Pesticides

Principles of Toxicology
 Pesticides

• EPA definition: “substances or mixtures

of substances intended for preventing,
destroying, repelling or mitigating any
pest…”
 A bit of history…
• 1930’s - modern era chemistry
– Alkylthiocyanate
– Dithiocarbamate
– Bromide compounds
• WWII -
– DDT
– Dinitrocresol
– 2,4 D
• Since then, synthesis with goal improved specificity,
reduced toxicity…

• No such a thing as “safe pesticide”

 Pathways of pesticide movement
• Runoff
• Chemical degradation
• Volatilize (gas vapor)
• Leaching and breakdown in soil
• Leaching and degradation by microbes
• Photo degradation (sun)
 Factors influencing a pesticide’s fate

• Properties of the pesticide

• Conditions where & when applied
• Application method
 Properties of the pesticide
• Vapor Pressure (volatility) – pesticides with
a high vp are more likely to change to a
gas and escape into the atmosphere.
• Sorption – attraction to soil surfaces,
pesticides with higher sorption values have
reduced leaching
 Properties of the pesticide
• Water Solubility/dissolvability - more
soluble pesticides have lower sorption and
are more mobile in the environment as
they are leached or moved with runoff.
• Persistence – the amount of time a
pesticide remains in the environment,
measured by half-life. Pesticides with
longer half-lives pose a greater threat to
the environment.
 Pesticides
•Organochlorines
•ChE inhibitors
•Organophosphates
•Carbamates
•Phenoxyherbicides
•Pyrethroids
•Bromine-based
•Phenol- derivatives
•Dipyridyl derivatives
INSECTICIDES
 1. Organochlorine insecticides
(CHLORINATED HYDROCARBONS)
)
Chemical structures of chlorinated hydrocarbon insecticides. 
 Organochlorine insecticides
• DDT
– first commercially produced insecticide (1940’s)
– banned in the US in the 1970’s but is still manufactured and
exported (1 ton/day)
• Cyclodienes
– Most toxic (CNS) and persistent pesticides known
• HCH and Cl-benzene
– Mixtures of isomers
– Medicinal use (lice shampoo) (lindane)
•t1/2 = 7-30y •Non-selective
•Bioaccumulates •Endocrine disrupter
•Persistent •Reproductive toxins
•Lipophilic •Neurotoxins (Lindane)
 Observed effects
• DDT
– Enzyme induction
• Cyclodienes
– Reproductive toxicity (reduced fertility, teratogenic)
– CNS toxicity
• HCH and Cl-benzene
– CNS toxicity
– Increased hepatocellular tumors (mice)
 DDT

» Very low vapor pressure, extremely low solubility in

water (1.2 ppb), and high solubility in oils
» The half-life of DDT is estimated to be 7 to 30 years,
depending on the environment
» The 96- hour LC for 19 species of fish ranges from 1.8
50

to 22 ug/l
» DDT is degraded to DDE (ethylene 1,1-dichloro-2,2-
bis(p-chlorophenyl) or dichlorodiphenyl dichlor-
oethylene) or DDD (ethane 1,1-dichloro-2,2-bis(p-
chlorophenyl))
 Cholinesterase inhibitors
• Organophosphates (OP) and Carbamates
– Strong Acute neurotoxicity -
– Nervous system toxins
2. ORGANOPHOSPHORUS COMPOUNDS

» Organophosphorus insecticides are the most

toxic among the insecticides; they are dangerous
not only to insects but also to mammals
» Many of these compounds, such as parathion,
paraoxon, timet, and tetram, are in the ‘‘super
toxic’’ category of human poisons
» Human fatal doses for these toxicants are <5
mg/kg, along with arsenic (As), cyanide (CN ) and
�

some others. As little as 2 mg of parathion has

been known to kill children.
 3. Carbamates
» The carbamates are derivatives of
carbamic acid (HO–CO–NH ). Carbamates
2

are widely used for worm control on

vegetables
» A monitoring program revealed that 1121
(13.5%) of 8404 wells tested exceeded the
state’s recommended guideline of 7 ppb
» Aldicarb and carbofuran
 1st OP: TEPP
(tetraethylpyrophosphate), followed by
parathion
1st carbamic: 1930

WWII chemical warfare

1988 Iraq- against Kurds
1994 Japan
1995 Tokyo subway
Cholinesterase
O
+
CH C - O - CH - CH - N(CH )
3 2 2 3 3

Esteratic Anionic

O
+
CH3C-O- + HO-CH2-CH2-N(CH3)3
 Organophosphates

R1 O
Parathion
P X
R2 Malathion
Soman
Ecothiophate

R1-2 = aliphatic X = e- withdrawing

Organophosphates
Strong Covalent Bond,
R1 O Inactivates Enzyme
(stable >100h)
R2 P X Aging of complex

Esteratic Anionic
 HERBICIDES 

» During the Vietnam War, the U.S. Air

Force’s defoliation program applied a huge
quantity of undiluted 2,4-D (2,4-
dichlorophenoxy acetic acid) and 2,4,5-T
(2,4,5-trichlorophenoxy acetic acid)
».
 Herbicides
• 1.9% increase/year between 1980-1985 (x2 of
insecticides) due to:
– Monoculture
– Mechanization of agricultural processes

• Categories by application:
– Pre-planting
– Pre-emergent
– Post-emergent
• Low mammal toxicity
• Suspected mutagens, carcinogens, teratogens
• Skin irritants
 Phenoxyherbicides
• Introduced in 1946
• 2,4Dichloro- and 2,4,5Trichloro
phenoxy acetic acids
• Defoliants (Vietnam war) -
Forestry
Chemicals that have an ACR of less than 10 typically have low to no chronic toxicity associated with them 
Thank You
 Pyrethroids
Newer (1980) but were 30% of all use by 1982

Extensive agricultural use

Indoor use
Pet flee control
Household plants

Modify Na+ channel kinetics

Abnormal repetitive discharges
Type A shorter action than type B
Avermectins
New generation pesticides
 Dipyridyl derivatives
“startling human toxicity”
Banned in many countries but still in use in 130 others
Lung is the most susceptible target organ
Highly polar- poor GI absorption (5-10%)

LD50=22-262mg/kg

LD50=100-400mg/kg
 Chloroacetanilides
Only slight acute toxicity but Carcinogens
of category 2B
Metabolic activation to mutagenic
metabolite (DEBQ1)
1985 Canada incident (well water
contamination)
 Phosphomonomethyl aminoacids

•Non-selective systemic
herbicides
•Free acids or salts -
ocular and mucus membrane
irritants
•Class E carcinogens (EPA)
•Solvent may be the toxic
compound (POEA)
 Fungicides
• Lipophilic, accumulate
• 90% are carcinogenic in
animals --> 75 mil pounds
produced annually
• 10% acreage but 60% of total
dietary carcinogenic risk
• Contaminants are dioxins and
furans

• Hexachlorobenzene (banned)
• Pentachlorophenol (banned)
• Phthalimides
• Dithiocarbamates
 Fungicides
• Dithiocarbamates
– Ferbam, ziram, maneb, zineb, nabam (metal-based names)
– Some reported as teratogenic
– Degradation to ethylene thiourea (ETU): a known mutagen,
carcinogen, teratogen and antithyroid compound.
– Some neurotoxicity at high doses
– May cross into CNS if bound to divalent metals
 Fumigants
• Very volatile - inhalation exposure
• Non-selective, highly reactive and cytotoxic
– acrylonitrile
– carbon disulfide
– carbon tetrachloride
– ethylene dibromide (gastric carcinomas, sterility)
– ethylene oxide (carcinogen, developmental tox.)
– phosphine (PH3) released from aluminum phosphide (AlP) in
moist conditions (grain storage)
Chemicals that have an ACR of less than 10 typically have low to no chronic toxicity associated with them