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Modern Toxicology and Research Methods

Modern toxicology is the study of various (chemical, physical, biological) harmful factors in human production and life practice from the perspective of modern medicine. science. It is not only a basic discipline of modern medicine, but also an applied discipline closely related to economic construction, people’s life and ecological environment protection. It will play a pivotal role in safeguarding human health, maintaining the balance of the ecological environment and promoting sustainable economic development in the 21st century.

The Formation and Characteristics of Modern Toxicology

The 20th century was a period of great development of toxicology, and also an era of stubbornness and rapid development of life sciences. It can be said that the development of modern toxicology and the development of life science are carried out simultaneously, and the new theories and new technologies of life science have promoted the rapid development of modern toxicology.
The discovery of the double helix structure of DNA in 1953 revealed the mystery of life. The deciphering of the genetic code, the establishment of the central dogma of genetic information transmission, the establishment of recombinant DNA technology, etc., promote the concept and technology of molecular biology to fully penetrate into all fields of life science, and also penetrate into modern toxicology, so in the concave After the 1940s, branches of modern toxicology have sprung up and developed vigorously.
The formation and development of modern toxicology is based on the modern toxicology, and after more than 100 years of development, the modern toxicology with strong application and marginality has been perfected.

The Characteristics of Multidisciplinary Interdisciplinary Development in the Post-India Age in the 20th Century

(1) Industrial toxicology, environmental toxicology, food toxicology, military toxicology, drug toxicology, clinical toxicology, forensic toxicology, analytical toxicology, veterinary toxicology, feed toxicology, management toxicology , Insect toxicology, animal toxicology, plant toxicology, radiotoxicology, toxicology history toxicology.
(2) Classification by target organ Liver toxicology, renal toxicology, lung toxicology, blood toxicology, ocular toxicology, neurological and psychotoxicology, behavioral toxicology, immunotoxicology, reproductive and developmental toxicology, skin toxicologyc
(3) Classification by mechanism research Biochemical toxicology, molecular toxicology, membrane toxicology, cytotoxicology, genetic toxicology, receptor toxicology, quantum toxicology.
(4) Classification by chemical substances Metal toxicology, pesticide toxicology, organic solvent toxicology, macromolecular compound toxicology, material toxicology.
The above-mentioned numerous sub-disciplines of toxicology not only form an intersection within the field of toxicology, but also intersect with related disciplines in the field of life sciences, which expands the scope of toxicology research. It can be expected that new sub-disciplines will emerge in the future.

Research methods

The research method of modern toxicology, because it includes many sub-disciplines, has established its own research method in the corresponding discipline field, and is now classified into two categories.

Experimental Research (Microscopic Research)

The method of animal experiments is still one of the important methods of modern toxicology experiments. Traditional toxicology has provided humans with a large number of dose-response (response)-based databases through overall animal experiments. Substances were evaluated for safety (risk level). Due to the huge amount of exogenous substances, the overall animal experiment consumes a lot of time and funds, and it cannot meet the toxicity evaluation requirements of tens of thousands of exogenous chemical substances. On the other hand, in order to protect animals and minimize the use of animals, so From the past dominated by the concept of overall animal testing, to the trend of in vitro testing. However, it should also be pointed out that the development of in vitro experiments does not exclude the importance of the overall experiment. The two complement each other and verify each other in order to provide reliable data for scientific research. With the development of life science, the theory and technology of molecular biology have been introduced. Modern toxicology has come to establish many new methods at the molecular level.

1. In vivo test

Mammalian in vivo test, also known as whole animal test, generally includes: acute toxicity test, subacute toxicity test, subchronic toxicity test and chronic toxicity test. There are also special toxicity tests, such as mammalian mutagenicity tests, teratogenicity tests, and carcinogenicity tests. The above tests are collectively referred to as “three properties” and “three coherence” tests in toxicology.
Commonly used experimental animals: rats, mice, guinea pigs, hamsters, rabbits, dogs, monkeys, etc. Toxic tests to detect environmental pollutants, fish, fleas or other aquatic organisms are often used. Tests can also be performed on birds and insects.
In order to explore the mutagenic and carcinogenic mechanisms at the molecular level, transgenic animals have been used in toxicology experiments. Transgenic animal is an experimental animal that integrates the overall level, the cellular level and the molecular level, which can better reflect the effect of the overall study of life. It combines classical and modern toxicology research methods, which will undoubtedly promote modern toxicology. Development of experimental research.

2. In vitro test

The use of free organs, cultured cells, organelles, and microorganisms for toxicity studies are in vitro tests. This method is mostly used to observe the preliminary screening of the specific toxicity of exogenous substances to organisms, as well as the in-depth study of the mechanism of action and the metabolic transformation process.
Both in vivo and in vitro experiments have their own advantages and limitations, and a group of experiments should be selected according to the purpose and requirements of the experiment to make up for each other’s advantages and disadvantages.

Population surveys (macro studies)

Population survey, also known as population toxicology, is to study the rules of the toxic effects of exogenous substances on the human body in the population, and to provide more direct and reliable toxicological data for population detection and formulation of preventive measures than animal tests, mainly including the following 3 aspect:

1. Clinical observation of poisoning

Common in accidental accidents, such as accidental ingestion, suicide, toxic disasters, etc., through the treatment and treatment of acute poisoning accidents, the symptoms of poisoning can be directly observed and the target organs of possible toxic effects can be analyzed.

2. volunteer trial

Under the principle of not harming human health, some controlled experiments that do not harm human health can sometimes be designed, which are limited to low-dose, short-term exposure to chemicals with reversible toxic effects. The uncertainty of the extrapolation of animal test results, especially the toxic effects of some neurotoxicants, such as dizziness, dizziness, diplopia and other poisoning symptoms that need to be expressed, can only be truly reflected by humans. Toxicological research data has received much attention.

3. Epidemiological Investigation

The results of animal experiments are further verified in the population survey, and data that cannot be obtained from animal experiments can be obtained from the direct observation of the population. The advantage is that the contact conditions are real, and the observation object is a large group. Provide more direct and reliable scientific data than animal experiments, but there are also many difficulties:
① Most of the toxic effects of exogenous substances observed in the population are chronic toxic effects, especially the carcinogenic effects of human carcinogens take too long;
② The observation indicators used in the exposed population are non-specific, and a sufficient number of cases is required to compare with the control population:
③ The external environmental factors are mixed, there are many kinds of exogenous substances and a variety of chemical substances can have a joint effect, so it is difficult to determine the toxic effect of a specific chemical substance and its causal relationship. Due to the development and penetration of molecular biology, population detection methods at the cellular and molecular levels have been introduced in traditional epidemiological investigation methods, such as biomarkers as information for early diagnosis of cancer, and the combination of molecular biology and epidemiology is One development is molecular epidemiology. This emerging discipline uses molecular biology, molecular genetics, biochemistry, immunology and other means of research to evaluate the carcinogenic risk and its mechanism of different populations or individuals, so that modern toxicology develops from experimental animal research to population and individual susceptibility A new phase of research. It can answer a series of continuous changes in the process of the human body from exposure to chemical substances to the occurrence of diseases, extract more information on precancerous lesions, and provide a scientific basis for early diagnosis and early prevention of cancer. It can be predicted that molecular epidemiology will be further developed in the 21st century.
To sum up, the correct method is to organically combine macroscopic research with microscopic research. Macroscopic research provides clues for microscopic research, and microscopic research provides basis for macroscopic research. The combination of the two can accurately determine the risk of exogenous chemical substances. Evaluation.

AxisPharm is a San Diego based bioanalytical LC/MS/MS service provider with more than 25 years experience in the field. Our bioanalytical chemistry department specializes in developing and validating robust bioanalytical methods for PK/TK sample analysis of small molecules, proteins, peptides, and metabolites using LCMS/MS (HPLC, UPLC, on-line SPE), HPLC/UV, and HPLC/FL. We have experience analyzing API and metabolites in various biological matrices and can provide bioanalytical support throughout all the stages of drug development.

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