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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