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Lecture notes Toxicology (2021)
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  • Microbiology - Toxicology (AB_1139)
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  • Vrije Universiteit Amsterdam (VU)

Lecture notes of the Toxicology part of the Microbiology-Toxicology course. This course is part of the first-year Biomedical Sciences curriculum at the Vrije Universiteit Amsterdam. Note: these notes were written based on pre-recorded lectures (due to COVID-19), so the content might be different th...

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  • 16 de febrero de 2021
  • 15
  • 2020/2021
  • Notas de lectura
  • Timo hamers
  • Todas las clases

Temas

  • toxicology
  • environmental toxicology
  • mictox
  • microbiology
  • biomedical sciences
  • vu
  • vrije universiteit

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  • Vrije Universiteit Amsterdam (VU)
  • Biomedical Sciences
  • Microbiology - Toxicology (AB_1139)
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Toxicology

TOX01 – Introduction to toxicology (open textbook 1.3)
Toxicology = science of poisons
Paracelsus, “Luther of medicine”: “All things are poisonous and nothing is not poisonous. Only the
dose makes something not being a poison.”

Phases in toxic response:

1. Exposure
- External exposure
- Dose
- Internal exposure
 Human exposure routes are oral, dermal, respiratory, “special routes” (injection etc.)
2. Toxicokinetics  what does the body do to the compound
- Absorption
- Distribution
- Metabolism (biotransformation)
- Elimination (excretion)
3. Toxicodynamics  what does the compound do to the body
- Irritation, inflammation, etc.

Classification of toxic effects:

 Rate
- Acute effect (inhibition of cellular respiration)
- Chronic effect (carcinogenesis)
 Possibility for repair
- Reversible (DNA damage)
- Irreversible (tumor progression)
 Site of action
- Local effect at site of first contact (epithelium lesion)
- Systemic effect (target organs)

Dose-response curve:

 LD50: Median Lethal Dose (mg/kg)
 ED50: Median Effect Dose (mg/kg)
 LOAEL: Lowest Observed Adverse Effect Level (dose)
 NOAEL: No Observed Adverse Effect Level (dose)
 LC50: median Lethal Concentration in water/air/soil (mg/kg)
 EC50: median Effect Concentration
 LOEC: Lowest Observed Effect Concentration
 NOEC: No Observed Effect Concentration

, TOX02 – Absorption Distribution (open textbook 4.1.2)
Absorption = uptake
Intake ≠ uptake
Total absorption = ∑(fi x Ii)  with f being the absorption efficiency

Absorption after oral intake (+ passing the gastro-intestinal track without absorption):

 Entherohepatic circulation (repeat of ADME)
 Presystemic elimination (elimination before systemic distribution can take place)
 Portal vein

Absorption after intake by inhalation (+ exhaling of non-absorbed gasses):
Gasses get absorbed very quickly; this is due to the Henry coefficient = p air / Cwater. Transport via
osmosis takes places, and there is a continuous bloodstream, which causes further osmosis to take
place.

Distribution depends on the volume of body water.
Concentration = Dose / Volume

Lipophilic compunds (high Kow) in fat tissue:

- Released during fat mobilization
- Risk in case of small fat deposits

Accumulation:
Selective binding or uptake into specific tissues

 In most cases not biologically available, i.e. not toxic
 Can be mobilized from deposit
 Dynamic equilibrium with concentration in blood

Barriers in distribution:

 Blood-Brain Barrier (BBB)
- Endothelial cells  tight junctions, efflux by transporter proteins, no pinocytosis,
biotransformation capacity
- Astrocytes (gliacells)  physicial support, (efflux by transporter proteins,
biotransformation capacity)
 Placenta
- Not a true “barrier”  many lipophilic compounds diffuse through the placenta
- Defense  active transport, biotransformation capacity

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