TOXICOLOGY OF PESTICIDES

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TOXICOLOGY OF PESTICIDES

• Pesticides are preparations for the eradication
  of plant and animal pests, for the protection of
  plants, animals and man.
• About 800 compounds of active ingredients of
  pesticides have been registered world-wide.

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Historical background

• alkaloids nicotine and anabasine contained in
  tobacco insecticides
• pyrethrines contained in plants of the genus
  Pyrethrum insecticides
• Pyrethrines later became the prototype for
  synthetic pyrethroids
• rotenon is highly toxic to all forms of life,
  is from roots of lianas. Rotenon was used as a
  piscicide and insecticide
• an important milestone was introduction of phenyl
  mercury in 1913 for the protection of seed
  fungicide
• insecticidal effect of DDT was discovered in 1939
  by the Swiss Paul Müller

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Classification of pesticides

• fungicides
• zoocides (insecticides, rodenticides,
  molluscocides)
• herbicides including desiccants
• selective
• non-selective
• plant growth regulators (to shorten the straw of
  cereals)
• Desiccation drying
• desiccant drying agent
• Desiccants are used for alfalfa (lucern) or
  clover for seed plants dry up and can be
  harvested.

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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.

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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)

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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

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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).

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Carbamate pesticides- insecticides-
herbicides- fungicides

• Mechanism of the toxic action reversible
  inhibition of acetylcholinesterase (by
  carboxylation of hydroxyl group of serine bound
  in the active centre of ACHE).
• Carbofuran is very up-to-date substance in
  toxicology. It is used to control vermin (foxes)
  and is used in baits. Birds are 10 times more
  sensitive to carbofuran than mammals (LD50 for
  mammals 3 19 mg/kg body weight). Frequent
  carbofuran poisoning cases among predatory birds.

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Pyrethroids- insecticides- antiparasitics

• Mechanism of the toxic action -
• pyrethroids T (tremor) contain no a-cyano group
  
• cause reversible block of sodium channels (e.g.
  permethrin)
• pyrethroids CS (choreoatetosis, salivation)
  contain a-cyano group
• cause reversible block of sodium channels and
  inhibition of GABA (e.g. deltamethrin)

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Pyrethroids are- highly toxic for fish (LC50
below 0,1 mg/l)- toxic for bees (LD50 2 11
µg/bee)- not very toxic for mammalsCats 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.
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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 energy metabolism).
• 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.

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Urea based pesticides - herbicides

• 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

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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

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Serious risk of triazine based pesticides

• very low biodegradability (risk for drinking
  water)
• triazines are secondary amines (secondary amines
  nitrosation agents
• nitrosamines)
• atrazine has xenoestrogenic effects (causes
  abnormal development of gonads, turns amphibians
  into hermaphrodites)

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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

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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
leucocytesSymptoms of poisoning pulmonary
oedema, fibrotic pneumonia
fetotoxicity,retardation of ossification
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Metal based pesticides

• arsenic 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 water quality

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Phenylpyrazoles - insecticides- antiparasitics

• Mechanism of the toxic action inhibition of
  GABA
• 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.