Occupational Toxicology

- deals with the chemicals found in the workplace.

-identify the agents of concern, identify the acute and chronic diseases that they cause, define the
conditions under which they may be used safely, and prevent absorption of harmful amounts of
these chemicals.
-treat the diseases caused by these chemicals if he or she is a physician.
threshold limit values (TLVs)
Environmental toxicology
-deals with the potentially deleterious impact of chemicals, present as pollutants of the
environment, on living organisms
acceptable daily intake (ADI)
-to denote the daily intake of a chemical from food that, during an entire lifetime, appears to be
without appreciable risk.
Ecotoxicology
-is concerned with the toxic effects of chemical and physical agents on populations and
communities of living organisms within defined ecosystems
-one of the foremost areas of study for toxicologists.
*Traditional toxicology is concerned with toxic effects on individual organisms; ecotoxicology is
concerned with the impact on populations of living organisms or on ecosystems.
Hazard
-is the ability of a chemical agent to cause injury in a given situation or setting
Risk
-is defined as the expected frequency of the occurrence of an undesirable effect arising from
exposure to a chemical or physical agent.
Routes of Exposure
-inhalation is the major route of entry.
The transdermal route is also quite important, but oral ingestion is a relatively minor route.
*primary prevention should be designed to reduce or eliminate absorption by inhalation or by
topical contact. Atmospheric pollutants gain entry by inhalation and by dermal contact. Water and
soil pollutants are absorbed through inhalation, ingestion, and dermal contact.
Quantity, Duration, & Intensity of Exposure
Acute exposure (accidental discharge)
- indicates a single exposure or multiple exposures that occur over a brief period from seconds
to 1–2 days.
*rapidly absorbed acute doses of substances that may ordinarily be detoxified by enzymatic
mechanisms in small doses may overwhelm the body’s ability to detoxify the substance and may
result in serious or even fatal toxicity
*The same amount of the substance, absorbed slowly, may result in little or no toxicity。
*Rhodanese, a mitochondrial enzyme present in humans, effectively detoxifies cyanide to
relatively nontoxic thiocyanate when cyanide is presented in small amounts, but the enzyme is
overwhelmed by large, rapidly encountered cyanide doses, with lethal effect
Chronic exposure (repetitive handling of a chemical)
-Single or multiple exposures over a longer period of time
Bioaccumulation
-organismic level
-amount taken in would not be effectively metabolized and secreted
-If the intake of a long-lasting contaminant by an organism exceeds the latter's ability to metabolize
or excrete the substance, the chemical accumulates within the tissues of the organism.
Biomagnification
-environmental level
-food chain
-poisoned pray will poison predator
-Although the concentration of a contaminant may be virtually undetectable in water, it may be
magnified hundreds or thousands of times as the contaminant passes up the food chain.

AIR POLLUTANTS
carbon monoxide (about 52%); sulfur oxides (about 14%); hydrocarbons (about 14%); nitrogen
oxides (about 14%) and ozone, their breakdown product; and particulate matter (about 4%).

Carbon Monoxide
-a colorless, tasteless, odorless, and nonirritating gas, a byproduct of incomplete combustion
Mechanism of action: CO combines tightly but reversibly with the oxygen-binding sites of
hemoglobin and has an affinity for hemoglobin that is about 220 times that of oxygen. The product
formed—carboxyhemoglobin—cannot transport oxygen. Furthermore, the presence of
carboxyhemoglobin interferes with the dissociation of oxygen from the remaining oxyhemoglobin
as a result of the Bohr effect. This reduces the transfer of oxygen to tissues. Organs with the highest
oxygen demand (the brain, heart, and kidneys) are most seriously affected.
Clinical effects: The principal signs of CO intoxication are those of hypoxia. They progress in the
following sequence: (1) psychomotor impairment; (2) headache and tightness in the temporal area;
(3) confusion and loss of visual acuity (4) tachycardia, tachypnea, syncope, and coma; and (5) deep
coma, convulsions, shock, and respiratory failure. Treatment: Patients who have been exposed to
CO must be removed from the exposure source immediately. Respiration must be maintained and
high flow and concentration of oxygen—the specific antagonist to CO—should be administered
promptly.

Sulfur Dioxide
-is a colorless, irritating gas formed from the combustion of fossil fuels
Mechanism of action: Because of its high solubility, when SO2 contacts moist membranes, it
transiently forms sulfurous acid. This acid has severe irritant effects on the eyes, mucous
membranes, and skin. Approximately 90% of inhaled SO2 is absorbed in the upper respiratory tract,
the site of its principal effect.
Treatment : Removal from exposure to SO2 and relief of irritation and inflammation constitute the
major treatment.

Nitrogen Oxides
-a brownish irritant gas, is the principal member of this group. It is formed in fires and in silage on
farms
Mechanism of action: NO2 is a relatively insoluble deep lung irritant. It is capable of producing
pulmonary edema and acute adult respiratory distress syndrome (ARDS). Inhalation damages the
lung infrastructure that produces the surfactant necessary to allow smooth and low-effort lung
alveolar expansion
Effects : Farm workers exposed to high concentrations of the gas within enclosed silos may die
rapidly of acute pulmonary edema. Irritation of the eyes, nose, and throat is common. Today, the
most common source of human exposure to oxides of nitrogen, including NO2, is automobile and
truck traffic emissions.
Treatment—No specific treatment is available. Measures to reduce inflammation and pulmonary
edema are important.

Ozone
-is a bluish irritant gas produced in air and water purification devices and in electrical fields.
Mechanism and Effects—Exposure to 0.01–0.1 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.
Treatment—No specific treatment is available. Measures that reduce inflammation and pulmonary
edema are emphasized.

Solvents
A. Aliphatic Hydrocarbon
-This group includes halogenated solvents such as carbon tetrachloride, chloroform, and
trichloroethylene.
-Solvents 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.
Treatment—Removal from exposure is the only specific treatment available.

B. Aromatic Hydrocarbons
- Benzene- clastogen, ie, a mutagen that acts by causing chromosomal breakage
-toluene, and xylene are important aromatic hydrocarbons.
Effects—Acute exposure to any of these hydrocarbons leads to CNS depression with ataxia and
coma. Long-term exposure to benzene is associated with hematotoxicity
Treatment—Removal from exposure is the only specific way to reduce toxicity. CNS depression is
managed by support of vital signs

PESTICIDES
-These agents interfere with inactivation of the sodium channel in excitable membranes and cause
rapid repetitive firing in most neurons. Calcium ion transport is inhibited. These events affect
repolarization and enhance the excitability of neurons. The major effect is CNS stimulation.
Chlorinated Hydrocarbons/Organophosphorus Chlorine (rin,ane,chlor)
-These agents are persistent, poorly metabolized, lipophilic chemicals that exhibit significant
bioaccumulation.
-Effects—Chlorinated hydrocarbons block physiologic inactivation 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.
Treatment—No specific treatment is available for the acute toxicity caused by chlorinated
hydrocarbons.
Cholinesterase Inhibitors/Organophosphorus Pesticides (on,os,-methyl) and Carbamates
(an,yl,carb)
- 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.
-neuropathy target esterase (NTE).
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
paralysis. The most common cause of death is respiratory failure.
Treatment—Atropine is used in large doses to control muscarinic excess; pralidoxime is used to
regenerate cholinesterase .
Botanical Insecticides
1. Nicotine—Nicotine 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. Rotenone—This plant alkaloid pesticide causes gastrointestinal distress when ingested and
conjunctivitis and dermatitis after direct contact with exposed body surfaces. Treatment is
supportive.
3. Pyrethrum—The 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 supportive with anticonvulsants if necessary.

HERBICIDES
A. Chlorophenoxy Acids
-The 2 most important members of this group are 2,4-dichlorophenoxyacetic acid and 2,4,5-
trichlorophenoxyacetic acid, the compound in Agent Orange.
B. Glyphosate
-is the principle ingredient in Roundup brand weed killer and is now the most widely used herbicide
in the world. Its target, 5-enolpyruvylshikimate-3-phosphate synthase, a key enzyme involved in
aromatic amino acid biosynthesis in plants.
Effects—Glyphosate exposure causes significant eye and skin irritation and can be fatal when
ingested in large quantities.
treatment—Supportive, no specific treatment is available.
C. Paraquat
-a bipyridyl herbicide, is used extensively to kill weeds on farms and for highway maintenance.
Effects—The compound is relatively nontoxic unless ingested. After ingestion, the initial effect is
gastrointestinal irritation with hematemesis and bloody stools. Within a few days, signs of
pulmonary impairment occur and are usually progressive, resulting in severe pulmonary fibrosis
and often death.
Treatment—No specific antidote is available
ENVIRONMENTAL POLLUTANTS
A. 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 known. They are poorly metabolized and lipophilic. They are
therefore highly persistent in the environment, and they accumulate in the food chain.
Effects—In 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
Source—The 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.
Effects—In 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 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. Many countries have banned all use of asbestos because of its toxicity and strictly
regulate handling of preexisting asbestos building products.
Effects—Inhalation 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.

Heavy Metals
LEAD
-absorbed via the respiratory and gastrointestinal tracts.
-Lead is subsequently distributed to soft tissues such as the bone marrow, brain, kidney, liver,
muscle, and gonad

Mercury interacts with sulfhydryl groups in vivo, inhibiting enzymes and altering cell membranes