BIO545 Pesticide Slides

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Pesticides
(Organophosphates & Glyphosates)
By Samantha Schulman
Introduction
I chose to do organophosphorus and glyphosate
pesticides because these are two of the most
dangerous types of pesticides.
While they do have certain benefits such as killing
pests and weeds, the proposed risk of serious
adverse health effects is increasing rapidly.
As I researched several studies on different types
of pesticides, it became evident that these
chemicals can in fact be a direct link to various
types of cancer.
The general public should be made more aware of
these potential dangers.
Introduction: What to Expect
You will learn about two of the deadliest types of
pesticides, their history, and what they are used
for.
Their mechanisms of action and why they are so
toxic.
Treatments when exposed to these pesticides.
Current research and what can be done to
prevent the adverse effects of these pesticides.
What is an Organophosphorus Pesticide?
Organophosphates are the most commonly used
insecticides.
There are almost 900 different bug killers that can
be used in the United States; 37 belong to this
specific class of insecticides.
About 70% of the insecticides
in current use in the U.S. are
organophosphorous
pesticides, a total of ~90
million pounds per year.
What is an Organophosphorus Pesticide?
Two of the deadliest types appear to be malathion
and parathion.
Organophosphates are so toxic to humans that the
U.S. Environmental Protection Agency has taken
steps to limit their availability to the public.
They have the same mechanism of action as nerve
gases. That is, they kill insects by disrupting their
brains and nervous systems.
These chemicals can also harm the brains and
nervous system of animals and humans.
Mechanism of Action of Organophosphorus
Pesticides
 It blocks the enzyme
acetylcholinesterase,
an enzyme that
hydrolyzes the
neurotransmitter
aceytlcholine.
 Acetylcholine is
mainly found at
neuromuscular
junctions and
cholinergic brain
synapses of mammals
and insects; its activity
serves to terminate
synaptic transmission.
Mechanism of Action of Organophosphorus
Pesticides
 When
acetylcholinesterase is
inhibited, acetylcholine
builds up in the nerves,
which become
overactive.
 As a result of being
inhibited, the
diaphragm can’t
contract.
 Victims of OP
poisoning often die
due to this nerve and
respiratoy failure, as
they cannot breathe.
Uses for Organophosphorus Pesticides
They are applied to crops, buildings, ornamental
plants and lawns.
Agricultural uses include field applications on corn,
cotton, canola, alfalfa, produce and nuts.
Exterminators use them in residential and
commercial structures.
Certain pest control products for cats and dogs
contain organophosphorus compounds.
History of Organophosphate Use
Originally developed in the 1940s as highly toxic
biochemical warfare agents (known as nerve
agents).
Two relatively recent examples of terrorist use
occurred in Matsumoto, Japan in 1994 and in the
Tokyo subway in 1995.
Both incidents used Sarin, an extremely deadly
OP poision; both incidents caused 18 deaths.
Fortunately, terrorist or warfare use of OP is rare,
but the potential exists to expose many people at
once.
What is a Glyphosate Pesticide?
A non-selective herbicide, meaning it will kill most
plants.
The active ingredient [glyphosate] is a derivative
of glycine, the smallest amino acid found in
proteins.
In a glyphosate molecule, one of the amino
hydrogen atoms of glycine is replaced with a
phosphonomethyl group.
Uses for Glyphosate Pesticides
It is applied to the leaves of plants to kill both
broadleaf plants and grasses.
Usually applied in agriculture, forestry, lawns
and gardens.
History of Glyphosate
First registered for use in the U.S. in 1974.
One of the most widely used herbicides in the U.S.,
the active ingredient in Roundup.
Roundup is a broad-spectrum herbicide and quickly
became one of the best-selling herbicides since
1980.
Mechanism of Action of Glyphosate
Pesticides
They prevent the plants from making certain
proteins that are needed for plant growth.
It stops the shikimic acid pathway, a specific
enzyme pathway only found in plants and some
microorganisms.
This pathway is essential for aromatic amino
acids, hormones, vitamins, and other key plant
metabolites.
Mechanism of Action of Glyphosate
Pesticides
 Glyphosate binds to
and blocks
enolpyruvylshikimate3-phophate synthase
enzyme (EPSPS).
 This enzyme is located
within the chloroplasts.
 It catalyzes the
reaction of shikimate3-phosphate (S3P)
and phosphoenol
pyruvate to form 5enolpyruvyl-shikimate3-phosphate (ESP).
Mechanism of Action of Glyphosate
Pesticides
 Phosphoenol pyruvate
enables glyphosate to
bind to the substrate
binding site of the
EPSPS, inhibiting its
activity and blocks its
import to the cholorplast.
Exposure Pathways of Organophosphates &
Glyphosates
Pathways:
Ingestion
Hand-to-mouth
contact with
contaminated
surfaces
Inhalation
Dermal contact
 OP pesticides have better
gastrointestinal than
dermal absorption.
 Glyphosate isn’t likely to
vaporize after it is sprayed.
Symptoms of Exposure for
Organophosphates and Glyphosate
Acute symptoms may include but are not limited to:
Nausea
Vomiting
Cholinergic
effects
Weakness
Paralysis
Seizures
Coma
Death
Mild to severe
peripheral
neuropathies
Residual deficits
in neurocognitive
functioning
Many other
organs/physical
processes may
also be affected
Symptoms of Exposure for
Organophosphates and Glyphosate
Chronic exposure may include:
Birth defects
Toxicity to fetus
Production of benign or
malignant tumors
Genetic changes
Blood disorders
Nerve disorders
Endocrine disruption
Reproduction effects
Symptoms of Exposure for
Organophosphates and Glyphosate
Most common route of exposure is by ingesting
contaminated food and hand-to-mouth contact with
surfaces containing these pesticides.
Less common routes are inhalation and dermal
contact.
Glyphosate does not easily pass through skin; if
taken in by skin or mouth it goes through the body
in less than 1 day, and leaves in urine and feces.
Inhalation of glyphosate mist can cause irritation of
the nose and throat.
Symptoms of Exposure for
Organophosphates and Glyphosate
Swallowing glyphosate can cause increased
saliva, burning of mouth and throat, vomiting and
diarrhea.
Pets exposed to glyphosate may drool, vomit,
have diarrhea, lose their appetite or seem sleepy.
Rat studies have shown ~1/3 of a dose of
glyphosate was absorbed by the rats’ intestines:
½ of the dose was found in the rats’ stomachs
and intestines 6 hours later.
All traces were gone within 1 week.
Who is at the Most Risk of Exposure?
Farm workers, gardeners, florists, pesticide
applicators and manufacturers of these
pesticides.
Children likely to be more vulnerable than adults
because they spend more time close to the
ground/floor where pesticides are applied.
Due to their growing bodies, the brain and
reproductive organs of children may be altered in
long-term or permanent ways after being
exposed.
 Any exposure increases cancer risk.
Treatment for Pesticide Poisoning
Depending on symptoms and exposure duration,
hospitals may use the following treatments:
Activated charcoal
Breathing support, including tube through the
mouth into the lungs, and breathing machine
(ventilator)
Bronchoscopy -- camera down the throat to
see burns in the airways and lungs
Chest x-ray
Treatment for Pesticide Poisoning
EKG (heart tracing)
Endoscopy -- camera down the throat to see
burns in the esophagus and the stomach
Fluids by IV (through the vein)
Medicine (antidote) to reverse the effect of the
poison
Tube through the mouth into the stomach to
empty the stomach (gastric lavage)
Treatment for Pesticide Poisoning
Surgical removal of burned skin (skin
debridement)
Washing of the skin (irrigation) -- perhaps every
few hours for several days
If you are unsure of what to do, the National
Poison Control Center (1-800-222-1222) can be
called from anywhere in the U.S. This national
hotline number will let you talk to experts in
poisoning and will give you further instructions.
Current Research Relating Pesticides to
Cancer
According to several studies, exposure to
pesticides can result in various health effects.
In humans, several pesticides have been
recognized as carcinogens and strong immunosuppressors.
Relative risks of cancer occurrence in children are
associated with parental exposure to occupational
or non-occupational pesticides.
Studies have shown an increase in the risk of
leukemia, non-Hodgkin’s lymphoma, brain tumors,
Wilm’s tumors, Ewing’s sarcomas, and germ cell
tumors in children.
Current Research Relating Pesticides to
Cancer
A positive link between pesticides and prostate
cancer has also been put forward:
OP pesticides and polymorphisms of
xenobiotic metabolizing enzymes, particularly
CYP1A1, are reported to be associated with
the possible risk of prostate cancer.
CYP1A1 enzyme metabolizes several
carcinogens and estrogens.
This increases cancer risk.
Current Research Relating Pesticides to
Cancer
 A positive link between pesticides and breast cancer
has also been put forward.
Results from studies have shown that estrogen
combined with malathion or parathion altered
cell proliferation and induced cell transformation.
It also exhibited significant invasive capabilities
as compared to the control cell line.
Therefore, researchers suggest that pesticides
and estrogens affect human breast cells
inducing molecular changes indicative of
transformation.
Current Research Relating Pesticides to
Cancer
Epithelial cells are more susceptible to the
cytotoxic and DNA-damaging properties of
Roundup.
With glyphosate, researchers found genotoxic
effects after short exposure concentrations that
corresponded to a 450-fold dilution of spraying
used in agriculture.
Recent findings indicate that inhalation of this
glyphosate spraying, particularly exposure to
Roundup, may cause DNA damage and cancer
in exposed individuals.
Current Research Relating Pesticides to
Cancer
Despite all of this current research, the
mechanism triggering the induction of
carcinogenesis by pesticides is still unknown.
More studies are therefore needed.
Summary and Conclusions
Organophosphorus pesticides:
Originally developed for use as chemical warfare
nerve agents.
Today, they are mainly used as insecticides.
These pesticides block the enzyme
acetylcholinesterase, which causes acetylcholine
to build up in the nerves.
This over activity of the nerves leads to nerve and
respiratory damage, or death from suffocation.
Summary and Conclusions
Glyphosate:
The active ingredient in Roundup, the most
widely used herbicide in the U.S.
It works by stopping the shikimic acid pathway
of plants, a process needed for the biosynthesis
of aromatic amino acids.
In humans, spraying of glyphosate, especially in
Roundup, may potentially cause DNA damage
and cancer in exposed individuals.
Summary and Conclusions
Therefore, due to the impact these pesticides
can potentially have on human health, more
restrictions need to be implemented.
Possibly implement a ban on Roundup as
well, since it is the most widely used pesticide
and more and more studies are showing an
increased risk of cancer.
References
 Calaf, G.M., and D. Roy. "Cancer Genes Induced by Malathion and Parathion
in the Presence of Estrogen in Breast Cells." International Journal of Molecular
Medicine 21 (2008): 261-68. Print.
 George, Jasmine, and Yogeshwer Shukla. "Pesticides and Cancer: Insights
into Toxicoproteomic-based Findings." Journal of Proteomics 74.12 (2011):
2713-722.
 Gilbert, Steven. "Organophosphates." Toxipedia. 30 May 2014. Web. 3 Feb.
2015. <http://www.toxipedia.org/display/toxipedia/Organophosphates>.
 "Glyphosate: General Fact Sheet." National Pesticide Information Center.
Web. 11 Apr. 2015. <http://npic.orst.edu/factsheets/glyphogen.html>.
 "Glyphosate: Mechanism of Action." Glyphosate Facts: Transparency on
Safety Aspects and Use of Glyphosate-Containing Herbicides in Europe.
Industry Task Force on Glyphosate, 19 June 2013. Web. 11 Apr. 2015.
<http://www.glyphosate.eu/glyphosate-mechanism-action>.
 "Insecticide Poisoning." Medline Plus. National Institues of Health. Web. 2 Apr.
2015. <http://www.nlm.nih.gov/medlineplus/ency/article/002832.htm>.
References
 Koller, Verena, Maria Furhacker, Armen Nersesyan, Miroslav Misik, Maria Eisenbauer, and
Siegfried Knasmueller. "Cytotoxic and DNA-Damaging Properties of Glyphosate and
Roundup in Human-derived Buccal Epithelial Cells." Archives of Toxicology 86.5 (2012):
805-13.
 Kumar, Vivek, Chandra Shekhar Yadav, Satyender Singh, Sanjay Goel, Rafat Sultana
Ahmed, Sanjay Gupta, Rajesh Kumar Grover, and Basu Dev Banerjee. "CYP1A1
Polymorphism and Organochlorine Pesticide Levels in the Etiology of Prostate Cancer."
Chemosphere 81.4 (2010): 464-68.
 "Nerve Agent and Organophosphate Pesticide Poisoning." Centers for Disease Control and
Prevention. 14 Feb. 2013. Web. 2 Apr. 2015.
<http://emergency.cdc.gov/agent/nerve/tsd.asp>.
 Organophosphorus Insecticides: Diakyl Phosphate Metabolites. Centers for Disease
Control and Prevention, 4 Dec. 2013. Web. 3 Feb. 2015.
<http://www.cdc.gov/biomonitoring/OP-DPM_BiomonitoringSummary.html>.
 "Pesticides: What You Need to Know." Natural Resources Defense Council. 7 Feb. 2012.
Web. 3 Feb. 2015. <http://www.nrdc.org/health/pesticides/>.
 Than, Ker. "Organophosphates: A Common Deadly Pesticide." National Geographic 18
July 2013.
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