Pesticides in Clinical Care
Part I
What is a Pesticide?
A substance or mixture used for preventing,
destroying, repelling, or mitigating any pest.
A pest is any harmful, destructive, or
troublesome animal, plant or microorganism.”
Environmental Protection Agency (EPA)
Federal Insecticide, Fungicide and Rodenticide Act
What is a Pesticide? Examples
Herbicides
Generally not very toxic to humans: a few
exceptions
Fungicides
More frequently sensitizers. Some are carcinogenic,
mostly not acutely toxic
Insecticides
Generally acutely toxic group of pesticides
Fumigants
Gasses that kill most everything
Rodenticides
Newer rodenticides primarily anticoagulants
Disinfectants
Nano-silver (a recent EPA decision). Toxicity yet to be
determined
What Do We Know About a Pesticide?
Pesticide Registration by EPA
• EPA responsible for registering pesticides
– Toxicity tests required in registration process
• Acute toxicity (LD50)
– Oral, Dermal, Inhalational
• Subchronic and Chronic toxicity
– Delayed neurotoxicity
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Reproductive toxicity
Teratotogenicity
Developmental toxicity
Mutagenesis-oncogenesis-genotoxicity
Metabolism and fate studies
What Don’t We Know
• Long term effects of low level exposure on
human populations
• Long term neurodevelopmental effects on
humans
• Effects of Mixtures
• Effects of “inert ingredients”
• Effects of some newer pesticides on humans
• Non specific toxicological mechanisms and
consequences of some pesticides
Brief History of Major Pesticides
• Prehistory: Sulfur
– First seen in Egyptian writings 2400 B.C.
and Chinese writings 1500 B.C.
– Greek writings
• 700 BC
Before World War II
Metals and Salts
Arsenites. Paris Green,
A gem of a pesticide - copper acetoarsenite.
circa 1867 This was introduced and used first as
a pigment, known as Emerald Green, later as a
pesticide.
Other arsenic preparations and products of the dye
industry were also used
Paris Purple
London Purple
The Control of Other Pests
• Bordeaux mixture
– (copper sulfate and
hydrated lime)
• First effective fungicide,
1882
– Pierre M. A. Millardet,
– French National Hero
Before World War II
Lead Arsenate Very Important
Lead Arsenate to fight the gypsy moth 1892.
• Heavily used in much of agriculture
• Heavily used in apples
• Soil contamination remains a problem today in
many old orchard soils in the Northwest
Other Non-metalic Pesticides
• Pyrethrum
– A carefully held secret for many
years 1850– Source is Chrysanthemums
• Nicotine
– Widely used until WWII
– Extremely toxic (LD50 = 1mg/kg)
Discover of New
Insecticides
• Discovery of organophosphates
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Gerhard Shrader: A German Scientist
Attempting to replace Nicotine
Developed organophosphate esters
Tabun, sarin, soman (G gases), parathion
First to be poisoned by nerve gas (tabun)
Discover of New Insecticides
• DDT
– First synthesized by a
German graduate student
Othmar Zeidler in 1873
– Rediscovered by Paul
Mueller, a Swiss
entomologist, in 1939
– World War II, Use of DDT
to control typhus and
malaria.
Paul Müller
Nobel Prize 1948
• “My fly cage was so toxic after
a short period that even after
very through cleaning of the
cage, untreated flies, on
touching the walls fell to the
floor. I could only carry on my
trials after a thoroughly
cleaning and after that leaving
it for about one month in open
air.” Muller Nobel Prize
acceptance speech 1948.
DDT
Safe, Effective, Inexpensive
Used Everywhere
Rachael Carson: A Silent Spring
– January 1, 1973 (EPA)
canceled all uses of DDT in
the US
– By the time of its
cancellation, more than 1
billion kilograms of DDT had
been introduced into the
United States.
When Did We Become Aware of
Pesticide Health Issues?
• Physicians discussed Lead and Arsenic toxicity in
the 1700-1800s
• Animal & human studies on arsenic up to 1940s
• The new pesticides showed some early problems
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1950s reports of pesticide toxicity from OP’s & OC’s
1960s Increasing literature about DDT Health effects
1960s 15 labs in US study health effects of pesticides
1966 First organized study of human OP Persistent
Health effects Tabershaw and Cooper
– Studies of Neurotoxicity of Organophosphates 19702000’s
– Parkinson’s and pesticides 1990-2009- still working