Xbet3103 PDF

Faculty of Science and Technology
XBET3103
Environmental and
Occupational Toxicology
Copyright © Open University Malaysia (OUM)

XBET3103
ENVIRONMENTAL
AND OCCUPATIONAL
TOXICOLOGY
Dr Ashima Srivastara
Dr Pratibha Singh
Harimah Hamdan

Project Directors: Prof Dato’ Dr Mansor Fadzil
Assoc Prof Dr Norlia T. Goolamally
Open University Malaysia
Module Writers: Dr Ashima Srivastara

Dr Pratibha Singh
Acme Learning Private Limited
Harimah Hamdan
Moderator: Suhaila Abdul Hamid

Developed by: Centre for Instructional Design and Technology

First Edition, December 2012

Second Edition, December 2015 (rs)
Copyright © Open University Malaysia (OUM), December 2015, 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, Open University Malaysia (OUM).

Table of Contents
Course Guide xi-xvii
Topic 1 Introduction to Environmental and Occupational Toxicology 1

1.1 Environmental Toxicology 2
1.2 A Brief History of Environmental Toxicology 4
1.3 Scope of Toxicology 4
1.4 An Interdisciplinary Science 6
1.5 Applications of Toxicology 7
1.5.1 Clinical Toxicology 7
1.5.2 Forensic Toxicology 8
1.5.3 Industrial Toxicology 9
1.5.4 Environmental Toxicology 9
1.5.5 Biochemical and Molecular Toxicology 9
1.5.6 Product Development Toxicology 10
1.5.7 Regulatory Toxicology 10
1.5.8 Reproductive Toxicology 10
1.5.9 Occupational Toxicology 11
1.6 Fundamentals of Toxicology and Environmental Toxicology 16
1.6.1 Dose-effect Relationship 16
1.6.2 Routes of Exposure 18
1.6.3 Effects of Toxins 19
1.6.4 Hazardous Substances 19
1.6.5 Classification of Toxic Agents 20
1.6.6 Physiological Classification of Toxic Materials 21
1.7 Health Hazards 23
1.7.1 Toxic and Highly Toxic Substances 24
Summary 25
Key Terms 26
Topic 2 Environmental and Occupational Changes towards Health 27

2.1 The Changing Environment and Disease Pattern 28
2.2 Epidemiological Transition 28
2.2.1 Human Activity 30
2.2.2 Climate Instability 30
2.2.3 Socioeconomic Inequities and Disparities 30
2.2.4 Higher Change of Incidence in Disease 30

iv  TABLE OF CONTENTS
2.3 Chemical Usage 31

2.3.1 Type of Toxicants 31
2.4 Pollutant Sources 32
2.4.1 Environmental Perspective 32
2.4.2 Occupational Perspective 34
2.4.3 Occupational Diseases 34
Summary 35
Key Terms 35
Topic 3 Occurrence of Toxicants 36

3.1 Toxicants 36
3.1.1 Concentration Range 37
3.2 Smog 38
3.2.1 Physical Description of Smog 39
3.2.2 Automobiles 40
3.2.3 Smog and Health 41
3.3 Smoke 42
3.3.1 Smoke from Fire 43
3.3.2 How Smoke Inhalation Damages the Body 45
3.3.3 Diagnosis of Smoke Inhalation Damage 46
3.3.4 Treatment 46
3.4 Offensive Odours 47
3.4.1 Sources of Environmental Odours 49
3.4.2 How Do You Measure Odour? 50
3.4.3 Odours and Health 51
3.4.4 Odour Control 52
3.4.5 Absorption 53
3.4.6 Liquid Scrubbing 53
3.4.7 Biofiltration 54
3.4.8 Bioscrubbers 54
3.4.9 Confirmation of Odour Removal Efficiency 54
3.5 Agriculture Damage 55
3.5.1 Use of Pesticides 55
3.5.2 Dust 56
3.5.3 Toxic Gases 59
3.6 Malaysian Environmental Quality Act 1974 60
3.6.1 Objectives of the Act 61
3.6.2 Implementation Strategies 61
Summary 62
Key Terms 62

TABLE OF CONTENTS  v
Topic 4 Damage Process and Action of Toxicants 63

4.1 Mechanism of Action 64
4.2 Factors Affecting Xenobiotic Action 65
4.2.1 Physiochemical Properties 66
4.2.2 Dose or Concentration 66
4.2.3 Time and Mode of Exposure 66
4.2.4 Environmental Factors 67
4.3 Metabolism of Environmental Chemicals 68
4.4 Defence Responses to Toxicants 69
Summary 71
Key Terms 72
Topic 5 Toxic Action of Pollutants 73

5.1 Toxins and Pollutants 74
5.2 Sources of Pollutants 75
5.3 Toxic Action of Major Pollutants 77
5.3.1 Metals 77
5.3.2 Toxic Chemicals in Air 86
5.3.3 Safe Drinking Water 87
5.3.4 Carcinogens (Cancer Causing Chemicals) 88
5.3.5 Cyanide 90
5.3.6 Methyl Isocyanate 91
5.4 Effects of Toxicants on Plants 92
5.4.1 Harmful Effects of Metals 93
5.4.2 Harmful Effects of Gases in Air 96
Summary 99
Key Terms 99
Topic 6 Industrial Toxicants (PCBs, PBBs, Dioxin and Fluoride) 100

6.1 Industrial Process 101
6.2 Polychlorinated Biphenyls (PCBs) 102
6.2.1 Properties of PCBs 102
6.2.2 Sources of PCB Pollution 103
6.2.3 Polychlorinated Biphenyls Contamination Incident 103
6.2.4 Effect of PCBs 103
6.3 Polybrominated Biphenyls (PBBs) 104
6.3.1 Properties of PBBs 105
6.3.2 Sources of PBBs 105
6.3.3 Polybrominated Biphenyls Contamination Incidents 105
6.3.4 Effects of PBBs 105

vi  TABLE OF CONTENTS
6.4 Dioxins 106

6.4.1 Properties of Dioxins 106
6.4.2 Sources of Dioxins 107
6.4.3 Dioxin Contamination Incidents 107
6.4.4 Effects of Dioxins 108
6.5 Fluoride 109
Summary 110
Key Terms 111
Topic 7 Target Organs 112

7.1 Toxicants and Their Exposure in the Human Body 112
7.2 Our Human Body in Physiological Perspective 113
7.3 Toxicants and Their Disruptions to Our Physiological
Function 115
7.3.1 Effects of Toxicants on the Respiratory System 115
7.3.2 Effects of Toxicants on the Integumentary System 118
7.3.3 Effects of Toxicants on the Circulatory System 119
7.3.4 Effects of Toxicants on the Liver 122
7.3.5 Effects of Toxicants on the Kidney 127
7.3.6 Effects of Toxicants on the Reproductive System 131
Summary 137
Key Terms 138
Topic 8 Endocrine Disruption and Mutagenic Pollutants 139

8.1 The Endocrine System 140
8.2 Endocrine Disruptors 142
8.3 Review of Hormonal Function 143
8.4 Characteristic of an Endocrine Disruptor 144
8.4.1 Chemical Structures of EDCs 145
8.4.2 Sources of Endocrine Disruptors 145
8.5 Mode of Action 146
8.5.1 Interaction with Lipids or Amino Acids 146
8.5.2 Direct Effect on Genes 146
8.5.3 EDs Interference 146
8.6 Hormones and Cancers 147
8.7 Testing Estrogenicity 148
8.8 Mutagen 149
8.9 Mutation 150
8.10 Types of Mutation 152

TABLE OF CONTENTS  vii
8.11 Effect of Mutagens 155

8.11.1 Mutagens and Their Effects 156
8.11.2 The Effect of Mutations 157
8.11.3 Harmful Mutations 157
8.11.4 Beneficial Mutations 157
8.11.5 Neutral Mutations 158
8.12 Induction of Mutation 158
8.12.1 Causes of Inductions 159
Summary 160
Key Terms 161
References 162

viii  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 material. 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 material as it will help you to clarify
important study components or points that you might miss or overlook.
INTRODUCTION
XBET3103 Environmental and Occupational Toxicology is one of the courses
offered by the Faculty of Science and Technology 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 designed for learners taking the Bachelor of Occupational Health
and Safety Management in OUM. This module aims to impart knowledge on the
principles of environmental and occupational toxicology.
As an open and distance learner, you should be acquainted with learning

independently and being able to optimise the learning modes and environment
available to you. Before you begin this course, please ensure that you have the
right course materials and understand the course requirements as well as how the
course is conducted.
STUDY SCHEDULE
It is OUMÊs standard practice that learners should accumulate 40 study hours for
every credit hour. As such, for a three credit hour course, you are expected to
spend 120 study hours. Table 1 gives an estimation of how the 120 study hours
could be accumulated.

xii  COURSE GUIDE
Table 1: Estimation of Time Accumulation of Study Hours
Study
Study Activities
Hours
Briefly go through the course content and participate in initial discussion 3
Study the module 60
Attend 3 to 5 tutorial sessions 10
Online participation 12
Revision 15
Assignment(s), Test(s) and Examination(s) 20
TOTAL STUDY HOURS ACCUMULATED 120
COURSE OUTCOMES
By the end of this course, you should be able to:
1. Explain environmental toxicology;

2. Explain ways in which toxicology is relevant to the industry;
3. Explain the fundamental principles of environmental and occupational
toxicology; and
4. Explain the health effects of toxic chemicals.
COURSE SYNOPSIS
This course is divided into eight topics. The synopsis for each topic listed is as
follows:
Topic 1 describes environmental toxicology, including a brief history, its scope,

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

transition, chemical usage and pollutant sources.
Topic 3 discusses the occurrence of toxicants, generated from open burning, as well
as industrial and agriculture activities.
Topic 4 explores the effects of toxicants on living organisms.

COURSE GUIDE  xiii
Topic 5 discusses the toxic action of pollutants. The toxic chemicals are discharged
into air, water and soil and get into human food chain via the environment.
Topic 6 discusses industrial toxicants such as Polychlorinated Biphenyls (PCBs),

Polybrominated Biphenyls (PBBs), Dioxins and Fluoride.
Topic 7 covers 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, kidney and reproductive system.
Topic 8 discusses endocrine disruption and mutagenic pollutants. It explains the

endocrine system, the function of the endocrine system, endocrine disruptors and
the mode of action associated with endocrine disruptors. It also covers mutation,
types of mutation and effects of mutagens.
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:
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.
Self-Check: This component of the module is inserted at strategic locations

throughout the module. It may be inserted after one sub-section or a few sub-
sections. It usually comes in the form of a question. When you come across this
component, try to reflect on what you have already learnt thus far. By attempting
to answer the questions, you should be able to gauge how well you have
understood the sub-section(s). Most of the time, the answers to the questions can
be found directly from the module itself.
Activity: Like Self-Check, the Activity component is also placed at various

locations or junctures throughout the module. This component may require you
to solve 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

xiv  COURSE GUIDE
yourself in higher order thinking where you might be required to analyse,

synthesise and evaluate instead of only having to recall and define.
Summary: You will find this component at the end of each topic. This component
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.
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.
References: The References section is where a list of relevant and useful

textbooks, journals, articles, electronic contents or sources can be found. The list
can appear in a few locations such as in the Course Guide (at 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 sources to obtain the additional
information needed and to enhance your overall understanding of the course.
PRIOR KNOWLEDGE
No prior knowledge is required.
ASSESSMENT METHOD
Please refer to myINSPIRE.
REFERENCES
American Chemical Council. (2012). Rapid changes of chemical usage in industry.
Retrieved from http://www.americanchemistry.com/
Clean Air Partnership. (2006). Air pollutants. Retrieved from

http://www.cleanairpartnership.org/air_pollutants
Cotton, F. A., & Wilkinson, G. (1988). Advanced inorganic chemistry (5th ed.).
New York, NY: Wiley-Interscience.

COURSE GUIDE  xv
Emily, M. (2008). Absorption of toxicants. In C. J. Cleveland, Encyclopedia of

Earth. Washington, DC: Environmental Information Coalition, National
Council for Science and the Environment. Retrieved from
http://www.eoearth.org/article/Absorption_of_toxicants.
Emily, M. (2010). Toxicity. In C. J. Cleveland, Encyclopedia of Earth. Washington,

DC: Environmental Information Coalition, National Council for Science and
the Environment. Retrieved from http://www.eoearth.org/article/
Toxicity.
Elschenbroich, C. & Salzer, A. (2006). Organometallics: A concise introduction

(2nd ed.). Weinheim, Germany: Wiley-VCH.
Fishbein, L. (1978). Environmental sources of chemical mutagen. II. Synthetic

Mutagen. In W. G. Flamm & M. A. Mehlman (Eds), Mutagenesis.
Washington, DC: Hemisphere, pp. 257-348.
Fishbein, L. (1979). Potential industrial carcinogen and mutagens. Washington,

DC: Elsevier.
Friend, M. (2005). Special education: Contemporary perspectives for school

professionals. Boston, MA: Pearson Education.
Gargiulo, R. (2003). Special education in contemporary society: An introduction

to exceptionality. Belmont, CA: Wadsworth/Thomson Learning.
Griffiths, A. J. F., Miller, J. H., Suzuki, D. T., Lewontin, R. C., & Gelbart, W. M.
(1999). An introduction to genetic analysis. New York, NY: W.H. Freeman.
Hallahan, D., & Kauffman (2003). Exceptional children: Introduction to special

education. Boston, MA: Allyn and Bacon.
Heward, W. (2003). Exceptional children: An introduction to special education.
Upper Saddle River, NJ: Merrill Prentice Hall.
Hodgson, E. (2010). A textbook of modern toxicology. Hoboken, NJ: John Wiley

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

New York, NY: McGraw Hill.
Luttrell, W. E., Jederberg, W. W., & Still, K. R. (2008). Toxicology principles for the
industrial hygienist. Fairfax, VA: American Industrial Hygiene Association.

xvi  COURSE GUIDE
Maton, A., Hopkins, J., McLaughlin, C. W., Johnson, S., Warner, M. Q., LaHart D.,
& Wright, J. D. (1993). Human biology and health. Englewood Cliffs, NJ:
Prentice Hall.
Michael, J. P. (1973). Fluoride in the air. Retrieved from

http://www.fluoridealert.org/environment-73.htm.
Ming, H. Y. (2000). Environmental toxicology: Biological and health effects of

pollutants. Boca Raton, FL: CRC Press.
National Center for Biotechnology Information. (2000). Relation between
mutagens and carcinogens. Retrieved from http://www.ncbi.nlm.nih.gov
Nims, D. K. (1999). Basic of industrial hygiene. Canada: John Wiley & Sons.
Chapter 2: Toxicology Review.
Ringer, R. K. (1989). Ecology and climate: Effects on domestic animals. New York,
NY: John Wiley & Sons.
Rose, R. L., & Hodgson, E. (2004). Chapter 7: Metabolism of toxicants. In E.

Hodgson, A textbook of modern toxicology (3rd ed.). Hoboken, NJ: John
Wiley & Sons.
Scott, D. D. (2008). Toxicology principles for the industrial hygienist. American

Industrial Hygiene Association. Chapter 20: Toxicology of Gases.
Shull, L. R., & Cheeke, P. R. (1983). Effects of synthetic and natural toxicants on
livestock. Animal Science Journal, 57 (2), 330-354.
Spencer, L. S. & Slabaugh, M. R. (2004). Chemistry for today: General, organic,

and biochemistry. Pacific Grove, CA: Thomson Brooks/Cole.
Susan, S. (2008). Chapter 4: Disposition of toxicants. In W. E. Lutrell, W. W.
Jederberg, & K. R. Still (Eds.), Toxicology principles for the industrial
hygienist. Fairfax, VA: American Industrial Hygiene Association.
Walter, F. B., & Emile, L. P. (2004). Medical physiology: A cellular and molecular
approach. Philadelphia, PA: Elsevier/Saunders.
World Health Organisation. (2012).

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 the
use of its learners. This comprehensive digital library, which is accessible through
the OUM portal, provides access to more than 30 online databases comprising e-
journals, e-theses, e-books and more. Examples of databases available are
EBSCOhost, ProQuest, SpringerLink, Books24x7, InfoSci Books, Emerald
Management Plus and Ebrary Electronic Books. As an OUM learner, you are
encouraged to make full use of the resources available through this library.

xxvi X COURSE ASSIGNMENT GUIDE

Topic  Introduction to
1 Environmental
and
Occupational
Toxicology
LEARNING OUTCOMES
By the end of this topic, you should be able to:
1. Describe environmental toxicology as an interdisciplinary science;
2. Describe the scope of toxicology;
3. Explain the fundamentals of toxicology and environmental
toxicology; and
4. Discuss the various classes of health hazards.
 INTRODUCTION
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

2  TOPIC 1 INTRODUCTION TO ENVIRONMENTAL AND OCCUPATIONAL
TOXICOLOGY
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, 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.
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 is quite different. It has evolved
rapidly, being driven by worries about the environmental devastation caused by
human activity.
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.

TOPIC 1 INTRODUCTION TO ENVIRONMENTAL AND OCCUPATIONAL  3
TOXICOLOGY
Environmental toxicology can be defined as:
Environmental toxicology is a newly-developed field which is concerned

with 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.
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). It understands natural and
anthropogenic pollutants, anthropogenic pollutantsÊ life cycles and their impact
upon the structure and functions of biological and ecological systems.
Figure 1.1: Components of the environment

Source: http://extoxnet.orst.edu/newsletters/ucd2010/etxlogo.JPG
SELF-CHECK 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:
1. List the factors leading to pollution in environment.

2. Why is it important to study those factors?

TOXICOLOGY
1.2 A BRIEF HISTORY OF ENVIRONMENTAL

TOXICOLOGY
In this subtopic, we will highlight a brief history of environmental toxicology.
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: French physiologist Claude Bernard introduced a more strategic

approach to toxicology by performing experiments on animals. The conclusion
and theories produced by Orfila and Bernard over a 100-year span highlight the
foundation of toxicology as a science.
In the 19th century came the Chemical Revolution, with a rapid expansion in the
extraction of natural chemicals and 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.
Environmental toxicology 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.
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 ecological systems.

TOXICOLOGY
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 postdoctoral fellowship training. Scientists with years of
experience enjoy fulfilling, exciting careers and advocate positive changes in
environmental protection.
Several divisions of toxicology are described in Figure 1.2.
Figure 1.2: Scope of environmental toxicology

TOXICOLOGY
1.4 AN INTERDISCIPLINARY SCIENCE

As a scientific discipline, environmental toxicology represents the interface
between chemistry and biology.
Figure 1.3: Interdisciplinary core of environmental toxicology
The interdisciplinary core of environment toxicology (as in Figure 1.3) borrows

heavily from a variety of disciplines shown below:
(a) Environmental science;
(b) Chemistry;
(c) Biology;
(d) Computer and mathematics; and
(e) 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.

TOXICOLOGY
ACTIVITY 1.1
Before we continue reading, discuss the following with your coursemates:

1. The scope of environmental toxicology.
2. The interdisciplinary nature of environmental toxicology.
1.5 APPLICATIONS OF TOXICOLOGY
Toxicology is the scientific discipline of poisonous substances.
There are many applications when it comes to toxicology. We will discuss this
further in this section.
1.5.1 Clinical Toxicology

Clinical toxicology deals with the toxic effects of agents (drugs) whose purpose is
to ameliorate or prevent a disease.
Clinical toxicology is further explained as below:
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. The study
of the chemical processes going on in the body is called Biochemistry.
Pharmacology deals with the actions of drugs in the body, while 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. The toxic effects of various
drugs are studied. Their main concern is the treatment and prevention of drug
toxicity in the population.

TOXICOLOGY
1.5.2 Forensic Toxicology

The legal outcome of the toxicological investigation is not the primary concern for
forensic toxicology.
Various kinds of samples can be analysed through 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.
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:
(a) Medical-legal aspects of poisonings;

(b) Identification and quantification of poisons; and
(c) Establishing relationship between tissue residual level and probable cause
of death.

TOXICOLOGY
1.5.3 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:
(a) Chemistry;
(b) Biology;
(c) Pharmacology;
(d) Physiology; and
(e) Pathology.
1.5.4 Environmental Toxicology
Environmental toxicology is a study of the effects of environmental

contaminants on organisms.
Motivations for such a topic are because of the human exposure to the environment
and the health of the ecosystem.
It is used to identify:
(a) Movement of chemicals in the environment ă soil, air, water; and

(b) Residual life of chemicals in the environment.
1.5.5 Biochemical and Molecular Toxicology

Biochemical and molecular toxicology is used for determining:
(a) Mode of action of chemicals at the molecular level; and

(b) Effect of chemicals on DNA, cancer genes.

TOXICOLOGY
1.5.6 Product Development Toxicology

Product development toxicology provides:
(a) Service and pre-clinical toxicology for product development;

(b) Evaluation of full toxic potential of chemicals destined for drug use; and
(c) Establishment of safe doses for people.
1.5.7 Regulatory Toxicology

Regulatory toxicology is related with the industry and government setting. It
provides:
(a) Solvent vapour thresholds in industry;

(b) Safe levels for human drugs;
(c) Safe levels of heavy metals in water;
(d) Safe levels of pesticides; and
(e) Deciphers and analyses toxicological data 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:
(a) The potential effects of environmental chemicals and toxins on human

offspring;
(b) Certain birth defects and disorders due to direct result of certain chemicals
used in many households; and
(c) Direct result of toxins.

TOXICOLOGY
ACTIVITY 1.2
In a group of three, discuss about the applications of toxicology.
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 associations 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.
(a) Objectives of Occupational Toxicology

The objectives of occupational toxicology are to:
(i) Identify chemical, physical or biological hazards in the work
environment;
(ii) Identify adverse health effects that arise out of workers' exposure to
these toxicants; and
(iii) Set up control measures to prevent or minimise exposure.
In many countries, workers are asked to work ă with little or no protection ă

with chemicals that are recognised to be dangerous to human health.
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 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

TOXICOLOGY
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 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
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 sophisticated toxicological and epidemiological techniques. Some
consideration is needed on how exposures outside the workplace may affect
workers within 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.
(b) 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, vapours and gases.
Much of the testing done on industrial and commercial chemicals relates to
ingestion through Lethal Dose (LD) and other tests rather than Lethal
Concentration tests (LC) 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 a substance a worker may be
exposed to by a combination of routes of entry. Much of this research is still
relatively speculative as indeed have been studies in the past which can

TOXICOLOGY
accurately assess exposures from multiple routes of entry or even the

effectiveness of Personal Protective Equipment (PPE) especially gloves in
reducing contamination in 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 in the workplace whereas the chronic
effects may not.
(c) 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 USA
Environmental Protection Agency (EPA) and the ÂQstarÊ (Q*) system as too
speculative and reliant on statistical methods with flawed inputs. 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 ă along the lines of the
EPA ă are the ones which offer the greatest protection to workers.
Indeed Kraus and her colleagues, in a large study of the US and

Scandinavian toxicologists found that Âcontroversies over chemical risks
may be fuelled as much by limitations of risk assessment and disagreements
among experts as by public misconceptionsÊ. Toxicology risk assessments
may rely on combining both mechanistic and quantitative methods. The
convention for setting ÂthresholdsÊ in many countries related to ÂsafeÊ
standards set for most of the working population for the most of the time
over an eight hour working day and a 40 hour working week. Some

TOXICOLOGY
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:
(i) No Observable Effect Levels (NOELs)

This is the highest exposure level at which no morphological,
physiological or functional modification of any kind is detectable under
the test conditions.
(ii) No Observable Adverse Effect Levels (NOAELs)

This is the highest dose level at which no biological adverse effects
occur.
(iii) Lowest Observable Adverse Effect Level (LOAELs)

This operates to set exposure levels when data are lacking to set the
NOAEL.
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.
Following are the objectives of the regulations:
(a) 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;
(b) To protect persons at a place of work other than persons at work against
risks to safety or health arising out of the activities of persons at work;
(c) To promote an occupational environment for persons at work which is

adapted to their physiological and psychological needs; and
(d) 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.

TOXICOLOGY
Figure 1.4: Working around chemicals without

proper protection can lead to serious accidents
Source: http://actrav.itcilo.org/actrav-english/telearn/osh/kemi/7-6.jpg
Exposure to harmful chemicals can result in higher rates of accidents at work (see
Figure 1.4). 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 „blame the victim‰ trend 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.
ACTIVITY 1.3
List down some industrial accidents due to chemicals you have heard or
seen happened. What were the after effects on the workers? Discuss with
your coursemates.

TOXICOLOGY
SELF-CHECK 1.2
1. What is environmental toxicology?

2. Discuss the brief history of toxicology and environmental toxicology.
3. Discuss the scope of toxicology in detail.
4. What do you understand by occupational toxicology?
1.6 FUNDAMENTALS OF TOXICOLOGY AND

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

Toxicologists normally look at two types of dose-response relationships (see
Figure 1.5).
Figure 1.5: Dose-effect relationship

Source:
http://www.stewardshipcommunity.com/uploads/pics/hhnoaelgraph558.342.png

TOXICOLOGY
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-
effect Level (NOEL) except for those that bring about their outcomes through
mutation, most notably 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 differences among species in the consumption,

metabolic process and disposal of chemicals is also important. There is a
substantial similarity 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 1.4
Give some instances of laboratory examples of dose-effect relationship.

Compare your answers with your coursemates.

TOXICOLOGY
1.6.2 Routes of Exposure

There are three routes by which the toxic chemicals can enter the body
(see Figure 1.6):
Figure 1.6: Routes of toxic exposure

Source: http://www.stewardshipcommunity.com/uploads/pics/hhroutes280.426.jpg
(a) Inhalation
Inhalation or breathing of chemicals is one of the most common routes of
entry for a chemical to enter the body.
(b) Ingestion
Ingestion means absorbing chemicals by the way of mouth while eating or
drinking.
(c) Absorption
Chemicals can enter the body through the skin, hair follicles, sebaceous
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.

TOXICOLOGY
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.
(a) Acute Effects

The effects may be acute; subsequent to a short exposure a quick effect may
be experienced.
(b) Chronic Effects

Chronic effects generally call for repeated exposure and a delay is observed
between the first exposure and visual aspect of harmful health effects.
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

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:
(a) Explosive substances release pressure, gas and heat suddenly when they are
subjected to shock, heat or high pressure. Some celebrations use many types
of explosive substances that require careful storage and handling to avoid
injury.

TOXICOLOGY
(b) Flammable and combustible substances are easy to ignite. Paint thinners,
charcoal lighter fluid and silver polish are all highly flammable. Oxidisers,
which will lend oxygen readily to support a fire, and reactive materials,
which are unstable and may react violently if mishandled, pose related
hazards.
(c) Poisons (or toxic materials) can cause injury or death when they enter the
bodies of living things. Such substances can be classified by chemical nature
(for example, 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.
(d) Radioactive materials are a category of hazardous materials that release

harmful radiation. They are not addressed specifically in this course.
These categories are not mutually exclusive. For example, acids and bases are
listed as corrosive materials, but can also act as poisons.
SELF-CHECK 1.3
List down the various routes of exposures of toxicants in the body.
1.6.5 Classification of Toxic Agents

Toxic substances are classified into the following:
(a) 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 ă first, by increasing
the presence of heavy metals in air, water, soil and food; and second, by
changing the structure of the chemical. For example, chromium III can be
converted to or from chromium VI, the more toxic form of the metal.

TOXICOLOGY
(b) Solvents and Vapours

Almost everyone is exposed to solvents. Occupational exposures can range
from the use of „white-out‰ by administrative personnel, to the use of
chemicals by technicians. When a solvent evaporates, the vapours may also
pose a threat to the exposed population.
(c) 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.
(d) Dioxin/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.
(e) Pesticides
The EPA 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.
(f) Plant Toxins

Different portions of a plant may contain different concentrations of
chemicals. Some chemicals made by plants can be lethal. For example, toxin
used in chemotherapy to kill cancer cells is produced by a species of the
yew plant.
(g) 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 in part or in their whole, are toxic.
1.6.6 Physiological Classification of Toxic Materials

This classification identifies toxic materials based on their biological action.
(a) Irritants
It refers to some sort of aggravation of whatever tissue the material comes
in contact with. e.g., ammonia, nitrogen dioxide.

TOXICOLOGY
(b) Asphyxiants
They exert their effects through a depletion of oxygen to the tissues.
Examples of simple asphyxiants: carbon dioxide, nitrogen, methane,
hydrogen and examples of chemical asphyxiants: carbon monoxide,
hydrogen cyanide, and hydrogen sulphide.
(c) Narcotics or Anaesthetics

The main toxic action is that it has a depressant effect upon the central
nervous system. Examples: many organic solvents such as chloroform and
xylene.
(d) Systemic Poisons

The main toxic action includes the production of internal damage. Examples
of hepatotoxic agents (toxic effects that cause liver damage, such as carbon
tetrachloride), nephrotoxic agents (toxic effects that cause kidney damage,
such as some halogenated hydrocarbons).
(e) Carcinogens
These are agents/compounds that will induce cancer in humans. Examples
are, benzene, arsenic, inorganic salts of chromium, nickel, beryllium.
(f) Mutagens
They are agents that affect the cells of the exposed person in such a way that
it may cause cancer or an undesirable mutation to occur in some later
generation. Radiation and selected chemical agents can be mutagens.
(g) Teratogens
Teratogens are agents or compounds that generate defects in the foetus
when taken by a pregnant woman. An example of teratogen is thalidomide.
(h) Sensitisers
These agents that may cause allergic or allergic-like responses to occur.
After an initial exposure to a substance, an individual may become
sensitised to that substance. Frequent exposure to the same substance, at a
much lower concentration than before, can generate an allergic response.
This response can be a skin rash (dermatitis) or an asthmatic-like attack,
depending on the route of exposure. E.g. cutting oils, isocyanates in
polyurethane foam operations and paint spraying operations, as well as
some laboratory solvents.

TOXICOLOGY
1.7 HEALTH HAZARDS

Examples of health hazards can be seen in Figure 1.7.
Figure 1.7: Health hazards
The following are health hazard classes as defined by the Occupational Safety
and Health Administration (OSHA), USA:
(a) Carcinogens;
(b) Corrosives;
(c) Irritants;
(d) Mutagen;
(e) Sensitiser;
(f) Teratogen; and
(g) Target organ effects:
(i) Cutaneous hazards ă damages the skin.
(ii) Eye hazards ă damages the eye.
(iii) Hematopoietic toxins ă damages the blood and/or blood forming
organs.
(iv) Hepatotoxic ă damages the liver.

TOXICOLOGY
(v) Nephrotoxic ă damages the kidneys.

(vi) Neurotoxins ă damages the nervous system.
(vii) Pulmonary toxins ă damages the lungs.
(viii) Reproductive toxins ă affects the foetus.
1.7.1 Toxic and Highly Toxic Substances

According to 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.
(a) Very Toxic

(i) 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
(ii) 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 0.5mg/litre (administered for a minimum period of
four hours).
(b) Toxic
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
(iii) Substances and preparations which are defined as carcinogenic,

teratogenic or mutagenic.

TOXICOLOGY
(c) Harmful
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).
(d) Corrosive
Substances and preparations which may, on contact with living tissues,
destroy them.
(e) Irritant
Non-corrosive substances and preparations which, through immediate,
prolonged or repeated contact with the skin or mucous membrane, can cause
inflammation.
ACTIVITY 1.5
In a group, list down some 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 our 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.
 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.

TOXICOLOGY
 Environmental toxicology is devoted to the general chemistry, environmental

behaviour and fate, toxicology, and ecotoxicology of xenobiotics and natural
toxins.
 The hazards of chemicals vary widely and appropriate caution must always
be used. Every chemical can be hazardous in certain circumstances.
Acute effect Toxic symptoms

Chronic effect Toxicant
Environmental toxicology Toxicity
Scope of toxicology Toxin

Topic  Environmental
2 and
Occupational
Changes
towards
Health
LEARNING OUTCOMES
1. Relate the changing pattern of environmental and occupational
changes towards health;
2. Explain epidemiological transitions;
3. Describe the use of chemicals; and
4. Identify the source of pollutants.
 INTRODUCTION
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,

28  TOPIC 2 ENVIRONMENTAL AND OCCUPATIONAL CHANGES TOWARDS
HEALTH
extensive usage of various types of chemicals, as well as dumping of industrial

wastes which are directly affecting the ecosystem and our current living status.
2.1 THE CHANGING ENVIRONMENT AND

DISEASE PATTERN
The 20th century witnessed profound, unprecedented changes in the natural,
built 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 were inevitable. This is
supported by many well-known international bodies or organisations. This can
be seen as below:
(a) „The sustainability of many vital ecosystems has been strained on many
fronts, with varying health impacts ă 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 ă
at the personal, community and population level ă rely on the continued
stability of life-supporting ecosystems‰ (WHO, 2012).
(b) 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 nowadays, we can see the pros and
cons. This significantly affects the environment and occupation thus affecting
human 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.

TOPIC 2 ENVIRONMENTAL AND OCCUPATIONAL CHANGES TOWARDS  29
HEALTH
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). Usage of chemicals can cause catastrophic events
and disasters through mismanagement (e.g., Bhopal Disaster, Piper Alpha
Incident, Sungai Buloh Firecrackers factory). Look at Figure 2.1.
Figure 2.1: Epidemiologic transition

Source: http://www.pitt.edu/~super 1/lecture/lec33241/005.htm
ACTIVITY 2.1
Take a look at our drinking and eating habits today. In a small group,
discuss how the modern environment affects our lifestyle and creates new
disease patterns.
Now let us discuss the epidemiological transition of the modern era.

HEALTH
2.2.1 Human Activity

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

Climate instability talks about the greenhouse effect, extreme heat phenomena
and the effect on the ozone layer.
2.2.3 Socioeconomic Inequities and Disparities

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

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.
ACTIVITY 2.2
1. Check your family background. Is there a history of communicable

diseases among your ancestors?
2. Do you have relatives who suffer from NCD? Observe their lifestyle
and eating habit. What is your opinion?

HEALTH
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.
A source from American Chemistry Council says:
„Every year, the American Chemistry Council tabulates the U.S. production
volume of the top 100 basic chemicals. In 2000, the aggregate production
volume of the top 100 chemicals totaled 502 million tons, up from 397 million
tons in 1990.‰
Rapid industrialisation with increasing usage of chemical causes adverse effects

to humans and the environment. Examples of catastrophic accidents involving
chemicals include:
(a) Minamata Disaster in Japan ;
(b) Love Canal Tragedy in New York;
(c) Bhopal Gas Tragedy in India; and
(d) Seveso Disaster in Italy.
2.3.1 Type of Toxicants

The following are types of toxicants:
(a) Pesticides
There is an increase of pesticide usage in the agricultural industry.
This raises concerns on residual pesticides and its impact on human health.
(b) 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. E.g., the accumulation of:
(i) Lead ă Osteomalacia;
(ii) Cadmium ă Kidney problem; and
(iii) Arsenic ă Dermatological problem.

HEALTH
(c) Persistent Organic Chemicals (POCs)

POCs are a type of toxic chemical compounds that can go through the process
of bioaccumulation and they are persistent in the tissues of organisms,
including humans. POCs are regulated under the Stockholm Convention
worldwide. Some toxic POCs commonly found in the environment include:
(i) PAHs (Polycyclic Aromatic Hydrocarbons);
(ii) Dioxin;
(iii) Lindane;
(iv) PCBs (Polychlorinated Biphenyls);
(v) Benzene;
(vi) DDT (Dichlorodiphenyltrichloroethane);
(vii) Phenols; and
(viii) Xylene.
(d) Environmental Toxins

These toxins are detectable in the tissues of animals, including humans, and
plants worldwide. They include:
(i) Ubiquitous;
(ii) Toxic; and
(iii) Bioaccumulate (Ability to accumulate in an organism).
2.4 POLLUTANT SOURCES

We will further our discussion with sources of pollutants. Let us start by taking a
look from the environmental perspective.
2.4.1 Environmental Perspective

We can classify the pollutant sources into Point Sources and Non-Point Sources
(as in Figure 2.2).

HEALTH
Figure 2.2: Pollutant sources
(a) 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. E.g., waste from factories and industrial production facilities,
wastewater treatment plants and power plants are in this category.
(b) Non-Point Sources

Here, there is no specific source of pollutants. They occur over a broad area
and are associated with particular land uses, as opposed to individual point
source discharges. E.g., include pollution due to storm water run-off,
pesticide and herbicide application, and vehicle exhaust.
SELF-CHECK 2.1
1. Give examples for point source and non-point source of pollutant
sources.
2. Which one of the source is much more difficult to be treated
before being released to the environment?
3. What would you suggest as treatment or controlling the amount
of the pollutants released?

HEALTH
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.
There are many hazards which can be commonly found in the workplace such as:
(a) Biological hazard;
(b) Physical hazard;
(c) Chemical hazard;
(d) Psychosocial hazard; and
(e) Ergonomic hazard.
These hazards, without proper control and preventive methods, can cause effects
such as occupational diseases or even catastrophic events.
2.4.3 Occupational Diseases

Occupational diseases are any chronic ailments that occur as a result of work or
occupational activity. Occupational diseases and injuries have probably always
been under-recognised and under-reported, and estimates of the degree to which
workplace conditions contribute to disease patterns widely.
In compliance with Occupational Safety and Health (Notification of Accident,

Dangerous Occurrence, Occupational Poisoning and Occupational Disease)
Regulations 2004, accidents, occupational diseases, near miss and occupational
poisoning should be reported to the Department of Occupational Safety and
Health (DOSH).
SELF-CHECK 2.2
1. Define hazards.
2. List four types of common hazards that occur in the industrial
workplace.
3. What does ÂNADOPODÊ stand for?

HEALTH
 The changing patterns of environment and occupation have had a profound

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

diseases.
 Chemical usage has been around since the 20th century, and there are many
types and characteristics of toxicants.
 Chemical exposure sources include point and non-point sources.
Catastrophic disaster Occupational hazards

Chemical usage Persistent organic chemicals
Communicable disease Pesticides
Epidemiological transition Point source
Non-communicable disease Pollutants source
Non-point source Type of toxicants

Topic  Occurrence
3 of Toxicants
LEARNING OUTCOMES
1. Define what is toxicant;
2. Describe visible smoke or smog;
3. Identify offensive odours; and
4. Recognise agricultural damage.
 INTRODUCTION
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 solids, liquids or gases and can be produced by anthropogenic
activities or natural sources. Air quality is worsening in virtually all Asian cities.
Air pollutants, mainly in the form of suspended particulate and sulphur dioxide
are most common in the cities of the developing countries.
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. „Toxicant‰ can be
considered a synonym for poisonous, while „developmental toxicant‰ can be
considered a synonym for teratogen.

TOPIC 3 OCCURRENCE OF TOXICANTS  37
3.1.1 Concentration Range

The effects depend on the concentration of the compound as illustrated in
Figure 3.1.
Figure 3.1: Concentration of compound
(a) Too Little

The metabolic behaviour deviates more from the natural behaviour for
decreasing concentrations.
(b) Enough
The metabolic behaviour is rather insensitive to changes in the concentration.
(c) Too Much

The metabolic behaviour deviates more from the natural behaviour for
increasing concentrations.
Classification of Toxicants I
(a) Target organ ă Hepatotoxin, neurotoxin.
(b) Intended use ă Pesticide, solvent.
(c) Source ă Natural, synthetic.
(d) Special effect ă Carcinogen, mutagen, endocrine disruptor.
Classification of Toxicants II
(a) Physical state ă Gas, solid.
(b) Toxicity ă Extremely, slightly.
(c) Chemical composition ă Heavy metal, organophosphate.
(d) Mechanism of action ă Anti-cholinergic, inhibitor, uncoupler.

38  TOPIC 3 OCCURRENCE OF TOXICANTS
Types of Toxic Responses I

(a) Immediate ă Minutes to hours after a single exposure.
(b) Delayed ă Days to years after exposure.
(c) Some both.
(d) Local ă Effect at site of contact, gastrointestinal tract (GIT), lungs.
(e) Systemic ă Effect distant from exposure site, centreal nervous system (CNS),
kidney, lungs.
(f) Some both.
Types of Toxic Responses II

(a) Reversible versus Irreversible
(b) Largely determined by tissue involved, length of exposure and magnitude
of toxic insults.
(c) Reversible ă Rapidly regenerating tissue, liver, intestinal mucosa, blood
cells.
(d) Irreversible ă CNS damage, carcinogenesis, mutagenesis, teratagenesis.
3.2 SMOG
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. 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. Look at Figure 3.2.

Figure 3.2: Smog in air

Source:
http://upload.wikimedia.org/wikipedia/commons/1/17/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
cause eye-watering. The yellowish colour is owed to whilst the irritant substances
include ozone, aliphatic aldehydes and organic nitrates. 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 for human health (refer to
Figure 3.3).
The four conditions necessary before smog can develop are:

(a) Sunlight;
(b) Hydrocarbons;
(c) Nitrogen oxides; and
(d) Temperatures above 18ÀC.

Figure 3.3: Formation of smog

Source: http://www.energyeducation.tx.gov/environment/section_2/topics/what_
is_smog/img/422a_smog.jpg
3.2.2 Automobiles
Automobiles are identified as the leading contributor to smog. Car engines,
especially diesel engines are huge contributors to the smog problem. 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 (refer to Figure 3.4).

Figure 3.4: Number of registered vehicle (2012 to 2013)

Source: www.jpj.gov.my
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 with both short and long term exposure can suffer
ill 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 aging 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
What causes smog? How do automobiles contribute to it?
3.3 SMOKE
Figure 3.5: Smoke inhalation affecting lungs

Source: http://demos.biemedia.com/omp-
demos/www.itriagehealth.com/disease/smoke-inhalation.html
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 ă the harmful gases, vapours and
particulate matter (soot, etc.) contained in smoke (refer Figure 3.5). Combustion
produces these gases, vapours and particulate matter that results 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 different
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:
(a) Heat damage;
(b) Tissue irritation by irritant compounds; and
(c) 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 W.R. Clark, Jr., „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 centage, 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 particulates, 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 stimulation of
the inflammatory response.
Smog particulates can create a similar irritation, but are derived from other
environmental particulates 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
Figure 3.6: Smoke from fire

Source: http://www.yourerdoc.com/smoke-inhalation/

Look at Figure 3.6. Smoke from different sources looks similar to the eye;
however, it is quite different in terms of its chemical and physical properties as
follow.
(a) Carbon Dioxide and Water

Carbon dioxide and water are major components in completing the
combustion during fire.
(b) Carbon Monoxide

Carbon monoxide (CO) is the most abundant emission product from
wildlife fire. Its negative effect on human health depends on the duration of
exposure, CO concentration and level of physical activity during the
exposure.
(c) Hydrocarbons
It contains hydrogen, carbon and sometimes oxygen.
(d) Nitrogen Oxides

It contributes to ozone formation.
The effects of smoke on Brunei, Indonesia, Philippines, Malaysia, Singapore and

Thailand, and occasionally Guam and Saipan are tremendous. The economic
losses of the fires in 1997 have been estimated at more than US$9 billion. This
includes damages in agriculture production, destruction of forest lands, health,
transportation, tourism and other economic endeavours. Not included are 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
lung, it is the deposition of particles, derived from the products burning, together
with toxic gases given off by the fire.
ACTIVITY 3.1
With your coursemate, find out more on the haze that affected Malaysia
in recent years.

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) ă a process described scientifically as
phagocytosis. The function of these large white immune cells is 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 particulates 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 this so important? If either the delivery of oxygen or use of oxygen is
inhibited, cells will die. 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, lung and respiratory damage can occur and, if for an extended
period, you 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 ordered. 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.
A blood test after smoke inhalation should include the following, if possible:
(a) 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;
(b) 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;
(c) 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;
(d) 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; and
(e) 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 your throat to keep
the airway from closing due to swelling.
In the case of respiratory distress or mental status changes, intubations will often
be done to ease breathing, suction off mucous and keep the victim from breathing
the content of the stomach. Patients with a wheezing cough (bronchospasm)
indicating bronchial airways are constricted or blocked often are given a
bronchodilator to relax muscles and increase ventilation.

In the cases of severe carbon monoxide or cyanide poisoning, HBO (hyperbaric

oxygenation) is the process of receiving oxygen in a compression chamber at
three times the normal atmospheric pressure.
3.4 OFFENSIVE 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
industrial facilities where extremely hazardous substances are manufactured, used
or stored and in communities along the nation's railways and highways are
potentially at risk of being exposed to airborne extremely hazardous substances
during accidental releases. Intentional releases by terrorists are 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 someone else, 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. EPA
can therefore, only trigger an investigation into an odour complaint when odour
is reported by a community member as being offensive.

Figure 3.7: Fumes from chemical factory leading to offensive odour

Source: http://www.deadseaimages.com/wp-
content/gallery/dedindustry/NB_DED_07911.jpg
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?

3.4.1 Sources of Environmental Odours

Odour can come from many different sources as illustrated in Figure 3.8, but EPA
becomes involved when offensive odour is generated from industrial processes.
Most odours from domestic sources and commercial premises, such as shops and
restaurants, will be addressed by Local Council Officers.
Figure 3.8: Sources of environmental odours
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 odours a
long way from their 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. However, when odours are persistent or strong, they can
have a significant effect on the lifestyle and amenity of residents. Calls to EPA's
pollution watch line shows odour to be among the most disruptive issue
individuals and local communities face.
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. 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 sensory
and chemical techniques.
Sensory techniques utilises human assessors to assess odour. The most commonly
applied sensory technique is olfactometry, which is used to measure the
concentration of an odour in terms of European Odour Units ( OU E / m 3 ).
Techniques also exist for assessment of odour character (e.g. triangular testing
and odour mapping), intensity and/or relative pleasantness/unpleasantness (e.g.
hedonic tone analysis).
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. The disadvantage of the
approach is that it is non-specific and does not identify specific chemical(s)
responsible for the odour. It means the approach measures the total odour of the
sample in terms of odour units ( OU E / m 3 ). Sensory techniques such as
olfactometry are commonly used for:
(a) Quantifying odours that can be used to assess the impact of the odour on
human subjects; and
(b) Assessing the efficiency of odour abatement systems in terms of total odour.
Chemical techniques utilises conventional analytical techniques to measure the

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 advantage of chemical measurement techniques are ease of use, and the
fact that the techniques are capable of identifying and quantifying specific
chemical odorant compounds. 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 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:
(a) Defining design criteria for odour abatement plant;
(b) Evaluating compliance to specific chemical emission limits; and
(c) 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 effect:
(a) Mucous membranes;
(b) Upper and lower respiratory airways;
(c) Heart and blood vessels;
(d) Stomach and intestines;
(e) Brain; and
(f) General well-being.
Odours have been recognised as signs of potential risks to human health as well
as direct cause of some symptoms of diseases in humans. Odorous gases
commonly become an issue because of their nuisance value. It is rare that adverse
health effects arise from exposure to odour. However, when odours are persistent
or strong, they can have a significant effect on the lifestyle and amenity of
residents. Calls to EPA's pollution watch line shows odour to be among the most
disruptive issue individuals and local communities face. Toxic chemicals with
strong odours can come from:
(a) Perchloroethylene from drycleaners;
(b) Benzene from gasoline released when the gas tank is filled; and
(c) Sulphur dioxide from electric utilities.
SELF-CHECK 3.4
What are the sources of odour?

3.4.4 Odour Control

Odours can be controlled by modifications to process to prevent odour
generation at source, or 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:
(a) Physical
(i) Dilution;
(ii) Physic absorption;
(iii) Coverage; and
(iv) Masking.
(b) Chemical
(i) Scrubbing;
(ii) Oxidation; and
(iii) Incineration.
(c) Biological
(i) Biofiltration.
(d) Combined
(i) Bioscrubbers.
Besides the above mentioned bad odour control measures, some other technologies
may be used to reduce the odour generation, for example:
(a) Replace the raw material to control the generation of less odorous emissions;
(b) Change the production process to reduce the generation of odorous
compounds; and
(c) 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 used 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 vapours, some
inorganic gases and some metallic vapours. 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 or
with a boiling point over 0ºC 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 not to clog 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 5000 cubic meters per hour.
Liquid scrubbing of gases involves bringing the odorous gas stream into 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 (the indirect condenser is preferred).
The most frequently used absorbing solutions are:
(a) Sodium hydroxide

Ideal for absorbing hydrogen sulphide and mercaptans.

(b) Amine
Used to trap hydrogen sulphide of hydrocarbon gases from petroleum
refinery.
(c) Chlorine, sodium hypochlorite, potassium permanganate, ozone or

hydrogen peroxide
Effective to absorb unsaturated organic compounds.
(d) Diluted sulphuric acid

Used to absorb ammonia.
3.4.7 Biofiltration
For biological odour control, the odour is removed by biological processes ă
bacterial action. The bacteria grow on inert supports, allowing intimate contact
between the odorous gases and the bacteria. The process is self-sustaining.
Biofilters require careful attention to ensure continued operation.
3.4.8 Bioscrubbers
Bioscrubbers use the combined principles of liquid scrubbing and the 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 odorous gases and the quantity of the production. After the
odour control technologies being 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
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 ă killing insects, weeds and diseases, and thus allowing the crops
and animals to flourish. Yet there has been a hidden cost to pay. Harm to
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 alternative, cheaper and safer
management methods have been developed and now adopted by several million
farmers. 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.
Agriculture plays an important role in the Malaysian economy. Malaysia is

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 food and beverage industry. The pesticide industry is the main
support in agriculture. These pesticides have adverse effect on water, soil, crops,
man, 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 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 prevalent but 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
Among other agricultural damage, we will look at dust and its features
(see Figure 3.10).

Figure 3.10: Dust

Source: http://www.politifact.com/tennessee/article/2012/apr/30/does-epa-really-
want-regulate-farm-dust
(a) 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 work spaces. Very high concentrations of inorganic
dusts are generated by field activities such as ploughing, tilling, haying and
harvesting. The bulk of the inorganic dusts are 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 greater than OSHA permissible levels.
(b) 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.
(c) 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: http://www.health.com/health/
static/hw/media/medical/hw/h9991456_001.jpg
(d) Endotoxins and Inflammation

Endotoxins are found where organic dust is produced and raised by animal
and human activities. These conditions are found in animal confinement
structures (swine and poultry), livestock farming, grain elevators, cotton
industry, potato processing, flax industry and the animal feed industry.
(e) 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; 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 death.
Lower level exposure may produce transient pulmonary decompensation, but
pulmonary disease can be a long-term sequelae 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.
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 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:
(a) Use of personal respiratory is adequate;

(b) Decreasing dust generation by adding mist, adding vegetable oil to feed,
sprinkling oil on the animals and using wet methods to clean surfaces;
(c) Ventilation with proper mixing of air improves air quality by decreasing
dust and gas levels;
(d) Concentrations of gases should be monitored periodically by the use of

simple colorimetric tubes or direct-reading electronic monitors;
(e) Applying newer methods of storing;
(f) 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
(g) 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 agriculture damage in detail.
3.6 MALAYSIAN 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 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.
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 has been
entrusted to administer this legislation to ensure that Malaysia will continue to
enjoy both industrial grow and a healthy living environment.

3.6.1 Objectives of the Act

The objectives of the Malaysian Environmental Quality Act are:
(a) To maintain a clean and healthy environment;
(b) To maintain the quality of the environment relative to the needs of the
growing population;
(c) To 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;
(d) To 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;
(e) To 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
(f) To 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 the following:
(a) Monitoring and Enforcement

The main environmental agency involved in controlling environmental
issues is the Department of Environment (DOE). DOE has recently taken a
more complete and integrated role, deviating from „problem-solving
approaches‰ to more systematic and holistic approaches that encompass
monitoring enforcement, development and planning.
(i) Monitoring
It includes water quality monitoring, noise and air quality monitoring.
(ii) Enforcement
It includes control on pollution from vehicles, control of agro-based
prescribes and non-prescribed premises, waste management.

(b) Public Awareness

Another aspect of the development function of the Environment Agency is
to promote environmental awareness largely through formal and informal
education, wide dissemination of environmental information through
environmental publication, seminars, workshops, lectures and the mass
media.
(c) Environmental Cooperation

DOE has been a significant environmental player, especially in the interest
of developing countries. It aims at regional cooperation.
 Toxicant (or toxic) is a chemical compound that has an effect on organisms.
 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

malaria linked to irrigation, pesticide poisoning and diseases transmissible
from farm animals to humans in intensive livestock systems.
Acute effect Odour

Agriculture damage Offensive odour
Animal intoxication Smog
Chronic effects injury Smoke
Injurious to humans Toxicant

Topic  Damage
4 Process and
Action of
Toxicants
LEARNING OUTCOMES
1. Describe the mechanism of action;
2. Explain the factors affecting xenobiotic action;
3. Discuss the metabolism of environmental chemicals; and
4. Discuss the defence responses to toxicants.
 INTRODUCTION
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. In addition, toxic effects depend on the physical and chemical
properties of the chemical, e.g., 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.

64  TOPIC 4 DAMAGE PROCESS AND ACTION OF TOXICANTS
4.1 MECHANISM OF ACTION

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. 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.
(a) 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.
(b) 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.
(c) General mechanism of toxicity includes:
(i) Interference with the Action of Enzyme Systems

Toxic substances can interfere with the action of enzyme systems by
inhibiting and inducing the enzyme.
(ii) Uncoupling of Biochemical Reactions

Some chemicals can uncouple biochemical reactions or disrupt specific
cellular functions.
(iii) Inhibition of Oxygen Transfer

A number of chemicals cause toxicity by interfering with either the use
or transport of oxygen in the cell.
(iv) Blockade of Haemoglobin Oxygen Transport

Other substances can block haemoglobin oxygen transport through
preferential binding.
(v) Synthesis of a Toxic Metabolite

A toxic metabolite can be synthesised through bioactivation process of
a chemical.

TOPIC 4 DAMAGE PROCESS AND ACTION OF TOXICANTS  65
(vi) Removal of Metallic Co-Factors

Certain chemicals are potentially toxic because they can bind necessary
metal ions making them unavailable to enzymes.
(vii) Interference with General Cellular Functions

Toxic substances can interfere with neurotransmission, nucleic acids,
protein synthesis and lipids.
(viii) Immunosuppression and Hypersensitisation

Some chemicals can cause immunosuppression or hypersensitisation
by interacting with the cells of the immune system.
(ix) Direct Chemical Irritation of Tissues

Unlike sensitisers, chemical irritants react directly with the
components of various tissues leading in most cases to immediate
local effects.
(x) Direct Cellular Toxicity

Toxic substances can cause direct damage to cellular structures.
(xi) Sequestration of Toxic Substances

Some toxic substances can undergo sequestration by being deposited
and stored in certain tissues for long periods of time.
ACTIVITY 4.1
1. Define the meaning of interaction of two chemicals: synergistic

effect, additive effect and antagonism.
2. Mixes of toxicants may cause effect greater than the sum of their
individual. Explain why.
4.2 FACTORS AFFECTING XENOBIOTIC ACTION

Many factors can affect toxicity of xenobiotics. Some of the factors include
physicochemical properties of toxicants, dose or concentration, mode and
duration of exposure and environmental factors. Let us now discuss this further.

4.2.1 Physicochemical Properties

Physical and chemical characteristics (e.g.; 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, in 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.
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 4.1 on exposure to pollutants). Also, continuous
exposure is more injurious than intermittent exposure, with other factors being the
same.

Figure 4.1: Exposure to pollutants

Source: http://fanaticcook.blogspot.com/2011/02/greatest-exposure-to-
pollutants-from.html
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. The mode of exposure (e.g., 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 otherwise
toxic doses of chemical substances.
4.2.4 Environmental Factors

Temperature changes in a volume of water 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 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 are shown; for example, gladiolus plants
appeared to be more sensitive to fluoride as relative humidity increased from 50
to 80 per centage.
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 4000 fc (foot-candle). In contrast, the sensitivity of pinto beans to
PAN increases with increasing light intensity. Plants exposed to pollutants in the
dark are generally not sensitive.
4.3 METABOLISM OF ENVIRONMENTAL

CHEMICALS
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. 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.
(a) Anabolism 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).
(b) Catabolism refers to the degradation of larger molecules to smaller ones,

e.g., 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, intestines, 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 the biotransformation are named mixed-function oxidase
(MFO), commonly known as cytochrome P450. The liver metabolises not only
many xenobiotics, but also drugs to which the body is exposed.
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 4.1
1. What do metabolism and homeostasis mean?
2. Describe the process of biotransformation.
4.4 DEFENCE RESPONSES TO TOXICANTS

The human body is an amazingly complex defence and self-healing system. 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 and 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
outside the body, internal organs, tissues and cells. 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 invader. This intricate system of protection is increasingly under
attack. The invader, which can be odourless and invisible, rides 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 (as can be
seen in Figure 4.2). 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.

Figure 4.2: The nose and throat

Source: http://entertainment.howstuffworks.com/arts/circus-arts/human-
blockhead1.htm
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 under-lying cilia. This mucociliary escalator transports deposited particles
and particle-laden macrophages upward to the pharynx, where they are
swallowed and pass through the gastrointestinal (GI) tract. Besides, toxicants
may dissolve from the surface and be removed via bloodstreams or lymphatic.
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 and 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 4.2
1. Name three routes of exposure by which xenobiotics can gain

entry into the body.
2. Explain briefly the process of absorption, ingestion and inhalation.
What is the difference between absorption and adsorption?
 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.
 Metabolism of environmental chemicals includes biotransformation and may

occur in any of several body tissues and organs, including the skin, lungs,
intestines, liver and kidney.
 The human body has an amazing defence response to toxicants. Different

parts of our body react differently when it comes to defending itself against
invaders.

Biotransformations Inflammation
Central nervous system Mechanism of action
Exposure Metabolism
Gastrointestinal tract Respiratory tract
Homeostasis Xenobiotic action

Topic  Toxic Action
5 of Pollutants
LEARNING OUTCOMES
1. Discuss the meaning of toxic pollutants;
2. List the toxic pollutants;
3. Describe the toxic action of major pollutants on humans;
4. Explain the toxic action of major pollutants on plants; and
5. Describe the mechanism of their action.
 INTRODUCTION
The earth has undergone massive changes due to human activities. 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 on the verge of extinction. 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 particulates from air.
A pollutant is a substance which is released in the environment and it adversely

affects the usefulness of the resource. 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.

74  TOPIC 5 TOXIC ACTION OF POLLUTANTS
There are a number of 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, they disturb the biochemical processes and occasionally lead to
fatal results.
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.
Schwartz used the term "concentration window" to draw the arbitrary lines of
demarcation which are:
(a) Essential at trace level for sustenance of life processes;
(b) ÂDeficientÊ at lower level than (a) causing metabolic disorder; and
(c) ÂToxicÊ at higher level than (a) causing adverse effects.
Even the well-known toxic elements (arsenic, lead and cadmium) are required in
trace quantities for the growth of animals. The so-called biologically inert
aluminium causes brain damage, bone disease and anaemia in patients subjected
to haemodialysis using water containing 100 to 1000 parts per billion of
aluminium.
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. 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
benefit to increasing production, living standards and health, many of them are
potentially toxic.

TOPIC 5 TOXIC ACTION OF POLLUTANTS  75
When present at a sufficiently high concentration, a pollutant can bring 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. This topic discusses the general ways
in which the environmental pollutants exert their action on plants, animals and
human beings.
5.2 SOURCES OF POLLUTANTS

Sources of pollutants include vehicles, chemical and petroleum refineries,
manufacturing facilities, commercial operations like dry-cleaning, ships and
airplanes. (see Figure 5.1).
Figure 5.1: Sources of pollutants
Pollutants are generally distributed in the environment through water movement

and air movement.

The types of pollutants and their effects are shown in Table 5.1 below.
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 disulfide Menstrual disorders, spontaneous abortion, adverse effects
on sperm
Chlorinated compounds Eye, ear and oral cleft defects, CNS disorders, perinatal
deaths, childhood leukaemia
1,2-Dibromo-3- Adverse effects on sperm, sterility
chloropropane
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
Polychlorinated biphenyls Preterm delivery, low birth weight, reduced head
circumference, growth deficiencies, neurobehavioural
effects
Trichloroethylene Congenital heart disease
SELF-CHECK 5.1
What are the major sources of pollutants?

ACTIVITY 5.1
List the major industries in Malaysia which are contributing to

environment pollution.
5.3 TOXIC ACTION OF MAJOR POLLUTANTS

In this subtopic, we will discuss toxic action of the major pollutants.
5.3.1 Metals
Metals are the major category of globally distributed pollutants; they have a
tendency to accumulate in select 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 in Figure 5.2). Other metals are
xenobiotics. 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.
Figure 5.2: Sources of toxic substances exposure

Source: http://www.freecoloring.ca/food/food010.jpg

These toxic substances affect the kidney, digestive tracts, liver, bones, brain and
other organs in the body causing diseases like cancer and breathing problems.
(a) Lead
Lead is widely used in industrial and household products. Lead is found in
air, soil, food, drinking water and house 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 (refer to Figure 5.3). Normal and daily
activities give enough opportunities for children to come in contact with
lead toxicity. Even small doses of lead can cause irreversible damage to
children's intelligence. Lead is especially harmful to children ages three and
under whose brains and nervous systems are still in the developmental
stage.
Figure 5.3: Lead

Source: http://img.allvoices.com/thumbs/event/609/480/56834116-lead-poisoning.jpg
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 when compared to school children from 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.
The levels of poisoning can be seen as below.
(i) Acute Poisoning

In acute poisoning, typical neurological signs are pain, muscle weakness,
paraesthesia and, rarely, symptoms associated with encephalitis.
Gastrointestinal problems, such as constipation, diarrhoea, poor

appetite or weight loss, are common in acute poisoning.
(ii) Chronic Poisoning

Chronic poisoning is usually there with symptoms affecting multiple
systems, but is 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 found in chronic lead poisoning.
(iii) Mechanism of Action

On a molecular level, proposed mechanisms for toxicity involve
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 bodyÊs ability to make haemoglobin by interfering

with several enzymatic steps in the haem pathway.
 Specifically, lead decreases haem biosynthesis by inhibiting d-

Aminolevulinic Acid Dehydratase (ALAD) and ferrochelatase
activity.
 Ferrochelatase, which catalyses the insertion of iron into

protoporphyrin IX, 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. It is used in paint, batteries many other
industrial and household uses. Mercury is also well known to be used in
thermometers. 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 vapours 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 comes in skin

or eye contact with 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 (see Figure 5.4).

Figure 5.4: Entry of mercury into the food chain

Source: http://www.extension.umn.edu/distribution/
naturalresources/images/6946f2h1.gif
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.
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.

(i) Acute exposure caused by inhaled elemental mercury can lead to

pulmonary 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 causing a life-threatening
pulmonary embolism.
(ii) Chronic and intense acute exposure causes cutaneous and neurological
symptoms. The classic triad found in chronic toxicity is tremors,
gingivitis and erethism (i.e., a constellation of neuropsychiatric findings
that includes insomnia, shyness, memory loss, emotional instability,
depression, anorexia, vasomotor disturbance, uncontrolled perspiration
and blushing).
(iii) Organic mercury poisoning usually results from ingestion of

contaminated food. The long chain and aryl forms of organic mercury
have similar 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 (precentral and postcentral 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 (e.g. inorganic or organic) and the
oxidation state of the arsenical. It is generally considered that inorganic
arsenicals are more toxic than organic arsenicals, 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 skin, respiratory, cardiovascular, immune, genitourinary,
reproductive, and gastrointestinal and nervous systems.
Here, we will 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
increased risks of cancer in the skin, lungs, bladder and kidney, 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
ingestion of drinking-water at concentrations 50øg arsenic/litre.
Different parts of the body can be affected by arsenic, including the

skin, lungs, heart, blood vessels, immune system, kidney, reproductive
system, gut and nervous system. Chronic arsenic exposure in 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 fumes. 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 bone.
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 Cd 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 is stored in the body
and gradually accumulates with age.
(e) Nickel
Pure nickel is a hard, silvery-white metal (as in Figure 5.5), which 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 sulfides.
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.
Figure 5.5: Pure nickel

Source: http://bardawily.com/Default.asp?ProductId=66&PageName=Product_Show

Nickel is released into the air by 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 wastewater streams.
The larger part of all nickel compounds that is released into the environment will
adsorb to sediment or soil particles and become immobile as a result. 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 nickels will

not biomagnify up the food chain.
SELF-CHECK 5.2
Discuss the toxic effects of mercury on mammals.
ACTIVITY 5.2
Collect the case studies related with mercury poisoning and make a chart
of all of them and discuss the details 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.
(a) Carbon Monoxide

It is a toxic gas in air which is produced by the way of combustion.
(i) 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.
(ii) 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.
(iii) Mechanism of Action

Carbon monoxide exerts its toxic effects by means of a combination of
tissue asphyxia and inflammatory activity. Hypoxia occurs from three
primary mechanisms: 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 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 cause collapse, rapid burning and swelling of tissues in
the throat and upper respiratory tract, difficult breathing, throat spasms and
fluid build-up in the lungs. It can 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 a 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.
(i) 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 particulates.
(ii) 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, NOxx 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

The safe drinking water is affected by water pollution (see Figure 5.6). There is
risk to health because lead, pesticides and chemicals. are found in public water
supplies. Contaminants can enter drinking water by variety of mechanisms, 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 (see Figure 5.6). The disease can lead to infection and can result in liver,
intestine, lung 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 guidelines. This was done under the guidance of experts from
the World Health Organisation.
Figure 5.6: Water contamination by industrial and household wastes

Source: http://superiorsites3.com/Images/GroundWaterPollute.jpg
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 imitates 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.
Some chemicals which are carcinogens are listed in Table 5.2:
Table 5.2: Carcinogenic Chemicals
2-aminonaphthalene Benzidine Sulphur mustard

4-aminobiphenyl Chromium compounds Tobacco smoke
5-azacytidine Coal tars Treosulphan
Aflatoxins Mineral oils Triethylenethiophosphoramide
Alcohol Nickel compounds Vinyl chloride
Arsenic Nitrogen mustard
Benzene Shale oils
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, lung and lymphatic
system. In 1974, more than 40 years after the introduction of vinyl chloride into
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 association 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.
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

protective masks, and initiated a urine monitoring programme for the early
detection of bladder cancer.
Many carcinogens come from natural sources. A variety of different types of

carcinogens is 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. 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 these other health
effects as well:
(a) Convulsions;
(b) Low blood pressure;
(c) Slow heart rate;
(d) Loss of consciousness;
(e) Lung injury; and
(f) Respiratory failure leading to death.
SELF-CHECK 5.3
Discuss the harmful effects of cyanide inhalation.

5.3.6 Methyl Isocyanate

Methyl isocyanate (MIC) is used in the production of pesticides, polyurethane
foam and plastics.
Effects noted from acute inhalation exposure to methyl isocyanate in humans are
respiratory tract irritation, difficulty breathing, blindness, nausea, gastritis,
sweating, fever, chills, and liver and kidney damage. Survivors continue to
exhibit 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 cataracts).
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.
(a) Thallium
Short-term exposure to thallium can cause gastrointestinal irritation and
nerve damage if 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.
(b) Copper
If the level of contamination is above the MCL in water or food supply, and
then people exposed to it can be affected by stomach and intestinal distress,
liver and kidney damage and anaemia.
(c) Selenium
Selenium is an essential nutrient at low levels but above MCL even for
relatively short period of time, hair and fingernail changes, there is 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.
(d) 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 child's blood and health
deteriorates rapidly over a period of days with symptoms of shortness of
breath and blueness of the skin.

Long-term exposure can cause diuresis, increased starchy deposits and

haemorrhaging of the spleen.
(e) Antimony
Short-term consumption of drinking water with contamination above MCL
of 6ppb can cause nausea, vomiting and diarrhoea; while long-term
consumption can cause cancer as antimony is a known human carcinogen.
(f) Beryllium
Short-term exposure to beryllium above 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.
(g) 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.
(h) Barium
Consumption of water above MCL for relatively short period of time can
cause gastrointestinal disturbances and muscular weakness, whereas long-
term exposure can cause high blood pressure.
(i) 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 5.3
Discuss the worst environmental disaster on record of methyl isocyanate
with your friends and tutor. What were the toxic effects of MIC on the
people over a period of time?
5.4 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 (see Figure
5.7). 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.
Figure 5.7: Effects of toxicants on plants

Source: http://i.treehugger.com/images/2007/10/24/ozone%20pollution-jj-001.jpg
5.4.1 Harmful Effects of Metals

In this section, we will proceed with the harmful effects of metals.
(a) Arsenic could be the essential element for its growth, but it has not been
proved. It is chemically similar to phosphorous, an essential plant nutrient
that can substitute phosphorous in plant nutrition. When arsenic in 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
(as in Figure 5.8), caused by 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.

Figure 5.8: Wilting-loss of non-woody part of the plant

Source: http://upload.wikimedia. org/wikipedia/commons/thumb/6/64/Fig_leaves.
jpg/220px-Fig_leaves
(b) 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 (as in
Figure 5.9), leaf rolls and stunting are the main and easily visible symptoms
of cadmium toxicity in plants. It is extremely toxic to chloroplast, as it is to
mitochondria. It decreases photosynthesis and increases photorespiration.
Figure 5.9: Chlorosis

Source: http://www.dias.kvl.dk/plantvirology/esymptoms/symp-color.html

(c) Lead is considered a general protoplasmic poison, which is cumulative,

slow acting and subtle. Soils contaminated with lead cause 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 physiological processes. Nutrient uptake: High concentrations of lead in
soil environment causes imbalance of mineral nutrients in growing plants
(see in Figure 5.10). Many of the observed actions of lead appear to be
indirect as a result of mineral imbalance within the tissues.
Figure 5.10: Damaged roots and stunted growth

Source: http://c.photoshelter.com/img-get/I0000.AaIXWkK8TQ/s
(d) 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

Next, we will cover the harmful effects of gases in the air.
(a) 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 is also hard on plants damaging ecosystems and

leading to reduced crop and forest yields. In the US alone, for example,
ground-level ozone accounts for an estimated $500 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. PAN is more toxic to
plants than ozone.
(c) Exposure to higher levels of the 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 becomes
maximum when the stomata are open i.e. during daytime.

Case Study: Chernobyl Accident
The Chernobyl accident on April 26, 1986, the world's largest reactor explosion occurred at
unit four of the graphite moderated, 1,000 MW, 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 4 s 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.
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 -1.
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) (Anspaugh et al., 1988). In Sweden, the fallout was identified as containing
radioactive krypton, xenon, iodine, caesium, and cobalt (Megaw, 1987). Through
integration of environmental data, it is estimated that some 100 petabequerel of 137 Cs (1
Pbq = 10 15 Bq) were released during and subsequent to the accident. Total release of
radioactivity exceeded 3 æ 10 18 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 (Megaw, 1987). 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.
Contd...

Although no acute effects occurred outside the USSR, the risk for lifetime expectation of
fatal radiogenic cancer increased from 0 to 0.02% in Europe and 0 to 0.003% in the
northern hemisphere (Anspaugh et al., 1988). 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 (Kolpakov et al., 1992). 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 (Bidnenko et al., 1992). Likhatarev et
al. (1993) 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 -1 dry wt)
following the accident. 137 Cs concentrations in lichens and mosses in some areas were
significantly elevated five years after the accident. The implications for food-chain transfer
were discussed in Section 8.5.3. 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. Populations had recovered
by the summer of 1988 (Krivolutzkii et al., 1992).
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?

 Pollutants are generally distributed in the environment through water

movements, and air movements.
 Metals are the major category of globally distributed pollutants; they have a
tendency to accumulate in select tissues of the body. Lead is widely used in
industrial and household products.
 Lead is found in air, soil, food, drinking water and house paint.
 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. Women who have been exposed to
mercury in pregnancy have sometimes given birth to children with serious
birth defects.
 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.
 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.
Carcinogens Poisoning
Lead Pollutants
Mercury Toxicants
Metals Wilting

Topic  Industrial
6 Toxicants
(PCBs, PBBs,
Dioxins and
Fluoride)
LEARNING OUTCOMES
1. Explain the industrial process;
2. Discuss the properties of PCBs, PBBs, Dioxins and Fluoride; and
3. Discuss the health effects caused by PCBs, PBBs, Dioxins and
Fluoride.
 INTRODUCTION
The Industrial Revolution of 19th century marked the development of many
factories especially in Western countries. The high demand for raw materials and
growing use of chemicals became a phenomenon in the industrial process.
The Industrial Revolution started in the West and 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.

TOPIC 6 INDUSTRIAL TOXICANTS (PCBs, PBBs, DIOXIN AND FLUORIDE)  101
ACTIVITY 6.1
With the help of a friend, find out when the Industrial Revolution started.
Discuss its implications to the development rate of industry as well as
usage of chemical and raw materials.
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 industrial process.
Industrial processes are 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 seen
as below.
(a) Acheson Process

An industrial process for making graphite by heating a mixture of coke and
clay.
(b) Bessemer Process

An industrial process for making steel using a Bessemer converter to blast
air through molten iron and thus burn the excess carbon and impurities; the
first successful method of making steel in quantity at a low cost.
(c) Cyanide Process

An industrial process for extracting gold and silver by treating ore with a
sodium cyanide solution.
(d) Haber Process

Industrial process for producing ammonia from nitrogen and hydrogen by
combining them under high pressure in the presence of an iron catalyst.

102  TOPIC 6 INDUSTRIAL TOXICANTS (PCBs, PBBs, DIOXIN AND FLUORIDE)
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)

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) and 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 PCB molecules can be formed. Some
PCBs are more harmful than others. Each PCB molecule contains two phenyl
rings. A phenyl ring is 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. At high temperatures, PCBs can burn and generate dangerous by-
products such as dioxins. PCBs tend not to evaporate or to 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 PCB Pollution

Sources of PCB pollution are:
(a) Landfills containing transformers, capacitors and other PCB waste can
release PCBs into the air. This environmental contamination may continue
to occur due to the disposal of old electrical equipment containing PCBs.
(b) The incineration of municipal waste may lead to PCB pollution and produce
dangerous by-products, such as hydrogen chloride (HCl) and dioxins
(polychlorinated dibenzo-dioxins and polychlorinated dibenzo-furanss).
(c) PCBs can also evaporate from contaminated water bodies.
6.2.3 Polychlorinated Biphenyls Contamination

Incident
The dangers of PCB's were first recognised in 1968 in Yusho, Japan, when more
than 1,000 people were contaminated after using rice oil which was tainted with
PCB's 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 PCB's 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 PCB's
after 2 July, 1979. Although the hazard exists, economic consideration prompted
the EPA to allow alder industrial equipment containing PCB's to continue in
operation.
6.2.4 Effect 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 through the skin. The main
PCB elimination routes are through the faeces, urine and breast milk.
Once in the gastrointestinal tract, ingested PCBs diffuse across cell membranes
and enter 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.

In mothers, PCBs have also been found to pass into the placenta, umbilical cord
blood and breast milk.
PCBs can undergo different transformations in the body and then either be stored
in certain tissues or excreted.
(a) Transformations that Lead to Accumulation

PCBs can easily be transformed into persistent metabolites that are not
readily excreted and that can accumulate in specific tissues and body fluids.
The biological half-life of these persistent metabolites depends on the
structure of the original PCB.
(b) Transformations that Lead to Excretion

PCBs can leave the blood and enter tissues very rapidly and be transformed
into water-soluble substances. They can combine with 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, levels of PCBs in blood dropped more rapidly in the
children. This may be partly explained by the childrenÊs growth, as their
increasing tissue mass may lower the PCB concentration in blood due to
dilution, rather than elimination.
SELF-CHECK 6.2
1. List source of PCBs pollution.
2. What happens when polychlorinated biphenyls enter the body?
6.3 POLYBROMINATED BIPHENYLS (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 one to ten 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 Sources of PBBs

Polybrominated biphenyls are made from a chemical known as benzene
(sometimes referred to as „phenyl‰) which is derived from coal tar.
6.3.3 Polybrominated Biphenyls 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 PBB-based
flame retardants. In 1973 and 1974, several thousand pounds of FireMaster BP-6
were accidentally mixed with livestock feed that was distributed to farms
in Michigan, USA.
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 PBB-exposed Michigan residents 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 PBB and other related chemicals, such as
Polychlorinated Biphenyls and Polybrominated Diphenyl Ethers, may interact
with the endocrine system and disrupt its natural balance.
SELF-CHECK 6.3
What are other names of polybrominated biphenyls?
6.4 DIOXINS
Dioxins refer to a group of chlorinated organic chemicals with similar chemical
structures. Some have harmful properties, depending on the number and position
of chlorine atoms in their chemical structure. One of the most harmful dioxins is
known as TCDD. Some PCBs, which have similar properties, are considered
"dioxin-like".
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 dioxin release into the environment,
uncontrolled waste incinerators (solid waste and hospital waste) are often the
worst culprits, due to incomplete burning. 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. Very low levels are found in plants, water and
air.
6.4.3 Dioxin Contamination Incidents

Some dioxin 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 continuing to determine the long-
term human health effects from this incident. These investigations, however, are
in a weak position by the lack of appropriate exposure assessments. A minor
increase in certain cancers and effects on reproduction has been detected and are
being further investigated. Possible effects on the 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 ă guar gum ă
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

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 on 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 the 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 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. List the sources of dioxin.

2. What was one of the toxic chemicals released during the accident
at the factory in Seveso, Italy?
6.5 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 caused by airborne flourida.
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 drinking water.
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 steel industry, phosphate fertiliser
industry, aluminium industry, ceramics industry (brick, tile, glass), non-ferrous
metal foundries, welding operations and coal-burning power plants. Fluorides
emitted into the atmosphere from different sources include both gaseous and
particulate forms.
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 the 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.
 The industrial process is defined as a systematic series of mechanical or

chemical operations that produces or manufactures something.
 PCBs belong to a broad family of man-made organic chemicals known as

chlorinated hydrocarbons. PCBs alter 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. 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 highly toxic and can cause
reproductive and developmental problems, damage the immune system,
interfere with hormones and also cause cancer.

 Fluoride is found naturally in water, foods, 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.
Acheson process Polychlorinated biphenyls (PCBs)

Bessemer process Polybrominated biphenyls (PBBs)
Haber process Dioxin
Industrial process Fluoride

Topic  Target Organs
7
LEARNING OUTCOMES
1. Explain toxicants and their exposure in the human body;
2. Describe the human body in a physiological perspective; and
3. Explain toxicants and its disruptions to our physiological system.
 INTRODUCTION
Gandhi once quoted „It is health that is real wealth and not pieces of gold and
silver‰. Surprisingly, it is true; there is no meaning of wealth without good health
in our daily life. 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 are still facing many chronic diseases caused by exposure toward
toxicants which disrupt our bodyÊs physiological functions.
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‰. Looking at the world nowadays, we can find varieties of chemicals in
our daily life. The big questions are how the chemical enters the body; how it is
distributed; how it is metabolised; and how it is excreted from the body.

TOPIC 7 TARGET ORGANS  113
To understand and answer this question, we must first understand toxicology.

The basic understanding should include four important stages. These four
important stages in toxicology that we should understand in order to relate the
toxicant, exposure toward it and its effect are:
(a) Absorption of toxicant:

(i) Route of entry;
(ii) Duration of exposure; and
(iii) Degree of exposure.
(b) Distribution of toxicant:

(i) Local distribution; and
(ii) Systemic distribution.
(c) Metabolism of toxicant:

(i) Metabolism of the toxicant in our body; and
(ii) Disruption of biochemical pathway.
(d) Excretion of toxicant:

(i) How will the toxicant be excreted in our body?
ACTIVITY 7.1
1. Name one toxicant and its common effect to your health that you
can observe in your daily life.
2. What are the four important stages in a toxicology study? Explain

these stages.
7.2 OUR HUMAN BODY IN PHYSIOLOGICAL

PERSPECTIVE
Have we ever wondered what makes up our body? Through the advances and
evolution of modern technology, we can discover the complex human 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 etc. Combination of many cells to
perform certain functions will form the organ. Skin, eye and heart are examples

114  TOPIC 7 TARGET ORGANS
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 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 environment generally. Now, let us discover our body system
briefly and common effects of toxicants to it.
SELF-CHECK 7.1
1. What is the basic unit of our body?

2. State four levels in our body organisation.

7.3 TOXICANTS AND THEIR DISRUPTIONS TO

OUR PHYSIOLOGICAL FUNCTION
Through this subtopic, we will briefly learn about how toxicants affects our:
(a) Respiratory system;
(b) Integumentary system;
(c) Circulatory system;
(d) Liver;
(e) Kidney; and
(f) Reproductive system.
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 one responsible for
the 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:
(a) Providing an extensive area for gas exchange between the air and the
circulating blood.
(b) Moving air to and from the exchange surfaces of the lungs.
(c) Protecting respiratory surfaces from dehydration, temperature changes or
other environmental variations and defending the respiratory system and
other tissues from invasion by pathogens.
(d) Producing sounds involved in speaking, singing and non-verbal
communication.
(e) Providing olfactory sensations.

Basically, the component of the human respiratory system consists of two parts
which are as below:
(a) Upper respiratory system (nose, nasal cavity, paranasal sinus and pharynx);
and
(b) Lower respiratory system (bronchioles, alveoli of the larynx (voice box),
trachea (windpipe), bronchi and lungs.
Refer to Figure 7.2 to get a better understanding.
Figure 7.2: The anatomy of respiratory system
The anatomy of the lungs is described in these points:
(a) It is a paired organs located in the thoracic cavity; enclosed and protected
by the pleural membrane (two layers)
(i) Parietal pleura (outer layer) ă attached to the wall of the thoracic
cavity; and
(ii) Visceral pleural (inner layer) ă covering the lungs.

(b) The lungs are between the pleurae ă the pleural cavity ă which are filled
with lubricating fluid.
(c) Each lung is a blunt cone, with the tip, or apex, pointing superiorly.
(d) The lungs have distinct lobes separated by deep fissures.
(e) The right lung has three lobes and the lobes are separated by two fissures.
(f) The left lung has two lobes and the lobes are separated by one fissure.
(g) The lungs consist of numerous numbers of alveoli.
The alveoli can be described as follows:

(a) Alveoli are tiny thin-wall sacs where gas exchange occurs.
(b) Each lung contains about 150 million alveoli, and their abundance gives the
lung an open, spongy appearance.
(c) An extensive network of capillaries is associated with each alveolus.
Many respiratory problems arise from its exposure toward varieties of chemical
in our daily life. Among these problems include:
(a) Irritation (ammonia, chlorine, hydrogen fluoride, sulphur dioxide);

(b) Asbestosis (asbestos);
(c) Silicosis (silica, sand blasting activities);
(d) Oedema (phosgene, tetrachloroethylene, nickel);
(e) Occupational induced asthma (particulate matter, dust);
(f) Pneumonia;
(g) Emphysema;
(h) Bronchitis; and
(i) Lung cancer (carcinogenic substances).
Protection for respiratory system against these toxicants can be taken by applying
the dental mask, dust mask, half face piece, full face piece, PAPR, SCBA and air
line.

SELF-CHECK 7.2
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
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 organ or a

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:

(a) Cutaneous membrane; and
(b) Accessory structure.
General functions of the integumentary system are:

(a) Protection;
(b) Excretion;
(c) Temperature regulation;
(d) Synthesis of vitamin D; and
(e) Cutaneous sensation.

Our skin is undeniably the primary defence to any exposure. It goes against scar,
biological microorganisms, chemicals and many other substances. We can see
many effects that commonly affect the skin due to exposure to chemicals such as
skin burn, irritation and skin cancer.
Protection for the integumentary system includes glove, apron and covering all
on oneself.
7.3.3 Effects of Toxicants on the Circulatory System

„Oh dear, my hand is bleeding‰ ă this may be a common experience that we
might face in our daily lives when our hands or other parts of the body 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 this question,
the next step is to read the content of this subtopic.
Blood is actually one of the main parts in the circulatory system. Without 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 we know that blood is a part of the circulatory system in our body. In this
subtopic, we will learn more on the 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:
(a) Heart;
(b) Blood; and
(c) Blood vessel.
Let us discuss further.

(a) 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. The diagram of
the heart can be referred to in Figure 7.3.
Figure 7.3: The diagram of the heart

Source: http://science6shms.pbworks.com/w/page/24477490/Heart%20Diagram
(b) Blood
Blood actually is 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, while
the solid portion consists of red blood cells, white blood cells and platelets.

Basically 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:
(i) Plasma ă the liquid portion;
(ii) Platelets ă the clot forming components;
(iii) White blood cells ă the infection fighters; and
(iv) Red blood cells ă the oxygen transporters.
The function of the blood is for transportation, regulation and protection.
(c) Blood Vessel

The blood vessels are the part of the circulatory system that transport
blood throughout the body. There are three major types of blood vessels:
(i) The arteries ă which carry the blood away from the heart;
(ii) The capillaries ă which enable the actual exchange of water and
chemicals between the blood and tissue; and
(iii) The veins ă which carry blood from the capillaries back to the heart.
The common effects of toxicants on the circulatory system include:

(a) Methemoglobinemia;
(b) Anaemia;
(c) Aplastic anaemia;
(d) Drug induced autoimmune haemolytic anaemia;
(e) Drug induced nonautoimmune haemolytic anaemia;
(f) Haemolytic anaemia (lead poisoning);
(g) Leukaemia (benzene);
(h) Drug induced cardiovascular disease; and
(i) Heart cancer.

7.3.4 Effects of Toxicants on the Liver

The human bodyÊs detoxifying site is liverÊs most prominent function. Sometimes
we might ingest foreign substances such as weak poisons and drugs. Do 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, 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?
(b) What are the effects of toxicants on our liver?
So let us find the answers here.
(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:
http://www.merckmanuals.com/home/liver_and_gallbladder_disorders/biology_of_th
e_liver_and_gallbladder/overview_of_the_liver_and_gallbladder.html

The processes for liver metabolism are as follows:

(i) Cytochrome P450 mono oxidase;
(ii) Glucuronidation;
(iii) Sulfation; and
(iv) Glutathione-S-Transferase.
(b) What are the effects of toxicants on our liver?

According to a study by Proper and Schaffer (1959), damage to the liver
which is caused by chemicals can be explained through a few classifications
which are:
(i) Zonal hepatocellular alteration without inflammatory reaction:
 Necrosis and steatosis.
(ii) Intrahepatic cholestasis:

 Bilestasis.
 Dilatation of the canaliculi with subsequent loss of microvilli.
(iii) Focal necrosis.

(iv) Hepatic necrosis with inflammatory reaction.
(v) Unclassified.
(vi) Hepatocarcinogen.
There are few factors that are involved in liver injury which include:
(i) Biotransformation of toxicant:

 To more active metabolite
(Eg. Chloroform  phosgene) lead to depletion of hepatic
glutathione and alkylation of macromolecules.
(ii) Alteration of hepatic blood flow:

 Haemorrhagic necrosis by Dimethylnitrosamine.
 Coagulative necrosis by Carbon Tetrachloride.

(iii) Potentiation of Hepatotoxicity:

 Ethanol ă increase damaging properties of haloalkanes.
 Acetone and other form of ketones potentiate Carbon

Tetrachloride (CCl4) hepatotoxicity.
 n-hexane intermediate potentiate chloroform toxicity.
 Diabetic state enhances hepatotoxicity of Carbon Tetrachloride

(CCl4), chloroform.
The liver injury usually comes through few mechanisms which include:
 Accumulation of lipids  Protein synthesis  Lipid peroxidation 

Calcium homeostasis  Immunologic reaction  Cholestasis 
Cirrhosis  Carcinogenesis
The mechanism can be explained by:
(a) Accumulation of Lipids

(i) Accumulation of advance beneficiary notice of non-coverage (AbN)
amount of fat predominantly in parenchymal cells and decrease
plasma lipid and lipoprotein.
 Interfere 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.
(ii) CCl4 , ethionine, phosphorus, tetracycline.
(b) Protein Synthesis (Lead to Necrosis)

(i) Inhibit incorporation of amino acid into liver protein.
(ii) Ethionine, Carbon Tetrachloride (CCl4), dimethylnitrosamine.
(iii) Ethionine ă replace methionine cause decrease adenosine triphosphate
(ATP) synthesis and inhibition of (ribonucleic acid) RNA synthesis.

(iv) Dimethylnitrosamine ă loss of mRNA.

(v) CCl4 ă ribosome.
(vi) Galactosamine ă decrease synthesis of RNA.
(c) Lipid Peroxidation

(i) Peroxidation cleavage of unsaturated Fatty Acids and release of
carbonyl compound.
(ii) CCl4 ------- formation of free radicals
 Alteration of ER;
 Loss of G6P activity enzyme;
 Loss of protein synthesis; and
 Loss of capacity to form and excrete VLDL.
(d) Calcium Homeostasis

(i) Accumulation of Calcium (Ca2+) in the liver leads to cell death
(influence cell metabolism, motility and division).
(ii) Activation of molecular Oxygen (O2) (oxidative stress) at plasma
membrane, endoplasmic reticulum, mitochondria, cytosol.
(iii) Carbon Tetrachloride (CCl4 ), bromobenzene, adriamycin.
(e) Immunologic Reaction

(i) Covalent binding with hepatic protein.
(ii) Mainly by many drugs such as phenytoin, sulfonamides, erythromycin.
(f) Cholestasis
(i) Decrease microvilli canaliculi.
(ii) Golgi apparatus dilated and vacuolated.
(iii) E.g. Manganese.

(g) Cirrhosis
(i) Chronic morphological alteration of the liver (appear as nodules).
(ii) Mechanism:
 Single cell necrosis + deficiency in repair mechanism of residual

cells.
 Alteration of intrahepatic vasculature.
(iii) Enhance by deficiency in protein, vitamin B12 , folic acid;

(iv) E.g. ă CCl4, aflatoxin, alcohol (ethanol);
(v) Chronic liver disease;
(vi) Damage of liver tissue, scarring of the liver (fibrosis ă nodular
regeneration);
(vii) Progressive decrease in liver function;
(viii) Excessive fluid in the abdomen (ascites);
(ix) Bleeding disorders (coagulopathy);
(x) Increased pressure in the blood vessels (portal hypertension); and
(xi) Brain function disorders (hepatic encephalopathy).
Take a look at Figure 7.5 where an example of healthy liver and liver
scarred by cirrhosis is displayed.
Figure 7.5: Healthy and cirrhosis liver

(h) Carcinogenesis
(i) Initiation, promotion and progression.
(ii) Pseudofetal configuration of liver cells
 Increase foetal isozyme, alfa feto protein, foetal antigen.
(iii) Examples of carcigonesis are as follows:
 Vaflatoxin B1;
 Dimethylnitrosamine;
 Dimethylbenzoanthracene;
 Dimethylaminoazobenzene;
 Organochlorine pesticide;
 Polychlorinated biphenyl; and
 CCl4.
(i) Angiosarcoma
(i) Uncommon malignant neoplasms characterised by rapidly
proliferating, extensively infiltrating anaplastic cells derived from
blood vessels and lining irregular, blood-filled spaces.
(ii) Malignant endothelial vascular neoplasms that affect a variety of sites.
(iii) Angiosarcomas are aggressive and tend to recur locally, spread
widely, and have a high rate of lymph node and systemic metastases.
(iv) The rate of tumour-related death is high.
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, performs the filtering
system in order to ensure our blood is free from harmful substances, ensures
good regulation of our urinary system, as well as, ensures our body is in a good
state.

Many people nowadays are heavily dependent on artificial machines which

replace the function of their malfunctioned kidney at a high expense and cost.
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.
In order to understand the kidney and its functions in the human body, as well as
to understand the effects of toxicants on it, this subtopic will detail out:
(a) How does our kidney look like?

(b) What are the functions of our kidney?
(c) What are the common effects of toxicants on our kidney?
Let us proceed to find the answers.
(a) What is the structure of our kidney?

Three primary components:
(i) The tubular elements;
(ii) The glomerulus; and
(iii) The vascular element.
A general overview of the kidney and its other sections and parts can be
seen in Figure 7.6 to 7.8.
Figure 7.6: General overview of the kidney

Source: http://bharathgramaarogya.net/urosymptoms.htm

Figure 7.7: Cut section of kidney (vascular elements ă renal arteries)

Source: http://kidneycares.com/forPatients.aspx
Figure 7.8: Basic functional unit in our kidney (tubular ă tubule and glomerulus)
Source: http://www.ratical.org/radiation/vzajic/8thchapter.html

(b) What are the functions of our kidney?

(i) Excretion of waste;
(ii) Acid-base homeostasis;
(iii) Osmolality regulation;
(iv) Blood pressure regulation; and
(v) Hormone secretion.
(c) What are the common effects of toxicants on our kidney?

There are many types of nephrotoxicants that can threaten our kidney.
These include:
(i) Heavy metals;
(ii) Halogenated hydrocarbons;
(iii) Petroleum hydrocarbons; and
(iv) Therapeutic agents.
Common heavy metal such as mercury, cadmium, chromium, arsenic, gold,

lead, iron, antimony, uranium and thallium could pose risk to our body.
The effects are categorised as:
(i) Most-potent nephrotoxicants;
(ii) Low dose ă glucosuria, polyuria;
(iii) High dose ă renal necrosis, anuria, death;
(iv) Similar damage by similar mechanisms; and
(v) Histologically ă 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 HgĈ, Hg+, Hg++, MeHg and PhHg. The
toxicity it causes varies with 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 in 24 to 48 hours after a large dose of 1 to 4g.
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:
(i) ATP production decreased ă Mercury binding to sulfhydrals in

mitochondrial enzymes;
(ii) Altered Ca2+ homeostasis ă Hg effects blocked by Ca2+ uptake blocker;
(iii) Phospholipid derangements ă lead to decreased membrane function
resulting in further free Ca ă a cascading effect; and
(iv) Leads to necrotic injury of the tubule.
7.3.6 Effects of Toxicants on the Reproductive

System
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 7.9.

Figure 7.9: 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. Basic components of this system include:
(a) Testis;
(b) Penis;
(c) Urethra;
(d) Prostate gland;
(e) Seminal vesicle; and
(f) Vas deferens.
The sperm production (as in Figure 7.10) in the testis originates from indifferent
gonads during the embryonic phase. 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 and intratubular.
(a) Extratubular ă vascular and interstitial divisions (inclusive of lymphatic

channels and Leydig cells); and
(b) Intratubular ă basal and adluminal divisions. This compartment is located

in the seminiferous tubules.
Figure 7.10: Sperm production
The effects of toxicants on the male reproductive system through lead, EDB,
carbon disulphide and drug abuse are as explained in the following.
(a) In lead, 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 increase, the hypothalamic-pituitary-
testicular axis could be disturbed. However it is unclear how long these
effects may last in humans after lead exposure ceases.

(b) EDB (Ethylene Dibromide or 1,2-dibromoethane) is a colourless, water

soluble liquid and used as pesticide and gasoline additive absorbed through
the lungs, digestive tract and 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 show that those workers exposed to EDB have more sperm
with tapered heads and fewer sperm per ejaculate.
(c) Carbon Disulphide 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/mò) 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.
(d) Drug Abuse 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 you can refer to
in Figure 7.11.

Figure 7.11: Female reproductive system

Source: http://fau.pearlashes.com/anatomy/Chapter%2042/Chapter%2042.htm
The basic component of female reproductive system includes 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:
(a) Fimbriae ă at the periphery of oviduct, functions to assist in supporting

uterus.
(b) Infundibulum ă funnel-shaped structure near ovary, functions to catch

ovulated ovum.

(c) Ampulla ă distal oviduct and is enlarge, functions as site of fertilisation.
(d) Isthmus ă 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 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 entry of bacteria into 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, halogenated polycyclic hydrocarbons, organic solvents and
pharmacological agent.
(a) Polycyclic Aromatic Hydrocarbon (PAH)

(i) Produced by cigarette smoke;
(ii) Ovarian toxicity and oocyte destruction;
(iii) Caused by reactive electrophilic metabolites generated by parent
hydrocarbon; and
(iv) Inducers of hepatic enzyme including microsomal monooxygenases
and transferase.
(b) Halogenated Polycyclic Hydrocarbon

(i) Includes DDT, PBB and PCB;
(ii) DDT will cause damage to uterus and affect fertility;

(iii) Cause an estrogenic response in rats; and

(iv) Thickening of the endometrium and increase in uterus weight
competitive inhibition of the binding of estradiol to receptors sites in
uterus.
(c) Organic Solvents

(i) Carbon disulphide causes irregular menstrual flow;
(ii) Benzene alters the ovarian function; and
(iii) Carbon tetrachloride alters the ovarian function.
(d) Pharmacology Agents

(i) Adverse effect on the menstrual cycle;
(ii) Mediated through binding to steroid receptor and exertion of
estrogenic or anti-estrogenic effects;
(iii) Stimulation of an increase in serum prolactin level;
(iv) Direct toxic effect on the ovary; and
(v) Examples are oral contraceptives and tricyclic anti-depressants.
 Exposure to toxicants may lead to the disruption of the bodyÊs respiratory

system, integumentary system, circulatory system, liver, kidney and
reproductive system.
 When the body is exposed to toxicant, the physiological system will be

compromised.
 Depending on the toxicant, effects of exposure differ from one to another.

Circulatory system Physiological system

Human body organisation Reproductive system
Kidney Respiratory system
Liver Toxicant

Topic  Endocrine
8 Disruption
and
Mutagenic
Pollutants
LEARNING OUTCOMES
1. Describe the endocrine system and mutagen;
2. Describe the characteristics of endocrine disruptors;
3. Explain the types of mutation; and
4. Discuss the effects of endocrine disruptors and mutagens to human.
 INTRODUCTION
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. However even though the nervous system
and endocrine system are separate systems, they often work together to help the
body function properly.

140  TOPIC 8 ENDOCRINE DISRUPTION AND MUTAGENIC POLLUTANTS
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
factors such as stress, infection and changes in the balance of fluid and minerals
in blood.
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.
Some 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). 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 ă such as the brain, heart, lungs, kidneys, liver, thymus,
skin and placenta ă also produce and release hormones. Take a look at Figure 8.1
to see the major glands and non-endocrine organs.

TOPIC 8 ENDOCRINE DISRUPTION AND MUTAGENIC POLLUTANTS  141
Figure 8.1: Major glands and non-endocrine organs of the endocrine system
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 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 a negative feedback system.
8.2 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. A wide range of substances, both
natural and man-made, are thought to cause endocrine disruption, including:
(a) Pharmaceuticals;
(b) Dioxin and dioxin-like compounds;
(c) Polychlorinated biphenyls;
(d) DDT and other pesticides; and
(e) 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 and 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 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. The human effects are more difficult to definitively associate with
environment chemicals and some effects are controversial. However, 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 hormone balance which may result in 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.
8.3 REVIEW OF HORMONAL FUNCTION

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 (maintain 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 ultimately
responsible for stimulating or regulating proper metabolism, development,
growth, reproduction and behaviour.

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.
Timing of hormone release is often critical for normal 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.
ACTIVITY 8.1
From the blood, how do hormones send messages to the target cells?
Discuss with a coursemate.
8.4 CHARACTERISTIC 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:
(a) By mimicking the sex steroid hormones oestrogen and androgen by binding
to their natural receptors either as agonists or antagonists.
(b) By altering the synthesis and breakdown of natural hormones.
(c) By 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.

8.4.1 Chemical Structures of EDCs

Interestingly, the chemical structures of 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.
Because the structures of endocrine disruptors are so variable and unpredictable,

they are sometimes synthesised unintentionally. A couple of examples include
the pesticide DDT and polychlorinated biphenyls (PCBs), both of which have
estrogenic activity, but were originally synthesized for a completely unrelated
purpose.
8.4.2 Sources of Endocrine Disruptors

Chemicals capable of acting as endocrine disruptors are ubiquitous in our
environment. They can be found in:
(a) The natural environment (air, water, soil);
(b) Food products (soybeans, legumes, flax, yams and clover);
(c) Plants (phytoestrogens are chemicals naturally found in plants that can act
as endocrine disruptors and are present in fruits, veggies, beans and
grasses);
(d) Household products (breakdown products of detergents and associated
surfactants, including nonylphenol and octylphenol);
(e) Pesticides (o,pÊ-DDT, endosulfan, atrazine, nitrofen and tributyl tin);
(f) Plastics (bisphenol A, phthalates);
(g) Pharmaceuticals (drug oestrogens ă birth control pills, DES, cimetidine);
(h) Industrial chemicals (polychlorinated biphenyls (PCBs), dioxin and
benzo(a)pyrene);
(i) By-products of incineration, paper production and fuel combustion; and
(j) Metals (cadmium, lead, mercury).
We are exposed to these various endocrine disruptors by eating and drinking

them, breathing them, and using them whether at home or at work.

ACTIVITY 8.2
1. List down the most frequent EDCs exposed to you daily.
2. State the reason why you are exposed to these EDCs based on your
routine activity and your environment.
3. What is your plan of action to reduce your exposure to these EDCs?
8.5 MODE OF ACTION

Here, we discuss the mode of action associated with endocrine disruptors.
8.5.1 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, effects of EDs through steroid receptors on
peptide/protein hormones are common.
8.5.2 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 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.
8.5.3 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. Figure 8.2 shows 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
8.6 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. Other studies suggest that

specific phytoestrogens and certain PCBs and dioxins can block oestrogen from
promoting some forms of breast cancer.
Speculated health effect from EDCs can be seen as below:
(a) Reproductive effects/birth defects;

(b) Cancer;
(c) Low sperm count/sexual dysfunction;
(d) Heart disease;
(e) Cognitive disorders;
(f) Sex reversal;
(g) Premature puberty; and
(h) Altered immune function.
8.7 TESTING ESTROGENICITY

Although oestrogen is often considered the 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 a 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:

(a) Estradiol E2: Predominant type of oestrogen in a menstruating woman;
(b) Estriol E3: Predominant type of oestrogen in a pregnant woman; and
(c) Estrone E1: Predominant type of oestrogen in a post-menopausal woman.
Oestrogen tests may be used for a variety of reasons:
(a) Estrone 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) Estradiol levels are used in evaluating ovarian function. Estradiol 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 ă 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. Estradiol is also sometimes used to monitor
menopausal hormone replacement therapy. A doctor may sometimes order a
total oestrogen test. This test measures oestrone and estradiol together but
does not measure estriol.
(c) Estriol 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 estriol test, one that measures estriol
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.
SELF-CHECK 8.1
1. Describe the endocrine system, the function of hormones and

endocrine disruptors.
2. Discuss the relation between hormones and cancers.
8.8 MUTAGEN
A mutagen is a natural or man-made agent (physical or chemical) which can alter
the structure or sequence of DNA.
Characteristics of mutagens can be seen as follows:
(a) Causing DNA damage that can be converted to mutations.
(b) Physical mutagens

(i) High-energy ionising radiation;
(ii) X-rays and γ-rays  strand breaks and base/sugar destruction;

(iii) Non-ionising radiation; and

(iv) UV light  pyrimidine dimers.
(c) Chemical mutagens

(i) Base analogues  direct mutagenesis
(ii) Nitrous acid  deaminates C to produce U
(iii) Alkylating agents
(iv) Arylating agents indirect-lesion mutagenesis
(v) Intercalators: e.g. EB
8.9 MUTATION
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.
The definition of mutation can be summed up as:

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 and cytosine (C).
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 (see Figure 8.3).

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. Occurrence of mutation,
however, depends on the nature of the initial lesion and the response of cells to
the DNA damage.
Figure 8.3: The structures of the five bases in DNA and RNA
Mutation happens due to several reasons:
(a) DNA Fails to Copy Accurately

Most of the mutations that people think matter to evolution are "naturally
occurring‰. For example, when a cell divides, it makes a copy of its DNA ă
and sometimes the copy is not quite perfect. That small difference from the
original DNA sequence is a mutation.
(b) External Influences can Create Mutations

Mutations can also be caused by exposure to specific chemicals or radiation.
These agents cause the DNA to break down. This is not necessarily
unnatural ă 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.

ACTIVITY 8.3
1. Referring to the acronyms of DNA and RNA, what does it mean by

„D‰ and „R‰?
2. What does it mean by „ionising‰ and „non-ionising‰ radiation?
8.10 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). Such a substitution could:
(i) Change a codon to one that encodes a different amino acid and cause 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 and

cause an incomplete protein. This can have serious effects since the
incomplete protein probably would not function.
Figure 8.4: Change of codon

Illustrations of codon changes can be further seen in Figures 8.5, 8.6 and 8.7.
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 8.8).
Figure 8.8: 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 DNA is lost, or deleted (as in Figure 8.9).
Figure 8.9: 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.
Figure 8.10: Illustration of frame shift
SELF-CHECK 8.2
1. Describe mutagen and discuss what causes mutation.

2. Name four types of mutations that have been identified.
3. What is the difference between insertion and deletion mutations?
8.11 EFFECT 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 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.
8.11.1 Types of Mutagens

The types of mutagens are as follows:
(a) Ionising Radiation

Nuclear radiation, X-rays, gamma rays (e.g. medical treatment) associated
with development of cancers (e.g. leukaemia, thyroid cancer and skin
cancer).
(b) Viruses and Microorganisms

These integrate into human chromosome, upset genes and can trigger
cancer.
(c) Environmental Poisons

Organic solvents such as formaldehyde, tobacco, coal tars, benzene,
asbestos, some dyes.
(d) Alcohol and Diet

High alcohol intake increases the risk of some cancers. Diet high in fat and
containing burned or highly preserved meat.

8.11.2 The Effects of Mutations

The effects of mutations are:
(a) Not all are harmful;
(b) Survival advantage;
(c) Most common among bacteria and viruses but also seen in insects; and
(d) If there is no selective pressure, it may remain in population.
ACTIVITY 8.4
In your own words, explain where a mutation must occur to be inherited
and give a brief reason why. Explain why inherited mutations are
important in an evolutionary sense.
8.11.3 Harmful Mutations

Harmful mutations can be seen as:
(a) Cystic fibrosis and sickle cell anaemia;

(b) Dysfunctional proteins; and
(c) Albinism ă caused by mutation in gene of enzyme pathway of melanin.
8.11.4 Beneficial Mutations

Beneficial mutations include:
(a) Bacteria ă antibiotic resistance through mutation, transfer between bacterial

species;
(b) Superbugs such as methicillin resistant Staphylococcus (MRSA) have arisen
this way; and
(c) RNA viruses ă such as HIV ă mutate its protein coat so that the host human
is unable to make antibodies quick enough against it.

8.11.5 Neutral Mutations

Neutral mutations are:
(a) Neither harmful or beneficial to the organism but may be important in an

evolutionary sense;
(b) Silent mutations; and
(c) Virtually impossible to detect because no observable effect.
ACTIVITY 8.5
1. Define briefly what you understand about MRSA.
2. Give examples of albinism based on a few species.
8.12 INDUCTION OF MUTATION

An induction of mutation is a mutation that is produced by treatment with a
physical or chemical agent that affects the deoxyribonucleic acid 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. Example, 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.

8.12.1 Causes of Inductions

Induced mutations on the molecular level can be caused by:
(a) Chemicals
(i) Hydroxylamine NH2OH.
(ii) Base analogues (e.g. BrdU).
(iii) Alkylating agents (e.g. N-ethyl-nitrosourea) These 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.
(iv) Agents that form DNA adducts (e.g. ochratoxin metabolites).
(v) DNA intercalating agents (e.g. ethidium bromide).
(vi) DNA crosslinkers.
(vii) Oxidative damage.
(viii) 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.
(b) Radiation
Ultraviolet radiation (non-ionising radiation). Two nucleotide bases in DNA
ă cytosine and thymine ă 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.
Mutation rates also 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).

SELF-CHECK 8.3
Discuss and compare spontaneous and induced mutations.
 The endocrine system is a widespread group of glands and organs that acts as
the body's 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.
 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 endocrine function by a

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

alter the structure or sequence of DNA.

 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.
 Types of mutations are substitution, insertion, deletion and frame shift.
 Effects of mutation can be harmful, beneficial and neutral.
 Mutations which are artificially induced with the help of mutagenic agents
are called induced mutations.
Beneficial mutations Harmful mutations

Codon Induced mutations
Deletion Insertion
DNA Lipids or amino acids
Endocrine Mutagen
Endocrine disrupting chemicals Mutations
Estradiol Neutral mutations
Estriol Non-endocrine organ
Estrone Oestrogen
Frame shift Protein-coding
Genes RNA
Glands Substitution
Hormones

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Earth. Washington, DC: Environmental Information Coalition, National
Council for Science and the Environment. Retrieved from
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DC: Environmental Information Coalition, National Council for Science and
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professionals. Boston, MA: Pearson Education.
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Reviews in Toxicology, 16(2), 105-156.
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to exceptionality. Belmont, CA: Wadsworth/Thomson Learning.

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(1999). An introduction to genetic analysis (6th ed.). New York, NY: W. H.
Freeman.
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education. Boston, MA: Allyn and Bacon.
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World Health Organisation. (2012).

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Faculty of Science and Technology

Copyright © Open University Malaysia (OUM)

Copyright © Open University Malaysia (OUM)

Module Writers: Dr Ashima Srivastara

Moderator: Suhaila Abdul Hamid

Developed by: Centre for Instructional Design and Technology

First Edition, December 2012

Copyright © Open University Malaysia (OUM)

Topic 1 Introduction to Environmental and Occupational Toxicology 1

Topic 2 Environmental and Occupational Changes towards Health 27

Copyright © Open University Malaysia (OUM)

2.3 Chemical Usage 31

Topic 3 Occurrence of Toxicants 36

Copyright © Open University Malaysia (OUM)

Topic 4 Damage Process and Action of Toxicants 63

Topic 5 Toxic Action of Pollutants 73

Topic 6 Industrial Toxicants (PCBs, PBBs, Dioxin and Fluoride) 100

Copyright © Open University Malaysia (OUM)

6.4 Dioxins 106

Topic 7 Target Organs 112

Topic 8 Endocrine Disruption and Mutagenic Pollutants 139

Copyright © Open University Malaysia (OUM)

8.11 Effect of Mutagens 155

Copyright © Open University Malaysia (OUM)

Copyright © Open University Malaysia (OUM)

Copyright © Open University Malaysia (OUM)

COURSE GUIDE DESCRIPTION

As an open and distance learner, you should be acquainted with learning

Copyright © Open University Malaysia (OUM)

Table 1: Estimation of Time Accumulation of Study Hours

1. Explain environmental toxicology;

Topic 1 describes environmental toxicology, including a brief history, its scope,

Topic 2 describes the changing environment and disease pattern, epidemiological

Topic 4 explores the effects of toxicants on living organisms.

Copyright © Open University Malaysia (OUM)

Topic 6 discusses industrial toxicants such as Polychlorinated Biphenyls (PCBs),

Topic 8 discusses endocrine disruption and mutagenic pollutants. It explains the

TEXT ARRANGEMENT GUIDE

Self-Check: This component of the module is inserted at strategic locations

Activity: Like Self-Check, the Activity component is also placed at various

Copyright © Open University Malaysia (OUM)

yourself in higher order thinking where you might be required to analyse,

References: The References section is where a list of relevant and useful

Clean Air Partnership. (2006). Air pollutants. Retrieved from

Copyright © Open University Malaysia (OUM)

Emily, M. (2008). Absorption of toxicants. In C. J. Cleveland, Encyclopedia of

Emily, M. (2010). Toxicity. In C. J. Cleveland, Encyclopedia of Earth. Washington,

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

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

Fishbein, L. (1979). Potential industrial carcinogen and mutagens. Washington,

Friend, M. (2005). Special education: Contemporary perspectives for school

Gargiulo, R. (2003). Special education in contemporary society: An introduction

Hallahan, D., & Kauffman (2003). Exceptional children: Introduction to special

Hodgson, E. (2010). A textbook of modern toxicology. Hoboken, NJ: John Wiley

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

Copyright © Open University Malaysia (OUM)

Michael, J. P. (1973). Fluoride in the air. Retrieved from

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

Rose, R. L., & Hodgson, E. (2004). Chapter 7: Metabolism of toxicants. In E.

Scott, D. D. (2008). Toxicology principles for the industrial hygienist. American

Spencer, L. S. & Slabaugh, M. R. (2004). Chemistry for today: General, organic,

Copyright © Open University Malaysia (OUM)

TAN SRI DR ABDULLAH SANUSI (TSDAS) DIGITAL