Toxicology (E07U2A)

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General

Important concepts

  • Parameters in toxicology
  • Units
  • Detoxification and poisoning
  • Dose-response relationship
  • Absorption (different routes), –distribution, biotransformation (bioactivation), excretion, toxicokinetics (inasmuch this was not covered in pharmacology)
  • Interactions of products: Modalities of the interaction, mechanism, induction, inhibition

Specific items

  • Dosage in newborns and children
  • Symptoms and treatment of poisoning

Medical applications

  • Antitumoral drugs
  • Cardiovascular drugs
  • Analgetic, antipyretic en anti-inflammatory drugs
  • Psychotropic drugs
  • Alcohol: interaction with different classes of pharmaca; impact on society and public health


Part 2: Pre-clinical testing

  • Introduction: background, goal
  • General principles
  • Acute toxicology: acute lethal toxicity,eye & skin irritation, strategies
  • Genotoxicology: requirements in different areas, testing
  • Multidose (from sub-chronic to chronic): requirements in different areas, study design, most important end points, target organs
  • Carcinogenesis: specific requirements
  • Developmental and reproductive toxicity: Structure (segments I - III and the reproductive cycle)
  • Immunotoxicity: Specific (Immunosuppression , Hypersensibilisation, Autoimmunity)
  • Safety Pharmacology” (SP): Goal and principles, SP vs toxicology, Most important tests
  • Alternative tests: Goal, status, examples
  • Risk assessment – (without exposure evaluation): Approaches in different areas (strategies and differences) human health
  • Risks in the lab (personal risk evaluation) 

Exam form

Oral with written preparation, closed book, final examination during examination period


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Exam questions

(Click here to add examquestions.) Everybody has different questions. 2 question from Hoet. 1 question from the second but a lot of side questions.

Hoet

  1. A graph with BW for acute toxicity. Priciples of this test, what is on the grapth, contrary 3R concept?
  2. Timing, dosing in reproductivity and toxicity testing (pay attention on the dose graph, he asked about it but there are no explanations on slides only graphs.
  3. Example of a table for a skin irritation assay. explain what to do before you can do the test, why or why not the test was perfomed according to regulation and what an eye test would add to this knowledge.
  4. What is safety pharmacology, why and how do you perform it
  5. Acute toxicity: what do you need to do before performing animal test? Table with the weight of organs: what are your conclusion and is it according to OECD guidelines?
  6. Biopharmaceuticals: what is special about their production and toxicity testing?
  7. Does a positive acute irritation/corrosive skin or eye test mean the substance is an allergen? (no, only 1 exposure, local reaction, say how you could suspect if substance could be an allergen --> LLNA)
  8. table with bloed pressures and heart rate. in what part of toxicology does this test belong, what can you conclude and how is dose chosen in this type of testing.
  9. What is the acute toxicity? Table about a study. The table presents the effect and lethal death points. What kind of study is this? Was this study is conducted under current OECD?
  10. Why is dose-response assessment important for risk assessment?
  11. discuss, timing and dosage in reproductive and developmental toxicology? Explain Ames test + table with results from Ames test: discuss
  12. A table of a carcinogenicity test of a chemical via inhalation, they test the lung exposure and nose exposure.
  13. Is it necessary to perform the carcinogenicity test for both chemical and pharmaceutical product?
  14. What are the tests done in this study? And what other tests should be done in general? Can you directly relate the animal carcinogenicity test to human?
  15. The mutagenecity test showed negative results, but the carcinogenicity showed positive results, why?
  16. What is 3R, which do you think is the most important and why?
  17. Table of Ames Test: a) Explain Ames test b) Discuss the results c) Was this performed according to the rules?
  18. acute toxicity test 2000 mg/kg of methanol extract, not lethal. In mice, compare males and females. Treated and control group. a) explain the procedure b) what can you conclude from the graphs? c) are the 3R's considered?
  19. discuss the timing and dosing of reproductive and developmental toxicity testing.
  20. A table with data from acute toxicity test - what can you conclude? Did they use the right conditions - did they follow the right guidelines
  21. Table with carcinogenicity test - Do all substances require carcinogenicity testing? ⇒ No only the ones that will be exposed for more than 6 months or if they accumulate in the environment - Are the right concentrations used? (→ look at max dose)
  22. Table with oral acute toxicity data in mice. Can you determine the LD50? What is LD50 and when do you assess it? What is the conclusion you can make from the table? Is it done according to the OECD guidelines? (The dosages were in g/kg instead of mg/kg so you had to pay attention to detail!)
  23. About alternative tests. Are they working out? Was is the most important thing you have to consider while developing one, and how would you develop one? What happens if it doesn’t work out.(He wanted EVERYTHING -replacement of animal tests, how to reduce the No of animals used, how you can have less harsh endpoints).
  24. Give the schematic of Risk Assessment and Risk Management and explain all the factors. (explain difference between dose-response and exposure, explain hazard ID, explain how you can manage risks using protection etc)
  25. Explain DNEL and DMEL
  26. Discuss Risk assessment-risk management + how can we use toxicity studies to determine a safe dose (extra is the NOAEL used for all cases -- > no benchmark approach and explain how it works?
  27. Why is the dose response relationship important for risk assessment
  28. Table with results from an eye test (only the ocular lesions part): how is this test done, give the procedure? Is this done according to the rules? Which precautions must be taken? Is this test a valid test? What can you conclude from this data?
  29. Discuss NOEL, NOAEL, LOAEL, and MTD. What do they mean and what can they be used for?
  30. Table with results from a skin irriation test and an eye irritation test. Describe the general principle of these tests, what can you conclude from these tables and did they take the 3 R’s into account?
  31. Table Ames test: what is Ames test? What can you conclude from data? According to guidelines? Is it sufficient as genotoxicity test? (explain that you also need in vitro/in vivo tests to confirm)
  32. Dosing in carcinogenicity studies? Do you need to do carcinogenicity studies for every compound?


Tytgat

  1. Give an overview of the phase 2 reactions (extra: why is UDPGA so important -> comes from glucose)
  2. What is an air pollutant?
  3. Give an overview of agricultural chemicals relevant to toxicology.
  4. Explain agriculture materials in toxicology.
  5. Illustrate physical and chemical analytic tests.
  6. Explain the physiological aspects that affect the metabolism of xenobiotics (side question about TTX).
  7. Demonstrate some physical and chemical methods for analytical toxicology.
  8. Explain the definition of "acute toxicity".
  9. give an overview of the phase II reactions.
  10. Explain what is acute Toxicity, give example + mechanisms of action. Explain the Dose/response relationship
  11. Give the difference between Phase 1 and 2 reactions
  12. Give example of animal toxins + mechanism of action (therapy?)
  13. What is the minamata bay incident - explain mechanism (also given as side question)
  14. What are phase I reactions? (extra: Why CYPs are called monooxygenases? What does the P450 in their name stand for? What is a mycotoxin, is it different than an Aflatoxin?)
  15. Explain the difference between Air and Soil Pollutants
  16. Give an overview of the Phase 2 reactions (extra question: how is UDPGA made, is acetylicacid an example from the mercapturic acid route?,) (extra question: what is GST made from? Do you think that alcohol is also a substrate for phase 2 reactions?)
  17. What is the definition of reactive metabolites?
  18. Give examples of activating examples. Side questions about everything what he told during the lecture (just remember everything what he told).

2017-2018

HOET

- Explain NOEL, NOAEL, LOAEL, MTD. How are they derived and what are they used for?

- Table with results from a skin irritation test in rabbits & table with eye irration test in rabbits. Explain the protocol of these tests briefly, what can you conclude from these tables & are the 3R’s respected?

- Graphs with results from acute toxicity test performed in male and female mice. Explain test, explain conclusions of the test and say if it was performed according to 3R’s.

- Timing and Dosing in reproductive and developmental toxicity

TYTGAT

- Explain phase 2 reactions in toxicology (+ side questions)

- Explain phase 1 reactions in toxicology (+ a lot of side questions about ethanol metabolism)