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  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  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.

 Glyphosate binds to and blocks enolpyruvylshikimate- 3-phophate synthase enzyme (EPSPS).  This enzyme is located within the chloroplasts.  It catalyzes the reaction of shikimate- 3-phosphate (S3P) and phosphoenol pyruvate to form 5- enolpyruvyl-shikimate- 3-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. Mechanism of Action of Glyphosate Pesticides

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

 Birth defects  Toxicity to fetus  Production of benign or malignant tumors  Genetic changes  Blood disorders  Nerve disorders  Endocrine disruption  Reproduction effects Chronic exposure may include: 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. Symptoms of Exposure for Organophosphates and Glyphosate

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.

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 ( ) 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 immuno- suppressors.  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.

 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. Current Research Relating Pesticides to Cancer

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.

 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. Summary and Conclusions

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): Print.  George, Jasmine, and Yogeshwer Shukla. "Pesticides and Cancer: Insights into Toxicoproteomic-based Findings." Journal of Proteomics (2011):  Gilbert, Steven. "Organophosphates." Toxipedia. 30 May Web. 3 Feb  "Glyphosate: General Fact Sheet." National Pesticide Information Center. Web. 11 Apr  "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 Web. 11 Apr  "Insecticide Poisoning." Medline Plus. National Institues of Health. Web. 2 Apr

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):  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):  "Nerve Agent and Organophosphate Pesticide Poisoning." Centers for Disease Control and Prevention. 14 Feb Web. 2 Apr  Organophosphorus Insecticides: Diakyl Phosphate Metabolites. Centers for Disease Control and Prevention, 4 Dec Web. 3 Feb  "Pesticides: What You Need to Know." Natural Resources Defense Council. 7 Feb Web. 3 Feb  Than, Ker. "Organophosphates: A Common Deadly Pesticide." National Geographic 18 July 2013.