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College notes Toxicology and Development (AB_1026)
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Hoorcollege aantekeningen Toxivologyand Development
January 2021 (P3)
,Inhoud
Introcollege ............................................................................................................................................. 3
HC 1: Toxicology I .................................................................................................................................... 3
HC 2: Toxicology II ................................................................................................................................... 6
HC 3: Toxicology III .................................................................................................................................. 7
HC 4: Toxicology IV ................................................................................................................................ 11
HC 5: Eurion-AOP................................................................................................................................... 14
HC 6 & 7: PBTK modelling...................................................................................................................... 16
HC 8 & 9: Teratogens and birth defects ................................................................................................ 21
HC 10: Developmental toxicity .............................................................................................................. 24
HC 11 & 12: Human biomonitoring and the exposome ........................................................................ 27
HC 13: Introduction Metabolomics ....................................................................................................... 30
HC 14: Chromatography & Mass spectometry ...................................................................................... 33
HC 15: Data interpretation .................................................................................................................... 36
HC 16: Application environmental metabolomics ................................................................................ 37
HC 17: Epidemiology and exposure assessment ................................................................................... 38
HC 18: Human health risk assessment .................................................................................................. 41
2
,Introcollege
Chemistry: analysis of the concentrations of contaminants in the environment (indoor and outdoor),
measurement of endogenous substances and contaminate in organisms.
Toxicology: analysis the effect of contaminants in the environment, determine safe concentration,
understanding mechanisms of actions
Teacher of courses within Bachelors and minors.
Content: studying toxicological effects on the development is an
multidisciplinary research field. First we have to identify the compounds
we are exposed to (analytical chemistry). Then we have to apply
epidemiological studies to identify correlation between development
and …
All lectures are prerecorded and every lecture has an assignment which
you have to submit before the 20th of January (after 20-01-2021 the
correct answers will be posted). Assignments are important for the
exam! Won’t be checked on plagiarism.
In the discussion groups you can ask questions about the lectures and
assignments.
General assignment is making a E-book where the chapters are divided
among groups. This will be graded (30% of the final mark) and needs to
be a 5.5 to pass. Also counts for the written exam (70%): 29-01-2021
13:00-15:00. Besides that, all assignments need to be done.
HC 1: Toxicology I
Toxicology = multidisciplinary (biology/chemistry/biochemistry, physiology, genetics,
mathematics/statistics, medicine, pharmacology and much more)
Definitions:
- Compound = a chemical compound that is composed of a particular set of molecules or ions.
- Toxicant or xenobiotic = a type of poison that is made by humans or introduced into the
environment by human activity,
- Toxin = poison produced naturally by an organism.
- Contaminant or pollutant = biological, chemical, physical, or radiological substance (normally
absent in the environment) which can adversely affect living organisms.
Paracelsus = the founder of modern toxicology, chemicals may have specific effect (“Everything is
poisons’, but the concentration/amount determines how toxic it is.”)
3
, Dose-response curves are characterized by:
1. Location (ED50 and potency (how toxic/potent is the
compound))
2. Maximum response (effectiveness)
3. Steepness of the curve
With these dose-response curves we can predict effect size/what might happen. We can also do the
‘backward use’ to determine the toxicity/characteristics of the compound.
- ED50: effect dose 50%. Concentration where 50% of the treated animals are affected.
- LD50: lethal dose 50%. Concentration where 50% of the treated animals are death.
o The smaller this value, the more toxic the compound is.
o Food additive are the least toxic
- LOAEL: lowest observed adverse effect level (dose). Lowest concentration with effects
compared to the control group.
- NOAEL: no observed adverse effect level (dose). Highest concentration with no effects
compared to the control group.
- Threshold value: the value where we see adverse effects
In aquatic studies In studies with rodents
LC50 Median lethal concentration in water LD50 Median lethal dose (mg/kg body
(𝜇mol/L, % alcohol) weight)
EC50 Lowest concentration with 50% effect ED50 Dose with 50% effect (mg/kg body
weight)
LOEC Lowest observed adverse effect LOAEL Lowest observed adverse effect level
concentration (dose)
NOEC No observed effect concentration NOAEL No observed adverse effect level
(dose)
Teratogenicity refers to the developmental malformations. The higher the
TI, the more specific teratogenic effects of the chemical can be expected
compared to overall embryotoxicity, as measured by mortality of
organisms.
- Teratogenic index (TI) = LD50/ED50 (→ the gap)
- Relative TI = LC1/EC5
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