Добавил:
ivanov666
Опубликованный материал нарушает ваши авторские права? Сообщите нам.
Вуз:
Предмет:
Файл:Fundamentals of Toxicology. Tutorial
.pdf
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
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
ISBN 978-5-7882-3418-2
©
S. Garmonov, L. Nugbienyo, 2023
©
Kazan National Research Technological
University, 2023
UDC 615.9(075)
of the Kazan National Research Technological University
Reviewers:
PhD., Professor G. Budnikov
PhD., Professor S. Egorova
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.
2
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
3
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 5
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.
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).
6
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
MPC
– average daily MPC
avd
MPCf – MPC for food
MPC
MPC
– industrial MPC
ind
– random or one-time
rand
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
LD
LD
– absolute lethal dose
100
– minimal lethal dose
0-10
MO – microsomal oxidase
7
NAT – N-acetyltransferase
TCDD – 2,3,7,8-tetrachlorodibenzo-p-dioxin
Zac – zone of acute toxic effect
Zch – zone of chronic toxic effect
Z
– zone of biological effect
bef
8
1 . 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,
9
10
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
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
0.0003
0.001
2
2
3
8
9
10
14
200
500
8600
10000
90000
1000000
Соседние файлы в предмете [НЕСОРТИРОВАННОЕ]