1. The Effects of Organophosphate Insecticides on Human Development
Carly Gehler1, Emily Roderick1, Kathryn Egleston1
1. Colorado State University: Department of Food Science and Human Nutrition | Fall 2015
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References
Organophosphate (OP) insecticide use in America recently gained attention due
to its negative health impacts. Our research evaluates the effects of OP insecticides
on the physiological health of farmworkers because of their increased exposure.
OPs block the enzyme acetylcholinesterase and cause oxidative stress on the body.
The consequential build-up of acetylcholine contributes to reduced fertility, altered
glucose metabolism, and cognitive decline. We recommend that it may be helpful
for farmworkers to increase antioxidant sources in their diet to counter the effects of
oxidative stress caused by OP poisoning.
Abstract
Introduction
The enzyme acetylcholinesterase (AChE) controls the extensive hydrolysis
(breakdown) of acetylcholine.5 Acetylcholine is a neurotransmitter that affects neurons
throughout the body.6 Organophosphates (OPs) act as latent or direct inhibitors of
AChE.7 Latent inhibitors require activation in the body whereas direct inhibitors enter
the body activated.7 When an OP contacts AChE, the phosphorous ester group of the
OP covalently modifies the enzyme through phosphorylation. The phosphorylation
deactivates AChE and prevents it from hydrolyzing acetylcholine.7 Depending on the
group attached to the phosphate, this phosphorylation is irreversible.7 OP poisoning
occurs when concentrations of OPs in the system phosphorylate additional AChE
enzymes. Ultimately, the inhibition of AChE leads to an accumulation of acetylcholine
and contributes to reduced fertility, altered glucose metabolism, and cognitive decline.8
Physiological Aspects
Oxidative stress caused by organophosphate (OP) poisoning leads to cellular
damage of reproductive gametes, pancreatic beta cells, and neurons.8,9,13 Lipid-
soluble vitamins A and E reduce oxidative stress in cellular membranes by
neutralizing the unpaired electrons in reactive oxygen species (ROS).14,15 This
mechanism implies that vitamin A and E intake may be beneficial in reducing
cellular oxidative stress in farmworkers.
Antioxidants
In October of 2015, the EPA proposed further bans on organophosphate (OP)
use in agriculture.16 These additional precautionary measures strengthen OP
poisoning as a public health issue. The scientific literature suggests that increased
exposure to OPs may reduce fertility, alter glucose metabolism, and attribute to
cognitive decline.8,9,13 OPs contribute to oxidative stress in the body and we
recommend to those with increased exposure, such as farmworkers, consume
antioxidants as a preventative measure.12 In addition, nutrition professionals need
to be aware of this issue and understand the impact of OPs on the health of
farmworkers.
Conclusions
Recently, the EPA developed stricter workers’ protection guidelines for
farmworkers using organophosphate (OP) insecticides.1 The EPA estimates that
10,000-20,000 physician-diagnosed pesticide poisonings occur each year among
the two million American farmworkers.2 Farmworkers have an increased risk for
developing diabetes, infertility, and brain damage due to prolonged exposure to OP
insecticides.3,4 Health professionals need to understand the mechanism behind the
effect of OP insecticides on human development to properly diagnose and treat
patients.
• To describe the mechanism of organophosphate poisoning
• To educate health professionals about consequences of organophosphate
poisoning on human development
• To provide nutrition recommendations for prevention through antioxidants
Objectives
Outcome Mechanism/Physiology
Reduced
fertility
• Inhibition of AChE in the hypothalamus causes inconsistent release
of sex hormones (such as GnRH, FSH, and LH), thereby creating an
imbalance that can lead to infertility.8,9
• Oxidative stress from high levels of OPs causes DNA damage to
both sperm and eggs which decreases quality.9
Altered glucose
metabolism
• Increased acetylcholine leads to pancreatic beta cells with reduced
glucose sensitivity which contributes to insulin resistance seen in
chronic OP exposure.13
• Damaged beta cells produce insufficient insulin and contribute to the
development of diabetes.8
• The induction of oxidative stress by OPs on beta cells alters glucose
metabolism.8
Cognitive
decline
• From OP-induced oxidative stress and mitochondrial dysfunction,
dopamine released at toxic levels can result in the development of
Parkinson’s disease.8
• Damage from cholinergic neuronal dysfunction and excitotoxicity can
cause memory, cognitive, emotional, sensory, and motor skill
damage.8
History reveals that pest control is not a new idea. Farmers in ancient Rome
used natural pesticides such as salt and sulfur to control unwanted weeds and
insects to thereby increase yields.11 After the Roman Empire and throughout the
1800s, laboratory-synthesized pesticides became an effective way to control pests.
Unfortunately, due to similarities in physiology between insects and humans, most
of the effective chemicals also compromised human health.
Unwanted side effects remained inevitable until, in the early 1900s, a
breakthrough emerged with the discovery of organophosphates (OPs). The term
“organophosphates” encompasses a broad group of insecticides that acts on an
enzyme called acetylcholinesterase (AChE). At certain doses, OP-induced inhibition
of acetylcholinesterase affects insects lethally. Use of OPs on crops expanded
across America in the late 1900s because they effectively controlled pests with
seemingly no harmful side effects to humans.
However, some scientists questioned the safety of OPs due to their original use
as biological weapons. During World War II, Germans used OPs on humans
because they inhibited the same enzyme, AChE, in humans.10 The lethal dose of
OP is considerably higher in humans than in insects, therefore OP use on crops
continued. Nonetheless, evidence showing the harmful effects of lower exposure to
OPs solidifies daily. In the early 2000s, the EPA began regulating use of OPs.10 The
future use of OPs in agriculture is being reevaluated.
Organophosphates
We would like to thank Ashley Colpaart MS RDN for her professional assistance
and guidance.
Acknowledgement
Created by Emily Roderick
Created by Emily Roderick