Pesticides

• Physical, chemical or biological agent intended to kill an

undesirable plant/animal pest
• Major classes: insecticides, fungicides, herbicides
• Most pesticides are synthetic agents new to humans and
the environment
– Developed since 1940’s
– 891 pesticidal “active ingredients” licensed by US EPA*
– 523 used on food or feed
• Inherent toxicity
– 140 pesticides currently considered neurotoxic by EPA
 Acute, High Dose Toxicity
US Poison Control (2000)
• 11,000 unintentional organophosphate (OP)
exposures; 3000 treated in health care facility
• includes 4000 children < 6 yr
World Health Organization
• 3 million acute, severe poisonings/yr
• 220,000 deaths/yr
 Background Pesticide
Exposures Widespread
• Reported use: 98% of families, 80% during pregnancy
• In Food - detectable residues of at least one pesticide on
72% fruits/vegetables
• In Homes – 3 to 9 pesticide residues in typical
• In Air - indoor air levels 10-100X higher than outdoor air
• In Water - >90% stream samples, 50% of wells
Minnesota Children's Pesticide
Exposure Study
Urinary metabolites in 90 urban and non-urban Minnesota children, 3-
13 yrs old (Adgate 2001):
Metabolite Parent Pesticides
– 3,5,6-trichloro-2-pyrifinol (TCPy) chlorpyrifos & related
cmpds
– 1-naphthol (NAP) carbaryl or napthalene
– malathion dicarboxylic acid (MDA) malathion

Detections in first-morning-void samples

• TCPy 93%
• 1-NAP 45%
• MDA 37%
 Insecticide Sites of Action
Organochlorines Enzymes
Pyrethroids
Axonal Membranes
Ions (Na+, K+, Ca++, Cl-)

Organophosphorus Enzymes
and
Carbamate Esters Neurotransmitters

Figure 22-4. Potential sites of action of classes of insecticides

on the axon and the terminal portions of the nerve.
Casarett and Doull’s Toxicology: The Basic Science of Poisons, 5th Edition, Ed: Klaassen, CD.
McGraw-Hill, New York, 1996. P. 649
Example of Pesticide Mechanism:

Organophosphate (OP)

Blocks function of cholinesterase

Increases levels of acetylcholine,

an important neurotransmitter

Effecting:
*Nerve impulse transmission
*Brain growth and development
 Normal Functions of Acetylcholine &
Acetylcholinesterase

ACh Choline
AChE +
Acetate
Transmits nerve impulse
across synapse
Morphogen in developing
brain affecting:
– cell division
– differentiation Neurite growth
– synaptogenesis
– apoptosis
 Organophosphate Pesticides (OP)
Mechanisms of Toxicity

1. Normal:
ACh Choline + Acetate
AChE

2. With OP pesticide:

ACh Choline + Acetate

OP - AChE
 Disruption of ACh & AChE
Function by Dursban
ACh Choline + Acetate
Dursban-AChE
Transmission of nerve impulses
Altered morphogenesis
• Cell division
• Differentiation Neurite growth
• Synaptogenesis
• Apoptosis

Noncholinergic Dursban effects:

DNA synthesis, interfering with cell signaling cascades
(cholinergic and noncholinergic cells)
 Organophosphate Pesticide (OP)
Effects in Laboratory Animals
OP Cellular effect Behavior
DFP muscarinic cholinergic hyperactivity
receptors in brain

Dursban muscarinic cholinergic altered reflexes

receptors in brain righting
cliff avoidance

brain weight auditory startle

Diazinon delayed reflexes

contact placing
All low dose (<7 mg/kg/day) coordination
Early developmental exposure endurance
 Organochlorine Pesticides

• Background Information
• 7 Common Characteristics
• 5 Major Groups of OC’s
 Background
• DDT’s success stimulated the production
of several OC pesticides
• Successful eradicators
• Severe toxic effects
• Currently in the U.S. and Europe OC’s are
not a major pesticide, but they are in
developing countries and tropical regions
• Cost-benefit
 7 Common Characteristics
1. Atomic structure
2. Lipid solubility
3. Persistence
4. Bioaccumulation
5. Toxicity
6. Physiological Response
7. Interactions
 1. Atomic Structure
• Characterized by the presence of carbon,
chlorine, and hydrogen (sometimes
oxygen)
• Cyclic carbon chains (benzene ring)
Atomic Structure
 2. Lipid Solubility
• High lipid solubility (non-polar)
• High log Kow
• Stored in lipids/fat
– Fasting can cause reentry into circulation
 3. Persistence
• Persistence is based on the half lives in
the organism and in the environment
• Stable compounds
• Physical and biological influences
– Environmental
– Organism
 Persistence
• Dependent on the compound…
– Aldrin is rapidly metabolized
– Endrin and dicofol have short half lives in an
organism and in the environment
– DDT, it’s metabolites and dieldrin are
extremely persistent
 4. Bioaccumulation
• Accumulation of pesticides through absorption through
skin, gills, or food
• Bioconcentration and biomagnification
• Aquatic organisms vs. terrestrial organisms

80.000x

85.000x

500x

265x
 5. Toxicity
• Biochemical lesions
• Neuroactive agents
• Ingestion, inhalation and dermal
absorption
• Mortality
– Lethal brain and liver residues indicate
biochemical lesions
• Influences on toxicity
 Toxicity
• DDT
– Acts on CNS by interfering with ion movement
through neuronal membranes
– 4 mechanisms
• Na2+ and K+
• ATP
• Ca 2+ inhibition
• Ca2+Mg2+
– Maintain depolarization, which leads to hypersensitive
neurons
– Persistent tremoring, seizures or convulsions
 Toxicity
• Cyclodienes
– Alter the neurotransmitter gamma-
aminobutyric acid (GABA)
– Inhibit Na2+, K+, and Ca2+Mg2+ channels
• HCH
– Block chloride ion
– Alter Ca2+ levels
 6. Physiological Response
• Induced enzyme activity
– Species variations
• Persistence and excretion
• Endocrine disruptors
 7. Interactions
• Synergism, potentiation, antagonism, or
additive toxic effects
– Antagonistic: Japanese quail were treated
with chlordane and later with parathion
– Synergism: Aldrin increases the storage of
DDT
– Additive effects are most common for
industrial chemicals and pesticides
 5 major groups of OC’s
1. Dichlorodiphenylethane
– DDT, dicofol, and methoxychlor
2. Cyclohexane
– Hexachlorocyclohexane (HCH)
3. Chlorinated cyclodiene
– Aldrin, dieldrin, and endrin
4. Toxaphene
5. Mirex and chlordecone
 DDT, DDD, and DDE
(Dichlorodiphenylethane)
• Paul Muller (1939)
• Subsequent discovery of large-scale
mortality of birds, insects, and
invertebrates
• Determination lethal brain residues
• DDE
 DDT, DDD, and DDE
• Adverse affects on wildlife
– Avian populations
• Brown pelicans
• Peregrine falcons
• Osprey and bald eagles
– Fish and bats
 DDT, DDD, and DDE
• DDD sprayed 3 times on Clear Lake,
which lead to bioaccumulation data
• Resistance to DDT
• DDT was banned in 1972
• DDT has estrogenic activity
 Aldrin/Dieldrin (cyclodiene)
• Very toxic
• Aldrin is quickly transformed into Dieldrin
• Adverse affects on wildlife
– Aldrin/Dieldrin spraying in 1960 and 1961 for
Japanese beetles
– Whistling ducks, snow geese, and others
– Gray bats in Missouri
• The combined effects of DDE and Dieldrin
• Aldrin/Dieldrin were banned in 1974
 Endrin (cyclodiene)
• Short half life, but very acutely toxic
• Adverse affects on wildlife
– Brown pelican
– Voles, birds, and quail
• Metabolic pathways
– 12-Ketoendrin is more toxic than endrin
• Endrin was banned in 1979
 Hexachlorocyclohexane (HCH)
(Cyclohexane)
• Lindane (gamma isomer)
• Persistent or easily eliminated?
• Some isomers were voluntarily canceled
by the primary manufacturer in 1978;
lindane is still in use
 Dicofol (dichlorodiphenylethane)
• Produced from DDT
• Persistence or Elimination?
– Adverse affects on wildlife
– Ecotoxicological studies
• Dicofol products that contain >1% of DDT
ceased in 1989, products with <1% are
still in use
 Methoxychlor
(dichlorodiphenylethane)
• Replaced DDT in treating Dutch elm
disease
• Rapidly broken down
• Estrogenic activity
• Still in use
 Thank you
Salam dari kebun buah jambu Kristal bebas pestisida