Introduction and Basic Concepts of Toxicology
Introduction to toxicology
1. Three major fields of modern toxicology research:
- Descriptive toxicology
- Mechanism toxicology
- Management toxicology
The core
is toxicological safety evaluation and health risk assessment.
2. Modern Toxicology
The science that studies the damaging
effects and biological mechanisms of all exogenous harmful factors
(xenobiotics) on biological systems, and conducts safety evaluation and risk
assessment.
3. Hygiene Toxicology
The branch of toxicology directly
related to preventive medicine.
4. Descriptive toxicology
Through toxicology tests (toxicity
identification) and population observation studies, the toxicity and toxicity
characteristics of exogenous chemicals are found, and toxic and harmful
substances are identified. (Provide information for safety evaluation and risk
management, and provide clues for the toxic mechanism of chemicals)
5. Mechanistic toxicology
Clarify the mechanism of
interaction between exogenous chemicals and the body from the cellular and
molecular levels, including the initiation of toxic effects, mode and process
of action, and harmful outcome pathways. (Confirmation of harmful effects
observed in animal studies relevant to humans - organophosphorus, verification
of adverse effects in experimental animals that may not be relevant to humans -
saccharin, design and manufacture of safer chemicals and rational treatment of
chemical poisoning and Clinical Diseases - Thalassemia, further understanding
of basic medicine)
6. Management toxicology
According to the description and mechanism toxicology research data, carry out the safety evaluation and risk assessment of exogenous chemicals, assist the management department in scientific decision-making and management, and achieve the purpose of protecting human health.
(It is also necessary to formulate relevant health
standards based on the principles and methods of risk assessment, combined with
the scientific information provided by descriptive toxicology and mechanism toxicology
studies)
7. Signs of the rise of modern toxicology
Chemical analysis
and identification of poisons in tissues and body fluids; systematic
application of experimental animals.
8. Safety evaluation
According to the toxicological
requirements of regulations, the toxic effects of chemicals are tested. The
results of comprehensive toxicity tests illustrate the characteristics of toxic
effects of chemicals, and propose no observed harmful effects or toxic
threshold doses. Whether it is safe for human health under the following
conditions. Through in vivo and in vitro test methods, combined with population
exposure assessment, clarify the toxicity and potential hazards of the test
substance, and achieve the purpose of ensuring the health of the population.
9. Hazard/Risk Analysis
The process of controlling the
potential exposure of an organism, system or population to a hazard. Risk
analysis consists of risk assessment, risk management and risk communication
for the purpose of predicting and controlling risk.
10. Risk assessment/risk assessment
Including hazard identification, dose-response assessment (hazard characterization), exposure/exposure assessment and risk/risk characterization (including quantitative and qualitative risk and uncertainty).
Specific The process of
calculating or estimating the expected risk, including attendant uncertainties,
of a target organism or population exposed to a hazard, taking into account the
relevant factors, inherent characteristics and characteristics of the characteristic
target system.
1) Hazard identification
Identify the type and nature of the deleterious effects of factors that have the inherent capacity to cause an organism, system or (sub)population.
To determine the potential harmful effects of human exposure to chemicals, the likelihood, certainty and uncertainty of such harmful effects. Through SAR/QSAR analysis, in vivo/in vitro tests and population epidemiological surveys.
2) Hazard representation
Qualitatively/quantitatively describes the nature of a factor
or situation that has the ability to cause an adverse effect. Determining the
relationship between exposure levels of exogenous chemicals and the incidence
of adverse effects by dose-response assessment (causal or not)
3) Exposure assessment
Evaluate the evaluation of a factor/derivative thereof by an
organism, system or (sub)population.
4) Risk characterization
Qualitative/quantitative determination of the probability,
and the associated uncertainty, of known and potentially harmful effects of a
specified organism, system or (sub)population under specified conditions.
What is the Basic Concepts of Toxicology?
1. Exogenous chemicals xenobiotics
Some chemicals that exist
in the external environment, may come into contact with the body and enter the
body, and show certain biological effects in the body, which are the main
research objects of toxicology.
2. Poisons
Substances that can cause damage to the body at
low doses under certain conditions. All exogenous chemicals can be toxic,
depending on the dose and conditions of exposure.
3. Toxin
A very small amount of toxic substances produced by
organisms that can cause poisoning to humans and animals, often some
non-protein substances such as proteins or alkaloids that can interfere with
the biological effects of other macromolecules in organisms.
4. Toxicity
An inherent and inherent ability of a chemical
to cause harmful effects on the body under specific conditions, mainly
depending on its chemical structure and physicochemical properties. Generally, this refers to acute toxicity, expressed by the median lethal dose.
5. Selective toxicity
The differences in the toxicity of
chemicals among different species are manifested by different susceptibility of
individuals.
6. Accumulation toxicity/effect
When exogenous chemicals enter the body continuously and repeatedly, and the absorption rate/amount exceeds the rate/total amount of metabolic conversion and excretion, the chemical toxicants or their metabolites gradually increase and decrease in the body.
It is the basis for the subchronic and chronic toxic effects of
exogenous chemicals.
7. Substance accumulation
After repeated exposure, the
chemical analysis method can detect the presence of the compound or its
metabolites in the body or in some organs and tissues.
8. Functional/damage accumulation
As a result of the
accumulation of damage effects, after repeated exposure, although the body
cannot detect chemical poisons or metabolites, the body appears chronic
poisoning.
9. Repository depot
The accumulation site of exogenous
chemicals or their metabolites in the body. Not necessarily a target organ.
10. Toxicity/Effect
Under certain conditions, a chemical
causes harmful biological changes in the body. Altered conditions may affect toxic
effects. (Toxic effect spectrum manifestations—increased body load of exogenous
chemicals, physiological and biochemical changes of unknown significance,
subclinical changes, clinical poisoning, death)
11. Poisoning
A disease state that occurs after an organism
is poisoned by a functional or organic change.
12. Acute toxicity
The toxic effect that occurs in a short
period of time after one or more exposure to a chemical in a short period of
time.
13. Chronic toxicity
Long-term, or even life-long, exposure
to a small dose of chemicals slowly produces toxic effects.
14. Delayed toxicity
It does not cause obvious lesions at
the time of exposure to chemicals, or it can be temporarily recovered after
acute poisoning, but after a period of time, some obvious lesions or clinical
symptoms appear, such as organophosphorus pesticide poisoning. (Immediate - one
exposure, instant poisoning within a short period of time)
15. Long-term toxic effects remote toxicity
After a chemical
acts on the body or stops contact, after several years, a toxic effect
different from the pathological changes of poisoning occurs.
16. Local toxicity
The direct damage caused by exogenous
chemicals in the exposed parts of the body.
17. Systemic toxicity
After the poison is absorbed, it is
distributed to the target organs or the whole body with the blood circulation.
18. Reversible toxic effect
After stopping exposure to the
poison, the toxic effect can gradually subside.
19. Irreversible toxic effects
After stopping exposure to
the poison, the toxic effects continue to exist, and even the damage can be
further developed. Often caused by high doses, prolonged exposure.
20. General toxicity
Chemical substances may have some toxic
effects within a certain dose range after a certain exposure time and according
to a certain exposure method.
21. Special specific toxicity
After exposure to chemical
substances, it will cause toxic effects that are different from the general
rules of toxic effects or have special pathological changes.
22. Adverse effect
Biochemical changes, functional disorders
or pathological damage that affect the behavior of the body, or the reduction
of the ability to respond to external environmental stress, or the decline of
the body's compensatory ability, or the abnormal susceptibility of the body to
other harmful environmental factors Wait.
23. Non-damaging effects
The biological changes caused by
exogenous chemicals to the body are reversible, and within the range of the
body's ability to adapt and compensate, the body's susceptibility to other
external adverse factors does not increase accordingly.
24. Adverse reactions
Adverse reactions that occur when
normal doses of drugs are used to prevent, diagnose, treat diseases or regulate
physiological functions of the body and are not related to the purpose of the
drug. Drug side effects are the most common adverse drug reactions.
25. Biological marker
After the exogenous chemical passes
through the biological barrier and enters the tissue or body fluid, the
detection index of the exogenous chemical or biological consequence.
i) Exposure biomarkers
Measure the absorption of exogenous
chemicals, their metabolites, or reaction products with endogenous substances
in tissues, body fluids, or excreta, as indicators of absorbed dose or target
dose, providing information on exposure to external sources. Information on
source chemicals - assessing exposure levels
ii) Biomarkers of effect
Indicators of measurable biochemical,
physiological, behavioral, or other changes in the body that suggest
information about adverse health effects associated with different target doses
of exogenous chemicals or their metabolites, evaluating the effects of
exogenous chemicals on human health.
iii) Biological markers of susceptibility
Indicators that
reflect the innate or acquired ability of the body to respond to exposure to
exogenous substances - screening of susceptible people
26. Dose
An important factor that determines the damage
effect of exogenous chemicals on the body. Sub-exposure/external dose,
absorbed/internal dose, applied dose, delivered dose, biologically
effective/target dose (the part of the delivered dose that reaches the site of
toxic effects)
27. Dose-response/effect relationship
The interrelationship
between the dose of an exogenous chemical acting on an organism and the
incidence or intensity of the resulting biological change. Dose-response
(applies to free systems and individuals), dose-response (applies to
populations).
28. Toxicological significance of dose-response relationship (application value)
- This helps to discover the properties of toxic effects of chemicals
- The obtained relevant parameters can be used to compare the toxicity of different chemicals
- Helps to determine the distribution of susceptibility in the body
- It is an important basis for judging that there is a causal relationship between a chemical and a certain damage to the body
- It is an important content of safety evaluation and risk evaluation
29. Potency
The difference in dose for equal effects.
30. Efficacy
The difference in effect, expressed as the
maximum effect (Emax), depends on the intrinsic activity and toxicity
characteristics of the chemical itself.
31. Toxic low-dose hormesis
Exposure of an organism to a
low-dose detrimental factor does not produce a detrimental effect (appropriate
stimulatory response-beneficial), but produces a protective effect (inhibitory
effect) on subsequent high-dose exposure to the same type of detrimental
factor.
32. LD50
The dose that causes half of the deaths in a group
of experimental animals. (the smaller the more toxic)
33. Maximum no-effect dose (NOAEL)
Exogenous chemicals are
exposed to the body in a certain way and within a certain period of time. With
the existing detection methods and the most sensitive observation indicators,
no damage can be found. highest dose.
34. LOAEL
The lowest dose/concentration at which a substance
causes an adverse effect in the body under specified exposure conditions.
35. Threshold dose
The minimum dose (= minimum effective
dose, between NOAEL-LOAEL) required for exogenous chemicals to start the effect
of the contact object (with threshold: general toxicity, teratogenic effect; no
threshold: carcinogenic , mutagenic)
36. Safety limit
Long-term exposure below the safety limit,
based on current knowledge, no direct or indirect harmful effects/health
hazards will occur. Safety Limit = NOAEL/Uncertainty Factor or Safety Factor.
(tolerable daily intake, reference dose, reference concentration, maximum
allowable concentration)
37. Comparative dose-response relationship
Acute toxicity
zone Zac (ratio of LD50 to acute threshold dose), chronic toxicity zone Zch
(ratio of acute to chronic threshold dose)
38. Therapeutic index
Therapeutic index(TI) = LD50/ED50, safety margin (MOS) = LD01/ED99, exposure range (MOE) = NOAEL/population exposure.
Name: Gwynneth May
Educational Qualification: MBBS, MD (Medicine) Gold Medalist
Profession: Doctor
Experience: 16 Years of Work Experience as a Medical Practitioner
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