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Principles of Toxicology

1) Some theorists argue that there may be no clear threshold for effects such as carcinogenesis & mutation. What arguments do you think they might put forward in support of this?

2) It is important to understand the physiological means by which toxic agents cross cellular membranes & enter the cells of human body. Define & describe both passive & active transport?

3) Definition of toxicology?

4) What do you understand by the term dose? How can you estimate it?

5) What do you understand by the term effect? How is it measured?

6) Using examples distinguish between local and systemic and acute and chronic effects?

7) What do you understand by the term dose - effect and dose - response relations?

8) What is the impact on this relationship if there is more than one effect of a chemical?

9) What do you understand by the term 'threshold of effect'?

10) Define the terms toxico - kinetics and toxico - dynamics?

11) What factors influence chemical:

- Absorption
- Distribution and deposition
- Biotransformation
- Accumulation and elimination?

12) What do you understand by the term biological half time?

13) What is the significance, when setting threshold for adverse effects, of the fact that, broadly speaking, solid particulates have much longer biological half times than gases and vapours?

14) Briefly, what is the major underlying difference in body handling of a chemical between one and two compartment models of distribution and elimination?

15) Outline some general mechanisms of toxicity?

16) Describe a range of short and long-term toxicity testing methods?

17) Discuss the limitations of animal testing methods in the evaluation of human toxic potential of chemicals?

18) Outline a strategy for testing for carcinogenicity of industrial chemicals

Solution Preview

1) Some theorists argue that there may be no clear threshold for effects such as carcinogenesis & mutation. What arguments do you think they might put forward in support of this?

Yes, this is true that there may be no clear threshold between carcinogenesis and mutation because the accumulation of mutation can lead to carcinogenesis or the development of cancer. Carcinogenesis is defined as the process when normal cells are transformed into cancerous cells. (1) This transformation is characterized by a change in cellular, genetic and epigenetic level that reprogram the cell to undergo uncontrolled cell division. (1) This change in the normal cell to a cancer cell is caused by mutations. (1) In fact, carcinogenesis "is caused by mutation of the genetic material of normal cells". This mutation cause a change in the normal balance between proliferation and cell death. The mutation cause uncontrolled cell division and cancer. In order for carcinogenesis to occur, more than one mutations are necessary. There is a series of mutations on a normal cell in order to cause the normal cell to transform into cancer cell. (1) "Mutation is the hallmark of cancer" and is fundamental to how cancers evolve. (2)

2) It is important to understand the physiological means by which toxic agents cross cellular membranes & enter the cells of human body. Define & describe both passive & active transport?

Difference between passive transport and active transport

Passive transport always operates from a regions of higher concentrations to regions of lower concentration.
It involves carriers, channels, or direct diffusion through a membrane. There is no external source of energy that is required.
Three type of passive transport are simple diffusion, channel diffusion, and facilitated diffusion. Examples are below:

Reference: http://biology.kenyon.edu/HHMI/Biol113/passive_vs_active.htm

Active transport is the transport that go against the concentration gradient. In active transport, a source of energy is required to move the carrier and its materials against the concentration gradient. This source of energy is called ATP. An example of primary active transport is the sodium potassium pump. (3)

Example are below:

Reference: http://biology.kenyon.edu/HHMI/Biol113/passive_vs_active.htm

3) Definition of toxicology?

Toxicology is defined as "the study of the adverse effects of chemicals on living organisms and symptoms, mechanisms, treatments, and detection of poisoning in human. (4) One key factor regarding toxicity of a chemical is the dose; the amount of exposure to the substance. (4)

4) What do you understand by the term dose? How can you estimate it?

The term dose is the main criterion regarding the toxicity of a chemical. The dose is the amount of exposure to the substance. To measure the dose, the term LD50 refers to the dose of a toxic substance that kills over 50 percent of a sample population. You can only measure it by looking at its LD50 level; that is when 50 percent of a sample population is killed. The dose is really the amount of poison that a body received. You can also measured dose by observing the response because there is always a dose below which no response occurs and a maximum response in which further dose will not increase the response.

5) What do you understand by the term effect? How is it measured?

The dose response relationship is a example of the dose and the effect that result from the dose. Toxicology is the study of the relationship between a toxic reaction ( the effect) and the dose. In fact, the amount of dose will determine the degree of effect it produces. Let take alcohol as the poison being studied. The individual sensitivity to alcohol varies. If you drink 2 bottle of beer, you may get drunk. But your friend may needs 5 ...

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