Transcript Lecture No. 12+13

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.
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
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.
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
trichlorfon
diazinon
DDT
paraoxon – a powerful ACHE
inhibitor
dichlorvos
diazooxon
DDE (extremely persistent and
xenoestrogenic)
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).
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.
Pyrethroids
- insecticides
- antiparasitics
Mechanism 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 and
inhibition 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 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.
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
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 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
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.