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
The risk of non-Hodgkin´s lymphoma is increased in persons with elevated oxychlordane residues.

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. Nicotine, rotenone, pyrethrum
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.

43. Katzung, Masters, Trevor.
Basic and clinical pharmacology.
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