Transcript Introduction to adverse effect and risk management

Introduction to adverse effect
Two major problems in food safety
assessment
Food toxicologists are confronted with two major
problems:
• food and food products are complex chemical
mixtures of variable composition;
• the existing procedures for extrapolation of
animal toxicity data to man are incompatible with
Recommended Dietary Allowances (RDAs) for
many essential nutrients and also with the
normal use of many common foods and food
products.
Toxicity (testing) of food chemicals and foods
Toxicity (studies) of single food components
(additives, contaminants, natural toxins and
nutrients) in experimental animals with special
attention to (macro)nutrients
Toxicity (studies) of food and food products in
experimental animals
Toxicity (studies) of food components, food
products and foods in humans with emphasis on
special subpopulations (e.g. identification of
individuals hypersensitive to certain nutrients
like cow milk protein)
two lines are combined using this approach:
• from single substances to complex mixtures,
• from studies in experimental animals to
studies in humans.
Toxicity of (food) chemicals
• Toxicity (or hazard) is the potential of a chemical to
induce an adverse effect in a living
organism e.g., man.
• Each chemical, each food component, has its own
specific toxicity
essential amino acid,
a trace element,
vitamin,
contaminant or additive
• Whether a food component is of natural origin or is
man-made is irrelevant for its health hazard.
Information on the toxicity (hazard) of
food chemicals is obtained
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from studies in experimental animals,
in vitro studies,
studies in volunteers,
or epidemiological studies.
The main goals of these studies are to
determine
(a) the type of adverse effects,
(b) dose–effect relationships including the noobserved-adverse-effect levels,
(c) the mechanisms underlying the adverse
effects.
The interaction of a substance with a
living organism
• can be divided into a kinetic phase and a dynamic
phase.
• The kinetic phase comprises absorption, distribution,
metabolism, and excretion.
• An inhaled substance reaches the blood circulation
through the lungs, while a food component passes the
liver, which is the main organ involved in
biotransformation.
• These mechanisms are aimed at detoxication of the
substances that enter the body. However, the systems
involved in detoxication may be saturated with certain
chemicals. But also, they may convert the parent
substance into a toxic reactive intermediate
(bioactivation).
Food, a complex mixture of variable
composition
• the chemical composition of food can be
extremely complex and variable.
• the toxicity of such a complex mixture does
not simply depend on the toxicities of the
individual components.
• Interactions may occur that lead to synergism
or antagonism.
the development and implementation
of a priority-setting system based on
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the amount ingested,
the number of consumers,
potential toxic effects of food components,
or combinations of groups of food
components,
• and possible interactions between
components.
Problems in toxicity testing and
extrapolation of animal data to man
• For most food additives and for many
contaminants, the amount allowed for human
consumption is at most 1% of the highest dose
shown to cause no adverse effect in an
appropriate animal study.
• the safety data base of such food products
should be expanded beyond the traditional
requirements
• studies on absorption, distribution, metabolism, and
excretion
• from in humans and non-human primates
• from longterm studies in appropriate primates,
• from studies in humans on the possible effects on
vitamin and mineral state
• and from very specific toxicity tests,
• e.g., for immunotoxicity and neurotoxicity.
• the safety evaluation of macronutrients
requires more fundamental information on
their effects on physiology and their
toxicology.
Categories of food components
are classified into four groups:
1. Nutrients
2. non-nutritive naturally occurring components,
including antinutritives and natural toxins,
3. man-made contaminants
4. additives
• the information on the (chronic) toxicity of
natural food components is insufficient.
• a number of important health problems such
as cardiovascular disorders, diabetes,
osteoporosis, obesity, allergy, and cancer are
believed to be related to nutrition
nutritionists and food toxicologists
food hazards should decrease
Wrong dietary habits
• main causes for the nutrition-related disorders
• A more balanced diet means changes in
dietary habits: energy according to need, and
less fat, cholesterol, salt, sugar, and alcohol,
and more dietary fiber.
• the margin between physiological need and
safe dose
• require information on the physiology and
toxicology of macro- and micronutrients
Microbial contamination
Natural toxins
Man-made contaminants
 substances unintentionally present in foodstuffs or
their raw materials.
 They may occur as the result of
• production,
• processing,
• preparation,
• packaging,
• transport or storage of foods or their raw materials,
• or as a result of environmental contamination.
 By definition, contaminants are unintentional, but
some are present as a result of intentional applications,
e.g., residues of pesticides, additives to feedstuffs, or
veterinary drugs.
Additives
Toxicological data are generally
obtained
• from various types of animal experiments,
• in vitro studies,
• and studies in humans.
• Studies in experimental animals have become
the main source of toxicological data,
although ideally the data should be obtained
from humans because the ultimate goal is to
assess the health risk from chemicals to
humans.
• In vitro studies using organ and cell cultures of
animal and human origin are increasingly used
to study the mechanisms underlying the
adverse effects.
• Epidemiological studies are one type of
studies in humans.
in vitro systems are:
• toxic effects can be studied independent of other
compartments in the body;
• the systems are often very sensitive, and effects can be
measured or calculated directly;
• in vitro systems are excellent tools for screening
substances for organ-directed toxicity;
• molecular studies are easier than in vivo studies;
• phenomena and mechanisms can be studied in human
cells which allows direct comparison of effects on
human cells with effects on animal cells, which possibly
makes extrapolation of toxicity data from animal to
man more meaningful.
Table 8.1 Microorganisms causing food-infections or
food intoxications Microorganism Pathogenicity
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Salmonella
Shigella
Escherichia coli
Yersinia enterocolitica
Campylobacter jejuni
Listeria monocytogenes
Vibrio parahaemolyticus
Aeromonas hydrophila
infection
infection
infection
infection
infection
infection
infection
infection
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Staphylococcus aureus
Clostridium botulinum
Clostridium perfringens
Bacillus cereus
Aspergillus flavus
Penicillium citrinum
Aspergillus ochraceus
Aspergillus versicolor
Penicillium claviforme
Fusarium graminearum
enterotoxin
botulinum toxins
enterotoxin
enterotoxin, emetic toxin
aflatoxins
citrinin
ochratoxin
sterigmatocystin
patulin
zearalenone
Table 8.2 Classification of natural toxins
according to their origin
Toxins
Organism
Toxic product (examples)
Bacterial
toxins
BacteriaBotulinum toxin
Mycotoxins Fungi
Aflatoxin
Fycotoxins
Algae
Diarrhetic shellfish poison
Fytotoxins
Plants
Solanin