Please describe the difference between HAZARD and RISK:
What is Pharmacodynamics (PD) …
investigates the action of a substance and the
cellular or biological response to stimuli
the biological pharmacodynamical effects are
always evident and the same, independent of the concentration of a substance or
intensity of a stimulus
PD focusses on mechanisms, while pharmacokinetic
(PK) investigates substance levels (that cause the effect observed in PD) over
time
The therapeutic window is the amount of a
medication between the amount that gives an effect (effective dose) and the
amount that gives the maximum desired effect
Pharmacodynamics places particular emphasis on dose–response relationships
Define “Volume of Distribution “
The half-life (t1/2)
is the time it takes for concentration to be
reduced to half its initial value
is dependent on the concentration in plasma
can range from seconds to months or even years
is only relevant in pharmacology but not in
toxicology
biological effects may still be present although the concentration has dropped below the minimal effective concentration
In postmortem toxicology which one of the following is the matrix of choice
for the quantitative analysis of most drugs to derive their acute effect at the
time of death:
Larvae that are feeding on the corpse
Cardiac blood from the right ventricle
Whole blood from the femoral vein
Filtered stomach contents
Vitreous humour
What does the abbreviation NPS stand for?
Name three classes of drugs that are classified as NPS.
Name an antidote for bradycardia induced by cardiac glycosides. Where is it
working?
Which of the following information on cocaine and its derivates is wrong?
Cocaine derivates like procaine and lidocaine
are used as local anesthetics
Lidocaine is also used as antiarrhythmic drug
Amide derivates of cocaine are metabolized to
para-aminobenzoic acid, which can induce allergic reactions.
Cocaine inhibits Na+/K+ channels and the
reuptake of (nor)epinephrine.
Cocaine addiction results in cardiomyopathy and
a reduced blood ejection.
Which of the following drugs or toxins blocks acetylcholine release?
Atropine
Toxin from Clostridium botulinus
α-Latratoxin
Aconitine
Tetrodotoxin
Why is the metabolite of acetylsalicylic acid (ASA) salicylic acid secreted more efficiently in a basic urine?
Which skin layer typically determines the resorption speed of a toxicant
through the skin (one answer is correct)?
basal membrane
dermis
stratum corneum
stratum spinosum
stratum basale
stratum granulosum
Which of the following adverse reactions is a typical reaction for eye
toxicity (one answer is correct)?
contact urticaria
allergic alveolitis
pancytopenia
immunosupression
corneal deposits
Which statements about methemoglobinemia are correct (two answers are
correct)?
In methemoglobinemia, all iron ions bound to heme are in the ferrous (Fe2+) state
Methemoglobin cannot bind O2, but results in
increased O2 affinity in the remaining heme sites.
The heme-bound iron must be in the Fe3+ state to
bind oxygen.
Nitrobenzenes can lead to methemoglobinemia
There is no autooxidation of iron under physiological conditions
Name the three major compartments of the respiratory tract. For each compartment, delineate one possible clearance route
Name
two agents that cause different types of
lung injury and/or disease. Describe the major
hallmarks of the resulting disease and name what is currently known about the underlying molecular mechanisms
Please mark the right word to complete the sentence: The
_____________________ the LD50 measurement, the more toxic the substance.
higher
lower
The LD50 for Vitamin A is 200.000 mg/kg. How many chewable vitamin tablets
would a 10 kg child have to consume to reach the LD50 if each tablet contains 1
mg Vitamin A?
2.000 tablets
20.000 tablets
tablets
10.000 tablets
What was Thalidomide prescribed for?
Which major side effects have been observed after Thalidomide treatment?
What is true about developmental toxicology? (Indicate all that apply).
Mutation can be a mechanism underlying
teratogenesis.
Decreased nutrient supply can be a mechanism
underlying teratogenesis.
The majority of the birth defects are caused by
exposure to radiation, drugs, chemicals or maternal metabolic imbalances.
Teratogenic agents can have an effect on the placenta only.
Humans are exposed to 4-aminobiphenyl which is metabolized and reacts with
biomolecules such as DNA and blood proteins (hemoglobin, albumin). Which
biomarker can still be found 3 months after a single exposure (one answer is
correct)?
urinary metabolites of 4-aminobiphenyl
hemoglobin adducts of 4-aminobiphenyl
DNA adducts of 4-aminobiphenyl
exhaled 4-aminobiphenyl
Some environmental and occupational pollutants form covalent adducts with blood proteins. What are the advantages to measure such adducts instead of measuring only the concentration of the chemicals in the environment?
Complexes of Cyclins and Cyclin-dependent kinases drive and control the cell
cycle. How can their activities be regulated? Mark the correct answers (more
than one answer can be correct)
Expression of the correct Cyclin in the
respective cell cycle phase
Inactivation by cyclin kinase inhibitors
Activating phosphorylation on Cdk
Inhibiting phosphorylation on Cdk
Apoptotic cells can be distinguished from necrotic and healthy cells by
FACS. Which statements are correct?
Healthy cells are perfectly stained by propidium
iodide (PI).
Annexin V FITC conjugate stains external
phosphatidylserine on apoptotic cell membranes.
Necrotic cells are stained by both Annexin V AND
PI.
Necrotic cells are not stained by Annexin V and
PI.
Typically, one can distinguish two modes of mitochondria initiated/executed cell death. One is called MAC, the other MPT. What do these abbreviations mean? How do they lead to cell death?
Explain the general differences between the concepts of „General Unknown Screening, GUS“ and “Targeted Compound Analysis, TCA” when analyzing any sample for the presence of any poison.
Electrospray ionization (ESI) is a common and highly robust and beneficial
technique for ionization of analytes often coupled to chromatographic
separation. Which statements are correct?
ESI induces fragmentation of analytes by
bombardment with electrons submitted from an emitter electrode.
ESI applied in positive mode typically transfers
protons to the analytes thus producing positively charged ions suitable for
mass spectrometric detection.
ESI is a technique best suited for online
coupling to UV- and fluorescence detection of drugs of abuse.
ESI belongs to the techniques for soft
ionization of analytes to convert them into ions thereby typically not inducing
fragmentation.
ESI belongs to the techniques for soft ionization of analytes to convert them into ions thereby typically not inducing fragmentation.
(Blood) plasma, urine and hair are typical specimens for toxicological and
forensic analysis. Which statements are correct?
Hair analysis is best suited to document the
acute phase of poisoning and clearly indicates toxicants that were incorporated
a few hours before.
Urine analysis is best suited for post-exposure
evidence of all polar poisons that were incorporated more than 3 months before
sample drawing.
Plasma is the ideal specimen to provide data on
acute exposure to any poison documenting the actual concentrations influencing
the organism.
For urine analysis phase II conjugates of
analytes (e.g. drugs and drugs of abuse) are typically subjected to enzymatic
degradation using e.g. glucuronidases prior to instrumental analysis thus
enhancing analyte concentrations.
Chronic poisoning and continuous drug consumption might be documented by the analysis of hair cut into small segments thus allowing the estimation of past periods of drug or poison incorporation.
Which cancers can be caused by the occupational exposure to the following
toxicants: Aflatoxins, Aromatic amines, Asbestos, Ultraviolet irradiation,
Benzene Write the right toxicant behind the corresponding cancer type.
Cancer:
Leukaemia
Mesothelioma
Hepatocellular carcinoma
Skin Cancer
Bladder Cancer à
DALYs (Disability Adjusted Life Years) are sometimes used to estimate the
quantitative role of occupational toxicology in preventing diseases due to
occupational toxicants. What do they consist of (multiple answers possible)?
Years After the Diagnosis (YAD) of a disability
related to the occupational exposure to a toxicant
Occupational Exposure Years (OEY) based on the
time of a known exposure to a toxicant
Years of Life Lost due to premature death (YLL)
based on the number of deceased persons and the life expectancy at birth
Years between Disability Onset and first
Exposure (YDOE) to an occupational toxicant
Years Lived with Disability (YLD) based on the prevalence and a disability weight
Regulatory Toxicology
is a subdiscipline of environmental toxicology.
aims to protect human beings (and nature) from
toxic effects.
enacts laws.
does not include biocides and drugs.
Which statement about human exposure assessment is true?
External and internal exposure are related by a
simple calculation factor.
Internal exposure to a substance can be
estimated on the basis of external exposure data.
Internal exposure to a substance can exclusively
be determined by measurement (human biomonitoring).
Measurement of internal exposure to a substance
(e.g. in blood) generally causes higher costs than measurement of external
exposure (e.g. in ambient air).
Which statement about ADI (acceptable daily intake) values is true ?
ADI values can in principle be derived for all
kinds of potentially toxic substances.
Exposure to a potentially toxic substance
exceeding the ADI value always implies high acute risk of health damage.
ADI values are usually derived from
toxicological findings in humans.
ADI values are defined for lifetime exposure and are valid for all groups of humans (including e.g. children, pregnant women).
How would you define a Maximum Residue Level (MRL)?
In EU chemical legislation, REACH stands for … (Only one answer is correct)
Risk and Exposure Assessment of Chemicals
Regulation, Assessment and Control of Chemicals
Registration, Evaluation and Authorisation of
Chemicals
Regulation on Environmental Analysis and Control
of Hazards
The European Food Safety Authority (EFSA) … (Only one answer is correct)
authorises both active ingredients and plant
protection products.
accepts only animal studies for toxicity
testing.
identifies endocrine disruptors using a
different methodology from that used by the European Chemicals Agency (ECHA).
assesses risks to both human health and the environment.
How many DNA molecules are in a healthy diploid human cell nucleus (genome
size 6,2x109 base pairs)?
What is the predominant DNA damage mechanism during ionizing radiation
exposure? (Only one answer is correct)
direct ionization
single strand break formation
radical attack
lipid oxidation
Which of the following 2 pathways repair DNA double strand breaks? (Two correct
answers)
TC-NER
HR
SSBR
NHEJ
Please name three cellular consequences of DNA damage.
Which of the following statements are true?
Base excision repair is responsible for the
repair of “small” DNA lesions introduced by reactive oxygen species or
methylating/ethylating agents.
DNA glycosylases are responsible for the sealing
of DNA single strand gaps after excision of the DNA lesion and resynthesis of
the missing bases.
Non-homologous end joining (NHEJ) is the main
repair pathway responsible for the repair of DNA SINGLE strand breaks?
Nucleotide excision repair is responsible for
the repair of big bulky DNA adducts.
Pharmacological targeting of DNA repair factors
can be employed in cancer therapy.
DNA polymerases that are responsible for DNA translation synthesis have a very HIGH catalytic efficiency, fidelity and processivity.
What are the most permanent changes environmental carcinogens inflict? (Only
one answer is correct)
Protein changes
RNA changes
Epigenetic changes
DNA changes
All of the above
What are the molecular hallmarks of smoking-induced cancers? (Only one
answer is correct)
KRAS mutations
TP53 mutations
C > A transversions
High mutation burdens
All of the above
What are the potential environmental causes of lung cancer in addition to
smoking? (Only one answer is correct)
Human papillomavirus infection
Helicobacter pylori infection
Frequent gestations (pregnancies)
Frequent multi-partner sexual intercourse
Irradiation
Please list the main essential metals.
What are the most relevant (highly toxic) heavy metals for human?
Please, select the correct list of essential trace metals.
Lead, arsenic, cobalt and manganese.
Zinc, iron, cobalt, copper, cobalt and
manganese.
Calcium, magnesium, zinc and iron.
Cadmium, mercury, lead and arsenic.
Please describe briefly the molecular mode of action of botulinum toxin
within the cytoplasm of an axon ending.
Please mark correct statements:
Any incidence of intoxication with biological
toxins almost certainly indicates a terrorist attack.
Reliable diagnosis of biological toxins often
requires a combination of immunological, mass spectroscopic and functional
biological detection methods.
Standard therapy of intoxication by many
biological toxins is often only symptomatic, since specific antitoxins are not
always available.
All biological toxins show markedly specific
organ tropism.
Cyanotoxin poisoning occurs exclusively after
consumption of fish or shellfish.
Please mark correct statements regarding Botulinum toxin and Ricin:
Botulinum toxin belongs to the group of AB
toxins.
After surviving a botulinum intoxication,
patients develop lifelong immune protection through antibody formation.
Inhalation of botulinum toxin is a typical
mechanism of exposure.
Ricin causes a breakdown of DNA synthesis in
cells.
Past exposure to ricin can be detected by immunological tests.
What does NOAEL stand for?
What stands ADA for? In case ADA is developed what are the expected effects in toxicity studies
ADA stands for anti-drug antibodies. The
antibodies show effects by neutralization of the test item. This results in
higher direct test item related toxicity - but lower test item related
pharmacological efficacy.
ADA stands for anti-drug antibodies. The
antibodies show effects by neutralization of the test item. This results in
lower direct test item related toxicity and in addition in in putative ADA
related immunotoxic effects.
ADA stands for Adalimumab which is an antibody
used in therapy of Rheumatoid Arthritis. ADA increases the risk of cancer in
patients which might be wrongly addressed to the test substance in toxicity
studies.
ADA stands for anti-drug antibodies. An immunotoxic effect related to ADA could develop. However, the exposure with the test item is not changed and no effect on the data obtained on toxicity is expected.
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Last Update: 30. Dezember 2022