ORGANOPHOSPHATES
Organophosphates were first developed by Germany during World War II by the I.G. Farben
Company, which developed them as nerve gas agents in warfare. When two or more
organophosphates are absorbed, the effect is potentiation (more than additive) since enzymes
critical to degrading one are inhibited by the other.1 Organophosphates can damage
autonomic nerves, peripheral nerves and the brain.1 Organophosphates interfere with the
function of the nervous system by interfering with nerve transmitters, including muscarinic,
nicotine, and brain nerve transmitters. Muscarinic nerve receptors, which are located in
organs such as the heart, endocrine glands, blood vessels, and other smooth muscle organs
have altered function resulting in symptoms such as wheezing, nausea, abdominal cramps,
visual disturbance, and even vomiting. Nicotinic nerve receptors are located in the nerves of
skeletal muscles and the ganglia of the autonomic nervous system and interference with their
function causes symptoms such as muscle twitching and cramping, fatigue, weakness, rapid
or irregular heart rate, and changes in blood pressure. Delayed effects can occur as well
following acute or repeated chronic exposures. These can involve the peripheral nerves
resulting in impaired balance and increased weakness. The nerves controlling the intestinal
and urinary tract can be interfered with causing reduced control of bladder and bowel
function.
Neurotransmitters in the brain can also be affected by organophosphate compounds resulting
in symptoms such as confusion, tremors, poor coordination, sleep disturbance, weakness,
anxiety, impaired coordination, mood alterations, etc. Persistent neurobehavioral alterations
in brain function can also result. There are also reports in the literature for both humans and
animals of disturbances of porphyrin metabolism, which can be persistent following
exposure to organophosphates. Other changes with organophosphates includes increased
susceptibility to infectious diseases, possibly because of disturbances of immune function,
impaired liver function, loss of vigor and acceleration of the aging process as well as loss or
decline in potency and libido. Both chlorpyrifos and diazinon have been associated with
alterations in brain function in humans consistent with the general description for
organophosphates above.
Organophosphates have been rated by other authors to exacerbate fatigue and cause toxicity
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to the brain and other parts of the nervous system.2 3 4 5 6 7 8 9 10 They can also induce
heightened sensitivity.11
Organophosphate pesticides are potent neurotoxins that can cause long term, persisting
neurologic and neurotoxic damage to humans.12
Organophosphates stimulate muscarinic receptors by their inhibition of acetylcholine.
Muscarinic receptors are known to increase nitric oxide. Increased nitric oxide production
can then lead to neural sensitization with heightened response to many chemicals at low
doses. This is the biochemical basis of the observations decades ago by Tabershaw and
Cooper of heightened sensitivity to chemicals in organophosphate exposed persons.11
Organophosphates
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1
Recognition and Management of Pesticide Poisonings, US EPA, 1989 and 1999. (This reference focuses on acute poisoning
effects, not chronic effects).
2 Sherman JD., “Organophosphate pesticides-neurological and respiratory toxicity”, Toxic and Indust Health 11(1): 33-39, 1995.
3 Duffy FH., et al, “Long-term effects of an organophosphate upon the human electroencephalogram”, Toxic and App Pharm 47:
161-176, 1979.
4 Rosenstock L., et al, “chronic neuropsychological sequelae of occupational exposure to organophosphate insecticides” Am J Indus
Med. 18: 321-325, 1990.
5 Gershon S., Shaw FH., “Psychiatric sequelae of chronic exposure to organophosphorus insecticides” Lancet June 24 1961, pp
1371-1376.
6 Savage EP., et al., “Chronic neurological sequelae of acute organophosphate pesticide poisoning”, Arch Environ Health 43: 3845, 1988.
7 Stalberg E., et al., “effect of occupational exposure to organophosphorus insecticides on neuromuscular function”, Scand J Work
Environ Health 4: 255-261, 1978.
8 Ernest K., et al., “Delayed effects of exposure to organophosphorus compounds”, Inter J Med Res 101:81-84, 1995.
9 Steenland K., et al., “Chronic neurological sequelae to organophosphate pesticide poisoning”, Am J Pub Health 84(5): 731-736,
1994.
10 Korsak RJ., Sato MM., “Effects of chronic organophosphate pesticide exposure on the central nervous system”, Clin Toxic 11(1):
83-95, 1977.
11 Tabershaw IR., Cooper WC., "Sequelae of acute organic phosphate pesticide poisoning." Journal of Occupational Medicine 8:520, 1966.
12 El-Fawal HA, et al, “Neuroimmunotoxicology: humoral assessment of neurotoxicity and autoimmune mechanisms.” Environ
Health Perspect 107 Suppl 5:767-75, Oct, 1999.