CHAPTER 2

TOXICOLOGY
•Many years ago, toxicology defined as the science of poisons.
But nowadays, toxicology is defined as a study of the adverse effects of
toxicants on biological organisms.

•A toxicant can be a chemical or physical agent including dusts, fibers,

noise, and radiation. A good example of a physical agent is asbestos
fiber, a known cause of lung damage and cancer.

•Toxicity is a property of the agent describing its effect on biological

organisms of a chemical or physical agent.

•Toxic Hazard is the likelihood of damage to biological organism based

on exposure resulting from transport and other physical factors of
usage.
Because of the quantity and variety of chemicals used by the
chemical process industries, chemical engineer must be knowledgeable
about;

1. How toxicants enter biological organisms

After the toxicant enters the organism, it moves into bloodstream
and is eventually eliminated or transported to the target organ. The
damage is exerted at the target organ where the toxicant is most
concentrated.

Toxicants enter biological organisms by the following routes:

• ingestion: through the mouth into the stomach
• inhalation: through the mouth or nose into the lungs.
 • injection: through cuts into the skin
• dermal absorption: through skin membrane.
The gastrointestinal tract, the skin and the respiratory system play
significant role in various routes entry.
•Gastrointestinal (GI) Tract
It plays the most significant role in toxicants entering the body
through ingestion. Food is the usual mechanism of exposure. The rate
and selectivity of absorption by the GI tract are highly dependent on
many conditions. The type of chemical, its molecular weight, molecule
size and shape, acidity, susceptibility to attack by intestinal flora and
many factors affect the rate of absorption.
•Skin
Injection includes both entry by absorption through cuts and
mechanical injection with hypodermic needles. Mechanical injection
can occur as a result of improper hypodermic needle storage in
laboratory.
Stratum corneum- an outer layer of skin consist of dead, dried
cells that resistant to permeation by toxicants.
•Respiratory System
It plays significant role in toxicants entering the body through
inhalation. The main function of respiratory system is to exchange
oxygen and carbon dioxide between blood and inhaled air.
Respiratory System is divided into two areas; the upper and lower
respiratory system
•Upper
Respiratory System- is responsible for filtering, heating
and humidifying the air.
 •Lower Respiratory System- the bronchial tubes carry fresh hair
from the trachea through a series of a branching tubes to alveoli. The
alveoli are small blind air sacs where the gas exchange with the blood
occurs.
2. How Toxicants are Eliminated from Biological Organism
Toxicants are eliminated and rendered inactive by the following
routes:
(a.) Excretion- through kidney, liver, lungs or other organs.

•Kidney- they eliminated substances that enter the body by ingestion,

inhalations, injections and dermal absorption. The toxicants are
extracted by kidney from the bloodstream and are excreted in urine.
•Lungs- elimination of substances particularly those that are volatile.
Example, chloroform and alcohol are excreted by this route.
•Liver- is the dominant organ in the detoxification process by bio
transform, in which the chemical agents are transformed by reaction
into either harmless or less harmful substance.

(b.) Detoxification- by changing the chemical into something less

harmful by transformation.

(c.) Storage- It involves depositing the chemical agent mostly in

fatty areas of the organism but also in bones, blood and, liver and
kidney. It can create future problem if the organisms’ food supply is
reduced and fatty deposits are metabolized.
 VARIOUS RESPONSES TO TOXICANT

Effects that irreversible

Carcinogen Causes cancer

Mutagen Causes chromosome damage

Reproductive Hazard Causes damage to reproductive

system

Effects that may or may not be

reversible

Dermatotoxic Affects skin

Hemotoxic Affects blood

Hepatotoxic Affects liver

Nephrotoxic Affects kidney

Neutrotoxic Affects nervous system

Pulmonotoxic Affects lungs

3. Effects of toxicants on biological organism

•Respiratory Problem- are diagnosed using a spirometer. The
patient exhale as hard and as fast as possible into device. The
spirometer measures;
1. Force Vital Capacity (FVC)- total volume exhaled.
2. Force Expired Volume (FEV)- measured at 1 second with units in
liters per second.
3. Force expiratory flow in the middle range of vital capacity (FEV 25 –
75%). Measured in liter per second.
4. Ratio of the observed FEV to FVC (FEV/FVC%)
Nervous System Disorder- diagnosed by examining the patient’s
mental status, cranial nerve function, motor system reflexes and
sensory system.
An electroencephalogram (EEG)- test the higher brain and
nervous system function, changes in skin texture, pigmentation,
vascularity and hair nail appearance are in dicative of possible toxic
exposures.
Blood Counts- it measure the red and white blood cells, hemoglobin
content and platelet count are performed easily and inexpensively.
Kidney Function- determined the variety of tests that measure the
chemical content and quantity of urine.
Liver Function- determined the variety of chemical tests on the blood
and urine.
4. TOXICOLOGY STUDIES
Before undertaking a toxicological study , the
following items must be identified;
•the toxicant
•the target of test organism
•the effect or response to be monitored
 •the dose range
•the period of test

Dose versus Response

• Biological organisms respond differently to the same dose of a
toxicant. These differences are a result of age, sex, weight, diet,
general health, and other factors. For example, consider the
effects of an irritant vapor on human eyes. Given the same dose
of vapors, some individuals will barely notice any irritation (weak
or low response), whereas other individuals will be severely
irritated (high response).
Consider a toxicological test run on a large number of
individuals. Each individual is exposed to the same dose and the
response is recorded.
A plot of the type shown in Figure 2-2 is prepared with the data.
The fraction or percentage of individuals experiencing a specific
response is plotted. Curves of the form shown in Figure 2-2 are
frequently represented by a normal or Gaussian distribution,
given by the equation.

Where:
f(x) is the probability (or fraction) of individuals experiencing a
specific response,
X is the response,
Ơ is the standard deviation, and
μ is the mean.
 • The standard deviation and mean characterize the shape and the
location of the normal distribution  curve, respectively. They are
computed from the original data f (xi) using the equations :

where :
n is the number of data points
The quantity Ơ2 is called the variance

The mean determines the location of the

curve with respect to the x
Figure 2-3 Effect of the standard deviation on a normal distribution with
a mean of 0. The distribution becomes more pronounced around
the mean as the standard deviation decreases
 The toxicological experiment is repeated for a number of different
doses, and normal curves similar to Figure 2-3 are drawn. The standard
deviation and mean response are determined from the data for each
dose. A complete dose-response curve is produced by plotting the
cumulative mean response at each dose. Error bars are drawn at (+and
-) Ơ around the mean.

A typical result is shown in Figure 2-6.For convenience, the response

is plotted versus the logarithm of the dose, as shown in Figure2-7.

This form provides a much straighter line in the middle of the response
curve than the simple response versus dose form of Figure 2-6. If the
response of interest is death or lethality, the response versus log dose
curve of Figure 2-7 is called a lethal dose curve. For comparison
purposes the dose that results in 50% Lethality of the
subjects is frequently reported. 
This is called the
• LD 50  dose (lethal dose for 50% of the subjects) other
values such as LD 10 or LD 90 are sometimes also reported.
• For gases, LC (Lethal concentration) data are used.
• If the response to the chemical or agent is minor and
reversible (such as minor eye irritation), the response-log dose
curve is called the effective dose (ED) curve. Values for ED 50
ED 10 and so forth are also used.
• Finally, if the response to the agent is toxic (an undesirable
response that is not lethal but is irreversible, such as liver or
lung damage), the response-log dose curve is called the toxic
dose, or TD curve.
Most often, response-dose curves are developed using acute toxicity
data. Chronic toxicity data are usually considerably different.
Furthermore, the data are complicated by differences in group age, sex,
and method of delivery. If several chemicals are involved, the toxicants
might interact :
• additively (the combined effect is the sum of
the individual effects)
•  synergistically (the combined effect is more
than the individual effects)
• potentiately (presence of one increases the effect of the other)
• antagonistically (both counteract each other)

Models for Dose and Response Curves

Response versus dose curves can be drawn for a wide variety
of exposures, including exposure to heat, pressure, radiation, impact,
and sound. For computational purposes the response versus dose
curve is not convenient; an analytical equation is preferred.
For single exposures the probit (probit =probability unit) method is
particularly suited, providing a straight-line equivalent to the response-
dose curve. The probit variable Y is related to the probability P by
Eq.2-4A
This equation provides a relationship between the probability P and
the probit variable Y. This relationship is plotted in Figure 2-9 and
tabulated in Table 2-4.

This equation provides a relationship between the probability P and

the probit variable Y. This relationship is plotted in Figure 2-9 and
tabulated in Table 2-4.

Table 2-5 lists a variety of probit equations for a number of

different types of exposures. The causative factor represents the dose
V .The probit variable Y is computed from
For spreadsheet computations a more useful expression for performing
the conversion from probits to percentage is given by

where erf is the error function

Relative Toxicity
Table 2-6 shows the Hodge-Sterner table for the
degree of toxicity. This table covers a range of doses from 1.0 mg/kg to
15,000 mg/kg. Toxicants are compared for relative toxicity based on the
LD, ED, or TD curves.

If the response dose curve for chemical A is to the right of the response-

dose curve for chemical B, then chemical A is more toxic. Care must be
taken when comparing two response-dose curves when partial data are
available. If the slopes of the curves differ substantially, the situation
shown in Figure2-13 might occur. If only a single data point is
available in the upper part of the curves, it might appear that chemical
A is always more toxic than chemical B.
The complete data show that chemical B is more toxic at lower doses.

Threshold Limit Values

 The lowest value on the response versus dose curve is called the
threshold dose.
 The American Conference of Governmental Industrial Hygienists
(ACGIH) has established threshold doses, called
threshold limit values (TLVs), for a large number of chemical
agents.
 The TLV was formerly called the maximum allowable
concentration (MAC).
 There are three different types of TLVs (TLV-TWA, TLV-STEL,
and TLV-C) with precise definition provided in Table 2-7.

 More TLV-TWA data are available than TWA-STEL or TLV-

C data.
 OSHA has defined its own threshold dose, called a permissible
exposure level (PEL).
  PEL values follow the TLV-TWA of the ACGIH closely.
However, the PEL values are not as numerous and are not
updated as frequently. 
 TLVs are often somewhat more conservative
 For some toxicants (particularly carcinogens) exposures at any
level are not permitted. These toxicants have zero thresholds.
 Another quantity frequently reported is the amount immediately
dangerous to life and health (IDLH).
 Exposures to this quantity and above should be avoided under
any circumstances.
 TLVs are reported using ppm (parts per million by volume),
mg/m3 (milligrams of vapor per cubic meter of air), or, for
dusts, mg/m3or mppcf (millions of particles per cubic foot of
air).For vapors, mg/m3 is converted to ppm using the equation:

Where:
T is the temperature in Kelvin
P is the absolute pressure in atm, and
M is the molecular weight in g/g-mol.

Some TLV and PEL values for a variety of toxicants are provided in Table
2-8.