Toxic Effects of Pesticides

Toxic Effects of Pesticides

• Pesticides are substances or mixtures intended to prevent, destroy, repel, or mitigate pests.
• The target organisms' nervous systems get poisoned.
• Herbicides are compounds that kill or severely injure plants.
• Fungicides are chemicals that prevent fungal growth and reproduction.

Pesticide Exposures

• Accidental and/or suicidal poisonings
• Occupational exposure (manufacturing, mixing/loading, application, harvesting, and handling of crops)
• Bystander exposure to off-target drift from spraying operations
• Consumption of food items containing pesticides

Pesticide Classification

• Insecticides (insects)
• Herbicides (weeds)
• Fungicides (fungi and molds)
• Rodenticides (rodents)
• Acaricides (mites)
• Molluscides (snails and other mollusks)
• Miticides (mites)
• Larvicides (larvae)
• Pediculocides (lice)

Pesticides - Economics, Public Health

• DDT undergoes bioaccumulation in the environment.
• Impacts on bird reproduction.
• DDT was banned in many countries by the mid-1970s.
• Significant reduction of malaria cases after banning DDT.

Pesticides - Human Poisoning

• Exposure occurs via oral or dermal routes or by inhalation.
• High oral doses are from pesticide ingestion or suicidal intent or accidental ingestion due to improper storage.
• Chronic low doses result from pesticide residues in food and water contamination.

Pesticide LD50 values

• Class Ia: Extremely hazardous (5 or less mg/kg for solids and 20 or less mg/kg for liquids)
• Class Ib: Highly hazardous; ranging from 5–50 (solids) to 20–200 (liquids).
• Class II: Moderately hazardous; ranging from 50–500 (solids) to 200–2000 (liquids).
•  Class III: Slightly hazardous; (solids over 500, liquids over 2000).

Pesticides - Regulatory Mandate

• Environmental Protection Agency (EPA) regulates pesticide use.
• The Food Quality Protection Act mandates risk assessments of pesticides concerning infants and children for the EPA.
• Large number of studies are required (over 140) which take several years.

Pesticides - Regulatory Mandate - Additional Points

• Product and residue chemistry, environmental fate, toxicology; biotransformation, degradation; occupational exposure and reentry protection, spray drift, environmental impact on non-target species, environmental persistence and
• Toxicity testing requirements for pesticide registration.

Organophosphorus- Toxicity

• OP insecticides have high acute toxicity.
• Oral LD50 values in rats often below 50.
• Symptoms: "cholinergic syndrome" (increased sweating, salivation, bronchial secretion)
• Diagnosis: includes bronchoconstriction,miosis, increased gastrointestinal motility, diarrhea, tremors, and muscular twitching.
• Additional symptoms: respiratory failure.
• Overstimulation of muscarinic and nicotinic cholinergic receptors.

Organophosphorus-Intermediate Syndrome

• Manifested in 20% to 50% of acute OP poisoning.
• Symptoms: Weakness of respiratory, neck, and proximal limb muscles.
• Hypothesis: Muscle weakness from nicotinic receptor desensitization due to prolonged cholinergic stimulation.

Organophosphorus-Polyneuropathy

• Organophosphate-induced Delayed Polyneuropathy (OPIDP).
• Rare occurrence in humans.
• Symptoms include tingling of hands and feet, followed by sensory loss, progressive muscle weakness, and flaccidity of distal skeletal muscles of lower and upper extremities, and ataxia.
• Primary lesion: Bilateral degenerative change in distal levels of axons and their terminals.

Organophosphorus-Long-Term and Developmental Toxicity

• Long-term adverse health effects.
• Particular impact on the CNS.
• Dose-dependent effects: no cholinergic signs at lower doses, but long-term effects at higher doses.
• Mechanisms: Effects on cellular processes (e.g., DNA replication,), neuronal survival, and neurite outgrowth, as well as non-cholinergic pathways.

Carbamate Insecticides

• Derivatives of carbamic acid, mostly N-methylcarbamates.
• Toxicity: from low to extremely high, depending on the specific chemical.
• Symptoms:
• Miosis, urination, diarrhea, salivation, and CNS effects.
• Increased by organic solvents and emulsifiers

Pyrethroids

• Derived from Chrysanthemum cinerariifolium.
• High insecticidal potency, low mammalian toxicity.
• Mechanism:
• Change the normal function of insect voltage-sensitive sodium channels. Increase sodium permeability of the nerve membrane.

Organochlorine Compounds

• Chlorinated ethane derivatives (e.g., DDT and its analogs).
• Cyclodienes: (e.g., chlordane, aldrin, dieldrin, heptachlor, endrin, and toxaphene).
• Hexachlorocyclohexanes: (e.g., lindane).
• Mechanism:
• Interfere with sodium channels in axonal membrane.

Neonicotinoids

• Nicotine-based insecticides effective toward a wide range of insects, including aphids, thrips, and whiteflies.
• Mechanism:
• Activation of nAChRs (in the CNS).
• At high doses, parasympathetic stimulation and ganglionic and neuromuscular blockade predominate.

Other Old and New Insecticides

• Rotenoids: Inhibit the mitochondrial complex I, particularly in organic formulations.
• Symptoms:
• Initial increased respiratory and cardiac rates; clonic and tonic spasms; and muscular depression.
• Avermectins: Parasitic control in humans and veterinary medicine; mostly for the control of mites and other kinds of parasites.
• Symptoms: Hyper excitability; tremors; incoordination followed by ataxia and a coma-like sedation.

Fumigants

• Compounds used for fumigation (particularly for soil treatments, and to control a wide range of pests)
• These agents are highly reactive and cytotoxic.
• Agents: Methyl bromide;1,3-Dichloropropene;Sulfur.
• Mechanisms:
• Respiratory and gastrointestinal effects.
• Neurological symptoms (lethargy, headache, seizures; and potentially paresthesias, peripheral, neuropathy, and ataxia).

Herbicides

• Chemicals that kill or harm plants.
• Preplanting herbicides applied to soil before planting; preemergent herbicides applied to soil before the appearance of unwanted vegetation. Postemergent herbicides applied after unwanted vegetation appears.
• Modes of action: Inhibit photosynthesis, respiration, protein/lipid synthesis, specific enzymes (e.g., glutamine synthetase, and acetolactate synthase).

Chlorophenoxy Compounds

• Auxin-like hormones critical to broadleaved plant growth, but not for grasses.
• Suppress the growth of weeds (e.g., dandelions) without directly affecting the targeted grasses
• Mechanism:
• Affect plant growth hormone synthesis; mostly by acting as auxin mimics and inhibitors.
• Symptoms:
• Vomiting; burning of the mouth; abdominal pain; hypotension; and myotonia; CNS involvement including coma.

Bipyridil Compounds

• Paraquat is a fast-acting contact herbicide. It's used to control broadleaf weeds and grasses, in plantations and fruit orchards; for general weed control.
• Mechanisms: Redox cycling leading to lipid peroxidation and a metabolic process.
• Chronic exposure to paraquat leads to serious damage to the alveolar system, and can be irreversible.
• Symptoms: nausea, vomiting; diarrhea; ulceration of mouth and esophagus; decline in renal function; and neurologic effects*.

Chloroacetanilides

• Examples include alachlor, acetochlor, and metolachlor
• Probable human carcinogens.
• Exposure mostly through drinking water or eating contaminated food, can affect the body weight.

Phosphonomethyl Amino Acids

• Herbicides.
• Inhibiting glutamine synthetase.
• Mild intoxication mainly causes transient gastrointestinal symptoms.
• Moderate/severe poisoning leads to gastrointestinal bleeding, hypotension, and pulmonary dysfunction; renal damage.
• Developmental toxic effects observed in rabbits (deliveries, abortions, and dead fetuses).

Fungicides

• Chemicals capable of killing or harm fungi.
• Types:
• Dithiocarbamates (e.g., maneb, zineb, metiram):
• Symptoms: hypertrophy and hyperplasia of thyroid follicular cells.
• Metals (e.g., copper sulfate):
• High usage for the prevention of seed-borne diseases in crops.
• Triphenyltin acetate; tributyltin acetate
• Symptoms: Moderate to high acute toxicity, but may cause reproductive/endocrine disruption.

Rodenticides

• Used to control rodents in structures and farms.
• Types:
• Fluoroacetic acid derivatives:
• Symptoms:
• Initial gastrointestinal symptoms followed by severe cardiovascular effects (ventricular tachycardia, fibrillation, and hypotension), and CNS effects (agitation, convulsions, and coma).
• Coumarin derivatives (e.g., warfarin):
• Symptoms:
• Anticoagulant activity; severe internal bleeding; potentially severe health risks to humans.

Insect Repellents

• DEET and Picaridin are effective at repelling insects; mainly mosquitoes, ticks, and flies.
• Used for topical treatments for scabies and headlice; effective methods to reduce insect bites and insect infestations.
• Mechanisms:
• Interaction with specific olfactory receptors of the arthropods

Explore the various toxic effects of pesticides, including their classifications and the different types of exposures individuals may face. Understand the implications for public health and the environment, especially concerning bioaccumulation. Test your knowledge about pesticides and their impact on ecosystems.