Fundamentals of Toxicology

The Ministry of Science and Higher Education of the Russian Federation 
Kazan National Research Technological University 
S. Garmonov, L. Nugbienyo
FUNDAMENTALS OF TOXICOLOGY
Tutorial 
Kazan 
KNRTU Press 
2023 

UDC 615.9(075) 
Published by the decision of the Editorial Review Board  
of the Kazan National Research Technological University 
Reviewers: 
PhD., Professor G. Budnikov 
PhD., Professor S. Egorova 
Garmonov S. 
Fundamentals of Toxicology : Tutorial / S. Garmonov, L. Nugbienyo; 
The Ministry of Education and Science of the Russian Federation, Kazan 
National Research Technological University. – Kazan : KNRTU Press, 
2023. – 96 p. 
ISBN 978-5-7882-3418-2 
This tutorial describes the properties of toxic chemical compounds, as well as 
the characteristics of the process of intoxication by these compounds. It explores toxicometric and toxicokinetic parameters of mechanisms of toxic activity of chemical substances. Substantial focus is placed on the stages of poisoning, the use of antidotes, and 
the problems of ecotoxicology. 
This is a teaching and learning resource for undergraduate and postgraduate students of pharmaceutical, ecological and food sciences. 
Developed at the Department of Analytical Chemistry, Certification and Quality 
Management. 
UDC 615.9(075) 
ISBN 978-5-7882-3418-2 
© S. Garmonov, L. Nugbienyo, 2023 
© Kazan National Research Technological 
University, 2023 
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C O N T E N T S
Introduction ............................................................................................................ 5 
List of abbreviations 
............................................................................................... 7 
1. TOXIC PROPERTIES OF CHEMICAL SUBSTANCES 
................................ 9 
1.1. Concepts of toxicity 
...................................................................................... 9 
1.2. Characteristics of toxicity 
........................................................................... 14 
1.3. Toxicity of nanomolecules ......................................................................... 19 
Questions & Assignments ................................................................................. 24 
2. TOXICOMETRY 
............................................................................................. 25 
2.1. Toxicometric parameters 
............................................................................ 25 
2.2. Regulation of toxicants in environmental samples .................................... 28 
2.3. Dose-effect relationships 
............................................................................ 31 
2.4. Characteristics of combined and complex toxic effects............................. 35 
Questions & Assignments ................................................................................. 38 
3. TOXICOKINETICS ........................................................................................ 40 
3.1. Interaction of toxicants  with biological systems 
....................................... 40 
3.2. Transport of toxicants across biomembranes 
............................................. 41 
3.3. Toxicokinetic processes ............................................................................. 45 
3.4. Quantitative characteristics of toxicokinetics ............................................ 48 
3.5. Biotransformation and excretion of xenobiotics ........................................ 50 
3.6. Individual toxicological reactions .............................................................. 64 
Questions & Assignments ................................................................................. 70 
4. POISONING AND ITS TREATMENT .......................................................... 72 
4.1. Stages of poisoning .................................................................................... 72 
4.2. Antidotes 
..................................................................................................... 76 
Questions & Assignments ................................................................................. 79 
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5. ECOTOXICOLOGY ....................................................................................... 80 
5.1. Environmental xenobiotic profile 
............................................................... 80 
5.2. Ecotoxicokinetics ....................................................................................... 82 
5.3. Ecotoxicodynamics .................................................................................... 88 
Questions & Assignments ................................................................................. 92 
CONCLUSION .................................................................................................... 93 
LITERATURE ..................................................................................................... 94 
4 

 
I N T R O D U C T I O N  
 
The human organism and its environment consists of many chemical 
compounds and elements. The life of all living things on our planet is accompanied by the movement and transformation of chemical substances. From 
an ecological point of view, the localization and transformation of various 
forms of compounds require the maintenance of definite equilibrium between 
components of the environment. The accidental, unintentional or anthropogenic disruption of this can cause serious disturbances not only to the life of 
the human organism but also to the functioning of natural objects and systems. 
The influence of various substances on living organisms has a history of 
more than a thousand years. Legends have existed for centuries about people’s 
encounters with poisonous plants and animals in religious cults, the use of poisons for hunting, as well as for military purposes, among others. Hippocrates 
(about 460–377 BC), Galen (about 130–200), Paracelsus (1493–1541), Ramazzini (1633–1714) had carried out studies on the harmful effects of substances 
on the human organism. 
In the eighteenth and nineteenth centuries, developments in chemistry 
gave a new impetus to studies of toxins, which by that time had lost their 
mystical attribution. These studies, thus, began to be based on the knowledge 
of properties and structure of chemical substances. The problem of the impact of chemical substances on living organisms became particularly significant, following the scientific, technological and industrial revolution of 
the twentieth century. Currently, scientific and economic activities have led 
to the impact on the human organism and the environment of millions of 
chemical substances, many of which were previously unfamiliar in our biosphere. 
The history of toxic substances is inextricably linked with the history 
of development of human societies. Toxins were used as a “tool” and weapon 
for hunting wild animals, as well as to exterminate opponents, competitors, 
or enemies. With the development of chemical science and technology, toxins have become a formidable weapon of mass destruction in chemical warfare. The development, production and use of chemical compounds also pursue purely peaceful goals: chemical technology of medicinal substances, production of energy, fertilizers, food additives, fuel, and polymeric materials. 
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Chemical pollution is a fundamental harmful effect of economic activity on humans and the environment. In general, factors that impact ecosystems and living organisms can be divided into three groups: physical (mechanical, thermal, noise, radiation), biological (microorganisms and their 
metabolic wastes), and chemical (various chemical compounds). 
Toxicology (from Greek toxicon – poison, logos – study) is the science 
of potential hazards and harmful effects of substances on living organisms 
and ecosystems. It also studies mechanisms of toxic activity of substances, 
diagnosis, prevention and treatment of intoxication. The subject can be divided into the following areas: 
Experimental and theoretical toxicology studies the basic principles of 
interaction of substances with biological systems.  
Preventive toxicology deals with the prevention of potential hazards 
and harmful effects of substances on living organisms and ecosystems. 
Clinical toxicology explores diseases that arise from exposure to chemical substances. 
Industrial toxicology is of particular importance to the study of the impact of harmful chemical substances in industrial environments. It also explores the development of sanitary, preventive and treatment standards aimed 
at creating optimal conditions in working environments. 
Ecological toxicology studies the effect of chemical substances on living organisms, populations, and ecosystems. In this regard, emphasis is laid 
not on individual organisms, but on their associations; that is, biocenosis and 
ecosystems, as well as the transformation of chemical substances in the environment. 
Chemical pollution of the environment, in many respects, has become 
a determining factor in the development of humanity. Meanwhile, attention 
to the problem of the level of training of chemists and chemical technologists 
of various specialties of universities is clearly insufficient. And this is in a situation, where chemistry is already firmly integrated into the complex of life 
sciences. 
Authored by specialists in pharmaceutical and toxicological chemistry, 
chemical safety, Prof. Garmonov S. Yu., PhD. Chemical Sciences (Kazan 
National Research Technological University, Russia) and Nugbienyo L., 
PhD. Chemical Sciences (Accra Technical University, Ghana). 
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L I S T  O F  A B B R E V I A T I O N S
ААТ – arylamine acetyltransferase 
ACE – angiotensin I converting enzyme 
AchE – acetylcholinesterase 
ADH – alcohol dehydrogenase 
ADI – acceptable daily intake 
ApoE – apolipoprotein E 
CC16 – club cell secretory protein  
CCR-5 – C-C chemokine receptor 
CNS – central nervous system 
DNA – deoxyribonucleic acid 
G6PD – glucose-6-phosphate dehydrogenase 
GSTM1 – glutathione S-transferase mu 1 
ATP – adenosine triphosphate 
ATPase – adenosine triphosphatase 
DDT – dichloro-diphenyl-trichloroethane 
AWI – acceptable weekly intake 
MGM – molecular genetic methods 
MPC – maximum permissible concentration 
MPCavd – average daily MPC 
MPCf – MPC for food 
MPCind – industrial MPC 
MPCrand – random or one-time 
MPCs – MPC for soil 
MPCw – MPC for water 
MPCwf – MPC for fishery 
mEPHX – microsomal epoxide hydrolase enzyme 
MTHFR – methylenetetrahydrofolate reductase 
PAH – polycyclic aromatic hydrocarbon 
PCB – polychlorinated biphenyl 
TEOA – Triethanolamine 
TLV – threshold limit value 
LC50 – median lethal concentration 
LD50 – median lethal dose 
LD100 – absolute lethal dose 
LD0-10 – minimal lethal dose 
MO – microsomal oxidase 
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NAT – N-acetyltransferase 
TCDD – 2,3,7,8-tetrachlorodibenzo-p-dioxin 
Zac – zone of acute toxic effect 
Zch – zone of chronic toxic effect 
Zbef – zone of biological effect 
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.  T O X I C  P R O P E R T I E S  O F  C H E M I C A L
S U B S T A N C E S  
1 . 1 .  C o n c e p t s  o f  t o x i c i t y
Out of the huge number of chemical compounds that are currently 
known, most of them, under particular instances, can cause serious harm not 
only to human health but also to other living organisms. The contact of living 
systems with chemical substances can have detrimental effects due to their 
property of toxicity. The ability of a substance to be toxic or useful to life is 
determined by its concentration and conditions of interaction with an organism (Fig. 1.1). 
Fig. 1.1. Effect of exposure of living systems to chemical substances 
Toxicity is a property of chemical compounds that can cause damage 
or death to biological or living systems, and particularly to humans – disease or death. In fact, toxicity is a measure of incompatibility of a substance with life. Chemical safety protocols are established based on 
the toxic properties of substances, inherent in almost all compounds of 
both natural and anthropogenic origins. The risk of a substance is a fairly 
broad concept that characterizes the likelihood of harmful effects of a substance in real conditions of production, as well as application. Thus, the 
risk of substances cannot be characterized by a quantity for all instances, 
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but is dependent on a number of parameters. Toxicity of substances is significantly of varying degrees. The smaller the amount of a substance is 
capable of causing injury to systems or a whole organism, the more toxic 
it is. Comparative characteristics of toxicity of some substances are presented in Table 1.1.  
Probably, there are no substances devoid of toxic impacts. Under one 
condition or the other, the impact of a substance on a living organism is detected at definite doses, characterized by impairment of its functions. 
For most substances, there are zones of negative effects at both high and low 
concentrations. For example, chromium compounds, present in some biogeochemical anomalies or released into the environment in industrial and domestic waste-waters, pose hazards to living organisms. At the same time, 
chromium is a biologically active element that is involved in the metabolism 
of nucleic acids and serves as a co-factor to some enzymes. The average daily 
physiological requirement of chromium for adults is 150 to 200 μg. The lack 
of chromium contributes to growth inhibition, reduction in life expectancy, 
corneal damage (which can result in visual impairment), as well as abnormalities in glucose and protein metabolism. Replaceable substances may not 
have any zone of negative effects at low doses, and the lack of them can be 
compensated for by alternative substances. 
 
                                                                                                        Table 1.1 
Toxicity of some chemical substances (median lethal dose for mice) 
Chemical substance 
Source 
Toxicity (LD50), µgkg-1 
0.0003 
0.001 
2 
2 
3 
8 
9 
10 
14 
200 
500 
8600 
10000 
90000 
Botulinum toxin 
Tetanotoxin 
Batrachotoxin 
Taipoxin 
Ricin 
Tetrodotoxin 
Saxitoxin 
Latrotoxin 
Bungarotoxin 
Dioxin 
Coumarin 
Mustard gas 
Sodium cyanide 
Atropine 
Methanol 
Bacteria 
Bacteria 
Amphibians 
Snakes 
Plants 
Fishes 
Protozoa 
Spiders 
Snakes 
Synthetic 
Plants 
Synthetic 
Synthetic 
Plants 
Synthetic 
1000000 
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