Summary Food Toxicology TOX-30306

SUMMARY FOR FOOD TOXICOLOGY (TOX-30306)

Lecture 2: Risk Assessment

Basic principles of risk assessment

Key terms

 Risk assessment = the systematic scientific evaluation of potential adverse health effects
resulting from (human) exposure to hazardous agents or situations
 Dose-response relationship= Increased dose, is increased response, is increased adverse
health effect
 Hazard = potential danger of chemical or process
 Risk = probability that adverse effect will occur
 Risk = hazard + exposure

4 Steps of risk assessment

 1. Hazard identification
o Source of potential harm
o Intrinsic toxic properties of the (chemical) agent
 2. Hazard characterisation (dose-response)
o Some compounds are more hazardous than others, is defined by median effect dose,
how lower that dose he more hazardous the chemical is, because you need less of
the dose to see toxicity
o Dose-response helps to characterize he potency of chemicals
 3. Exposure assessment
o 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
o Ideally, it describes the sources, transport, routes and the uncertainties in the
assessment
o Assess applied dose
o Consider exposure continuum and associated modelling and measurement tools to
define applied dose

,  4. Risk characterisation
o Probability of an adverse outcome based upon the exposure and potency of (a)
hazardous agent(s)
 4.1 Risk management
o 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
 4.2 Risk communication

Risk management vs risk assessment




What is a hazardous agents?

 In toxicology focus on chemicals, but can also be biological or physical hazard

Regulatory Agencies Performing Risk Assessments

 European Medicines Agency
 European Food Safety Authority
 European Chemicals Agency

,Discriminate between 2 types of chemicals

1. Non-genotoxic chemicals
2. Genotoxic chemicals (chemicals causing DNA damage)

Type of risk assessment dependent on type

Risk assessment of non-genotoxic chemicals

Risk assessment non-genotoxic chemicals in food

 Non-genotoxic compounds have defined
threshold (safe level of exposure) e.g. receptor
inhibition
 Median effective dose (EC50) = for comparing
chemical potency
 Lowest Observed Adverse Effect Level (LOAEL)
= lowest tested dose at which adverse effect
was observed
 No Observed Adverse Effect Level (NOAEL) =
Highest tested dose at which no adverse effect
was observed

Toxicity testing scheme

 Chemical characterization: What type of chemical is it?
 Literature review: What information is already there?
 Structure-Activity Assessment: What does the compound look like?
 (Sub)Acute Toxicity: Test exposing animals with an increasing (single) dose and observe what
happens
 Sub chronic Toxicity: give animal chemical at certain dose for 90 days, NOAEL and reference
dose established
 Chronic Toxicity: give animals compound for entire life time and see what happens
 Reproductive/ Teratology: Give chemical for entire life time and look at the reproductivity
 Oncogenicity: What potential is there for the chemical to produce tumour formation

, Choice of Dose-response relationship

Dose response relationship for target organ (i.e., most sensitive organ)
Which dose response to start with? Response at lowest dose, and most critical effect which is
clinically relevant.

Reference Dose (RfD) setting

 Establish causality that the chemical has in fact induced the observed effects
 Establish NOAEL, LOAEL (to ID point of departure, POD)
 Determine rate at which injury builds up: slope of dose response curve
 Apply uncertainty factors

Uncertainty Factors (UF) in RfD setting

 UF = Uncertainty/safety factors used to extrapolate from a group of test animals to an
average human and from average humans to potentially sensitive sub-populations
 RfD = NOAEL / / other UFs  quality of data type exposure

Toxicokinetics vs toxicodynamics

 Dynamics = What the chemical does to the body
 Kinetics = What the body does to the chemical  Absorption, Distribution, Metabolism,
Excretion

ADI vs TDI

 Reference doses determined by EFSA to indicate doses of chemical which we can safely be
exposed to daily
 ADI = Acceptable daily intake (voluntary exposure)
 TDI = Tolerable daily intake (involuntary exposure)