HSCI 560 Exam 2: Toxicity of Pesticides

EPA Legal Definition of Pesticides

any substance or mixture of substances intended for preventing, destroying, repelling, or mitigating pests

Acaracides

additional class of pesticides: mites or ticks

Miticides

additional class of pesticides: mites only

Pediculicides

additional class of pesticides: lice

800 B.C.

pesticides have been used since what year? specifically, burning sulfur to get rid of a courthouse

1935 and 1950

use of pesticides boomed between what years

1942

after finding out that DDT was poisonous to insects, commercialization started in what year

organophosphorus

what type of insecticide was:

• Much more toxic than chlorinated insecticides

• Could be used as warfare agents

agricultural productivity

what is the 1st importance of pesticides

economic impact

what is the 2nd importance of pesticides

public health

what is the 3rd importance of pesticides (control vector-borne diseases and prevent contamination)

technological and environmental role

what is the 4th importance of pesticides

human health

1st risk of pesticide use:

1 – Acute toxicity

2 – Chronic exposure

3 – Occupational risk

environmental impact

2nd risk of pesticides:

1 – Persistence and bioaccumulation

2 – Non-target toxicity

3 – Soil degradation

4 – Antimicrobial and herbicide resistence

food safety and residues

3rd risk of pesticides:

1 – Pesticide residues in food and water sources

2 – Cuulative dietary exposure and mixture effects

societal regulatory challenges

4th risk of pesticides:

1 – Unequal exposure in low-and middle-income countries

2 – Illegal and unsafe use due to lack of regulation or enforcement

3 – Public percepetion

agricultural

majority of pesticide use is in what type of setting

80 million

there are still how many US householes that use pesticides in the home (usually insecticides)

skin and eye irritation, dizziness, headache, nausea, and vomiting

what are examples of acute toxicity of pesticides

cancers, neurodegenerative diseases like Parkinson's, and reproductive harm such as birth defects and infertility

what are examples of chronic toxicity of pesticides

40s-late 60s

what time was dominated by insecticide use

70s

when was there a massive increase in herbicide Usage

corn

what crop arepestides most used on

1. Glyphostae

2. Atrazine

what are the two most used pesticides

herbicides

what’s the most used pesticide, globally?

USA

what country uses the most pesticides

• inhalation

• oral/ingestion

• dermal

what are the main routes of exposure for pesticides

oral (bc of chronic low doses through contaminated drinking water)

what exposure route is the most common for the general population

inhalation and dermal

what exposure routes are typically occupational

occupaitonal

populations at risk: farmers, pesticide applicators, agricultural workers

para-occupational

populations at risk: family members of workers (take-home exposure)

general population

populations at risk: dietary residues, contaminated water/air

sensitive groups

populations at risk: children, pregnant women, immunocompromised individuals

agricultural

exposure context: field application, storage, disposal

residential

exposure context: household pest control, lawn/garden products

public health control

exposure context: vector control (e.g., mosquito spraying)

environmental contamination

exposure context: drift, leaching, runoff, groundwater contamination

failure to account for sensitive groups

why is it problematic that pesticide standards are typically based on healthy adults

endocrine disruptors

Evidence that some pesticides are ________, contributing to various effects like cancer and reproductive and developmental toxicity

hazard

pesticides are classified by ________

insecticides

• Organophosphates (Parathion, Malathion, Chlorpyrifos)

• Carbamates (DDT)

herbicides

• Triazines (Atrazine)

• Bipyridyl Compounds (Paraquat)

• Phosphonomethyl Amino Acids (Glyphosate)

fungicides

• Thiophthalimide fungicides (Captan and Folpet)

• Dithiocarbamates

rodenticides

• Warfarin

• Strychnine

acetylcholinesterase

Organophosphates inhibit ______ in insects

EPSP synthase

herbicides like glyphosate inhibit ________ in plants

poisoning the nervous system of the target organism

how do insecticides work

similarities in CNS and PNS

insecticides have higher acute toxicity toward nontarget species compared to other pesticides. why?

phosphorylate the serine residue in the active site of AChE, preventing ACh breakdown → continuous stimulation of cholinergic receptors → overstimulation of nerves & muscles; AChE breaks down ACh into 2 pieces; when OP present it blocks AChE and causes more ACh increasing more firing and signaling leading to death in individual

What is the main mechanism of AChE inhibitors like organophosphates (OPs)?

Only compounds with a P=O bond can inhibit AChE.

What structural feature makes OPs active?

By CYP450 oxidative desulfuration → forms toxic oxon analog (active inhibitor).

How are OPs activated in the body?

• Parathion → activated by CYP3A4/5, detoxified by CYP2B6

• Chlorpyrifos → activated by CYP2B6, detoxified by CYP2C19

What enzymes activate or detoxify specific OPs?

CYP enzyme variants can alter detoxification → increased susceptibility.

How do genetic polymorphisms affect OP toxicity?

rapid detoxification by Carboxylesterases (CarE) → mammals have high CarE activity.

Why is malathion less toxic to mammals?

OP

the following are what type of poisoning symptoms in humans (acute and chronic):

• Muscarinic symptoms: salivation, lacrimation, urination, diarrhea, vomiting (SLUDGE)

• Nicotinic symptoms: muscle fasciculations, weakness, paralysis

• CNS: anxiety, confusion, seizures, respiratory failure

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• Neurobehavioral effects: memory impairment, attention deficits, mood disorders

• Potential developmental neurotoxicity (prenatal exposure)

•Aquatic organisms: behavioral changes, decreased growth, reproductive impairment

•Birds & mammals: AChE inhibition leading to neurotoxicity

•Pollinators (bees): impaired foraging, learning, and colony collapse

What are OP poisoning effects on non-target organisms?

remove clothing and wash skin

treatment for dermal OP exposure is…?

administer atropine or 2PAM

treatment for oral OP exposure is…?

atropine

prevents the action of acetylcholine from accumulating in the

receptors; OP treatment

2PAM

facilitiates dephosphorylation of AChE, restoring the catalytic site to its function (Can only be used in specific circumstances if caught early); OP treatment

Dementia, chronic CNS/PNS effects, carcinogenicity (parathion, malathion), age-dependent susceptibility in young animals.

What are the long-term risks of OP exposure?

parathion

between parathion and malathion, which one has been banend

malathion

between parathion and malathion, which one has been only regulated

Also inhibit AChE, but reversibly and short-term, resolving in hours.

How do carbamates act compared to OPs?

Binds to open sodium channels, stabilizing them open → prolonged depolarization (banned due to persistence).

What is the mechanism of DDT (organochlorine compound) toxicity?

mechanism of toxicity absent in humans and mammal

Why is Bt toxin safe for mammals?

activated by alkalis and/or digestion in the gut of the insect

• Bt genes are expressed in crops (corn, cotton)

What is the mechanism for Bt toxin

Voltage-gated sodium channels (VGSCs) in nerve membranes.

What is the target of pyrethroids (Used pharmacologically to treat lice and scabies control)

prolongs sodium channel opening → delayed repolarization → repetitive firing/hyperexcitation.

What is the mechanism of pyrethroid toxicity?

Different sodium channel isoforms & lower body temperature slow detoxification.

Why are insects more sensitive to pyrethroids?

Rapidly via esterases and CYP450 enzymes.

How do mammals detoxify pyrethroids?

pyrethroids

The following are symptoms of what type of insecticide exposure?

• Acute: Tingling/burning skin, headache, nausea, seizures (high dose)

• Chronic: Possible endocrine disruption, neurobehavioral effects (under study)

• Aquatic species: Highly toxic (slow metabolism)

• Bees: Impaired navigation/foraging

• Birds/mammals: Lower risk, but harm at high environmental levels

What are pyrethroid effects on non-target species?

slow metabolism

Why are pyrethroids more toxic in fish than humans?

herbicides

• represent almost 1/2 of the pesticides used in the US and more than 1/3 of the pesticides used worldwide

• low acute toxicity generally to humans but cna still have adverse effects (usually as endocrine disruptors)

70 million

it’s estimated that how many farmers would be requred to work to make up for weeding to prevent crop yield losses without herbicides

triazine

what’s the most used herbicide

inhibit photosynthesis, preventing growth of broadleaf and grassy weeds.

What is the main mechanism of triazine herbicides?

atrazine

What is the most commonly used triazine herbicide in the U.S.?

contaminated drinking water

What is the primary route of human exposure to triazines?

yes, but exposures often exceed the maximum contaminant level (MCL).

Are atrazine levels in the environment regulated?

No, it’s not clearly defined, but atrazine is recognized as an Endocrine Disrupting Chemical (EDC).

Is the mechanism of atrazine toxicity fully understood?

disrupts the neuroendocrine system by altering GnRH regulation, which dysregulates the luteinizing hormone (LH) surge

How does atrazine affect the endocrine system?

Adverse reproductive outcomes in mammals and other species.

What are the main health effects of low-dose, environmentally relevant atrazine exposure?

paraquat

What is the main bipyridyl herbicide?

cell membrane disruptor used to control broadleaf and grassy weeds.

What is Paraquat’s primary function as a herbicide?

Its redox potential interferes with photosynthesis, leading to oxidative damage and plant death.

What is the main mode of action of Paraquat in plants?

They generate reactive oxygen species (ROS) through redox cycling, causing cellular oxidative damage.

How do Paraquat’s redox properties cause mammalian toxicity?

lungs

What is the major site of Paraquat accumulation and damage in humans? small portion of it is metabolized, most excreted

kidneys

What secondary organ does Paraquat accumulate in?

Paraquat is reduced to a free radical, which re-oxidizes in the presence of oxygen, producing superoxide radicals (O₂⁻) → oxidative stress and tissue injury.

What chemical reaction underlies Paraquat’s toxicity?

glyphosate

What is the most common phosphonomethyl amino acid herbicide?

It’s a broad-spectrum, nonselective herbicide for postemergent control of annual and perennial plants.

What is glyphosate’s main agricultural use?

5-enolpyruvylshikimate-3-phosphate synthase (EPSPS) — key in amino acid biosynthesis in plants.

What enzyme does glyphosate inhibit?

EPSPS pathway is absent in mammals, so humans don’t share the herbicide’s target mechanism.

Why is glyphosate highly selective for plants?

Other formulation components, especially POEA (a surfactant), which increases cell permeability to glyphosate.

What is the main source of glyphosate toxicity in formulations like Roundup?

Glyphosate, POEA (surfactant), and water.

What are the components of Roundup?

It’s toxic to rats and may enhance glyphosate absorption, increasing adverse effects.

How does POEA contribute to toxicity?

Genotoxicity, oxidative stress, and carcinogenicity in humans.

What potential health effects has IARC linked to glyphosate itself?

Fungal diseases are nearly impossible to control without chemical use; even organic farmers rely on sulfur, copper, and lime sulfur.

Why are fungicides essential in agriculture? they’re also dervied from both in/organic comps