Neurological Effects of Pesticides
- Associate Professor Medicine and Environmental Health Sciences
- Director, International Scholars in Occupational and Environmental Health
Neurological Effects of Pesticides
- Big Disasters-Famous events
- The pesticides that target the nervous system
- Cholinesterase inhibitors
- Others with suspected neurological effect
Famous Events Neurological Pesticide History
- Mercury flour consumed in Iraq
- In 1956 and again in 1961 households consumed Mercury treated flour
- Over 100 died and many were left with permanent neurological damage
- Mercury treated wheat seed 1971. Methyl mercury treated grain used for bread. 50 thousands poisoned, 5 thousand dead.
- Poor families consumed methyl mercury treated seeds in 1963-64.
- Tens of children poisoned.
- A family consumed pigs fed organomercurials.
- Two children remain in coma, an in utero child developed an evolving neurological syndrome with hypotonia, irritability and nystagmus
Ginger Jake Not a Pesticide Incident
- Tri-Ortho Cresyl Pyrophosphate (TOCP)
- Lindol (TOCP containing solvent)
- Added to Jake, a popular ginger flavored concoction
- Thousands, potentially 50,000 people developed peripheral and central long tract disease.
- The event became folklore
- 30 years later, survivors still affected
- “Jake Leg” 13 folk songs describe it.
TOCP in South Africa & Morocco
- Triortho-cresyl-phosphate a lubricating fluid additive sold in cooking oil
- 60 people suffered paralysis
- A cohort of workers in Hopewell VA at a Chlordecone factory, exposed to work conditions which resulted in significant over-exposure
- Tremors, anxiety, irritability, memory loss
- Myoclonic jerking, ataxia
- One rock group and one Dead Kennedy’s song
Structure of the Nervous System
- Central Nervous system (CNS)
- Peripheral Nervous System (PNS)
- Peripheral sensory nerves
Nervous System is Vulnerable
- Limited regenerative capacity
- Damage may not be repaired
Pesticides Which Target the Nervous System
- Organophosphates/ Carbamates
- CNS Alpha receptor agonists
Organophosphates and Carbamates
- Cholinesterase is found in the nerve junction
- It turns off the chemical messenger that tells muscles, glands and nerves to function
- When it is inhibited the messenger builds up and overstimulates muscles, glands and nerves
Organophosphates The Target: Cholinesterase
- Essential for nervous system function
- Important in voluntary muscles, autonomic & central nervous system
- The target of a specific group of widely used pesticides
Toxicity of Cholinesterase Inhibitors Organophosphates /Carbamates
Organophosphate Induced Peripheral Neuropathy
- Rare complication of a few pesticides
- Generally believed to require high level intoxication
- Inhibition of Neuropathy Target Esterase (NTE)
- Pain followed by weakness in legs
- Loss of reflexes, Flaccid paralysis
Persistent CNS Effects after Acute OP Poisoning
- Altered attention, memory, higher cognitive function
- Reported by patients and families
- Four Population Investigations Support this
- Savage, Rosenstock, Steenland Wesseling
- Chronic low level exposure Does not appear to do this. A few studies to the contrary.
- “ COPIND” chronic organophosphate induced neuropsychiatric disorders.
Long-Term Effects of Acute Organophosphate Poisonings
- The British Ministry of Health, 1999
- “Neuropsychological abnormalities can occur as a long-term complication of acute OP poisoning”
- “Peripheral neuropathy .. Is a well established complication of poisonings by OPs that inhibit Neuropathy Target Esterase”
- Other OPs can do similarly but the neuropathy is less severe
OP-induced Intermediate Syndrome
- Respiratory paralysis (may require respiratory support)
- May be due to cholinesterase inhibition
- May be due to receptor exhaustion
- Thought to be a rare outcome
- Only in severe intoxications
Organochlorines DDT, Cyclodienes, Lindane
- Interfere with sodium-channel gating of neurons.
- Cause uncontrolled depolarization of nervous tissue.
- Seizures, Myoclonic Jerking, Coma
- Some reports of Long-Term CNS changes from prolonged DDT use.
Parasthesias and Pyrethroids
- Interfere with sodium channel gating in nervous tissue.
- Acute symptoms include tingling and burning
- Usually acral parasthesias
- Mucous membranes affected if exposed
- High dose may result in clonic spasm or tremors
- No evidence to date of long term neurological effects
- Acute central nervous system effects
- Ataxia, tremor, slurred speech, coma.
- May result in persistent myoclonic jerking, tremors and behavioral disturbances.
Nicotine Green Tobacco Illness
- Dermal nicotine absorption
- Occurs in Tobacco Pickers
- Nausea, headache, tremor,
- Imidocloprid (Admire, Condifor, Gaucho, Premier)
- Stimulates Nicotinic receptors.
- Few human poisonings as yet.
- Expected to cause nicotinic symptoms.
- No long term effects reported as yet.
- Manganese containing compounds
- To control gypsy moth in 1892.
- Still contaminates agricultural land.
- CCA a wood preservation, to be removed.
- Both Lead and Arsenic are neurotoxins
- Both cause peripheral neuropathy
- Both cause central nervous system effects if high enough concentration achieved
- Rarely used today as a pesticide
- Past experience shows it dramatic neurotoxicity
- Withdrawal, memory loss, vasomotor disturbances
- Spontaneous abortion, neurological effects on fetus
- Used as antifouling agents in marine paints
- Headache, photophobia, convulsions, loss of consciousness.
- Ethylene Bis Dithiocarbamates
- Generally low acute toxicity
- Have been associated with Parkinsonian syndrome in pesticide exposed workers
- Consistent with manganese poisoning in miner and smelters.
- A light metal treated like potassium by the body
- Broadly toxic metal to many tissues
- Severe painful peripheral neuropathy
Alpha-2 Receptor Stimulants
- Amitraz (Baam, Aazdieno, Acarac, Mitac)
- Appears to simulate an overdose of Clonidine
- Bradycardia, hypotension, hypothermia, hyperglycemia.
- No long term effects described in animal testing or in humans so far.
- Block the GABA-gated chloride channel.
- Also some old favorites: Alpha-endosulfan, lindane, picrotoxin
- Seizure inducing in high dose.
- New GABA blockers are more active but more discriminating for insect GABA receptors.
- The metabolic activation to the
- Manganese containing Pesticides include
- Farmaneb, Manesan, Manex, Manzate, Nereb, and Newspor
- Carbon Disulfide (a fumigant)
- What are the culture free tests that identify neurobehavioral problems?
- How do we address the low-level exposure question
- Most are relatively rare diseases
- Exposure quantification is the key
Something to Think About