TOXICOLOGY

Dr. M. Masoom Akhtar

 TOXICOLOGY
Toxicology is the branch of
pharmacology that encompasses the
deleterious effects of chemicals on
biologic systems.

A number of chemicals in the

environment (eg, atmosphere, home,
workplace) pose important health
hazards.
 Pollution
When harmful substances
contaminate the environment it is
called pollution.

Pollution refers to the very bad

condition of environment in terms of
quantity and quality .
 AIR POLLUTANTS
The major air pollutants in industrialized
countries include
Carbon monoxide (which accounts for about
50% of the total amount of air pollutants),
sulfur oxides (18%),
hydrocarbons (12%),
particulate matter (eg, smoke particles, 10%),
nitrogen oxides (6%)
Air pollution appears to be a contributing
factor in bronchitis, obstructive pulmonary
disease, and lung cancer.
 Carbon Monoxide
Carbon monoxide (CO) is an odorless,
colorless gas that competes avidly
with oxygen for hemoglobin.
The affinity of CO for hemoglobin is
more than 200-fold greater than that
of oxygen.
The threshold limit value of CO for an
8-h workday is 25 parts per million
(ppm);
in heavy traffic, the concentration of
CO may exceed 100 ppm.
 1. EffectsCO causes tissue hypoxia.
Headache occurs first, followed by confusion,
decreased visual acuity, tachycardia,
syncope, coma, seizures, and death.
Collapse and syncope occur when
approximately 40% of hemoglobin has been
converted to carboxyhemoglobin.
Prolonged hypoxia can result in irreversible
damage to the brain and the myocardium.
2. TreatmentRemoval of the source of CO
and 100% oxygen are the main features of
treatment.
Hyperbaric oxygen accelerates the clearance of
carbon monoxide.
 Sulfur Dioxide
Sulfur dioxide (SO2) is a colorless,
irritating gas formed from the combustion
of fossil fuels.
1. EffectsSO2 forms sulfurous acid on
contact with moist mucous membranes;
this acid is responsible for most of the
pathologic effects.
Conjunctival and bronchial irritation
(especially in individuals with asthma) are
the primary signs of exposure.
Presence of 510 ppm in the air is enough
to cause severe bronchospasm.
 Heavy exposure may lead to delayed
pulmonary edema. Chronic low-level
exposure may aggravate
cardiopulmonary disease.

2. TreatmentRemoval from exposure

to SO2 and relief of irritation and
inflammation constitute the major
treatment.
 Nitrogen Oxides
Nitrogen dioxide (NO2), a brownish irritant gas, is
the principal member of this group. It is formed
in fires and in silage on farms.
1. EffectsNO2 causes deep lung irritation and
pulmonary edema. Farm workers exposed to
high concentrations of the gawithin enclosed
silos may die rapidly of acute pulmonary edema.
Irritation of the eyes, nose, and throat is
common.
2. TreatmentNo specific treatment is
available. Measures to reduce inflammation and
pulmonary edema are important.
 Ozone
Ozone (O) is a bluish irritant gas produced in
air and water purification devices and in
electrical fields.
1. EffectsExposure to 0.010.1 ppm may cause
irritation and dryness of the mucous membranes.
Pulmonary function may be impaired at higher
concentrations.
Chronic exposure leads to bronchitis, bronchiolitis,
pulmonary fibrosis, and emphysema.
2. TreatmentNo specific treatment is
available. Measures that reduce inflammation and
pulmonary edema are emphasized.
 SOLVENTS
Solvents used in industry and
solvents to clean clothing are a major
source of direct exposure to
hydrocarbons and also contribute to
air pollution.

A. Aliphatic Hydrocarbons
B. Aromatic Hydrocarbons
 A. Aliphatic Hydrocarbons
This group includes halogenated solvents
such as carbon tetrachloride, chloroform, and
trichloroethylene.
1. EffectsSolvents are potent CNS
depressants.
The acute effects of excessive exposure are
nausea, vertigo, locomotor disturbances,
headache, and coma. Chronic exposure leads
to hepatic dysfunction and nephrotoxicity.
Long-term exposure to tetrachloroethylene or
to trichloroethane has caused peripheral
neuropathy.
2. TreatmentRemoval from
exposure is the only specific
treatment available. Serious CNS
depression must be treated with
support of vital signs.
 B. Aromatic Hydrocarbons
Benzene, toluene, and xylene are important
aromatic hydrocarbons.
1. EffectsAcute exposure to any of these
hydrocarbons leads to CNS depression with
ataxia and coma.
Long-term exposureto benzene is associated with
hematotoxicity (thrombocytopenia, aplastic
anemia, pancytopenia) and various types of
hematologic cancers, especially leukemia.
2. TreatmentRemoval from exposure is
the only specific way to reduce toxicity. CNS
depression is managed by support of vital signs.
 PESTICIDES

1. Chlorinated hydrocarbons -
Dichlorodiphenyltrichloroethane (DDT)
and its analogs),
2. Acetylcholinesterase inhibitors
(carbamates, organophosphates),
and
3. Botanical agents (nicotine, rotenone,
pyrethrum alkaloids).
 Chlorinated Hydrocarbons
1. Dichlorodiphenyltrichloroethane
(DDT)
2. Methoxychlor
3. Tetrachlorodiphenylethane (TDE)

These agents are persistent, poorly

metabolized, lipophilic chemicals that
exhibit significant bioaccumulation.
 1. EffectsChlorinated hydrocarbons
block physiologic inac tivation in the
sodium channels of nerve membranes and
cause uncontrolled firing of action potentials.
Tremor is usually the first sign of acute
toxicity and may progress to seizures.
Chronic exposure of animals to these
pesticides is tumorigenic.
The toxicologic impact of long-term exposure
in humans is unclear. Although no relationship
has been shown in humans between the risk
of breast cancer and serum levels of DDT
metabolites, recent evidence suggests an
association with brain and testicular cancer.
 2. TreatmentNo specific
treatment is available for the acute
toxicity caused by chlorinated
hydrocarbons.
Because of their extremely long half-
lives in organisms and in the
environment (years), their use in North
America and Europe has been curtailed.
 Cholinestersase Inhibitors
The carbamates (eg, aldicarb, carbaryl) and
organophosphates (eg, dichlorvos, malathion,
parathion) are effective pesticides with short
environmental half-lives.
These inexpensive drugs are heavily used in
agriculture.
1. Effects Cholinesterase inhibitors
increase muscarinic and nicotinic cholinergic
activity. The signs and symptoms include
pinpoint pupils, sweating, salivation,
bronchoconstriction, vomiting and diarrhea,
CNS stimulation followed by depression, and
muscle fasciculations, weakness, and
 2. TreatmentAtropine is used in
large doses to control muscarinic excess;
pralidoxime is used to regenerate
cholinesterase.

Mechanical ventilation may be necessary.

 Botanical Insecticides
1. NicotineNicotine has the same effects on nicotinic
cholinoceptors in insects as in mammals and probably kills by
the same mechanism (ie, excitation followed by paralysis of
ganglionic, CNS, and neuromuscular transmission).
Treatment is supportive.
2. RotenoneThis plant alkaloid pesticide causes
gastrointestinal distress when ingested and conjunctivitis
and dermatitis after direct contact with exposed body
surfaces.
Treatment is symptomatic.
3. PyrethrumThe most common toxic effect of this
mixture
of plant alkaloids is contact dermatitis. Ingestion or inhalation
of
large quantities may cause CNS excitation (including seizures)
and peripheral neurotoxicity. Treatment is symptomatic, with
anticonvulsants if necessary.
 HERBICIDES

A. Chlorophenoxy Acids
The 2 most important members of this group
are 2,4-dichloro- phenoxyacetic acid and
2,4,5-trichlorophenoxyacetic acid, is longer
used because it is often contaminated during
manufacturing with dioxin and other
polychlorinates.
Large doses of these drugs cause muscle
hypotonia and coma.
Long-term exposure has been associated
with an increased risk of non-Hodgkins
lymphoma.
 B. Glyphosate

Glyphosate is the most widely used

herbicide in the world. It is a key
enzyme involved in aromatic amino
acid biosynthesis in plants.
1. EffectsGlyphosate exposure
causes significant eye and skin
irritation.
2. TreatmentNo specific
treatment is available.
ENVIRONMENTAL POLLUTANTS
Chemical compounds that contribute
to environmental pollution include:
polychlorinated biphenyls,
dioxins,
asbestos,
heavy metals.
 A. Polychlorinated Biphenyls
1. SourceThe polychlorinated biphenyls
(PCBs) were used extensively in manufacturing
electrical equipment until their potential for
environmental damage was recognized.
PCBs are among the most stable organic
compounds. They are poorly metabolized and
lipophilic. They are therefore highly persistent in the
environment, and they accumulate in the food chain.
2. EffectsIn workers exposed to PCBs, the
most common effect is dermatotoxicity (acne,
erythema, folliculitis, hyperkeratosis).
Less frequently, mild increases in plasma
triglycerides and
Elevated liver enzymes have been observed.
 B. Dioxins
1. SourceThe polychlorinated
dibenzo-p-dioxins (dioxins) are a large
group of related compounds of which the
most important is 2,3,7,8-
tetrachlorodibenzo-p-dioxin (TCDD).
The dioxins have appeared in the
environment as unwanted by-products of the
chemical industry.
They are chemically stable and highly
resistant to environmental degradation.
 2. EffectsIn laboratory animals,
exposure to TCDD causes a wasting
syndrome, hepatotoxicity, immune
dysfunction, teratogenicity, and cancer.
In humans, the most common signs of
toxicity are dermatitis and chloracne,
which are cystic acneiform lesions that
typically form on the face and upper
body.
Epidemiologic evidence suggests that
the dioxins also have carcinogenic and
teratogenic effects in humans.
 C. Asbestos
1. SourceAsbestos is a group of naturally
occurring long, flexible mineral fibers, most
commonly containing silicon.
Asbestos has been used widely in manufacturing
and building.
Because it is poorly metabolized and lipophilic, it is
highly persistent in the environment and
accumulates in the food chain.
2. EffectsInhalation of asbestos fibers can
cause a fibrotic lung disorder called asbestosis,
which is characterized by shortness of breath.
Asbestos is also associated with several cancers
including lung cancer, mesothelioma, and cancers
of the gastrointestinal tract.