Industrial Toxicology Module

FACULTY OF
APPLIED SCIENCES
XBET3103
Industrial Toxicology
Copyright © Open University Malaysia (OUM)
XBET3103
INDUSTRIAL
TOXICOLOGY
Dr Ashima Srivastara
Dr Pratibha Singh
Harimah Hamdan

Third edition 2022
Second edition 2015
First edition 2012
Developed by Centre for Instructional Design and Technology, OUM.

Copyright © Open University Malaysia (OUM), XBET3103
All rights reserved. No part of this work may be reproduced in any form or by any means without
the written permission of the President of Open University Malaysia (OUM).
www.oum.edu.my

Course Guide xi–xviii
Topic 1: Introduction to Environmental and Occupational Toxicology 1
1.1 Environmental Toxicology 2

1.2 A Brief History of Environmental Toxicology 5
1.3 Scope of Toxicology 5
1.4 An Interdisciplinary Science 7
1.5 Applications of Toxicology 8
1.5.1 Clinical Toxicology 9
1.5.2 Forensic Toxicology 9
1.5.3 Industrial Toxicology 10
1.5.4 Environmental Toxicology 11
1.5.5 Biochemical and Molecular Toxicology 11
1.5.6 Product Development Toxicology 11
1.5.7 Regulatory Toxicology 11
1.5.8 Reproductive Toxicology 12
1.5.9 Occupational Toxicology 12
1.6 Fundamentals of Toxicology and Environmental Toxicology 18
1.6.1 Dose-effect Relationship 18
1.6.2 Routes of Exposure 20
1.6.3 Effects of Toxins 21
1.6.4 Hazardous Substances 22
1.6.5 Classification of Toxic Agents 23
1.6.6 Physiological Classification of Toxic Materials 24
1.7 Health Hazards 25
1.7.1 Toxic and Highly Toxic Substances 26
Summary 28
Key Terms 29
References 29

iv  TABLE OF CONTENTS
Topic 2: Environmental and Occupational Changes Towards Health 31
2.1 The Changing Environment and Disease Pattern 32

2.2 Epidemiological Transition 33
2.2.1 Human Activity 34
2.2.2 Climate Instability 34
2.2.3 Socioeconomic Inequities and Disparities 34
2.2.4 Higher Change of Incidence in Disease 34
2.3 Chemical Usage 35
2.3.1 Type of Toxicants 31
2.4 Pollutant Sources 38
2.4.1 Environmental Perspective 38
2.4.2 Occupational Perspective 39
2.4.3 Occupational Diseases 40
Summary 41
Key Terms 42
References 42
Topic 3: Occurrence of Toxicants 43
3.1 Toxicants 43
3.1.1 Concentration Range 43
3.2 Smog 46
3.2.1 Physical Description of Smog 46
3.2.2 Automobiles 47
3.2.3 Smog and Health 48
3.3 Smoke 49
3.3.1 Smoke from Fire 51
3.3.2 How Smoke Inhalation Damages the Body 52
3.3.3 Diagnosis of Smoke Inhalation Damage 53
3.3.4 Treatment 54
3.4 Offensive Odours 54
3.4.1 Sources of Environmental Odours 56
3.4.2 How Do You Measure Odour? 57
3.4.3 Odours and Health 58
3.4.4 Odour Control 59
3.4.5 Absorption 60
3.4.6 Liquid Scrubbing 61
3.4.7 Biofiltration 61
3.4.8 Bioscrubbers 62
3.4.9 Confirmation of Odour Removal Efficiency 62

TABLE OF CONTENTS  v
3.5 Agriculture Damage 62

3.5.1 Use of Pesticides 63
3.5.2 Dust 64
3.5.3 Toxic Gases 66
3.6 Malaysian Environmental Quality Act 1974 68
3.6.1 Objectives of the Act 69
3.6.2 Implementation Strategies 69
Summary 70
Key Terms 71
References 71
Topic 4: Damage Process and Action of Toxicants 73
4.1 Mechanism of Action 74

4.2 Factors Affecting Xenobiotic Action 76
4.2.1 Physiochemical Properties 76
4.2.2 Dose or Concentration 76
4.2.3 Time and Mode of Exposure 77
4.2.4 Environmental Factors 78
4.3 Metabolism of Environmental Chemicals 79
4.4 Defence Responses to Toxicants 80
Summary 83
Key Terms 84
References 84
Topic 5: Toxic Action of Pollutants 85
5.1 Toxins and Pollutants 86

5.2 Sources of Pollutants 87
5.3 Toxic Action of Major Pollutants 89
5.3.1 Metals 90
5.3.2 Toxic Chemicals in Air 99
5.3.3 Safe Drinking Water 101
5.3.4 Carcinogens (Cancer Causing Chemicals) 102
5.3.5 Cyanide 104
5.3.6 Methyl Isocyanate (MIC) 106
5.4 Effects of Toxicants on Plants 107
5.4.1 Harmful Effects of Metals 107
5.4.2 Harmful Effects of Gases in Air 111
Summary 116
Key Terms 117
References 118

vi  TABLE OF CONTENTS
Topic 6: Industrial Toxicants (PCBs, PBBs, Dioxins and Fluoride) 119
6.1 Industrial Process 120

6.2 Polychlorinated Biphenyls (PCBs) 121
6.2.1 Properties of PCBs 122
6.2.2 Sources of PCBs Pollution 123
6.2.3 PCBs Contamination Incident 123
6.2.4 Effect of PCBs 123
6.3 Polybrominated Biphenyls (PBBs) 125
6.3.1 Properties of PBBs 125
6.3.2 Source of PBBs 125
6.3.3 PBBs Contamination Incidents 125
6.3.4 Effects of PBBs 126
6.4 Dioxins 126
6.4.1 Properties of Dioxins 127
6.4.2 Sources of Dioxins 127
6.4.3 Dioxins Contamination Incidents 128
6.4.4 Effects of Dioxins 129
6.5 Fluoride 130
Summary 132
Key Terms 133
References 133
Topic 7: Target Organs 134
7.1 Toxicants and Their Exposure in the Human Body 135

7.2 Our Human Body in Physiological Perspective 136
7.3 Toxicants and Their Disruptions to Our Physiological Function 137
7.3.1 Effects of Toxicants on the Respiratory System 138
7.3.2 Effects of Toxicants on the Integumentary System 141
7.3.3 Effects of Toxicants on the Circulatory System 142
7.3.4 Effects of Toxicants on the Liver 144
7.3.5 Effects of Toxicants on the Kidney 150
7.3.6 Effects of Toxicants on the Reproductive System 153
Summary 159
Key Terms 161
References 161

TABLE OF CONTENTS  vii
Topic 8: Endocrine Disruption and Mutagenic Pollutants 163
8.1 The Endocrine System 164

8.2 Endocrine Disruptors 166
8.2.1 Characteristics of an Endocrine Disruptor 167
8.3 Review of Hormonal Function 169
8.4 Modes of Action 171
8.4.1 Interaction with Lipids or Amino Acids 171
8.4.2 Direct Effect on Genes 171
8.4.3 EDs Interference 171
8.5 Hormones and Cancers 172
8.6 Testing Oestrogenicity 174
8.7 Mutagen 175
8.7.1 Types of Mutagens 176
8.7.2 Effects of Mutagens 176
8.8 Mutation 177
8.8.1 Types of Mutation 179
8.8.2 Effects of Mutations 183
8.9 Induction of Mutation 184
8.9.1 Causes of Inductions 185
Summary 186
Key Terms 188
References 188

vii  TABLE OF CONTENTS

COURSE GUIDE

COURSE GUIDE  xi
COURSE GUIDE DESCRIPTION

You must read this Course Guide carefully from the beginning to the end. It tells
you briefly what the course is about and how you can work your way through
the course materials. It also suggests the amount of time you are likely to spend
in order to complete the course successfully. Please keep on referring to the
Course Guide as you go through the course materials as it will help you to
clarify important study components or points that you might miss or overlook.
INTRODUCTION
XBET3103 Industrial Toxicology is one of the courses offered at Open University
Malaysia (OUM). This course is worth 3 credit hours and should be covered over
8 to 15 weeks.
COURSE AUDIENCE
This course is offered to all learners taking the Bachelor of Occupational Health
and Safety Management programme. It aims to impart knowledge on the
principles of environmental and occupational toxicology.
As an open and distance learner, you should be able to learn independently

and optimise the learning modes and environment available to you. Before you
begin this course, please ensure that you have the correct course materials,
understand the course requirements, and know how the course is conducted.

xii  COURSE GUIDE
STUDY SCHEDULE
It is a standard OUM practice that learners accumulate 40 study hours for
every credit hour. As such, for a 3 credit hour course, you are expected to
spend 120 study hours. Figure 1 shows the student learning time (SLT).
Figure 1: Student Learning Time
COURSE LEARNING OUTCOMES

By the end of this course, you should be able to do the following:
1. Explain the fundamental principles of environmental and occupational
toxicology.
2. Analyse the effects of environmental and occupational toxicants risks toward
the community.
3. Initiate the solution for occupational and environmental health hazards in a
specified industry using related good practices obtained from various
literatures.

COURSE GUIDE  xiii
COURSE SYNOPSIS
This course is divided into 8 topics. The synopsis for each topic listed is as follows
(refer to Table 1):
Table 1: Synopsis for Each Topic
Topic Description
1 Describes environmental toxicology, including its brief history, scope,

interdisciplinary nature, applications, fundamentals, as well as health hazards.
2 Explains the changing environment and disease pattern, epidemiological

transition, chemical usage, and pollutant sources.
3 Discusses the occurrence of toxicants, generated from open burning, as well as

industrial and agriculture activities.
4 Explores the effects of toxicants on living organisms.
5 Discusses the toxic action of pollutants. The toxic chemicals are discharged into
the air, water, and soil, and get into human food chain via the environment.
6 Identifies industrial toxicants such as polychlorinated biphenyls (PCBs),

polybrominated biphenyls (PBBs), dioxins, and fluoride.
7 Explores toxicants and how our bodies are exposed to them. It elaborates on the
effects of toxicants on the respiratory system, integumentary system, circulatory
system, liver, kidneys, and reproductive system.
8 Discusses endocrine disruption and mutagenic pollutants. It explains the

endocrine system and its functions, endocrine disruptors, and the mode of
action associated with endocrine disruptors. It also covers mutagens, mutations,
their types and effects.

xiv  COURSE GUIDE
TEXT ARRANGEMENT GUIDE

Before you go through this module, it is important that you note the text
arrangement. Understanding the text arrangement will help you to organise your
study of this course in a more objective and effective way. Generally, the text
arrangement for each topic is as follows:
(a) Learning Outcomes

This section refers to what you should achieve after you have completely
covered a topic. As you go through each topic, you should frequently refer to
these learning outcomes. By doing this, you can continuously gauge
your understanding of the topic.
(b) Self-Check
This component of the module is included in strategic locations throughout
the module. It may be located after one subtopic or a few subtopics.
It usually comes in the form of a question. When you come across this
component, reflect on what you have already learnt thus far. By attempting
to answer the question, you should be able to gauge how well you have
understood the subtopic(s). Most of the time, the answers to the questions
can be found directly in the module itself.
(c) Activity
Similar to Self-Check, the Activity component is also placed at various
locations or junctures throughout the module. This component may
require you to answer questions, explore short case studies, or conduct
an observation or research. It may even require you to evaluate a given
scenario. When you come across an Activity, you should try to reflect
on what you have gathered from the module and apply it to real situations.
You should, at the same time, engage in Higher Order Thinking skills
(HOTs) i.e. analysing, synthesising, and evaluating instead of only recalling
and defining.
(d) Summary
You will find this component at the end of each topic. It summarises various
important parts of each topic and helps you to recap the whole topic.
By going through the summary, you should be able to gauge your knowledge
retention level. Should you find points in the summary that
you do not fully understand, it would be a good idea for you to revisit the
details in the module.

COURSE GUIDE  xv
(e) Key Terms

This component can be found at the end of each topic. You should
go through this component to remind yourself of important terms or
jargon used throughout the module. Should you find terms here that you
are not able to explain, you should look for the terms in the module.
(f) References
A list of relevant and useful textbooks, journals, articles, electronic contents,
and sources can be found in this section. The list may appear in a few
locations such as in the Course Guide (in the References section), at the end
of every topic, or at the back of the module. You are encouraged to read or
refer to the suggested references to obtain additional information and
enhance your overall understanding of the course.
PRIOR KNOWLEDGE
No prior knowledge is required.
ASSESSMENT METHOD
Please refer to .
REFERENCES
Boron, W. F., & Boulpaep, E. L. (2009). Medical physiology: A cellular and
molecular approach (2nd ed.). Elsevier/Saunders.
Department of Health and Human Services. (2011). Report on carcinogens

(12th ed.). Department of Health and Human Services.
Elschenbroich, C., & Salzer, A. (2006). Organometallics: A concise introduction

(2nd ed.). Wiley-VCH.
Fries, G. F. (1985). The PBB episode in Michigan: An overall appraisal. Critical

Reviews in Toxicology, 16(2), 105–156.
GreenFacts. (2006). PCBs Polychlorinated biphenyls. https://bit.ly/3pZSN6z
Griffiths, A. J. F., Miller, J. H., Suzuki, D. T., Lewontin, R. C., & Gelbart, W. M.
(1999). An introduction to genetic analysis (6th ed.). W. H. Freeman.

xvi  COURSE GUIDE
Hodgson, E. (2010). A textbook of modern toxicology (4th ed.). John Wiley and
Sons.
LaDou, J. (2006). Current occupational and environmental medicine (4th ed.).

McGraw Hill.
Luttrell, W. E., Jederberg, W. W., & Still, K. R. (2008). Toxicology principles for the
industrial hygienist. American Industrial Hygiene Association.
Maton, A., Hopkins, J., McLaughlin, C. W., Johnson, S., Warner, M. Q., LaHart, D.,
& Wright, J. D. (1993). Human biology and health. Prentice Hall.
Ming, H. Y. (2000). Environmental toxicology: Biological and health effects of

pollutants. CRC Press.
Monosson, E. (Ed.). (2013). Absorption of toxicants. The Encyclopedia of Earth.

https://editors.eol.org/eoearth/wiki/Absorption_of_toxicants
Monosson, E. (Ed.). (2013). Toxicity. The Encyclopedia of Earth.

https://editors.eol.org/eoearth/wiki/Toxicity
National Center for Biotechnology Information. (2000). Relation between

mutagens and carcinogens. https://bit.ly/3ECvnsd
Seager, S. L., & Slabaugh, M. R. (2004). Chemistry for today: General, organic
and biochemistry. Thomson Brooks/Cole.
Stenerson, J. (2004). Chemical pesticides: Mode of action and toxicology. CRC Press.
United States Environmental Protection Agency (EPA). (2021). What is a pesticide?

https://www.epa.gov/minimum-risk-pesticides/what-pesticide
Watterson, A. (2005). Toxicology in the working environment. In J. Rose (Ed.),

Environmental toxicology: Current developments, 7 (pp. 229–254). Gordon
and Breach Science Publishers.
World Health Organization (WHO). (2011). Global status report on

noncommunicable disease 2010. https://bit.ly/3c2jXBS
World Health Organization (WHO). (2016). Dioxins and their effect on human
health. https://bit.ly/3nSAVYG

COURSE GUIDE  xvii
TAN SRI DR ABDULLAH SANUSI (TSDAS) DIGITAL

LIBRARY
The TSDAS Digital Library has a wide range of print and online resources for
learners. This comprehensive digital library, which is accessible through the
OUM portal, provides access to more than 30 online databases and several of
them are shown in Figure 2. As an OUM learner, you are encouraged to make
full use of the resources available through this library.
Figure 2: Among the Online Databases Available at TSDAS Digital Library

xviii  COURSE GUIDE

Topic  Introduction to
Environmental
1 and
Occupational
Toxicology
By the end of this topic, you should be able to do the following:

1. Define environmental toxicology and its brief history.
2. Identify the scope of toxicology.
3. Explain environmental toxicology as an interdisciplinary
science.
4. Identify the applications of toxicology.
5. Describe the fundamentals of toxicology and environmental
toxicology.

2  TOPIC 1 INTRODUCTION TO ENVIRONMENTAL AND
OCCUPATIONAL TOXICOLOGY
Growing industrialisation and advances in technology have resulted in numerous

environmental issues. Poisonous substances in the air, water, soil, food, etc., are
issues that the world is confronting that are becoming a threat to the environment
today. These substances can be life-threatening to humans, animals, and other
living organisms, if not controlled immediately.
As part of the progressive world today, Malaysia has also experienced major
industrial and social changes leading to more poisonous substances in the
environment; and this have resulted in growing health problems and disorders in
Malaysia. During the early years of industrialisation in our country from 1983 to
1997, little attention was given towards environmental issues, and the nation had to
go through some of the most harmful consequences arising from pollution.
The poisonous substances in the air were causing respiratory disease, chronic heart
disease, and also weakening of the immune system and lungs. All such forms of
diseases were being encountered and the government chose to formulate a
blueprint that comprised programmes like the Malaysian Air Quality Guidelines,
Haze Action Plan and Air Pollution Index. All of these programmes were goal
oriented, but the common intention was to deal with the growing environmental
threat.
Let us get to know more on the environmental and occupational toxicology in this
first topic. Happy reading!
1.1 ENVIRONMENTAL TOXICOLOGY

Traditionally, environmental toxicology has been defined as the science of the
study of qualitative and quantitative aspects of injurious effects of chemical and
physical agents in the environment.
Generally, the evolution of a scientific subject is slow, commencing with

investigations of fundamental mechanisms, followed by an understanding of these
mechanisms, and moving to prediction and global understanding. Environmental
toxicology, however, is quite different. It has evolved rapidly, being driven by
worries about the environmental devastation caused by human activity.

TOPIC 1 INTRODUCTION TO ENVIRONMENTAL AND  3
Realising the potential for toxicity of agents found in nature has been a
requirement for human survival. One of the first acknowledged instances of the
unwanted toxicity of a fabricated product was lead intoxication in Roman times,
due to the prevalence of lead plumbing and lead dishware.
Today, the stress of toxicology is on discovering and preventing unwanted

outcomes of chemical and physical agents.
Environmental toxicology is a young field that has developed rapidly over the past
40 years. It involves the studying of sources, pathways, transformations, and
effects of chemicals that are harmful in the environment. The study of these
harmful effects extends from individuals and population of organisms to the
ecosystem level.
So what is environmental toxicology? The following is the definition of

environmental toxicology.
Environmental toxicology is a newly-developed field which is concerned with

the harmful effects of chemical, physical, and biological agents on living
organisms, including humans, plants, and animals.
Environmental toxicology utilises a variety of methods to study the force of toxic

agents on living organisms and supplies powerful tools for considering the risks
associated with the presence of these agents.
In other words, environmental toxicology is the study of nature, properties, effects,

and detection of toxic substances in the environment and in any environmentally-
exposed species, including humans (see Figure 1.1).

Figure 1.1: Components of the Environment
Source: http://extoxnet.orst.edu/newsletters/ucd2010/etxlogo.JPG
It involves the understanding of natural and anthropogenic pollutants,

anthropogenic pollutantsÊ life cycles, and their impact upon the structure and
functions of the biological and ecological systems.
SELF-CHECK 1.1
Define environmental toxicology.
ACTIVITY 1.1
You have been exposed to the concept of environmental toxicology. Based

on your current understanding of the subject and your knowledge about
toxicants, answer the following questions:
(a) List the factors leading to pollution in environment.
(b) Why is it important to study those factors?
Discuss your answers with your coursemates in the myINSPIRE forum.

1.2 A BRIEF HISTORY OF ENVIRONMENTAL

TOXICOLOGY
In this subtopic, we will highlight a brief history of environmental toxicology. Let
us see Table 1.1 for the history of environmental toxicology.
Table 1.1: A Brief History of Environmental Toxicology
Time Description
1499 to 1541 Physicians and alchemists were the first students of toxicology.
Paracelsus, the Swiss physician was well-known mostly for the
formulation of the dose-response relationship. Paracelsus observed that
some chemicals administered to patients at low concentrations had a
therapeutic effect, while high concentrations produced toxic effects.
1787 to 1853 The Spanish physician, Mattieu Orfila, brought in the major advances in
toxicology. Orfila published a complete paper on the toxicity of natural
substances. He acknowledged a relationship between the toxic
symptoms of the patients (pathology) and the chemical content of the
tissues.
1813 to 1878 The French physiologist, Claude Bernard, introduced a more strategic
approach to toxicology by performing several experiments on animals.
The conclusion and theories produced by Orfila and Bernard over a
100-year span became the foundation of toxicology as a science.
19th century The Chemical Revolution started with a rapid expansion in the
extraction of natural chemicals and the production of new synthetic
compounds.
1.3 SCOPE OF TOXICOLOGY

Environmental toxicology is committed to the general chemistry, environmental
behaviour and fate, toxicology, and ecotoxicology of xenobiotics and natural
toxins. It is the systematic study of the effects of chemicals on the environment and
how natural and man-made pollutants impact the health of humans, wildlife, and
the entire ecosystem.
In addition, environmental toxicology covers more than just chemicals passed into
the environment; it also includes examining and interpreting the harmful
outcomes induced by these chemicals on living systems such as wildlife, marine
species, pets, humans, and the ecological systems.

Environmental toxicology research not only adds to the collective knowledge

about pollutants, but studies can also help land developers and protection agencies
make better decisions regarding environmental policy.
Environmental toxicology today has a wide scope in terms of career. To begin a

career in this field, a person usually needs to obtain at least a bachelor's degree. A
four-year degree in environmental science, biology, or chemistry may be sufficient
to become a field researcher. An individual who wants to design and lead
independent studies typically needs a PhD in environmental toxicology and
several years of post-doctoral fellowship training. Scientists with years of
experience enjoy fulfilling, exciting careers, and advocate positive changes in
environmental protection.
There are several divisions of toxicology. These divisions are shown in Figure 1.2.
Figure 1.2: Scope of Environmental Toxicology

1.4 AN INTERDISCIPLINARY SCIENCE

As a scientific discipline, environmental toxicology represents the interface
between chemistry and biology. Let us see Figure 1.3 which shows you the
interdisciplinary core of environment toxicology.
Figure 1.3: Interdisciplinary Core of Environmental Toxicology
As you can see in Figure 1.3, the interdisciplinary core of environment toxicology
borrows heavily from a variety of disciplines such as:
• environmental science
• chemistry
• biology
• computer and mathematics
• toxicology
The interdisciplinary nature of environmental toxicology concentrates on the

application of science in environmental decision-making, regulation, and
management.

Collectively, they assist the professionals in academia, business, government, and

other sections of society involved in the consumption, protection, and management
of the environment for the enhancement of ecological wellness and human well-
being. They conjointly develop the potentialities for the forecasting, measurement,
and judgment of the fate and outcomes of chemicals in the environment.
SELF-CHECK 1.2
Describe the scope of environmental toxicology and its interdisciplinary

nature.
1.5 APPLICATIONS OF TOXICOLOGY

Before we learn the applications of toxicology, let us get to know the meaning of
toxicology.
Toxicology is the scientific discipline of poisonous substances.
There are many applications when it comes to toxicology. Among them are listed
in Figure 1.4.
Figure 1.4: Nine Applications of Toxicology
These nine applications are further explained in the next subtopics.

1.5.1 Clinical Toxicology

Clinical toxicology deals with the toxic effects of agents (drugs) whose purpose is
to ameliorate or prevent a disease. In other words, clinical toxicology focuses on
the diseases associated with short-term and long-term exposure to various toxic
chemicals. It usually coincides with other sciences such as biochemistry,
pharmacology, and pathology.
• Biochemistry is the study of the chemical processes going on in the body.
• Pharmacology deals with the actions of drugs in the body.
• Pathology deals with disease and its diagnosis through the examination of
tissues and bodily fluids.
Individuals who specialise in clinical toxicology are called clinical toxicologists.

Identification, diagnosis, and treatment of conditions resulting from exposure to
harmful agents are their main job responsibilities. In addition, they study the toxic
effects of various drugs. Their main concern is the treatment and prevention of
drug toxicity in the population.
1.5.2 Forensic Toxicology

What is forensic toxicology?
Forensic toxicology is the use of toxicology and other disciplines such as

analytical chemistry, pharmacology, and clinical chemistry to aid medical or
legal investigation of death, poisoning, and drug use.
Take note that the legal outcome of the toxicological investigation is not the
primary concern for forensic toxicology.
There are various kinds of samples that can be analysed through toxicology. A
forensic toxicologist must consider the situation of an investigation such as any
physical symptoms recorded or any evidence collected at a crime scene that may
be of great help like pill bottles, powders, trace residue, and any available
chemicals.

Given all information needed and samples to work on, the forensic toxicologist
concludes which toxic substances are present, in what concentrations, and the
possible effect of those chemicals on the individual. Verifying the substance
ingested is made complicated by the body's natural processes, because it is
unusual for a chemical to remain in its original form once it is in the body.
For example, heroin is more or less immediately metabolised into another

substance and further to morphine; making detailed investigation into factors such
as injection marks and chemical purity necessary to confirm the diagnosis.
The substance could have been diluted by spreading through the body; while a pill
or other regulated dose of a drug may have grams or milligrams of the active
constituent, an individual sample under investigation may only contain
micrograms or nanograms.
Forensic toxicology mainly covers:
• medical-legal aspects of poisonings;
• identification and quantification of poisons; and
• establishing a relationship between tissue residual level and probable cause of

death.
1.5.3 Industrial Toxicology

What is industrial toxicology?
Industrial toxicology is a science that deals with potential harmful effects of

materials, products, and wastes on health and environments.
Toxicology combines the knowledge from the following fields:
• chemistry
• biology
• pharmacology
• physiology
• pathology

1.5.4 Environmental Toxicology

Let us learn the definition of environmental toxicology first before we go further.
Environmental toxicology is a study of the effects of environmental

contaminants on organisms.
People are motivated to learn this topic because human beings are constantly
exposed to the environment and need to understand the health of our ecosystem.
It is used to identify:
• movement of chemicals in the environment (soil, air, water); and
• residual life of chemicals in the environment.
1.5.5 Biochemical and Molecular Toxicology

Biochemical and molecular toxicology is used for determining:
• the modes of action of chemicals at the molecular level; and
• the effects of chemicals on DNA, cancer genes.
1.5.6 Product Development Toxicology

Product development toxicology provides:
• service and pre-clinical toxicology for product development;
• evaluation of full toxic potential of chemicals destined for drug use; and
• establishment of safe doses for people.
1.5.7 Regulatory Toxicology

Regulatory toxicology is related with the industry and government setting. It
provides:
• solvent vapour thresholds in the industry;
• safe levels for human drugs;

• safe levels of heavy metals in water;
• safe levels of pesticides; and
• analyses of toxicological data, deciphered for risk estimation.
1.5.8 Reproductive Toxicology

It is a study and treatment of chemicals and their effects on reproduction in
humans. It includes the causes of infertility and the outcome some substances have
on the ova and spermatozoa, and the possible effects these substances have on
young ones.
There are many case studies which indicate that chemicals being used in food and
drugs are harmful, and the environment may have a direct impact on reproductive
health. It studies:
• the potential effects of environmental chemicals and toxins on human

offspring;
• certain birth defects and disorders due to the direct result of certain chemicals
used in many households; and
• the direct result of toxins.
1.5.9 Occupational Toxicology

For centuries, the work environment has contributed significant risk of adverse
health effects due to chemical and biological hazards. It applies the basics of
toxicology and epidemiology in setting up possible relationships between
occupational exposure and adverse health effects. Identification and monitoring of
potential hazardous exposure in the work environment is the key to preventing
adverse health effects.
What is the objectives of occupational toxicology? The objectives of occupational

toxicology are to:
• identify chemical, physical, or biological hazards in the work environment;
• identify adverse health effects that arise out of workers' exposure to these
toxicants; and
• set up control measures to prevent or minimise exposure.

In many countries, workers are asked to work – with little or no protection – with
chemicals that are recognised to be dangerous to human health. In fact, workers in
many developing countries are frequently asked to work with toxic chemicals that
have been banned in developed countries because of their dangerous consequences.
Likewise, agriculture workers in developing countries (and in non-union agriculture
occupations in some developed countries) frequently spray herbicides and
pesticides without any kind of protection.
In most developed countries, workers applying those same chemicals wear

preventive attires to avoid contamination from the chemicals, and are furnished
with proper washing facilities and orderly medical check-ups.
Through toxicological methods, toxicology applied to the working environment

entails the study of any substances, metals, or other materials which may affect
people at work. Working environments may cover those in industry, commerce,
education, the health sector, the leisure sector, and transport. The term
occupational toxicology and not industrial toxicology is therefore most accurate.
Occupational toxicology, and the risk assessments, control standards, and auditing
of those standards have provided many of the early warnings about wider
environmental problems through illnesses detected in production workers and
other users of toxic substances. The working environment is often the frontline and
source of wider environmental pollution. Workers are the „canaries‰ for
populations outside the workplace.
There are 10 million known chemical substances in the world and around
1,000 new chemicals introduced each year. Working out the interactions between
the two substances in the workplace is still beyond the capacity of advanced
industrial society.
Working out the uptake, distribution, storage, metabolism, excretion, and effect of
even a single substance on this list in a vast range of working conditions is a
mammoth task. Working out the interactions between these substances in the
workplace is still beyond our capacity as advanced industrial societies. Trying to
assess the long-term low level effects of workersÊ exposures to such substances is
not possible, even with the use of sophisticated toxicological and epidemiological
techniques. Some consideration is needed on how exposures outside the
workplace may affect workers within the company and vice versa.
The inter-relationship between toxic substances inside and outside the workplace
has been increasingly recognised in recent decades. The capacity of toxicology to
predict the likely human effects of workplace exposures to toxic substances may
be better than for some areas of environmental exposure but it is limited. The limits

partly relate to the wide range of conditions (temperature, humidity, ventilation,

noise, vibration, physical and mental stress and exertion), length of exposure, and
the wide range of other substances and processes to which employees may be
exposed to in the workplace. Toxicity may also be affected by age, gender, health
status, and ethnicity.
Now, let us discuss the exposure of toxic substance at the workplace. The routes
of entry into the body of substances found in the workplace are through inhalation,
ingestion, and skin absorption. Substances in the workplace may take the shape of
dusts, fumes, mists, vapour, and gases.
Much of the testing done on industrial and commercial chemicals relate to

ingestion through lethal dose (LD) and other tests, rather than lethal concentration
(LC) tests or skin penetration and absorption indicators; yet ingestion is often the
least likely source of occupational exposure. Skin and lung exposure are usually
far more important.
There is, therefore, a need to weigh the significance of routes of entry in terms of a
particular occupation. We must also consider the total dose of substance a worker
may be exposed to by a combination of routes of entry. Much of this research is
still relatively speculative as indeed there have been studies in the past which can
accurately assess exposures from multiple routes of entry or even the effectiveness
of personal protective equipment (PPE), especially gloves, in reducing
contamination at the workplace.
Toxic substances may have local or systemic effects, or both. The former is often
easier to identify than the latter in the workplace. Likewise, the acute effects of
exposure to a substance may be relatively easily recognised at the workplace,
whereas the chronic effects may not.
What are the problems with occupational toxicology? Human beings have always
been intuitive toxicologists, relying on their senses of sight, taste, and smell to
detect harmful or unsafe food, water, and air. As we have come to recognise that
our senses are not adequate to assess the dangers inherent in exposure to a
chemical substance, we have created the sciences of toxicology and risk assessment
to perform this function.
Yet, despite this great effort to overcome the limitations of intuitive toxicology, it
has become evident that even our best scientific methods still depend heavily on
extrapolations and judgements in order to infer human health risks from animal
data.

The latest emphasis among many toxicologists has been to claim a detailed
understanding of the mechanisms of toxicity of particular chemicals and to avoid
quantitative risk assessments used by agencies like the Environmental Protection
Agency (EPA) and the „Qstar‰ (Q*) system found in the US as too speculative and
reliant on statistical methods with flawed inputs. What is a Q* system?
The Q* is the quantitative assessment of a chemical's oncogenicity based on

the slope of the dose response curve from animal tests producing a positive
oncogenic response.
The slope describes the change in tumour incidence over the change in dose. The
assumptions are that mechanistic assessments do not fall into the same traps as
exclusively statistical methods and that somehow individual risk assessments so
derived will allow us to assess the many thousands of substances to which workers
are exposed to in a wide range of occupational activities and conditions. This is
fallacious and the risk assessments with the greater margins for error – along the
lines of the EPA – are the ones which offer the greatest protection to workers.
Indeed, Kraus and her colleagues, in a large study by the US and Scandinavian
toxicologists found that „controversies over chemical risks may be fuelled as much
by limitations of risk assessment and disagreements among experts as by public
misconceptions‰ (Watterson, 2005).
Toxicology risk assessments may rely on combining both mechanistic and

quantitative methods. The convention for setting „thresholds‰ in many countries
related to „safe‰ standards set for most of the working population for most of the
time over an eight-hour working day and a 40-hour working week.
Some formulae, based on the toxicity data, were provided for calculating safe
limits over a longer working week and also for mixtures. The validity and value of
the thresholds require careful scrutiny and there may be debates about the toxicity
data generated, the toxicity models developed, the specific mechanisms of toxicity
at work, and the significance of the data gaps which exist on a particular substance.
Toxicologists typically attempt to establish data for the following levels (see
Table 1.2).

Table 1.2: Three Levels of Toxicity
Level Description
No observed effect This is the highest exposure level at which no morphological,

level (NOEL) physiological, or functional modification of any kind is
detectable under the test conditions.
No observed adverse This is the highest dose level at which no biological adverse
effect level (NOAEL) effects occur.
Lowest observed This operates to set exposure levels when data are lacking to
adverse effect level set the NOAEL.
(LOAEL)
Occupational Safety and Health (Use and Standards of Exposure of Chemicals

Hazardous to Health) Regulations 2000 support the objectives of OSHA 1994 by
promoting the excellence in the management of chemicals at the workplace. The
objectives of the regulations are as follows:
• to secure the safety, health, and welfare of persons at work against risks to
safety or health arising out of the activities of persons at work;
• to protect persons at a place of work other than persons at work against the
risks to safety or health arising out of the activities of persons at work;
• to promote an occupational environment for persons at work which is adapted

to their physiological and psychological needs; and
• to provide the means whereby the associated occupational safety and health
legislations may be progressively replaced by a system of regulations and
approved industry codes of practice operating in combination with the
provisions of this act designed to maintain or improve the standards of safety
and health.

Exposure to harmful chemicals can result in higher rates of accidents at work. Look
at Figure 1.5 which shows you an example.
Figure 1.5: Working Around Chemicals Without Proper Protection Can Lead to
Serious Accidents
For instance, chemicals such as solvents and asphyxiants might slow your reaction
time by impacting your nervous system or restraining the quantity of oxygen that
gets to your lungs. A slow reaction can be very dangerous (or even fatal) if you are
in a serious situation that demands a quick reaction.
Unfortunately, when accidents take place in the workplace, management frequently

blames the worker, claiming he or she was reckless. This trend of blaming the victim
is yet another reason to study about the substances you work with, to make sure the
proper control measures are in place, and to know your rights.
SELF-CHECK 1.3
There are many applications when it comes to toxicology. Briefly describe

five of them.

ACTIVITY 1.2
List down some industrial accidents due to chemicals you have heard or
seen happened. What were the after effects on the workers? Discuss the
answers with your coursemates in the myINSPIRE forum.
1.6 FUNDAMENTALS OF TOXICOLOGY AND

ENVIRONMENTAL TOXICOLOGY
Now, let us discuss the fundamentals of toxicology and environmental toxicology.
First, we will look at the dose-effect relationship.
1.6.1 Dose-effect Relationship

Toxicologists normally look at two types of dose-effect relationship (see
Figure 1.6).
Figure 1.6: Dose-effect Relationship
One bears a threshold below through which no outcome is anticipated. For

instance, one drop of smoking sulphuric acid will burn a hole in the skin. However,
a drop in a bucketful of water dilutes the sulphuric acid to a degree at which no
consequences will come about. This is also known as no observed adverse effect
level (NOAEL) except for those that bring about their outcomes through mutation,
most notably due to numerous cancer-causing agents.

A mutation can in theory take place by a single chemical particle bringing about a
particular alteration in the chemical structure of a DNA particle, thereby changing
the genetic code from that of a normal cell to that of a mutated cell.
Additionally, knowledge about the differences among species in the consumption,

metabolic process, and disposal of chemicals is also important. However,
substantial similarity can be observed among mammalian species. Where conflicts
exist, attention to the dynamics of the processes that ascertain how an external
exposure level is transformed to the dose of a chemical at a target organ, allows
information of value to cross-species extrapolation.
There are several critical issues which make the interpretation of toxicological data
often controversial. Among them the most important ones are species-to-species
extrapolation and high-to-low dose extrapolation. The critical issue here is the
existence or lack of existence of a threshold dose below which no adverse effect
will occur. The other critical issue is the evaluation of the toxicity of mixtures
particularly in light of potential synergistic interactions.
In species-to-species extrapolation, the toxicity of chemicals cannot be studied in

humans for ethical reasons using priori-designed toxicological experiments.
Therefore, most toxicological information has been generated in surrogates via

animals. In general, animals are good but imperfect surrogates for humans. Dose-
and-time dependent functions may be different in animals. These result in a shift
of the dose-time-response in animals in comparison to the human dose-time-
response, either towards more or less susceptibility to a given compound.
Therefore, testing for toxicity always involves multiple species to identify the most
sensitive.
ACTIVITY 1.3
Give some instances of laboratory examples of dose-effect relationship.

Compare your answers with your coursemates in the myINSPIRE forum.

1.6.2 Routes of Exposure

There are three routes by which the toxic chemicals can enter the body
(see Figure 1.7).
Figure 1.7: Routes of Toxic Exposure
These three routes are further explained in Table 1.3.
Table 1.3: Three Routes of Toxic Exposure
Route Description
Inhalation Inhalation or breathing of chemicals is one of the most common routes of

entry for a chemical to enter the body.
Ingestion Ingestion means absorbing chemicals by way of mouth, while eating or

drinking.
Skin Chemicals can enter the body through the skin, hair follicles, sebaceous
absorption glands, sweat glands, and cuts or abrasions of the skin. Direct contact
effects and absorption of chemicals through the skin depend on a number
of factors.

SELF-CHECK 1.4
Explain the three routes of exposure of toxicants into the body.
1.6.3 Effects of Toxins

The adverse consequences of chemical substances depend upon the toxicity and
the exposure to that chemical. Toxicity is an attribute of the chemical substance,
whilst the exposure depends upon the path by which the chemical is used. The
level of exposure depends upon the absorption of the hazardous chemical and on
the period of contact time. Numerous substances do not give any signal by odour,
although they may exist at harmful concentrations in the air. There are two types
of toxin effects as explained in Table 1.4.
Table 1.4: Two Types of Toxin Effects
Type Description
Acute The effects may be acute; subsequent to a short exposure, a quick effect
effects may be experienced.
Chronic Chronic effects generally call for repeated exposure and a delay is
effects observed between the first exposure and visual aspect of harmful health
effects.
Take note that both acute and chronic circumstances can result in lasting injury.
Injury from exposure to a chemical substance can be impermanent, i.e. changeable.

It will go away when exposure to that chemical stops. Exposure to solvents may
cause contact dermatitis, headache, or nausea. These consequences could be both
acute and temporary. Solvents can also cause chronic effects and result in an
irreversible, lasting injury to the nervous system.

1.6.4 Hazardous Substances

What is hazardous subtances?
Hazardous substances are substances or materials, which because of their

chemical, physical, or biological nature, present a likely danger to life, health,
or material possession, if they are released.
A „release‰ may take place by spilling, leaking out, emitting toxic vapours, or some
other method that enables the material to break away from its container, come in
the environment and produce a likely hazard. Hazards are classed in many
different ways. The following brings out some more common terms (see Table 1.5).
Table 1.5: Four Categories of Hazards
Category Description
Explosive Release pressure, gas, and heat suddenly when they are subjected to
substances shock, heat, or high pressure. Some festivals use many types of explosive
substances that require careful storage and handling to avoid injury.
Flammable These substances are easy to ignite. Paint thinners, charcoal lighter fluid,
and and silver polish liquid are all highly flammable. Oxidisers, which will
combustible lend oxygen readily to support a fire, and reactive materials, which are
substances unstable and may react violently if mishandled, pose related hazards.
Poisons (or These can cause injury or death when they enter the bodies of living
toxic things. Such substances can be classified by chemical nature (for example,
materials) heavy metals and cyanides) or by toxic action (such as irritants, which
inflame living tissue, and corrosives, which destroy or irreversibly
change it). One special group of poisons includes etiological (biological)
agents. These are live micro-organisms or toxins produced by these
micro-organisms that are capable of producing a disease.
Radioactive These are a category of hazardous materials that release harmful

materials radiation. They are not addressed specifically in this course.
Take note that these categories are not mutually exclusive. For example, acids and
bases are listed as corrosive materials, but can also act as poisons.

1.6.5 Classifications of Toxic Agents

Toxic substances are classified into seven categories as described in Table 1.6.
Table 1.6: Seven Categories of Toxic Agents
Heavy metals Metals that differ from other toxic substances are neither created nor
destroyed by humans. Their use by humans plays an important role
in determining their potential to be detrimental to oneÊs health. Their
effect on health could occur through at least two mechanisms:
• by increasing the presence of heavy metals in air, water, soil, and
food; and
• by changing the structure of the chemical.
For example, chromium III can be converted into or from chromium

VI, the more toxic form of the metal.
Solvents and Almost everyone is exposed to solvents. Occupational exposures can

vapours range from the use of „white-out‰ by administrative personnel, to the
use of chemicals by technicians. When a solvent evaporates, the
vapour may also pose a threat to the exposed population.
Radiation Radiation is the release and propagation of energy in space in the form
of waves, the transfer of heat or light by waves of energy, or the stream
of particles from a nuclear reactor.
Dioxins/furans Dioxin was originally discovered as a contaminant in the herbicide

„Agent Orange‰. Dioxin is also a side-effect of chlorine processing in
paper producing industries.
Pesticides The US Environmental Protection Agency or EPA (2021) defines

pesticide as any mixture of substances intended to prevent, destroy,
repel, or mitigate any pest. Pesticides are described as any physical,
chemical, or biological agent that will kill an undesirable plant or
animal pest.
Plant toxins Different portions of a plant may contain different concentrations of

chemicals. Some chemicals found in plants can be lethal. For example,
toxin used in chemotherapy to kill cancer cells is produced by a
species of the yew plant.
Animal toxins These toxins can result from venomous or poisonous animal releases.
Venomous animals are those that are capable of producing a poison
in a highly developed gland or group of cells and can pass that toxin
through biting or stinging. Poisonous animals are generally those
whose tissues, either as a whole or in part, are toxic.

1.6.6 Physiological Classifications of Toxic Materials

Toxic materials can be classified based on their biological action, and there are
eight categories (see Table 1.7).
Table 1.7: Eight Categories of Toxic Materials
Irritants It refers to some sort of aggravation of whatever tissue the material

comes in contact with. Examples of irritants include ammonia and
nitrogen dioxide.
Asphyxiants They exert their effects through a depletion of oxygen to the tissues.
Examples of simple asphyxiants are carbon dioxide, nitrogen, methane,
and hydrogen; while some examples of chemical asphyxiants are carbon
monoxide, hydrogen cyanide, and hydrogen sulphide.
Narcotics or The main toxic action is that it has a depressant effect upon the central
anaesthetics nervous system. Many organic solvents are either narcotics or
anaesthetics, for instance chloroform and xylene.
Systemic The main toxic action includes the production of internal damage.
poisons Examples are hepatotoxic agents (toxic effects that cause liver damage,
such as carbon tetrachloride) and nephrotoxic agents (toxic effects that
cause kidney damage, such as some halogenated hydrocarbons).
Carcinogens These are agents/compounds that will induce cancer in humans.

Examples are benzene, arsenic, and also inorganic salts of chromium,
nickel, and beryllium.
Mutagens They are agents that affect the cells of the exposed person in such a way
that they may cause cancer or an undesirable mutation to occur in some
later generation. Radiation and selected chemical agents can be
mutagens.
Teratogens Teratogens are agents or compounds that generate defects in the foetus
when taken by a pregnant woman. An example of teratogen is
thalidomide.
Sensitisers These agents that may cause allergic or allergic-like responses to occur.
After an initial exposure to this substance, an individual may become
sensitised to it. Frequent exposure to the same substance, at a much lower
concentration than before, can trigger an allergic response. This response
can be a skin rash (dermatitis) or an asthmatic-like attack, depending on
the route of exposure. Examples of sensitisers are cutting oils, isocyanates
in polyurethane foam operations and paint spraying operations, as well
as some laboratory solvents.

1.7 HEALTH HAZARDS

Lastly, let us identify the health hazards caused by toxic materials. Examples of
health hazards are given in Figure 1.8.
Figure 1.8: Health Hazards
The following are health hazard classes as defined by the Occupational Safety and
Health Administration (OSHA), USA:
• carcinogens
• corrosives
• irritants
• mutagens
• sensitisers
• teratogens
• target organ effects

As for target organ effects, these are further classified into eight categories (see
Table 1.8).
Table 1.8: Eight Categories of Target Organ Effects
Category Effect
Cutaneous hazards Damage the skin.
Eye hazards Damage the eye.
Hematopoietic toxins Damage the blood and/or blood forming organs.
Hepatotoxic Damages the liver.
Nephrotoxic Damages the kidneys.
Neurotoxins Damage the nervous system.
Pulmonary toxins Damage the lungs.
Reproductive toxins Affect the foetus.
1.7.1 Toxic and Highly Toxic Substances

According to the Occupational Safety and Health (Classification, Packaging, and
Labelling of Hazardous Chemicals) Regulations 1997, substance of health hazards
can be categorised as very toxic, toxic, harmful, corrosive, and irritant. These five
categories are further explained in Table 1.9.
Table 1.9: Five Categories of Substance of Health Hazards
Very toxic This can be:

• Substances and preparations which if inhaled or ingested or
penetrated into the skin may involve extremely serious, acute or
chronic health risks, or even death; or
• Substances and preparations for which the LD-50 absorbed orally in
rats is less than 25mg/kg or the LD-50 percutaneous absorption in
rats or rabbits is less than 50mg/kg, or the LC-50 absorbed by
inhalation in rats is less than 0.5 mg/litre (administered for a
minimum period of four hours).

Toxic This includes:

penetrated into the skin may involve serious, acute or chronic health
risks, or even death;
rats is between 25 to 200mg/kg or the LD-50 percutaneous absorption
in rats or rabbits is between 50 to 400mg/kg, or the LC-50 absorbed by
inhalation in rats is between 0.5 to 2mg/litre (administered for a
minimum period of four hours); or
• Substances and preparations which are defined as carcinogenic,
teratogenic, or mutagenic.
Harmful This consists of:

penetrated into the skin may involve limited health risks; or
rats is between 200 to 500mg/kg or the LD-50 percutaneous
absorption in rats or rabbits is between 400 to 2,000mg/kg, or the LC-
50 absorbed by inhalation in rats is between 2 to 20mg/litre
(administered for a minimum period of four hours).
Corrosive Substances and preparations which may, on contact with living tissues,
destroy them.
Irritant Non-corrosive substances and preparations which, through immediate,

prolonged or repeated contact with the skin or mucous membrane, can
cause inflammation.
SELF-CHECK 1.5
List down five hazardous substances that cause fatal diseases.

• Chemicals are the basic elements of life and the world around us. Materials
made from chemicals can be found in cars, clothing, furniture, tools, and many
other things we come in contact with daily.
• Environmental toxicology is a new and rapidly developing field which is

concerned with the harmful effects of chemical, physical, and biological agents
on living organisms, including fish, plants, animals, and humans.
• It is the study of nature, properties, effects, and detection of toxic substances in

the environment and in any environmentally-exposed species, including
humans.
• Environmental toxicology started from 1499 and it has evolved until today.
• However, the study of the toxic effects of environmental contaminants really

began in the 1960s, evolving from the traditional field of human or classical
toxicology. The first writings of toxicology relate back to prehistoric times
when various chemicals, or mixtures of chemicals, were used as both tonics
and poisons, with particular references to arsenic and mercury-based
compounds.
• Environmental toxicology is devoted to the general chemistry, environmental

behaviour and fate, toxicology, and ecotoxicology of xenobiotics and natural
toxins.
• The interdisciplinary core of environment toxicology borrows heavily from a

variety of disciplines of environmental science, chemistry, biology, computer
and mathematics, and toxicology.
• There are many applications when it comes to toxicology. Among them are
clinical toxicology, forensic toxicology, industrial toxicology, environmental
toxicology, and biochemical and molecular toxicology.
• The fundamentals of toxicology and environmental toxicology are dose-

response relationships, routes of exposure, effects of toxins, hazardous
substances, classification of toxic agents, and physiological classification of
toxic materials.
• Among the health hazards related to toxicology are cancer, skin rashes,
nervous system damage, and development problems in children.

• Some of the health hazard classes are carcinogens, corrosives, irritants, and
mutagen.
• Substance of health hazards can be categorised as very toxic, toxic, harmful,

corrosive, and irritant.
Applications Health hazards

Environmental toxicology Scope
Fundamentals Toxicology
Cotton, F. A., & Wilkinson, G. (1988). Advanced inorganic chemistry (5th ed.).
Wiley-Interscience.

Fishbein, L. (1979). Potential industrial carcinogen and mutagens, Vol 4. Elsevier.
Fries, G. F. (1985). The PBB episode in Michigan: An overall appraisal. Critical

Reviews in Toxicology, 16(2), 105–156.
Sons.




Nims, D. K. (1999). Basic of industrial hygiene. John Wiley & Sons.



Topic  Environmental
and
2 Occupational
Changes
Towards
Health

1. Relate the changing pattern of environmental and
occupational changes on health.
2. Explain epidemiological transitions.
3. Describe the use of chemicals.
4. Identify the source of pollutants.

32  TOPIC 2 ENVIRONMENTAL AND OCCUPATIONAL CHANGES
TOWARDS HEALTH
The Industrial Revolution in Western countries signifies the change in the

modernisation of the world that we live today. It began in the United Kingdom, and
subsequently spread throughout Western Europe, North America, Japan, and
eventually the rest of the world. This also indicates our ever-changing
environmental and occupational nature. People are shifting from the old traditional
nature of work in agricultural areas to industrialised areas.
This has led to an extensive change in the environment such as the opening of new
industrial areas, extensive usage of various types of chemicals, as well as dumping
of industrial wastes which are directly affecting the ecosystem and our current living
standard. How do these changes affect our health? Let us find out the answer in this
topic. Happy reading!
2.1 THE CHANGING ENVIRONMENT AND

DISEASE PATTERN
The 20th century witnessed profound, unprecedented changes in the natural, man-
made, and social environments. Countless new technologies were introduced into
diverse societies around the globe and altered the way we live. Dramatic changes
in the patterns and distribution of human disease are inevitable. This is supported
by World Health OrganizationÊs statements as follows (WHO, 2012):
• „The sustainability of many vital ecosystems has been strained on many fronts,
with varying health impacts – some direct, but mostly indirect and involving
complex ecological mechanisms. These global changes are synergistic. They
constitute a new type of health challenge; one that transcends the traditional
definitions of environmental health issues and that demands a recognition that
the foundations of long-term good health – at the personal, community, and
population level – rely on the continued stability of life-supporting
ecosystems.‰
• „The pattern of the diseases is shifting from communicable disease (traditional

or prevalent issue in the past) into non-communicable disease (present
challenges such as diabetes, disasters from usage of man-made substances
which include chemicals, road traffic accidents, occupational diseases, etc.).‰
Through the profound change of the world today, we can see the pros and cons of
industrialisation in our daily life. This significantly affects our environment and
occupation, thus affecting our health as well.

TOPIC 2 ENVIRONMENTAL AND OCCUPATIONAL CHANGES  33
TOWARDS HEALTH
2.2 EPIDEMIOLOGICAL TRANSITION

Have you noticed that our epidemiological situation has changed during the past
few decades? It is undeniable that there have been new changes in our technology
to the point where we could even boost the life expectancy of human beings.
Previous problems such as communicable diseases have been controlled to

tolerable risk and low occurrence due to increased life expectancy. There is a lower
mortality rate caused by communicable diseases compared to the previous record.
One significant proof would be the eradication of smallpox. Many vaccines were
introduced and made accessible to healthcare providers.
However, new patterns came to light. There is re-emergence of disease,

introduction of new serotype and virus strains, as well as increased cases of non-
communicable diseases (NCD). In fact, usage of chemicals can cause catastrophic
events and disasters through mismanagement (Bhopal disaster, Piper Alpha
incident, and Sungai Buloh firecrackers incident). This epidemiologic transition is
shown in Figure 2.1.
Figure 2.1: Epidemiologic Transition

TOWARDS HEALTH
Next, let us discuss the epidemiological transition of the modern era from the
perspective of human activity, climate instability, socioeconomic inequities and
disparities, and higher change of incidence in disease in the following subtopics.
2.2.1 Human Activity

Human activities can disturb the ecological balance. The destruction and clearing
of forests, and also the indiscriminate dumping of chemical waste, industrial
waste, and physical waste, and many other human activities have altered our
ecological systems. Certainly, this imbalance of ecological systems has an effect on
human lives too.
2.2.2 Climate Instability

Climate instability covers various issues like the greenhouse effect, extreme heat
phenomena, and the effect on the ozone layer. Some of the effects of extreme heat
phenomena are rising sea levels, shrinking glaciers, and higher ocean
temperatures.
2.2.3 Socioeconomic Inequities and Disparities

Generally, poor and underprivileged people are at greater risk of suffering both
chronic illness and environmental threats. For instance, there is high mortality due
to dengue in poorer countries compared to developing and developed countries.
2.2.4 Higher Change of Incidence in Disease

As stated before, disease patterns have changed from communicable diseases
(past) to non-communicable diseases (current). There have been increased
reported cases of chronic non-communicable disease problems (e.g., diabetes, road
traffic fatalities, and catastrophic disasters through use of chemical).
Through the changing nature of our environment and occupation facilitated by the
industrial and technological revolution, we can see clear effects to our health
today, to the extent of a change in epidemiological transition.

TOWARDS HEALTH
SELF-CHECK 2.1
What are the factors that contribute to the current epidemiological

transition?
ACTIVITY 2.1
Discuss the following questions in the myINSPIRE forum:
(a) Take a look at our occupations today. How do our occupations

contribute to the non-communicable disease (NCD) patterns?
(b) Check your family background. Do you have relatives who do not
suffer from NCD? Observe their lifestyle and eating habit. In your
opinion, do lifestyle and eating habit prevent a person from
contracting NCD?
2.3 CHEMICAL USAGE

Since the 20th century, rapid industrialisation and nearly ubiquitous contamination
of air, soil and water with hazardous waste, by-products of resource extraction,
fossil fuel combustion, and synthetic chemicals has continued.
Let us look at the following infographic of chemical usage in the US as for July 2021
(see Figure 2.2).

TOWARDS HEALTH
Figure 2.2: The Business of Chemistry in the US
Source: ACC (2021)
Rapid industrialisation with increasing usage of chemical causes adverse effects to

humans and the environment. Examples of catastrophic accidents involving
chemicals include:
• Minamata disaster in Japan;
• Love Canal tragedy in New York;
• Bhopal gas tragedy in India; and
• Seveso disaster in Italy.

TOWARDS HEALTH
ACTIVITY 2.2
Create a table that summarises the catastrophic accidents listed earlier in

terms of causes and effects. Share your table for discussion in the
myINSPIRE forum.
2.3.1 Types of Toxicants

Now, let us get to know the types of toxicants. There are four types of toxicants as
explained in Table 2.1.
Table 2.1: Four Types of Toxicants
Type Description
Pesticides There is an increase of pesticide usage in the agricultural industry.

This raises concerns on residual pesticides and its impact on human
health.
Toxic metals Some metals are toxic to humans and other living organisms when
they accumulate to sufficiently high concentration in body tissues,
such as blood or adipose (fat) tissue. For example, the accumulation of:
• lead – osteomalacia;
• cadmium – kidney problem; and
• arsenic – dermatological problem.
Persistent POCs are a type of toxic chemical compounds that can go through the
organic process of bioaccumulation and they are persistent in the tissues of
chemicals organisms, including humans. POCs are regulated under the Stockholm
(POCs) Convention worldwide. Some toxic POCs commonly available include:
• PAHs (polycyclic aromatic hydrocarbons)
• dioxin
• lindane
• PCBs (polychlorinated biphenyls)
• benzene
• DDT (dichlorodiphenyltrichloroethane)
• phenols
• xylene

TOWARDS HEALTH
Environmental • These toxins are detectable in the tissues of animals, including

toxins humans, and plants worldwide. These toxins are both ubiquitous
and toxic, and can bioaccumulate (accumulate in an organism).
2.4 POLLUTANT SOURCES

Now, let us discuss further on the sources of pollutants. Generally, the sources of
pollutants comes from the:
• environmental perspective
• occupational perspective
• occupational diseases
Let us start by taking a look from the environmental perspective.
2.4.1 Environmental Perspective

From the environmental perspective, we can classify the pollutant sources into
point sources and non-point sources (see Figure 2.3).
Figure 2.3: Pollutant Sources

TOWARDS HEALTH
These two sources are further explained in Table 2.2.
Table 2.2: Two Sources of Environmental Perspective
Source Description
Point sources This is a single identifiable localised source of something. These are
waste-producing facilities that can be identified as a discrete input of
contaminants. Examples are waste from factories and industrial
production facilities, wastewater treatment plants, and power plants.
Non-point Here, there is no specific source of pollutants. They occur over a broad
sources area and are associated with particular land uses, as opposed to
individual point source discharges. Examples include pollution due to
storm water run-off, pesticide and herbicide application, and vehicle
exhaust.
SELF-CHECK 2.2
Give three examples for point source and non-point source of pollutant
sources.
ACTIVITY 2.3
(a) Which one of the source is much more difficult to be treated before
being released into the environment?
(b) What would you suggest as treatment or controlling the amount of
the pollutants released?
2.4.2 Occupational Perspective

Workplace conditions and hazardous exposures have always been major
determinants of health risks among workers and in communities where hazardous
substances are released.

TOWARDS HEALTH
There are many hazards which can be commonly found in the workplace, such as:
• biological hazards
• physical hazards
• chemical hazards
• psychosocial hazards
• ergonomic hazards
These hazards, without proper control and preventive methods, can cause harmful
consequences such as occupational diseases or even catastrophic events.
2.4.3 Occupational Diseases

What is occupational disease?
Occupational diseases are any chronic ailments that occur as a result of work
or occupational activity.
Occupational diseases and occupational injuries have probably always been

under-recognised and under-reported, and estimates of the degree to which
workplace conditions contribute to disease patterns vary widely.
In compliance with Occupational Safety and Health (Notification of Accident,

Dangerous Occurrence, Occupational Poisoning and Occupational Disease,
NADOPOD) Regulations 2004, accidents, occupational diseases, near miss, and
occupational poisoning should be reported to the Department of Occupational
Safety and Health (DOSH). You can read more on this regulations at DOSH
website at https://bit.ly/3mJ4w6l.

TOWARDS HEALTH
SELF-CHECK 2.3
1. Define occupational disease.
2. List four types of common hazards that occur at the industrial

workplace.
3. What does NADOPOD stand for?
• The changing patterns of environment and occupation have had a profound

effect on human health.
• Epidemiological transition discusses both communicable and non-

communicable diseases.
• Communicable diseases have been controlled to tolerable risk and low

occurrence due to the increase in life expectancy.
• However, there is a re-emergence of disease, introduction of new serotype and

virus strains, as well as increased cases of non-communicable diseases (NCDs).
• Other factors that affects epidemiological transition are human activity,

climate instability, socioeconomic inequities and disparities, and higher
change of incidence in disease.
• Chemical usage has been around since the 20th century. Therefore, rapid
industrialisation has led to contamination of air, soil and water with hazardous
waste, by-products of resource extraction, fossil fuel combustion, and synthetic
chemicals.
• There are four types of toxicants: pesticides, toxic metals, persistent organic
chemicals (POCs), and environmental toxins.
• The sources of pollutants comes from the environmental perspective,

occupational perspective, and occupational diseases.
• Pollutants sources from the environmental perspective are point sources and
non-point sources.

TOWARDS HEALTH
• Pollutants sources from the occupational perspective are biological hazards,

physical hazards, chemical hazards, psychosocial hazards, and ergonomic
hazards.
• Occupational diseases are any chronic ailments that occur as a result of work
or occupational activity.
Chemical usage Occupational hazard

Communicable disease Persistent organic chemical (POC)
Epidemiological transition Pesticide
Environmental toxin Point source
Non-communicable disease Pollutants source
Non-point source Toxic metals
Occupational disease
American Chemistry Council (ACC). (2021). The business of chemistry by the

numbers. https://bit.ly/30mSrfX
Sons.
World Health Organization (WHO). (2011). Global status report on

noncommunicable disease 2010. https://bit.ly/3c2jXBS

Topic  Occurrence
of Toxicants
3
1. Define what is toxicant.
2. Describe visible smoke or smog.
3. Explain smoke and offensive odours.
4. Elaborate agriculture damage.
5. Explain the objectives and implementation strategies of the
Malaysian Environmental Quality Act 1974.
6. Discuss the various classes of health hazards.
In Asia, the concept of air pollution has changed significantly during the past
several decades. Thirty or fifty years ago, air pollution was only associated with
smoke, soot, and odour.
However, in present times, air pollution is the presence of any substance in the
atmosphere at a concentration high enough to produce an objectionable effect on
humans, animals, vegetation or materials, or to alter the natural biogeochemical
cycling of various elements and their mass balance. These substances can be in the
form of solid, liquid, or gas and can be produced by anthropogenic activities or
natural sources. Air quality is worsening in virtually all cities in the Asian region.
Air pollutants, mainly in the forms of suspended particulate and sulphur dioxide
are most common in the cities of the developing countries.

44  TOPIC 3 OCCURRENCE OF TOXICANTS
Let us learn more on toxicant, smog, smoke and offensive odours, and agriculture
damage, and how Malaysian government handles these pollutions in the next
subtopics. Happy reading!
3.1 TOXICANTS
Toxicants are typically introduced into the environment by human activity.
A distinction can be drawn between „toxic‰ and toxin, with the latter being a
subcategory of the former. Many toxicants are pesticides or are unwanted by-
products of some production process, or accidental spoils.
What is toxicant? „Toxicant‰ can be considered a synonym for poisonous, while

„developmental toxicant‰ can be considered a synonym for teratogen.
3.1.1 Concentration Range

There are three categories of concentration range for all chemical compounds and
the effects depend on these categories. Let us look at Figure 3.1 to know more.
Figure 3.1: Concentration of Chemical Compounds
These concentration ranges are further explained in Table 3.1.
Table 3.1: Three Categories of Chemical Compound Concentration
Too little The metabolic behaviour deviates more from the natural behaviour for
decreasing concentrations.
Enough The metabolic behaviour is rather insensitive to changes in the

concentration.
Too much The metabolic behaviour deviates more from the natural behaviour for
increasing concentrations.

TOPIC 3 OCCURRENCE OF TOXICANTS  45
There are two classifications of toxicants as explained in Table 3.2.
Table 3.2: Two Classification of Toxicants
Classification Characteristics
Toxicants I • Target organ – hepatotoxin, neurotoxin.

• Intended use – pesticide, solvent.
• Source – natural, synthetic.
• Special effect ‒ carcinogen, mutagen, endocrine disruptor.
Toxicants II • Physical state – gas, solid.

• Toxicity – extremely, slightly.
• Chemical composition – heavy metal, organophosphate.
• Mechanism of action – anti-cholinergic, inhibitor, uncoupler.
Next, let us look at Table 3.3 that explains two types of toxic responses.
Table 3.3: Two Types of Toxic Responses
Type Characteristics
Toxic responses I • Immediate – minutes to hours after a single exposure.

• Delayed – days to years after exposure.
• Some both.
• Local – effect at the site of contact, gastrointestinal tract (GIT),
lungs.
• Systemic – effect is distant from exposure site, central nervous
system (CNS), kidney, lungs.
• Some both.
Toxic responses II • Reversible versus irreversible.
• Largely determined by tissue involved, length of exposure, and
magnitude of toxic insults.
• Reversible – rapidly regenerating tissue, liver, intestinal
mucosa, blood cells.
• Irreversible – CNS damage, carcinogenesis, mutagenesis,
teratagenesis.

3.2 SMOG
What is smog?
The word „smog‰ is a combination of smoke and fog. Visible smoke or smog
is a type of air pollution.
Smog is also caused by large amounts of coal burning in an area caused by a

mixture of smoke and sulphur dioxide. Modern smog is a type of air pollution
derived from vehicular emission from internal combustion engines and industrial
fumes that react in the atmosphere with sunlight to form secondary pollutants that
also combine with the primary emissions to form photochemical smog. Let us look
at Figure 3.2 which shows you the smog phenomena in Kuala Lumpur.
Figure 3.2: Smog in the Air of Kuala Lumpur
Source: https://commons.wikimedia.org/wiki/File:Haze_in_Kuala_Lumpur.jpg
3.2.1 Physical Description of Smog

Physical characteristics of smog include a yellow-brown haze, which reduces
visibility and the presence of substances which irritate the respiratory tract and
causes watery eyes. The yellowish colour is owed to the presence of nitrogen
dioxide whilst the irritant substances include ozone, aliphatic aldehydes, and
organic nitrates (see Figure 3.3).

Figure 3.3: Formation of Smog
Ozone is one of the primary components of smog. Ground-level ozone is formed

by emissions from vehicles, industries, etc. While ozone in the stratosphere
protects the earth from harmful UV radiations, ozone in the ground is harmful to
human health.
There are four conditions needed before smog can develop. These conditions are:
• sunlight
• hydrocarbons
• nitrogen oxides
• temperatures above 18ÀC
3.2.2 Automobiles
Did you know that automobiles are identified as the leading contributor to smog?
Car engines, especially diesel engines are huge contributors to the smog problem.
This is because diesel engines emit particles that enter the atmosphere.
Lead is also a major problem, especially when found in gasoline that is combusted
in automobiles. Asian countries are more dependent on lead as compared to
European countries. Smog problems created by cars are becoming increasingly
severe as there is a rise in the number of vehicles. Let us take Malaysia for example.
Every year, the number of motorcycles and cars in Malaysia are increasing as
shown in Figure 3.4.
Figure 3.4: Number of Registered Vehicles in Malaysia (2012 to 2016)
Source: Data Terbuka (2018)
3.2.3 Smog and Health

According to doctors, the lungs and heart can be permanently affected by air
pollution and smog. The young and elderly are the most susceptible to the effects
of pollution.
However, anyone after both short- and long-term exposure can suffer from its
harmful health effects. Health problems such as shortness of breath, coughing,
wheezing, bronchitis, pneumonia, inflammation of pulmonary tissues, heart
attacks, lung cancer, increased asthma-related symptoms, fatigue, heart
palpitations, and even premature ageing of the lungs and death can happen.
In August 2010, Malaysia declared a state of emergency because of dangerous

levels of air pollution. Smoke from forest fires from Indonesia has blown over
Kuala Lumpur, which when mixed with dust, carbon dioxide, and sulphur dioxide
formed dangerous smog. It covered the tops of buildings in the capital city and
people experienced breathing problems. Schools were closed and people were
advised to stay indoors.

SELF-CHECK 3.1
1. What causes smog?
2. Describe the physical characteristics of smog.
3. How do automobiles contribute to it?
4. What are the effects of smog to our health?
3.3 SMOKE
The major reason of cause of death related to fire is smoke inhalation (airway or
pulmonary parenchymal injury). Smoke inhalation occurs when you breathe in the
products of combustion during a fire, such as harmful gases, vapour, and
particulate matter (soot, etc.) contained in smoke. Figure 3.5 shows you how smoke
inhalation affects your lung.
Figure 3.5: Smoke Inhalation Affecting Lungs
Combustion produces these gases, vapour, and particles of matter that result from
burning or the rapid breakdown of a substance by heat. The exact composition of
smoke produced by any individual fire cannot be predicted because of the varying
temperatures, the products being burned in the fire, and the amount of oxygen
available to each individual fire.

The harmful materials given off by combustion injure the airways and lung by:
• heat damage;
• tissue irritation by irritant compounds; and
• oxygen starvation of the tissues known as asphyxiation.
Smoke inhalation victims do not show injury symptoms until 24 to 48 hours after
the inhalation event. Also, children under 11 years of age and adults over 70 years
of age are most vulnerable. The degree of heat involved in the fire creating the
smoke is directly related to the seriousness of potential damage from smoke
inhalation.
According to Clark, Jr. (1992), „The mortality rate of smoke inhalation victims
without a burn is less than 10 per cent. With a burn, the mortality rate is 30 to 50
per cent, suggesting that thermal injury or its treatment is responsible for further
lung damage.‰
The primary source of injury in the upper respiratory tract is heat, but the thermal
injury does not usually extend beyond the bifurcation or forking of the trachea
(commonly known as the windpipe). Within the lung the particulate, or particles
of matter resulting from the combustion, combined with the toxic gases, cause the
majority of damage in what appears to be a response to the stimulation of
inflammatory response.
Smog particulate can create a similar irritation, but is derived from other
environmental particles of matter such as auto emissions and industry pollutants.
Unless this particulate matter is removed, the continued presence may lead to
damage and an impaired respiratory function.

3.3.1 Smoke from Fire

Smoke from a large open fire is very dangerous (see Figure 3.6).
Figure 3.6: Smoke from Fire
Source: http://www.yourerdoc.com/wp-content/uploads/2008/10/so-cal-fire.jpg
Smoke from different sources may look the same to the human eye; however, it is
quite different in terms of its chemical and physical properties (see Table 3.4).
Table 3.4: Smoke Chemical and Physical Properties
Property Description
Carbon dioxide These are the major components in completing the combustion
and water during fire.
Carbon monoxide This is the most abundant emission product from wildlife fire. Its
(CO) negative effect on human health depends on the duration of
exposure, CO concentration, and level of physical activity during
the exposure.
Hydrocarbons It contains hydrogen, carbon, and sometimes oxygen.
Nitrogen oxides It contributes to ozone formation.

The effects of smoke on Brunei, Indonesia, the Philippines, Malaysia, Singapore,

and Thailand, and occasionally the islands of Guam and Saipan are tremendous.
The economic losses of the fires in 1997 have been estimated at more than
USD9 billion. This includes damages in agriculture production, destruction of
forest lands, health, transportation, tourism, and other economic endeavours. This
does not include costs in terms of social, environmental, and psychological
problems and long-term health effects.
Smoke inhalation typically occurs in residential or forest fires. Note that cigarette
smoking causes similar damage on a smaller scale over an extended period. The
primary source of injury in the upper respiratory tract is heat, but within the lungs,
it is the deposition of particles, derived from the products burning, together with
toxic gases given off by the fire.
ACTIVITY 3.1
Plantation open burning has been the major cause of haze in the South
East Asia region. However, during the COVID-19 pandemic, this activity
has ceased. How long do you think this will last? Discuss this issue of
plantation open burning in the myINSPIRE forum.
3.3.2 How Smoke Inhalation Damages the Body

The primary function of the leukocyte immune cells known as alveolar
macrophages in the lungs is to engulf and dispose of any matter entering the lungs
not produced by the body (non-self) – a process described scientifically as
phagocytosis. These large white immune cells play an important function that is
as a part of the innate immune response of the body. For the body to be able to
fight back successfully against the soot, carbon, and other particulate matters from
the smoke inhalation and smog, these macrophage cells, or "immune soldiers",
must be in peak condition and not be suppressed or damaged.
If suppressed or damaged, the immune response cannot naturally dispose of the

invasive and damaging pathogens in an orderly manner and the signs and
symptoms of smoke inhalation, including asthma and severe respiratory
problems, can occur.

Chemical asphyxiants from a fire can produce compounds that damage the body
by interfering with the oxygen use at the cellular level. Carbon monoxide,
hydrogen cyanide, and hydrogen sulphide are all examples of such chemicals.
Why is it important for macrophage cells be in peak condition? If either the
delivery of oxygen or use of oxygen is inhibited, then the cells will die. In fact,
carbon monoxide is the leading cause of death in smoke inhalation for this reason.
Simple asphyxiation refers to combustion using up all oxygen near a fire, which
then leaves no oxygen to breathe. When you have no oxygen to breathe for even a
brief period, then lung and respiratory damage can occur and, if for an extended
period, you will die. Asphyxiation is recognised by shortness of breath, blue grey
or bright-red skin colouration, and in extreme cases by loss of consciousness or
breathing.
SELF-CHECK 3.2
How can smoke inhalation damage the body?
3.3.3 Diagnosis of Smoke Inhalation Damage

In most cases of smoke inhalation, when the victim has a shortness of breath or a
persistent cough, a chest X-ray is required. An initial chest X-ray often appears
normal, even with significant signs such as coughing and shortness of breath
because many times damage does not appear for the first 24 to 48 hours. A delayed
second chest X-ray after 48 hours is recommended.
After smoke inhalation, a blood test is also needed. It should include the following,
if possible:
• Complete blood count to determine if there are enough red blood cells to carry
oxygen, enough white blood cells (including alveolar macrophages) to fight
infection, and enough platelets to assure clotting can occur.
• A basic metabolic profile to reveal the change of pH in the blood that occurs
because of interference with oxygen diffusion, transport, or use. Serum
electrolytes in the form of sodium, potassium, and chloride can be monitored,
along with renal (kidney) function test involving creatinine and blood urea
nitrogen.
• An arterial blood gas test is indicated for victims with significant respiratory
distress, acute mental status changes, or shock. This test helps in determining
the degree of oxygen shortage.

• Carboxyhaemoglobin and methaemoglobin levels should be checked if there

is respiratory distress, altered mental status, low blood pressure, seizures,
fainting, and/or blood pH changes.
• Symptoms of smoke inhalation damage should be checked.
3.3.4 Treatment
The primary objective of treatment is to provide an adequate level of oxygen while
re-establishing and maintaining an open airway. If the airway is open and stable,
high-flow humidified oxygen may be applied with a mask, nose tube, or tube
down the throat. If signs and symptoms of upper airway problems such as
hoarseness are observed, a doctor will incubate a tube down the patient's throat to
keep the airway free from closing due to swelling.
In the case of respiratory distress or mental status changes, intubations will often
be done to ease breathing, mucous will be suction off and steps will be taken to
ensure the patient does not breathe in the content of the stomach. Patients with a
wheezing cough (bronchospasm) indicating the bronchial airways are constricted
or blocked will often be given a bronchodilator to relax the muscles and increase
ventilation.
In the cases of severe carbon monoxide or cyanide poisoning, hyperbaric

oxygenation or HBO will be given. What is HBO? HBO is the process of receiving
oxygen in a compression chamber at three times the normal atmospheric pressure.
3.4 OFFENSIVE ODOURS

What is odours?
Odours are light, volatile (easy to evaporate) chemicals that float through the
air into receptors in the nose.
Extremely hazardous substances can be released accidentally as a result of chemical

spills, industrial explosions, fires, or accidents involving railroad cars and trucks
transporting them. Workers and residents in communities surrounding the
industrial facilities where extremely hazardous substances are manufactured, used,
or stored and in communities along the nation's railway tracks and highways are
potentially at risk of being exposed to airborne extremely hazardous substances
during accidental releases. Intentional release by terrorists is also cause for concern.

The receptors send messages to the brain for processing which results in the
sensation of smell. It is thought that there are hundreds of different receptors
within the human nose and this differs from one person to another. Each receptor
is coded by different DNA to detect different odours. This is one of the reasons
why different people will have dissimilar sensitivity and reactions to smell.
Reactions to odours can be very subjective. A smell may be pleasant to one person
and unpleasant to another, making objective assessment of odour difficult to
achieve. Scientists also suggest that the sense of smell is intimately associated with
the formation of memories.
Odours and smells are an unfortunate part of living in any major city. Bad smell
such as blocked drains, fumes, compost, and rubbish can be a nuisance to the
neighbours and in severe cases, can also affect people's health.
The Environment Protection Act 1970 does not define the term „offensive to the
senses of human beings‰. People experience odours differently, so offensiveness
can only be determined by the individual being affected. Look at Figure 3.7. The
Act can therefore, only trigger an investigation into an odour complaint when the
odour is reported by a community member as being offensive.
Figure 3.7: Fumes from a Chemical Factory Leading to Offensive Odour
Offensive odour affects the general life, health, and well-being of an individual, as
a result of the intensity, character, frequency, and duration of the odour. The basis
for acting against offensive odours may vary according to where the odour occurs.
As an example, the normal agricultural odours present in a rural environment may
not be considered offensive in an open paddock, but may be considered offensive
in a residential area.
SELF-CHECK 3.3
What is odour? When can odours be offensive?
3.4.1 Sources of Environmental Odours

What are the sources of environmental odours? Odours can come from many
different sources (see Figure 3.8).
Figure 3.8: Sources of Environmental Odours
The Environment Protection Authority or EPA will become involved when the
offensive odour is generated from industrial processes. Most odours from
domestic sources and commercial premises, such as shops and restaurants, will be
addressed by the local council officers.
Odours can smell worse on hot days. Odour can also be more obvious during
colder months or at night when the amount of mixing is reduced, or odour is
trapped by colder air coming in over the warm earth. Wind can carry odour a long
way from its source, as well as disperse the odour before it can be investigated.
The offensiveness of the odour perceived by a receptor is a factor that will

determine the likelihood of annoyance. More offensive odours cause annoyance at
lower concentrations, while less offensive odours cause annoyance at higher
concentrations. Odorous gases commonly become an issue because of their
nuisance to the public. It is rare however that adverse health effects arise from
exposure to odour.

Nevertheless, when odours are persistent or strong, they can have a significant
effect on the lifestyle and amenity of residents. Calls to the EPA's Pollution Watch
Line shows odour to be among the most disruptive issue individuals and local
communities face.
The range between the annoyance criteria applied for the most offensive and least
offensive odours is typically in the region of a factor 10. For example, in the
Netherlands, the most stringent criterion is 0.5 to 1 OU E / m 3 (for extremely
offensive odours generated from rendering operations) and least stringent is
around 8 to 10 OU E / m 3 (for relatively pleasant odours generated by bakeries,
etc.) It should be noted that even pleasant odours (bakeries, perfumeries) can cause
irritation to people if the concentration, frequency, and duration of exposure is
great enough.
3.4.2 How Do You Measure Odour?

The techniques available to measure odours can be broadly divided into both
sensory and chemical techniques. These two techniques are further explained in
Table 3.5.
Table 3.5: Two Techniques to Measure Odour
Technique Description
Sensory This technique utilises human assessors to assess odour. The most
techniques commonly applied sensory technique is olfactometry, which is used to
measure the concentration of an odour in terms of European Odour
3
Units ( OU E / m ). Techniques also exist for the assessment of odour
character (e.g. triangular testing and odour mapping), intensity and/or
relative pleasantness/unpleasantness (e.g. hedonic tone analysis).
Olfactometry are commonly used for:

• quantifying odours that can be used to assess the impact of the odour
on human subjects; and
• assessing the efficiency of odour abatement systems in terms of total
odour.
The advantage of sensory methods is that they provide a direct link to

how odours are perceived by humans. This is particularly useful for
studies that involve assessment of annoyance or nuisance, or indeed,
how effective odour control techniques are at mitigating such issues.

However, the disadvantage of the approach is that it is non-specific and

does not identify the specific chemical(s) responsible for the odour. It
means the approach measures the total odour of the sample in terms of
3
odour units ( OU E / m ).
Chemical It utilises conventional analytical techniques to measure the

techniques concentration of specific odorous compounds within the sample gas.
This can be achieved by gas chromatography/mass spectroscopy
analysis (GC/MS), the use of specific chemical analysers (e.g. chemical
cells for hydrogen sulphide analysis), wet chemical techniques
(mercaptans), indicator tubes, and electronic noses.
The key advantages of chemical measurement techniques are ease of

use, and the fact that the techniques are capable of identifying and
quantifying specific chemical odorant compounds.
However, the disadvantage of this approach is that it does not provide

any insight into the intensity or offensiveness of odours in human terms
(the commonly applied assumption is that the contribution of specific
odorants can be simply added to assess the odour concentration of the
mixture is rarely applicable).
Hence, chemical techniques are not suitable for measuring odours for
impact assessment purposes. These techniques are commonly used for:
• defining the design criteria for odour abatement plant;
• evaluating compliance to specific chemical emission limits; and
• measurement of surrogate compounds that can be used to predict
odour impact.
3.4.3 Odours and Health

Odours can have many detrimental effects on health. It can affect:
• mucous membranes
• upper and lower respiratory airways
• heart and blood vessels
• stomach and intestines
• the brain
• general well-being

Odours have been recognised as signs of potential risks to human health as well
as the direct cause of some symptoms of diseases in humans.
Toxic chemicals with strong odours can come from:
• perchloroethylene from drycleaners;
• benzene from gasoline released when the gas tank is filled; and
• sulphur dioxide from electric utilities.
SELF-CHECK 3.4
1. What are the sources of odour?
2. How do we measure odour?
3.4.4 Odour Control

Odours can be controlled by making modifications to the process, in order to
prevent odour generation at source, or through containment, collection, and
treatment of odorous emissions using end-of-pipe techniques. The
appropriateness and applicability of-end-of pipe solutions will be dependent upon
the characteristics of the gas stream to be treated. The following technologies for
odour control methods are available (see Table 3.6).
Table 3.6: Four Technologies for Odour Control
Technology Method
Physical • Dilution
• Physical absorption
• Coverage
• Masking
Chemical • Scrubbing
• Oxidation
• Incineration
Biological • Biofiltration
Combined • Bioscrubbers

Besides the technologies mentioned in Table 3.6, some other technologies may be
used to reduce odour generation such as:
• Replacing the raw material to control the generation of less odorous emissions.
• Changing the production process to reduce the generation of odorous

compounds.
• Diet optimisation for animals to limit odour produced from livestock.
Other ‰innovative„ techniques are also available, including the use of:
• odour counteracts
• masking agents
• plasma technology
• surfactant enhanced adsorption
• ozone and ultraviolet techniques
3.4.5 Absorption
Absorbers commonly use empty activated carbon or alumina pellets impregnated
with permanganate. These materials are highly porous and consequently there is a
large surface area upon which absorption of odorous compounds may occur.
Activated carbon is generally considered for organic gases and vapour, some
inorganic gases and some metallic vapour.
The mechanism which attracts and attaches the molecules to the surface of the pores
is known as Van der Waals forces. It is generally accepted that compounds with a
molecular weight of at least 45 g/mol per mole or with a boiling point of over 0ÀC
will be well absorbed on activated carbon.
The odorous stream needs to be pre-treated before it passes through activated

carbon when its temperature is high, moisture content is high, or it contains dusts.
The odorous stream should be free of dust in order to avoid clogging the surface
of activated carbon. Activated carbon needs to be replaced before it is saturated.
The used activated carbon can be regenerated, otherwise it should be disposed.

3.4.6 Liquid Scrubbing

Liquid scrubbing of gases for the removal of odours can involve either adsorption
in a suitable solvent or chemical treatment with a suitable reagent. Liquid
scrubbing becomes economically attractive compared with incineration and
absorption on activated carbon when the volume of odorous gas to be treated is
great than 5,000 cubic metres per hour.
Liquid scrubbing of gases involves bringing the odorous gas stream to initiate
contact with the scrubbing liquid. Liquid scrubber needs to be well designed to
ensure adequate contact between the gas and liquid phases. The treatment ability
should be sufficient enough to treat the odorous gases generated.
The principal types of gas absorption equipment include packed towers, plate or
tray towers, spray towers, venturi, and fluidised bed scrubbers.
It is important that hot moist vapour streams be cooled before contacting

scrubbing solutions. Direct or indirect condenser can be used to condense the
moisture from the odorous stream (an indirect condenser is preferred). The most
frequently used absorbing solutions are explained in Table 3.7.
Table 3.7: Most Frequently Used Absorbing Solutions
Solution Description
Sodium hydroxide Ideal for absorbing hydrogen sulphide and

mercaptans.
Amine Used to trap hydrogen sulphide of hydrocarbon gases

from petroleum refinery.
Chlorine, sodium Effective to absorb unsaturated organic compounds.

hypochlorite, potassium
permanganate, ozone, or
hydrogen peroxide
Diluted sulphuric acid Used to absorb ammonia.
3.4.7 Biofiltration
For biological odour control, the odour is removed by biological processes –
bacterial action. The bacteria grow on inert supports, allowing intimate contact
between the odorous gases and the bacteria. The process is self-sustaining.
However, biofilters require careful attention to ensure continued operation.

3.4.8 Bioscrubbers
Bioscrubbers use the combined principles of liquid scrubbing and biofiltration in
order to remove vapour pollutions from waste gases. Bioscrubbers can only be
used successfully if the contaminants can be removed from the waste gas by
absorption in a water/activated sludge mixture. Furthermore, the contaminants
must be biologically degradable.
3.4.9 Confirmation of Odour Removal Efficiency

Different odour control measures may be combined to achieve high removal
efficiency. The odour control technologies being used will depend on the
characteristics of the odorous gases and the quantity of production. After the
odour control technologies have been used and the facilities installed, odour
removal efficiency should be checked for a certain period of time. This
confirmation is necessary for the effective operation and maintenance of the odour
removal facilities applied.
SELF-CHECK 3.5
Explain odour control technologies.
3.5 AGRICULTURE DAMAGE

Since the early 1960s, the world population has more than doubled, and the
agricultural production per person has increased by a third. Over the same period,
the use of modern inputs for farming has grown dramatically, and they have been
very effective in helping to increase agricultural yields.
Pesticides are now available in the remotest regions of the world. Farmers can see
their short-term effect – killing insects, weeds and diseases, and thus allowing the
crops and animals to flourish.
Yet, there is a hidden cost to pay. Harm to the environments and human health
has accompanied some of these fundamental changes in the food production
systems. For far too long, we have accepted these costs as the unfortunate but
necessary side-effects of progress.

Yet in the last decade of the 20th century, many communities around the world
have begun to see some remarkable revivals. The pesticides that harm
environments and human health are increasingly being identified, and
alternatives, providing cheaper and safer management methods, have been
developed and now adopted by several million farmers around the world. An
example of pesticide application can be seen in Figure 3.9.
Figure 3.9: Pesticide Application
Source: http://jmowings.wordpress.com/category/uncategorized
3.5.1 Use of Pesticides

Pesticides are intended to kill unwanted organisms. Most act by interfering with a
variety of biochemical and physiological processes that are common to a wide
range of organisms. Unfortunately, besides targeting pests, weeds and fungi, they
also affect wildlife and human beings. Some can be lethal, and many can cause
illness at sub-lethal levels.
However, the risks differ greatly from pesticide to pesticide. Some are acutely toxic
but produce no long-term effects, whilst others have long-term health or
environmental concern.
Certainly, agriculture plays an important role in the Malaysian economy. Malaysia

is the primary exporter of natural rubber and palm oil. These together with cocoa,
pineapple, pepper, and tobacco comprise the main crops responsible for the
growth of this sector. Agriculture is also important for other manufacturing sectors
such as the food and beverage industry. The pesticide industry is the main support
in agriculture. These pesticides however, have adverse effects on water, soil, crops,
mankind, domestic animals, wildlife, and the overall environment.

Agriculture is a very diverse industry that includes multiple occupational and

environmental exposures and widely varying work practices. There are specific
respiratory hazards associated with the various commodities and associated work
practices.
Respiratory disease is one of the main chronic conditions among farmers and also
affects those in the agricultural-related industries. For example, respiratory
symptoms have been reported in as many as 93 per cent of veterinarians treating
swine.
Bioaerosols comprising organic dusts, microorganisms, and bacterial endotoxins,

and chemical toxicants from fermentation and bacterial degradation of grain and
animal wastes are the major environmental/occupational health hazards commonly
encountered by farmers, their families, and other agricultural workers.
Inorganic dusts are also prevalent but there are less clinically significant. Exposure
to each of these toxicant classes or to a combination of these toxicants constitutes a
risk of respiratory injury.
3.5.2 Dust
As stated earlier, dust is one of the hazards of agricultural damage (see Figure 3.10).
Figure 3.10: Dust
Source: https://bit.ly/31yVsdj

Let us learn the characteristics of dust in Table 3.8.
Table 3.8: Characteristics of Dust
Feature Description
Inorganic A tractor tilling a field trailed by large plumes of dust is a common sight
throughout the rural landscape, but that is not the only method of
exposure to inorganic dusts. Diatomaceous earth containing respirable
silica is not an uncommon source of respiratory exposure in different
agricultural settings and may be a cause of bronchitis in workers
processing sugar beets and potatoes in enclosed workspaces. Very high
concentrations of inorganic dusts are generated by field activities such
as ploughing, tilling, haying, and harvesting.
The bulk of inorganic dusts is in the form of silicates. These include

crystalline silica (quartz) and non-crystalline amorphous silica
(diatomite). Newer tractors with enclosed cabs containing air filtration
can decrease respirable dust exposure from an average of 2 to 20 mg/m3
to 0.1 to 1 mg/m3. Inorganic dust can constitute from 15 to 43 per cent
of the total dust exposure in grain handling. Manual tree fruit and grape
harvesting are associated with inorganic dust levels that are greater than
OSHA (Occupational Safety and Health Administration) permissible
levels.
Organic Grain dust is a complex mixture of components including vegetable

product, insect fragments, animal dander, bird and rodent faeces,
pesticides, microorganisms, endotoxins, and pollens. The primary
sources of toxic and allergenic contributors in animal confinement
facilities are animal faeces, endotoxins, and pollens. Other high dust-
generating environments and work practices include silos, chopping
straw for bedding, unloading grain silos, shovelling feed, opening bales
of hay for feed, and cleaning old animal housing structures.
Under certain conditions, organic dusts contain biologically active

proteins that may be allergenic and pro-inflammatory. The biologically
active compounds contained in dust, along with coexisting toxicant
gases, raise concerns regarding possible additive or synergistic toxic
exposures and respiratory health.
Allergens Allergens encountered include animal dander in confinement facilities

and allergenic protein components in grain dusts, particularly those from
wheat sorghum and soy. Biologic mechanisms involved in the
inflammatory response include complement activation, neutrophil
chemotactic activity, and increased peripheral blood neutrophil response.
Pollens, insect fragments, fungal moulds, and bacteria are ubiquitous
allergens and can occur at high levels in grain or animal confinement
enclosed space settings (see Figure 3.11).

Figure 3.11: Allergens and Allergic Symptoms
Source: https://bit.ly/3H0V1IX
Endotoxins Endotoxins are found where organic dust is produced and raised by
and animal and human activities. These conditions are found in animal
inflammation confinement structures (swine and poultry), livestock farming, grain
elevators, cotton industry, potato processing, flax industry, and the
animal feed industry.
Infection Farming, animal husbandry, and animal production environments can

be reservoirs of human exposure to exotic and common infectious
agents, resulting in zoonoses. For example, hog confinement workers
can be at risk for acquiring swine influenza. Poultry workers,
particularly those working with turkeys and ducks, are at risk for
psittacosis caused by Chlamydia psittacosis. Veterinarians and zoo
workers are also at risk for developing psittacosis.
3.5.3 Toxic Gases

The toxic gas nitrogen oxides (NOx), the cause of silo filler's disease, are formed
during the fermentation of silage, with levels reaching concentrations of several
hundred to several thousand parts per million. NOx are poorly soluble and heavier
than air and collect in pockets and depressions. Corn and other grain grown under
drought conditions with heavy fertilisation can produce extremely high levels of
NOx. NOx gases are of low solubility, penetrating to the lower respiratory tract,
and are severe respiratory irritants.

Fermentation occurs within hours of filling a silo and NOx may reach lethal levels
within 12 hours; these dangerous levels can persist for two weeks afterward. Silos
should not be entered during this time without proper respiratory protection and
only after running blowers for at least 30 minutes. Measurement of the NOx prior
to entry of the silo is recommended, even after ventilation.
Acute, usually accidental, high-level exposure can be a cause of acute

haemorrhagic pulmonary oedema and even death. Meanwhile, lower-level
exposure may produce transient pulmonary decompensation, but pulmonary
disease can be a long-term effect as a result of fibrotic scarring.
Besides the attendant health risks of organic dusts, high-density animal

confinement facilities and in particular, swine confinement operations, generate
high levels of gases as part of the by-products of animal waste. These gases include
hydrogen sulphide (H2S), ammonia, carbon dioxide, and methane. The gases of
primary concern are H2S and ammonia.
Accidental death due to H2S asphyxiation and/or cardiogenic pulmonary oedema

is rare but can occur in those swine or dairy confinement buildings with under-
building manure pits. H2S at low levels is a respiratory irritant and at higher levels,
a chemical asphyxiant.
Meanwhile, ammonia is a common gas found in animal and poultry confinement

operations. Ammonia is a respiratory and mucous membrane irritant. It is very
soluble and associated with upper airway irritation, sinusitis, chronic obstructive
pulmonary conditions, and mucous membrane inflammation syndrome.
Tolerance can develop with prolonged exposure, leading to fewer irritant
symptoms with greater pulmonary exposure.
Unlike H2S, carbon dioxide and methane are simple asphyxiants and generally are
not the primary causes of adverse health effects. Carbon dioxide, produced by
animal respiration, serves as an indirect indicator of ventilation.
Prevention of improper use can be achieved by adhering to the following

guidelines:
• use of personal respiratory is adequate;
• decreasing dust generation by adding mist, adding vegetable oil to feed,

sprinkling oil on the animals, and using wet methods to clean surfaces;
• ventilation with proper mixing of air improves air quality by decreasing dust
and gas levels;

• concentrations of gases should be monitored periodically by the use of simple

colorimetric tubes or direct-reading electronic monitors;
• applying newer methods of storing;
• harvesting and storing hay, straw, and grains with moisture content below 30
to 35 per cent and adding urea as a preservative decreases mould and bacteria
growth; and
• adding a quart of water to a bale of hay before chopping decreases dust release
by as much as 85 per cent.
ACTIVITY 3.2
Discuss in the myINSPIRE forum the condition of agriculture damage in

Malaysia.
3.6 ENVIRONMENTAL QUALITY ACT 1974

Malaysia has undergone phenomenal economic growth in the last two decades. It
has moved from agriculture to manufacturing-based economy, with significant
social changes. This development has brought about significant concerns to the
natural environment.
Sustainable development cannot have lasting benefits unless the environmental

considerations and related ecosystems are protected as integral parts of
development planning and decision making. This can only be done by formulating
appropriate policies and programmes.
The Government of Malaysia has taken concrete steps by introducing an enabling

legislation called the Environmental Quality Act 1974. The main objective of this
Act is to prevent, abate and control pollution, and further enhancing the quality of
the environment in this country. The Department of Environment (DOE) has been
entrusted to administer this legislation to ensure that Malaysia will continue to
enjoy both industrial growth and a healthy living environment.

3.6.1 Objectives of the Act

There are five objectives of the Malaysian Environmental Quality Act, which
are to:
• maintain a clean and healthy environment;
• maintain the quality of the environment relative to the needs of the growing
population;
• minimise the impact of the growing population and human activities relating
to mineral exploration, deforestation, agriculture, urbanisation, tourism, and
the development of other environmental resources;
• balance the goal for socio-economic development and the need to bring the
benefits of development to a wide spectrum of the population, keeping in mind
the maintenance of sound environmental conditions;
• place more emphasis on prevention through conservation rather than on the

curative measure, inter alia by preserving the country's unique and diverse
cultural and natural heritage; and
• incorporate an environment dimension in project planning and

implementation, inter alia by determining the implications of the proposed
projects and the cost of the required environmental mitigation measures.
3.6.2 Implementation Strategies

The implementation of this Act involves three strategies (see Table 3.9).
Table 3.9: Three Implementation Strategies of the Malaysian Environmental

Quality Act 1974
Strategy Description
Monitoring The main environmental agency involved in controlling

and environmental issues is the DOE. DOE has recently taken a more
enforcement complete and integrated role, deviating from „problem-solving
approaches‰ to more systematic and holistic approaches that
encompass monitoring enforcement, development, and planning.
Monitoring includes monitoring of water quality, noise, and air

quality. Meanwhile, enforcement includes control on pollution from
vehicles, control of agro-based prescribed and non-prescribed
premises, waste management.

Public Another aspect of the development function of the DOE is to promote

awareness environmental awareness largely through
• formal and informal education;
• wide dissemination of environmental information through
environmental publication, seminars, workshops, and lectures; and
• the mass media.
Environmental DOE has been a significant environmental player, especially in the

cooperation interest of developing countries. It aims at regional cooperation.
• Toxicant (or toxic) is a chemical compound that has an effect on organisms.
• There are three categories of compound concentration namely too little,

enough, and too much.
• Toxicants can be classified into two categories namely toxicants I and toxicants
II.
• As for toxic responses, there are two categories of them: toxic responses I and
toxic responses II.
• Visible smoke or smog is a type of air pollution. The word „smog‰ is a

combination of smoke and fog.
• Modern smog is a type of air pollution derived from vehicular emission from
internal combustion engines and industrial fumes that react in the atmosphere
with sunlight to form secondary pollutants that also combine with the primary
emissions to form photochemical smog.
• The major reason of cause of death related to fire is smoke inhalation (airway
or pulmonary parenchymal injury).
• Smoke inhalation occurs when you breathe in the products of combustion

during a fire – the harmful gases, vapour and particulate matter (soot, etc.)
contained in smoke.
• Odours are light, volatile (easy to evaporate) chemicals that float through the
air into receptors in the nose.

• Offensive odour affects the general life, health and well-being of an individual,
as a result of the intensity, character, frequency, and duration of the odour.
• Agriculture can pose major threats to health through increased incidence of

pesticide poisoning, and diseases transmissible from farm animals to humans
in intensive livestock systems.
• The Government of Malaysia has taken concrete steps by introducing an

enabling legislation called the Environmental Quality Act 1974.
• The main objective of this Act is to prevent, abate and control pollution, and
further enhancing the quality of the environment in this country.
• Implementation strategies for this Act includes monitoring and enforcement,

public awareness, and environmental cooperation.
Acute effect Odour

Agriculture damage Offensive odour
Animal intoxication Smog
Chronic effects injury Smoke
Injurious to humans Toxicant
Malaysian Environmental
Quality Act 1974
Clark Jr., W. R. (1992). Smoke inhalation: Diagnosis and treatment. World Journal
of Surgery, 16, 24–29.
Data Terbuka. (2018). Private vehicles, goods vehicles and others registered
2004–2016. https://bit.ly/3kvoYaD
Sons.



Ringer, R. K. (1989). Ecology and climate: Effects on domestic animals. In

P. Bourdeau, J. A. Haines, W. Klein, & C. R. Krishna Murti (Eds.),
Ecotoxicology and climate (pp. 225–232). John Wiley & Sons.



Topic  Damage
Process and
4 Action of
Toxicants

1. Describe the mechanism of action.
2. Identify the factors affecting xenobiotic action.
3. Explain the metabolism of environmental chemicals.
4. Discuss how the human defence system responses to
toxicants.
Have you ever heard the term „pharmacodynamics‰?
Pharmacodynamics is the study of the biochemical and physiological effects

of chemicals on living systems and the mechanisms of their actions.
The initial interaction starts a set of chemical processes that may result in a toxic
effect. The degree of effect is directly related to the concentration of the toxic
substance at the target site.

74  TOPIC 4 DAMAGE PROCESS AND ACTION OF TOXICANTS
In addition, toxic effects depend on the physical and chemical properties of the
chemical, such as solubility, vapour pressure, molecular weights, physical state,
the concentration, the duration, exposure situation, and susceptibility of the
biological system or subject. In this topic, we will further discuss on its effect and
damage process on living organisms. Let us continue with the lesson!
4.1 MECHANISM OF ACTION

Before we learn mechanism of action, let us know the meaning of interaction first.
Interaction is the effect that one chemical has on the toxic effect of another
chemical.
Chemical interactions include additive interactions and synergistic interactions as

well as potentiation and antagonism. These interactions can result in a reduction
or an increase in toxicity of one or both of the chemicals. When present at a
sufficiently high concentration, a pollutant can elicit adverse effects on the living
processes of an organism.
To exert damage to an exposed organism, a pollutant must first enter the host and
reach its target site. A complex pathway exists between the time of initial toxicant
exposure and the manifestation of damage by the organism.
Toxicants can chemically bind to target molecules through covalent and non-
covalent reactions. These reactions can change the target molecules by causing
radical formation or electron transfer, or they can change them enzymatically.
Let us look at Table 4.1 which explains the general mechanisms of toxicity.
Table 4.1: General Mechanisms of Toxicity
Mechanism Description
Interference with the Toxic substances can interfere with the action of enzyme
action of enzyme systems systems by inhibiting and inducing the enzyme.
Uncoupling of Some chemicals can uncouple biochemical reactions or

biochemical reactions disrupt specific cellular functions.
Inhibition of oxygen A number of chemicals cause toxicity by interfering with

transfer either the use or transport of oxygen in the cell.

TOPIC 4 DAMAGE PROCESS AND ACTION OF TOXICANTS  75
Blockade of haemoglobin Other substances can block haemoglobin oxygen transport

oxygen transport through preferential binding.
Synthesis of a toxic A toxic metabolite can be synthesised through

metabolite bioactivation process of a chemical.
Removal of metallic co- Certain chemicals are potentially toxic because they can
factors bind necessary metal ions making them unavailable to
enzymes.
Interference with general Toxic substances can interfere with neurotransmission,

cellular functions nucleic acids, protein synthesis, and lipids.
Immunosuppression and Some chemicals can cause immunosuppression or

hypersensitisation hypersensitisation by interacting with the cells of the
immune system.
Direct chemical irritation Unlike sensitisers, chemical irritants react directly with the
of tissues components of various tissues leading, in most cases, to
immediate local effects.
Direct cellular toxicity Toxic substances can cause direct damage to cellular
structures.
Sequestration of toxic Some toxic substances can undergo sequestration by being

substances deposited and stored in certain tissues for long periods of
time.
SELF-CHECK 4.1
1. Define the meaning of interaction.
2. List the interactions that can happen between chemicals.
ACTIVITY 4.1
Discuss in the myINSPIRE forum why combinations of toxicants may
cause effect greater than the sum of their individual.

4.2 FACTORS AFFECTING XENOBIOTIC ACTION

There are many factors that can affect the toxicity of xenobiotics. Some of them are
stated in the following Figure 4.1.
Figure 4.1: Four Factors Affecting Xenobiotic Action
Let us learn more on these factors in the next subtopics.
4.2.1 Physicochemical Properties

Physical and chemical characteristics (such as a pollutant which is solid, liquid or
gas, soluble in water or in lipid, organic or inorganic material, ionised or non-
ionised) can affect the ultimate toxicity of a pollutant.
For instance, a non-ionised substance may be more toxic than an ionised or

charged counterpart because the non-ionised species can pass through the
membrane more easily than the ionised species and, therefore, is more readily
absorbed and able to elicit its toxic action.
4.2.2 Dose or Concentration

Dose or concentration of any pollutant to which an organism is exposed to is often
the most important factor affecting its toxicity. Once a pollutant gains entry into a
living organism and reaches its target site, it may exhibit an injurious action. For
this reason, any factors capable of modifying internal concentrations of the
pollutant can alter its toxicity. The effect of the pollutant is therefore a function of
its concentration at the locus of its action.

A pollutant may either depress or stimulate normal metabolic function. In general,

minute amounts of a pollutant may stimulate metabolic function, whereas large
doses may impede or destroy its activity.
For example, a recent epidemiological study showed that in the area of Kuitan, a
city situated in the western part of China, many residents suffer from arsenism, a
disease caused by arsenic poisoning, after consuming well water containing high
levels of the mineral. Residents who had consumed well water containing 0.12mg
As/l for 10 years manifested arsenism with a prevalence rate of 1.4 per cent of the
city population. However, among residents who had consumed water containing
0.6mg As/l for only six months, the prevalence rate increased to 47 per cent, and
the patients showed more severe symptoms (Wang et al., 1997).
4.2.3 Time and Mode of Exposure

Exposure time is another important determinant of toxic effects. Normally, one can
expect that for the same pollutant, the longer the exposure time the more detrimental
the effects (see Figure 4.2). Also, continuous exposure is more injurious than
intermittent exposure, with other factors being the same.
Figure 4.2: Exposure to Pollutants
Source: https://bit.ly/3myZDht
For example, continuous exposure of rats to ozone for a sufficient period of time
may result in pulmonary oedema.

However, when the animals were exposed to ozone at the same concentration
intermittently, no pulmonary oedema was observed. Hence, the mode of exposure
(such as continuous or intermittent) is an important influence on pollutant toxicity
because living organisms often can, to a certain degree, repair injuries caused by
environmental agents. In addition, organisms may be able to develop tolerance so
that they will be able to withstand the otherwise toxic doses of chemical
substances.
4.2.4 Environmental
Temperature changes in a volume of water can affect the amount of dissolved
oxygen (DO) available in aquatic systems. The amount of DO present at saturation
in water decreases with increasing temperature.
On the other hand, the rate at which chemical reactions occur increases with
increased temperatures. This leads to faster assimilation of waste and therefore
faster depletion of oxygen.
Fish and other aquatic life can live only within certain temperature ranges, and the
range in which well-being exists is narrower than the range in which survival is
possible. Subtle behaviour changes in fish are known to result from temperature
changes but it is too small to cause injury or death.
Generally, the sensitivity of plants to air pollutants increases as relative humidity

increases. However, the relative humidity differential may have to be greater than
20 per cent before differences can be seen; for example, gladiolus plants appeared
to be more sensitive to fluoride as relative humidity increased from 50 to 80 per
cent.
The effect of light intensity on plant response to air pollutants is difficult to

generalise because of several variables involved. For example, light intensity
during growth affects the sensitivity of pinto beans and tobacco to a subsequent
ozone exposure. Sensitivity increases with decreasing light intensities within the
range of 900 to 4000fc (foot-candle).
In contrast, the sensitivity of pinto beans to peroxyacetyl nitrate (PAN) increases

with increasing light intensity. Plants exposed to pollutants in the dark are
generally not sensitive.

4.3 METABOLISM OF ENVIRONMENTAL

CHEMICALS
What is metabolism?
Metabolism is defined as the sum of all chemical reactions that occur within a
living cell.
The purpose of cellular metabolism is to maintain the homeostasis of the cell

within a population of other cells. What is homeostasis?
Homeostasis refers to a tendency toward maintenance of a relatively stable

internal environment in the bodies of higher animals through a series of
interacting physiological processes.
Metabolism is usually subdivided into two categories, anabolism and catabolism.

These two categories are further explained in Table 4.2.
Table 4.2: Two Categories of Metabolism
Anabolism It is the synthesis of larger molecules from smaller ones. The synthesis of
a protein from its amino acid building blocks is an example. Anabolism
generally requires input of energy from an energy source, such as
adenosine triphosphate (ATP).
Catabolism This refers to the degradation of larger molecules to smaller ones, such as
the breakdown of starch to glucose. In higher organisms, catabolism of
carbohydrates and fats results in the production of ATP.
Following their absorption into mammals, xenobiotics are subjected to metabolic

conversion in the body, resulting in structural changes. The metabolic process is
called biotransformation.
Biotransformation may occur in any of several body tissues and organs, including
skin, lungs, intestine, liver, and kidney. The liver carries out the majority of the
chemical reactions because it contains a large number of non-specific enzymes
capable of biotransformation of xenobiotics.

The enzymes involved in biotransformation are named mixed-function oxidase

(MFO), or commonly known as cytochrome P450. The liver metabolises not only
many xenobiotics, but also drugs to which the body is exposed to.
Biotransformation in the liver is thus a critical process in the bodyÊs defence against
the toxic effects of a wide variety of xenobiotics.
SELF-CHECK 4.2
1. What do metabolism and homeostasis mean?
2. Describe the process of biotransformation.
4.4 DEFENCE RESPONSES TO TOXICANTS

The human body has an amazingly complex defence and self-healing system. For
example, our body has its own fight-or-flight mechanism that engages quickly
when danger is near while the nose, mouth, and throat filter air, food, and water
as they come into the body. The skin, the largest organ of the body, protects the
internal system from knocks, scrapes and cuts, senses changes in the environment,
controls the body temperature, acts as a waterproof barrier, a screen against the
sun's damaging radiation, and protects underlying tissues from infection. The
brain and nervous system make direct interpretation and react to sensations from
the environment surrounding the body, and also sensations internally such as
internal organs, tissues, and cells. In fact, the body has its own fight or flight
mechanism that engages quickly when danger is near.
If bacteria, viruses or other toxic enemies invade the body, white blood cells come
to the body's defence and kill the invaders. This intricate system of protection is
increasingly under attack. The invaders, which can be odourless and invisible, ride
quietly on the most essential element in the human environment. Toxicants such
as toxins, particulate matter, and ozone are the invaders that can break down the
body's defences, or at least contribute to burden this elegant defence system.

The main route for air pollutants is through the nose, mouth, and throat (see
Figure 4.2).
Figure 4.3: Nose, Mouth, and Throat are the Main Routes for Air Pollutants
Source: https://bit.ly/2Y8FWnl
The nose is very efficient at trapping and holding some inhaled pollutants.
Concentrations of chemicals build up in the nose as the air is cleaned. The cell
damage caused by exposure to chemical pollutants puts the body's defence system
on alert and initiates an inflammatory response, similar to an allergic response.
The clearance of deposited particles is an important aspect of lung defence. Rapid

removal lessens the time available to cause damage to the pulmonary tissues or
permit local absorption. The specific mechanisms available for the removal of
particles from the respiratory tract vary with the site of the deposition. The mucous
layer covering the tracheobronchial tree is moved upward by the beating of the
underlying cilia. This mucociliary escalator transports deposited particles and
particle-laden macrophages upward to the pharynx, where they are swallowed
and passed through the gastrointestinal (GI) tract.
Besides, toxicants may dissolve from the surface and be removed via bloodstreams
or lymphatic drainage. They may be phagocytised by macrophage and removed
through the lymphatic drainage.

The skin and the mucous membranes which cover the openings of our bodies to
the external environment (such as in the nose and mouth) form protective barriers
which keep water inside the body, and keep external environment (filled with
bacteria, fungi, dust, dirt, etc.) from coming in. The skin is really an organ of the
body and a large one at that. The skin is much more than just a simple covering. It
is multi-layered and underneath the surface (which is composed of dead cells), are
other layers composed of living cells which react to irritants when they get
through.
When an irritant reaches these sensitive live skin cells, they can only respond in a
limited number of ways; the first of which is a general response to any irritating
chemical or physical agent (like sunlight), which is inflammation. Inflammation
has four components:
• redness
• pain
• heat
• swelling
The degree of inflammation is a direct result of the degree of chemical or physical

irritation (dose-response). If the damage is great enough to cause cell death, then
the response will be much more severe, and can result in areas of the skin
becoming „denuded‰ (loss of the layers, with the deeper layers being exposed to
the surface).
SELF-CHECK 4.3
1. Name three routes of exposure by which xenobiotics can gain

entry into the body.
2. Define inflammation and its four components.
ACTIVITY 4.2
Is having an allergic reaction considered as toxic effect? Discuss this

matter in the myINSPIRE forum.

• The effect that one chemical has on the toxic effect of another chemical is
known as interaction.
• Chemical interactions include additive and synergistic interactions as well as

potentiation and antagonism.
• The mechanism of action may be reflected in the inhibition of oxidative

metabolism and the central nervous system (CNS), or interaction with nucleic
acids resulting in carcinogenesis or injury to the reproductive system.
• There are many factors that can affect toxicity of xenobiotics. Some of them are
physicochemical properties of toxicants, dose or concentration, time and mode
of exposure, and environmental.
• Metabolism is defined as the sum of all chemical reactions that occur within a
living cell.
• Metabolism of environmental chemicals includes biotransformation and may

occur in any of several body tissues and organs, including the skin, lungs,
intestine, liver, and kidney.
• The human body has an amazing defence response to toxicants; it is a complex

defence and self-healing system.
• Different parts of our body react differently when it comes to defending itself
against invaders.
• For example, our body has its own fight-or-flight mechanism that engages
quickly when danger is near.

Biotransformation Mechanism of action

Chemical interactions Metabolism
Defence Physicochemical properties
Dose or concentration Respiratory tract
Environmental Time and mode of exposure
Homeostasis Xenobiotic action

Sons.


Ringer, R. K. (1989). Ecology and climate: Effects on domestic animals. In

P. Bourdeau, J. A. Haines, W. Klein, & C. R. Krishna Murti (Eds.),
Ecotoxicology and climate (pp. 225–232). John Wiley & Sons.
Wang, G. Q., Huang, Y. Z., Xiao, B. Y., Qian, X. C., Yao, H., Hu, Y., Gu, Y. L., Zhang,
C., & Liu, K. T. (1997). Toxicity from water containing arsenic and fluoride in
Xingjiang. Fluoride, 30(2), 81–84.

Topic  Toxic Action
of Pollutants
5
1. Describe toxins and pollutants.
2. Identify the sources of pollutants.
3. Explain the toxic action of major pollutants on humans.
4. Discuss the effects of toxicants on plants.
The earth has undergone massive changes due to human activities. For example,
the concentration of carbon monoxide has increased by 30 per cent since the
beginning of the Industrial Revolution, more than half of fresh water has been
used, and many animals and species are either extinct or on the verge of extinction.
Furthermore, trees are being cut down, which is one of the major causes of the
increase in pollution. This is a cause for concern as trees provide shade which cools
urban areas; they have an aesthetic value as well; and they trap polluted storm
water runoff via the soil held by their roots. Trees also trap air pollutants, trap
gaseous pollutants by the stomata in their leaves; sticky or hairy leaves also filter
particulate matters from air.

86  TOPIC 5 TOXIC ACTION OF POLLUTANTS
What is pollutant?
A pollutant is a substance which is released in the environment and it

adversely affects the usefulness of the resource.
For instance, oil enclosed within a water tanker is not a pollutant but if it spills in
the environment it can cause major health effects. Almost any chemical, any
substance, any material, whether generated by human beings or nature can
pollute.
There are numerous chemicals in the environment. Some of these are toxic and the
rest are non-toxic. The toxic chemicals are discharged into air, water, and soil. They
get into the human food chain via the environment. Once they enter our biological
system at a sufficiently high concentration, they disturb the biochemical processes
in our body and occasionally this may lead to fatality. A complex pathway exists
between the time of initial toxicant exposure and the manifestation of damage by
the organism. Thus, this topic discusses the general ways in which the
environmental pollutants exert their action on plants, animals, and human beings.
Let us continue with the lesson!
5.1 TOXINS AND POLLUTANTS

The list of toxic chemicals is very long. It is interesting that even now, there are
many cases where one is not sure whether a particular chemical is toxic or not.
There is valid confusion with respect to elements; where will the line be drawn
between the „essential limit‰ and „toxic limit‰? Such subdivisions are artificial and
can be misleading.
Many metals listed as environmental hazards are essential dietary trace elements
required for the normal growth and development of animals and human beings.
These elements are aluminium, antimony, arsenic, barium, beryllium, bismuth,
cadmium, cobalt, copper, cerium, indium, lead, mercury, molybdenum, silver,
tellurium, thallium, tin, titanium, and zinc.

TOPIC 5 TOXIC ACTION OF POLLUTANTS  87
Schwartz (1977) used the term „concentration window‰ to draw the arbitrary lines
of demarcation which are as follows:
• essential ‒ at trace level for sustenance of life processes;
• deficient ‒ at lower level than essential, causing metabolic disorder; and
• toxic ‒ at higher level than essential, causing adverse effects.
Even the well-known toxic elements (arsenic, lead, and cadmium) are required in
trace quantities for animals to grow. Conversely, the so-called biologically inert
aluminium causes brain damage, bone disease, and anaemia in patients subjected
to haemodialysis using water containing 100 to 1,000 parts per billion of
aluminium.
Toxic substances may be classified according to their function and effects as

mutagens (causing mutations), carcinogens (causing cancer)/food additions/
heavy metals, metal carbonyls, organochlorine compounds, and others.
According to the International Register of Potentially Toxic Chemicals of the

United Nations Environment Programme, there are four million known chemicals
in the world today, and another 30,000 new compounds are added to the list every
year. Among these, 60,000 to 70,000 chemicals are commonly used. Apart from
their benefits to increasing production, living standards and health, many of them
are potentially toxic.
5.2 SOURCES OF POLLUTANTS

What are the sources of pollutants? Sources of pollutants include vehicles,
chemical and petroleum refineries, manufacturing facilities, commercial
operations like dry-cleaning, ships, and airplanes. Let us look at Figure 5.1 which
summarises these sources of pollutants.

Figure 5.1: Four Major Sources of Pollutants
Pollutants are generally distributed in the environment through water and air
movements. There are many types of pollutants and their effects. Table 5.1 explains
the effects of environmental toxicants on human reproductive outcomes.
Table 5.1: Environmental Toxicants and Adverse Reproductive Outcomes
Chemical Adverse Effect
Aldrin Spontaneous abortion, premature labour.
Arsenic Spontaneous abortion, decreased birth weight.
Benzene Spontaneous abortion, low birth weight, menstrual

disorders.
Cadmium Low birth weight.
Carbon disulphide Menstrual disorders, spontaneous abortion, adverse

effects on sperm.
Chlorinated compounds Eye, ear and oral cleft defects, central nervous system
(CNS) disorders, perinatal deaths, childhood leukaemia.
1, 2-Dibromo-3- Adverse effects on sperm, sterility.

chloropropane (DBCP)
Dichloroethylene Congenital heart disease.

Dieldrin Premature labour, spontaneous abortion.
Hexachlorocyclohexane Hormonal imbalances, premature labour, spontaneous

abortion.
Lead Still birth, low birth weight, spontaneous abortion,

neurobehavioural deficits, mental retardation, delayed
development, brain damage.
Mercury Menstrual disturbances, spontaneous abortion, blindness,

deafness, mental retardation, delayed development, brain
damage.
Polycyclic aromatic Decreased fertility.

hydrocarbons (PAHs)
Polychlorinated Preterm delivery, low birth weight, reduced head

biphenyls (PCBs) circumference, growth deficiencies, neurobehavioural
effects.
Trichloroethylene (TCE) Congenital heart disease.
SELF-CHECK 5.1
What is pollutant and its the major sources?
ACTIVITY 5.1
Identify the major industries in Malaysia which are contributing to

environmental pollution. Share your finding in the myINSPIRE forum for
discussion with your coursemates.
5.3 TOXIC ACTION OF MAJOR POLLUTANTS

In this subtopic, we will discuss toxic action of the major pollutants which are
metals, toxic chemicals in the air and water, carcinogens, cyanide, and methyl
isocyanate (MIC).

5.3.1 Metals
Did you know that metals fall under the major category of globally distributed
pollutants? This is because they have a tendency to accumulate in selected tissues
of the body. Metals like copper and iron are essential for life as they contribute
towards the functioning of critical enzyme systems.
However, they can be detrimental to health if the level of exposure is high. For
example, through inhalation or food as shown in Figure 5.2.
Figure 5.2: Sources of Toxic Substances Exposure
Source: http://www.freecoloring.ca/food/food010.jpg
Other metals are xenobiotics. What is a xenobiotic?
A xenobiotic is a chemical compound such as drug or pesticide which is

foreign to the human body and they have no useful role.
Xenobiotics, like mercury and lead, can be toxic to human health even at the lowest
levels of exposure. These toxic substances affect the kidneys, digestive tract, liver,
bones, brain, and other organs in the body causing diseases like cancer and
breathing problems. The toxic action of lead, mercury, arsenic, cadmium, and
nickel are further explained as follows:

(a) Lead
Lead is widely used in industrial and household products. It is found in air,
soil, food, drinking water, and paint. It affects human health because the
body cannot break it down. Ingesting or inhaling lead particles found in the
air and the environment causes lead poisoning.
Major sources of the toxic heavy metal include leaded paint, leaded gasoline,
recycled oil, ceramics, contaminated soils, and smelters. Dietary sources of
lead include contamination of agricultural crops, lead in food containers, and
contaminated drinking water.
When high levels of lead are present, the entire body is affected, especially
the nervous system and kidneys (see Figure 5.3).
Figure 5.3: Lead Poisoning
Source: https://bit.ly/3jYGIee
Did you know that normal daily activities give enough opportunities for
children to come in contact with lead toxicity? Even small doses of lead can
cause irreversible adverse effect on children's intelligence. Lead is especially
harmful to children ages three and under whose brains and nervous systems
are still in the developmental stage.

In a recent study conducted in Malaysia, the percentage of school children

with excessive blood lead was highest for Kuala Lumpur. Kuala LumpurÊs
school children are 25 times at greater risk of having excessive blood lead
levels as compared to school children from rural areas like Kemaman and
Setiu. Urban school children acquire higher blood lead levels than their rural
and semi-urban counterparts, even after controlling for age, sex, parentsÊ
education, and income levels.
There was a case in South China where a battery factory was closed due to
lead poisoning. Forty four children living in the area near to the factory were
found to have excessive levels of lead in their blood before the cityÊs
environmental bureau took over the battery plant to conduct tests on the
factoryÊs water discharge.
There are three levels of lead poisoning as discussed in Table 5.2.
Table 5.2: Three Levels of Lead Poisoning
Level Description
Acute Typical neurological signs are pain, muscle weakness,

poisoning paraesthesia and, rarely, symptoms associated with encephalitis.
Gastrointestinal problems, such as constipation, diarrhoea,
poor appetite or weight loss, are common in acute poisoning.
Chronic Comes with symptoms affecting multiple systems, but is

poisoning associated with three main types of symptoms: gastrointestinal,
neuromuscular, and neurological. Central nervous system and
neuromuscular symptoms usually result from intense exposure,
while gastrointestinal symptoms usually result from exposure
over longer periods.
Signs of chronic exposure include loss of short-term memory or

concentration, depression, nausea, abdominal pain, loss of
coordination, and numbness and tingling in the extremities.
Fatigue, problems with sleep, headaches, stupor, slurred speech
and anaemia are also the harmful results of chronic lead
poisoning.

Mechanism of On a molecular level, proposed mechanisms for toxicity involve

action fundamental biochemical processes. These include leadÊs ability
to inhibit or mimic the actions of calcium (which can affect
calcium-dependent or related processes) and to interact with
proteins (including those with sulfhydryl, amine, phosphate, and
carboxyl groups.
Lead inhibits the body's ability to make haemoglobin by

interfering with several enzymatic steps in the haem pathway.
Specifically:
• Lead decreases haemoglobin biosynthesis by inhibiting
d-Aminolevulinic Acid Dehydratase (ALAD) and
ferrochelatase activity.
• Lead creates ferrochelatase, which catalyses the insertion of
iron into protoporphyrin IX, which is quite sensitive to lead.
• A decrease in the activity of this enzyme results in an
increase of the substrate, erythrocyte protoporphyrin (EP)
and in the red blood cells (also found in the form of
ZPP-bound to zinc rather than to iron).
• Lead is also associated with lead exposure is an increase in
blood and plasma d-Aminolevulinic Acid (ALA) and free
erythrocyte protoporphyrins (FEP).
(b) Mercury
Mercury is a natural and very poisonous substance. It is used in many
different forms in our society, such as in paint, batteries and many other
industrial, and household uses. Mercury is also well known to be used in
thermometers.
How does mercury affect us? Mercury damages the central nervous system,
endocrine system, kidneys, and other organs, and adversely affects the
mouth, gums, and teeth. Women who have been exposed to mercury during
pregnancy have sometimes given birth to children with serious birth defects.
The inhalation of elemental mercury vapour can cause neurological and
behavioural disorders, such as tremors, emotional instability, insomnia,
memory loss, neuromuscular changes, and headaches. Mercury poisoning
occurs when a person inhales or ingests or the skin or eye comes into contact
with mercury.
What are the sources of mercury? Mercury is widely found in water, soil, and
air in various forms. Fish and shellfish are the major sources of mercury
poisoning in humans.

As Malaysia becomes more and more industrialised, the amount of solid

waste being generated is getting out of hand. One example of evidence is the
landfills that are fast filling up in the Klang Valley region. Solid waste
includes e-waste, i.e. electronic and computer equipment that has been
thrown out as junk. With shortening useful life cycles for computer
equipment, the e-waste problem can only grow in size. Solid waste can be
hazardous to health too, e.g. e-waste that contains components made of toxic
materials.
Other examples of hazardous waste include toxic chemicals such as mercury

and cadmium, radioactive materials, and biomedical waste generated by
clinics, hospitals, and scientific research institutes.
Another case of mercury poisoning happened in Minamata, Japan where

people were poisoned due to their eating of fish that had been contaminated
by mercury, discharged from factories into the surrounding marine
environment, just like the one shown in Figure 5.4.
Figure 5.4: The Process of Mercury Entering the Food Chain
The clinical presentation of mercury toxicity can manifest in a variety of

ways, depending on the nature of the exposure, the intensity of the exposure,
and the chemical form. Acute toxicity usually is related to the inhalation of
elemental mercury or ingestion of inorganic mercury. Exposure to organic
mercury leads to chronic toxicity and occasionally, acute toxicity. These types
of toxicity are explained in Table 5.3.

Table 5.3: Three Types of Mercury Toxicity
Type Description
Acute Caused by inhaled elemental mercury can lead to pulmonary

exposure symptoms. Initial signs and symptoms, such as fever, chills,
shortness of breath, metallic taste, and pleuritic chest pain, may
be confused with metal fume fever. Other possible symptoms
could include stomatitis, lethargy, confusion, and vomiting. In
addition, elemental mercury can also be injected to a person
causing a life-threatening pulmonary embolism.
Chronic and Causes cutaneous and neurological symptoms. The classic triad
intense acute found in chronic toxicity comprises tremors, gingivitis, and
exposure erethism (i.e., a constellation of neuropsychiatric findings that
includes insomnia, shyness, memory loss, emotional instability,
depression, anorexia, vasomotor disturbance, uncontrolled
perspiration, and blushing).
Organic Usually comes from ingestion of contaminated food. The long

mercury chain and aryl forms of organic mercury have similar
poisoning characteristics of inorganic mercury toxicity as below:
• The onset of symptoms usually is delayed (days to weeks)
after exposure.
• Organic mercury targets enzymes and the depletion of these
enzymes must occur before the onset of symptoms.
• Symptoms related to toxicity are typically neurological, such
as visual disturbance (e.g. scotomata, visual field
constriction), ataxia, paraesthesias (early signs), hearing loss,
dysarthria, mental deterioration, muscle tremor, movement
disorders, and, with severe exposure, paralysis and death.
• Organic mercury targets specific sites in the brain, including
the cerebral cortex (especially visual cortex), motor and
sensory centres (pre-central and post-central cortex), auditory
centre (temporal cortex), and cerebellum.
(c) Arsenic
Both inorganic and organic forms of arsenic may cause adverse effects in
laboratory animals. The effects induced by arsenic range from acute lethality
to chronic effects such as cancer. The degree of toxicity of arsenic is basically
dependent on the form (inorganic or organic) and the oxidation state of the
arsenic object.

It is generally considered that inorganic arsenic is more toxic than organic

arsenic, and within these two classes, the trivalent forms are more toxic than
the pentavalent forms, at least at high doses.
Several different organ systems are affected by arsenic, including the skin,
respiratory, cardiovascular, immune system, genitourinary, reproductive,
gastrointestinal, and nervous system.
Now, let us discuss its effects on human health and our bodyÊs mechanism of
action.
(i) Effects on Human Health

Long-term exposure to arsenic in drinking water is causally related to
an increase in risks of cancer in the skin, lungs, bladder and kidneys, as
well as other skin changes such as hyperkeratosis and pigmentation
changes. Increased risks of lung and bladder cancer and of arsenic-
associated skin lesions have been reported to be associated with the
ingestion of drinking water at concentrations of 50øg arsenic/litre.
Different parts of the body can be affected by arsenic, including the skin,
lungs, heart, blood vessels, immune system, kidneys, reproductive
system, gut, and nervous system. Chronic arsenic exposure in human
beings has been shown to cause Black Foot disease, a severe form of
peripheral vascular disease (PVD), which leads to gangrenous changes.
(ii) Mechanism of Action

By virtue of its similarity to phosphorus, arsenic interferes with some
biochemical processes involving phosphorus. This is observed in the
biochemical generation of the key energy yielding substance, ATP.
Arsenic (III) compounds at high concentrations coagulate proteins,

possibly by attacking the sulphur bonds maintaining the secondary
and tertiary structures of proteins.
The three major biochemical actions of arsenic are coagulation of

proteins, complexation with coenzymes, and uncoupling of
phosphorylation.

(d) Cadmium
Acute cadmium intoxication is caused by inhalation of high concentrations
of cadmium, usually as fume. There may be no immediate warning signs
(symptoms) of irritation. More typically, the first symptoms may appear
within 4 to 10 hours, although coughing and breathing difficulties may
progress rapidly to pulmonary oedema. The dust of cadmium can also be
ingested, resulting in abdominal pain, nausea, and vomiting. Chronic
cadmium toxicity tends to be progressive.
Repeated exposure to lower levels of cadmium dust in the air may result in
chronic poisoning characterised by irreversible lung injury. Renal tubular
damage is also likely to occur because of the inability of the kidneys to
effectively filter cadmium. Cadmium in the kidneys, causing excess calcium
to be excreted instead of absorbed, may affect the mineralisation of bones.
Occupational exposure to cadmium has also been associated with a

significant increase in kidney stones, urinary tract cancer, and prostate
cancer.
A major portion of cadmium ingested into our body is trapped in the kidneys
and eliminated. A small fraction is bound effectively by the body proteins,
metallothionein, present in the kidneys, while the rest are stored in the body
and gradually accumulate with age.
(e) Nickel
Pure nickel is a hard, silvery-white metal (see Figure 5.5).
Figure 5.5: Pure Nickel

Nickel has properties that make it very desirable for combining with other
metals to form mixtures called alloys. There are also compounds consisting
of nickel combined with many other elements, including chlorine, sulphur,
and oxygen. Many of these nickel compounds are water soluble (dissolve
fairly easily in water) and have a characteristic green colour. Nickel and its
compounds have no characteristic odour or taste.
Nickel combined with other elements occurs naturally in the earthÊs crust. It
is found in all soil, and is also emitted from volcanoes. In the environment, it
is primarily found combined with oxygen or sulphur as oxides or sulphides.
How does nickel get into the atmosphere? Nickel is released into the
atmosphere during nickel mining and by industries that make or use nickel,
nickel alloys, or nickel compounds. These industries also might discharge
nickel in waste water. Nickel is also released into the atmosphere by
oil-burning power plants, coal-burning power plants, and trash incinerators.
It will than settle to the ground or fall down after reactions with raindrops.
It usually takes a long time for nickel to be removed from air. Nickel can also
end up in surface water when it is a part of the wastewater streams.
The larger part of all nickel compounds that is released into the environment
will adsorb to sediment or soil particles and consequently become immobile.
In acidic ground, however, nickel is bound to become more mobile and it will
often rinse out to the groundwater.
There is not much information available on the effects of nickel upon

organisms other than humans. The high nickel concentrations on sandy soils
can clearly damage plants and high nickel concentrations in surface waters
can diminish the growth rates of algae.
Microorganisms can also suffer from growth decline due to the presence of
nickel, but they usually develop resistance to nickel after a while. For
animals, nickel is an essential mineral in small amounts.
However, nickel is not only favourable as an essential element; it can also be

dangerous when the maximum tolerable amounts are exceeded. This can
cause various kinds of cancer on different sites within the bodies of animals,
mainly of those that live near refineries.
Nickel is not known to accumulate in plants or animals. As a result, this

mineral will not biomagnify up the food chain.

SELF-CHECK 5.2
Describe the toxic effects of lead, mercury, arsenic, cadmium, and nickel
on human beings.
ACTIVITY 5.2
Collect three case studies related with mercury poisoning and make a
chart of all of them. Discuss your findings in the myINSPIRE forum with
your coursemates.
5.3.2 Toxic Chemicals in Air

The toxic chemicals that are airborne may be filled with poisonous substances.
Here, we highlight the toxic chemicals in the air which are carbon monoxide, nitric
oxide, sulphur dioxide, and ozone and peroxyacetyl nitrate (PAN).
(a) Carbon Monoxide

What is carbon monoxide?
Carbon monoxide is a toxic gas in air which is produced by way of

combustion.
In acute poisoning, problems may include difficulty with higher intellectual

functions, short-term memory loss, dementia, amnesia, psychosis,
irritability, a strange gait, speech disturbances, ParkinsonÊs disease-like
syndromes, cortical blindness, and a depressed mood. Depression may even
occur in those who did not have pre-existing depression.
Next is chronic poisoning. Chronic exposure to relatively low levels of

carbon monoxide may cause persistent headaches, light-headedness,
depression, confusion, memory loss, nausea, and vomiting. It is unknown
whether low-level chronic exposure may cause permanent neurological
damage.

Lastly, we look at mechanism of action of carbon monoxide. Carbon

monoxide exerts its toxic effects by means of a combination of tissue asphyxia
and inflammatory activity. Hypoxia occurs from three primary mechanisms,
that is when carbon monoxide:
• diminishes the oxygen carrying capability of haemoglobin;
• decreases the uptake of bound oxygen into tissues; and
• impairs the mechanisms of cellular respiration.
Carbon monoxide readily crosses capillary membranes in the lungs and

binds the haem moiety on the erythrocyte haemoglobin complex with an
affinity of 200 to 300 times greater than that of oxygen. This binding
drastically decreases binding spots available for oxygen transport. The
amount of oxygen that is able to bind haemoglobin in the setting of carbon
monoxide exposure is proportional to the partial pressure of oxygen (PO2) in
respired air and can be increased by giving supplemental O2.
(b) Nitrogen Oxides

Nitric oxide (NOx) is less toxic than nitrogen dioxide. Like CO, it forms bonds
with haemoglobin and reduces oxygen transport efficiency. In polluted air,
NOx is present at much lower concentration than CO, so that the effect on
haemoglobin is much less.
Exposure to high industrial levels of nitric oxide and nitrogen dioxide can
cause death. It can lead to collapse, rapid burning and swelling of tissues in
the throat and upper respiratory tract, difficulty in breathing, throat spasms,
and fluid build-up in the lungs. It can also interfere with the blood's ability
to carry oxygen through the body, causing headache, fatigue, dizziness, and
a blue colour to the skin and lips.
Industrial exposure to nitrogen dioxide may cause genetic mutations,

damage developing foetus and decrease fertility in women. Repeated
exposure to high levels of nitrogen dioxide may lead to permanent lung
damage. Exposure to low levels of nitrogen oxides in smog can irritate the
eyes, nose, throat, and lungs. It can cause coughing, shortness of breath,
fatigue, and nausea.
(c) Sulphur Dioxide

It is one of the major pollutants in the air and it can significantly affect
humans, plants, and animals. These pollutants are the precursors of acid rain
and atmospheric particulate.

(d) Ozone and Peroxyacetyl Nitrate (PAN)

Ozone is considered a secondary pollutant because it is formed in the
atmosphere by the reaction of other pollutants. Tropospheric (ground-based)
ozone is harmful to human health. When gasoline and coal are burned,
nitrogen oxide gases (NOx) and volatile organic compounds (VOC) are
released into the air.
During the warm, sunny days of spring, summer, and early fall, NOx and
VOC are more likely to combine with oxygen and form ozone. During those
seasons, high concentrations of ozone are often formed during the heat of the
afternoon and early evening, and are likely to dissipate later in the evening
as the air cools.
PAN is an oxidising agent formed by the reaction of organic compounds

(e.g. aldehydes) with OH radicals, followed by the addition of O2 and NO2 .
5.3.3 Safe Drinking Water

Safe drinking water is affected by water pollution. What are the sources of water
pollution? The sources of water pollution are shown in Figure 5.6.
Figure 5.6: Sources of Water Contamination by Industrial and Household Wastes
Source: http://superiorsites3.com/Images/GroundWaterPollute.jpg
There is risk to health because lead, pesticides, and chemicals are found in public
water supplies. Contaminants can enter drinking water by a variety of ways, the
major sources being animal wastes, industrial wastes, and household wastes.

Diseases caused by contaminated water are hepatitis, cholera, bacterial dysentery,

digestive or kidney problems, diarrhoea, and fever. People can get arsenicosis,
cholera, fluorosis, Guinea worm disease, malaria, schistosomiasis, and typhoid
fever from contaminated water.
Schistosomiasis is a disease caused by parasitic worms that penetrate skin when

people swim in, bathe, or wash in contaminated water. The disease can lead to
infection and can result in liver, intestine, lungs, and bladder damage.
In response to the need for a realistic and appropriate set of guidelines regarding
safe and potable water supply throughout Malaysia, the Drinking Water Quality
Surveillance Unit, Engineering Services Division, Ministry of Health Malaysia
prepared a set of standard. This was done under the guidance of experts from the
World Health Organization. You can read the standard at https://bit.ly/3lEOBqz.
5.3.4 Carcinogens (Cancer Causing Chemicals)

Cancer is one of the greatest causes of death in many countries. Under normal
circumstances, the body's cells reproduce in a consistent mode, so that broken
tissues are replaced, injuries are revived, and development of the body continues.
Nevertheless, under few circumstances, certain cells experience a poorly

understood transformation that alters the cells. This transformation occurs due to
damage to the cell's DNA (deoxyribonucleic acid), the material of inheritance
found in the nucleus of the cell. Cells can often repair damage done to the DNA,
or the immune system may acknowledge that a cell has been destroyed and then
kill the cell so that it does not prevail to cause cancer.
If neither of these events happens, the destroyed cell may stay on to split and
develop, making more broken-down duplicates of it. A cell that has sustained
impairment once to its DNA, particularly cells which first lose the power to repair
themselves, will frequently carry on to accumulate more impairment. If the
impairment does not kill the cells it will cause the cells to appear and behave
differently from normal healthy cells.

There are many chemicals which are carcinogens. They are:
• 2-aminonaphthalene • mineral oils
• 4-aminobiphenyl • nickel compounds
• 5-azacytidine • nitrogen mustard
• aflatoxins • shale oils
• alcohol • sulphur mustard
• arsenic • tobacco smoke
• benzene • treosulphan
• benzidine • triethylenethiophosphoramide
• chromium compounds • vinyl chloride
• coal tars
A typical confirmed human carcinogen is vinyl chloride. This is used for the
production of polyvinyl chloride (PVC), which in turn is mainly used in the
production of plastic pipes. PVC pipes are widely used in plumbing. Vinyl
chloride has been associated with tumours of the liver, brain, lungs, and lymphatic
system.
In 1974, more than 40 years after the introduction of vinyl chloride into the
industry, an association of exposure to this chemical with human cancer was
reported. Three cases of liver cancer were reported in men who were employed in
the manufacture of PVC resins in a single plant in the US. By reviewing medical
records, the relationship between exposure to vinyl chloride and tumours of the
liver was confirmed. Once a chemical is recognised as a human carcinogen, many
countries set strict limits for its use in the workplace and its release into the
environment.
Aluminium is also carcinogen. The International Agency for Research on Cancer

(IARC) found that aluminium production is a carcinogenic agent to human beings.
There is an increased risk of lung cancer among people that work in aluminium
production. In Canada, an increased risk of bladder cancer was found to be
associated with work in aluminium production. To decrease the risk of cancer,
companies introduced the use of a different processing method, improved the
ventilation, required workers to wear protective masks, and initiated a urine
monitoring programme for the early detection of bladder cancer.

Many carcinogens come from natural sources. Different types of carcinogens are
produced by plants. The best known of these, accounting for at least 30 per cent of
all cancers in the US, are agents found in the tobacco plant. Tobacco contains
certain carcinogens such as nitrosonornicotine. Tobacco smoke is a complex
chemical mixture and contains many different types of carcinogens, including
polycyclic aromatic hydrocarbons (PAHs).
5.3.5 Cyanide
Cyanide is a rapidly acting, potentially deadly chemical that can exist in various
forms. The extent of poisoning caused by cyanide depends on the amount of
cyanide a person is exposed to, the route of exposure, and the length of time that
a person is exposed to it.
Breathing cyanide gas causes the most harm, but ingesting (swallowing) cyanide
can be toxic as well. Cyanide gas is most dangerous in enclosed places where gas
will be trapped. It prevents the cells of the body from using oxygen. When this
happens, the cells die. Cyanide is more harmful to the heart and brain than to other
organs because the heart and brain use a lot of oxygen.
Exposure to a large amount of cyanide by any route may cause other health effects
such as:
• convulsions
• low blood pressure
• slow heart rate
• loss of consciousness
• lung injury
• respiratory failure leading to death
SELF-CHECK 5.3
1. Define carcinogens. Name five of them.
2. Why is cyanide very deadly?

ACTIVITY 5.3
Cyanide has been used as a chemical weapon since World War I. Do you
agree with this practice? Discuss this issue in the myINSPIRE forum.
5.3.6 Methyl Isocyanate (MIC)

MIC is used in the production of pesticides, polyurethane foam, and plastics.
How does MIC affect us? Acute inhalation exposure to MIC in humans results in
respiratory tract irritation, difficulty breathing, blindness, nausea, gastritis,
sweating, fever, chills, and liver and kidney damage. Damage to the lungs (e.g.
bronchoalveolar lesions and decreased lung function) and the eyes (e.g. loss of
vision, loss of visual acuity, and cataract) continue to happen to the survivor.
Animal studies have reported increased incidence of foetal deaths and decreased
fertility, live litter size, foetal body weight, and neonatal survival following
inhalation exposure to methyl isocyanate during pregnancy.
We have discussed toxic action of metals, toxic chemicals in the air and water,
carcinogens, cyanide, and MIC. Take note that there are other pollutants that are
harmful to human beings. These pollutants are summarised in Table 5.4.
Table 5.4: Other Pollutants and Their Effects to Human
Pollutant Effect
Thallium Short-term exposure to thallium can cause gastrointestinal irritation

and nerve damage if the contaminant levels are above the maximum
contaminant level (MCL). Long-term level exposure to thallium above
MCL can cause changes in blood chemistry, damage to liver, kidney,
intestinal and testicular tissues, and hair loss.
Copper If the level of contamination is above the MCL in water or food supply,
people exposed to it can be affected by stomach and intestinal distress,
liver and kidney damage, and anaemia.

Selenium Selenium is an essential nutrient at low levels but above MCL even
for relatively short period of time, can lead to hair and fingernail
changes, damage to the peripheral nervous system and fatigue cum
irritability. Long-term exposure can cause hair and fingernail loss,
damage to the kidney and liver tissues, as well as the nervous and
circulatory systems.
Nitrates/nitrites Excessive levels of nitrates in drinking water have caused serious

illness and sometimes death in short-term exposure. The serious
illness in infants is due to the conversion of nitrate to nitrite by the
body which interferes with the oxygen-carrying capacity of the
infant's blood. The infant's health then deteriorates rapidly over a
period of days with symptoms of shortness of breath and blueness of
the skin appear.
Long-term exposure can cause diuresis, increase starchy deposits,

and haemorrhaging of the spleen.
Antimony Short-term consumption of drinking water with contamination

above MCL of 6ppb can cause nausea, vomiting, and diarrhoea;
while long-term consumption can lead to cancer, as antimony is a
known human carcinogen.
Beryllium Short-term exposure to beryllium exceeding the MCL can cause

inflammation of the lungs when inhaled, but is less toxic in water;
whereas long-term exposure can cause damage to bones and lungs,
and can cause cancer.
Asbestos When the level of asbestos in drinking water is above MCL and this
continues for a long period of time, it can cause cancer and lung
disease.
Barium Consumption of water above MCL for relatively short period of time
can cause gastrointestinal disturbances and muscular weakness,
whereas long-term exposure can lead to the occurrence of high blood
pressure.
Chromium Short-term exposure above MCL causes skin irritation and

ulceration, whereas long-term exposure causes damage to liver,
kidney, circulatory and nerve tissues, as well as skin irritation.
Chromium is very persistent in water as sediment and has a tendency
to accumulate.

ACTIVITY 5.4
Find out the worst environmental disaster on record of MIC. What were
the toxic effects of MIC on the people over a period of time? Share your
findings for discussion in the myINSPIRE forum.
5.4 EFFECTS OF TOXICANTS ON PLANTS

Now, let us find out the effects of toxicants on plants. Plants may absorb toxicants
either directly from the atmosphere, through the leaves, or from the soil or water
through the roots. The usual pathway is through the leaves, as with gaseous
chemicals including principally, sulphur and nitrogen oxides, photochemical
pollutants, fluoride, chlorine, and ammonia.
Other chemicals, present in the atmosphere in particulate forms, may be impacted

onto the leaf surface but rarely enter the leaf unless dissolved. Such toxicants
include heavy metals such as lead, zinc, cadmium, copper, and nickel.
5.4.1 Harmful Effects of Metals

Firstly, let us look at the harmful effects of metals to the plant. The metals discussed
in this subtopic are arsenic, cadmium, lead, and mercury.
(a) Arsenic
Arsenic could be an essential element for plant growth, but it has not been
proven. It is chemically similar to phosphorous, an essential plant nutrient
that can substitute phosphorous in plant nutrition. When arsenic in a
solution penetrates the cuticle and enters the apoplast system (the non-living
cell wall phase), it bathes the external surface of the plasmalemma of the
symplast. This is the location of at least some of the enzymes of a living plant.
One of the first symptoms of injury due to sodium arsenite is wilting (see
Figure 5.7).

Figure 5.7: Wilting Loss of Non-woody Part of the Plant
Source: https://commons.wikimedia.org/wiki/File:Fig_leaves.jpg
Wilting causes the loss of turgor, and this immediately suggests the change
in the membrane integrity. Reaction of trivalent arsenic with sulfhydryl
enzymes could well explain the effects of membrane degradation injury and
eventually death.
(b) Cadmium
Cadmium is a non-essential element that negatively affects plant growth and
development. Cadmium can alter the uptake of minerals by plants through
its effects on the availability of minerals from the soil, or through a reduction
in the population of soil microbes. Stomatal opening, transpiration, and
photosynthesis have been reported to be affected by cadmium in nutrient
solutions, but the metal is taken up into plants more readily from nutrient
solutions than from soil.
However, plants grown in soil are generally insensitive to the effects of

cadmium except at high doses. Chlorosis, leaf rolls, and stunting are the main
and easily visible symptoms of cadmium toxicity in plants. Figure 5.8 shows
you how chlorosis happens to a leaf.

Figure 5.8: Chlorosis
Cadmium is extremely toxic to chloroplast, as it is to mitochondria. It decreases

photosynthesis and increases photorespiration.
(c) Lead
Lead is considered a general protoplasmic poison, which is cumulative, slow
acting, and subtle. Soils contaminated with lead will see a sharp decrease in
crop productivity, thereby posing a serious problem for agriculture.
The visual non-specific symptoms of lead toxicity are rapid inhibition of root
growth, stunted growth of the plant, and chlorosis. When lead enters inside
the cells even in small amounts, it produces a wide range of adverse effects
on the plant's physiological processes.
Meanwhile, high concentrations of lead in soil environment causes

imbalance of mineral nutrients in growing plants (see Figure 5.9).

Figure 5.9: Damaged Roots and Stunted Growth
Source: https://bit.ly/3pYvfzh
Many of the observed actions of lead appear to be indirect as a result of

mineral imbalance within the tissues.
(d) Mercury
Mercury affects both light and dark reactions of photosynthesis. The most
noticeable and consistent effect is the induction of c-mitosis through
disturbance of the spindle activity, resulting in the formation of polyploid
and aneuploid cells, and c-tumours. Organomercurials have been reported
to be 200 times more potent than inorganic mercury. Exposure to inorganic
mercury reduces mitotic index in the root-tip cells and increases the
frequency of chromosomal aberrations in degrees directly proportional to the
concentrations used and to the duration of exposure.

5.4.2 Harmful Effects of Gases in Air

Now, let us look at the harmful effects of gases in the air. These gases are:
(a) Nitrogen-containing Air Pollutants

Nitrogen-containing air pollutants can affect vegetation indirectly, via
photochemical reaction products, acid rain, or directly after being deposited
on vegetation, soil, or water surface. The impacts of increased nitrogen
deposition upon biological systems can be the result of direct uptake by
foliage or uptake via the soil. At the level of individual plants, the most
relevant effects are injury to the tissue, changes in biomass production, and
increased susceptibility to secondary stress factors.
Nitric acid is formed from the reaction of water with NO2. Both natural
vegetation and crops are affected by acid rain. Soil nutrients are destroyed
by acid, while plant germination is hampered by acid rain.
(b) Ground-level Ozone

Ground-level ozone is also hard on plants, by damaging the ecosystems and
leading to reduction in crop and forest yields. In the US alone, for example,
ground-level ozone accounts for an estimated USD500 million in reduced
crop production annually.
Ground-level ozone also kills many seedlings and damages foliage, making
trees more susceptible to diseases, pests, and harsh weather. Ozone and PAN
inhibit the primary process of photosynthesis in plants which can stop or
reduce growth in plants. In fact, PAN is more toxic to plants than ozone.
(c) Sulphur Dioxide

Exposure to higher levels of sulphur dioxide causes destruction of leaf tissue
(leaf necrosis) and damage of the edges of leaves and the areas between the
veins. Chronic exposure of SO2 leads to chlorosis, i.e. bleaching or yellowing
of the normally green portions of the leaves. As relative humidity increases,
plant injury is also enhanced. Such injury reaches maximum level when the
stomata are open i.e. during daytime.

SELF-CHECK 5.4
1. What are the effects of arsenic, cadmium, lead, and mercury to plant?
2. How does nitrogen-containing air pollutants, ground-level ozone,

and sulphur dioxide affect plants?
ACTIVITY 5.5
Read the following case study and answer the given questions. Share
your answers for discussion in the myINSPIRE forum.
Case Study: Chernobyl Accident

The Chernobyl accident on 26 April, 1986, happened when the world's
largest reactor exploded. This accident occurred at unit four of the
graphite moderated, 1,000MW, boiling water pressure tube reactor at
Chernobyl, 80km north of Kiev in Ukraine, which was then part of the
USSR.
At the time of the accident, this type of reactor was one of 14 such
reactors in the USSR, comprising more than half of the nuclear-
powered electricity generation capacity of the country. The accident
followed a dramatic and cumulative series of errors incurred while
conducting a series of tests and included a blatant disregard of safety
procedures, which were exacerbated by design faults of the RMBK
reactor itself. Several safety systems were deliberately disabled.
The single most important design problem was that steam generation
in the fuel channels caused an increased number of neutrons to collide
with the graphite leading to an increased rate of fission.
Under such circumstances, a last desperate attempt to stop the

reaction by inserting the control rods had the opposite effect, and
within four seconds the reactor power reached more than 100 times its
capacity. The resultant explosion sheared all 1,661 water pipes, blew
the 1,000-tonne cap off the top of the core and ruptured the concrete
walls of the reactor hall.

Radioactive dust, including pulverised fuel, was thrown at least 7.5km

into the air and the intense heat started at least 30 fires. The radioactive
release lasted about 10 days, and despite attempts to quench the
reaction through air drops of boron carbide, sand, clay, and lead, there
was a complete meltdown of the reactor core.
Nine days following the initial explosion, the daily release rate of
radioactive material was nearly as high as it was at the time of the
initial release. As an immediate result of the accident, 31 people were
killed, and another 65 of the original staff of the reactor had died by
1991. As a group, they experienced a death rate more than 100 times
that of a comparable, unexposed population.
In the months following the explosion, more than half a million people
were involved with the construction of a sarcophagus around the
melted core. In some areas, the radiation fields were as high as
66 rad/min.
Despite the stated intent to limit workers to maximum doses of 20 rad

(500 rad is regarded as a lethal dose), it can be appreciated that, in such
an environment, many were probably exposed to considerably higher
levels of radiation, and many probably received doses comparable to
survivors of the Hiroshima and Nagasaki explosions. Including the 31
deaths, the USSR had a total of 237 cases of acute radiation sickness as
a result of the accident.
Released radionuclides included essentially all the noble gases,

volatile elements (i.e., 131 I and 134,137 Cs) and some refractory
materials (i.e., 89,90 Sr, 141,144 Ce, 238,239,240 Pu).
In Sweden, the fallout was identified as containing radioactive

krypton, xenon, iodine, caesium, and cobalt.
Through integration of environmental data, it is estimated that some

100 petabequerel of 137 Cs (1 Pbq = 1015 Bq/kg) were released during
and subsequent to the accident. Total release of radioactivity exceeded
3 1018 Bq.

Due to the prevailing weather patterns at the time of the accident, the
spread of the fission product plume from Chernobyl was sustained for
11 days and affected many countries including Finland, Sweden,
Denmark, Germany, France, Italy, Austria, Poland, the United
Kingdom, and Czechoslovakia. Japan, the United States, and Canada
were slightly affected.
In Poland, the closest country to Ukraine, the government banned the sale
of milk from cows on pasture, and children were treated with potassium
iodide to reduce their uptake of 131 I. In parts of Sweden, where rain or
snow had fallen since the accident, people were advised not to drink water,
which might be 100 times more radioactive than normal.
Although no acute effects occurred outside the USSR, the risk for
lifetime expectation of fatal radiogenic cancer increased from 0 to 0.02
per cent in Europe and 0 to 0.003 per cent in the northern hemisphere.
During the years following the Chernobyl accident, there have been
numerous clinical studies of human populations exposed to radiation,
some of which continue today.
Several reveal symptoms both directly and indirectly related to the

radiation. Distinct changes in the clinical picture of acute pneumonia
were noted in patients subjected to constant, prolonged (1986–1990)
effect of small doses of ionising radiation as a result of residing in the
contaminated territory after the accident. These changes included
increased duration of the disease and the frequency of protracted
forms as well as suppression of the immune system.
The small radiation doses in Kiev, 80km away from the accident, had
a significant impact on the humoral immunity of the population. It
was predicted a 1.4-fold increase in thyroid cancer morbidity (relative
to spontaneous incidence) in children who lived in the heavily
contaminated region of Ukraine in 1986.
Ecological effects many European species of mycorrhizal fungi,

including several edible ones, were found to contain unacceptably
high levels of 137 Cs (>1,000 Bq/kg dry weight) following the
accident. 137 Cs concentrations in lichens and mosses in some areas
were significantly elevated five years after the accident.

A study of earthworm populations in a 30km zone around the

Chernobyl nuclear power plant following the accident indicated a
significant, but temporary, depression in recruitment relative to
control plots. The populations however, had recovered by the summer
of 1988.
Questions
1. What are the principal forms of ionising radiation? Give specific

examples of radionuclides responsible for each of these different
types of emission.
2. Describe the effects of ionising radiation at the molecular level.

Give two ways in which radiation may cause cell death. In what
ways does radiation affect the immune system?
3. Give an account of the chronic effects of radiation exposure.

What are the difficulties in assessing the risk from low levels of
ionising radiation?
4. Write a short essay on how electricity is produced from nuclear

power, including a brief description of the major steps in the
nuclear fuel cycle.
5. Give an account of the treatment of waste products from nuclear

power generation, including both reprocessing and waste
management.
6. Give short accounts of the environmental significance of radon

(222 Rn), caesium (137 Cs), strontium (90 Sr), and iodine (131 I).
7. Describe the immediate and long-term effects of the Chernobyl

reactor accident. What were the lessons from this incident for the
nuclear power industry?

• Toxic substances may be classified according to their function and effects as

mutagens (causing mutations), carcinogens (causing cancer) or food additions,
or heavy metals, metal carbonyls, organochlorine compounds, etc.
• Sources of pollutants include vehicles, chemical and petroleum refineries,

manufacturing facilities, and transportations.
• Pollutants are generally distributed in the environment through water and air
movements.
• Metals fall under the major category of globally distributed pollutants; they
have a tendency to accumulate in selected tissues of the body.
• Lead is widely used in industrial and household products. It is found in air,

soil, food, drinking water, and paint. It affects human health because the body
cannot break it down.
• Mercury is a natural and very poisonous substance. It damages the central

nervous system, endocrine system, kidneys, and other organs, and adversely
affects the mouth, gums and teeth.
• Both inorganic and organic forms of arsenic may cause adverse effects ranging
from acute lethality to chronic effects such as cancer.
• Repeated exposure to lower levels of cadmium dust in the air may result in
chronic poisoning characterised by irreversible lung injury.
• Nickel can be dangerous when the maximum tolerable amounts are exceeded.
This can cause various kinds of cancer on different sites within the bodies of
animals, mainly of those that live near refineries.
• Toxic chemicals in the air include carbon monoxide and nitrogen oxides.
• The safe drinking water is affected by water pollution. There is a risk to health
because lead, pesticides, and other chemicals are found in public water
supplies.
• Plants may absorb toxicants either directly from the atmosphere, through the
leaves or from the soil, or water through the roots.

• The usual pathway is through the leaves, as with gaseous chemicals including
principally sulphur and nitrogen oxides, photochemical pollutants, fluoride,
chlorine, and ammonia.
• Other metals that are harmful to plants are arsenic, cadmium, lead, and
mercury.
• One of the first symptoms of injury to plant due to sodium arsenite is wilting.
• Chlorosis, leaf rolls, and stunting are the main and easily visible symptoms of
cadmium toxicity in plants.
• Soils contaminated with lead cause a sharp decrease in crop productivity,

thereby posing a serious problem for agriculture.
• Mercury affects both light and dark reactions of photosynthesis.
• Harmful gases such as nitrogen-containing air pollutants, ground-level ozone,

and sulphur dioxide can also affect vegetation.
Arsenic Nickel
Cadmium Plant
Drinking water Poisoning
Effects Pollutants
Human Sources
Lead Toxic action
Mercury Toxin
Metals





Schwartz, K. (1977). Clinic chemistry and chemical toxicology of metals. Elsevier.

Topic  Industrial
Toxicants
6 (PCBs, PBBs,
Dioxins, and
Fluoride)

1. Explain the industrial process.
2. Identify the properties, sources, contamination incident, and
effects of polychlorinated biphenyls (PCBs), polybrominated
biphenyls (PBBs), and dioxins.
3. Discuss the sources and effects of fluoride.
The Industrial Revolution of the 19th century saw the rapid growth of factories
especially in Western countries. The high demand for raw materials and growing
use of chemicals became a phenomenon in the industrial process.

120  TOPIC 6 INDUSTRIAL TOXICANTS (PCBs, PBBs, DIOXINS, AND FLUORIDE)
The Industrial Revolution started in the West and quickly spread to Europe, the
US, and Japan. Exploration for new resources became a significant activity for
modern countries. During World War I and World War II, exploration for new
countries and resources became one of the most significant objectives. Of course,
along with the Industrial Revolution comes industrial toxicants too.
Thus, this topic explores what are the industrial toxicants, their properties, sources,
contamination incident, and effects. Let us get started!
ACTIVITY 6.1
Find out when the Industrial Revolution started in Malaysia. Identify its
implications to the development rate of industry as well as usage of
chemical and raw materials. Discuss your findings in the myINSPIRE
forum.
6.1 INDUSTRIAL PROCESS

In our daily life, we go to the grocery store to shop for our daily needs. Have we
ever wondered how all these products are manufactured? How are they made,
from the point of origin up to when we buy them at our grocery store? These
products are produced through a specific industrial procedure in factories known
as the industrial process. What is industrial process?
Industrial process is defined as a systematic series of mechanical or chemical

operations that produce or manufacture something.
For example, we can see many factories set up in order to achieve the objective of
producing something through industrial processes. These processes can be
categorised into four types as explained in Table 6.1.

TOPIC 6 INDUSTRIAL TOXICANTS (PCBs, PBBs, DIOXINS, AND FLUORIDE)  121
Table 6.1: Four Types of Industrial Processes
Type Definition
Acheson An industrial process for making graphite by heating a mixture of

process coke and clay.
Bessemer An industrial process for making steel using a Bessemer converter to

process blast air through molten iron and thus, burn the excess carbon and
impurities; this is the first successful method of making steel in large
quantities at a low cost.
Cyanide process An industrial process for extracting gold and silver by treating ore
with a sodium cyanide solution.
Haber process Industrial process for producing ammonia from nitrogen and
hydrogen by combining them under high pressure in the presence of
an iron catalyst.
SELF-CHECK 6.1
1. What is the meaning of industrial process?
2. Name a few types of industrial processes and the end products.
6.2 POLYCHLORINATED BIPHENYLS (PCBs)

What is PCBs?
Polychlorinated biphenyls, in short PCBs, are a group of man-made

chemicals.
PCBs have been used in many different products, including electrical equipment,
surface coatings, inks, adhesives, flame-retardants, and paints. PCBs may be
released into the environment, for instance when waste that contains PCBs is
incinerated or stored in landfills.
Due to the possible impacts on human health and the environment, the use and
production of PCBs are now banned or severely restricted in many countries.

PCBs were manufactured and sold under a variety of trade names, including:
• Aroclor
• Pyranol
• Pyroclor (US)
• Phenochlor
• Pyralene (France)
• Clophen
• Elaol (Germany)
• Kanechlor
• Santotherm (Japan)
• Fenchlor
• Apirolio (Italy)
• Sovol (USSR)
6.2.1 Properties of PCBs

All PCBs are man-made and have a similar basic structure. They are made of
carbon, hydrogen, and chlorine atoms. Since these atoms can be combined in
many different ways, a total of 209 different PCBs molecules can be formed.
Take note, that some PCBs are more harmful than others. Each PCB molecule
contains two phenyl rings. Each phenyl ring consists of a ring of six carbon atoms
to which hydrogen atoms are attached. In PCBs, chlorine atoms replace some of
these hydrogen atoms.
Generally, PCBs are very stable which explains their persistence in the
environment. However, at high temperatures, PCBs can burn and generate
dangerous by-products such as dioxins.
PCBs tend not to evaporate or dissolve easily in water. However, they are
very soluble in fat and similar a substances, which explains why PCBs can build
up in animal fat and along the food chain.

6.2.2 Sources of PCBs Pollution

What are the sources of PCBs pollution? The sources of PCBs pollution are:
• Landfills containing transformers, capacitors, and other PCBs waste can

release PCBs into the air. This environmental contamination may continue to
occur due to the disposal of old electrical equipment containing PCBs.
• The incineration of municipal waste may lead to PCBs pollution and produce
dangerous by-products, such as hydrogen chloride (HCl) and dioxins
(polychlorinated dibenzo-dioxins and polychlorinated dibenzo-furans).
• PCBs can also evaporate from contaminated water bodies.
6.2.3 PCBs Contamination Incident

The dangers of PCBs were first recognised in 1968 in Yusho, Japan, when more
than 1,000 people were contaminated after using rice oil which was tainted with
PCBs from a leaking heat exchanger. Many of the victims suffered adverse effects,
which prompted the Japanese government to ban the production, import, and
export of PCBs in 1972.
The „Yusho case‰ and other PCB's incidents along with studies conducted by
many people prompted the EPA to ban the manufacture and processing of PCBs
after 2 July, 1979. Although the hazard exists, economic consideration prompted
the EPA to allow older industrial equipment containing PCBs to continue their
operation.
6.2.4 Effects of PCBs

PCBs can enter human cells and tissues when contaminated air is breathed in,
when contaminated food enters the digestive system, or through skin contact.
Tests on laboratory animals show that PCBs are readily absorbed through the
digestive tract when swallowed, and to a lesser extent absorbed through the skin.
The main PCBs elimination routes are through the faeces, urine, and in
mothers, PCBs have also been found to pass into the placenta, umbilical cord
blood, and even breast milk.
Once in the gastrointestinal tract, ingested PCBs diffuse across cell membranes and
enter into blood vessels and the lymphatic system. PCBs, especially those that
contain a greater number of chlorine atoms, are readily soluble in fats and thus,
tend to accumulate in fat-rich tissues such as the liver, brain, and skin.

PCBs can undergo different transformations in the body and then either be stored
in certain tissues or excreted. These two transformations are further explained in
Table 6.2.
Table 6.2: Two Transformations of PCBs in the Body
Transformation Definition
Transformations PCBs can easily be transformed into persistent metabolites that are
that lead not readily excreted and that can accumulate in specific tissues and
to accumulation body fluids. The biological half-life of these persistent metabolites
depends on the structure of the original PCBs.
Transformations PCBs can leave the blood and enter tissues very rapidly; and be
that lead to transformed into water-soluble substances. They can combine with
excretion glutathione and glucuronic acid, that are naturally present in the
body, forming a substance that is then excreted in urine and faeces.
The speed of this process depends on the number and position of

chlorine atoms of the original PCB. It is, for instance, slower when
there are more chlorine atoms on both phenyl rings and faster if there
are two carbon atoms without any attached chlorine atoms next to
each other.
In a case where both children and their mothers were exposed to

PCBs through their diet, the levels of PCBs in blood dropped more
rapidly among children. This may be partly explained by the
childrenÊs growth, as their increasing tissue mass may lower the
PCBs concentration in blood due to dilution, rather than elimination.
SELF-CHECK 6.2
1. State the sources of PCBs pollution.
2. What happens when PCBs enter the body?

6.3 POLYBROMINATED BIPHENYLS (PBBs)

What is PBBs?
Polybrominated biphenyls (PBBs), also called brominated biphenyls or

polybromobiphenyls, are a group of manufactured chemicals, of the
polyhalogenated compounds.
Polybrominated biphenyls (PBBs) are man-made chemicals that were used as fire
retardants in plastics in a variety of consumer products.
6.3.1 Properties of PBBs

PBBs are a class of biphenyl compounds with 1 to 10 hydrogen atoms replaced by
bromine. PBBs with three or more bromine atoms are solids with low volatility as
volatility decreases with increasing numbers of bromine atoms. PBBs are
extremely stable and therefore, persistent in the environment. PBB is a relatively
stable substance that is insoluble in water but highly soluble in fat.
6.3.2 Source of PBBs

What is the source of PBBs? PBBs are made from a chemical known as benzene
(sometimes referred to as „phenyl‰) which is derived from coal tar.
6.3.3 PBBs Contamination Incidents

Before the 1970s, PBBs were widely used commercially as a flame retardant.
Michigan Chemical Corporation (owned by Velsicol Chemical Corporation) in St.
Louis, Michigan was a major producer of the FireMaster range of PBBs-based
flame retardants.
In 1973 and 1974, several thousand pounds of FireMaster BP-6 were accidentally
mixed with livestock feed that was later distributed to farms in Michigan, in the
US. Michigan residents were exposed to meat, milk, butter, cheese, and eggs
contaminated with PBBs.

A general-population survey subsequently conducted in Michigan found that 90

per cent of the population had detectable levels of PBBs in their blood. Since PBBs
are biologically stable and eliminated slowly, significant body burdens could
persist throughout the lifetime of exposed individuals.
6.3.4 Effects of PBBs

It is not known whether PBBs can cause cancer in humans, but it is known that
they can cause liver cancer in rats and mice. Some Michigan residents exposed to
PBBs complained of nausea, abdominal pain, loss of appetite, joint pain, fatigue,
and weakness.
However, it could not clearly be established that PBBs were the cause of these
health problems. There is stronger evidence that PBBs may have caused skin
problems, such as acne, in some people who ate the contaminated food. Some
workers exposed to PBBs by breathing and skin contact for days to months also
developed acne.
Recent studies have suggested that PBBs and other related chemicals, such as PCBs
and polybrominated diphenyl ethers (PBDEs), may interact with the endocrine
system and disrupt its natural balance.
SELF-CHECK 6.3
1. What are the other names of PBBs?
2. State the source of PBBs.
3. What are the effects of PBBs to human beings?
6.4 DIOXINS
Let us get to know dioxins.
Dioxins refers to a group of chlorinated organic chemicals with similar

chemical structures.

Some dioxins have harmful properties, depending on the number and position
of chlorine atoms in their chemical structure. One of the most harmful dioxin is
known as tetrachlorodibenzo-p-dioxin or TCDD. Some PCBs, which have similar
properties, are considered „dioxin-like‰ too.
Unlike PCBs which were used in several industrial applications, dioxins have no
uses. They are formed unintentionally and predominantly released as by-products
of human activities such as incineration and fuel combustion. They are also formed
in minor quantities by natural processes such as forest fires and volcanoes.
Dioxins travel through the air and deposit on water or land. In water, dioxins
initially bind to small particles or plankton. On land, dioxins deposit on plants or
bind to the soil, most often without contaminating groundwater. Animals
accumulate dioxins in fat through their food and concentrations increase at each
step in the food chain.
6.4.1 Properties of Dioxins

The term „dioxins‰, commonly covering polychlorinated dibenzo-dioxins
(PCDDs) and polychlorinated dibenzo-furans (PCDFs), refers to a group of
chlorinated organic chemicals with similar chemical structures.
Chlorine atoms can be attached to eight different places on the molecule, numbered
from 1 to 8. Dioxins can have varying harmful health effects depending on the
number and position of the chlorine atoms. 2,3,7,8-TCDD or simply TCDD, a
molecule with four chlorine atoms, is one of the two most toxic dioxins. Only dioxins
having more chlorine atoms added to the 2,3,7,8-TCDD structure are also toxic, but
to a lesser extent. Other dioxins do not show this dioxin-type toxicity.
6.4.2 Sources of Dioxins

Dioxins are mainly by-products of industrial processes but can also result from
natural processes, such as volcanic eruptions and forest fires. Dioxins are
unwanted by-products of a wide range of manufacturing processes including
smelting, chlorine bleaching of paper pulp, and the manufacturing of some
herbicides and pesticides.
In terms of dioxins release into the environment, uncontrolled waste incinerators

(solid waste and hospital waste) are often the worst culprits, due to incomplete
burning. Fortunately, the latest technology is available that allows for controlled
waste incineration with low emissions.

Although formation of dioxins is local, environmental distribution is global.

Dioxins are found throughout the world in the environment. The highest levels of
these compounds are found in some soils, sediments and food, especially dairy
products, meat, fish, and shellfish. Meanwhile, very low levels are found in plants,
water, and air.
6.4.3 Dioxins Contamination Incidents

Some dioxins contamination events have been more significant, with broader
implications in many countries. Large amounts of dioxins were released in a
serious accident at a chemical factory in Seveso, Italy, in 1976. A cloud of toxic
chemicals, including 2,3,7,8-Tetrachlorodibenzo-p-dioxin or TCDD, was released
into the air and eventually contaminated an area of 15 square kilometres where
37,000 people lived.
Extensive studies in the affected population are ongoing to determine the long-
term human health effects from this incident. These investigations, however, are
facing a setback due the lack of appropriate exposure assessments. A slight
increase in certain cancers and effects on reproduction has been detected and are
being further investigated. The possible effects on children of exposed people are
currently being studied.
TCDD has also been extensively studied for health effects linked to its presence as
a contaminant in some batches of the herbicide „Agent Orange‰, which was used
as a defoliant during the Vietnam War. A link to certain types of cancers and also
to diabetes is still being investigated.
In 1999, high levels of dioxins were found in poultry and eggs from Belgium.
Subsequently, dioxin-contaminated animal-based food (poultry, eggs, pork), were
detected in several other countries. The cause was traced to animal feed
contaminated with illegally disposed PCB-based waste industrial oil.
In July 2007, the European Commission issued a health warning to its member
states after high levels of dioxins were detected in a food additive – guar gum –
used as thickener in small quantities in meat, dairy, dessert or delicatessen
products. The source was traced to guar gum from India that was contaminated
with pentachlorophenol (PCP), a pesticide no longer in use. PCP contains dioxins
as contamination.

In late 2008, Ireland recalled many tonnes of pork meat and pork products when
up to 200 times more dioxins than the safe limit were detected in samples of pork.
This finding led to one of the largest food recalls related to a chemical
contamination. Risk assessments performed by Ireland indicated no public health
concern. The contamination was traced back to contaminated feed.
6.4.4 Effects of Dioxins

Now, let us identify the effects of dioxins. Short-term exposure of humans to high
levels of dioxins may result in skin lesions, such as chloracne and patchy darkening
of the skin, and altered liver function. Long-term exposure is linked to impairment
of the immune system, the developing nervous system, the endocrine system, and
reproductive functions.
Chronic exposure of animals to dioxins has resulted in several types of cancer.

TCDD was evaluated by the WHOÊs International Agency for Research on Cancer
(IARC) in 1997. Based on animal data and human epidemiology data, TCDD was
classified by IARC as a „known human carcinogen„.
However, TCDD does not affect genetic material and there is a level of exposure
below which cancer risk would be negligible.
Due to the presence of dioxins, all people have background exposure and a certain
level of dioxins in their body, leading to the so-called "body burden." Current
normal background exposure is not expected to affect human health on average.
However, due to the high toxic potential of this class of compounds, efforts need
to be undertaken to reduce the current background exposure.
Whereas for an unborn child, the effects are through the placenta rather than
through breast feeding. These effects even occurred at background levels, but only
affected the infants with the highest exposure.
SELF-CHECK 6.4
1. Define dioxin and its properties.
2. What are the sources of dioxins?
3. State the effects of short-term exposure of humans to dioxins.

6.5 FLUORIDE
Lasty, let us learn about fluoride.
Fluorine is the lightest element in Group VII of the periodic table, with the
atomic number 9 and the atomic weight 18.998. It has a single isotope, and its
valence in all naturally occurring compounds is one.
Although fluoride is not listed as one of the „Criteria Air Pollutants‰ regulated by
US EPA, it is nevertheless a very important gaseous air pollutant. Indeed, fluoride
is the most phytotoxic air pollutant because it can damage plants at extremely low
concentrations.
Additionally, adverse effects are not limited to those affected by airborne fluoride.
High levels of waterborne fluoride are also hazardous to both human and animal
health. For example, in China and India, millions of people are suffering from
dental and skeletal fluorosis mainly due to the consumption of high levels of
fluoride in the drinking water.
What are the sources of fluoride? Fluoride is ubiquitous. It occurs naturally in the
atmosphere through volcanic eruption and in the earthÊs crust. It rarely occurs
freely in nature but combines with a variety of elements to form fluorides that exist
in minute amounts in air, water, minerals and soils, vegetation, and body tissues.
Fluoride emissions into the atmosphere are derived mainly from modern day
anthropogenic sources, particularly industrial sources. They include the steel
industry, phosphate fertiliser industry, aluminium industry, ceramics industry
(brick, tile, glass), non-ferrous metal foundries, welding operations, and coal-
burning power plants. Fluorides are emitted into the atmosphere from different
sources including both gaseous and particulate forms.
What are the effects of fluoride? Absorption of fluoride from the gastrointestinal
tract occurs through a passive process; it does not involve active transport.
Absorption is rapid and probably occurs in the lumen. Once taken up, about
50 per cent of the absorbed fluoride is excreted by the kidneys, while the remainder
is stored primarily in calcified tissues. Almost all of the remaining 50 per cent of
absorbed fluoride is fixed in bones. The effectiveness of low levels of fluoride
intake in reducing dental caries in humans, rats, and some other species of animals
has been well recognised.

Fluorides are released into the air in both a gaseous state (as hydrogen fluoride
and silicon tetrafluoride) and in solid particles. The particles fall on, and the gases
are absorbed by, vegetation near the polluting industry. If this vegetation includes
forage crops which are fed to cattle, sheep, horses or pigs, serious problems may
ensue, since these animals, particularly cattle, are vulnerable to fluoride.
Ninety six per cent of the ingested fluoride that accumulates in the bodies of
animals is incorporated into the crystal structure of bone and tooth mineral. When
fluoride is ingested with food or water, most of that which is not deposited in the
bones, teeth, and other calcified tissue is excreted in the urine within hours of
ingestion. Thus, it is not surprising that fluoride mainly affects the bones and teeth.
Airborne fluoride can damage either the foliage or the fruit of a wide range of
plants, and the amount of fluoride necessary for this depends on the species
involved. The most characteristic type of lesion is „tip burn‰, in which the tips and
edges of leaves turn brown in a characteristic pattern. The dead tissue may
separate from the rest of the leaf and fall off, decreasing the rate at which the whole
plant grows.
SELF-CHECK 6.5
1. Define fluoride and its properties.
2. What are the sources of fluoride?
3. State the effects of fluoride to humans.
ACTIVITY 6.2
Many toothpastes contain fluoride. Is fluoride safe in toothpastes?

Discuss the benefit(s) and risk(s) of the use of fluoride in toothpastes in
the myINSPIRE forum.

• The industrial process is defined as a systematic series of mechanical or

chemical operations that produces or manufactures something.
• Polychlorinated biphenyls (PCBs) belong to a broad family of man-made

organic chemicals (consisting of carbon, hydrogen, and chlorine atoms).
• Sources of PCBs pollution are landfills containing transformers, capacitors,

and other PCBs waste, incineration of municipal waste, and evaporation from
contaminated water bodies.
• PCBs alter the major systems in the body (immune, hormone, nervous, and
enzyme systems). Therefore, PCBs affect a wide variety of body organs and
functions.
• Polybrominated biphenyls (PBBs), also called brominated biphenyls or

polybromobiphenyls, are a group of manufactured chemicals, of the
polyhalogenated compounds.
• PBBs are made from a chemical known as benzene (sometimes referred to as

„phenyl‰) which is derived from coal tar.
• It is not known whether PBBs can cause cancer in humans, but it is known that
they can cause liver cancer in rats and mice.
• Dioxins are a group of chemically-related compounds that are persistent

environmental pollutants.
• Dioxins are mainly by-products of industrial processes but can also result from
natural processes, such as volcanic eruptions and forest fires.
• Dioxins are highly toxic and can cause reproductive and developmental
problems, damage to the immune system, interfere with hormones and also
cause cancer.
• Fluoride is found naturally in water, food, soil, and several minerals such as
fluorite and fluorapatite.
• Consumption of fluoride at levels beyond those used in fluoridated water for

a long period of time causes skeletal fluorosis.

Contamination incident Polychlorinated biphenyls (PCBs)

Dioxin Polybrominated biphenyls (PBBs)
Effects Properties
Fluoride Sources
Industrial process
GreenFacts. (2006). PCBs Polychlorinated biphenyls. https://bit.ly/3pZSN6z
Sons.

Topic  Target Organs
7
1. Identify toxicants and their exposure in the human body.
2. Describe the human body from a physiological perspective.
3. Explain toxicant and its disruptions to our physiological
system.
Gandhi once quoted, „It is health that is real wealth and not pieces of gold and
silver.‰ This is indeed true; having a lot of wealth is meaningless without good
health.
However, because the world has changed so much, we are facing many types of
toxicants, both natural and man-made, which disrupt our health. Even though the
medical field has evolved and many good medicines have been created, we still
succumb to many chronic diseases caused by exposure to toxicants which disrupt
our bodyÊs physiological functions. How do we recognise the toxicants that cause
us harm? Let us find out the answer in this topic.

TOPIC 7 TARGET ORGANS  135
7.1 TOXICANTS AND THEIR EXPOSURE IN

THE HUMAN BODY
The father of toxicology, Paracelsus, once said, „All substances are poisons, there
is none that is not a poison, and the right dose differentiates a poison and a
remedy.‰ Do you agree with his statement?
Looking at the world today, we can find a myriad of chemicals in our daily life.
The big questions are:
• How does chemical enter the body?
• How is it distributed in the body?
• How is it metabolised in the body?
• How is it excreted from the body?
To understand and answer these questions, we must first understand toxicology.

The basic understanding of toxicology should include four important stages. These
four important stages can make us understand the toxicant, exposure towards it,
and its effect. These four stages are explained in Table 7.1.
Table 7.1: Four Stages in Toxicology
Stage Aspect
Absorption of toxicant • Route of entry.

• Duration of exposure.
• Degree of exposure.
Distribution of toxicant • Local distribution.

• Systemic distribution.
Metabolism of toxicant • Metabolism of the toxicant in our body.

• Disruption of biochemical pathway.
Excretion of toxicant • How will the toxicant be excreted from our body?
SELF-CHECK 7.1
What are the four important stages in a toxicology study? Briefly

explain them.

136  TOPIC 7 TARGET ORGANS
ACTIVITY 7.1
Name one toxicant and its common effect to your health that you can
observe in your daily life. Share your answer for discussion in the
myINSPIRE forum.
7.2 OUR HUMAN BODY FROM THE

PHYSIOLOGICAL PERSPECTIVE
Have you ever wondered what makes up your body? Through the advances and
evolution of modern technology, we can discover the complexity of our body.
Basically, a cell is the basic unit in our body. We can see many types of cells in our
body such as smooth cells, squamous cells, and many more. A combination of
many cells to perform certain functions will form the organ. Hence, the skin, eyes,
and heart are examples of the organs in our body.
A system, on the other hand, is combination of a few organs to complete one

particular task in our body. For example, the integumentary system consists of skin
and the components of the skin that perform the integumentary tasks in our body.
We could summarise the human body organisation as depicted in Figure 7.1.
Figure 7.1: Organisation in the Human Body

How are we going to relate our body to the toxicants that are present in our
surrounding? Basically, as we have stressed earlier, we are exposed to many
chemicals nowadays. Just imagine the excessive amounts of preservatives and
flavouring substances in our food that we eat today which might become
hazardous to our body. The exposure also might come from our occupation
specifically or our work environment, generally. Now, let us discover our body
system briefly and the common effects of toxicants to it.
SELF-CHECK 7.2
1. What is the basic unit of our body?
2. What are the components that make up a human body?
7.3 TOXICANTS AND THEIR DISRUPTIONS TO

OUR PHYSIOLOGICAL FUNCTION
Toxicants can affect our:
• respiratory system
• integumentary system
• circulatory system
• liver
• kidneys
• reproductive system
The effects are further explained in the next subtopics.

7.3.1 Effects of Toxicants on the Respiratory System

We inhale and exhale air every day, but do we know what system is responsible
for it? What is the purpose of it?
The respiratory system is the system responsible for inhaling and exhaling of
air in our body.
We might ask ourselves the purpose of inhaling and exhaling in our body. This
can be explained through five basic functions of the respiratory system. They are
as follows:
• providing an extensive area for gas exchange between the air and the
circulating blood;
• moving air to and from the exchange surfaces of the lungs;
• protecting the respiratory surfaces from dehydration, temperature changes, or

other environmental variations, and defending the respiratory system and
other tissues from invasion by pathogens;
• producing sounds involved in speaking, singing, and non-verbal

communication; and
• providing olfactory sensations.
Basically, the components of the human respiratory system consist of two parts as
Table 7.2: Two Parts of Human Respiratory System
Part Component
Upper respiratory system Nose, nasal cavity, paranasal sinus, and pharynx.
Lower respiratory system Bronchioles, alveoli of the larynx (voice box), trachea
(windpipe), bronchi, and lungs.

Let us look at Figure 7.2 to get a better understanding.
Figure 7.2: The Anatomy of Respiratory System
Lungs and alveoli are part of the lower respiratory system. They are further
Table 7.3: Lungs and Alveoli
Organ Description
Lung • It is a paired organs located in the thoracic cavity; enclosed and protected
by the pleural membrane (two layers). These layers are:
− Parietal pleura (outer layer): Attached to the wall of the thoracic cavity.
− Visceral pleural (inner layer): Covering the lungs.
• The lungs are between the pleurae – the pleural cavity – which are filled
with lubricating fluid.
• Each lung is a blunt cone, with the tip, or apex, pointing superiorly.
• The lungs have distinct lobes separated by deep fissures.
• The right lung has three lobes and the lobes are separated by two fissures.
• The left lung has two lobes and the lobes are separated by one fissure.
• The lungs consist of a large number of alveoli.

Alveoli • Alveoli are tiny thin-walled sacs where gas exchange occurs.
• Each lung contains about 150 million alveoli, and their abundance gives
the lung an open, spongy appearance.
• An extensive network of capillaries is associated with each alveolus.
Many respiratory problems arise from its exposure toward a variety of chemicals
in our daily life. Among these problems include:
• irritation (due to ammonia, chlorine, hydrogen fluoride, sulphur dioxide)
• asbestosis (caused by asbestos)
• silicosis (due to silica, sand blasting activities)
• oedema (due to phosgene, tetrachloroethylene, nickel)
• occupational induced asthma (caused by particulate matters, dust)
• pneumonia
• emphysema
• bronchitis
• lung cancer (due to carcinogenic substances)
So how do we protect our respiratory system against these harmful toxicants?

Protection for the respiratory system against these toxicants can be taken by
wearing dental mask, dust mask, half-face mask, full-face mask, powered air
purifying respirator (PAPR), self-contained breathing apparatus (SCBA), and
airline mask.
SELF-CHECK 7.3
1. What are the basic components of the respiratory system and the
main functions of it?
2. What are the common effects of toxicant on the respiratory system?
3. What equipment can we use to protect ourselves from inhaling

toxicants?

7.3.2 Effects of Toxicants on the Integumentary

System
Now, let us move on to integumentary system. What is the integumentary system?
What organs are included in this integumentary system and how do they function?
Do we know what common problems will occur when it is exposed to toxicants
such as chemicals? Let us find the answers to all these questions.
The integumentary system is actually a large, highly complex, or structurally

integrated organ system.
It makes up 16 per cent of our total body weight and its 1.5 to 2m2 surface is
continuously abused, abraded, attacked by microorganisms, irradiated by
sunlight, and exposed to environmental chemicals.
Two major components of the integumentary system are:
• cutaneous membrane
• accessory structure
What are the general functions of the integumentary system? General functions of
the integumentary system are:
• protection
• excretion
• temperature regulation
• synthesis of vitamin D
• cutaneous sensation
Our skin is undeniably the primary defence to any exposure. It reacts against
injuries, biological microorganisms, chemicals, and many other occurrences and
substances. We can see many effects that commonly affect the skin due to exposure
to chemicals such as skin burn, irritation, and skin cancer.
So how do we protect our integumentary system? Protection for the integumentary

system includes wearing a glove, apron, and coverall on oneself.

7.3.3 Effects of Toxicants on the Circulatory System

„Oh dear, my hand is bleeding‰ – this may be a common statement at some point
of our lives when our hands get injured accidentally. The question is, do we know
what is the purpose of the blood? Which system in our body is responsible for it?
To answer these questions, the next step is to read the rest of this subtopic.
Blood is actually one of the main parts of the circulatory system. If there is a lack
of it, the circulatory system might not function well or not even work at all and can
be fatal. That is the reason why excessive bleeding could pose a serious risk to the
victim.
So, what is circulatory system?
The circulatory system is an organ system that passes nutrients (such as amino
acids, electrolytes, and lymph), gases, hormones, and blood cells to and from
cells in the body to help fight diseases, stabilise body temperature and pH,
and to maintain homeostasis.
There are three important components of the circulatory system which are:
• heart
• blood
• blood vessel
These three components are further explained in Table 7.4.
Table 7.4: Three Important Components in the Circulatory System
Organ Description
Heart Our heart is like a muscular pump that pushes blood to all parts of our body.
It provides the force that powers the cardiovascular system and is able to
pump approximately five to six litres (about 1.5 gallons) of blood per minute,
even when we are at rest.
The size of the heart is that of a personÊs clenched fist, and it weighs
280 to 340 grams. It is hollow and roughly conical in shape, the narrow end
pointing downward to the left, situated between the lungs. An illustration of
the heart can be seen in the following Figure 7.3.

Figure 7.3: The Diagram of the Heart
Source: https://bit.ly/3EwStjK
Blood Did you know that blood is actually a type of connective tissue in the form
of fluid? It is a part of extracellular fluid within the cardiovascular system.
The average adult has approximately five litres (about 10 pints) of blood.
Blood is made up of both liquid and solid components:
• the liquid portion is called plasma; and
• the solid portion consists of red blood cells, white blood cells, and
platelets.
Basically, the blood consists of 55 per cent plasma and 45 per cent blood cells
(which include erythrocytes, leukocytes, and thrombocytes). The basic
components of blood can be divided into the following:
• plasma ‒ the liquid portion;
• platelets ‒ the clot forming components;
• white blood cells ‒ the infection fighters; and
• red blood cells ‒ the oxygen transporters.
What is the function of the blood? The function of the blood is for
transportation, regulation, and protection.

Blood The blood vessels are part of the circulatory system that transport blood
vessel throughout the body. There are three major types of blood vessels:
• the arteries – carry the blood away from the heart;
• the capillaries – enable the actual exchange of water and chemicals
between the blood and tissue; and
• the veins – carry blood from the capillaries back to the heart.
What are the common effects of toxicants on the circulatory system? The common
effects of toxicants on the circulatory system include:
• methemoglobinemia
• anaemia
• aplastic anaemia
• drug induced autoimmune haemolytic anaemia
• drug induced nonautoimmune haemolytic anaemia
• haemolytic anaemia (lead poisoning)
• leukaemia (benzene)
• drug induced cardiovascular disease
• heart cancer
7.3.4 Effects of Toxicants on the Liver

The human bodyÊs detoxifying site is known as the liver. Sometimes, we might
ingest foreign substances such as weak poisons and drugs. Did you know that the
little warriors inside our body will try to detoxify it in order to prevent it from
harming our body? Yes, it truly is one of the little warriors that work hard to
detoxify all those harmful substances that enter our body.

So, in this subtopic, the structure of the liver and the effects of toxicants on it will
be explained through the following questions:
(a) What is Our Liver Structure Like?

Let us see the overview of our liver structure in Figure 7.4.
Figure 7.4: General Overview of the Liver
Source: https://bit.ly/3j2SQu4
The processes for liver metabolism are as follows:
• cytochrome P450 (CYP) mono oxidase (MOA)
• glucuronidation
• sulfation
• glutathione-S-transferase

(b) What are the Effects of Toxicants on Our Liver?

Damage to the liver which is caused by chemicals can be explained through
a few classifications which are:
• Zonal hepatocellular alteration without inflammatory reaction:

− necrosis
− steatosis
• Intrahepatic cholestasis:
− bilestasis; and
− dilatation of the canaliculi with subsequent loss of microvilli.
• Focal necrosis.
• Hepatic necrosis with inflammatory reaction.
• Unclassified.
• Hepatocarcinogen.
There are a few factors involved in liver injury as explained in Table 7.5.
Table 7.5: Factors Involved in Liver Injury
Factor Description
Biotransformation of • More active metabolite (such as chloroform
toxicant phosgene) lead to depletion of hepatic glutathione
and alkylation of macromolecules.
Alteration of hepatic • Haemorrhagic necrosis by dimethylnitrosamine.
blood flow • Coagulative necrosis by carbon tetrachloride.
Potentiation of • Ethanol increases damaging properties of
hepatotoxicity haloalkanes.
• Acetone and other form of ketones potentiate carbon
tetrachloride (CCl4) hepatotoxicity.
• n-hexane intermediate potentiates chloroform
toxicity.
• Diabetic state enhances hepatotoxicity of carbon
tetrachloride (CCl4), chloroform.

The liver injury usually comes through few mechanisms as shown in

Figure 7.5.
Figure 7.5: Few Mechanisms for Liver Injury
These mechanisms are further explained in Table 7.6.
Table 7.6: Mechanisms of Liver Injury
Mechanism Description
Accumulation of This is the accumulation of advance beneficiary notice of non-

lipids coverage (AbN) amount of fat predominantly in parenchymal
cells and decrease in plasma lipid and lipoprotein. This will
result in the:
• interference with synthesis of the protein moiety;
• coupling phase of triglycerides (TG) secretion;
• impaired released of very low-density lipoprotein
(VLDL);
• increase synthesis of TG;
• inhibition of beta oxidation of fatty acids; and
• increase mobilisation of fatty acids from adipose tissue.
Consists of CCl4 , ethionine, phosphorus, tetracycline.

Protein synthesis • Inhibit incorporation of amino acid into liver protein.

(lead to necrosis)
• Ethionine, carbon tetrachloride (CCl4), dimethylnitrosamine.
• Ethionine replaces methionine cause decrease adenosine
triphosphate (ATP) synthesis and inhibition of
(ribonucleic acid) RNA synthesis.
• Dimethylnitrosamine indicates loss of mRNA.
• CCl4 indicates ribosome.
• Galactosamine decreases synthesis of RNA.
Lipid Peroxidation cleavage of unsaturated fatty acids and release

peroxidation of carbonyl compound. CCl4 is a formation of free radicals and
it causes:
• alteration of ER;
• loss of G6P activity enzyme;
• loss of protein synthesis; and
• loss of capacity to form and excrete VLDL.
Calcium • Accumulation of Calcium (Ca2+) in the liver leads to cell

homeostasis death (influencing cell metabolism, motility, and
division).
• Activation of molecular oxygen (O2) (oxidative stress) at
plasma membrane, endoplasmic reticulum, mitochondria,
cytosol.
• Carbon tetrachloride (CCl4 ), bromobenzene, adriamycin.
Immunologic • Covalent binding with hepatic protein.

reaction
• Mainly by many drugs such as phenytoin, sulfonamides,
erythromycin.
Cholestasis • Decrease microvilli canaliculi.

• Golgi apparatus dilated and vacuolated.
• Example for cholestasis is manganese.
Cirrhosis Chronic morphological alteration of the liver (appear as

nodules).
Mechanisms involved are:

• Single cell necrosis + Deficiency in repair mechanism of
residual cells.
• Alteration of intrahepatic vasculature.

This injury is further enhanced by deficiency in protein,

vitamin B12, and folic acid. Examples for cirrhosis are CCl4,
aflatoxin, alcohol (ethanol). It can cause:
• chronic liver disease;
• damage of liver tissue, scarring of the liver (fibrosis –
nodular regeneration);
• progressive decrease in liver functions;
• excessive fluid in the abdomen (ascites);
• bleeding disorders (coagulopathy);
• increased pressure in the blood vessels (portal
hypertension); and
• brain function disorders (hepatic encephalopathy).
Let us look at Figure 7.6 which shows you an example of

healthy liver versus liver scarred by cirrhosis.
Figure 7.6: Healthy Liver versus Cirrhosis Liver

Carcinogenesis This involves initiation, promotion, and progression.

Pseudofetal configuration of liver cells; increase foetal
isozyme, alfa feto protein, and foetal antigen. Examples of
carcigonesis include:
• vaflatoxin B1
• dimethylnitrosamine
• dimethylbenzoanthracene
• dimethylaminoazobenzene
• organochlorine pesticide
• polychlorinated biphenyl
• CCl4
7.3.5 Effects of Toxicants on the Kidney

The kidney is one of the vital organs in the excretory system of our human body.
It is also involved in the thermoregulation for our body, carrying out the function
of the filtering system in order to ensure our blood is free from harmful substances,
ensuring good regulation of our urinary system, as well as, ensuring our body is
in a generally good state.
Those affected by kidney failure will have to depend on artificial machines which
replace the functions of their malfunctioned kidney; and this treatment can be very
costly. Thus, to prevent it from happening to us, it is wise to really understand
how our kidneyÊs function and the possible threat of toxicants to our kidneys.
Firstly, what is the structure of our kidney? Three primary components of our
kidney are:
• the tubular elements
• the glomerulus
• the vascular element

A general overview of the kidney and its other sections and parts can be seen in
Figure 7.7.
Figure 7.7: Human Kidney
(a) General overview of the kidney (b) Basic functional unit in our kidney
(tubular – tubule and glomerulus)
Source: http://bharathgramaarogya. Source: http://www.ratical.org/

net/urosymptoms.htm radiation/
vzajic/8thchapter.html
(c) Cut section of the kidney (vascular elements – renal arteries)
Source: http://kidneycares.com/forPatients.aspx

What are the functions of our kidney? The functions of our kidney are:
• excretion of waste
• acid-base homeostasis
• osmolality regulation
• blood pressure regulation
• hormone secretion
Now, what are the common effects of toxicants on our kidney? There are many
types of nephrotoxicants that can threaten our kidney. These include:
• heavy metals
• halogenated hydrocarbons
• petroleum hydrocarbons
• therapeutic agents
Common heavy metal such as mercury, cadmium, chromium, arsenic, gold, lead,
iron, antimony, uranium, and thallium could pose risk to our liver. The effects can
be broken down into the following categories:
• most-potent nephrotoxicants;
• low dose – glucosuria, polyuria;
• high dose – renal necrosis, anuria, death;
• similar damage by similar mechanisms; and
• histologically – necrotic proximal tubules, protein casts plug tubular lumen.
We will now take a look at how mercury affects the kidney. Mercury is recognised
in many forms such as Hg°, Hg+, Hg++, MeHg, and PhHg. The toxicity it causes
varies with the types. The kidney and the GI tract are targets of suicide using Hg
salts. This will cause proximal tubule damage and renal failure. One can see the
effects within 24 to 48 hours after receiving a large dose of 1 to 4g of mercury.
Chronic effects can also be seen in the proximal tubule, though the onset is longer.
Primary toxicity is neurological. Renal toxicity is most likely due to dealkylation
or dearylation back to the Hg salt.

The initial stage of the effects of this toxicant in the kidney starts with low renal
blood flow and glomerular filtration rate (GFR). Tubular dysfunction will then set
in, where there are sodium and glucose excretion and loss of secretory function.
In the ultrastructural alterations, there will be loss of proximal tubular. The brush
border enzymes decrease within 15 minutes; and within eight hours, the
membrane clumps in cytoplasm which will be followed by vacuolisation of plasma
membrane. This will ultimately lead to mitochondrial rupture (necrosis). The
progression to disease can be seen through the following:
• ATP production decreased – mercury binding to sulfhydrals in mitochondrial

enzymes;
• altered Ca2+ homeostasis – Hg effects blocked by Ca2+ uptake blocker;
• phospholipid derangements – lead to decreased membrane function resulting

in further free Ca – a cascading effect; and
• leads to necrotic injury of the tubule.
7.3.6 Effects of Toxicants on the Reproductive System

Certainly, the reproductive system is important to ensure of offspring production
in any living being. It ensures that our genes will be passed on to the next
generation and ensures the survival of the human population.

Let us take a look at the male reproductive system as in Figure 7.8.
Figure 7.8: Male Reproductive System
Source: http://healthfitnesscentre.blogspot.com/
The function the male reproductive system is for the production of spermatozoa
after puberty for fertilisation with the ovum from the female, coitus process, and
the production of androgens. The basic components of this system include:
• testis
• penis
• urethra
• prostate gland
• seminal vesicle
• vas deferens

The sperm production (as in Figure 7.9) in the testis originates from indifferent
gonads during the embryonic phase.
Figure 7.9: Sperm Production
It contains 200 to 300 lobules which are separated by septum. Each lobule has four
seminiferous tubules. Blood is supplied from the testicular artery and drains
through the pampiniform plexus into the testicular vein. The seminiferous
epithelium contains sertoli cells (sustentacular cells) and germ cells.
Meanwhile, the Leydig cells exist in between tubules and produce spermatozoa
and androgens. This is divided into two compartments:
• extratubular ‒ vascular and interstitial divisions (inclusive of lymphatic

channels and Leydig cells); and
• intratubular ‒ basal and adluminal divisions; this compartment is located in

the seminiferous tubules.

The effects of toxicants on the male reproductive system through lead, EDB, carbon
disulphide, and drug abuse are explained in Table 7.7.
Table 7.7: The Effects of Toxicants on the Male Reproductive System Through Lead, EDB,
Carbon Disulphide, and Drug Abuse
Toxicant Description
Lead The effect begins at 40 øg/dL of blood lead level. The occupational
exposure will decrease sperm count totals and increase abnormal
sperm frequencies. In long-term exposure, sperm concentrations,
total sperm counts, and total sperm motility may diminish. There
is also a decrease in the function of prostate and seminal vesicles
as well as in sexual drive and impotence. These effects could be the
result of direct testicular toxicity of lead but as the duration of
exposure increases, the hypothalamic-pituitary-testicular axis
could be disturbed. However, it is unclear how long these effects
may last in humans after lead exposure ceases.
EDB (Ethylene It is a colourless, water-soluble liquid, and used as pesticide and

Dibromideor 1, gasoline additive absorbed through the lungs, digestive tract, and
2-dibromoethane) skin. It is extensively metabolised to 2-bromoacetaldehyde (toxic)
and excretion occurs primarily in the urine. It will result in
testicular atrophy which is a medical condition in which testes was
diminished in size and loss of function were observed in rodents
exposed to 37 to 41mg/kg/day, five days a week for a period of
53 to 61 weeks. Study shows that those workers exposed to EDB
have more sperm with tapered heads and fewer sperm per
ejaculate.
Carbon disulphide It is a clear, colourless, or faintly yellow and liquid at room

temperature and used primarily as solvent in the viscose rayon
and cellophane. Study in rats show that male rats exposed to
approximately 610ppm (1,900mg/m³) of this toxicant for six hours
per day, five days per week for 10 weeks resulted in significant
reduction in sperm counts by the seventh week. However, caudal
epididymal sperm counts were not depressed and the testes
appeared histologically normal. Carbon disulphide does not exert
a direct effect on the testes, but may interfere with sperm transport
and ejaculation.
Drug abuse This affects the three stages of male sexual function which are
erection, ejaculation, and orgasm. Anti-depressants, testosterone
antagonists, and stimulants of prolactin reduce libido in men.
Anti-hypertensive drugs which act on the sympathetic nervous
system-induce impotence in some men. Cocaine, heroin, and high
doses of cannabinoids also reduce the libido, while opiates may
delay or impair ejaculation.

We will now move on to the female reproduction system which is shown in

Figure 7.10.
Figure 7.10: Female Reproductive System
Source: http://fau.pearlashes.com/anatomy/Chapter%2042/Chapter%2042.htm
The basic components of female reproductive system include the ovary, oviduct,
uterus, cervix, and vagina.
The ovary developed from gonadal cortex. During foetal development, oogonia
are formed by mitosis followed by meiosis with the production of millions of
oocytes. Atresia occurs due to hypoxia resulting in less number of oocytes. Women
are born with a fix number of oocytes. Its function is to produce ova as well as two
hormones; progesterone and oestrogen.

The oviduct floats in mesosalpinx. It consists of four segments (see Table 7.8).
Table 7.8: Four Segments of Oviduct
Segment Description
Fimbriae Situated at the periphery of oviduct, functions to assist in supporting

uterus.
Infundibulum A funnel-shaped structure near ovary, functions to catch ovulated

ovum.
Ampulla Distal oviduct and is enlarge, functions as site of fertilisation.
Isthmus Proximal oviduct and is narrow, functions to connect oviduct to

uterine cavity.
The uterus is a simplex form in human. There are three layers which are the serous
membrane (perimetrium), myometrium (thickest), and endometrium. Its function
is for embryo implantation and to support and house the foetus throughout
pregnancy.
The cervix is the sphincter muscle situated between the uterus and vagina. Most
cervixes have an annular ring structure. It contains goblet cells that secrete mucous
and consistency varies with menstrual cycle. Mucous consistency can be used to
detect fertility. It functions to stop the entry of bacteria into the uterine cavity. The
cervical canal usually closes and only opens during parturition. The cervix also
functions to form a cervical plug during pregnancy.
The vagina is divided into two parts which are the vestibule (external) and
posterior vagina (internal). The hymen is a thin connective tissue which forms a
transverse fold to partially close vaginal opening in virgins. It functions to accept
ejaculated semen from penis during coitus. It also has an acidic environment to kill
bacteria and foreign bodies.
The effects of toxicants on the female reproductive system include exposure to the
common reproductive toxicants such as heavy metal, polycyclic aromatic
hydrocarbon (PAH), halogenated polycyclic hydrocarbons, organic solvents, and
pharmacological agents. Four of these toxicants are further explained in Table 7.9.

Table 7.9: Toxicants and Their Effects on the Female Reproductive System
Segment Description
Polycyclic • Produced by cigarette smoke.

aromatic
• Causes ovarian toxicity and oocyte destruction.
hydrocarbon
(PAH) • Caused by reactive electrophilic metabolites generated by parent
hydrocarbon.
• Inducers of hepatic enzyme including microsomal
monooxygenases and transferase.
Halogenated • Includes DDT, PBBs, and PCBs.

polycyclic
• DDT will cause damage to uterus and affect fertility.
hydrocarbon
• Causes an estrogenic response in rats.
• Thickening of the endometrium and increase in uterus weight
competitive inhibition of the binding of estradiol to receptors sites
in uterus.
Organic • Carbon disulphide causes irregular menstrual flow.

solvents
• Benzene alters the ovarian function.
• Carbon tetrachloride alters the ovarian function.
Pharmacology • Adverse effect on the menstrual cycle.

agents
• Mediated through binding to steroid receptor and exertion of
estrogenic or anti-estrogenic effects.
• Stimulation of an increase in serum prolactin level.
• Direct toxic effect on the ovary.
• Examples are oral contraceptives and tricyclic anti-depressants.
• There are many chronic diseases caused by exposure toward toxicants and this
leads to the disruption of our bodyÊs physiological functions.
• There are four important stages in toxicology: absorption of toxicant,

distribution of toxicant, metabolism of toxicant, and excretion of toxicant.
• The organisation of the human body starts from the cellular level, followed by
the organ, system, and lastly the human body.

• Exposure to toxicants may lead to the disruption of the bodyÊs respiratory

system, integumentary system, circulatory system, liver, kidney, and
reproductive system.
• Many respiratory problems arise from its exposure toward a variety of

chemical in our daily life. Among these problems are irritation, asbestosis,
silicosis, and pneumonia.
• Our skin is part of the integumentary system and it is undeniably the primary
defence to any exposure. Exposure of chemicals to skin results in skin burn,
irritation, and skin cancer.
• The common effects of toxicants on the circulatory system include anaemia,

leukaemia, and heart cancer.
• Damage to the liver which is caused by chemicals can be explained through a

few classifications. Among them are intrahepatic cholestasis, focal necrosis,
and hepatocarcinogen.
• Common heavy metal could pose risk to our liver such as renal necrosis,
anuria, and death.
• Some of the effects of toxicants on the male reproductive system are testicular
atrophy (exposure to EDB), and decrease in the function of prostate and
seminal vesicles (exposure to lead).
• Some of the effects of toxicants on the female reproductive system are ovarian
toxicity and oocyte destruction (exposure to PAH), and direct toxic effect on
the ovary (exposure to pharmacology agents).

Absorption Liver
Cellular level Metabolism
Circulatory system Organ
Distribution Physiological system
Excretion Reproductive system
Exposure Respiratory system
Human body System
Integumentary system Toxicant
Kidney

Wiley-Interscience.
Department of Health and Human Services. (2011). Report on carcinogens (12th

ed.). Department of Health and Human Services.
Fishbein, L. (1978). Environmental sources of chemical mutagen. II. Synthetic

mutagen. In W. G. Flamm & M. A. Mehlman (Eds.), Mutagenesis,
5 (pp. 257–348). Hemisphere Publishing Corporation.
Sons.



Topic  Endocrine
Disruption and
8 Mutagenic
Pollutants

1. Describe the endocrine system and the characteristics of the
endocrine disruptors.
2. Explain hormonal function and mode of action.
3. Describe the relationship between hormones and cancers as
well as the importance of testing oestrogenicity.
4. Identify the types and effects of mutagens and mutations.
5. Discuss induction of mutations.
What is the endocrine system? Although we rarely think about them, the glands
of the endocrine system and the hormones they release influence almost every cell,
organ, and function of our bodies. The endocrine system is instrumental in
regulating mood, growth and development, tissue function, and metabolism, as
well as sexual function and reproductive processes.
In general, the endocrine system is in charge of body processes that happen slowly,
such as cell growth. Faster processes like breathing and body movement are
controlled by the nervous system.

164  TOPIC 8 ENDOCRINE DISRUPTION AND MUTAGENIC POLLUTANTS
However, even though the nervous system and endocrine system are separate
systems, they often work together to help the body function properly. In this last
topic, you will learn how endocrine disruption happened and what are mutagenic
pollutants. Let us wrap this lesson!
8.1 THE ENDOCRINE SYSTEM

The foundations of the endocrine system are hormones and glands. As the body's
chemical messengers, hormones transfer information and instructions from one set
of cells to another. Although many different hormones circulate throughout the
bloodstream, each one affects only the cells that are genetically programmed to
receive and respond to its message. Hormone levels can be influenced by certain
factors such as:
• stress
• infection
• changes in the balance of fluid and minerals in the blood
What is a gland?
A gland is a group of cells that produces and secretes, or gives off, chemicals.
A gland selects and removes materials from the blood, processes them, and
secretes the finished chemical product for use somewhere in the body. Certain
types of glands release their secretions in specific areas.
For instance, exocrine glands, such as the sweat and salivary glands, release
secretions in the skin or inside of the mouth. Endocrine glands, on the other hand,
release more than 20 major hormones directly into the bloodstream where they can
be transported to cells in other parts of the body.
The major glands that make up the human endocrine system are the hypothalamus,
pituitary, thyroid, parathyroids, adrenals, pineal body, and the reproductive glands,
which include the ovaries and testes (see Figure 8.1).

TOPIC 8 ENDOCRINE DISRUPTION AND MUTAGENIC POLLUTANTS  165
Figure 8.1: Major Glands and Non-endocrine Organs of the Endocrine System
The pancreas is also part of this hormone-secreting system, even though it is also
associated with the digestive system because it also produces and secretes digestive
enzymes.
Although the endocrine glands are the body's main hormone producers, some
non-endocrine organs – such as the brain, heart, lungs, kidneys, liver, thymus,
skin, and placenta – also produce and release hormones. Can you identify the
major glands and non-endocrine organs in Figure 8.1?
Once a hormone is secreted, it travels from the endocrine gland through the
bloodstream to target cells designed to receive its message. Along the way to the
target cells, special proteins bind to some of the hormones. The special proteins act
as carriers that control the amount of hormone that is available to interact with and
affect the target cells.
Also, the target cells have receptors that latch onto only specific hormones, and
each hormone has its own receptor, so that each hormone will communicate only
with specific target cells that possess receptors for that hormone. When the
hormone reaches its target cell, it locks onto the cell's specific receptors and these
hormone-receptor combinations transmit chemical instructions to the inner
workings of the cell.

When hormone levels reach a certain normal or necessary amount, further

secretion is controlled by important body mechanisms to maintain that level of
hormone in the blood. This regulation of hormone secretion may involve the
hormone itself or another substance in the blood related to the hormone.
For example, if the thyroid gland has secreted adequate amounts of thyroid
hormones into the blood, the pituitary gland senses the normal levels of thyroid
hormone in the bloodstream and adjusts its release of thyrotropin, the pituitary
hormone that stimulates the thyroid gland to produce thyroid hormones.
Another example is the parathyroid hormone, which increases the level of calcium
in the blood. When the blood calcium level rises, the parathyroid glands sense the
change and decrease their secretion of parathyroid hormone. This turnoff process
is called the negative feedback system.
8.2 ENDOCRINE DISRUPTORS

What are endocrine disruptors?
Endocrine disruptors are chemicals that may interfere with the bodyÊs
endocrine system and produce adverse developmental, reproductive,
neurological, and immune effects in both humans and wildlife.
What are the sources of endocrine disruption? A wide range of substances, both
natural and man-made, are thought to cause endocrine disruption, including:
• pharmaceuticals
• dioxins and dioxin-like compounds
• polychlorinated biphenyls (PCBs)
• DDT and other pesticides
• plasticisers, such as bisphenol A
Endocrine disruptors may be found in many every day products such as plastic
bottles, metal food cans, detergents, flame retardants, food, toys, cosmetics, and
pesticides.

A few researches and studies have been carried out to determine whether exposure
to endocrine disruptors may result in human health effects including lowered
fertility, an increased incidence of endometriosis, and some cancers. Research
shows that endocrine disruptors may pose the greatest risk during prenatal and
early post-natal development when organ and neural systems are forming.
Exogenous substances which cause adverse health effects in an intact organism or

its progeny subsequent to changes in endocrine function are called endocrine
disruptors (EDs) or endocrine disrupting chemicals (EDCs).
Over the recent years, a number of coincident observations have led scientists to
the conclusion that chemical substances in the environment may be interfering
with the endocrine systems of humans and various animals.
These so-called endocrine disruptors may be responsible for a range of

dysfunctions in the reproductive system of humans and a variety of animals in the
wild. The wildlife effects are well documented and some can be reproduced
experimentally. However, the chemical effects on humans are more difficult to
prove definitively; and some effects are controversial. Fortunately, there is
considerable interest in the area which is potentially of great importance.
It is widely accepted that chemicals that are capable of causing endocrine

disruption have been released into the environment. These chemicals may act as
oestrogen mimics, as anti-oestrogens, or as anti-androgens. The end result is a
change in the hormonal balance which may lead to a variety of physiological and
pathological effects. The debate, however, is whether the concentrations of these
chemicals is sufficient to cause all of these effects undoubtedly observed in animals
and the effects suspected as being related in humans.
8.2.1 Characteristics of an Endocrine Disruptor

The endocrine system is a complex communication system between chemical
signals and their targets responsible for regulating internal functions of the body.
Any substance that alters the function of this system is termed an endocrine
disruptor. Endocrine disruptors or commonly referred to as ‰endocrine disrupting
chemicals‰ (EDCs) and can alter the endocrine function by a variety of different
mechanisms by:
• mimicking the sex steroid hormones oestrogen and androgen by binding to

their natural receptors, either as agonists or antagonists;
• altering the synthesis and breakdown of natural hormones; and
• modifying the production and functioning of hormone receptors.

In general, compounds that mimic oestrogens are termed environmental

oestrogens whereas compounds that block hormone action are termed anti-
oestrogens or anti-androgens (male sex hormone). Environmental oestrogens have
been the focus of the majority of research on endocrine disruptors. This includes,
but is not limited to, chemicals that mimic the female sex hormone estradiol-17b.
Now, let us identify the chemical structures of EDCs. Interestingly, the chemical
structures between natural hormones and environmental hormones are most often
very different. It is not possible to determine whether a chemical is an endocrine
disruptor or not by merely looking at its chemical structure. This is because the
structures of endocrine disruptors are so varied and unpredictable; sometimes
they are synthesised unintentionally.
Examples include the pesticide DDT and polychlorinated biphenyls (PCBs), both
of which have oestrogenic activity, but were originally synthesised for a
completely unrelated purpose.
What are the sources of endocrine disruptors? Chemicals capable of acting as

endocrine disruptors are ubiquitous in our environment. They can be found in:
• the natural environment (air, water, soil);
• food products (soybeans, legumes, flax, yams, and clover);
• plants (phytoestrogens are chemicals naturally found in plants that can act as
endocrine disruptors and are present in fruits, veggies, beans, and grasses);
• household products (breakdown products of detergents and associated

surfactants, including nonylphenol and octylphenol);
• pesticides (endosulfan, atrazine, nitrofen, and tributyltin);
• plastics (bisphenol A, phthalates);
• pharmaceuticals (drug oestrogens – birth control pills, DES, cimetidine);
• industrial chemicals (polychlorinated biphenyls (PCBS), dioxins, and

benzo[a]pyrene);
• by-products of incineration, paper production, and fuel combustion; and
• metals (cadmium, lead, mercury).
Whether we realise it or not, we are exposed to these various endocrine disruptors

by eating and drinking them, breathing them, and using them whether at home or
at work.

SELF-CHECK 8.1
1. What are the foundations of the endocrine system?
2. What are factors that can influence the hormone levels?
3. Define endocrine disruptors and their sources.
ACTIVITY 8.1
Discuss your answers for the following questions in the myINSPIRE

forum:
(a) List down the most frequent EDCs exposed to you daily.
(b) State the reason why you are exposed to these EDCs based on your
routine activity and your environment.
(c) What is your plan of action to reduce your exposure to these EDCs?
8.3 REVIEW OF HORMONAL FUNCTION

As stated before, the endocrine system is a system of glands that produces
chemical messengers (hormones) and the receptors in tissues that respond to them.
Examples include the thyroid, pituitary and adrenal glands, plus the male and
female reproductive systems.
The endocrine system is composed of ductless glands that secrete hormones into
the blood stream to act at distant sites. Together with the nervous system, the
endocrine system is responsible for the integration of many different processes
which allow complicated organisms to function as a unit (maintaining
homeostasis).
Hormones can be proteins, polypeptides, amino acids, or steroids. The most

well-known hormones are the sex steroids oestrogen, produced in the ovaries, and
testosterone, produced in the testes. Oestrogen and testosterone are also produced
in the adrenal glands of both sexes.

Other hormones include thyroxin, produced in the thyroid, and insulin, produced
in the pancreas. The pituitary and hypothalamus in the brain release a variety of
hormones that affect other organs, including the sex glands.
From the blood, hormones interact with cells by binding to special proteins called
receptors. The binding is specific, like a key in a lock. When enough binding sites
are occupied, then a message is passed on to the target cell nucleus unmasking
genetic information which results in physiological reactions; these are ultimately
responsible for stimulating or regulating proper metabolism, development,
growth, reproduction, and behaviour of a particular person.
For example, in women, oestrogen works in this way to control the menstrual
cycle, and in men, testosterone controls sperm production. Hormones are released
into the blood in very small amounts. Their levels are controlled by the rate of
release, and the rate of degradation, usually by the liver or kidneys.
The timing of hormone release is often critical for normal human function. This is
especially true during foetal development. Precise hormone control is important,
as too much or too little at the wrong time can result in dysfunction of one or
several body systems.
SELF-CHECK 8.2
1. Name five hormones.
2. What are the functions of hormones?
ACTIVITY 8.2
From the blood, how do hormones send messages to the target cells?
Discuss this process with your coursemates in the myINSPIRE forum.

8.4 MODES OF ACTION

Here, we will discuss the modes of action associated with endocrine disruptors:
• interaction with lipids or amino acids;
• direct effect on genes; and
• endocrine disruptors (EDs) interference.
Let us continue with the lesson.
8.4.1 Interaction with Lipids or Amino Acids

Most EDs may interact with the effects of lipids (steroid) or amino acid derived
(thyroid) hormones, while a few interact with peptide/protein hormone synthesis
or signalling. However, the effects of EDs through steroid receptors on
peptide/protein hormones are common.
8.4.2 Direct Effect on Genes

Other less well explored mechanisms of action of EDs are direct effects on genes.
Oestrogens and EDs with estrogenic action were, for example, suggested as
causing deoxyribonucleic acid (DNA) damage, thereby promoting malignant
differentiation of affected cells. A troubling new aspect is their epigenetic impact;
the amount of methylation of genes occurring early in life may have profound
effects years later and may even be transgenerationally inherited.
8.4.3 EDs Interference

Most EDs interfere with reproduction. They act as either agonists or antagonists of
the steroidal sex hormones, oestrogens, or androgens. A number of EDs interfere
with the daily necessity of coping with internal or environmental stress and other
adverse events. Fortunately, very few EDs exert a life-threatening impact through
interference with hormone systems necessary to maintain basic life-sustaining
mechanisms.
Nevertheless, the effects of some EDs may be life-threatening because they may
interfere with the normal functions of organs or cause malignancies of these organs.
Let us look at Figure 8.2 which shows you the mechanism of action of endocrine
disruptors.

Figure 8.2: Mechanism of Action of Endocrine Disruptors
Source: www.hormones.gr/pdf/HORMONES%202010%209-15.pdf
8.5 HORMONES AND CANCERS

There are a number of effects on the human reproductive system that have been
observed and documented. Although some are contentious, some are clearly
established. There has been an undeniable increase in testicular cancer and breast
cancer since 1945, particularly in certain countries.
Most scientists do not believe that hormones cause or initiate cancer, but some
hormones may promote cancer growth. This promotion may result in cancer that
appears at a younger age than expected, or in a cancer that grows at a faster rate.
These findings suggest that chemicals that act like hormones may also promote
cancers.

In women, oestrogen is thought to play a role in the promotion of some forms of

breast cancer. Based on a single epidemiological study, the presence of DDE, a
metabolite of DDT, has been associated with increased risk of breast cancer.
However, more recent studies provide strong evidence that there is no relationship
between DDE exposure and breast cancer. Meanwhile, other studies suggest that
specific phytoestrogens and certain PCBs and dioxins can block oestrogen from
promoting some forms of breast cancer.
Among the speculated health effects from EDCs include:
• reproductive effects/birth defects
• cancer
• low sperm count/sexual dysfunction
• heart disease
• cognitive disorders
• sex reversal
• premature puberty
• altered immune function
SELF-CHECK 8.3
Is there any relationship between hormones and cancers? What is

your opinion?
ACTIVITY 8.3
Does our lifestyle today (eating habits, physical activities, stress, and
others) affect our hormones and thus lead to cancer? What is your
opinion? Discuss this matter in the myINSPIRE forum.

8.6 TESTING OESTROGENICITY

Although oestrogen is often considered a female hormone, oestrogen hormones
play important developmental and sexual function roles in both women and men.
However, ensuring proper oestrogen levels is also important for other reasons.
Altered levels in women can signal pregnancy or menopause or more serious
medical problems in men.
Oestrogen tests can be conducted at the doctor's office, but many kits are also
available for at-home testing. Oestrogen can be either:
• good oestrogen 2 (methoxyestrone) which is cancer protective; or
• bad oestrogen 16 (hydroxyestrone) which is cancer causing.
There are three different types of oestrogen as explained in Table 8.1.
Table 8.1: Three Different Types of Oestrogen
Type Description
Oestradiol E2 Predominant type of oestrogen in a menstruating woman.
Oestriol E3 Predominant type of oestrogen in a pregnant woman.
Oestrone E1 Predominant type of oestrogen in a post-menopausal woman.
Why do we need oestrogen tests? Oestrogen tests may be used for a variety of
reasons:
(a) Oestrone levels may be elevated in patients with polycystic ovarian

syndrome and endometriosis. Tests may be used to aid in the diagnosis of an
ovarian tumour, Turner syndrome, and hypopituitarism. In males, it may
help in the diagnosis of the cause of gynecomastia or in the detection of
oestrogen-producing tumours.
(b) Oestradiol levels are used in evaluating ovarian function. Oestradiol levels
are increased in cases of early (precocious) puberty in girls and gynecomastia
in men. Its main use has been in the differential diagnosis of amenorrhea, for
example, to determine whether the cause is menopause, pregnancy, or a
medical problem. In assisted reproductive technology (ART), serial
measurements are used to monitor follicle development in the ovary in the

days prior to in-vitro fertilisation. Oestradiol is also sometimes used to

monitor menopausal hormone replacement therapy. A doctor may
sometimes order a total oestrogen test. This test measures both oestrone and
oestradiol together but does not measure oestriol.
(c) Oestriol may sometimes be ordered serially to help monitor a high-risk

pregnancy. When it is used this way, each sample should be drawn at the
same time each day. An unconjugated oestriol test, one that measures
oestriol that is not bound to a protein, is one of the components of the triple
or quad screen. Decreased levels have been associated with various genetic
disorders including Down syndrome, neural tube defects, and adrenal
abnormalities. It is ordered during pregnancy, along with maternal alpha-
fetoprotein (AFP maternal), human chorionic gonadotropin (hCG), and
inhibin-A tests, to assess the risk of carrying a foetus with certain
abnormalities.
8.7 MUTAGEN
What is a mutagen?
A mutagen is a natural or man-made agent (physical or chemical) which can

alter the structure or sequence of DNA.
What are the characteristics of mutagens? The characteristics of mutagens are:
• Causing DNA damage that can be converted to mutations.
• Physical mutagens:
− High-energy ionising radiation.
− X-rays and γ-rays causing strand breaks and base/sugar destruction.
− Non-ionising radiation.
− UV light which is pyrimidine dimers.

• Chemical mutagens:
− Base analogues causing direct mutagenesis.
− Nitrous acid causing deaminates C to produce U.
− Alkylating agents and rylating agents causing indirect-lesion mutagenesis.
− Intercalators such as EB.
8.7.1 Types of Mutagens

There are four types of mutagens as explained in Table 8.2.
Table 8.2: Four Types of Mutagens
Type Effect
Ionising Nuclear radiation, X-rays, gamma rays (e.g. medical treatment)

radiation associated with the development of cancers (e.g. leukaemia, thyroid
cancer, and skin cancer).
Viruses and These integrate into human chromosome, upset genes, and can
microorganisms trigger cancer.
Environmental Organic solvents such as formaldehyde, tobacco, coal tars, benzene,

poisons asbestos, some dyes.
Alcohol and High alcohol intake increases the risk of some cancers. Diet high in
diet fat and containing burned or highly preserved meat.
8.7.2 Effects of Mutagens

Mutagens cause changes to the DNA that can affect the transcription and
replication of the DNA, which in severe cases can lead to cell death. The mutagen
produces mutations in the DNA, and deleterious mutation can result in abnormal,
impaired or loss of function for a particular gene, and this accumulation of
mutations may lead to cancer.
Different mutagens act on the DNA differently. Powerful mutagens may result in
chromosomal instability, causing chromosomal breakages, and rearrangement of
the chromosomes such as translocation, deletion, and inversion. Such mutagens
are called clastogens.

Mutagens may also modify the DNA sequence. The changes in nucleic acid
sequences by mutations include substitution of nucleotide base-pairs, and
insertions and deletions of one or more nucleotides in DNA sequences.
Although some of these mutations are lethal or can cause serious disease, many
have minor effects as they do not result in residue changes that have significant
effect on the structure and function of the proteins. Many mutations are silent
mutations, causing no visible effects at all, either because they occur in non-coding
or non-functional sequences, or they do not change the amino-acid sequence due
to the redundancy of codons. Some mutagens can cause aneuploidy and change
the number of chromosomes in the cell.
However, some propose that low levels of some mutagens may stimulate the DNA
repair processes and therefore may not necessarily be harmful.
SELF-CHECK 8.4
Define mutagen, its types and effects to humans.
8.8 MUTATION
Generally, a mutation is a process by which the heredity constitution of a cell is
altered, ultimately resulting in a genetically altered population of cells or
organism. Although mutations can occur in the RNA of viruses and the DNA of
cytoplasmic organelles, the mutations of greatest interest occur within genes in the
nucleus of the cell. So, what can you summarise to define mutation?
Mutation is permanent, heritable alterations in the base sequence of DNA.
The human body is estimated to contain more than 10 trillion cells, and at some
stage in its life cycle contains a full complement of the genes needed by the entire
organism.
Genes, composed of DNA in the nucleus of cells, are clustered together in

chromosomes. In the chromosomes of all but the most primitive organisms, DNA
is combined with protein.

DNA, the molecular basis of heredity in higher organisms, is made up of a double

helix held together by hydrogen bonds between purine and pyrimidine bases, e.g.
between adenine (A) and thymine (T), and between guanine (G) and cytosine (C)
(see Figure 8.3).
Figure 8.3: The Structures of the Five Bases in DNA and RNA
The highly specific complementarity of these bases enables DNA to act as a

template for its replication by DNA polymerases, as well as the synthesis of RNA
transcripts by RNA polymerases.
For the information contained in DNA to be biologically expressed, the sequence

of the nucleotides in a gene is converted into a sequence that determines the
enzymatic and structural properties of the protein thus formed.
DNA clearly plays a pivotal role in the expression and perpetuation of life.
However, it is also a critical target for the action of many mutagenic environmental
chemicals; lesions in DNA may occur through the action of physical or chemical
agents found in the environment. The occurrence of mutation, however, depends
on the nature of the initial lesion and the response of cells to the DNA damage.

Why does mutation happen? Mutation happens due to several reasons. Two of the
reasons are described in Table 8.3.
Table 8.3: Reasons for Mutation
Reason Description
DNA fails to copy Most of the mutations that people think matter to evolution are
accurately „naturally occurring‰. For example, when a cell divides, it makes
a copy of its DNA; sometimes the copy is not quite perfect. That
small difference from the original DNA sequence is a mutation.
External influences Mutations can also be caused by exposure to specific chemicals or

can create radiation. These agents cause the DNA to break down. This is not
mutations necessarily unnatural – even in the most isolated and pristine
environments, DNA breaks down.
Nevertheless, when the cell repairs the DNA, it might not do a

perfect job of the repair. So, the cell would end up with DNA
slightly different than the original DNA and hence, a mutation.
Take note that mutation rates vary across species. Evolutionary biologists have
theorised that higher mutation rates are beneficial in some situations, because they
allow organisms to evolve and therefore, adapt more quickly to their
environments.
For example, repeated exposure of bacteria to antibiotics, and selection of resistant

mutants, can result in the selection of bacteria that have a much higher mutation
rate than the original population (mutator strain).
8.8.1 Types of Mutation

There are many different ways that DNA can be changed, resulting in different
types of mutation. They are:
(a) Substitution
A substitution is a mutation that exchanges one base for another (e.g., a
change in a single „chemical letter‰ such as switching an A to a G, as in
Figure 8.4.

Figure 8.4: Change of Codon
Such a substitution could:

(i) Change a codon to one that encodes a different amino acid and causes
a small change in the protein produced. For example, sickle cell
anaemia is caused by a substitution in the beta-haemoglobin gene,
which alters a single amino acid in the protein produced.
(ii) Change a codon to one that encodes the same amino acid and causes
no change in the protein produced. These are called silent mutations.
(iii) Change an amino-acid coding codon to a single „stop‰ codon, resulting
in an incomplete protein. This can have serious effects since the
incomplete protein probably would not function.

Illustrations of codon changes can be further seen in Figure 8.5.
Figure 8.5: Illustration of Codon Changes
(b) Insertion
Insertion is „the addition of one or more bases in a DNA region‰. Insertions
are mutations in which extra base pairs are inserted into a new place in the
DNA (as in Figure 8.6).
Figure 8.6: Insertions of Extra Base Pairs

(c) Deletion
Deletion is „the loss of one or more bases in a DNA region‰. Deletions are
mutations in which a section of the DNA is either lost or deleted (as in
Figure 8.7).
Figure 8.7: Illustration of Deletion
(d) Frame Shift

Since protein-coding DNA is divided into codons three bases long, insertions
and deletions can alter a gene, so that its message is no longer correctly
analysed.
These changes are called frame shifts. For example, consider the sentence,
„The fat cat sat.‰ Each word represents a codon. If we delete the first letter
and analyse the sentence in the same way, it does not make sense.
In frame shifts, a similar error occurs at the DNA level, causing the codons
to be analysed incorrectly. This usually generates shortened proteins that are
as useless as „hef atc ats at‰ is uninformative (see Figure 8.8).
Figure 8.8: Illustration of Frame Shift

SELF-CHECK 8.5
1. Describe the causes of mutation.
2. Name four types of mutations that have been identified.
3. What is the difference between insertion and deletion mutations?
8.8.2 Effects of Mutations

The effects of mutations are:
• not all harmful;
• survival advantage;
• most common among bacteria and viruses but also seen in insects; and
• if there is no selective pressure, it may remain in the population.
Simply, we can say that the effects of mutation can be categorised as harmful,
beneficial, and neutral. These three are further explained as follows:
(a) Harmful Mutations

Harmful mutations can be seen as:
• cystic fibrosis and sickle cell anaemia
• dysfunctional proteins
• albinism (caused by mutation in the gene of enzyme pathway of melanin)

(b) Beneficial Mutations

Let us look at Table 8.4 which explains the types of beneficial mutations.
Table 8.4: Types of Beneficial Mutations
Mutation Type Description
Bacteria Antibiotic resistance through mutation, transfer between

bacterial species.
Superbugs Such as methicillin-resistant Staphylococcus aureus (MRSA).
RNA viruses Such as HIV – mutate its protein coat so that the host human
is unable to make antibodies quick enough against it.
(c) Neutral Mutations

Neutral mutations are:
• neither harmful or beneficial to the organism but may be important in

an evolutionary sense;
• silent mutations; and
• virtually impossible to detect because there is no observable effect.
ACTIVITY 8.4
(a) Where does a mutation must occur to be inherited? Why?
(b) Why are inherited mutations important from an evolutionary

perspective?
8.9 INDUCTION OF MUTATION

Lastly, let us look at induction of mutation. What does it mean?
An induction of mutation is a mutation that is produced by treatment with a

physical or chemical agent that affects the DNA molecules of a living
organism.

Mutations which are artificially induced with the help of mutagenic agents are
called induced mutations.
Remember that the previous notes had mentioned that some mutations arise as
natural errors in DNA replication (or as a result of unknown chemical reactions);
these are known as spontaneous mutations. The rates of such mutations have been
determined for many species. For instance, E. coli has a spontaneous mutation rate
of 1/108 (one error in every 108 nucleotides replicated). Humans have a higher
spontaneous mutation rate; between 1/106 and 1/105 (probably as a result of the
higher complexity of human replication).
Mutations can also be caused by agents in the environment; these are induced
mutations. Induced mutations increase the mutation rate over the spontaneous
rate. Looking at a single mutation in an individual, one cannot tell if the mutation
is spontaneous or induced. Induced mutations can only be discerned by looking at
the mutation rate in a population, and comparing it to the spontaneous mutation
rate for the species. If the observed mutation rate is higher, then induced mutations
can be assumed. Agents in the environment that cause an increase in the mutation
rate are called mutagens.
8.9.1 Causes of Inductions

What are the causes of inductions? Induced mutations on the molecular level can
be caused by chemicals or radiation. These two causes are further explained in
Table 8.5.
Table 8.5: Two Causes of Induced Mutations
Cause Description
Chemicals Consist of two major classes: base analogues (e.g. BrdU) and alkylating
agents (e.g. N-ethyl-nitrosourea). Alkylating agents can mutate both
replicating and non-replicating DNA.
In contrast, a base analogue can only mutate the DNA when the
analogue is incorporated in replicating the DNA. Each of these classes
of chemical mutagens has certain effects that then lead to transitions,
transversions, or deletions. Other effects are:
• DNA adducts (e.g. ochratoxin metabolites)
• DNA intercalating agents (e.g. ethidium bromide)
• DNA crosslinkers
• oxidative damage

Nitrous acid converts amine groups on A and C to diazo groups,

altering their hydrogen bonding patterns which leads to incorrect base
pairing during replication.
Radiation This is caused by ultraviolet radiation (non-ionising radiation). Two

nucleotide bases in DNA – cytosine and thymine – are most vulnerable
to radiation that can change their properties. UV light can induce
adjacent pyrimidine bases in a DNA strand to become covalently joined
as a pyrimidine dimer. UV radiation, particularly longer-wave UVA,
can also cause oxidative damage to DNA.
SELF-CHECK 8.6
1. Compare between spontaneous and induced mutations.
2. What are the causes of induced mutations?
• The endocrine system is a widespread group of glands and organs that acts as
the bodyÊs control system for producing, storing and secreting chemical
substances called hormones.
• The endocrine system helps support cells, organs, and functions of our bodies,
and is in control of our hormones.
• The endocrine system controls processes in the body such as cellular growth
and uses hormones and glands to send messages to different parts of the body.
• Endocrine disruptors are chemicals that may interfere with the bodyÊs
endocrine system and produce adverse developmental, reproductive,
neurological, and immune effects in both humans and wildlife.
• The factors that define the characteristics of an endocrine disruptor are the
chemical structures and the sources of endocrine disruptor.
• The endocrine system is a system of glands that produces chemical messengers

(hormones) and the receptors in tissues that respond to them.

• Hormones can be proteins, polypeptides, amino acids or steroids. The most

well-known hormones are the sex steroids oestrogen, produced in the ovaries,
and testosterone, produced in the testes.
• Oestrogen and testosterone are also produced in the adrenal glands of both
sexes. Other hormones include thyroxin, produced in the thyroid, and insulin,
produced in the pancreas. The pituitary and hypothalamus in the brain release
a variety of hormones that affect other organs, including the sex glands.
• Endocrine disrupting chemicals (EDCs) can alter the endocrine function by a

variety of different mechanisms.
• Most scientists do not believe that hormones cause or initiate cancer, but some
hormones may indeed promote cancer growth.
• Testing oestrogenicity is based on the type of oestrogen.
• A mutagen is a natural or man-made agent (physical or chemical) which can

alter the structure or sequence of the DNA.
• There are four types of mutagens, namely ionising radiation, viruses and
microorganisms, environmental poisons, and alcohol and diet.
• Mutagens cause changes to the DNA that can affect the transcription and
replication of the DNA, which in severe cases can lead to cell death.
• A mutation is a process by which the heredity constitution of a cell is altered,

ultimately resulting in a genetically altered population of cells or organism.
Although mutations can occur in the RNA of viruses and the DNA of
cytoplasmic organelles, the mutations of greatest interest occur within the
genes in the nucleus of the cell itself.
• Four types of mutations are substitution, insertion, deletion, and frame shift.
• The effects of mutation can be harmful, beneficial, and neutral.
• Mutations which are artificially induced with the help of mutagenic agents are
called induced mutations.
• Induced mutations on the molecular level can be caused by chemicals or

radiation.

Beneficial mutations Insertion

Cancer Lipids or amino acids
Codon Mutagen
Deletion Mutations
DNA Neutral mutations
Endocrine disrupting chemicals (EDCs) Non-endocrine organ
Endocrine disruptors Oestradiol
Endocrine system Oestriol
Frame shift Oestrogen
Gene Oestrone
Gland Protein-coding
Harmful mutations Substitution
Hormone Testosterone
Induced mutations

Wiley-Interscience.

Fishbein, L. (1978). Environmental sources of chemical mutagen. II. Synthetic

mutagen. In W. G. Flamm & M. A. Mehlman (Eds.), Mutagenesis,
5 (pp. 257–348). Hemisphere Publishing Corporation.
Sons.
Maton, A., Hopkins, J., McLaughlin, C. W., Johnson, S., Warner, M. Q., La Hart, D.,


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Developed by Centre for Instructional Design and Technology, OUM.

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Topic 1: Introduction to Environmental and Occupational Toxicology 1

1.1 Environmental Toxicology 2

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Topic 2: Environmental and Occupational Changes Towards Health 31

2.1 The Changing Environment and Disease Pattern 32

Topic 3: Occurrence of Toxicants 43

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3.5 Agriculture Damage 62

Topic 4: Damage Process and Action of Toxicants 73

4.1 Mechanism of Action 74

Topic 5: Toxic Action of Pollutants 85

5.1 Toxins and Pollutants 86

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Topic 6: Industrial Toxicants (PCBs, PBBs, Dioxins and Fluoride) 119

6.1 Industrial Process 120

Topic 7: Target Organs 134

7.1 Toxicants and Their Exposure in the Human Body 135

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Topic 8: Endocrine Disruption and Mutagenic Pollutants 163

8.1 The Endocrine System 164

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Copyright © Open University Malaysia (OUM)

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COURSE GUIDE DESCRIPTION

As an open and distance learner, you should be able to learn independently

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Figure 1: Student Learning Time

COURSE LEARNING OUTCOMES

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Table 1: Synopsis for Each Topic

1 Describes environmental toxicology, including its brief history, scope,

2 Explains the changing environment and disease pattern, epidemiological

3 Discusses the occurrence of toxicants, generated from open burning, as well as

4 Explores the effects of toxicants on living organisms.

6 Identifies industrial toxicants such as polychlorinated biphenyls (PCBs),

8 Discusses endocrine disruption and mutagenic pollutants. It explains the

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TEXT ARRANGEMENT GUIDE

(a) Learning Outcomes

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(e) Key Terms

Department of Health and Human Services. (2011). Report on carcinogens

Elschenbroich, C., & Salzer, A. (2006). Organometallics: A concise introduction

Fries, G. F. (1985). The PBB episode in Michigan: An overall appraisal. Critical

GreenFacts. (2006). PCBs Polychlorinated biphenyls. https://bit.ly/3pZSN6z

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LaDou, J. (2006). Current occupational and environmental medicine (4th ed.).

Ming, H. Y. (2000). Environmental toxicology: Biological and health effects of

Monosson, E. (Ed.). (2013). Absorption of toxicants. The Encyclopedia of Earth.

Monosson, E. (Ed.). (2013). Toxicity. The Encyclopedia of Earth.

National Center for Biotechnology Information. (2000). Relation between

United States Environmental Protection Agency (EPA). (2021). What is a pesticide?

Watterson, A. (2005). Toxicology in the working environment. In J. Rose (Ed.),

World Health Organization (WHO). (2011). Global status report on

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TAN SRI DR ABDULLAH SANUSI (TSDAS) DIGITAL