Toxicology

1. BULE HORA UNIVERSITY
COLLEGE OF HEALTH AND MEDICAL
SCIENCES
DEPARTMENT OF PHARMACY
TOXICOLOGY
For 4th year Medical Laboratoy
Students
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Pesticides 1
By:Aliyi G.(B.Pharm)

2. 2 4. Pesticides
.Insecticides
.Rodenticides
.Herbicides
.Fungicides
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3. Pesticide
3
 Any substance or mixture of substances intended for
 preventing, destroying, repelling, or mitigating any pest.
 May also be described as any physical, chemical, or biological
agent that will
 kill an undesirable plant or animal pest.
 The term pest includes harmful, destructive or trouble
 animals, plants, or Mos.
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4. 4
 Pesticides are grouped based on their
targets of action as:
• Insecticides
• Herbicides
• Fungicides
• Rodenticides,…
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5. 5
Uses of pesticides
 Control of vector-borne diseases like
malaria.
 Promotion of agricultural production.
 For the control of domestic pests (e.g.
household & garden pests).
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6. 6
Individual may be exposed to pesticides
o Occupationally
o manufacturing, mixing/loading, application,
harvesting, and handling of crops.
o Environmentally
o e.g. from food products such as fruits &
vegetables treated for pests
o Residence
o e.g. from use as home or garden insecticides
by stander exposure
o Accidental/suicidal.
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7. A. INSECTICIDES
7
 They are substances that destroy or repel or prevent
harmful insects.
 All of the chemical insecticides in use today are
 neurotoxicants and
 act by poisoning the nervous systems of the target
organisms.
 Given the fact that insecticides are
 not selective and
 affect non target species as readily as target organisms.
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8. 8
 The target sites and/or mechanism(s) of
action may be similar in all species;
 only the dosage (level of exposure and
duration) will dictate the intensity of biological
effects.
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9. 9
Mechanism of action of insecticides
 Interference with the membrane transport of
sodium, potassium, calcium, or chloride
ions.
 Inhibition of selective enzymatic activities; or
 Contribution to the release and/or the
persistence of chemical transmitters at nerve
endings.
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10. Classes of insecticides
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A. Organochlorine insecticides
B. (Anticholinesterase agents)
 Organophosphate and
 carbamate insecticides
C. Biological origin insecticides
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11. a. Organochlorine (Chlorinated HCs)
insecticides
11
 No longer considered an important class of insecticides in
North America and Europe,
 the organochlorine insecticides continued use in developing,
tropical countries
 because they are effective, inexpensive.
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12. Organochlorine Cont’d,…
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 The properties
 low volatility,
 chemical stability,
 lipid solubility,
 slow rate of biotransformation and degradation
 made these chemicals such effective insecticides.

13. Organochlorine Cont’d,…
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 The organochlorine (chlorinated hydrocarbon) insecticides are
belongs to three distinct chemical classes:
 Dichlorodiphenylethane
 e.g. DDT, diclofol …
 Chlorinated cyclodiene and benzene
 e.g. aldrin, dieldrin, heptachlor, chlordane …
 Cyclohexane-related structures
 e.g. lindane

14. 14
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15. 15
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16. Organochlorine Cont’d,…
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DDT
 has fairly good safety record with few fatalities.
 High oral doses of DDT results in
 paresthesia of the tongue, lips, and face;
 apprehension;
 hyper susceptibilty to external (light, touch, sound) stimuli;
 irritability, dizziness, and vertigo;
 tremor and tonic and clonic convulsions
 which generally appear several hours (6 to 24 h) after exposure to
large doses

17. Organochlorine Cont’d,…
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 Little toxicity is for dermal exposure to DDT
 because poorly absorbed through the skin.
 There have been a number of fatalities following poisoning by
the cyclodiene and hexachlorocyclohexane type insecticides;
 these pesticides are efficiently absorbed through the skin and
 therefore pose an appreciable hazard to occupationally exposed
individuals.

18. Organochlorine Cont’d,…
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 Exposure to lindane (the gamma-isomer of
hexachlorocyclohexane, HCH)
 produces signs of poisoning that resemble those caused by DDT.
 Technical-grade HCH used in insecticidal preparations
contains a mixture of isomers:
 the gamma and alpha-isomer are convulsant poisons;
 the beta and delta –isomers are CNS depressants
 Only the gamma-isomer (lindane) sees any medicinal use
today,
 as a component of a pediculocide shampoo for head lice.

19. Organochlorine Cont’d,…
19
Treatment of Poisoning
 The life-threatening situation in organochlorine
insecticide.
 In addition to general decontamination and supportive
treatment,
 diazepam (0.3 mg/kg IV; maximum dose of 10 mg) or
 phenobarbital (15 mg/kg IV; maximum dose of 1.0 g) may
be administered by slow injection to control the convulsions.
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20. b. Anticholinesterase agents
(Organophosphate and carbamate)
insecticides
20
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21. Anticholinesterase agents Cont’d,…
21
 Organophosphates & carbamates
 are the most frequently used insecticides world
wide.
 These compounds cause 80% of the reported
toxic exposure to insecticides.
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22. Organophosphates
insecticides
22
 These agents are utilized to combat a large variety of
pests.
 Some of these agents are used in human and
veterinary medicine as local or systemic.
 Antiparasitics or in circumstances in which
prolonged inhibition of cholinesterase is indicated.
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23. OP cont’d,…
23
 compounds are absorbed by the skin as well as by the
respiratory and GITs.
 Biotransformation is rapid.
 In mammals as well as insects,
 the major effect of these agents is inhibition of acetyl
cholinesterase.
E.g.
 OP: malathion, parathion, diazinon, chlorpyrifos …;
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24. OP cont’d,…
24
Signs and symptoms
 characterize acute intoxication are due to
inhibition of this enzyme resulting in accumulation
of acetylcholine like
 diarrhea, urination, miosis, bradycardia, lacrimations
&salivation.
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25. OP cont’d,…
25
Treatment of Poisoning
General supportive measures
 Decontamination or gastric lavage
 Maintenance of a patent airway,
 Artificial respiration
 Treatment of convulsions with
 diazepam (5 to 10 mg, IV)
 Treatment of shock
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26. OP cont’d,…
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Treat with antidotes: Atropine and pralidoxime (2-PAM)
 Atropine to antagonize the actions at muscarinic receptor
sites;
 not prevent nicotinic effect and/or regenerate AchE
 2 – PAM reactivates the OP inhibited enzyme
 by the removal of the phosphate group that is bound to the esterase
site.

27. Carbamate insecticides
27
 Produce a milder form of toxicity, similar to that
produced by organophosphate compounds.
 These compounds inactivate
acetylcholinesterase
 leading to excessive accumulation of
acetylcholine.
 Eg. Carbamate insecticides: aldicarb, carbaryl …
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28. Carbamate cont’d,…
28
 The important differences distinguishing carbamates from OP
toxicity are
- Carbamate toxicity is typically short-lived in which
spontaneous regeneration of enzymatic activity usually occur
within 24hours.
- Carbamates produce little or no CNS toxicity because of
their inability to penetrate the blood-brain-barrier & affect
brain cholinesterase activity.
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29. Carbamate cont’d,…
29
 Sign & symptoms
 may be more rapid &
 usually abate within 24hrs regardless of therapy.
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30. Carbamate cont’d,…
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Treatment
• GI decontamination
• Atropine & pralidoxime can be used as an
antidote.
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31. C . Insecticides of biological origin
31
 Used in
 household insecticide and
 pet products (e.g. flea & tick)
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32. Insecticides of biological origin cont’d,…
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Pyrethrum and Pyrethrins
 Pyrethrum
 is a mixture of six insecticidal esters (pyrethrins I&II, cinerins I&II,
and jasmolins I&II)
 extracted from chrysanthemum flowers.
 Pyrethroids – are synthetic derivatives of pyrethrin.
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33. Insecticides of biological origin cont’d,…
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 Pyrethroids elicit little toxicity in either in animals or humans
due to
 may be little storage or accumulation and
 an efficient detoxification of the chemicals and
 also differences in Na channel more toxic to insects.
 However, their use in enclosed and poorly ventilated spaces
has resulted in some signs and symptoms of toxicity to
humans

34. Insecticides of biological origin cont’d,…
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 Exposure to the natural pyrethrum mixture
 is known to cause allergic reactions rather than direct toxicities.
 There has been little evidence of the allergic-type reactions in
humans exposed to
 synthetic pyrethroid esters.
 Pyrethroids with alpha-cyano substituent
 may cause cutaneous paresthesia and dizziness.

35. Insecticides of biological origin cont’d,…
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 Ingestion (poisoning/ suicide)
 cause epigastric pain, nausea and vomiting, headache, dizziness,
anorexia, fatigue, chest tightness, blurred vision, paresthesia,
palpitations, coarse muscular fasciculations in the large muscles of
the extremities, convulsive attacks (sever cases).
 Recovered completely within 2 to 3 weeks.
 No chronic toxicity has been reported

36. Insecticides of biological origin cont’d,…
36
Treatment of Poisoning
 Limited experience
 Removal from exposure
 Lavage with vegetable and/or vitamin E cream will
alleviate dermal paresthesia
 Symptomatic:
 topical steroids for contact dermatitis,
 antihistaminics,
 decongestants and
 steroid nasal spray for rhinitis and inhaled steroids for asthma.
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37. Insecticides of biological origin cont’d,…
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Rotenone
 Acute poisoning in animals
 is characterized by an initial respiratory stimulation
 followed by respiratory depression, ataxia, convulsions and
death by respiratory arrest – respiratory toxicant.

38. Insecticides of biological origin cont’d,…
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Rotenone
 has been used topically for treatment of
 head lice,
 scabies, and other ectoparasites,
 but the dust is highly irritating to
 the eyes (causing conjunctivitis),
 the skin (causing contact dermatitis), and
 the upper respiratory tract (causing rhinitis) and
 throat (cause pharyngitis).

39. B. HERBICIDES
39
 A herbicide is any compound that is capable of either killing or
severely injuring plants.
 It may be used for the elimination of plant growth or the
killing of plant parts.
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40. Herbicides Cont’d,…
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 The claim has been made that herbicides
 pose no risk of mammalian toxicity
 as the modes of action involve biochemical phytoprocesses with no
counterparts in mammals.
 With the exception of a few chemicals, the herbicides have
demonstrated low toxicity in mammals.

41. Herbicides Cont’d,…
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 General toxicity: because the major route of
exposure to herbicides is dermal,
 dermal irritants, can cause skin rashes and contact
dermatitis;
 hypersensitive individuals - may experience
severe contact dermatitis,
 asthma-like attacks, and
 even anaphylactic reactions following dermal or
inhalation contact

42. Chlorophenoxy compounds
42
 The major herbicides used for the destruction of broad
leaf weeds.
 2,4-Dichlorophenoxyacetic acid (2,4-D),
 2,4,5-Trichlorophenoxyacetic acid (2,4,5-T), and their salts
and esters
 2,4 -D + 2,4,5-T used in combination called Agent
Orange.
 In plants, these chemicals mimic the action of auxins,
hormones that stimulates growth,
less effect in non target organ.
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43. Chlorophenoxy compounds cont’d,…
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 Chloracne sever form of dermatitis,
 is observed involved in the manufacture of 2,4,5-T.
 An industrial accident in 1949 in a 2,4,5-T manufacturing
caused acute symptoms of exposure to the reaction products,
 including skin, eye, and respiratory tract irritation; headache; dizziness;
nausea; acneiform eruptions; severe muscle pain in the thorax,
shoulders and extremities; fatigue; nervousness; irritability; dyspnea;
complaints of decreased libido; and intolerance to cold

44. Bipyridyl Derivatives
44
Paraquat (1, 1’-dimethyl-4, 4’-bipyridylium dichloride, methyl
viologen) and
Diquat (1, 1’-ethylene-2, 2’-bipyridylium dibromide)
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45. Bipyridyl Derivatives cont’d,…
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 Paraquat is a nonselective contact herbicide,
 which is one of the most specific pulmonary toxicants.
 Its toxicity is not due to paraquat or its metabolites but rather
 to ROS formed during one-electron reduction of paraquat paired
with an electron donation to oxygen.
 Diquat is slightly less toxic than paraquat.

46. Bipyridyl Derivatives cont’d,…
46
Treatment of paraquat poisoning
 Gastric lavage, administration of mineral adsorbents [ kaolin,
bentonite clay, or activated charcoal], purgatives, aggressive
hemoperfusion through charcoal or by hemodialysis.
 Oxygen to maintain acceptable arterial oxygen tension (40 to
50 mmHg)
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47. c. Fungicides
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 Every year fungi cause crop losses in the United States
amounting to millions of dollars.
 Toxins and other airborne organic compounds released
from fungi are responsible for a number of adverse health
effects.
 Compounds produced to combat these losses and adverse
health effects are called fungicides.
 A number of these families have been around for years.
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48. Fungicides Cont’d,…
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Chlorothalonil (tetrachloroisophthalonitrile)
 is a broad-spectrum fungicide which is used widely in urban
environments.
 It is relatively cheap and
 controls some 140 species of organisms.
 As a result of the popularity of this compound,
 It is found routinely in surface waters entering public drinking water
supplies.
 In the formulation that can be purchased by the general public,
 it is relatively nontoxic.
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49. Fungicides Cont’d,…
49
 One family of fungicides are
 dithiocarbamates,
 sulfur derivatives of dithiocarbamic acid and
 metallic dimethyldithiocarbamates.
 The latter group includes
 mancozeb (a coordination product of zinc ion and manganese
ethylene bisdithiocarbamate),
 maneb (manganese ethylenebisdithiocarbamate) and
 zineb (zinc ethylenebisdithiocarbamate).
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50. Fungicides Cont’d,…
50
 All are effective fungicides and are used on a variety of crops
 including grapes, sugar beets, and ornamental plants.
 Although relatively nontoxic,
 they do hydrolyze producing known carcinogens such as
ethylthiourea (ETU).
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51. D. Rodenticides
51
 Definition: They are chemicals used to kill rodents
such as rats.
 Rodenticides must obey the following:
 Palatable to the rodent and potent.
 Chemically stable so can be stored for long time.
 Odorless and colorless
 Not easily tolerated by rodents.
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52. Rodenticides cont’d,…
52
Anticoagulant preparations
 currently the most widely used rodenticides
 are safer, although consequential human poisonings do
occur.
 Most pediatric ingestions occur accidentally, whereas ingestions
in adults tend to be deliberate.
 Coumarin derivatives (E.g. warfarin) are one of the
members of this class.
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53. Rodenticides cont’d,…
53
 The main features of warfarin poisoning in less
severe cases are
 excessive bruising, nose & gum bleeding, &blood in the
urine faeces.
 Bleeding from several organs within the body,
 leading to shock & possibly death, occurs in the more
severe cases.
 The onset of the signs of poisoning may not be evident until a
few days after exposure.
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54. Rodenticides cont’d,…
54
Red squill
 containing a cardiac glycoside as an active ingredient
 was used as a rodenticide for many years.
 In theory, rodents ingest the product and
 because they are incapable of vomiting, develop glycoside
intoxication and pulmonary edema.
 Because humans are capable of vomiting
 red squill was considered harmless, even to children.
 This product is not used much today because of its limited
effectiveness.
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55. Rodenticides cont’d,…
55
Strychinine
 In the past, was used widely as a rodenticide.
 This agent is not used much today but
 reported to have caused 3 deaths in 1998.
 Serve as antagonists of the neurotransmitter glycine at the
postsynaptic spinal cord motor neuron
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56. Rodenticides cont’d,…
56
Thallium
 Although thallium is not licensed for use in the United States,
 many case reports document thallium intoxications in third
world countries where
 this product is still used as a rodenticide.
 Consider thallium toxicity when treating a patient with a
 neuropathy and hair loss.
 Recent cases of thallium poisoning associated with
 malicious criminal activity have been reported in the United States.
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58. Quize#2
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