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CHAPTER 2

Toxicology
Because of the quantity and variety of chemicals
used by the chemical process industries, chemical
engineers must be knowledgeable about
the way toxicants enter biological organisms,
the way toxicants are eliminated from biological
organisms,
the effects of toxicants on biological organisms,
and
methods to prevent or reduce the entry of
toxicants into biological organisms.
The first three areas are related to toxicology.
The last area is essentially industrial hygiene.
"All substances are poisons; there is none which is
not a poison. The right dose differentiates a poison
and a remedy."
Harmless substances, such as water, can become
fatal if delivered to the biological organism in large
enough doses. A fundamental principle of toxicology
is: There are no harmless substances, only harmless
ways of using substances.
Today, toxicology is more adequately defined as
the qualitative and quantitative 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.
The toxicity of a chemical or physical agent is a
property of the agent describing its effect on
biological organisms.
Toxic hazard is the probability of damage to
biological organisms based on exposure
resulting from transport and other physical
factors of usage.

The toxic hazard of a substance can be


reduced by the application of appropriate
industrial hygiene techniques.

The toxicity, however, cannot be changed.


2-1 HOW TOXICANTS ENTER BIOLOGICAL
ORGANISMS

After the toxicant enters the


organism, it moves into the
bloodstream and is eventually
eliminated or it is transported to
the target organ.
The damage is exerted at the
target organ.
A common misconception is that damage
occurs in the organ where the toxicant is
most concentrated.
Lead, for instance, is stored in humans
mostly in the bone structure, but the
damage occurs in many organs.
For corrosive chemicals the damage to the
organism can occur without absorption or
transport through the blood stream.
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.
Entry Entry organ Method for control
route
Ingestion Mouth or Enforcement of rules on
stomach eating, drinking, and
smoking
Inhalation Mouth or nose Ventilation, respirators,
hoods, and other
personal protection
equipment
Injection Cuts in skin Proper protective
clothing
TABLE 2-1: ENTRY ROUTES
FOR TOXICANTS AND
Dermal Skin Proper protective
METHODS
absorption
FOR CONTROL
clothing

-1 :Inhalation
.

-2 :Absorption
.

-3 :Ingestion
:

- .
- .

-4 :Accidental Injection
.
Skin
SKIN
Injection includes both entry by absorption through cuts and

mechanical injection with hypodermic needles.

Most chemicals are not absorbed readily by the skin.

A few chemicals, however, do show remarkable skin

permeability. Phenol, for example, requires only a small area

of skin for the body to absorb an adequate amount to result

in death.

The skin on the palm of the hand is thicker than skin found

elsewhere. However, this skin demonstrates increased

porosity, resulting in higher toxicant absorption.


Respiratory System
RESPIRATORY SYSTEM
The respiratory system plays a significant role in toxicants

entering the body through inhalation.

The main function of the respiratory system is to

exchange oxygen and carbon dioxide between the blood

and the inhaled air.

In 1 minute a normal person at rest uses an estimated 250

ml of oxygen and expels approximately 200 ml of CO2.

Approximately 8L of air are breathed per minute.

Only a fraction of the total air within the lung is

exchanged with each breath.


The respiratory system is divided into two areas:
the upper and the lower respiratory system.
The upper respiratory system is composed of the
nose, sinuses, mouth, pharynx (section between
the mouth and esophagus), larynx (the voice
box), and the trachea or windpipe.
The lower respiratory system is composed of the
lungs and its smaller structures, including the
bronchi and the alveoli.
The bronchial tubes carry fresh air from the
trachea through a series of branching tubes to
The alveoli are small blind air sacs where the gas
exchange with the blood occurs.
An estimated 300 million alveoli are found in a
normal lung.
These alveoli contribute a total surface area of
approximately 70 m2.
Small capillaries found in the walls of the alveoli
transport the blood; an estimated 100 ml of blood
is in the capillaries at any moment.
The upper respiratory tract is responsible for
filtering, heating, and humidifying the air.
Fresh air brought in through the nose is
completely saturated with water and regulated to
the proper temperature by the time it reaches
the larynx.
The mucus lining the upper respiratory tract
assists in filtering
The upper and lower respiratory tracts respond
differently to the presence of toxicants.

The upper respiratory tract is affected mostly by


toxicants that are water soluble. These materials
either react or dissolve in the mucus to form acids
and bases.

Toxicants in the lower respiratory tract affect the


alveoli by physically blocking the transfer of gases
(as with insoluble dusts) or reacting with the wall of
the alveoli to produce corrosive or toxic substances.

Phosgene gas, for example, reacts with the water on


the alveoli wall to produce HCl and carbon monoxide.
Upper respiratory toxicants include hydrogen
halides (hydrogen chloride, hydrogen bromide),
oxides (nitrogen oxides, sulfur oxides, sodium
oxide), and hydroxides (ammonium hydroxide,
sodium dusts, and potassium hydroxides).
Lower respiratory toxicants include monomers
(such as acrylonitrile), halides (fluorine, chlorine,
bromine), and other miscellaneous substances such
as hydrogen sulfide, phosgene, methyl cyanide,
acrolein, asbestos dust, silica, and soot.
Dusts and other insoluble materials present a particular
difficulty to the lungs.
Particles that enter the alveoli are removed slowly.

For dusts the following simple rule usually applies:

The smaller the dust particles, the farther they penetrate

into the respiratory system.

Particles greater than 5 m in diameter are usually

filtered by the upper respiratory system.

Particles with diameters between 2and 5 m generally

reach the bronchial system.

Particles less than 1 m in diameter can reach the alveoli.


2-4 TOXICOLOGICAL STUDIES

A major objective of a toxicological study is to quantify the


effects of the suspect toxicant on a target organism. For most
toxicological studies animals are used, usually with the hope
that the results can be extrapolated to humans. Once the
effects of a suspect agent have been quantified, appropriate
procedures are established to ensure that the agent is handled
properly.
Before undertaking a toxicological study, the following items
must be identified:
the toxicant,
the target or test organism,
the effect or response to be monitored,
the dose range,
the period of the test.
The toxicant must be identified with respect to its chemical
composition and its physical state.

For example, benzene can exist in either liquid or vapor form.

Each physical state preferentially enters the body by a


different route and requires a different toxicological study.
The dose units depend on the method of delivery.

For substances delivered directly into the organism (by ingestion

or injection), the dose is measured in milligrams of agent per

kilogram of body weight.

For gaseous airborne substances the dose is measured in either

parts per million (ppm) or milligrams of agent per cubic meter of

air (mg/m3).

For airborne particulates the dose is measured in milligrams of

agent per cubic meter of air (mg/m3) or millions of particles per

cubic foot (mppcf).


2-5 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).
2-6 MODELS FOR DOSE AND RESPONSE CURVES

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

(probit =probability unit)


2-7 Relative Toxicity
2-8 Threshold Limit Values

The lowest value on the response versus dose


curve is called the threshold dose.
Below this dose the body is able to detoxify and
eliminate the agent without any detectable
effects. In reality the response is only identically
zero when the dose is zero, but for small doses the
response is not detectable.

There are three different types of TLVs (TLV-


TWA, TLV-STEL, and TLV-C) with definitions
provided in Table 2-7.
Table2-7 Definitions for Threshold Limit Values (TLVs)
TLV type Definition

TLV- Time-weighted average for a normal 8-hour workday or 40-


TWA hour work week, to which nearly all workers can be exposed,
day after day, without adverse effects. Excursions above the
limit are allowed if compensated by excursions below the limit.

TLV- Short-term exposure limit. The maximum concentration to


STEL which workers can be exposed for a period of up to 15 minutes
continuously without suffering (1) intolerable irritation, (2)
chronic or irreversible tissue change, (3) narcosis of sufficient
degree to increase accident proneness, impair self-rescue, or
materially reduce worker efficiency, provided that no more
than 4 excursions per day are permitted, with at least 60
minutes between exposure periods, and provided that the daily
TLV-TWA is not exceeded.

TLV-C Ceiling limit. The concentration that should not be exceeded,


even instantaneously.
Where:
T is the temperature in degrees Kelvin,
P is the absolute pressure in atm, and
M is the molecular weight in g/g-mol.
TLV and PEL values for a variety of toxicants are
provided in Table 2-8.
OSHA has defined its own threshold dose, called a permissible
exposure level (PEL).
Table 2-8 TLVs and PELS or a Variety of
Chemical Substances (OSHA Permissible
Exposure Limits)