TOXICOLOGY

TOXIC EFFECTS
OF PESTICIDES
INSECTICIDES
• neurotoxicants
• and act by poisoning the nervous systems of the target
organisms.
INSECTICIDES
• Organochlorine Compounds

✓used in developing, tropical countries because they are effective,

inexpensive, essential chemicals in agriculture, forestry, structural
protection, and public health.
INSECTICIDES
• Organochlorine Compounds

SIGNS AND SYMPTOMS

HIGH DOSES:
• paresthesia of the tongue, lips, and face
• hypersusceptibilty to external stimuli (light, touch, sound)
• irritability, dizziness, and vertigo
• tremor and tonic and clonic convulsions
INSECTICIDES
• Organochlorine Compounds

✓ poorly absorbed through the skin.

FATAL DOSE:
✓estimated 10 mg/kg dose
INSECTICIDES
INSECTICIDES
• Organochlorine
Compounds

TREATMENT
✓ General Decontamination and
Supportive Treatment
✓ Diazepam (0.3 mg/kg IV; maximum
dose of 10 mg)
✓ Phenobarbital (15 mg/kg IV;
maximum dose of 1.0 g) may be
administered by slow injection to
control the convulsions.
*It may be necessary to repeat the
treatment.
INSECTICIDES
• Anticholinesterase Agents

✓The agents comprising this type of insecticide have a common mechanism of

action but arise from two distinctly different chemical classes, the esters of
phosphoric or phosphorothioic acid and those of carbamic acid.
INSECTICIDES
• Anticholinesterase Agents

✓Tetraethylpyrophosphate (TEPP)
• The first organophosphorus ester insecticide to be used commercially.
• Although effective, it was extremely toxic to all forms of life and chemical stability was a
major problem in that TEPP hydrolyzed readily in the presenced of moisture.
INSECTICIDES
• Anticholinesterase Agents

✓The first pesticidal carbamic acid esters were synthesized in the 1930s and were
marketed as fungicides.

✓The insecticidal carbamates were synthesized on purely chemical grounds as

analogs of the drug physostigmine, a toxic anticholinesterase alkaloid extracted
from the seeds of the plant Physostigma venenosum, the Calabar bean.
INSECTICIDES
• Anticholinesterase Agents

✓TOXIC EFFECTS TO THE ANS:

➢ tachycardia, hypertension, muscle fasciculation, tremors, muscle
weakness, and/or flaccid paralysis

✓TOXIC EFFECTS TO THE CNS:

➢Restlessness, emotional liability, ataxia, lethargy, mental confusion,
loss of memory, generalized weakness, convulsion, cyanosis, coma
INSECTICIDES
• Anticholinesterase Agents

TREATMENT
✓Atropine is used to counteract the initial muscarinic effects of the accumulating
neurotransmitter.
✓ However, atropine is a highly toxic antidote and great care must be taken.

✓Oximes (Pralidoxime chloride or 2-PAM, Pralidoxime methanesulfonate or P2S)

✓ administered IV
✓ for moderate to severe poisonings
INSECTICIDES
• Pyrethroid Esters

✓A major class of insecticides

✓Entered the marketplace in 1980

✓These synthetics arise from a much older class of botanical insecticides,

pyrethrum.
INSECTICIDES
• Pyrethroid Esters

✓Natural pyrethrum consists of a mixture of six esters derived from two acids and
three alcohols producing an effective contact and stomach poison mixture
having both knockdown and lethality.
INSECTICIDES
• Pyrethroid Esters

SIGNS AND SYMPTOMS

❖Exposure to natural pyrethum mixture
✓contact dermatitis (localized erythema to a severe vesicular
eruption)
✓asthma-like attacks and anaphylactic reactions
✓peripheral vascular collapse
INSECTICIDES
• Pyrethroid Esters

SIGNS AND SYMPTOMS

Occupational Exposure
✓dizziness
✓The signs and symptoms disappeared by 24h after exposure.
INSECTICIDES
• Pyrethroid Esters

SIGNS AND SYMPTOMS

Ingestion
✓epigastric pain, nausea and vomiting, headache, dizziness, anorexia,
fatigue, tightness in the chest, blurred vision, paresthesia, palpitations
INSECTICIDES
• Pyrethroid Esters

SIGNS AND SYMPTOMS

Spilling these agents on the head, face, and eyes
✓pain, lacrimation, photophobia, congestion, and edema of the
✓conjunctiva and eyelids
INSECTICIDES
• Pyrethroid Esters

TREATMENT
✓Removal from exposure and lavage with vegetable and/or vitamin E cream will
alleviate dermal paresthesia
INSECTICIDES
• Avermectins

✓ Derived from 16-member macrocyclic lactones, three of which—avermectin B1a, the

homolog B1b (abamectin), and the semisynthetic ivermectin—have come into wide
use in veterinary medicine as potent insecticidal, acaricidal, and anthelmintic agents.
INSECTICIDES
• Avermectins

✓Ivermectin is used for a wide range of ecto- and endoparasites of domestic and
wild animals.
INSECTICIDES
• Newer Chemical Insecticides:

(1) the nitromethylene heterocycles, developed from the cyclodienes and

cyclohexanes
(2) the nitroimino derivatives (chloronicotinyl or neonicotinoids), similar to nicotine
(3) the phenylpyrazoles
INSECTICIDES
• Nitromethylenes

✓nitromethylene heterocycle (NMH) insecticides

✓fast-acting neurotoxicants
✓effective by both contact or oral ingestion
✓relatively safe to vertebrates and degrade rapidly in the environment
INSECTICIDES
• Chloronicotinyl

✓best known by the compound imidacloprid, developed in Japan in the mid-1980s.

INSECTICIDES
• Phenylpyrazoles

✓show extensive biological activity, including insecticidal, herbicidal, and miticidal

properties.

• Fipronil

✓insecticidal

✓acts at the GABA receptor to block the chloride channel

BOTANICAL INSECTICIDES
BOTANICAL INSECTICIDES
✓Naturally occurring agents of plant origin have been used to
control insect pests.

❖NICOTINE
❖ROTENOIDS
BOTANICAL INSECTICIDES
• Nicotine

✓first used as an insecticide in 1763,

✓also used as a contact insecticide,
stomach poison, and fumigant in
the form of nicotine alkaloid, the
sulfate salt, or in the form of other
derivatives

✓extremely toxic, the acute oral

LD50 in rats being on the order of
50 to 60 mg/kg
BOTANICAL INSECTICIDES
• Rotenoids
Rotenone

✓most potent and can be purified by solvent extraction and recrystallization.

✓It can be used either as a contact or a stomach poison.

✓However, it is unstable in light and heat and almost all toxicity can be lost after 2
to 3 days during the summer.
BOTANICAL INSECTICIDES
• Rotenoids

Rotenone

✓very toxic to fish, and one of its main uses by native people over the centuries was
to paralyze fish for capture and consumption
✓the mammalian toxicity varies greatly with the species exposed, the method of
administration, and the type of formulation
BOTANICAL INSECTICIDES
Rotenoids

Crystalline rotenone has an acute oral LD50 of:

• guinea pigs 60 mg/kg
• rats 132 mg/kg
• rabbits 3000 mg/kg
• human (rare) 10 to 30 mg/kg
FATAL DOSE:
• estimated fatal oral dose for a 70-kg man is of the order of 10 to 100 g.
HERBICIDES
✓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 off of plant parts.
HERBICIDES
HERBICIDES
• Chlorophenoxy Compounds

✓mimic the action of auxins, hormones chemically related to indoleacetic acid, that
stimulate growth

✓The chlorophenoxy herbicides are no longer the agents of choice because of

concerns over the formation of chlorinated dibenzofurans and dibenzodioxins,
particularly 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD).
HERBICIDES
• Chlorophenoxy Compounds

SIGNS AND SYMPTOMS

✓Chloracne, or “weed bumps
✓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
HERBICIDES
• Chlorophenoxy Compounds

FATAL DOSE
ESTIMATES:
Excess of 300 mg/kg, or as low as 80 mg/kg.

• The oral dose required to elicit symptoms 50 to 60 mg/kg.

HERBICIDES
• Bipyridyl Derivatives

✓chemical class of herbicides

➢paraquat (1,1'-dimethyl-4,4'- bipyridylium dichloride, methyl

viologen)
➢diquat (1,1'-ethylene- 2,2'-bipyridylium dibromide)
HERBICIDES
PARAQUAT

a nonselective contact herbicide, is one of the most specific pulmonary toxicants

known and has been the subject of intensive investigation because of the startling
toxicity observed in humans.
✓is a favored agent in suicide attempts in many parts of the world.
HERBICIDES
PARAQUAT

SIGNS AND SYMPTOMS

❖INGESTION
✓Initial irritation and burning of the mouth and throat, the necrosis and sloughing
of the oral mucosa, severe gastroenteritis with esophageal and gastric lesions,
abdominal and substernal chest pains, and bloody stools.
HERBICIDES
PARAQUAT

TREATMENT
✓Gastric lavage
✓Purgatives may be given.
✓Hemoperfusion through charcoal
or by hemodialysis.
✓To avoid excessive pulmonary
damage, supplemental oxygen.
HERBICIDES
• Phosphonomethyl Amino Acids

✓N-phosphonomethyl glycine and N-phosphonomethyl homoalanine

• Both agents are broad-spectrum nonselective systemic herbicides for
postemergent control of annual and perennial plants (grasses,
sedges, broad-leaf weeds) and woody plants
FUNGICIDES
FUNGICIDES
✓derived from a variety of structures ranging from simple
inorganic compounds, such as sulfur and copper sulfate,
through the aryl- and alkyl-mercurial compounds and
chlorinated phenols to metal-containing derivatives of
thiocarbamic acid.
FUNGICIDES
CLASSIFICATION ACCORDING OF FUNGICIDES TO CHEMISTRY AND THEIR
PROPERTIES:

⚫ Foliar fungicides
⚫ Soil fungicides
⚫ Dressing fungicides
FUNGICIDES
CLASSIFICATION ACCORDING OF FUNGICIDES TO MODE OF ACTION:

• Protective fungicides
• Eradicative fungicides
• Currative fungicides
FUNGICIDES
PROPERTIES OF AN EFFECTIVE FUNGICIDE:

(1) low toxicity to the plant but high toxicity to the particular fungus
(2) activity per se or ability to convert itself (by plant or fungal enzymes) into a toxic
intermediate
(3) ability to penetrate fungal spores or the developing mycelium to reach a site of
action
(4) formation of a protective, tenacious deposit on the plantsurface that will be
resistant to weathering by sunlight, rain, and wind
FUNGICIDES
• Hexachlorobenzene

✓From the 1940s through the 1950s, HCB saw extensive use as a fungidical dressing
applied to seed grain as a dry powder.
FUNGICIDES
• Hexachlorobenzene

SIGNS AND SYMPTOMS

✓The syndrome, called black sore, was characterized by dermal blistering and
epidermolysis, pigmentation and scarring, alopecia, photosensitivity, hepatomegaly,
porphyria, suppurative arthritis, osteomyelitis, and osteoporosis of the bones of
the hands
FUNGICIDES
• Hexachlorobenzene

SIGNS AND SYMPTOMS

✓High-level exposure can result in death, preceded by an elevated body
temperature (42°C or 108°F), profuse sweating and dehydration, etc.
FUNGICIDES
• Phthalimides

• folpet and captofol - true phthalimides

✓effective, persistent foliar fungicides for rusts and smut, for Botrytis mold on soft
fruit, apple and pear scab, black spot on roses, and as seed dressings

✓have high oral LD50 values of approximately 10,000 mg/kg in the rat.
FUNGICIDES
• Dithiocarbamates

✓Dimethyl- and ethylene-bisdithiocarbamate (EBDC) compounds have been

employed since the early 1950s as fungicides, and the EBDC chemicals saw
widespread use on a large variety of small fruits and vegetables.
FUNGICIDES
• Dithiocarbamates

✓Maneb, nabam, and zineb have been reported to be teratogenic.

✓Mancozeb has not been demonstrated to be teratogenic in the rat but has been
associated with abnormally shaped sperm.

✓Maneb has been associated with adverse reproductive outcomes (embryotoxicity:

changes in usual number of offspring per litter, pregnancy rate, estrous cycle, and
fetal development).
FUNGICIDES
• Dithiocarbamates

SIGNS AND SYMPTOMS

✓inability to walk, difficulty in talking, tremors in hands and feet, a short-stepped
gait with cogwheeling, and bradykinesia.
FUMIGANTS
✓Such agents are used to kill insects, nematodes, weed seeds, and fungi in soil as
well as in silo-stored cereal grains, fruits and vegetables, clothes, and other
consumables, generally with the treatment carried out in enclosed spaces because
of the volatility of most of the products.
FUMIGANTS
FUMIGANTS
✓Fumigants may be liquids, solids, or gases.
FUMIGANTS
• Phosphine

✓Used extensively as a grain fumigant, phosphine (PH3) is released from aluminum

phosphide (AlP) by the natural moisture in the grain over a long period of time,
giving continual protection during transhipment of the grain.
FUMIGANTS
• Phosphine

SIGNS AND SYMPTOMS

✓PH3 intoxication in the adults includes shortness of breath, cough and
pulmonary irritation, nausea, headache, jaundice, and fatigue
FUMIGANTS
• Ethylene Dibromide/ Dibromochloropropane

✓When inhaled at relatively high (200 ppm) concentrations, ethylene dibromide can
cause pulmonary edema and inflammation.
RODENTICIDES
RODENTICIDES
PROPERTIES OF A
RODENTICIDE:

(1) it must not be unpalatable to the target species and therefore must be potent
(2) it must not induce bait shyness, so that the animal will continue to eat it
(3) death should occur in a manner that does not raise the suspicions of the
survivors
RODENTICIDES
PROPERTIES OF A
RODENTICIDE:

(4) it should make the intoxicated animal go out into the open to die (otherwise the
rotting corpses create health hazards)
(5) it should be species-specific, with considerably lower toxicity to other animals
that might inadvertently consume the bait or eat the poisoned rodent
RODENTICIDES
• Zinc Phosphide

✓This agent is used in developing nations because it is both cheap and effective.
The toxicity of the chemical can be accounted for by the phosphine (PH3) formed
following a hydrolytic reaction with water in the stomach on ingestion.
RODENTICIDES
• Zinc Phosphide

SIGNS AND SYMPTOMS

• nausea, vomiting, headache, light-headedness, dyspnea, hypertension, pulmonary
edema, dysrrhythmias, and convulsions.

FATAL DOSE
✓4000 to 5000 mg
✓but other individuals have survived doses of 25,000 to 100,000 mg if
early vomiting has occurred.
RODENTICIDES
• Zinc Phosphide

TREATMENT
✓The usual decontamination measures and supportive therapy are often successful if initiated
early.
RODENTICIDES
• Fluoroacetic Acid and Derivatives

✓Sodium fluoroacetate (compound 1080) and fluoroacetamide (compound

1081) are white in color, odorless, and tasteless. The extreme toxicity of these two
chemicals has restricted their use to prepared baits.

FATAL DOSE
✓Estimates: 2 to 10 mg/kg.
RODENTICIDES
• Fluoroacetic Acid and Derivatives

SIGNS AND SYMPTOMS

✓Initial nausea, vomiting, and abdominal pain are replaced by sinus tachycardia,
ventricular tachycardia or fibrillation, hypotension, renal failure, muscle spasms,
and such CNS symptoms as agitation, stupor, seizures, and coma.
RODENTICIDES
• Fluoroacetic Acid and
Derivatives

TREATMENT

✓There are no known antidotes to

fluoroacetate intoxication,
although glycerol monoacetate
has proved beneficial in the
treatment of poisoned monkeys.
RODENTICIDES
• A-Naphthyl Thiourea

✓Following the discovery that phenylthiourea was lethal to rats but not toxic to
humans

✓relatively selective rodenticide

FATAL DOSE
rat (most sensitive) 3 mg/kg
monkey (least susceptible) 4 g/kg
RODENTICIDES
• Anticoagulants

✓Human poisonings by these agents are rare because they are dispensed in grain-
based baits.

✓However, there are sufficient numbers of suicide attempts, attempted murders.

RODENTICIDES
• Anticoagulants

SIGNS AND SYMPTOMS

✓bleeding of the gingiva and nose occurs, with bruising and hematomas developing
at the knee and elbow joints and on the buttocks, gastrointestinal bleeding with
dark tarry stools, hematuria accompanied by abdominal or low back (flank) pain,
epistaxis, and cerebrovascular accidents.
THE END