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Introduction, Basic Concepts of Toxicology

  

Introduction and Basic Concepts of Toxicology

 

Introduction to toxicology

1. Three major fields of modern toxicology research: 

  1. Descriptive toxicology
  2. Mechanism toxicology
  3. 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.

Concepts of Toxicology


 

What is the Basic Concepts of Toxicology?

The concept of toxicology can be understood by the following:

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)

  1. This helps to discover the properties of toxic effects of chemicals 
  2. The obtained relevant parameters can be used to compare the toxicity of different chemicals 
  3. Helps to determine the distribution of susceptibility in the body 
  4. It is an important basis for judging that there is a causal relationship between a chemical and a certain damage to the body 
  5. 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.


About Me 


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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