Toxicology

1. Pesticides
Domina Petric, MD

2. Pesticides can be devided into:
Organochlorine Pesticides
Organophosphorus Pesticides
Carbamate Pesticides
Botanical Pesticides

3. Organochlorine Pesticides
DDT (chlorophenothane) and its
analogs
Benzene hexachlorides
Cyclodienes
Toxaphenes

4. Organochlorine Pesticides
• They can be absorbed through
the skin and by inhalation or oral
ingestion.
• They cause severe
environmental damage and have
been largely abandoned.

5. Organochlorine Pesticides
• DDT continues to have very
restricted use for domestic
mosquito elimination in malaria-
infested areas of Africa.
• Organochlorine pesticide
residues in humans, animals and
environment.

6. Human toxicology
These agents interfere with
inactivation of the sodium
channel in excitable
membranes and cause rapid
repetitive firing in most
neurons.

7. Human toxicology
• Calcium ion transport is inhibited.
• These events affect
repolarization and enhance the
excitability of neurons.
• DDT causes tremor, as first
manifestation, and convulsions.

8. Human toxicology
There is no specific treatment
for the acute intoxicated state.
Management is symptomatic.

9. Human toxicology
• There is association between
prepubertal exposure to DDT
and brain cancer.
• The risk of testicular cancer is
increased in persons with
elevated DDT levels.

10. Human toxicology

11. Environmental toxicology
• The organochlorine pesticides
are persistent chemicals.
• Degradation is quite slow.
• Bioaccumulation is well
documented, especially in
aquatic ecosystems.

12. Environmental toxicology
• The presence of organic matter in the
soil favors the adsorption of these
chemicals onto the soil particles.
• Adsorption is poor in sandy soils.
• These compounds induce significant
abnormalities in the endocrine
balance of sensitive animal and bird
species.

13. Organophosphorus pesticides

14. Organophosphorus
pesticides
• azinphos-methyl
• chlorfenvinphos
• diazinon
• dichlorvos
• dimethoate
• malathion
• parathion…

15. Organophosphorus
pesticides
• Useful pesticides and plant
systemics.
• They are based on soman, sarin and
tabun, which were developed for use
as war gases.
• Also used in human and veterinary
medicine as local or systemic
antiparasitics.

16. Organophosphorus
pesticides
The compounds are absorbed by
the skin and by the respiratory
and gastrointestinal tract.
Biotransformation is rapid.

17. Human toxicology
The major effect is inhibition of
acetylcholinesterase through
phosphorylation of the esteratic site
• inhibition of acetlycholinesterase
• accumulation of acetylcholine
• direct cholinergic activity (some of
agents)

18. Human toxicology
• Exposure to
organophosphorus pesticides
cause altered neurologic and
cognitive functions, as well as
psychological symptoms of
variable duration.

19. Human toxicology
• Some of these agents are capable
of phoshporylating another enzyme
present in neural tissue:
neuropathy target esterase.
• This results in progressive
demyelination of the longest
nerves.

20. Human toxicology
• Organophosphorus ester-
induced delayed polyneuropathy
(OPIDP): paralysis and axonal
degeneration.
• Delayed central and autonomic
neuropathy may occur in some
poisoned patients.

21. Human toxicology
Neurotoxicity has been observed with:
• triorthocresyl phosphate (TOCP)
• dichlorvos
• trichlorfon
• leptophos
• methamidophos
• mipafox
• trichloronat

22. Human toxicology
• Polyneuropathy begins with
burning and tingling sensations,
particularly in the feet, with motor
weakness few days later.
• Sensory and motor difficulties
may extend to the legs and
hands.

23. Human toxicology
• Gait is affected.
• Ataxia may develop.
• Central nervous system and
autonomic changes may develop
later.
• There is no specific treatment for
delayed toxicity.

24. Acute treatment
• Atropine!
In order to achieve adequate
atropinization quickly, a doubling
approach is typically used:
• escalation of doses from 1 mg to
2 mg, 4 mg, 8 mg, 16 mg…

25. Environmental toxicology
• Organophosphorus pesticides are not
persistent pesticides.
• They are relatively unstable and
break down in the environment:
hydrolysis and photolysis.
• They have a small impact on the
environment.

26. Carbamate pesticides
Adicarb
Aminocarb
Carbaryl
Dimetan
Dimetilan
Isolan
Methomyl
Propoxur
Pyramat
Pyrolan
Zectran

27. Carbamate pesticides
• They inhibit acetylcholinesterase
by carbamoylation of the
esteratic site.
• They possess the toxic
properties associated with
inhibition of acetylcholinesterase.

28. Carbamate pesticides
• The clinical effects due to
carbamates are of shorter duration
than in the case of
organophosphorus compounds.
• Spontaneous reactivation of
cholinesterase is more rapid after
inhibition by the carbamates.

29. Carbamate pesticides
Carbamates are non
persistent pesticides
and have a small
impact on the
environment.

30. Botanical pesticides
Nicotine, rotenone,
pyrethrum

31. Botanical pesticides
• Nicotine is obtained from the dried
leaves of Nicotiana tabacum and
Nicotiana rustica.
• It is rapidly absorbed from mucosal
surfaces.
• Free alkaloid is readily absorbed from
the skin.

32. Botanical pesticides
Nicotine reacts with the
acetylcholine receptor of the
postsynaptic membrane:
• sympathetic and
parasympathetic ganglia
• neuromuscular junction

33. Botanical pesticides
• Nicotine results in
depolarization of the
membrane.
• Toxic doses cause stimulation
rapidly followed by blockade
of transmission.

34. Botanical pesticides
• Rotenone is obtained from Derris
elliptica, D. mallaccensis,
Lonchocarpus utilis and L. urucu.
• The oral ingestion of rotenone
produces gastrointestinal
irritation.

35. Botanical pesticides
Rotenone can also cause
conjunctivitis, dermatitis,
pharyngitis and rhinitis.
Tretment is symptomatic.

36. Pyrethrum
Consists of 6 known insecticidal esters:
• pyrethrin I
• pyrethrin II
• cinerin I
• cinerin II
• jasmolin I
• jasmolin II

37. Pyrethrum
• It may be absorbed after
inhalation or ingestion.
• Absorption from the skin is
not significant.
• The esters are extensively
biotransformed.

38. Pyrethrum
When absorbed in sufficient
quantities, the major site of toxic
action is central nervous system:
• excitation
• convulsions
• tetanic paralysis

39. Pyrethrum
• Voltage gated sodium, calcium
and chloride channels are
targets.
• Peripheral type of
benzodiazepine receptors are
also important targets of
pyrethrum.

40. Pyrethrum
• Treatment: management of
symptoms.
• Ivermectin, the chloride
channel agonist may be used.
• Pentobarbital and
mephenesin are also usefull.

41. Pyrethrum
• The pyrethroids are highly
irritating to the eyes, skin and
respiratory tree.
• They may cause irritant asthma,
reactive airways dysfunction
syndrome (RADS) and
anaphylaxis.

42. Pyrethrum
• Workers spraying synthetic
pyrethroids may have cutaneous
paresthesias.
• Flight attendants and other aircraft
workers use synthetic pyrethroids for
aircraft disinfection and may have
respiratory and skin problems and
neurologic complaints.