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Summary Food Toxicology (Grade: 9.8)

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I have summarized the lectures of Food Toxicology. It is a rather elaborate summary, as no reader is available for this course. This document would thus be an excellent exam preparation! Good luck studying for the exam :)

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  • March 8, 2023
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  • 2022/2023
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Lecture 1 - Risk Assessment (20/2/2023)


- Risk assessment: the systematic scientific evaluation of potential adverse health
effects resulting from (human) exposures to hazardous agents or situations.
- Hazard: potential danger of a chemical or process.
- Risk: probability that an adverse health effect will occur.
- Risk = hazard + exposure.

● Risk assessment questions:
○ What is the compound capable of doing to humans?
○ What is the likelihood of such an effect at the levels to which humans are
exposed.
○ What level of intake would be without an appreciable health risk, if consumed
daily over a lifetime.

● Steps of risk assessment:
1. Hazard identification.
2. Hazard characterization (dose-response).
3. Exposure assessment.
4. Risk characterization.
a. Risk management.
b. Risk communication.

1. Hazard identification:
● What types of adverse health effects can you expect?
● Hazardous agents may be:
○ Chemical.
○ Biological.
○ Physical.

2. Hazard characterization:
● How much of a chemical do you need to have an
effect?
● On the right you can see a picture of a dose
response curve.
○ X-axis: dose/concentration (mg/kg bw).
○ Y-axis: response
● The more toxic the chemical, the more the curve (in
dose response graph) shifts to the left.
● One defines the source of potential harm.
● Characterization of the intrinsic toxic properties of the
agent.

3. Exposure assessment:
- Exposure assessment: the process of estimating or measuring the magnitude,
frequency and duration of exposure to an agent, along with the number and
characteristics of the population exposed. Ideally, it describes the sources, transport,

, routes and the uncertainties in
the assessment.
● The level of exposure is a
function of the concentration and
exposure factors.

4. Risk characterization:
● Risk management and risk
communication are part of risk
characterization.
- Risk management: the process
of identifying, evaluating,
selecting and implementing scientifically
sound, cost-effective, integrated actions to
reduce risk to human health and
ecosystems while taking into account
social, cultural, ethical, economical, political
and legal considerations.
● The picture on the right illustrates the
differences between risk management and
risk assessment.
● There are several regulatory agencies that
perform risk assessments:
○ European Medicines Agency.
○ European Food Safety Authority
(EFSA).
○ European Chemicals Agency.

● When it comes to human risk assessment, one discriminates between 2 types of
chemicals:
○ Non-genotoxic chemicals.
○ Genotoxic chemicals.
● The risk assessment procedure differs for these different chemicals.

Non-genotoxic chemicals:

● Non-genotoxic compounds (do
not interact with genetic
material) have a defined
threshold (safe level of
exposure).
○ These chemicals can for
instance be receptor
inhibitors.
● The picture on the right shows
the procedure for how to obtain
a dose-response relationship.

,- Median effective dose (ED50): for comparing chemical
potency.
- Lowest observed adverse effect level (LOAEL):
lowest tested dose at which an adverse effect was
observed.
- No observed adverse effect level (NOAEL): highest
tested dose at which (statistically) no adverse effect was
observed. Most important point of departure for a risk
assessment.

● There are lots of effects one can observe within animals
upon exposure (liver enlargement, higher white blood
cell count, etc.). So, what dose-response curve should
you use for risk assessment.
● The effect has to be critical!
● One should pick the dose-response curve for the most sensitive organ (target
organ).

- Reference dose: maximum amount/dose one can be exposed to safely.
● Reference dose (RfD) setting:
1. Establish causality that the chemical has in fact induced the observed effects.
2. Establish NOAEL, LOAEL (to ID point of departure, POD).
3. Determine the rate at which injury builds up: slope of dose response curve.
4. Apply uncertainty factors.

● Uncertainty factors (UFs) are used to extrapolate from a group of test animals to an
average human and from average humans to potentially sensitive sub-populations.
● RfD (reference dose) = NOAEL / / other UFs.
○ If there is, for instance, no NOAEL available, another factor is added.




● There is both toxicokinetics vs. toxicodynamics.
○ Toxicokinetics is about what the body does to the chemical.
■ Absorption.
■ Distribution.
■ Metabolism.

, ■ Excretion.
○ Toxicodynamics is about what the chemical does to the body. The mechanism
of attack.

● Reference doses that are determined by a.o. EFSA are there to indicate doses of a
chemical which we can safely be exposed to daily.
- ADI: Acceptable Daily Intake (voluntary exposure). Used for chemicals that are
purposely added to food.
- TDI: Tolerable Daily Intake (involuntary exposure). You cannot stop being exposed
for compounds with a TDI.

● Examples of non-genotoxic risk assessment:
○ Cyclamate.
○ DON.
○ Dioxins.

Cyclamate:
● Artificial sweetener that causes testicular atrophy in rodents.
● NOAEL: 700 mg/kg bw/day.
● Is cyclamate’s RfD an ADI or TDI?
○ ADI.
● ADI = 700 mg/kg bw/day (NOAEL) / = 7 mg/kg bw/day.
● Re-assessment, as it is now more precise to assume that children consume 0.7 L of
soft drink a day.
● EDI = 0.7 L/day soft drink x 350 mg/L cyclamate in soft drink / 25 kg bw = 9.8 mg/kg
bw/day.
○ Above ADI!
● Should EFSA change the ADI or MPL?
○ The ADI does not change. The MPL should thus change (from 350 to 250
mg/L). Producers cannot add more than 250 mg/L cyclamate.

DON:
● Causes immunotoxicity, growth retardation in children. It is found on wheat.
● It is also known as “vomitoxin”.
● TDI = 1 microgram/kg bw/day.
● Chronic exposure is estimated to approximately 0.22-1.86 microgram/kg bw/day.
○ EDI > TDI!

Dioxins:
● Dioxins are unavoidable, so the reference dose is expressed as a
TDI.
● TDI = pg (peta gram) TEQ/kg bw/day.
- TEQ: toxic equivalency quotient. Refers to the toxicity of a mixture
of dioxin-like chemicals.
● The TEQ is calculated by the summation of all concentrations of dioxins one is
exposed to. This is subsequently multiplied by a toxic equivalency factor (TEF).

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