include apprehension and stimulation
• Also includes depression, restlessness, ataxia, stiffness of the neck, and coma.
• Death may occur due to respiratory failure and cardiac arrest.
• Poisoned individuals recover within 3–6 h with CMs and within 24 h with Ops given treatment.
• Some individuals exposed to OP nerve agents may show signs of toxicity for days.

Diagnosis and Treatment

• Diagnosis includes case history, clinical signs and levels of AChE inhibition in blood.
• Treatment includes antidotal treatment, respiratory support and correction of dehydration.

OP-Induced Delayed Neurotoxicity (OPIDN)

• Weak ChE inhibitors inhibit neurotoxic esterase (NTE) present in the CNS.
• Delayed neurotoxicity results from the inhibition and aging (no reactivation) of NTE.
• OP’s causing OPIDN include Ethyl p-nitrophenyl (EPN), leptophos, parathion, haloxon, diisopropylphosphorofluoridate, and tetraethyl pyrophosphate
• C.S includes muscle weakness and ataxia progressing to flaccid paralysis within 10-14 days after exposure
• No specific antidotes exist

Chlorinated Hydrocarbon Compounds Toxicity

• Organochlorines (OC) are a group of chlorinated compounds widely used as synthetic pesticides.
• Only lindane and methoxychlor are approved for use on or around livestock.
• Highly lipophilic leads to persistent tissue residues and chronic toxicity.
• BHC, heptachlor, heptachlor epoxide, lindane, and oxychlordane, can be found in fatty tissue after acute or chronic exposure.
• There are no specific antidotes.
• When exposure is by spraying, dipping, or dusting, bathe gently with detergent and water.
• For ingestion, gastric lavage, activated charcoal, and saline purgatives.
• Excitatory signs are treated with sedative anticonvulsants (barbiturate or diazepam).

Insecticides Derived from Plants

• Natural Plant Extracts
• Pyrethrins
• d-Limonene

Natural Plant Extracts

• Commonly used include nicotine, pyrethrum, rotenone (derris plant), and neem extracts.
• Generally non-toxic to humans and pets and safe for the environment
• Pets are exposed to tobacco by ingesting commercial tobacco products
• Toxicity include:
  • tremors, incoordination, nausea, and disturbed respiration
  • Muscle paralysis can lead to coma and death via paralysis of thoracic respiratory muscles and cardiac arrest.
• The material is removed by washing and/or gastric lavage with tannic acid and administering activated charcoal.
• Artificial respiration and treatment for cardia arrest and shock may be needed

Pyrethrins

• Insecticides are obtained from the flowers of C. cinerariafolium and have been used as insecticides for many years
• Toxicity primarily affects sodium, chloride, and calcium channels of nerve cells, as well as nicotinic ACh receptors.
• Synergists (piperonyl butoxide, sesamex, piperonyl cyclonene) added to increase stability and effectiveness
• Synergists inhibit mixed function oxidases, enzymes that detoxify pyrethrins.

D-Limonene

• A component of the oil extracted from citrus rind
• Used for the control of fleas on cats and other insect pests
• The toxic dose is 5-10 times the recommended dose.
• Toxicity signs include hyper-salivation, muscle tremors, ataxia, and mild-to-severe hypothermia.
• There is no antidote
• Supportive treatment involves treating clinical signs.

Synthetic Pyrethroid Insecticides

• Synthetic derivatives of natural pyrethrins, of which, there are two types
• Type I compounds produce a neurologic syndrome through their effects on the central and peripheral nervous systems
  • Signs include tremors, incoordination, prostration, seizures, and death
• Type II pyrethroids work primarily through CNS mechanisms
  • To exert the choreoathetosis/ salivation syndrome, hyperactivity, hunched back, salivation, tremors, and incoordination

Diagnosis of Pyrethroid Poisoning:

• Clinical signs
• History of exposure
• Determination of insecticide residue in body tissues and fluids.

Treatment of Pyrethroid Poisoning

• Includes symptomatic and supportive treatment, activated charcoal, and saline cathartic (if needed).
• Seizures are treated with diazepam, phenobarbital, or pentobarbital

Herbicide Toxicity

• Herbicides control weeds
• Imidazolinones: new herbicides with low toxicities to mammals, fish, insects, and birds, which, inhibit the action of acetohydroxyacid synthase.
• Chlorophenoxy herbicides
• Also included are 2,4-dichlorophenoxyacetic acid (2,4-D) and 2,4,5-trichlorophenoxyacetic acid (2,4,5-T) (low toxicity)
• Mixtures of 2,4-D and 2,4,5-T contain a contaminant, 2,3,7,8-tetrachlorodibenzo-pdioxin (TCDD) which are toxic.
• TCDD is a proven carcinogen in both mice and rats, with the liver being the primary target.

Triazines:

• Have carcinogenic effects
• Contaminates surface and ground water supplies

Bipyridylium:

• Includes paraquat (1,1-dimethyl-4,4-bipyridinium ion as the chloride salt) and diquat
• Paraquat is classified as a class I toxicant with an oral LD50 of 150 mg/kg (rat)
• Can cause ulceration and necrosis of the skin and mucous membranes
• Also causes progressive irreversible pulmonary fibrosis

Paraquat Mechanism of Action

• Actively taken up by the alveolar cells via a diamine or polyamine transport system.
• Results in (NADPH)- dependent reduction to form radical ions
• These radical ions generate superoxide radicals that react with unsaturated membrane lipids.
• The excess of superoxide anion radical O2− and H2O2 cause damage to the cellular membrane in lungs
• Reduces the functional integrity of lung cells, affecting efficient gas transport and exchange
• Results in respiratory impairment.

Diquat

• A reactive compound that affects the liver and kidney similarly
• Signs of CNS excitement and renal impairment occur in severely affected patients.
• Treatment is supportive and symptomatic.
• Oxygen therapy is contraindicated as it promotes the formation of more superoxides.