A Review On Chapter 6 Industrial Toxicology Reading Discussion Help i need a summary for this chapter 500 words . Industrial Toxicology by Richard Cohen, M

A Review On Chapter 6 Industrial Toxicology Reading Discussion Help i need a summary for this chapter 500 words . Industrial Toxicology
by Richard Cohen, MD, MPH
oxicology is the science that studies the harmful, or toxic,
properties o f substances. We are exposed daily to a variety
o f substances that are not hazardous under usual circumstances.
However, any substance contacting or entering the body is inju­
rious at some excessive level o f exposure and theoretically can
be tolerated without harmful effect at some lower exposure.
A toxic effect is any reversible or irreversible harmful effect
on the body as a result of contact with a substance via the
respiratory tract, skin, eye, mouth, or other route. Toxic
effects are undesirable disturbances of physiological func­
tion caused by an overexposure to chemical or physical
agents. They also arise as side effects in response to medi­
cation and vaccines. Toxicity is the capacity of a chemical
to harm or injure a living organism. Toxicity entails the
dimension of quantity or d ose; the toxicity of a chemical
depends on the quantity necessary to impact health.
Many chemicals essential for health in small quantities
are highly toxic in larger quantities. Small amounts of zinc,
manganese, copper, molybdenum, selenium, chromium,
nickel, tin, potassium, and many other chemicals are essen­
tial for life. However, severe acute and chronic toxicity may
result from an uptake of large amounts of these materials.
For example, nickel and chromium in some of their forms
are considered carcinogens.
The responsibility of the industrial toxicologist is to
define how much is too much and to prescribe precaution­
ary measures and limitations so that usual or recommended
use or exposure does not result in the absorption of a harm­
ful quantity of a particular substance. From a toxicological
viewpoint, the industrial hygienist must consider all types of
exposure and the subsequent effects on the living organism.
Toxicity versus Hazard
Toxicity and hazard differ. Toxicologists consider toxicity
as the ability of a substance to produce an unwanted effect
when the substance has reached a sufficient concentration at
a certain site in the body; hazard is regarded as the probabil­
ity that this concentration will occur at that site. Many fac­
tors contribute to determining the degree of hazard— route
of entry, quantity of exposure, physiological state, environ­
mental variables, and other factors. Assessing a hazard
involves estimating the probability that a substance will
cause harm. Toxicity, along with the chemical and physical
properties of a substance, determines the level or degree of
hazard. Two liquids can possess the same degree of toxicity
but present different degrees of hazard. One may be odor­
less and not irritating to the eyes and nose whereas the other
may produce a pungent or disagreeable odor at a harmless
concentration. The material with the warning properties
at harmless concentrations may present a lesser degree of
hazard; its presence can be detected in time to avert injury.
Some chemical agents are not selective in their action
on tissues or cells and can exert a harmful effect on all liv­
ing matter. Other chemical agents act only on specific cells.
Some agents are harmful only to certain species; other spe­
cies have built-in protective mechanisms.
The term toxicity is commonly used in comparing one
chemical agent with another, but is meaningless without
data designating the biological species used and the condi­
tions under which the harmful effects were induced.
A chemical stimulus can be considered to have pro­
duced a toxic effect when it satisfies the following criteria:
• An observable or measurable physiological deviation
has been produced in any organ or organ system. The
change can be anatomic in character and may accelerate
or inhibit a normal physiological process, or the deviation
can be a specific biochemical change.
• The observed change can be duplicated from animal to
animal even though the dose-effect relationships vary.
• The stimulus has changed normal physiological processes
in such a way that a protective mechanism is impaired in
its defense against other adverse stimuli.
• The effect is either reversible or at least attenuated when
the stimulus is removed; however, permanent anatomic
and/or physiologic changes can result.
• The effect does not occur without a stimulus or occurs
so infrequently that it indicates generalized or nonspe­
cific response. When high degrees of susceptibility are
noted, equally significant degrees of resistance should be
• The observation must be noted and must be reproducible
by other investigators.
• The physiological change reduces the efficiency of an
organ or function and impairs physiological reserve in
such a way as to interfere with the ability to resist or
adapt to other normal stimuli, either permanently or tem­
The toxic effects of many substances used in industry
are well known, but the toxicity of others is not yet well
defined. Although certain important analogies are apparent
between structure and toxicity, important differences exist
that require individual study of each compound.
In addition to establishing toxicity, evaluation of a
chemical hazard involves establishing the amount and dura­
tion of exposure, the physical characteristics of the sub­
stance, the conditions under which exposure occurs, and
the determination of the effects of other substances in a
combined exposure. All of these may significantly influence
the toxic potency of a substance.
The chemical properties of a compound are often one
of the main factors in its hazard potential. Vapor pressure
(an indicator of how quickly a liquid or solid evaporates)
partially determines whether a substance has the potential
to pose a hazard from inhalation. Many solvents are quite
volatile and vaporize readily into the air to produce high
concentrations of vapor. Hence, a solvent with a low boil­
ing point would be a greater hazard than an equally toxic
solvent with a high boiling point simply because it is more
volatile and it evaporates faster.
Chemical injury can be local or systemic, and the
toxicological reactions can be slight or severe. Local injury
results from direct contact of the substance with tissue. The
skin can be severely burned or the surface of the eye can be
injured to the extent that vision is impaired. In the respi­
ratory tract, the lining of the trachea and the lungs can
be injured as a result of inhaling toxic amounts of vapors,
fumes, dusts, or mists. Systemic toxicity usually involves
passage of the agent through the blood vessels with result­
ing contact and injury to various internal organs (e.g., liver,
kidney, nervous system).
In discussing toxicity, it is necessary to know how a sub­
stance enters the body and, if relevant, the bloodstream.
For an adverse effect to occur, the toxic substance must
first reach the organ or bodily site where it causes damage.
Common “routes of entry” are inhalation, skin absorption,
ingestion, and injection. Depending on the substance and its
specific properties, however, entry (absorption) can occur
by more than one route, such as inhaling a solvent that can
also penetrate the skin.
For industrial exposures, a major, if not predominant,
route of entry is inhalation. Any airborne substance can
be inhaled.
The respiratory system is composed of two main areas:
the upper respiratory tract airways (the nose, throat, tra­
chea, and major bronchial tubes leading to the lobes of
the lungs) and the lower respiratory tract, which includes
smaller airways and the alveoli, where the actual transfer of
gases across thin cell walls takes place. For particles, only
those smaller than about 5-10 pm in diameter are likely to
enter the alveolar sac (See Chapter 2, The Lungs, for more
The total amount of a toxic compound absorbed via
the respiratory route depends on its concentration in the
air, the duration of exposure, and the pulmonary ventilation
volumes, which increase with higher work loads.
Gases and vapors of low water solubility but high fat
solubility pass through the alveolar lining into the blood­
stream and are distributed to organ sites for which they
have special affinity. During inhalation exposure at a uni­
form level, the absorption of the compound into the blood
reaches equilibrium with metabolism and elimination. Small
fibers and particles (0.1-10 pm in diameter) may settle in the
alveoli; small molecules and nanoparticles may pass through
the alveolar wall and reach pulmonary blood vessels.
Skin Absorption
An important route of entry for many chemicals is absorp­
tion through skin. Contact of a substance with skin results
in these four possible actions:
• The skin acts as an effective barrier.
• The substance reacts with the skin and causes local irri­
tation or tissue destruction.
• The substance produces skin sensitization.
• The substance penetrates the skin to reach the blood ves­
sels under the skin and enters the bloodstream.
For some substances (such as parathion), the skin has
been the main portal of entry in many toxic occupational
exposures. For other substances (such as aniline, nitroben­
zene, and phenol), the amounts absorbed through the skin
are roughly equivalent to the amounts absorbed through
inhalation. For the majority of other organic chemicals,
the contribution from skin (cutaneous) absorption to the
total amount absorbed is significant. Hence, toxic effects
can occur because of cutaneous penetration.
The cutaneous absorption rate of some organic chemi­
cals rises when temperature and perspiration increase.
Therefore, absorption can be higher in warm climates or
seasons. The absorption of liquid organic chemicals may
follow surface contamination of the skin or clothes; for
other compounds, it may directly follow the vapor phase,
in which case the rate of absorption is roughly proportional
to the air concentration of the vapors. The process involves
a combination of deposition of the substances on the skin
surface followed by absorption through the skin.
The physicochemical properties of a substance deter­
mine absorption potential through intact skin. Among the
important factors are skin pH and the chemical’s extent of
ionization, aqueous and lipid solubility, and molecular size.
Human skin shows great differences in absorption at
different anatomic regions, primarily due to differences in
thickness. The skin on the palm of the hand has approxi­
mately the same penetration potential as that of the forearm
for certain organic phosphates. The skin on the back of the
hand and the skin of the abdomen have twice the penetra­
tion potential of the forearm, whereas follicle-rich sites such
as the scalp, forehead, and scrotum show a much greater
penetration potential. High temperatures generally increase
skin absorption by increasing vasodilation and sweating.
If the skin is damaged by abrasion dermatitis, the normal
protective barrier to absorption of chemicals is lessened and
penetration occurs more easily (See Chapter 3, The Skin, for
more information).
The problem of ingesting chemicals is not widespread in
industry; most workers do not deliberately swallow mate­
rials they handle. Nevertheless, workers can ingest toxic
materials as a result of eating in contaminated work areas;
contaminated fingers and hands can lead to accidental oral
intake when a worker eats or smokes on the job. They can
also ingest substances when contaminants deposited in the
respiratory tract are carried out of the lung to the throat by
the action of the ciliated lining of the respiratory tract and
then swallowed. Approximately one quart of mucus is pro­
duced daily in an adult’s lungs. This constant flow of mucus
can carry contaminants out of the lungs into the throat to be
swallowed with the saliva or coughed up and expectorated.
Absorption after ingestion is often less than with inha­
lation because of the action of stomach acid and intestinal
enzymes, dilution by intestinal contents, and greater thick­
ness of the intestinal wall.
Although infrequent in industry, a substance can be injected
into some part of the body. This can be done directly into
the bloodstream, peritoneal cavity, pleural cavity, skin,
muscle, or any other place a needle or high-pressure orifice
can reach. The effects produced vary with the location of
administration. In industrial settings, injection is an infre­
quent route of worker chemical exposure.
There is, however, increasing attention to prevention of
skin puncture and injection injuries associated with bloodborne pathogens (hepatitis B, HIV, and hepatitis C). Risk
of infection is significant following accidental skin puncture
by a needle or instrument contaminated with infected blood
or tissue.
In the laboratory, toxic substances are injected into ani­
mals because it is far more convenient and less costly than
establishing blood levels by inhalation or skin exposures.
Intravenous injection sidesteps protective mechanisms in the
body that prevent substances from entering the blood.
After absorption via any route into the bloodstream, the
substance may enter the liver, which metabolically alters,
degrades, or detoxifies many substances. This detoxification
process is an important body defense mechanism. Basically,
detoxification involves chemical reactions, which in some
cases change the substance to a less toxic or more watersoluble compound.
A fundamental consideration in toxicology is the d o s e response relationship. In animal studies, a dose is adminis­
tered to test animals and increased or decreased until a
range is found where at the upper end all animals show
a preselected health effect (e.g., death, injury) and, at the
lower end, all animals are absent the health effect. The data
collected are used to prepare a dose-response curve relating
health effect incidence to dose administered (Figure 6-1).
The doses given are expressed as the quantity adminis­
tered per unit body weight, quantity per skin surface area,
or quantity per unit volume of respired air. In addition, the
length of time during which the dose was administered may
be indicated.
The dose-response relationship can also be expressed
as the product of a concentration (C) multiplied by the time
duration (T) of exposure. This product is proportional more
or less to a constant (K); or mathematically, C x T » K. The
dose involves two variables— concentration and duration
of exposure. For certain chemicals, a high concentration
breathed for a short time produces the same effect as a lower
concentration breathed for a longer time. The CT value
provides a rough approximation of other combinations of
concentration of a chemical and time that would produce
similar effects. Although this concept must be used very cau­
tiously and cannot be applied at extreme conditions of con­
centration or time, it can be useful in predicting safe limits
Figure 6 -1 . D ose-response curves for a chemical agent administered
to a uniform population o f test anim als. (LD = lethal dose; number
show n after LD indicates the percent o f exposed anim als that are
affected. L D J0 is the dose given at which 5 0 percent o f exposed
anim als died.)
for some airborne contaminants in the workplace. Regula­
tory exposure limits are sometimes set so that the combina­
tion of concentrations and time durations are theoretically
below the levels that produce injury to exposed individuals.
To determine a dose-response relationship or curve,
the dose should be delivered over a specified length of
time followed by observation for another specified period
of time— this may be hours or days, or even several years
when testing for carcinogenesis. For example, in one study
animals were exposed for a short time to nitrogen dioxide
(NOz). Initially, there was no observable response, but 36
hours after the exposure, the animals developed a chemical
pneumonia and ultimately died. If the animals had been
observed for only the first 24 hours after the exposure, the
health effects that occurred in the second 24-hour period
would have been missed.
Threshold Concept
For most chemicals there is a threshold o f effect, a no-effect
level or a level at which the rate of disease in the exposed
population is no different than the rate in the unexposed
population or “background.” The most toxic chemical
known, if present in small enough amounts, produces no
measurable effect. It may damage one cell or several cells,
but no measurable or clinically significant health effect,
such as reduced lung capacity, will result. As the dose is
increased, there is a point at which the first measurable
effect is noted or at which the incidence of a health effect in
the exposed population exceeds its incidence in unexposed
populations. The (toxic) potency of a chemical is defined by
the relationship between the dose (amount) of the chemical
and the response produced in a biological system. A high
concentration of toxic substance in the target organ causes a
severe reaction and a low concentration causes a less severe
or no reaction.
The word tox ic relates to the dose or amount of a
substance necessary to cause injury, illness, or significant
adverse health effect. If that dose is low compared to the
harmful dose for other substances, it is described as more
toxic. In other words, although all substances produce
harmful effects at some dose, a toxic substance causes harm­
ful effects at low doses.
Although most exposures in industry occur by way of
the respiratory tract or skin, most published dose-response
data are found in studies of experimental animals. In these
experiments, the test substances were usually administered
by mouth (in food, in drinking water, or by intubation
[tube] directly into the stomach) or injection (intravenous,
intramuscular, intraperitoneal, etc.).
The harmfulness of a material depends on its chemi­
cal composition, the type and rate or level of exposure,
and the fate of the material in the body. For many sub­
stances, a single large dose of a toxic substance produces
a greater response than the same total dose administered
in small amounts over a long period of time. Each of the
small amounts can be detoxified quickly, but a large dose
produces its detrimental action before appreciable detoxi­
fication occurs. If a substance is detoxified or excreted at a
rate slower than the rate of intake, it may cause continuing
(cumulative) effects.
Accumulation of a substance in the body is understood
as a process in which the level of the substance increases
with the duration of exposure and can apply to both con­
tinuous and repeated exposure. Biological tests of exposure
show that an accumulation is taking place when rising levels
of the substance are seen in the urine, blood, or expired air
(Figure 6-2).
Exposure thresholds are most easily determined (and
more available) for effects occurring soon after exposure.
Other effects such as birth defects and cancer occur months
or years after exposure began. Dose-related data are often
imprecise in human epidemiological studies. For these and
other reasons, thresholds for most carcinogens (such as
asbestos) have not been identified and are considered to
be zero.
Because different biological mechanisms are involved in
reproductive toxicity, attempts are being made to identify
exposure levels (mostly from animal studies) below which
no evidence of injury or impairment can be found; these are
called the N o O bservable Adverse E ffect Level (NOAEL).
Figure 6 -2 . A ccum ulation o f a substance in a body is show n in this
curve; in this exam ple the level o f the substance increases with the
duration o f exposure.
Lethal Dose
If a number of animals are exposed to a toxic substance,
when the concentration reaches a certain level, some but not
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