Download - Toxicity of pesticides
Abdulrahman Mohammed
L-2012-V-21-D
School of Public Health & Zoonoses
GADVASU, Ludhiana
“Any substance or mixture of substances intended for preventing, destroying, repelling, or mitigating any insects, rodents, nematodes,
fungi, or weeds, or any other forms of life declared to be pests; any substance or mixture
of substances intended for use as a plant regulator, defoliant, or desiccant.”
--Federal Insecticide, Fungicide, and Rodenticide Act (US EPA)
Historical background:
- Alkaloids nicotine and anabasine contained intobacco – insecticides
- Pyrethrines contained in plants of the genusPyrethrum – insecticidesPyrethrines later became the prototype forsynthetic pyrethroids
- Rotenon – is highly toxic to all forms of life, is fromroots of lianas. Rotenon was used as a piscicide andinsecticide
- An important milestone was introduction ofphenyl mercury in 1913 for the protection of seed –fungicide
- Insecticidal effect of DDT was discovered in 1939by the Swiss Paul Müller
Classification of pesticides
General ClassesInsecticides
1. Organophosphates (OP)2. Carbamates3. Chlorinated Hydrocarbons (CHC)4. Pyrethroids5. Biologicals6. Metals/Elementals7. Insect Growth Regulators (IGR)
Fungicides1. Substituted benzenes
2. Thiocarbamates
3. EBDC (Ethylenebisdithiocarbamates)
4. Phthalates
5. Metals/Elements
6. Others
Rodenticides
1. Coumarins2. Indandiones3. Metals/Inorganics4. Convulsants
Herbicides1. Chlorophenoxy2. Nitro-phenolic/cresolic3. Dipyridyls4. Triazines5. Thiocarbamates6. Phosphonates7. Others
Pesticide degradation- in abiotic environment
the most important factors are light, temperature, photolysis, free radicals produced in photochemical reactions, hydrolysis
- in biotic environment
1. phase 2. phase
XH X – OH X – O – conjugate
The final products are inactive and are
excreted.
Pesticide transformation
- mostly detoxicative nature
- result may even be a more toxic substances (desulphuration of organophosphates)
parathion paraoxon – a powerful ACHE inhibitor
trichlorfon dichlorvos
diazinon diazooxon
DDT DDE (extremely persistent and
xenoestrogenic)
Dose/Response
Dose Terminology
LD50 = Lethal Dose 50% Test Population
LD0 = Highest Dose with no Lethality in the Test Population
LD100 = Lethal Dose 100% Test Population
LC50 = Lethal Concentration 50% Test Population
LOAEL =Lowest Observed Adverse Effect Level
NOAEL = No Observed Adverse Effect Level
Dose/ResponseExposure Terminology
Acute: Short term, high dose, usually measured in minutes to days, can be multiple
doses within a short period (burst hose on a azinphos-methyl application or a B.T. Collins Cocktail).
SubChronic: Intermediate term, moderate to low dose, measured in weeks to months
(exposure to a seasonal use material, e.g. triadimefon on grapes) .
Chronic: Long term, low dose, measured in months to years (exposure to a constant
use material, e.g. sulfuryl fluoride for home fumigation).
Pesticides:- Organochlorine pesticides
- Organophosphates
- Carbamate pesticides
- Pyrethroids
- Phenoxyacetic acid – based pesticides
- Urea – based pesticides
- Diazine and triazine pesticides
- Bipyridil – based pesticides
- Phenylpyrazoles
- Metal – based pesticides
Organophosphates- insecticides- antiparasitics
Mechanism of toxic action – irreversible
inhibition of enzymes, particularly of
acetylcholinesterase on nerve synapses (by
phosphorylation of hydroxyl group of serine
bound in the active centre of ACHE).
Action of Acetylcholine & Cholinesterase
- acetylcholine
- cholinesterase
- acetate
- choline
- organophosphate
- 2-PAM
nerve cell
muscle
Normal Electrical Nerve
Impulse Transmission
Carbamate pesticides- insecticides- herbicides- fungicides
Mechanism of the toxic action – reversibleinhibition of acetylcholinesterase (by carboxylationof hydroxyl group of serine bound in the activecentre of ACHE).
Carbofuran is very up-to-date substance intoxicology. It is used to control vermin (foxes) and isused in baits. Birds are 10 times more sensitive tocarbofuran than mammals (LD50 for mammals 3 –19 mg/kg body weight). Frequent carbofuranpoisoning cases among predatory birds.
Pesticides
Insecticide Toxicology
OP CarbamatesParathion Propoxur
Azinphos-methyl Methomyl
Diclorvos Carbofuran
Naled Aldicarb
Fenamiphos Carbaryl
Methidathion Fenoxycarb
Oxydemeton-methyl Thiodicarb
malathion Oxamyl
Pesticides
OPs and Carbamates
CarbarylParathion
Pesticides
CHCs
Dieldrin
DDT
Pyrethroids- insecticides- antiparasiticsMechanism of the toxic action -
- pyrethroids T (tremor) – contain no α-cyano group
cause reversible block of sodium channels (e.g.permethrin)
- pyrethroids CS (choreoatetosis, salivation) –contain α-cyano group
cause reversible block of sodium channels andinhibition of GABA (e.g. deltamethrin)
Pyrethroids are
- highly toxic for fish (LC50 below 0,1 mg/l)- toxic for bees (LD50 2 – 11 µg/bee)- not very toxic for mammals
Cats are most sensitive mammals to pyrethroids.Why?- Pyrethroids’ detoxification, similarly to other organic
toxicants, takes place in two phases. Activity of conjugation enzyme, especially of glucuronyl transferase, is very low in cats.
Phenoxyacetic acid – based pesticides (MCPA)- herbicides
Mechanism of the toxic action –
disruption of oxidation and phosphorylation processes(drop in the ATP production and disruption of energymetabolism).
They are little toxic for mammals, fish, bees.
Symptoms of poisoning: hypotermia, hypodynamia,
paresis, paralysis, tympania in ruminants.
But: In the production and use of those herbicides (2,
4-D; 2,4,5-T) dioxin was produced.
They cause damage of the thyroid gland and diuron may cause methaemoglobinemia.
In mammals linuron reduces haematopoiesis
In dogs triasulfuron causes cystic hyperplasia of the prostate, vacuolisation of liver cells, anaemia and accumulation of pigment in the liver
Diazine and triazine pesticides- herbicides
Diazine pesticides are less toxic than triazine ones
Mechanism of the toxic action –
- triazines are antimetabolites of pirimidine bases -components of nucleic acids and folic acid
- atrazine damages the liver detoxication functions
- simazine, prometryne, terbutryne – inhibit haematopoiesis
Toxicity: toxic for fish
relatively harmless for bees
LD50 for mammals exceeds 1000 mg.kg-1
live weight
Serious risk of triazine – based pesticides
1. very low biodegradability (risk for drinking water)
2. triazines are secondary amines (secondary amines + nitrosation agents
nitrosamines)
3. atrazine has xenoestrogenic effects (causes abnormal development of gonads, turns amphibians into hermaphrodites)
Bipyridil – based pesticides- herbicides- desiccant
They are very rapidly deactivated in soil, but leave
residues in plants: diquat for 3 – 5 days, paraquat for 21 days.
Diquat (Reglone)
LD50 for cattle 30 – 50 mg.kg-1 l.w.
for rabbit 280 mg.kg-1 l.w.
Symptoms of poisoning – pulmonary oedema, damage of liver and kidneys, arthritis, periarthritis
Paraquat (Gramoxone)
LD50 for man 40 mg.kg-1 l.w.for cattle and pigs 30 – 70 mg.kg-1 l.w.for dogs and cats 25 – 50 mg.kg-1 l.w.
Mechanism of toxic action – is mediated by- free oxygen radicals- proteolytic enzymes formed by active
neutrophilic leucocytes
Symptoms of poisoning – pulmonary oedema, fibrotic pneumonia
fetotoxicity,retardation of ossification
Metal – based pesticidesarsenic compounds – insecticides, rodenticides
phenylmercury – fungicide for treatment of seed (1913 –1993)
tributyltin – fungicide (xenoestrogenic effect)
thalium compounds – rodenticides
Today
Copper compounds – copper sulphate
- copper oxichloride
fungicides, algicides, molluscocides
Toxicity for fish – LC50 1 – 10 mg.l-1 depending on waterquality
Phenylpyrazoles - insecticides- antiparasitics
Mechanism of the toxic action – inhibition ofGABA
Fipronil is very toxic for bees (LD50 is 5 ng/bee)
It causes secondary toxicity in bees.
Its residua persists for 21 days.
It produces the „knock down“ effect.
Diagnosis of Pesticide Illness Exposure history most important
Occupational and environmental history
Duration, dose, route of potential exposure
Symptom review
Physical exam & lab findings
Health effects may be due to any component of pesticide formulations
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Aspects of History that Suggest Pesticide Illness
Multiple cases
Similar symptoms, exposure history
History of chemical application
Home or office
Accidental ingestion, esp. children
Suicide, homicide attempts
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Pesticide Illness Nonspecific Symptoms & Signs
Rash
Flu-like symptoms Dizziness, malaise, respiratory tract irritation
Gastrointestinal symptoms
Seizures
Odor-related effects Not toxicological effects of active ingredient
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Pesticide Illness May Mimic Common Medical Conditions
Mild:
Upper respiratory tract infection/influenza
Food-borne illness
Asthma
Plant-induced irritant or allergic dermatitis
Severe:
Cerebrovascular accident
Psychiatric dysfunction
Heat stroke
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Treatment of Pesticide IllnessDecontamination Shower, shampoo
Scrub under fingernails
Contain contaminated clothing, body fluids
Save for residue analysis
Protect treating staff
Body fluid precautions
Personal protective equipment if appropriate
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Pesticide IllnessMedical Treatment
Symptomatic treatment
Respiratory distress
Maintain airway, breathing, circulation
Oxygen, bronchodilators if indicated
Ingestion
Gastric lavage, charcoal if indicated
Specific antidotes where applicable
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