Summary Class notes - TOX20303

Course
- TOX20303
- Ivonne Rietjens
- 2016 - 2017
- Wageningen University (Wageningen University, Wageningen)
- Voeding en Gezondheid
290 Flashcards & Notes
1 Students
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Summary - Class notes - TOX20303

  • 1504562400 College 1 + 2

  • Toxicology
    Study of the adverse toxic effects of chemicals on living organisms
  • What is toxicology?
    Study of the adverse (toxic) effects of chemicals on living organisms
  • Hemlock
    State poison of the Greek
  • Historical perspective 

    phase 1: hunting, fishing, gathering 
    phase 2: agricultural development 
    phase 3: industrial development
  • Belladonna (atropin)
    To create wide pupils and cause hallucination in 'witches'
  • Wat voor kennis hadden we/ze in de periode 'hunting, fishing and gathering'?
    • Knowledge on acute toxic properties of plants, mushrooms and some minerals 
    • probably less knowledge of chronic effects 


    • used to poison hunting spears and enemy water supplies during war (monkshood)
  • Mycotoxicoses (of fungi)
    Reduce bloodsupply to hands and feed --> black limbs
  • Wat voor kennis hadden we/ze in de periode 'agricultural development'
    • Cooking allowed cultivation of new plants containing natural toxins as crop 
    • storage and transport introduced new toxic compounds such as moulds (mycotoxins)
  • St. Antony's fire
    People went to France to visit St. Antony. They went away from the source and got better (poison due to mycotoxicoses)
  • Greek and roman 

    hippocrates

    description of poisons and clinical toxicology principles like bioavailability 

    Socrates drinking hemlock greek state poison 
  • Monkshood
    Causes cardiac arrhytmias en hypertention. Used as a poison on hunting spears or enemy watersupplies
  • Paracelsus (1493-1541) ontdekte/nam waar dat:
    The dose matters 


    de dose maakt uit, alles is giftig de dose bepaald alleen wanneer het giftig is. 
  • Percivall Pott
    Scrotal cancer in chimney sweeps
  • Botulinum toxin
    It blocks ach release 

    you can find it in lakes and in vacuum potjes die niet goed zijn afgesloten 

    het wordt gebruikt voor medische treatment (botox)
  • Orfilla
    Target organ (if its safe, the rest is also safe)
  • Wat voor kennis hadden we/ze in de periode 'industrial development'
    • Distance between food sources and consumer increases
    • new preservation methods such as canning 
    • addition of chemical additives for preservation or coloring 
    • legal steps to guarantee good quality of food (end 19th century)
  • DDT
    Insecticide to fight malaria or thyphus --> fragile egg shells --> reproduction problems in birds
  • Wat heeft Percivall Pott ontdekt in 1775
    Chimney sweeps (schoorsteenvegers) had a very high incidence of scrotal cancer. Related to their constant exposure to soot (roet)

    We now know that it contains: polycyclic aromatic hydrocarbons (PAHs)
  • Agent orange (Dioxins)
    Causes malformations in unborn children
  • Orfila (1814)
    Introduction 'target organ' concept and animal experiments
  • Softanon
    Inhibits formation of bloodvessels
  • Welke toxische stoffen zijn er in de 20th eeuw ontstaan/ontdekt.
    • Many pesticides 
      • chlorinated hydrocarbon insecticides: DDT
    • war gasses, munition 
      • Sarin, soman, uranium, agent orange (dioxins)
    • Drugs 
      • Softenon (thalidomide), diethylstilbestrol (DES)
    • industrial chemicals 
    • synthetic fibers 
  • DES
    Sleeping aid/prevention miscarriages. It causes malformations in arms and legs in children
  • DDT (dichlorodiphenyltrichloroathane)

    • Het dood alle insecten maar niet ons de mens. 
    • het maakt eierschalen heel kwetsbaar en breekbaar waardoor er geen kuiken in kan groeien. 
  • Paracelsus
    The dose makes the poison
  • Rachel Carson 'Silent Spring' (boek) 1962
    Alles was dood gegaan en het gebruik van DDT was uit de hand gelopen. Silent spring niet veel vogels en insecten...

    challenged the notion that man was destined to control nature 
  • Major aims toxicology
    1. Toxicity, mechanisms of action, structure activity relationships
    2. Health and environmental hazards and risks
    3. Advise for authorities, industries and consumers
  • Dioxins (TCDD)
    agent orange (vietnam)
    • alle bladeren vielen van de bomen waardoor ze goed konden zien wat hun vijanden aan het doen waren. 
    • de ledematen van kinderen groeide niet goed (erg klein), vervormde gezichten. 
  • Hazard
    Potential danger
  • Softenon (thalidomide)
    For morning sickness, maar het had vele bijwerkingen, de kinderen raakte helemaal misvormd met rare ledematen.
  • Risk
    Probability that adverse effects will occure
  • Door de bijwerkingen op het kind, nadat de moeder softenon slikte voor morning sickness werd er voor de toekomst meer nadruk gelegd op: (3)
    • Reproduction & developmental toxicity 
    • stereochemistry: analytical techniques 
    • safety testing and risk assessment 
  • Risk management
    Based on risk assessment, social, economic and political aspects

    For example: BPA is safe, but in France there is a ban because of political reasons
  • The major aims of modern toxicology (3)
    1. Define toxicity, mechanisms of action and structure activity relationships for chemicals 
    2. evaluation of health and environmental hazards and risks 
    3. advisory task for authorities, industries and consumers 
  • Risk assessment
    Based on hazard, exposure and risk
  • Wat komt er allemaal bij risk assessment kijken? Hoe komt dit tot stand
    • Hazard identification 
    • hazard characterisation 
    • risk characterisation 
    • exposure assessment 
    • risk management 
    • risk communication 
  • Exposure assessment
    1. Route and site of exposure: oral, inhalation, dermal, injections
    2. Duration and frequency of exposure: acute, subacute, subchronic, chronic
  • Risk management =-->
    Select type of actions to be taken 
    • based on risk assessment and social, economic and political aspects 


    example:
    • fipronil in eggs (august 2017)
    • Bisphenol A (BPA)
  • Benzene
    - Acute: CNS depression
    - Chronic: Leukemia
  • Exposure assessment
    1. Route and site of exposure 
    2. duration and frequency of exposure 
  • Ethanol
    - Acute: CNS depression
    - Chronic: fatty liver
  • Exposure assessment: route & site of exposure
    • Gastrointestinal tract (oral)
    • lungs (inhalation)
    • skin (dermal)
    • injections
  • Arsenic
    - Acute: gastrointestonal damage
    - Chronic: skin/liver cancer
  • Exposure assessment: duration and frequency
    Acute: <24 hours, single dose 
    subacute: 1 month or less
    subchronic: 1-3 months 
    chronic: >3

    effect varies with dose & exposure regimen 
  • Harber's rule
    C * t = k

    C = concentration chemical
    t = time untill effect
    k = constant
  • Estimated daily intake
    Classical method:
    • EDI = [compound] in product X consumption of product 


    nogal method:
    • probabilistic exposure assessment (Monte Carlo simulations)
    • zie afbeelding
  • Receptor
    Part of the molecule affected by the toxic agent
  • Haber's rule
    C x t = k

    C = concentration or dose
    t = time of exposure needed to produce a given toxic effect
    K: a constant, depending on chemical and effect

    example: doubling the concentration will halve the time needed to produce an adverse effect
  • Primairy lesion
    Primairy molecular damage
  • Zie de afbeelding 


    hazard: types of biological responses
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Absorption: passing cell membranes via
  • Phospholipid
  • intergral proteins
  • cholesterol 
  • ion channel 
  • ligand 
Toxicokinetics (ADME) de letters staan voor...?
Absorption 
Distribution 
Metabolism 
Excretion 
Variation in toxic response (hangt af van)
  • Intra species or between individuals of one species 
  • age 
  • nutrition and life style diseases
  • gender 
  • combined exposures
Target organ =
Most sensitive organ
Primary lesion =
Primary molecular damage
Receptor =
The molecular structure affected by the toxic agent (DNA, protein like enzyme, ion channel)
Fibrosis
Excessive accumulation of extracellular matrix (collagen)
Necrosis
Severe damage 


  • loss membrane integrity 
  • swelling cytoplasm/mitochondria
  • cell lysis
  • no energy requirement 
  • inflammatory response 
  • non physiological stimuli 
Apoptosis
Programmed cell death 
  • membrane intact 
  • shrinking cytoplasm/nucleus
  • cell fragmentation 
  • ATP dependent
  • no inflammatory response 
  • physiological stimuli 
Cellular repair:
Apoptosis of necrosis