Lecture 1 introduction
What are the three phases from historical perspective + what was
known?
1. Hunting, fishing, gathering: Knowledge on acute toxic properties of plants,
mushrooms and some minerals; Probably less knowledge of chronic
effects.
2. Agricultural development: Cooking allowed cultivation of new plants
containing natural toxins as crop; Storage and transport introduced new
toxic compounds such as moulds (mycotoxins).
3. Industrial development: Distance between food sources and consumer
increases; New preservation methods such as canning; Addition of
chemical additives for preservation or colouring; Legal steps to guarantee
good quality of food.
What are the five hazards of the modern food chain? Mention the
examples of two of them.
1. Natural toxins: phytotoxins, fycotoxins, mycotoxins, animal toxins,
bacterial toxins.
2. Additives
3. Contaminants: pesticide residues, food processing products, packaging
contaminants veterinary drugs, metals, environmental pollutants.
4. Functional food ingredients and supplements
5. Nanomaterials
What are the most important food-related health risks from consumer
and science perspective?
Consumer:
1. Food additives
2. Environmental contaminants
3. Unbalanced diet
4. Natural toxins
5. Microbial toxins
Science:
1. Unbalanced diet
2. Microbial toxins
3. Natural toxins
4. Environmental contaminants
5. Food additives
Lecture 2 introduction
What are the three important questions you ask with in vitro toxicity
testing and which test do you use to answer those questions (give short
explanation of each test)?
1. Does the chemical cause DNA damage?
Ames test for genotoxicity; Bacterial reverse mutation assay; In absence of
histidine, bacteria cannot form colonies, unless reversion of the mutation
restores biosynthesis.
2. Does the chemical affect a specific cell signalling pathway?
Reporter gene assay for intracellular signalling; Cell signalling pathways
regulated by different receptors: estrogen receptor, androgen receptor,
aryl hydrocarbon receptor, Nrf2, p53.
3. Does the chemical affect metabolism enzymes in the liver?
1
, EROD assay for modulation of biotransformation; CYP1A activation; Role in
bioactivation of carcinogenic compounds.
Lecture 3 risk assessment
What are the components of risk assessment and what do they include?
1. Hazard identification: chemical properties, structural similarities,
uses/sources/ epidemiological and experimental data, critical effect, target
organ. [Qualitative aspects toxicity: Mechanism of action e.g. inhibition of
specific enzymes (COX, AChE), specific reaction (DNA binding), competition
with hormones, vitamins, metabolites. Acute (short exposure, high dose)
VS chronic (long exposure, low dose) toxicity]
2. Hazard quantification/characterisation: dose-response curve, NOAEL, BMD,
extrapolation from experimental animals to humans, determine
ADI/TDI/VSD.
3. Exposure assessment: levels in food/drinking water, consumer
questionnaires/production volume data, EDI, which population groups to be
considered?
4. Risk characterisation: compare ADI/TDI/VSD with EDI, determine MOS or
MOE, which population groups are most at risk?
What are the disadvantages of animal studies?
1. Ethical objections
2. Expensive
3. Time-consuming
4. Relevance of effects observed in animals at high dose levels to the human
situation in questionable.
What are alternatives for animal testing?
1. Structure Activity Relationships (SAR)
2. In silico (computer models)
3. In vitro research with animal/human cells e.g. Embryonic Stem cell Test
(EST) for developmental toxicology.
What are the disadvantages of the NOAEL?
1. NOAEL dependent on sample size: more dose groups, more animals →
lower NOAELs; better experimental designs are penalized
2. NOAEL limited to experimental dose
3. NOAEL differ across studies
4. Only one experimental data point is used
What are the advantages of BMD over the NOAEL?
1. Not dependent on set-up of experiment
2. Making use of all toxicity data
3. BMDL has on average about same level of protection as NOAEL
4. Same uncertainty factors can be used
What is used for unavoidable genotoxic carcinogens instead of the ADI?
1. ALARA: As Low As Reasonable Achievable
2. Virtual safe dose (VSD): dose that gives 1 in 10 6 extra cancer risk upon life
time exposure
3. Margin of Exposure (MOE) approach (good because extrapolation (and
VSD) differs with the approach by several orders of magnitude).
2
What are the three phases from historical perspective + what was
known?
1. Hunting, fishing, gathering: Knowledge on acute toxic properties of plants,
mushrooms and some minerals; Probably less knowledge of chronic
effects.
2. Agricultural development: Cooking allowed cultivation of new plants
containing natural toxins as crop; Storage and transport introduced new
toxic compounds such as moulds (mycotoxins).
3. Industrial development: Distance between food sources and consumer
increases; New preservation methods such as canning; Addition of
chemical additives for preservation or colouring; Legal steps to guarantee
good quality of food.
What are the five hazards of the modern food chain? Mention the
examples of two of them.
1. Natural toxins: phytotoxins, fycotoxins, mycotoxins, animal toxins,
bacterial toxins.
2. Additives
3. Contaminants: pesticide residues, food processing products, packaging
contaminants veterinary drugs, metals, environmental pollutants.
4. Functional food ingredients and supplements
5. Nanomaterials
What are the most important food-related health risks from consumer
and science perspective?
Consumer:
1. Food additives
2. Environmental contaminants
3. Unbalanced diet
4. Natural toxins
5. Microbial toxins
Science:
1. Unbalanced diet
2. Microbial toxins
3. Natural toxins
4. Environmental contaminants
5. Food additives
Lecture 2 introduction
What are the three important questions you ask with in vitro toxicity
testing and which test do you use to answer those questions (give short
explanation of each test)?
1. Does the chemical cause DNA damage?
Ames test for genotoxicity; Bacterial reverse mutation assay; In absence of
histidine, bacteria cannot form colonies, unless reversion of the mutation
restores biosynthesis.
2. Does the chemical affect a specific cell signalling pathway?
Reporter gene assay for intracellular signalling; Cell signalling pathways
regulated by different receptors: estrogen receptor, androgen receptor,
aryl hydrocarbon receptor, Nrf2, p53.
3. Does the chemical affect metabolism enzymes in the liver?
1
, EROD assay for modulation of biotransformation; CYP1A activation; Role in
bioactivation of carcinogenic compounds.
Lecture 3 risk assessment
What are the components of risk assessment and what do they include?
1. Hazard identification: chemical properties, structural similarities,
uses/sources/ epidemiological and experimental data, critical effect, target
organ. [Qualitative aspects toxicity: Mechanism of action e.g. inhibition of
specific enzymes (COX, AChE), specific reaction (DNA binding), competition
with hormones, vitamins, metabolites. Acute (short exposure, high dose)
VS chronic (long exposure, low dose) toxicity]
2. Hazard quantification/characterisation: dose-response curve, NOAEL, BMD,
extrapolation from experimental animals to humans, determine
ADI/TDI/VSD.
3. Exposure assessment: levels in food/drinking water, consumer
questionnaires/production volume data, EDI, which population groups to be
considered?
4. Risk characterisation: compare ADI/TDI/VSD with EDI, determine MOS or
MOE, which population groups are most at risk?
What are the disadvantages of animal studies?
1. Ethical objections
2. Expensive
3. Time-consuming
4. Relevance of effects observed in animals at high dose levels to the human
situation in questionable.
What are alternatives for animal testing?
1. Structure Activity Relationships (SAR)
2. In silico (computer models)
3. In vitro research with animal/human cells e.g. Embryonic Stem cell Test
(EST) for developmental toxicology.
What are the disadvantages of the NOAEL?
1. NOAEL dependent on sample size: more dose groups, more animals →
lower NOAELs; better experimental designs are penalized
2. NOAEL limited to experimental dose
3. NOAEL differ across studies
4. Only one experimental data point is used
What are the advantages of BMD over the NOAEL?
1. Not dependent on set-up of experiment
2. Making use of all toxicity data
3. BMDL has on average about same level of protection as NOAEL
4. Same uncertainty factors can be used
What is used for unavoidable genotoxic carcinogens instead of the ADI?
1. ALARA: As Low As Reasonable Achievable
2. Virtual safe dose (VSD): dose that gives 1 in 10 6 extra cancer risk upon life
time exposure
3. Margin of Exposure (MOE) approach (good because extrapolation (and
VSD) differs with the approach by several orders of magnitude).
2
