Introduction
- three major aims of the field of food toxicology.
Define toxicity, mechanisms of action and structure activity relationships for chemicals
to which humans are exposed via food; Evaluation of health and environmental
hazards and risks: risk assessment; Advisory task for authorities, industries, and
consumers
- difference between avoidable and unavoidable hazards
Avoidable chemicals: • Additives • Flavourings • Veterinary medicines • Pesticides •
Supplements
Unavoidable chemicals • Contaminants: persistent organic pollutants • Contaminants:
metals • Natural toxins: from plants • Natural toxins: from animals • Nanomaterials
risk assessment
Understand the role of risk assessment in the framework of risk reduction. - Understand why
risk management is not the same as risk assessment. - Understand risk characterisation for
man and the role of uncertainty factors therein.
Hazard = potential danger of a compound or process
Risk = probability that an adverse effect will occur = hazard + exposure
-differences between risk assessment for genotoxic and non-genotoxic chemicals.
Genotoxic carcinogenic compounds: damage DNA and cause mutations. a threshold cannot
be defined: every molecule increases risk on cancer.
Avoidable compounds: zero tolerance: Compound should not be present and cannot be used
Unavoidable compounds:
ALARA: As Low as Reasonably Achievable
Threshold of Toxicological Concern (TTC): TTC for genotoxins: 0.15 mg/person per day –
Virtual Safe Dose (VSD):
dose causing 1 in 106 additional cancer risk upon life-time exposure (quantitative risk
assessment)
Linear extrapolation from experimental data to zero risk at zero dose; define VSD at 1 in 106.
Margin of Exposure (MOE)
- BMDL10: Statistical lower confidence limit of the dose giving a 10% increase in effect over
background level.
- MOE should be at least • 100 to interspecies differences (10) and human variability (10) • 10
for uncertainties relating to carcinogenic process • 10 for BMDL10
- MOE to be used by risk managers:
to set priorities (MOE > 10 000 of low concern/health risk; MOE < 10 000 of concern; priority
for risk management)
to define an MOE that would be considered acceptable is a responsibility of risk managers
Non-genotoxic compounds: a safe level of exposure (threshold) can be defined,
Define Target organ = most sensitive organ
Dose response Relationship For target organ, NOAEL = No Observed Adverse Effect Level
ADI = Acceptable daily intake for avoidable contaminants like additives, pesticides
TDI = Tolerable daily intake for unavoidable contaminants like dioxins, mycotoxins, heavy
,metals
- advantages of the BMD approach and the disadvantages of the NOAEL approach.
NOAEL BMD
dependent on sample size: not dependent on set-up of experiment
- more dose groups, more animals more animals higher BMDL;
- lower NOAELs; better experimental designs better experimental designs are no longer
are penalized penalized
NOAEL limited to experimental dose BMDL has on average about same level of
protection as NOAEL
differs across studies same uncertainty factors can be used more
dose groups
only one experimental data point is used making use of all toxicity data
BMR = benchmark response pe 5% or 10% effect over background level; BMD = Benchmark
dose (dose causing the BMR); BMDL = lower confidence limit of the BMD
Food carcinogens
Genotoxic chemicals in food (unavoidable)
natural carcinogens
- Phytotoxins (from plants) DNA adduct formation
- Alkenyl benzenes
example: estragole & methyl eugenol in basil and other spices, some vegetables (fennel) products
made thereof (pesto)
intake from added uses MOE = 116 High priority! In EU actions taken
Intake from herbs and spices MOE = 4400 – 44000 low(er) priority
- Pyrrolizidine alkaloids: have been found in honey and tea(comfrey) every day 1 cup of tea a
whole lifetime
- Mycotoxins (from fungi/molds)
- Aflatoxins
Example: aflatoxin B1 (produced by Aspergillus flavus)
mutation hotspots P53 tumor suppressor gene (APC: mutated in most colon cancer) results liver
cancer, MOE: 88-483 priority for risk management
endogenously formed carcinogens
-nitrosamines: nitrite(vegetables) + amine (fish)=nitrosamines
Example: N-Nitroso dimethylamine (NDMA)
young children: MOE = 7250
in adults: MOE = 72500
carcinogens formed during food preparation
- PAHs (polycyclic aromatic hydrocarbons) Pyrolysis of fat (temp 300°C - 600°C)
e.g. benzo[a]pyrene-BaP smoked, grilled, barbecued or burned foods MOEs indicate a low concern
for consumer health
- HCAs (Heterocyclic amines) Maillard reactions: sugars-amino acids, proteins (temp < 250°C)
e.g. heterocyclic amines (PhIP) “hamburger carcinogen” MOE 15,000 low priority
- Acrylamide French fries, chips, bread MOE values 40-400 << 10 000 Of concern! Risk management
actions required
, -furans in coffee, canned and jarred food MOEs: 36 - 582 (methyl furans not yet included)
non-genotoxic chemicals in food
Coumarin ( in cinnamon): carcinogenicity secondary to liver toxicity
co-carcinogens and antimutagens/anticarcinogens
Chemicals in food may reduce cancer formation by various mechanisms:
▪Reduction of effects of carcinogens by modulation of biotransformation enzymes
▪Reduction of inflammation
▪Reduce oxidative/electrophilic stress
▪Reducing proliferation tumor cells
▪Reducing bioavailability
Possible binding of aflatoxin B1 to chlorophyllin (from green vegetables) reduces bioavailability
Food additives
the need for food additives in the modern food chain.
1) to maintain product consistency: emulsifiers, thickeners
2) to improve or maintain nutritional value: vitamin, mineral restauration & enrichments
3) to maintain palatability & wholesomeness: preservatives, antioxidants
4) to provide leavening or control pH
5) to enhance flavor or impact desired color
the requirements before additives can enter the market and get an E- number.
• anyone who wants to put an additive on the market must provide convincing evidence that the
proposed additive - performs as intended - will not cause adverse health effects and that - the use
does not mislead the consumer at expected levels of human consumption
• if additive is approved it gets an E-number
• only authorized additives may be used
how safety of additives is evaluated & why not all additives have an ADI and why additives
without an ADI are also of no concern.
• additives with a numerical ADI defined (azo dyes, aspartame, cyclamate, saccharin)
• additives with a temporary numerical ADI insufficient toxicological information, often an extra
safety factor is used (curcumin, gallates)
- three major aims of the field of food toxicology.
Define toxicity, mechanisms of action and structure activity relationships for chemicals
to which humans are exposed via food; Evaluation of health and environmental
hazards and risks: risk assessment; Advisory task for authorities, industries, and
consumers
- difference between avoidable and unavoidable hazards
Avoidable chemicals: • Additives • Flavourings • Veterinary medicines • Pesticides •
Supplements
Unavoidable chemicals • Contaminants: persistent organic pollutants • Contaminants:
metals • Natural toxins: from plants • Natural toxins: from animals • Nanomaterials
risk assessment
Understand the role of risk assessment in the framework of risk reduction. - Understand why
risk management is not the same as risk assessment. - Understand risk characterisation for
man and the role of uncertainty factors therein.
Hazard = potential danger of a compound or process
Risk = probability that an adverse effect will occur = hazard + exposure
-differences between risk assessment for genotoxic and non-genotoxic chemicals.
Genotoxic carcinogenic compounds: damage DNA and cause mutations. a threshold cannot
be defined: every molecule increases risk on cancer.
Avoidable compounds: zero tolerance: Compound should not be present and cannot be used
Unavoidable compounds:
ALARA: As Low as Reasonably Achievable
Threshold of Toxicological Concern (TTC): TTC for genotoxins: 0.15 mg/person per day –
Virtual Safe Dose (VSD):
dose causing 1 in 106 additional cancer risk upon life-time exposure (quantitative risk
assessment)
Linear extrapolation from experimental data to zero risk at zero dose; define VSD at 1 in 106.
Margin of Exposure (MOE)
- BMDL10: Statistical lower confidence limit of the dose giving a 10% increase in effect over
background level.
- MOE should be at least • 100 to interspecies differences (10) and human variability (10) • 10
for uncertainties relating to carcinogenic process • 10 for BMDL10
- MOE to be used by risk managers:
to set priorities (MOE > 10 000 of low concern/health risk; MOE < 10 000 of concern; priority
for risk management)
to define an MOE that would be considered acceptable is a responsibility of risk managers
Non-genotoxic compounds: a safe level of exposure (threshold) can be defined,
Define Target organ = most sensitive organ
Dose response Relationship For target organ, NOAEL = No Observed Adverse Effect Level
ADI = Acceptable daily intake for avoidable contaminants like additives, pesticides
TDI = Tolerable daily intake for unavoidable contaminants like dioxins, mycotoxins, heavy
,metals
- advantages of the BMD approach and the disadvantages of the NOAEL approach.
NOAEL BMD
dependent on sample size: not dependent on set-up of experiment
- more dose groups, more animals more animals higher BMDL;
- lower NOAELs; better experimental designs better experimental designs are no longer
are penalized penalized
NOAEL limited to experimental dose BMDL has on average about same level of
protection as NOAEL
differs across studies same uncertainty factors can be used more
dose groups
only one experimental data point is used making use of all toxicity data
BMR = benchmark response pe 5% or 10% effect over background level; BMD = Benchmark
dose (dose causing the BMR); BMDL = lower confidence limit of the BMD
Food carcinogens
Genotoxic chemicals in food (unavoidable)
natural carcinogens
- Phytotoxins (from plants) DNA adduct formation
- Alkenyl benzenes
example: estragole & methyl eugenol in basil and other spices, some vegetables (fennel) products
made thereof (pesto)
intake from added uses MOE = 116 High priority! In EU actions taken
Intake from herbs and spices MOE = 4400 – 44000 low(er) priority
- Pyrrolizidine alkaloids: have been found in honey and tea(comfrey) every day 1 cup of tea a
whole lifetime
- Mycotoxins (from fungi/molds)
- Aflatoxins
Example: aflatoxin B1 (produced by Aspergillus flavus)
mutation hotspots P53 tumor suppressor gene (APC: mutated in most colon cancer) results liver
cancer, MOE: 88-483 priority for risk management
endogenously formed carcinogens
-nitrosamines: nitrite(vegetables) + amine (fish)=nitrosamines
Example: N-Nitroso dimethylamine (NDMA)
young children: MOE = 7250
in adults: MOE = 72500
carcinogens formed during food preparation
- PAHs (polycyclic aromatic hydrocarbons) Pyrolysis of fat (temp 300°C - 600°C)
e.g. benzo[a]pyrene-BaP smoked, grilled, barbecued or burned foods MOEs indicate a low concern
for consumer health
- HCAs (Heterocyclic amines) Maillard reactions: sugars-amino acids, proteins (temp < 250°C)
e.g. heterocyclic amines (PhIP) “hamburger carcinogen” MOE 15,000 low priority
- Acrylamide French fries, chips, bread MOE values 40-400 << 10 000 Of concern! Risk management
actions required
, -furans in coffee, canned and jarred food MOEs: 36 - 582 (methyl furans not yet included)
non-genotoxic chemicals in food
Coumarin ( in cinnamon): carcinogenicity secondary to liver toxicity
co-carcinogens and antimutagens/anticarcinogens
Chemicals in food may reduce cancer formation by various mechanisms:
▪Reduction of effects of carcinogens by modulation of biotransformation enzymes
▪Reduction of inflammation
▪Reduce oxidative/electrophilic stress
▪Reducing proliferation tumor cells
▪Reducing bioavailability
Possible binding of aflatoxin B1 to chlorophyllin (from green vegetables) reduces bioavailability
Food additives
the need for food additives in the modern food chain.
1) to maintain product consistency: emulsifiers, thickeners
2) to improve or maintain nutritional value: vitamin, mineral restauration & enrichments
3) to maintain palatability & wholesomeness: preservatives, antioxidants
4) to provide leavening or control pH
5) to enhance flavor or impact desired color
the requirements before additives can enter the market and get an E- number.
• anyone who wants to put an additive on the market must provide convincing evidence that the
proposed additive - performs as intended - will not cause adverse health effects and that - the use
does not mislead the consumer at expected levels of human consumption
• if additive is approved it gets an E-number
• only authorized additives may be used
how safety of additives is evaluated & why not all additives have an ADI and why additives
without an ADI are also of no concern.
• additives with a numerical ADI defined (azo dyes, aspartame, cyclamate, saccharin)
• additives with a temporary numerical ADI insufficient toxicological information, often an extra
safety factor is used (curcumin, gallates)
