VIBS 422 Chapter 10

What is a pest?

unwanted organism that negatively impacts humans or competes for resources (ex. insects, rodents, microbes)

What is a pesticide?

any substance used to prevent, destroy, repel, or mitigate pests (includes insecticides, herbicides, fungicides, etc. )

What are the major pesticides?

• insectisides

• herbicides

• fungicides

• rodenticides

• nematicides

What are EDCs?

chemicals that interfere with hormone systems (synthesis, transport, receptors, metabolism)

What % of pesticides affect the endocrine system?

• 46% insecticides

• 21% herbicides

• 31% fungicides

Examples of endocrine-disrupting pesticides (EDCs)?

• Atrazine

• lindane

• endosulfan

• DDT

• Methoxychlor

• Malathion

• Vinclozolin

Where are humans exposed to pesticies?

• food residues

• tap water

• occupational exposure

• household dust

• pet flea treatments

• insect repellents

Routes of exposure

• dermal (skin)

• inhalation

• oral ingestion

• eye exposure

How do pesticides directly disrupt endocrine signaling?

bind to nuclear hormone receptors —> mimic/block hormones —> alter gene transcription

Result of receptor binding by pesticides?

• incorrect gene activation/repression

• hormonal imbalance

• disrupted physiological processes

How do pesticides indirectly disrupt endocrine function?

compete for cofactors needed for nuclear receptor signaling —> reduced hormone signaling

Key xenobiotic receptors involved?

• CAR (constitutive androstane receptor)

• PXR (pregnane X receptor)

Additional indirect disruption mechanism?

• increased hormone metabolism (CYP enzymes)

• Blocking DNA response elements

• protein degradation via ubiquitination

How do pesticides cause oxidative stress?

• increase ROS production

• damage DNA, lipids, proteins

• trigger apoptosis

How does oxidative stress lead to cancer?

• increase oncogene activation (ex. K-Ras)

• decrease tumor suppressor activity (p53)

• leads to uncontrolled cell growth

What do organophosphates & carbamates inhibit?

acetylcholinesterase (AChE)

Result of AChE inhibition?

ACh accumulation —→ receptor overstimulation —→ hyperexcitation

Downstream effects of ACh buildup?

• glutamate release

• NMDA activation

• Ca 2+ influx

• Mitochondrial damage

• ROS production

What type of pesticide is DDT?

organochlorine insecticide

Where is DDT found/exposure source?

agriculture (historically); still used in some countries for malaria control

Key properties of DDT?

• lipophilic (stored in fat)

• persistent (long half-life)

• bioaccumulation in food chain

Major effects of DDT

• nervous system disruption

• liver tumors

• reproductive toxicity

• endocrine disruption

Breakdown products of DDT?

• DDE

• DDD

• DDA

Environmental impact of DDT (bioaccumulation)?

higher concentrations in top predators (birds) —→ biomagnification

DDT effects on birds?

• thin eggshells

• embryo death

• population decline

Human health effects of DDT?

• decrease sperm quality

• spontaneous abortion

• low birth weight

• developmental delays

• breast cancer risk

What type of pesticide is atrazine?

herbicide

Key endocrine effect of atrazine?

alters sex ratios; increase females in fish

Effects of atrazine on reproduction?

• decreased testosterone

• testicular atrophy

• decreased spermatogensis

What is bioaccumulation?

increase in chemical concentration at higher trophic levels (stored in fat)

Effects of atrazine on non-target organisms?

Bees: colony collapse

Fish: reduced reproduction, growth, survival

Effects of atrazine on ecosystems?

• biodiversity loss

• food chain disruption

• pest resistance

WHy are children more vulnerable?

developing organs —> “critical windows of susceptibility”

Effects of pesticides on children?

• developmental disorder

• learning disabilities

• neurological damage

Active vs. Inert ingredients in pesticides?

Active = toxic agent

Inert = carries/solvents (can still be toxic, often unlisted)

Pesticide resistance?

genetic survival —→ resistant population dominates after repeated exposure

Pesticide movement in environment?

• air (drift)

• water (runoff, leaching)

• food chain transfer