Summary: General Toxicology

Read the summary and the most important questions on General Toxicology

• T2: Mechanisms

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• How does the structured approach of studying toxicity looks like?

  They look at the toxicant and the molecular interaction (MIE), then the key events are to look at the cellular response, the organ, and the organ systems. Then for adverse outcome they look further to organism and even population.

• What is the first step in studying the toxicant?

  Looking at the properties of the chemicals. It can directly be toxic or only with metabolic activation.
  
  Some metals are directly toxic, or strong acids/bases, nicotine and CO are also direct toxic.
  
  The most chemicals must be activated first.
  There can also be reactive metabolites be formed during biotransformation processes. This can happen because of insertion of electrons, or very reactive groups.

• What are the ways a toxicant can interact with a target molecule? (4)

  1) Non covalent binding 
       a. Structural similarity with natural ligand: competition for physiological receptor
       b. No structural similarity natural ligand
  2) Covalent binding: reactions with macromolecules
  3) Reactive oxygen species (hydrogen abstraction)
  4) Electron transfer.

• Non covalent binding (a, structural similarity with natural ligand)

  The toxicant can bind to a receptor and therefore work as an agonist, which stimulates signal transduction ect. Or it can work as a antagonist, which blocks the signals. This binding is in compatition with the natural ligand and this process will be prohibited.

• Non covalent binding (b, no structural similarity with natural ligand)

  Here the toxicant does not have any similarities with the natural ligand and therefore it can not bind. But it can block, which reduces the permability activation. Or it can modulate the process and this increases the permeability activity.

• Indicate what is true about mechanisms of toxicity

  
  -inhibition of oxygen binding to hemoglobin by CO is an example of non covalent binding causing toxicity
  -Lipid peroxidation is can be caused by reactive oxygen species (ROS)
  -Methemoglobinemia is caused by chemicals that cause electron transfer that oxidizes the Fe in hemoglobin from Fe2+ to Fe3+

• What is the main different between non covalent and covalent binding?

  Covalent binding is permanent binding to the molecule, non covalent is temporary.

• Which chemicals act by non-covalent interactions?

  Tetrodoxin and saxitoxin

• T1: Introduction. history, principles

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• Phase 2: Agriculture development

  They were cooking the food and this allowed them to cultivate new plants containing natural toxics. Through cooking they became save.
  Also they started storing and transporting the foods, this introduced new toxics like moulds (mycotoxins).

• Phase 3: Industrial development

  The distance between food sources and consumers increased so they developed new methods sush as canning. Also chamicals were added for preservation or coloring.
  There were also legal steps for guarantee food quality (end 19th century).