Summary: Toxicology For Food Hazards

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• 1 Introduction to toxicology, history and principles, mode of action of chemicals

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• What are the different uses of toxins in history?

  1. Phase 1 Hunting, fishing, gathering
  2. Phase 2 Agricultural development
  3. Phase 3 Industrial development 

• What is the contribution of Paracelsus to toxicology?

  the father of toxicology
  the beginning of the dose response relationship
  Living from 1493 to 1541
  Swiss alchemist
  He gave the notion of dose 
  “alle ding’ sind Gift und nichts ohn’ Gift; allein die Dosis macht, dass ein Ding kein Gift ist”
  “All things are poison and nothing without poison; only the dose makes that a thing is not a poison”

• What is the contribution of Percivell Pott to toxicology?

  - 1775      english Dr
  - first discovery of occupational hazard
  - Chimney sweeps and scrotal cancer
  - Exposure to soot
  - now we know it is bc it Contains PAH (polycyclic aromatic hydrocarbons)

• What stimulated the field of toxicology in the 20th C?

  Industrial revolution and WW2- Alarm phase
  - Many pesticides
  - War gasses, munition
  - Drugs
  - Industrial chemicals
  - Synthetic fibers
  - DDT banned for environemental reasons,
  - silent spring by Rachel Carson
  - Thalidomide (Softenon), 
  - Dioxins- war gas Agent Orange (TCDD) - effects in Vietnam on children due to high concentrations

• What are the main chemical classes?

  
  

  1. ●        polycyclic aromatic hydrocarbons (PAHs),
  2. ●        dioxins,
  3. ●        persistent organic pollutants (POPs).

• What did Rachel Carson do?

  She wrote a book ‘Silent spring’ raising awareness on the effects of chemicals. This then set in motion regulations on chemicals and toxicology to study adverse effects before allowing them on the market to prevent disasters.

• What is the importance of the Softenon (thalidomide) events? What were these events?

  Famous case as sleeping drug for pregnant women
  
  Was tested on animals and no adverse effect
  Off spring of the women had strong malformations for unborn and sever effects for surviving children
  The one animal tested was not as sensitive as humans to the chemical effects
  Result:
  Strict guidelines for safety testing animals- should identify the most sensitive species and several animals

• 3 Absorption, distribution and excretion of chemicals

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• How can common mechanisms of toxic action can be defined?

  Interaction between physico chemical properties and how these effect the interaction of molecules.
  Direct Some molecules are directly toxic and are able to directly
  Indirect Some need activation, some processes in our body to protect ourselves from exposure to change the chemicals to then excrete them, but sometimes this activates chemicals through metabolic bioactivation.
  This then is the ultimate toxicant
  Different reactions can take place between the ultimate toxicant and the target molecule.
  
  Most metals are directly toxic, does not need to be activated to be toxic e.g. nicotine, cleaning…

• What are the different type of interactions of toxicants with target molecules?

  1. Noncovalent binding – reversable, the interaction with molecules is temporary and the effect can fade away bc the chemicals can move away from the bond
  a. Structural similarity with ligand (bind to the receptor)
  i. Agonist- stimulate the receptor
  ii. Antagonist- blocks
  b. No structural similarity with ligand
  i. Blocker
  ii. modulator
  2. Covalent binding: irreversible, only way to get rid is to get rid of the DNA molecule or protein, persitant effect
  a.  Rna, protein, dna-> this determines the effect
  b. DNA can effect in gene mutations -> loss of function -> cancer

• What are causes and consequences of oxidative stress?

  1. Haber-Weiss reaction
  2. reactive oxygen species - CAUSE
  3. lipid peroxidation - CONSEQUENCE
  4. hydroxyl radicals - CAUSE