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CHAPTER 3(a)

Toxicology

Instructional Learning Objectives


After completing this chapter, students
should be able to do the following:
i. explain how toxicants enter biological
organisms
ii. explain how toxicants are eliminated
from biological organisms
iii. explain how biological organisms
respond to the dose of a toxicant
iv. determine threshold doses

Chapter 3(a): Toxicology

Outlines
1.
2.
3.
4.
5.
6.

Introduction - Toxicology Studies & Definition


Routes of Entry
Causes and Effects
Models of Doses
Response Curves
Threshold Limit Values

Chapter 3(a): Toxicology

Introduction Toxicological Studies


Objective To quantify effects of suspect
toxicant on target organism
Parameters that must be pre-identified
Toxicant
chemical composition + physical state
Target Organism
single cell higher animals
Effect @ response to be monitored
Dose Range
method of delivery
Period of Test
acute toxicity: short-term (single
exposure)
chronic toxicity: long-term exposure
Chapter 3(a): Toxicology

Introduction Definition
A. Toxicology: study of adverse effects of
toxicants on biological organisms
B. Toxicants: chemical or physical agent
including dusts, fibers, noise and radiation
C. Toxicity: property of the agent describing
its effect on biological organisms
D. Toxic Hazard: likelihood of damage to
biological organisms based on exposure

Chapter 3(a): Toxicology

Routes of Entry

There are four primary routes by which


organisms are exposed to toxic
INHALATION

INGESTION
ABSORPTION *
INJECTION

* Industrially most significant

Routes of Entry
INGESTION
Swallowing a
substance
causes
penetration
into the blood
stream via
the stomach
and small
intestine.

INHALATION
INGESTION

ABSORPTION
INJECTION

INHALATION
Breathing and
smoking causes
us to inhale
substances
which enter the
lungs.
Substance
inhaled into the
lungs are
readily
absorbed into
blood
the
stream.
INHALATION
INGESTION

ABSORPTION

Routes of Entry
INJECTION

ABSORPTION

Injection occurs
when
substances are
forced through
this skin. This
can occur as a
result of such
means as
compressed air,
or by having the
skin scratched
bya penetrating
INHALATION
object.

Entering the body


through the skin
causes substances
to enter the blood
stream at a slower
rate than by
inhalation or
absorption.
However, the
resulting entry and
distribution within

the body
is the
INHALATION
same.

INGESTION

ABSORPTION

INGESTION

ABSORPTION

Routes of Entry - How Toxicants are Removed


Excretion: through the kidneys, liver, lungs or
other organs,
Detoxification: by changing the chemical into
something less harmful by biotransformation,
Storage: in the fatty tissue.
The kidneys are the dominant means of
excretion process
The liver is the dominant organ in the
detoxification process
Storage in the fatty areas, bones, liver and
kidney.
e.g. Heavy metal, Hg, Pb
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Causes & Effect

Various Responses to Toxicants

DANGER

Effects that are irreversible:

CANCER
CAUSING
AGENT

Carcinogen causes cancer


Mutagen causes chromosome damage
Teratogen : (Latin - The Study of
Monsters) causes birth defects

Effects that may or may not be irreversible:


Dermatotoxic affects skin Nephrotoxic affects kidneys
Hemotoxic affects blood Neurotoxic affects nervous
system.
Hepatotoxic affects liver
Pulmonotoxic affects lungs

Dose Vs. Response

DOSE - amount of exposure to an agent.


RESPONSE - the reaction to the dose.
EXPOSURE - contact with an agent
Example - Eating a plate of NASI LEMAK AYAM and
ROTI CANAI TELUR may be just fine but eating six
plates at one time may produce a very undesirable
response.

The dose makes the poison


Therapeutic
Effect

Increasing Dose
Chapter 3(a): Toxicology

Toxic
Effect
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Dose Vs. Response


Dose-response curve
graphically represents
the relationship
between the dose of a
stimulant (e.g.
chemicals, drugs) and
the response
produced
Biological organism
respond differently to
the same dose
of a toxicant due to
age, sex, weight,
general health, etc.
Chapter 3(a): Toxicology

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Dose Vs. Response


From Chemical Process Safety, Third Edition,
By Daniel A. Crowl and Joseph F. Louvar (ISBN: 0131382268)

Figure 2-13 Two toxicants with differing relative toxicities at different doses.
Toxicant A is more
toxic at high doses, whereas toxicant B is more toxic at low doses.
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Dose Vs. Response


What Can Be Learned From A Dose-Response
Curve? (Assessment of toxicity)
The Median Lethal Dose
LD50
The amount (dose) of a
chemical which produces
death in 50% of a population
of test animals to which it is
administered by any of a
variety of methods

The Median Lethal Concentration


LC50
The concentration of a chemical
in an environment (generally
air or water) which produces
death in 50% of an exposed
population of test animals in a
specified time frame

mg/kg
Normally expressed as
milligrams of substance per
kilogram of animal body
weight

mg/L
Normally expressed as milligrams
of substance per liter of air or
water (or as ppm)

Dose vs. Response Probit Analysis


The dose level of the various hazard
event (e.g. toxic release) against fatality
(or severe injuries or damage) can be
conveniently determined using Probit
Analysis.
It is a Graphical and Look-up Table
approach to determine probability of
fatality (or damage or injuries)

Chapter 3(a): Toxicology

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Dose vs. Response Probit Analysis

The graph plots the


relationship between
percentages
(fraction), P and
Probit variable, Y as
given by the
equation :
2

u
Y 5
P
exp du
1 2
2
2

Chapter 3(a): Toxicology

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Dose vs. Response Probit Analysis


The relationship between percentages (fraction), P
and Probit variable, Y as given by the equation on
previous slide :

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Dose vs. Response Probit Analysis


The Probit variable
can be computed from :

Y = k1 +k2 ln V
Where
V is the causative
variables

Chapter 3(a): Toxicology

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Dose vs. Response Probit Analysis


Below is the correlation that can be used to convert
Probits to percentage (%) without table and graph.

Chapter 3(a): Toxicology

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Dose vs. Response Quick Exercise 1

Chapter 3(a): Toxicology

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Dose vs. Response Quick Exercise 1

Chapter 3(a): Toxicology

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Dose vs. Response Probit Analysis


As the plot of Response vs. Log Dose is obtained
(slide 12), the relevant Probit variables could be
obtained by transforming the plot to straight-line
Probit vs. Log Dose curve.

Establish the straight-line


equation

Y = mslopelog(dose) + intercept

Chapter 3(a): Toxicology

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Dose vs. Response Probit Analysis


From Chemical Process Safety, Third Edition,
By Daniel A. Crowl and Joseph F. Louvar (ISBN: 0131382268)

Figure 2-10 The probit transformation converts the sigmoidal response versus
log dose curve
into a straight line when plotted on a linear probit scale. (Source: D. J.
Finney,
Probit Analysis, 3rd ed. (Cambridge: Cambridge University Press,
1971), p. 24.
Chapter 3(a): Toxicology
Reprinted by permission.)
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Dose vs. Response Quick Exercise 2


A data was reported involving the toxicity of rotenone to the
insect species Macrosiphoniella sanborni. The rotenone was
applied in a medium of 0.5% saponin, containing 5% alcohol. The
insect were examined and classified one day after spraying.

Chapter 3(a): Toxicology

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Dose vs. Response Quick Exercise 2

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Dose vs. Response Quick Exercise 2

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Threshold Limit Values & Types


The lowest value on the response vs. dose curve is called
as the threshold dose
Below this value, the body can detoxify and eliminate the
agent without any effects
TLVTWA Time weighted average for a normal 8 hour
workday or 40 hour workweek
TLVSTEL Short-term exposure limit. The maximum
concentration can be exposed to for up to 15 minutes.
Four excursions per day with at least 60 minutes
between
TLVC Ceiling limit. This concentration should not be
exceeded
Chapter 3(a): Toxicology
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Threshold Limit Values

Converting from mg/m3 to ppm


C ppm

22.4 T 1
3

(
mg
/
m
)


M 273 P

M is molecular weight
T is temperature in Kelvin
P is pressure in atm

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