Examquestions Toxicology (translated from Dutch master) This type of questions often reoccur: Hoet: 2 questions - tables with results from a toxicity test. Discuss the test used. - questions about risk assessment Tyrgat: 1 question to prepare, 1 on the spot - questions about administration routes - recurring subjects: ethanol, CYP450 enzymes 2009 Hoet -objectives of reach - comparing 3 segments of reproductivetoxicity in the classical system with the new system - discuss immunotoxicity: expected effects? How are these tests performed (schematic) - what are the underlying principles in in descriptive toxicity tests in risk assesment Tytgat - discuss oral application and the rol of pH (no structural formulas) - Discuss the CYP2D6 gene and its role in poor and extensive metabolizers - extra questions about ethanol 2010 Hoet - table about acute toxicity testing with LD50determination. Was this done according to OECD guidelines? Why (not)? Important parameters can be derived from this? Extra question: is LD50 in general useful? - safety pharmacology: why is this performed and what are the most important core battery tests? - a table with values of DPM and SI of a LLNA. Explain what LLNA is, what is SI? - abbreviaties: RfC, ADI en MOE Tytgat: - compare oral exposure and pulmonary exposure - discuss metabolisation of ethanol and excretion of ethanol/methanol - extra: benzene en toluene. Which one is most toxic? Chemical names. 2011 Hoet : - Explain : Rfd - ADI - MOE. how are Rfd en ADI determined? How are these parameters coupled to MOE? - Table with results from a LLNA. Discus LLNA. Discus SI. What is its meaning? - Table with bloodtests and hematology of rats (21days dermal exposure). What kind of test is this and what are the results? Is the protocol acceptable? Are there alternatives? - Is pharmacokinetics useful for descriptive animal testing? Explain. - Table with data about BW and weight of the organs. Male and female rats with repeated exposure for 21 days. What kind of test is this and what are the results? Is the protocol acceptable? What would you conclude? - Discuss DNEL and DMEL. What are they used for and what are the differences. - Discuss LD50, Benchmark, Ames test, … Tytgat : - Discuss phase II reactions schematically - Discuss induction and inhibition of metabolic enzymes. Importance for toxicity testing. - discuss pulmonary uptake. Give examples. Extra: what is asbestos, difference between helium and amonium,what is the therapeutic index, - Discuss CYP450 enzymen, and CYP2D6 - Discuss hair analysis in toxicology 2012 Hoet: - Table with data about BW and weight of the organs. Male and female rats with repeated exposure for 21 days. What kind of test is this and what are the results? Is the protocol acceptable? What would you conclude? - what kind of tests are important for biotechnological products. Importance of species choice? - safety pharmacology: why is this performed and what are the most important core battery tests? - why is the dose-response concepts a fundamental part of risk-assesment? - How to tes immuunsupression? and benchmark method - Table with LD50, what can bederived from this data. Compliance with OECD guidelines? - Testing for hypersensitivity. Especially LLNA - Is pharmacokinetics useful for descriptive animal testing? Explain. - Table with results from an Ames test. What is the Ames test. Discuss the results. Is it according to current regulations - Why can NOAEL not be used for risk assesment? (benchmark should be used) - Discuss risk assessment and management (schematic) - application: table with testresults. Is a corrosivety test necessary. Tytgat: - Discuss induction and inhibition of metabolic enzymes. Importance for toxicity testing. - compare alcoholism and being drunk - explain NED, PROBIT, LD en LT - Discuss ionistaion of xenobiotics. Uptake, distribution and elimination. - uptake of xenobiotica via respiratory system - what is the role of blood in the distribution of xenobiotics? - Explain dose-response relationship - example of non-microsomal test reaction - example reasons for deviations of standard dose-response curve (polymorphisms, CYP450,..) - a bottle of alcohol. How much gram of alcohol? What is the promille. Extra: asbestos, EPV values, grapefruitjuice and CYP3A4, QT prolongation, methylenebridges, ethanol, isoniazide, Fugu (TTX), alcohol metabolism, Heavy metal poisoning and CNS , HERG … - is ethanol methabolized by CYP450? - how much methanol will lead to blindness - is formaldahyde intoxication as likely as methanolintoxication?