Introduction to Toxicology

Live in a chemical environment w/c inhale, ingest and absorb from the skin
-Toxicolgy deals with the deleterious effects of agents on all living systems.
-Is primarily concerned with the adverse effects in humans resulting from exposure to drugs and other
chemicals as well as the demonstration of safety or hazard associated with their use
-Occupational
-Environmental
-Ecotoxicology
Toxicologic Terms & Definitions
1.hazard- ability of a chemical to cause injury in a given situation or setting. It is often a description
based on subjective estimates rather than objective. Potential to cause harm
2.Risk- expected frequency of the occurrence of an undesirable effect arising from exposure to a
chemical or physical agent. Uses dose-response data. Likelihood of harm. defines risk as the product
of the probability of a hazard resulting in an adverse event, times the severity of the event.
Routes of exposure:
Respiratory - inhalation
Gastrointestinal - ingestion
Dermatological – contact
Duration of exposure:
Acute – seconds to 1 – 2 days
Multiple – continuing over long periods of time
Routes of exposure:
Respiratory - inhalation
Gastrointestinal - ingestion
Dermatological – contact
Duration of exposure:
Acute – seconds to 1 – 2 days
Multiple – continuing over long periods of time
Bioaccumulation – chemical accumulates within the tissue of organism when the intake exceeds the
ability to metabolize or excrete the substance
Biomagnification – the concentration of a contaminant maybe magnified a hundred or thousand times
as the chemical moves in the food chain. An increase in concentration of a substance that occurs in the
food chain. Ex. Polychlorinated biphenyls (PBC)
plankton→ rainbow smelt→lake trout→herring gull

Specific Chemicals
Air pollutants
Solvents
Pesticides
Herbicides
Environmental pollutants
Metals

Air Pollutants
Carbon monoxide – 52%
Sulfur oxides – 14%
Hydrocarbons – 14%
Nitrogen oxides – 14%
Particulate matter – 4%

Carbon monoxide – colorless, tasteless, odorless and non-irritating gas, by product of incomplete
combustion
Mechanism of action:
CO combines reversibly with the oxygen binding sites of hemoglobin and has affinity for hemoglobin
220x that of oxygen. The byproduct, carboxyhemoglobin cannot transport oxygen. It also interferes
with the dissociation of O2 from oxyhemoglobin, reducing the transfer of O2 to tissues. Brain and
heart most affected
Clinical effects:
Psychomotor impairment, headache, confusion, loss of visual acuity, coma, shock
<15% = headache, malaise
25% = fatigue, decrease attention span, loss of fine motor coordination
40% = syncope, collapse
60% = death
Treatment:
Removal of patient from place
O2 administration
Hyperbaric oxygen chamber

Sulfur dioxide – colorless, irritant gas generated by combustion of sulfur containing fossil fuels.
Mechanism of action:
SO2 + moisture = sulfurous acid
Clinical effects:
Irritation eyes, nose, throat
90% absorbed in the respiratory tract = bronchoconstriction/bronchospasm
Treatment: non-specific, symptomatic

Nitrogen oxides – brownish irritant gas associated w/fire

Mechanism of action:
Relatively insoluble lung irritant causing pulmonary edema
Clinical Effects:
Irritation eye, nose, cough, mucoid or frothy sputum, dysnea, chest pain
Treatment:
- non-specific, maintain adequate ventilation, bronchodilators, sedatives and antibiotics

Ozone – bluish gas usually found in the atmosphere, found in electrical equipment and for air/water
purification
Clinical Effects:
Upper/lower respiratory tract irritant with edema causing substernal pain, throat dryness, change in
vision
Chronic bronchitis, bronchiolitis, fibrosis, emphysema
Treatment:
- Non specific, symptomatic

Solvents: Aliphatic Hydrocarbons

Halogenated aliphatic hydrocarbons
Usually found in degreasing and cleaning agents
Carbon tetrachloride, chloroform, trichloroethylene, tetrachloroethylene
Carbon tetrachloride, trichloroethylene = carcinogenic
Water pollutants
Mechanism of Action:
Class 2A probable human carcinogen = renal, prostate and testicular cancer. Can cause impaired
memory, peripheral neuropathy, nephrotoxicity
Treatment:
- Non specific, symptomatic
Aromatic hydrocarbons
Used for its solvent properties & synthesis of other chemicals
Benzene, toluene, xylene
2.1 Benzene – used in premium gasoline
Acute effects depression of CNS
Chronic effect is bone marrow injury, aplastic anemia, leukopenia, pancytopenia, thrombocytopenia,
lymphomas, myeloma, leukemia
2.2 Toulene
Skin and eye irritant, CNS depressant, does not have myelotoxic effects of benzene
Fetotoxic
2.3 Xylene
Skin and eye irritant, CNS depressant, does not have myelotoxic effects of benzene

Pesticides
4 types
1. Organochlorine pesticides
DDT, benzene hexachlorides, cyclodienes, toxaphenes
2. Organophosphorous pesticides
malathion, parathion, parathion methyl, Table 56-3
3. Carbamates
aldicarb, isolan, dimetan, carbaryl, Table 56-4
4. Botanical pesticides
- nicotine, rotenone, pyrethrum

Pesticides: Organochlorine
Mechanism of action:
Interfere with the inactivation of sodium channel in excitable membranes causing rapid repetitive
firing of neurons enhancing excitability. Tremor, convulsion
In chronic exposure, DDT may cause brain CA. DDE may cause testicular CA. Oxychlordane may
cause non-Hodgkins lymphoma
In the environment, degradation is slow and may cause bioaccumulation

Pesticides: Organophosphorous
Used insects and based on soman, sarin, tabun
Mechanism of action:
- Inhibition of acetycholinesterase in esteratic site, increase acetycholine activity. (SLUDGEM
syndrome). May also cause demyelination of nerves (neuropathy target esterase). Tingling burning
sensation with gait or ataxia. Non specific treatment. Atropine, pralidoxime or other anticholinergics.
In the environment they are not considered to be persistent pesticides. They are relatively unstable and
break down easily.

Pesticides: Carbamates
Mechanism of action:
Inhibit acetylcholinesterase by carbomylation of the esteratic site
Treatment is symptomatic only like in organophosphate poisoning but pralidoxime is not used
Atropine
Considered non-persistent pesticides, has little effect or impact on the environment
Pesticides: Botanical pesticides
Nicotine – it acts with acetycholine receptor at the postsynaptic membrane resulting in the
depolarization of the membrane. Treatment is symptomatic
Rotenone – cause GI irritation, conjunctivitis, dermatitis, rhinopharyngitis. Treatment is symptomatic
Pyrethrum – target is the CNS causing excitation, convulsion, tetanic paralysis. Symptomatic
treatment. RADAS – reactive airways dysfunction syndrome caused by pyrethoids

Herbicides
1. Chlorophenoxy herbicides:
- 2,4 dichlorophenoxyacetic acid; 2,4,5 tricholophenoxyacetic acid
Used for the destruction of weeds
Agent orange, can cause generalized hypotonia and coma, dioxin = carcinogen
2. glycophosphate/glycine:
Most widely used herbicide in the world, nonselective; glycophosphate-resistant plants
Mostly minor injuries, eye skin irritant
3. Bipyidyl herbicides:
Parquat is the most important agent in its class
Accumulates slowly in the lungs causing edema, alveolitis, progressive fibrosis
First signs after exposure hematemesis, bloody stools, congestive hemorrhagic pulmonary edema
Treatment: gastric lavage, cathartics, absorbents

Environmental Pollutants
Polychlorinated biphenyls
Endocrine disruptors
asbestos

Polychlorinated biphenyls: PCB, coplanar biphenyls

Used in heat transfer fluids, lubricating oils, wax extenders, flame retardants. Resistant to
environmental degradation hence bioaccumulate in food chains.
s/sx: dermatologic chloracne, folliculitis, erythema,rash
Carcinogenic
Polychlorinated dibenzo p-dioxins, highly toxic and can cause reproductive and developmental
problems, damage the immune system, interfere with hormones
Dioxins are found throughout the world in the environment and they accumulate in the food chain,
mainly in the fatty tissue of animals.

Environmental pollutants
Due to the omnipresence of dioxins, all people have background exposure, which is not expected to
affect human health. However, due to the highly toxic potential of this class of compounds, efforts
need to be undertaken to reduce current background exposure
Prevention or reduction of human exposure is best done via source-directed measures, i.e. strict
control of industrial processes to reduce formation of dioxins as much as possible

Endocrine disruptors:
They mimic, enhance or inhibit hormonal action
Phytoestrogens, mycoestrogens, DDT, PCB
Bioaccumulate
Causal relation between exposure to a specific environmental agent and an adverse health effect due to
endocrine modulation has not been established
Indications that breast and reproductive cancers ↑ hence exposures should be reduced

Asbestos - Asbestos is a mineral fiber that has been used commonly in a variety of building
construction materials for insulation and as a fire-retardant. Because of its fiber strength and heat
resistant properties, asbestos has been used for a wide range of manufactured goods, mostly in
building materials (roofing shingles, ceiling and floor tiles, paper products, and asbestos cement
products), friction products (automobile clutch, brake, and transmission parts), heat-resistant fabrics,
packaging, gaskets, and coatings
When asbestos-containing materials are damaged or disturbed by repair, remodeling or demolition
activities, microscopic fibers become airborne and can be inhaled into the lungs, where they can cause
significant health problems.
- Asbestos has been classified as a known human carcinogen 
- mesothelioma is the most common form of cancer associated with asbestos exposure. In addition to
lung cancer and mesothelioma, some studies have suggested an association between asbestos exposure
and gastrointestinal, colorectal cancers, as well as an elevated risk for cancers of
the throat, kidney, esophagus, and gallbladder. However, the evidence is inconclusive.

Metals: beryllium and cadmium

Beryllium - is a hard, grayish metal naturally found in mineral rocks, coal, soil, and volcanic dust.
Beryllium is purified for use in nuclear weapons and reactors, aircraft and space vehicle structures,
instruments, x-ray machines, and mirrors, used to make specialty ceramics for electrical and high-
technology applications. Beryllium alloys are used in automobiles, computers, sports equipment (golf
clubs and bicycle frames), and dental bridges
- classified by IARC class 1 human carcinogen
- Chronic beryllium disease is inflammation (with a granulomatous reaction) and scarring of the
lung tissue. Symptoms include increasing shortness of breath, dry cough, fatigue, weight loss and
chest pain. Chronic beryllium disease can damage the lungs, leading to death

Cadmium – used in cadmium batteries, pigments, solder, tv phosphors, plating orations. It is toxic by
inhalation and ingestion. Due to its low permissible exposure limit (PEL), overexposures may occur
even in situations where trace quantities of cadmium are found in the parent ore or smelter dust.
Cadmium Fume Fever – characterized by shaking chills, cough, fever, malaise. Can also cause severe
kidney damage
- known human carcinogen listed Group 1