ENVIRONMENTAL AND OCCUPATIONAL TOXICANTS

DEFINITION OF TERMS:
TOXICOLOGY:
The study of how natural or synthetic cause undesirable
effects in living organism
OCCUPATIONAL TOXICOLOGY
Deals with chemicals in the workplace
Identify agents of concern
Define the conditions leading to their safe Define the
conditions leading to their safe use
Prevent absorption of harmful amounts
Guidelines: threshold limit values (TLV)
ENVIRONMENTAL TOXICOLOGY
Deals with the potentially deleterious impact of chemicals
(pollutants in the environment) on living organisms
Environment includes all surroundings (air, water, soil)
Air pollution, chemicals used in agriculture, foo processing,
etc
Guidelines: Acceptable Daily Intake (ADI)
TOXICOLOGIC TERMS
HAZARD
The ability of a chemical to cause injury in a given situation
or setting
To assess need knowledge on the chemicals inherent
toxicity and amounts to which individuals are liable to be
exposed
RISK
The expected frequency of the occurrence of an undesirable
effect arising from exposure to a substance
Estimation of risk use of dose-response data &
extrapolation from the observed relationships to the
expected responses at doses occurring in actual situations
ROUTES OF EXPOSURE
Route of entry into the body differs indifferent exposure
situations
Industrial setting inhalation is the major route of entry
Other routes: transdermal (important route), oral ingestion
(minor)
DURATION OF EXPOSURE
Acute exposure a single or multiple exposures occurring
over 1 or 2 days
Chronic exposure multiple exposures continuing over a
longer period of time
Occupational setting both acute and chronic may occur
Chemicals in the environmental exposure chronic exposure
ENVIRONMENTAL IMPACT
Prediction is based on the following properties of chemical
agents:
Degradability
Mobility through air, water and soil
Bioaccumulation
Biomagnification
BIOACCUMULATION
The accumulation of toxic chemicals in living things through
consumption of food or water
BIOMAGNIFICATION
The process by which a contaminant, which may be hardly
detectable in water, may be magnified or concentrated as it
passes up the food chain
AIR POLLUTANTS
Five major substances that account for 98% of air pollution:
Carbon monoxide 52%
Sulfur oxides 14%
Hydrocarbons 14%
Nitrogen oxides 14%
Particulate matter 4%
Major sources:
Transportation
Industry
Generation of electric power
Space heating
Waste Disposal
JMP =)

CARBON MONOXIDE
CO
Colorless, odorless, tasteless, non-irritating gas
Byproduct of incomplete combustion
Average concentration in the atmosphere: 0.1 ppm
In heavy traffic: may exceed 100 ppm
Mechanism of Action
Combines reversibly with the oxygen-binding sites of
hemoglobin
Has an affinity for hemoglobin about 220 times that of oxygen
Carboxyhemoglobin product formed, cannot transport oxygen;
interferes with the dissociation of oxygen from remaining
oxyhemoglobin reducing transfer of oxygen to tissues
Clinical Effects
Principal signs of intoxication: hypoxia & progress in sequence:
1. psychomotor impairment
2. headache & tightness in the temporal area
3. confusion & loss of visual acuity
4. tachycardia, tachypnea, syncope, coma
5. deep coma, shock, convulsions, respiratory failure
Treatment
Acute intoxication:
removal from exposure
maintenance of respiration
administration of oxygen
SULFUR DIOXIDE
SO2
Colorless, irritant gas
Generated primarily by the combustion of sulfur-containing fossil
fuels
Mechanism of Action
On contact with membranes, SO2 forms sulfurous acid_severe
irritant effects on the eyes, mucous membranes and skin
Approx 90% of inhaled SO2 is absorbed in the URT
Exposure to 5 ppm for 10 minutes leads to increased resistance
to airflow in humans
Clinical Effects & Treatment
Signs & symptoms of intoxication: irritation of the eyes, nose,
throat reflex bronchoconstriction
Severe exposure delayed onset pulmonary edema
Chronic exposure aggravation of chronic cardiopulmonary
disease
Treatment is non-specific; therapeutic maneuvers to address
respiratory tract irritation
NITROGEN OXIDES
NO2
Brownish, irritant gas
Associated with fires; also formed from fresh silage
Mechanism of Action
Deep lung irritant, may cause pulmonary edema
Type I alveoli chiefly affected in acute exposure
Exposure to:
25 ppm irritating to some individuals
50 ppm moderately irritating to eyes, nose
50 ppm for 1 hour pulmonary edema, subacute or chronic
pulmonary lesions
100 ppm pulmonary edema, death
Clinical Effects
Acute exposure irritation of eyes & nose, cough, mucoid or
frothy sputum production, dyspnea, chest pain
Clinical signs may subside in 2 weeks
Patient may pass into a 2nd stage of abruptly increasing severity,
w/recurring edema & fibrotic destruction of terminal bronchioles
Therapeutic measures employed for the management of deep
lung irritation and non-cardiogenic pulmonary edema

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OZONE
O3
Bluish irritant gas, occurs normally in the atmosphere (important
absorbent of UV light)
In the workplace: can occur around high-voltage electrical
equipment, ozone-producing devices used for air & water
purification
An important oxidant found in polluted urban air
Clinical Effects & Treatment
Irritant of mucous membranes; causes shallow rapid breathing,
decrease in pulmonary compliance
Mild exposure Upper respiratory tract irritation
Severe exposure deep lung irritation, pulmonary edema
O3 toxicity may result from the formation of reactive free
radicals
Exposure to
0.1 ppm for 10-30 mins irritation & dryness of the throat
> 0.1 ppm changes in visual acuity, substernal pain,
dyspnea
> 0.8 ppm impaired pulmonary function
Airway responsiveness & inflammation observed in humans
Therapeutic measures employed for the management of deep
lung irritation and non- cardiogenic pulmonary edems
SOLVENTS
Solvent a substance, usually a liquid, that can dissolve other
substances
1. Halogenated Aliphatic Hydrocarbons
2. Aromatic Hydrocarbons
HALOGENATED ALIPHATIC HYDROCARBONS
Agents used as industrial solvents, degreasing agents, cleaning
agents
Carbon tetrachloride
chloroform
trichloroethylene
tetrachloroethylene (perchloroethylene)
1,1,1-trichloroethylene (methyl chloroform)
Mechanism of Action & Clinical Effects
Depressants of the CNS in humans (chloroform most potent)
Chronic exposure to tetrachloroethylene impaired memory,
peripheral neuropathy
Hepatotoxicity ( carbon tetrachloride most potent)
Nephrotoxicity

carbon
tetrachloride,
chloroform,
trichloroethylene
Management of toxicity depends on organ involved
AROMATIC HYDROCARBONS
Benzene
Widely used, used as an intermediate in the synthesis of other
chemicals
Acute toxic effect: depression of the CNS
Exposure to:
7500 ppm for 30 mins_fatal
3000 ppm_euphoria, nausea, locomotor problems, coma
250-500 ppm_vertigo, drowsiness, headcahe, nausea
Chronic exposure: injury to the bone marrow_aplastic anemia,
leukopenia, pancytopenia, or thrombocytopenia
Toluene (methylbenzene)
CNS depressant
Exposure to:
800 ppm_severe fatigue, ataxia
10,00 ppm_rapid loss of consciousness
Chronic effects: not clear

INSECTICIDES
1. Organochlorine Insecticides
2. Organophosphorous Insecticides
3. Carbamate Insecticides
4. Botanical Insecticides

JMP =)

ORGANOCHLORINE INSECTICIDES
Classified into 4 groups:
1. DDT (chlorophenothane) & its analogs
2. Benzene hexachlorides
3. Cyclodienes
4. Toxaphenes
Are aryl, carbocyclic, or heterocyclic compounds containing
chlorine substituents
Can be absorbed through skin, by inhalation or oral ingestion
Human toxicology
Interfere with inactivation of the sodium channel in excitable
membranes, cause rapid repetitive firing in neurons
Calcium ion transport is inhibited
Major effect is CNS stimulation
Tremor (DDT) or convulsion may be the first sign of intoxication
Environmental Toxicology
Persistent chemicals
Degradation is slow compared with other insecticides
Bioaccumulation (particularly in aquatic ecosystems)
Presence or organic matter in soils favors adsorption onto soil
particles; poor adsorption in sandy soil
ORGANOPHOSPHOROUS INSECTICIDES
Utilized to combat a large variety of pests
Absorbed by the skin, respiratory & gastrointestinal tracts
Biotransformation is rapid
Human Toxicology
Inhibition of acetylcholinesterase, accumulation of acetylcholine
Exposure to high concentrations altered neurologic &
cognitive functions, psychological symptoms
Phosphorylation of neuropathy target esterase delayed
neurotoxicity (polyneuropathy, paralysis & axonal degeneration)
Environmental Toxicology
Not considered to be persistent pesticides
Relatively unstable and break down in the environment
CARBAMATE INSECTICIDES
Inhibit acetylcholinesterase by carbamoylation of the esteratic
site
Toxic properties similar to organophosphates
Clinical effects are of shorter duration than those of
organophosphates
Not persistent pesticides
BOTANICAL INSECTICIDES
Derived from natural sources: nicotine, rotenone, pyrethrum
Nicotine is rapidly absorbed from mucosal surfaces
Nicotine reacts with the acetylcholine receptor of the
postsynaptic membrane, resulting in depolarization
Toxic doses stimulation rapidly followed by blockade of
transmission
Rotenone produces gastrointestinal irritation with oral ingestion
Conjunctivitis, dermatitis, pharyngitis, rhinitis can occur
Treatment is symptomatic
Pyrethrum has six known insecticidal esters
Synthetic pyrethroids account for 30% of insecticide usage
worldwide
May be absorbed after inhalation or ingestion; skin
absorption not significant
Esters are extensively biotransformed, not highly toxic to
mammals
Major site of action: CNS
Excitation, convulsions, tetanic paralysis can occur
Targets are: voltage-gated sodium, calcium & chloride channels,
peripheral-type benzodiazepine receptors
Symptomatic treatment employed

HERBICIDES
1. Chloryphenoxy Herbicides
2. Bipyridyl Herbicides

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CHLORYPHENOXY HERBICIDES
2,4-Dichlorophenoxyacetic acid (2,4-D);
2,4,5-Trichlorophenoxyacetic acid (2,4,5-T) and their salts &
esters are the major compounds used to kill weeds
2,4-D in large doses coma, generalized muscle hypotonia
2,4,5-D coma may occur, less evident muscular dysfunction
BIPYRIDYL HERBICIDES
Paraquat is the most important agent
MOA: single-electron reduction of the herbicide to free radical
species
Clinical effects: oral exposure_Gastrointestinal irritation
(hematemesis, bloody stools)
delayed
toxicity_respiratory
distress,
congestive
hemorrhagic pulomonary edema with widespread cellular
proliferation
hepatic, renal, myocardial involvement
Interval between ingestion and death may be several weeks

Widely distributed initially to soft tissues:

bone marrow, brain, kidney, liver, muscle,
gonads subperiosteal surface of bone bone matrix
Crosses the placenta
Multisystemic toxic effects mediated by multiple modes of
action:
inhibition of enzymatic function
interference with the action of essential cations
disturbance of cellular redox status
alteration of the structure of cell membranes & receptors
Nervous system
Blood
Kidneys
Reproductive organs
Gastrointestinal tract
Cardiovascular system

Treatment
Prompt removal of paraquat in the GIT:
use of gastric lavage, cathartics, adsorbents to prevent
further absorption
Success of treatment in fewer than 50%
ENVIRONMENTAL POLLUTANTS
1. Polychlorinated biphenyls
2. Endocrine disruptors
POLYCHLORINATED BIPHENYLS
PCBs, coplanar biphenyls
Used as dielectric & heat transfer fluids, plasticizers, wax
extenders, flame retardants
Use has been terminated but persist in the environment
Highly stable, highly lipophilic, poorly metabolized, very resistant
to environmental degradation, bioaccumulate in food chain
Food is the major source in humans
Clinical effects
Effects on human reproduction & development, carcinogenicity
have yet to be established
Polychlorinated
dibenzo-p-dioxins
(PCDDs)
or
Dioxins,
Polychlorinated dibenzofurans (PCDFs): unwanted byproducts of
improperly controlled combustion processes, contaminants of
the environment
ENDOCRINE DISRUPTORS
Phytoestrogens, mycoestrogens, industrial Phytoestrogens,
mycoestrogens, industrial chemicals such as organochlorine,
PCBs chemicals such as organochlorine, PCBs
Estrogen-like or anti-androgenic properties Estrogen-like or antiandrogenic properties
Increasing
environmental
contamination,
Increasing
environmental contamination, bioaccumulation

HEAVY METALS
1. Lead
2. Arsenic
3. Mercury
LEAD
Lead poisoning is one of the oldest occupational and
environmental diseases
Lead continues to have widespread application: production of
storage batteries, metal alloys, solder, glass, plastics, ceramics
Low-level lead exposure
Pharmacokinetics
Inorganic lead is slowly but consistently absorbed via the
respiratory and GI tracts
Organic leads well absorbed through the skin
Most common cause of industrial poisoning lead dust
Non-industrial exposure primary route of exposure is intestinal
Lead is bound to erythrocytes
JMP =)

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