3.1 Pesticides

Pesticides are crucial tools in agriculture and public health, but they come with significant risks. These chemicals, designed to control pests, weeds, and diseases, are classified based on their targets and chemical structures. Understanding their modes of action, exposure routes, and toxicity is essential for assessing their impacts.

Pesticides can have wide-ranging effects on human health and the environment. From acute poisoning to chronic diseases, these substances pose risks through various exposure routes. Their environmental impacts include soil and water contamination, harm to non-target organisms, and potential for bioaccumulation in food chains.

Classification of pesticides

• Pesticides are classified based on their target organisms and chemical structures
• Understanding the different types of pesticides is crucial for assessing their toxicological properties and potential health and environmental impacts

Insecticides

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• Insecticides target insects that damage crops, spread diseases, or are considered pests (mosquitoes, aphids, beetles)
• Include organochlorines (DDT), organophosphates (malathion), carbamates (carbaryl), and pyrethroids (permethrin)
• Can have broad-spectrum effects, impacting both target and non-target insect species
• Some insecticides, such as neonicotinoids, have been linked to declining bee populations

Herbicides

• Herbicides are used to control unwanted plants or weeds that compete with crops for resources
• Glyphosate (Roundup) is one of the most widely used herbicides worldwide
• Selective herbicides target specific plant species, while non-selective herbicides kill all plants they come in contact with
• Herbicide resistance in weeds has become a growing concern, leading to the development of genetically modified crops resistant to certain herbicides

Fungicides

• Fungicides are designed to control fungal diseases in plants (powdery mildew, rust, blight)
• Can be applied as a preventive measure or to treat existing fungal infections
• Examples include copper-based fungicides (Bordeaux mixture), sulfur, and synthetic fungicides like triazoles and strobilurins
• Some fungicides have been linked to endocrine disruption and developmental toxicity in humans and wildlife

Rodenticides

• Rodenticides are used to control rodent populations (rats, mice) that can damage crops, spread diseases, and infest buildings
• Anticoagulant rodenticides (warfarin, brodifacoum) cause internal bleeding by inhibiting vitamin K-dependent blood clotting factors
• Non-anticoagulant rodenticides include zinc phosphide, which releases toxic phosphine gas, and bromethalin, a neurotoxin
• Secondary poisoning of predators (birds of prey, foxes) that consume poisoned rodents is a concern with some rodenticides

Other pesticide types

• Molluscicides target snails and slugs that can damage crops and ornamental plants (metaldehyde, iron phosphate)
• Nematicides control plant-parasitic nematodes in soil (1,3-dichloropropene, oxamyl)
• Plant growth regulators are used to control plant growth and development (gibberellins, cytokinins)
• Antimicrobials and disinfectants are used to control bacteria, viruses, and other microorganisms in various settings (hospitals, food processing, water treatment)

Modes of action

• Understanding the modes of action of pesticides is essential for predicting their toxicological effects and developing targeted control strategies
• Pesticides can disrupt various biological processes, leading to adverse health outcomes in target and non-target organisms

Nervous system disruption

• Many insecticides, such as organophosphates and carbamates, inhibit acetylcholinesterase (AChE), an enzyme that breaks down the neurotransmitter acetylcholine
• AChE inhibition leads to overstimulation of cholinergic receptors, causing neurotoxic effects (tremors, paralysis, respiratory failure)
• Pyrethroids and some organochlorines disrupt sodium channels in nerve cell membranes, leading to hyperexcitability and neurotoxicity
• Neonicotinoids bind to nicotinic acetylcholine receptors (nAChRs), causing overstimulation and eventual paralysis in insects

Endocrine system disruption

• Some pesticides can interfere with the normal functioning of the endocrine system, which regulates hormones and developmental processes
• Organochlorines like DDT and its metabolite DDE are known endocrine disruptors, mimicking or blocking the actions of natural hormones
• Endocrine disruption can lead to reproductive disorders, developmental abnormalities, and increased risk of certain cancers (breast, prostate)
• Atrazine, a widely used herbicide, has been linked to endocrine disruption in amphibians, causing feminization of male frogs

Cellular respiration inhibition

• Certain fungicides and insecticides can disrupt cellular respiration by inhibiting mitochondrial electron transport chain enzymes
• Strobilurin fungicides (azoxystrobin, pyraclostrobin) inhibit complex III (cytochrome bc1 complex) of the electron transport chain, leading to reduced ATP production and fungal growth
• Rotenone, a naturally occurring insecticide, inhibits complex I (NADH dehydrogenase) of the electron transport chain, causing mitochondrial dysfunction and oxidative stress
• Inhibition of cellular respiration can lead to energy depletion, oxidative damage, and cell death in target and non-target organisms

Other mechanisms

• Some herbicides, such as glyphosate, inhibit the shikimate pathway enzyme 5-enolpyruvylshikimate-3-phosphate (EPSP) synthase, disrupting aromatic amino acid synthesis in plants
• Triazine herbicides (atrazine, simazine) inhibit photosystem II in plant chloroplasts, blocking electron transport and leading to oxidative damage
• Dithiocarbamate fungicides (mancozeb, maneb) can disrupt the synthesis of microtubules, affecting cell division and growth
• Biopesticides, such as Bacillus thuringiensis (Bt) toxins, selectively target insect gut cells, causing pore formation and cell lysis

Exposure routes

• Pesticides can enter the body through various exposure routes, depending on their physical and chemical properties, as well as the circumstances of exposure
• Understanding exposure routes is crucial for assessing the potential health risks associated with pesticide use and developing appropriate protective measures

Inhalation

• Pesticides can be inhaled as vapors, gases, or particulates, especially during application or in enclosed spaces
• Inhalation exposure is particularly relevant for volatile pesticides or those applied as aerosols or fumigants
• Inhaled pesticides can directly enter the bloodstream through the lungs, bypassing first-pass metabolism
• Inhalation exposure can lead to respiratory irritation, asthma-like symptoms, and systemic toxicity, depending on the pesticide and exposure level

Dermal absorption

• Pesticides can be absorbed through the skin, especially when handling concentrated products or during application without proper protective equipment
• Dermal absorption is influenced by the pesticide's lipophilicity, molecular weight, and the condition of the skin (cuts, abrasions, hydration)
• Organophosphate and carbamate insecticides are readily absorbed through the skin, leading to potential systemic toxicity
• Dermal exposure can cause local skin irritation, allergic reactions, or contribute to the overall body burden of the pesticide

Ingestion

• Pesticides can be ingested accidentally through contaminated food, water, or by hand-to-mouth transfer after handling treated surfaces
• Children are particularly susceptible to accidental ingestion due to their exploratory behavior and hand-to-mouth activity
• Ingested pesticides can cause acute poisoning symptoms, such as nausea, vomiting, abdominal pain, and diarrhea
• Chronic ingestion of pesticide residues in food may contribute to long-term health effects, depending on the pesticide and exposure levels

Environmental contamination

• Pesticides can contaminate air, water, and soil, leading to indirect human exposure through inhalation, ingestion, or dermal contact
• Pesticide drift during application can result in off-target contamination and exposure to nearby communities
• Leaching of pesticides into groundwater can lead to contamination of drinking water sources
• Bioaccumulation of persistent pesticides in the food chain can result in higher exposures to humans and wildlife consuming contaminated prey

Toxicity assessment

• Toxicity assessment is the process of evaluating the potential adverse health effects of pesticides on humans and other organisms
• It involves determining the dose-response relationships, acute and chronic toxicity, and using various testing methods to characterize the hazards associated with pesticide exposure

Acute toxicity

• Acute toxicity refers to the adverse effects that occur shortly after a single or short-term exposure to a pesticide
• Commonly used measures of acute toxicity include the median lethal dose (LD50) and median lethal concentration (LC50)
• LD50 represents the dose that causes mortality in 50% of the exposed test animals, while LC50 is the concentration that causes mortality in 50% of the exposed test animals
• Acute toxicity can manifest as poisoning symptoms, such as nausea, vomiting, diarrhea, respiratory distress, and neurological effects, depending on the pesticide and exposure level

Chronic toxicity

• Chronic toxicity refers to the adverse health effects that occur after repeated or long-term exposure to a pesticide, even at low doses
• Chronic toxicity can lead to the development of diseases or disorders that may not be immediately apparent, such as cancer, neurodegenerative diseases, and reproductive or developmental abnormalities
• Chronic toxicity assessment involves long-term studies in animals, epidemiological studies in human populations, and the use of biomarkers to detect early signs of toxicity
• The no-observed-adverse-effect level (NOAEL) and lowest-observed-adverse-effect level (LOAEL) are used to establish safe exposure levels for humans

Dose-response relationships

• Dose-response relationships describe the relationship between the dose of a pesticide and the magnitude of the observed adverse effect
• Generally, as the dose increases, the severity or incidence of the adverse effect also increases
• The shape of the dose-response curve can provide insight into the mechanism of toxicity and help determine threshold doses for adverse effects
• Hormetic dose-response relationships, characterized by a biphasic response with low-dose stimulation and high-dose inhibition, have been observed for some pesticides

Toxicity testing methods

• In vitro tests use cell cultures or isolated organs to assess the toxicity of pesticides at the cellular or molecular level (cell viability assays, gene expression studies)
• In vivo tests involve exposing laboratory animals (mice, rats, rabbits) to pesticides to assess toxicity at the organismal level (acute and chronic toxicity studies, developmental and reproductive toxicity tests)
• In silico methods use computer models and structure-activity relationships (SARs) to predict the toxicity of pesticides based on their chemical structure and properties
• Toxicogenomic approaches (transcriptomics, proteomics, metabolomics) can provide mechanistic insights into pesticide toxicity by studying changes in gene expression, protein levels, and metabolite profiles

Health effects

• Pesticides can cause a wide range of adverse health effects in humans, ranging from acute poisoning symptoms to chronic diseases and disorders
• The severity and nature of health effects depend on the specific pesticide, the dose, duration, and route of exposure, as well as individual susceptibility factors

Acute poisoning symptoms

• Acute pesticide poisoning can occur after a single exposure to a high dose of a pesticide, often due to accidental ingestion, inhalation, or dermal exposure
• Symptoms of acute poisoning vary depending on the pesticide class but may include nausea, vomiting, diarrhea, abdominal pain, headache, dizziness, and respiratory distress
• Organophosphate and carbamate insecticides can cause cholinergic crisis, characterized by excessive sweating, salivation, bronchial secretions, and muscle twitching
• Pyrethroid insecticides can cause paresthesia (tingling sensation), while organochlorine insecticides can cause central nervous system stimulation and seizures

Chronic health impacts

• Chronic exposure to pesticides has been associated with various long-term health effects, including cancer, neurodegenerative diseases, and endocrine disruption
• Occupational exposure to pesticides has been linked to an increased risk of certain cancers, such as prostate cancer, non-Hodgkin lymphoma, and leukemia
• Parkinson's disease has been associated with exposure to herbicides, particularly paraquat and rotenone
• Endocrine-disrupting pesticides can interfere with hormone signaling, leading to reproductive disorders, developmental abnormalities, and increased risk of hormone-related cancers

Carcinogenicity

• Some pesticides have been classified as carcinogenic or probably carcinogenic to humans by the International Agency for Research on Cancer (IARC)
• Organochlorine insecticides, such as DDT and lindane, have been linked to an increased risk of breast cancer and non-Hodgkin lymphoma
• Arsenic-based pesticides, historically used as insecticides and wood preservatives, are known human carcinogens, associated with skin, lung, and bladder cancers
• The herbicide glyphosate has been classified as probably carcinogenic to humans by the IARC, although this classification remains controversial

Reproductive and developmental toxicity

• Pesticides can affect reproductive health and development by interfering with hormone signaling, causing oxidative stress, or directly damaging reproductive organs
• Exposure to organochlorine insecticides has been associated with reduced fertility, increased time to pregnancy, and increased risk of spontaneous abortion
• Some pesticides, such as the fungicide vinclozolin, can cause transgenerational effects, with adverse reproductive outcomes observed in multiple generations following exposure
• Prenatal exposure to pesticides has been linked to developmental abnormalities, low birth weight, and neurodevelopmental disorders, such as attention deficit hyperactivity disorder (ADHD) and autism spectrum disorder (ASD)

Neurotoxicity

• Many pesticides, particularly insecticides, target the nervous system and can cause neurotoxic effects in humans
• Acute neurotoxicity can manifest as seizures, tremors, and paralysis, while chronic neurotoxicity may lead to cognitive impairment, motor dysfunction, and neurodegenerative diseases
• Organophosphate insecticides can cause delayed neuropathy, characterized by weakness and paralysis of the extremities, several weeks after acute exposure
• Exposure to certain pesticides, such as paraquat and rotenone, has been associated with an increased risk of Parkinson's disease, possibly due to their ability to induce oxidative stress and mitochondrial dysfunction

Immunotoxicity

• Pesticides can modulate the immune system, leading to immunosuppression or hypersensitivity reactions
• Organochlorine insecticides, such as DDT and chlordane, have been shown to suppress immune function in animal studies, increasing susceptibility to infections and cancers
• Some pesticides, such as organophosphates and carbamates, can cause allergic reactions, including asthma and contact dermatitis
• Neonicotinoid insecticides have been implicated in the decline of bee populations, in part due to their immunosuppressive effects, which may increase susceptibility to pathogens and parasites

Environmental impacts

• Pesticides can have far-reaching environmental impacts, affecting soil, water, and air quality, as well as non-target organisms and ecosystems
• The persistence, mobility, and bioaccumulation potential of pesticides determine the extent and duration of their environmental effects

Soil contamination

• Pesticides can accumulate in soil, particularly those with high soil adsorption coefficients and low biodegradability
• Soil contamination can lead to reduced soil fertility, changes in microbial communities, and uptake of pesticides by plants
• Persistent pesticides, such as organochlorines, can remain in the soil for decades, leading to long-term environmental contamination
• Soil contamination can also facilitate the transport of pesticides to groundwater through leaching or to surface water through runoff

Water pollution

• Pesticides can enter water bodies through various routes, including surface runoff, spray drift, and leaching from contaminated soils
• Water pollution by pesticides can have adverse effects on aquatic ecosystems, such as reduced biodiversity, fish kills, and altered food web dynamics
• Some pesticides, such as atrazine and glyphosate, have been frequently detected in surface and groundwater, raising concerns about drinking water contamination
• Pesticide contamination of water can also impact human health through consumption of contaminated water or fish

Effects on non-target organisms

• Pesticides can unintentionally harm non-target organisms, including beneficial insects, birds, fish, and mammals
• Insecticides, particularly broad-spectrum ones, can cause significant declines in pollinator populations, such as bees and butterflies
• Herbicides can alter plant community composition, reducing food and habitat resources for wildlife
• Rodenticides can cause secondary poisoning in predators, such as birds of prey and foxes, that consume poisoned rodents
• Fungicides can impact soil fungi and other microorganisms, disrupting nutrient cycling and soil health

Bioaccumulation and biomagnification

• Some pesticides, particularly those that are lipophilic and persistent, can bioaccumulate in the tissues of organisms and biomagnify through food chains
• Bioaccumulation occurs when an organism absorbs a substance at a rate faster than it can eliminate it, leading to an increase in the concentration of the substance in the organism over time
• Biomagnification refers to the increasing concentration of a substance in the tissues of organisms at successively higher levels in a food chain
• Organochlorine insecticides, such as DDT and its metabolite DDE, are classic examples of pesticides that bioaccumulate and biomagnify, leading to high concentrations in top predators
• Bioaccumulation and biomagnification can