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...
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
The benefits of buying summaries with Stuvia:
Guaranteed quality through customer reviews
Stuvia customers have reviewed more than 700,000 summaries. This how you know that you are buying the best documents.
Quick and easy check-out
You can quickly pay through credit card or Stuvia-credit for the summaries. There is no membership needed.
Focus on what matters
Your fellow students write the study notes themselves, which is why the documents are always reliable and up-to-date. This ensures you quickly get to the core!
Frequently asked questions
What do I get when I buy this document?
You get a PDF, available immediately after your purchase. The purchased document is accessible anytime, anywhere and indefinitely through your profile.
Satisfaction guarantee: how does it work?
Our satisfaction guarantee ensures that you always find a study document that suits you well. You fill out a form, and our customer service team takes care of the rest.
Who am I buying these notes from?
Stuvia is a marketplace, so you are not buying this document from us, but from seller rbe239. Stuvia facilitates payment to the seller.
Will I be stuck with a subscription?
No, you only buy these notes for $4.24. You're not tied to anything after your purchase.
