Download 1_01a Food Chemical Risk Assessment

Chapter One – General Concepts on Food Chemical Risk
Assessment
Introduction to General Concepts of Food Chemical Risk Assessment
The objectives of this first section of the chapter is to introduce some very
general concepts about food and why chemicals in food are important, both in
the positive sense that many that occur naturally are essential for human and
animal nutrition and well-being, whilst some present naturally or which may be
added for various reasons can be unsafe, depending on the exposure.
The main questions we need to address are:
•Understanding what food chemicals are?
•Why are they present in food?
•Why some chemicals present in food are unsafe?
•What basic questions need to be answered when assessing their safety?
But before we address these concepts and questions we need to introduce
some general information that will be helpful to set the context. These are:
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Introduction to general risk analysis and risk assessment
Introduction to toxicity/toxicology
Hazard, exposure and risk – The dose makes the poison
General concepts of food and nutrition and lifestyle factors
Basic food chemistry -the elements, molecules, chemicals (wanted and
unwanted)
Food chain, food processing and farm to fork
Why perform a food chemical risk assessment?
Basic elements of food chemical risk assessment
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Chapter 1 – Part 1
Introduction to Risk Assessment
There are many definitions of risk assessment and it is not intended to elaborate on
all of them at this early stage of the module. A reasonable general explanation is
given in the Australian Department of Health document Environmental Health Risk
Assessment (2002) as “Risk assessment is the process of estimating the potential
impact of a chemical, physical, microbiological or psychosocial hazard on a specified
population (Environmental Health Risk Assessment : Guidelines for assessing
human health risks from environmental hazards. ENHRA, 2012). It should be noted
that there are different definitions of risk assessment and the above by ENHRA is
just one of them. The Codex Alimentarius, WHO/FAO and WTO have similar
versions but do not include “psychosocial” hazard in their definitions of risk
assessment.
The below diagrams taken from ENRHA shows one possible framework model that
encompasses the five stages of one example of a model for risk assessment and
their inter linkage with stages of risk management. Conceptually, the five stages are
closely linked and dependent on the preceding stages. The terminology is similar to
terminologies used by other major models such as Codex, FAO/WHO and WTO..
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Figure 1.
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The above Figure 2 is a more comprehensive version of the first diagram outlining
three phases: Phase I – Problem formulation and scoping; Phase II – Planning and
conduct of the risk assessment; and Phase III – Risk management. Under Phase II,
the usual steps in the conduct of the risk assessment are outlined under Stages I, II,
and III using a decision tree approach connecting to Phases I and III with ”yes” “no”
answers to the questions to ask yourself under Stage III - “Confirmation of Utility”.
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Risk Assessment is intended to “provide complete information to risk managers,
specifically policymakers and regulators, so that the best possible decisions are
made.” (Paustenbach, 1989).
There are uncertainties related to risk assessment and it is important to make
the best possible use of available information. Risk assessment may be done as a
relatively rapid ‘desk top’ study for simple issues or may be a large and complex
process where there are significant health concerns. There are numerous models of
risk assessment to suit the many contexts in which risk assessments are undertaken
(ENHRA, 2012). One of the concerns about some stakeholder perceptions of current
methodologies is that an impression may be given that the derived risk assessment
number, whether based on extrapolation or an Acceptable Daily Intake
(ADI)/Provisional Tolerable Daily Intake (PTDI) approach, can be taken as a ‘bright
line between possible harm and safety’ (NRC 2008 p. 8) or, in other words, the
separation between safe and unsafe exposures. While it is important to dispel this
myth in the risk communication process by explaining its inaccuracy because of
variability and uncertainty, one should not lose sight of the fact that an exceedance
of a standard or guideline or other indicator of ‘safety’ by a derived risk assessment
number should always trigger further consideration of the situation being assessed.
Such consideration could include refinement of the assumptions, modelling or input
values, and the magnitude of safety factors.
Food Chemical Risk Assessment
Food chemical risk assessment is a scientific discipline that uses a formal approach
which includes certain pre-defined terms such as “hazard”, and “hazard
identification” and “risk” which have been defined by the Codex Alimentarius
Commission (CAC) (Codex Handbook), the World Health Organisation (WHO) (Ref)
and World Trade Organisation (WTO) ( Ref). Nevertheless as a scientific discipline
it’s way of working can be derived from the questions that are posed to it. Hence it is
proposed to develop the concept of food chemicals risk assessment and its
principles together with the participants using examples rather than providing too
many terms and definitions.
A global food chemical training module faces the challenge that for some important
aspects of chemicals risk assessment, such as genotoxicity and carcinogenicity,
approaches applied by food safety authorities differ. In order to understand and
appreciate such differences, it is necessary to explain those without judging them or
even taking sides on controversial issues (e.g. GM foods and use of growth
hormones).
In relation to food chemical risk assessment in general, it is useful to introduce some
commonly accepted stages:
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Issue identification/Problem Identification (formulation)
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Hazard identification
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Dose-response assessment/Hazard Characterisation
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Exposure assessment for the relevant population
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Risk characterisation
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The concept of Toxicity
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The concepts that “The dose makes the poison” and “Risk = Hazard x
Exposure”.
The below table gives the example of lead exposure to try to explain the context of
each of the concepts.
Table 1.
Concept
Issue identification/Problem
Identification (formulation)
Hazard identification
(Dose response assessment)
Hazard Assessment followed by Hazard
Characterisation
Exposure assessment in relevant
population
Risk characterisation
Concept of toxicity
Example of Lead
Lead is a very toxic heavy metal
contaminant that is found in the
environment either occurring naturally
or as a result of human activity, and is
taken up by plants that are eaten by
humans
Lead is a neurotoxin even at very low
levels, and is especially toxic to the
foetus in utero and in infants and young
children, causing brain damage and
learning deficits. JECFA recently
removed the PTWI for lead on the basis
that no safe level of exposure could be
found on available data
Lead is toxic even at very low levels, but
the toxic effects are dose responsive so
that as the dose becomes larger, so
does the toxic effect get larger
Humans are exposed to lead via
contamination in the environment as a
result of contamination from natural or
man-made processes. The whole
population, adults and children, is at risk
from the toxic effects of lead, but the
most sensitive part of the population is
to the foetus whilst in utero, and in
infants and young children due to their
sensitivity to the neurotoxic effects of
lead exposure, even at very low doses
The risk to humans in general is high;
the risk from exposure to lead to the
foetus in utero, and in infants and young
children is very high to extreme
Lead produces a range of adverse
health effects in animals and humans
(toxic effects), by targeting body organs
especially the human brain
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Dose makes the poison
Risk = hazard x exposure
Lead has been shown to produce toxic
effects at even very low levels; the
higher the concentration of lead, the
more adverse is the toxic effect
Using this concept, the risk to humans
from the exposure to the hazard (lead
toxicity), especially the foetus, infants
and young children, is high to very high
(high to very high risk is interpreted to
mean a highly significant risk) even at
very low exposures
By introducing the terminology for these stages in general early, it will make it easier
to use some examples in the following sections, and the terms will be defined and
expanded upon in later modules. Only Issue Identification/Problem Identification,
Hazard Identification, Toxicity and the concept that “The dose makes the poison” will
be discussed in this early module. Note that here we have combined the concepts of
Issue Identification and Problem Identification to encompass different use of these
terms around the world but essentially the terms mean the same thing. Note also
that language used to describe the characterisation of the risk often varies across
the world. You may see terms used such as “low, medium and high” or “very low”
and “very high” or in some cases scorings are used. Whatever the description used,
there should be an attempt to put such term into suitable context and to explain what
they mean in plain simple language, including the level of uncertainty with the data
and methodologies used, and internationally there should be better coordination and
harmonisation on the risk characterisation terms used across the world.
Issue Identification/Problem Identification (formulation)
Issue Identification/Problem Identification identifies issues/problems amenable to risk
assessment and assists in establishing a context for the risk assessment by a
process of identifying the problems that the risk assessment needs to address. It
includes:
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What is the concern?
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What is causing the identified concern?
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Why is the concern an issue?
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How the concern was initially identified?
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How the concerns were raised?
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Whether the issue is amenable to risk assessment?
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Whether risk assessment is appropriate?
Hazards vs Issues/Problems
Food chemical “Hazards” need to be distinguished from food chemical “Issues” or
“Problems”. Issues/problems establish a context for the risk assessment and assists
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the process of risk management. Issues/problems have dimensions related to
perceptions, science, economics and social factors. Imagine a consumer who is
concerned, but is there really a concern? So an assessment needs to be done of the
possible hazard. But what does a hazard mean? Is the concern a perception or is it
real? Examples of food chemical issues include community concern over the use of
gene technology to produce foods, use of new food additives and a new food
microbiological standard.
Food chemical “Hazards” relate to the capacity of a specific agent to produce a
particular type of adverse health effect. Again there are some different definitions of
“hazard” and the Codex Alimentarius Commission defines “hazard” as the “agent”
that causes an adverse effect and not the capacity of the agent to cause the adverse
effect. These are fine distinctions that are often debated internationally. Examples of
food chemical hazards include the capacity of heavy metals found in food to cause a
variety of serious health problems (toxicity) at certain concentrations, and
cyanogenic glycosides in cassava that can cause cyanide poisoning.
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Chapter 1 – Part 2
Toxicity/toxicology
It is not intended in this module to produce a detailed and comprehensive course in
toxicology. However, in order to discuss food chemical risk assessment we need as
a starting point to introduce the concept of chemical toxicity, and the discipline of
toxicology which is used to examine chemical toxicity in a structured way.
An abbreviated history
The history of toxicology can be traced as far back as passages in the Bible in
relation to venoms and plant poisons (Deuteronomy 32:24, ”with the venom of
reptiles gliding in the dust”, and 32:33, ”poisonous are their grapes and bitter
clusters”. The ancient Egyptions studied lists of poisons as far back as 3,500-3,000
BC, whereas between 1553 and 1550 BC the German Egyptologist Georg Moritz
Ebers discovered the Eber Scrolls containing 110 pages of script, and identifying
more than 700 drugs in about 875-900 formulas used by Egyptians. For example,
Cleopatra’s alledged poisoning is attributed to using cosmetics containing lead. The
Chinese (Shen Nung), Greeks (Socrates, Hippocrates, Diocles, Aristotle), Romans
(Pliny the Elder) and Arabs, Jews, Swiss (Paracelsus), German s, French, Spanish
(Orifila), and many others made significant contributions to the study of toxicology.
However, it is not known how far back knowledge of poisonous plants and animals
and herbal remedies/pharmacology can be attributed, but is assumed that early
humans probably learned through experience about the harmful properties of insects
and animals (venoms) and plants (poisons) and used them to aid in hunting and
gathering.
Other examples of food toxicity are where mycotoxins killed 40.000 people of
ergotism in 992 in France and Spain, and microbiological contaminations have
caused numerous episodes of foodborne disease, resulting in serious sickness and
death since humans have inhabited the earth. For a contemporary example, it is
estimated that in Australia, there are over 4 million cases of foodborne disease per
year, with approximately 30 thousand hospitalisations and 80 deaths per year ina
population of 23 million.
In yet another example, the Greek philosopher, Socrates was ultimately sentenced
to death by drinking a hemlock-based extract. Hemlock contains the pyridine
alkaloids coniine, N-methylconiine, conhydrine, pseudoconhydrine and γ-coniceine.
The most toxic of these is coniine, which has a chemical structure similar to nicotine.
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Coniine containing plants have actions similar to nicotine. Clinical effects will depend
on the dose of coniine or coniine-like alkaloid ingested. The nicotinic effects are
biphasic, with stimulation followed by CNS depression and paralysis of respiratory
muscles. Initial symptoms may be vomiting, confusion, respiratory depression, and
muscle paralysis. Death, when it occurs, is usually rapid and due to respiratory
paralysis.
A major problem in early times was the detection of toxicants –first approached by
Orfila, the father of modern toxicology. Mathieu Joseph Bonaventure Orfila (24 April
1787 – 12 March 1853) was a Spanish born French toxicologist and chemist, often
seen as the founder of the science of toxicology.
Example: Role in Forensic Toxicology
If there is reason to believe that a murder or attempted murder may have been
committed using poison, a forensic toxicologist is asked to examine pieces of
evidence such as corpses and food items for poison content.
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At Orfila's time the primary poison in use was arsenic, but there were no reliable
ways of testing for its presence. Orfila developed new techniques and refined
existing techniques in his first treatise, Traité des poisons, greatly enhancing their
accuracy. In 1840, Marie LaFarge was accused for the murder of her husband using
arsenic. Mysteriously, although arsenic was available to the killer and was found in
the food, none could be found in the body. Orfila was asked by the court to make
further investigations. He discovered that the test used, the Marsh Test, had been
performed incorrectly, and that there was in fact arsenic in the body, allowing Marie
LaFarge to be found guilty.
Paracelsus (1493-1541)
One of the most important concepts in toxicology was determined by Paracelsus.
Paracelsus said “Alle Ding' sind Gift und nichts ohn' Gift; allein die Dosis macht, dass
ein Ding kein Gift ist. This translates from German into English as follows: "All things
are poison and nothing is without poison, only the dose permits something not to be
poisonous."
It cannot be stressed too strongly that this concept of “the dose makes the poison” is
extremely important to consider when undertaking a food chemical risk assessment.
The corollary is that “risk is equal to the hazard x exposure”. We have already
introduced the concept that all chemicals possess an intrinsic hazard (the capacity
for a specific agent to produce a particular type of adverse health effect). However,
for risk-based assessments, the actual risk will always depend on the exposure or
dose of the chemical. This is just common sense, but may often be overlooked by
the community and regulators alike. So if the dietary exposure (or environmental
exposure) is low, then the actual risk is also likely to be low, but this also depends on
the type of hazard the chemical presents. Food regulators therefore use an exposure
assessment, together with a hazard assessment, to determine the risk to human
health. For example, even water can be toxic if enough is ingested (deaths have
been recorded in people who have ingested approximately 10 litres of water in a 24
hour period).
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What can be Toxic?
Toxicity is often defined, amongst other definitions, as the harmful effect of a
chemical or a drug on a living organism. Toxic effects can be acute or chronic.
Acute, subchronic and chronic toxicities have been defined by various expert groups,
including the Organisation for Economic Cooperation and Development (OECD)
(Document 174 ). A chemical compound (or a mixture) that is toxic may e.g. be
called: a poison, a toxin,a biotoxin or a toxicant.
Answer this question as a short exercise : What are the differences?
http://en.wikipedia.org/wiki/Toxin
http://en.wikipedia.org/wiki/Toxicant
Many agents can be toxic. These can include elements, chemical compounds,
products, and plant toxicants that occur naturally. The following are some examples:
Elements - solid, liquid or gas ”element” (examples)!
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Lead (Pb) (metal found in some crops and seafoods). What is the
toxic/harmful concentration of lead?
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Arsenic (As) (metalloid in grains such as rice and in water supplies)
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Mercury (Hg) (converted to methylmercury in seafood, marine plants etc)
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Calcium, copper, iron, selenium, sodium, magnesium, manganese, potassium
(essential dietary minerals but can be toxic at high concentrations)
A chemical compound (examples)!
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Sodium Chloride (NaCl also known as salt!)
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Carbon dioxide (CO2)
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Ethanol (CH3CH2OH)
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Cyanide (HCN)
A ”product” (examples)!
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Agricultural and veterinary chemicals – pesticides, insecticides, fungicides
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Pollutants – lubricants, cleaning agents, dioxins and PCBs
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Food additives – preservatives, artificial colours, sweeteners, acidifiers etc
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Naturally Inherent Plant Toxicants (examples)!
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Macromolecular polyphenolic substances (hydrolysable and condensed
tannins)
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Toxic fatty acids/lipids
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Non-protein amino acids
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Alkaloids
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Furanocoumarins
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Polyacetylenes
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Mono-, sesqui- and diterpenes; and
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Toxic glycosides of various types (glucosinolates, cyanogenic glycosides,
saponins)
Naturally Inherent Plant Toxicants (examples)!
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Cyanogenic glycosides in casava and apricot kernels produce HCN.
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Proteinase inhibitors in legumes (e.g. Soybeans)
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Alkaloids in foods and beverages (e.g. quinine, caffeine)
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Pyrrolizidine Alkaloids in grains, teas and herbal supplements
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Gossypol in cotton seed oil
What is Toxicology
Toxicology is the study of toxins/toxicants (=toxic substances). One definition
according to Hayes ”Principles and Methods of Toxicology, Third Edition, is
”Toxicology is the study of adverse effects of chemical or physical agents on
biological systems; it is the science of poisons.” Toxic substances disturb the
physiological balance to the extent that the organism becomes ill. Toxicology is a
multidisciplinary field of science building on basic disciplines. Cassarett and Doull’s
(Toxicology, 5th Edition) defines toxicology as ”the study of adverse effects of a
chemical on biological systems”. There are several sub-disciplines of toxicology
including:

Analytical toxicology
http://www.who.int/ipcs/publications/training_poisons/analytical_toxicology/en/
index.html
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Clinical toxicology (see Ellenhorn, Medical Toxicology, 5th Edition)
Occupational toxicology (A.Wallace Hayes, Principles and Methods of
Toxicology, 3rd Edition; Casarett and Doull’s Toxicology, 5th Edition)
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Environmental toxicology(A.Wallace Hayes, Principles and Methods of
Toxicology, 3rd Edition; Casarett and Doull’s Toxicology, 5th Edition)
Food toxicology(A.Wallace Hayes, Principles and Methods of Toxicolog,
3rd Edition; Casarett and Doull’s Toxicology, 5th Edition)
Regulatory toxicology (A.Wallace Hayes, Principles and Methods of
Toxicology, 3rd Edition; Casarett and Doull’s Toxicology, 5th Edition)
http://www.ncbi.nlm.nih/gov/pubmed/11814699
The figure below illustrates how the various fields of toxicology interrelate with other
areas of biological science. For example, clinical pharmacology is associated with
medicine (therapeutics), pharmacy, clinical chemistry, drug trials and poisons
management (e.g drug overdose). Nutritional toxicology is associated with nutrition
science, food science and analytical chemistry, and so on.
Figure : Relationship of toxicology with other biological systems
Dose-Response Relationship
The dose-response relationship is one of the most important pillars in toxicology
theory and practice. It is not intended at this early stage to discuss dose-response
relationships in detail because this critical element of toxicology will be further
elaborated in Chapter 2 of this module.
In relation to acute toxic effects for example, according to A. Wallace Hayes
(Principles and Methods in Toxicology, Third Edition, Chapter 8, page 284), “The first
job of the toxicologist/risk analyst in assessing acute toxic effects is to define the
series of responses that link exposure to the critical effect in question. Ideally, the
analysis would attempt to determine (to whatever degree of precision is possible) the
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nature and magnitude of the dosage and disturbance of physiological parameters
that are necessary to cause each type of acute toxic response. In addition, the
analysis would determine the frequency of each response in a diverse human
population. Quantification of human inter-individual differences in pharmacokinetic
and pharmacodynamics parameters that affect individual susceptibility is critical if
risk assessment of these types of effects is to become more quantitative.” There are
mechanistic and statistically based models used. Use of mechanistic insights adds
value to the risk assessment process by reducing the uncertainty or potential bias
associated with arbitrary use of statistical methods or default values (e.g. safety
factors).
Toxic effects may be due to interaction with different targets through binding or
chemical interaction. Regardless of how an effect occurs, the concentration of the
toxicant at the site of action controls the effect. Dose-response data are typically
plotted with the dose or dose function (e.g. log10 dose) on the x-axis and the
measured effect (response) on the y-axis. Because a toxic effect is a function of
dose and time, such a graph is called the dose-response relationship and is
independent of time. Measured effects are most often recorded as maxima at the
time of peak effect. Effects may be quantified at the level of the molecule, cell,
tissue, organ, organ system or organism.
Toxicologists often obtain two types of data, quantal or “all-or-nothing” response, and
graded response which can be determined quantitatively and it is continuous. Some
general examples of quantal data include mortality and pharmacotoxic signs,
whereas some quantitative parameters include enzyme activity, protein
concentration, body weight, feed consumption and electrolyte consumption. A
specific example of a quantal response is the percentage of dead animals in an
experiment to describe the acute toxicity by determining the LD50 (Lethal Dose at
which 50% of the animals died; see Figure below). A specific example of a graded
response could be an increase in blood pressure for different groups of nimls
depending on the dosing of the group in question.
The below figure depicts the typical quantal dose=response relationship. The quantal
response can be viewed as a graded response if the whole population is considered
as an individual. This relationship can best be explained in terms of a probability
distribution. For a particular response, members of a population, for example, all the
rats in the world, respond differently to a particular stimulus such as exposure to a
chemical. Some rats will be highly sensitive whereas others will be very resistant. If
these different responses are distributed normally within the population (with most
members of the population being neither extremely sensitive or resistant), the wellknown bell-shaped distribution results. If the probability of dose-response is
expressed in terms of cumulative response, a sigmoidal curve can be obtained as
shown in the figure below. However, most biological response distributions are not
exactly normal and tend to be skewed to the higher dose, i.e. extreme resistors have
a larger range of dose to response that the extremely sensitive portion of the
population. In general, a logarithmic dose transformation can normalise the
distribution i.e. convert the skewed distribution to a normal distribution. After this
logarithmic dose transformation, if the probability of the log dose-response is
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expressed cumulatively, the sigmoidal response curve is obtained. Since a sigmoidal
curve is more difficult to analyse than a straight line, many experts feel that
transformations of the log-dose-response hyperbolic function is necessary to obtain
a straight line function curve.
The shape and the slope of the dose-response curve are therefore important in
predicting the toxicity of a substance at specific dose levels. Huge differences among
toxicants may exist not only in the point at which the threshold for the toxic effect is
reached, but also in the response increase per unit change in dose (i.e. the slope).
To summarise, toxic effects are the results of interactions between a toxicant and
one or more target molecules in one or more target tissues or organs. Any toxic
constituents will normally show a number of different toxic (adverse) effects, each of
which will be characterised by a threshold concentration/dose beyond which the
effect may be seen. A dose-response relationship will exist, which can be described
by a graph. The graphs for different effects of the same compound, as well as for
toxic effects of different compounds, may exhibit different slopes so that the
response increase per unit change in dose may vary.
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Chapter 1 – Part 3
Food Safety and Nutrition
We all eat and exercise to stay alive, to enjoy the taste of food and to socialise.
Economic and social differences in various parts of the world lead to problems for
food security and food safety. For example, insufficient food intake in poorer parts of
the world can lead to protein-energy malnutrition, which may be associated with
micronutrient deficiencies and disease e.g. iron, Vit A deficiency. On the other hand,
obesity, elevated blood pressure, cardiovascular disease and diabetes are now a
major problem in developed parts of the world and there is a clear association
between diet (overeating) and these diseases. Such problems give rise to the study
of nutritional risk which has become a very important consideration more recently
with the advent of Novel Foods and Functional Foods that may replace more
traditional sources of foods (see Chapter 6), especially staples.
Specific lifestyle factors also impact food chemical risk assessment and safety.
Human beings have different nutritional requirements and therefore different food
intakes that depend on the level of physical activity.
But we are all different!
Other factors – age, sex, pregnancy and general health status play an important role.
For example
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E.g. Men up to 60yrs and 76kg – approx. 0.16 Mj/kg BW/day energy
requirement with limited physical activity and 0.18 Mj/kg BW/day for
active lifestyle
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E.g. Women up to 60yrs and 62kg – approx. 0.15 Mj/kg BW/day for
active lifestyle; 0.14Mj/kg BW/day for decreased activity and age 6174yrs
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BUT children :
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0-6 months – approx.. xxMJ/kg BW/day
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6-9 months – approx. 0.35MJ/kg BW/day
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2-5yrs – approx. 0.33MJ/kg BW/day
•
6-9yrs – approx. 0.31MJ/kg BW/day
(Note: 1 Mj = 238 nutritional calories)
Lifestyle Factors and Impacts on Risk Assessment
The diet of the specific population should be taken into account with regard to toxicity
and exposure stages of the risk assessment.
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The more widespread the lifestyle factors are the greater the impact – e.g. different
diets, hobbies and sports, lifestyle factors such as tobacco smoking and alcohol
consumption will have an important influence on the risk assessment and need to be
identified clearly. Interactions between toxic metals and essential metals from the
diet can affect the risk of toxicity. Absorption of toxic metals from the lung and GI
tract may be influenced by the presence of an essential metal or trace element if the
toxic metal shares the same homeostatic mechanism. Lead and calcium, and
cadmium and iron are examples.
Other dietary interactions include an inverse relationship between protein content of
the diet and cadmium and lead toxicity. Vitamin C in the diet also reduces lead and
cadmium absorption.
Different types of food will have different amounts of chemical (and microbiological)
agents and hence cause a range of toxic effects depending on dietary habits.
The major pathway of exposure to many toxic metals in children is food, and children
consume more kilojoules/kg of body weight than adults do. Furthermore, children
have a higher gastrointestinal absorption of metals, particularly lead: CDC 2005;
JECFA 2014 “…data demonstrating that no “safe” threshold for blood lead levels in
young children has been identified…”
Alcohol ingestion may influence toxicity indirectly by altering diet and reducing
essential mineral intake. The ingestion of alcoholic beverages (ethanol), fats, protein,
calories and aflatoxins has been implicated in carcinogenesis (Klaassen, 1996).
Home grown produce such as vegetables has been associated with contamination of
heavy metals such as lead, arsenic and cadmium.
Free-range poultry tissue (meat, fat, skin) and eggs (egg yolk) has been associated
with contamination by organochlorine pesticides such as Aldrin, dieldrin and DDT
and hence consumption of these foods can lead to increased exposure to these
agents (Cross and Taylor, 1996).
Tobacco smoking also affects the toxicity assessment component of the food
chemical risk assessment. Report of the Surgeon General 2006 “The scientific
evidence indicates that there is no risk free level of exposure to second-hand
smoke.” Maternal cigarette smoking and passive smoking have been associated with
respiratory illness, acute toxicity and cardiotoxicity in newborns.
Epidemiological studies have shown evidence of synergistic interaction between
human carcinogens and long-term tobacco smoking (best studied interactions
include joint exposure to tobacco and radon and tobacco and asbestos, respectively,
with an additive or possible multiplicative increase in the number of cancers induced
and a synergistic decrease in the latency period for tumour induction).
Epidemiological studies have shown that asbestos and tobacco administered
together can produce an increased incidence in lung cancer that is greater than
either agent alone and the interaction is generally considered multiplicative (NRC,
1994).
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The type of diet can also influence the risk to exposure to hazardous chemicals.
Vegetarians may have a reduced exposure to zinc.
Individuals who consume barbecued foods can be exposed to relatively large
amounts of PAHs from the cooking process (especially if food is smoked).
Populations who consume seafood may be exposed to heavy metals such as
mercury in fish and zinc in shellfish (e.g. oysters).
Exposure to a hazard may also be influenced by lifestyle and hobbies. However it is
important to delineate between food chemical and other routes of exposure.
For example, the amount of time spent indoors (e.g. in the home, work
environment/office, factory), outdoors or travelling in the car, can present risks to
health (e.g. lead, benzene levels in the car, cosmic radiation in aeroplanes etc).
Hobbies such as pistol shooting in indoor shooting ranges, antique furniture
restoration, lead soldering, boat building and lead lighting can result in an increased
exposure to lead (Lead Safe, 1997). House renovating can result in an increased
exposure to hazardous agents such as lead and asbestos. Other hobbies involving
paint stripping using methylene chloride can cause exposure to its metabolic
breakdown product, carbon monoxide, and car maintenance can also result in an
increase in exposure to hydrocarbons and heavy metals.
That We Are All Different Affects Chemical Safety
So far we have learned that :
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Humans are different and have different nutritional status and food
consumption needs depending on a variety of factors including age, sex,
weight, physical activity, lifestyle factors etc
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Food contains chemicals that can be naturally occurring or added, wanted
and unwanted.
•
Chemicals have intrinsic hazards and some chemicals are toxic at certain
concentrations.
•
Some chemicals provide essential nutrition but some chemicals (naturally
occurring, added, unwanted) in food can constitute a food safety risk
depending on the intrinsic hazard of the chemical and the dietary exposure to
the chemical.
•
Chemical risk assessment is needed to deal with the possible negative
influences of chemical compounds on our health and how to reduce/avoid
these by combined clever use of risk assessment, risk management and risk
communication.
We have also now accumulated enough information to understand that risk
assessment gathers and organises information and enables:
19
•
Risks at a point in time (including baseline risks) and changes in risk over time
to be estimated and whether action is necessary.
•
Health Guidance Values (e.g. a maximum safe level of a heavy metal in food)
to be estimated for food chemical hazards that can be used and which will
adequately protect public health.
•
Assessments of new types of food chemical risk.
•
Assessments of different types of food chemical risks.
•
A comparison of the potential health impacts of various food chemical healthrelated interventions (thus enabling cost-effectiveness estimates).
•
The identification and comparison of different factors that affect the nature
and magnitude of the risk. Risk-based standards setting for regulatory
exposure limits, and clean-up standards
•
Prioritising issues according to their level of risks
•
Questionable theories, methods and data to be challenged and addressed by
providing a clearly documented and open process
•
Risk-based food safety policy-making; and
•
Consistent, transparent appraisal and recording of public health risks
20
Chapter 1 – Part 4
Unwanted Chemical Substances
In this section we discuss the important differences between elements and chemical
compounds with regard to their fate in organisms and the environment. We also
describe the different possible chemical identities/structures and discuss the different
possible origins of unwanted chemicals. It is important to note that not all of the
examples of unwanted chemicals in food pose a risk to human health and safety
because there is little chance of exposure and remembering that risk = hazard x
exposure.
Unwanted chemicals in food may come from a variety of sources and possess many
different chemical structures. Elements (distinguished by their atomic number – the
number of protons in the nucleus) occur naturally e.g. iron, lead, hydrogen, nitrogen
and oxygen, and may be present as solids (e.g. sodium), liquid metals (e.g.
mercury), one of the different forms of carbon (e.g. graphite, diamond), or the gases
(e.g. chlorine, oxygen and oxygen). Elements may form chemical compounds (pure
chemical substances consisting of two or more different elements – e.g. sodium
chloride (NaCL or salt), carbon dioxide (CO2) and methylmercury (CH3Hg+ or
MeHg+).Methylmercury is very lipophilic and can bio-accumulate after long term
exposure in fatty fish and other marine organisms to cause toxicity.
Chemical compounds can undergo transformation/degradation. For example,
degradation by solar light; degradation/ transformation by ionizing radiation.
Chemical reactions result in changes to molecular structure. Some examples include
hydrolysis of glycosides in cassava to toxic products, and metabolism after contact
with or absorption by a microorganism, plant or animal; ethanol is metabolised to
acetaldehyde which is toxic to the liver in excess. It can be noted that the elements
always stay with us as they may re-enter the food chain after excretion. For example,
mercury enters the food chain via a number of mechanisms; inorganic mercury is
converted to its most toxic form, methymercury, by a number of metabolic
processes, e.g. via bacteria and up through the food chain where it accumulates in
marine organisms.
Why Unwanted?
Chemical compounds and elements may be unwanted in food (and feed) because:
They may affect taste and smell. For example, fatty products become rancid.
Antioxidants are added to avoid degradation.
They may reduce intestinal absorption on important minerals such as calcium,
magnesium, iron and zinc. For example, phytic acid, a principle storage for of
phosphorous in many plant tissues especially bran and seeds. Minerals are bound
by phytic acid (or phytate in salt form) in cereals, leading to possible adverse health
effects.
21
They may degrade vitamins before these can be absorbed. For example,
Thiaminases are enzymes found in some plants and marine organisms (raw flesh)
which, when ingested split (degrade) thiamine (vitamin B1) and render it inactive.
These latter two examples are called anti-nutritional compounds or factors.
Finally, chemical compounds and elements may be unwanted in food (and feed)
because they may be toxic (see previous section on Toxicity)
Elements and Inorganic Compounds
Metals
Elements that have specific properties (e.g. good electrical conductivity, high density;
OR can be very reactive e.g. alkali). Metals may have positive (iron) and negative
health effects (cadmium, lead, mercury, tin). They may occur in elementary state or
as oxides and salts (e.g. CL-, (SO4-)2, and may be bound (chelated) to more
complex counterions such as phytate (an anit-nutrient; see previous slides), or
special metal-binding proteins (e.g. metallothionein which binds cadmium in the
liver), or may form parts of organometallic compounds. Some metals essential
‘dietary minerals’ e.g. calcium, copper, iron, magnesium, manganese, molybdenum,
potassium, sodium and zinc. Cobalt (as part of vitamin B12 – cyanocobalamin) and
chromium may also have some role in health benefits, although again excess
chromium can be toxic.
Rare Earth Metals
Rare earth metals can present hazards in some parts of the world such as China
where adverse effects have been reported from both exposure via foods that may be
contaminated by industrial pollution, and other environmental and occupational
exposures. Here's a closer look at some of the ways each rare earth element is
used:

Scandium: Added to mercury vapour lamps to make their light look
more like sunlight. Also used in certain types of athletic equipment —
including aluminium baseball bats, bicycle frames and lacrosse sticks — as
well as fuel cells.

Yttrium: Produces colour in many TV picture tubes. Also conducts
microwaves and acoustic energy, simulates diamond gemstones, and
strengthens ceramics, glass, aluminium alloys and magnesium alloys, among
other uses.

Lanthanum: One of several rare earths used to make carbon arc
lamps, which the film and TV industry use for studio and projector
22
lights. Also found in batteries, cigarette-lighter flints and specialized types of
glass, like camera lenses.

Cerium: The most widespread of all rare earth metals. Used in
catalytic converters and diesel fuels to reduce vehicles' carbon
monoxide emissions. Also used in carbon arc lights, lighter flints, glass
polishers and self-cleaning ovens.

Praseodymium: Primarily used as an alloying agent with magnesium
to make high-strength metals for aircraft engines. Also may be used
as a signal amplifier in fibre-optic cables, and to create the hard glass of
welder's goggles.

Neodymium: Mainly used to make powerful neodymium magnets for
computer hard disks, wind turbines, hybrid cars, earbud headphones
and microphones. Also used to colour glass and to make lighter flints and
welder's goggles.

Promethium: Does not occur naturally on Earth; must be artificially
produced via uranium fission. Added to some kinds of luminous paint
and nuclear-powered micro-batteries, with potential use in portable X-ray
devices.

Samarium: Mixed with cobalt to create a permanent magnet with the
highest demagnetization resistance of any known material. Crucial for
building "smart" missiles; also used in carbon arc lamps, lighter flints and
some types of glass.

Europium: The most reactive of all rare earth metals. Used for
decades as a red phosphor in TV sets — and more recently in
computer monitors, fluorescent lamps and some types of lasers — but
otherwise has few commercial applications.

Gadolinium: Used in some control rods at nuclear power plants. Also
used in medical applications such as magnetic resonance imaging
(MRI), and industrially to improve the workability of iron, chromium and
various other metals.
23

Terbium: Used in some solid-state technology, from advanced sonar
systems to small electronic sensors, as well as fuel cells designed to
operate at high temperatures. Also produces laser light and green phosphors
in TV tubes.

Dysprosium: Used in some control rods at nuclear power plants.
Also used in certain kinds of lasers, high-intensity lighting, and to
raise the coercivity of high-powered permanent magnets, such as those found
in hybrid vehicles.

Holmium: Has the highest magnetic strength of any known element,
making it useful in industrial magnets as well as some nuclear control
rods. Also used in solid-state lasers and to help colour cubic zirconia and
certain types of glass.

Erbium: Used as a photographic filter and as a signal amplifier (aka
"doping agent") in fibre-optic cables. Also used in some nuclear
control rods, metallic alloys, and to colour specialized glass and porcelain in
sunglasses and cheap jewlery.

Thulium: The rarest of all naturally occurring rare earth metals. Has
few commercial applications, although it is used in some surgical
lasers. After being exposed to radiation in nuclear reactors, it's also used in
portable X-ray technology.

Ytterbium: Used in some portable X-ray devices, but otherwise has
limited commercial uses. Among its specialty applications, it's used in
certain types of lasers, stress gauges for earthquakes, and as a doping agent
in fibre-optic cables.

Lutetium: Mainly restricted to specialty uses, such as calculating the
age of meteorites or performing positron emission tomography (PET)
scans. Has also been used as a catalyst for the process of "cracking"
petroleum products at oil refineries
24
Metaloids
Metaloids are elements that have specific properties of both metals and non-metals
(e.g. selenium and arsenic are present in the earth’s crust at different levels).
Selenium is essential for human health (although boron may also have a positive
role).
Elements and Inorganic Compounds
•
Both non-essential (lead, cadmium, mercury) and essential (selenium) metals
can be toxic depending on the dose.
•
For essential metals there is a window (upper and lower levels) between
lowest intakes to prevent deficiency and highest acceptable intakes that
cause toxicity.
Non metallic Compounds
•
Fluorine is one of the only non-metallic element of concern to human health.
Others might include iodine and boron.
•
Fluorine forms a single bond with itself to form F2 – extremely reactive
poisonous, yellow-brown gas.
•
Sodium fluoride (NaF) found in drinking water to help prevent dental caries,
and found in black tea.
Organic Compounds
•
Carbon atoms linked to each other in chains as supplemented with hydrogen
(e.g. CH2-CH2; ethane), but can incorporate oxygen and nitrogen (e.g.
nitrogen in alkaloids and non-protein amino acids from plants.
•
Substitutions include with other elements such as sulphur, phosphorous,
chlorine, fluorine and iodine, and may present important food safety problems.
•
A large number of organic compounds – e.g. 100,106 marketed between
1971-1981 (ELINCS).
•
Many more chemical compounds produced by degradations (incineration) and
side products of chemical processes.
Many chemical compounds are synthesised by industry – e.g. pesticides, medicines,
cosmetics and toiletries, packaging materials, and food additives – and most of these
will find their way into the food supply!
•
Pollution via a variety of pathways is an important source of many chemical
compounds in the food supply e.g. dioxins – very toxic, carcinogenic
compounds e.g. resulting from unwanted side products of the herbicide 2,4,5trichlorophenoxyacetic acid, and burning of waste materials; widespread
continuous into the environment
25
•
Persistent organic pollutants (POPs) found everywhere.
Organometallic Compounds
•
Chemical compounds such as methylmercury, selenium, tetraethyl lead (TEL)
and arsenic all mentioned previously).
•
May have different characteristics concerning absorption and distribution
leading to different toxic profiles compared to the elemental metals and
metalloids or their inorganic salts. Some examples include:
•
TEL in petrol is totally man-made and can be absorbed via the skin, but
is a pollutant that can end up in food and feed.
•
Methylmercury is synthesised by microorganisms, and was previously
used as a fungicide that proved highly toxic (CNS).
•
Mercury vapour and readily absorbed into lungs, past the blood-brain
barrier to cause CNS damage; ingested fluid metal mercury absorption
is restricted; inorganic mercury compounds affect the kidneys.
26
Chapter 1 – Part 5
Food Production and Processing Chain
Food Supply Chain from “Farm to Table”
Farm-to-table (or farm-to-fork) refers to the stages of the production of food:
 harvesting,
 storage,
 processing,
 packaging,
 sales, and
 consumption
Farm-to-table also refers to a movement concerned with producing food locally and
delivering that food to local consumers. Linked to the local food movement, the
movement is promoted by some in the agriculture, food service, and restaurant
communities. It may also be associated with organic farming initiatives, sustainable
agriculture, and community-supported agriculture.
The diagram below (Figure 3) gives an overview of the various stages from
harvesting to consumption, There are many sources of information available on food
safety and the production and processing chain.
27
Figure 3 : The Food Production Chain
Further, the next diagram (Figure 4) below shows the food production and
processing chain together with an example of how issues can occur in relation to
food safety along the various stages. For each stage the purpose is to point to
stages in the production where unwanted chemical substances can enter the product
or be formed in the product. Such a critical analysis of the full production chain for
potential hazards actually is the basis for the development of what is known as
Hazard Analysis Critical Control Points plan.
28
Figure 4 : From Farm to Fork – potential Hazards at each stage
29
Furthermore, in the below diagram (Figure 5) you can see the production and
processing stages for a common beverage, e.g. beer.
Figure 5 : Production steps in beer making
Food Raw Materials
Human beings are omnivorous i.e. we eat plants (primary producers) as well as from
secondary producers (animals) such as meat, eggs and milk for nutrition. After
production or gathering of raw materials these are further processed into different
kinds of intermediate products (to reduce weight prior to transport or obtain a
prolonged shelf-life) or ready-to-eat foods/dishes. In the following sections we will
examine different groups of raw food materials and how chemical compounds may
enter the food chain.
Terrestrial Plants
Most of the food consumed for the necessary energy production worldwide
originates from terrestrial plants. Examples include:
•
Rice (Oryza sativa),
•
Wheat, (Triticum, aestivium and other Triticum spp)
•
Maize (Corn, Zea Mays)
•
Starch rich tubers of Irish potato (Solanum tuberosum)
30
•
Cassava (Manihot esculenta)
•
Yam (includes a number of Dioscoria spp)
•
Sweet potato (Iponoea batatas)
•
Traditional cereals – sorghum, finger millet, teff, white fonio, kodo
millet, pearl millet
•
Pseudo cereals – quinoa, amaranth
Some starch-rich tubers such as cassava have low protein and vitamins and
essential fatty acids needed for adequate nutrition. Other protein-rich plants play a
particularly important role as protein and vitamin sources. Examples include:
•
Beans
•
Peas
•
Lentils
•
Fruits
Humans consume nearly every part of plants, including: immature seeds, seeds,
newly sprouted seeds seedlings, whole mature fruits, whole immature fruits,
pericarps, flower buds, flower stigmas, immature influorescences, influorescences,
leaves, leaf stalks, barks rhizomes/rootstocks and roots (for examples see Brimer,
Chapter 2).
Food safety problems may arise from meals prepared from different plant raw
materials. Examples include but not limited to:
•
Mycotoxins in cereals
•
Selenium in maize (e.g. in US states of Dakota, North Dakota, Missouri
and Kansas)
•
Glycoalkaloids in Irish potato
•
Cyanogenic alkaloids and their breakdown products in cassava
•
Trypsin inhibitors in different pulses
•
Pesticide, insecticide and fungicide levels in different crops
•
Toxic haemolysis in individuals deficient in the enzyme glucose-6phosphate dehydrogenase (G6PD) after intake of faba beans
•
Diarrhoea, failure to thrive and fatigue as symptoms of coeliac disease
(gluten intolerance) after eating wheat
Animals
Varied species are consumed as food (see Brimer, Chapter 3 p 6-7). Food safety
problems may arise from meals prepared from food of animal origin. Examples
include but not limited to:
31
•
Pig kidneys and livers may contain mycotoxins such as ochratoxin A
(OTA from animal feed)
•
Cattle kidneys and livers may contain concentrated levels of cadmium
•
Milk contaminated with aflatoxin M1 (AFM1) formed from the mycotoxin
B1 contained in animal feed
•
Fatty fish (e.g. salmon) may contain mercury, lead, dioxins and dioxinlike polychlorinated biphenyls (PCBs) at concentrations that may impair
health (cause toxicity)
•
Bivalve molluscs may contain toxic levels of algal toxins.
Fungi/Algae
Varied species consumed as food and used in production of foods (e.g. yeasts ;see
Brimer, Chapter 3 p7-9). Food safety problems may arise from meals prepared from
food of fungal and algal origin. Examples include but not limited to:
•
Mushrooms may contains naturally inherent liver, neurological and
gastrointestinal toxins and carcinogens if picked wrongly.
•
Mushrooms may contain high levels of heavy metals such as cadmium
and mycotoxins.
•
Algae (e.g. specific seaweeds) may contain high levels of iodine and
arsenic, and are being used more extensively as components of dietary
supplements.
Production of Raw Materials
See Brimer, Chap. 2, p9-12 for overview)
Production and processing parameters with influence on food safety through to the
consumers eating the final product, are:
•
Production
•
Processing
•
Packaging
•
Storage
•
Preparation
Production and Processing Parameters
Food raw materials are eaten “raw” and “processed” Processing may be used to
obtain:
32
•
Easier digestibility
•
Better tasting
•
Longer shelf-life
•
Safer
Food Processing and preservation technologies (sometimes called post-harvest
technology used for highly perishable raw materials of plant origin), includes :
•
•
primary processing or conversion of raw materials to food
commodities (e.g. milling of cereals to flours), and
secondary processing which is conversion of ingredients into
edible products (e.g. baking).
Some of the most common operations used by the modern food industry include:
•
Size reduction – grinding, cutting, emulsification
•
Mechanical separation – sieving, filtration, extrusion, centrifugation,
sedimentation and flotation
•
Mixing
•
Drying/dehydration/evaporation
•
Thermal processing – cooking, blanching, pasteurisation, baking,
roasting/frying, canning, smoking
•
Cold preservation – refrigeration (chilling), freezing
•
Contact equilibrium processes – extraction, washing, crystallisation,
membrane separations, distillations
•
Irradiation
•
Fermentation.
Examples of how chemical food safety may be affected when processed from raw to
modified include:
•
Raw products such as meat and vegetables may contain food contaminants
as a result of their production. This however should be reduced by good
manufacturing practices (GMP’s).
•
Both meat and vegetables occur as raw products that are usually processed
in some way by a food processing industry or sold as is through a wholesaler
and/or a specialized retail shop or supermarket.
•
A wholesaler may modify the raw products to some extent e.g. cut meat to
smaller portions.
33
•
After having processed/modified the raw products packaging usually follows.
•
During modification and storage it is important to avoid contamination with
moulds and bacteria. This should be controlled through application of GMP
and HACCP principles.
Food Chemical Safety - In the Shop or on the Market
The food product to be sold is usually put on display for the consumers. The type of
arrangement when on display has a great influence on contamination possibilities
and storage conditions. In shops situated inside buildings with drain and cooling
facilities etc. the risk of contamination could be assumed to always be less than in
shops or markets where these facilities are not present. However this assumption
can be proven wrong, if the storage and /or hygiene conditions are insufficient. In
open markets and small stalls along roads contamination can occur from air, dust
and lacking hygienic conditions etc.
After having bought a food item, it has to be transported to where it is destined for
consumption, usually at home. Transportation requires packaging /containers (bags),
and food items without any packaging may come in contact with the transportation
media or with other food or non-food items in the same bag. The conditions during
transportation may influence food safety (e.g. the weather, duration). Handling by the
consumer is yet another way of possible contamination: hygienic considerations
(hands/cross contamination between raw products), materials to come in contact
with food and duration and storage conditions.
Preparation can add or produce further toxicants, again materials in contact with
food (e.g. Teflon covered frying pans where the surface is incomplete) or process
toxins formed during heating (premelanoidines, Heterocyclic Aromatic Amine’s, and
Polycyclic Aromatic Hydrocarbons).
An example given in the slides is given for steak, where it can be seen that there are
several stages from “steak to plate” where food safety issues may arise. The final
product can contain many unintended compounds as a result of having been through
several steps in the manufacturing, distribution and sales chain and the preparation /
handling by the consumer.
Processing and Storage – Food Chemical Safety Examples
Lack of processing, or inefficient/faulty processing can lead to food safety risks e.g.
mycotoxins in dried raw materials that have not been processed and stored properly
according to GMP.
Processing generally leads to safer products, but can lead to formation or transfer of
toxic substances. Examples include:
•
Mechanical separation – sieving/floating used to separate toxic schlerotia in
grain contaminated with ergot
34
•
Size reduction (cutting/milling) – used to lessen concentrations of cyanogenic
glycosides in cassava root.
•
Thermal processing (grilling/frying/roasting) – can produce mutagenic and
carcinogenic compounds such as heterocyclic aromatic amines.
•
Contact equilibrium processes (extraction) – used to prevent contaminations
of certain legumes with lectins.
Note to Brimer: Can we include here the Fig 2.2 on page 14
of the book? Would be a good overview.
Examples on the Production and Processing Chain in Food Safety
From Plant to Processed Plant-based Food
1. Cereals to crisp bread
Crisp bread is a baked cereal-based product originating in the Scandinavian region.
There are a number of ingredients in commercially-produced varieties, some of
which are leavened with yeast or sourdough and contain wheat flour, spices and/or
seeds such as sesame seeds. Unwanted chemical substances in the final product
could include pesticide residues introduced by the flour(s), mycotoxins occurring the
flour(s) used and acrylamide formed during the baking process. With regard to the
mycotoxins, both Ochratoxin A and the so-called trichothecenes often contaminate
cereals under temperate conditions. Also, rye can be contaminated with the toxic
schlerotia of the fungus Claviceps purpuria ‘ergot’. These contain the toxic ergot
alkaloids e.g. ergotamine and ergocryptamine.
2. Cassava rootand is s to ‘garri’ (‘gari’)
Cassava root is often as a dried food product called “garri”, or as the cooked root eaten by
more than 800 million word wide as a staple food in South America,, Africa and many South
East Asian countries and in thew South Esat Pacific Islands. Cassava contains cyanogenic
glycosides such as linarmarin and lotastraulin, which liberate cyanide (HCN) upon
processing and chewing. Cassava must be prepared very carefully and cooked properly to
avoid cyanide poisoning, which has occurred in many cases in developing countries. The
toxicity seen after consumption includes acute poisoning, which can be fatal. Cassava
cultivars are classified as sweet or bitter depending on whether the tubers can be eaten
without any prior processing or not. The bitter tubers contain higher levels of the gylcosides
and in all cassava-consuming societies have developed and adopted effective processing
methods to reduce the potential toxicity of the root tubers upon consumption. These
35
processing steps include: grating, dewatering and roasting to remove the cyanogenic
glycosides.
3. From grapes to wine
Several moulds can develop on wine grapes. These include Botrytis cinera, and species of
Alternaria, Cladosporum, Fusarium, Aspergillus and Penicillium. Wines could also contain
levels of the mycotoxin Ochratoxin A (OTA), a nephrotoxic substance leading to irreversible
damaged to the kidneys. Studies in France have shown that Aspergillus carbinaris is the
major source of OTA. The fungus establishes itself at a very early stage of the development
of the grapes on the wine vines. It penetrates into the berry through already existing skin
damage and starts its OTA production.
From Plants to Animal Products
1. From feed to pig liver pate
Feedstuffs such as barley are often fed to pigs and OTA is a common contaminant
produced by Aspergillus and Penicillium fungi, sometimes occurring at unacceptable
levels during wet seasons. OTA causes depressed appetite and reduced growth
rate in pigs, impaired kidney function, necrosis of lymph nodes and fatty liver
changes. The feeding of pigs with OTA-contaminated material for finishing before
slaughter may lead to potentially unacceptable carry over levels of OTA in processed
food products from pigs such as pig liver pate.
2. From chicken feed to chicken meat
Feedstuffs such as cottonseed meal and cottonseed oil containing possibly high
levels of the natural plant toxin, gossypol, may be fed to chickens and carried over to
humans. Gossypol shows a variety of biological actions in all animals, including
laboured breathing and anorexia. Acute toxicity has been shown in the heart, lung,
liver and blood cells, resulting in increased erythrocyte fragility. Post-mortem findings
include generalised oedema and congestion of lungs and liver, fluid-filled thoracic
and peritoneal cavities, and degeneration of heart fibres. Reproductive toxicity is
seen particularly in males, where gossypol affects sperm motility, inhibits
spermatogenesis and depresses sperm counts. Generally the levels of gossypol
that enters the food supply are not of human health concern, but it is possible in
some parts of the world where cottonseed is fed to live stock in larger amounts, that
levels might represent a hazard for human health.
3. From Water Quality to Shellfish Dish
Water quality is important for the final quality of shellfish (molluscs and crustaceans)
for human consumption. Shellfish accumulate heavy metals such as arsenic, and
furthermore they may contain toxic levels of a number of algal toxins (marine
biotoxins) concentrated as the result of filter feeding.
36
What we have learned:
•
A thorough understanding of the existing interrelationships in the
overall production chain “from the paddock to the plate” is crucial for
the success of our work to ensure good chemical food safety.
•
Health-impairing chemical compounds may enter food (plants, animals,
fungi. Algae) at a number of different points of the food production and
processing chain.
•
For animal products, contamination can occur from plant contaminants
as well as inherent natural toxic plant constituents from feedstuffs, and
also residues of veterinary chemicals.
•
Food Production and Processing can make food safer, but may also
contribute to levels of toxic substances.
Suggested reading : Brimer, Chemical Food Safety, Chapter 2
37
Chapter 1 – Part 6
Case Studies
Case Study 1 : Pesticide
Imagine that a small child is served food that is mainly based on peaches (which
babies may begin to eat between 4-6 months old). The peaches may be
contaminated with one or more pesticides used during fruit production, including the
insecticide phosmet, often used agriculturally around the year 2000. Compared to an
adult who eats the same amount, the child normally will get higher blood levels as
well as tissue concentrations of phosmet because of the higher consumption of
peaches per kilogram of body weight and therefore more phosmet/kg bw. Phosmet
inhibits the enzyme acetylcholinesterase in certain nerve junctions resulting in acute
toxicity – abdominal cramps, convulsions, diarrhoea, vomiting and unconsciousness.
The child is at more risk to exceed the health reference endpoint, in this case the
ARfD of 0.046 mg/kg BW/day (FAO/WHO Joint Meeting on Pesticide Residues,
2002).
The ARfD is defined as ‘an estimate of the amount of a substance in food or drinking
water, normally expressed on a body weight basis, that can be ingested in a period
of 24h or less without appreciable health risks to the consumer on the basis of all
known facts at the time of the evaluation’. (JECFA, 2002). The acute reference dose
is much higher for a child because of the higher intake of the food /kg/bw. Obviously
the child – if very unlucky – more easily risks exceeding this dose.
This is a good case to remind us of the principle that the dose makes the poison!
(Paracelsus). And that certain parts of the population are more at risk due to their
particular sensitivity to certain toxic effects of poisons due to their higher exposures.
Case Study 2 : Lead
Using the heavy metal lead as a further example, even more factors influence what
will happen to a child compared to an adult. Lead was for many years an additive in
gasoline to make it more efficient in cars. Car engines convert tetraethyl lead to
small particles of lead oxide after combustion and these are deposited on the soil as
well as on the surface of feed and food crops, giving rise to high lead levels in many
food products. Excessive blood lead is associated with:
•
Nervous system impairment
•
Including cognitive difficulties and behavioural problems
•
Can stunt children’s growth at high enough levels
•
Cause permanent brain damage and mental retardation.
Lead is still a significant problem in the world because of various sources of
pollution, even though now not used in gasoline mostly nowadays. So this is an
38
example of an ongoing contemporary issue faced by government, the food industry
and consumers alike.
The reasons for young children to be most sensitive to the chemical threat to lead
include:
•
Small children eat more food per kg/bodyweight
•
The brain is the main target for the toxic effect
•
Lead can reach the foetus through the mother’s blood and already at this
stage can damage brain development
•
Small children typically absorb a higher percentage (around 50%) of the lead
ingested compared with an adult person, who typically absorbs less than
10%.
•
So the differences between us (infant/adult; sex; reproductive status;
nutritional needs and status etc) influence the risks we meet from chemical
compounds in our food (as well as the environment and workplace, etc.).
What we have learned:
•
Chemicals in food have different effects on human health depending on age,
sex, vulnerable populations (infants and children, elderly, pregnant women
including human foetus).
•
That human infants and young children are especially vulnerable because of
their higher intake of food per kg bodyweight.
Case Study 3 : Bisphenol A (BPA)
BPA is an industrial chemical used as a starting material for the production of
polycarbonate plastics and synthetic resins. BPA is found in containers that come
into contact with foodstuffs such as drinking vessels, baby bottles, plastic tableware
and the internal coating of tins.
Bisphenol BPA (formula) is a monomer, an organic chemical used in the
manufacture of polycarbonate (PC) plastics, epoxy resins and other polymeric
materials and also for certain paper products (thermal paper e.g. for cash receipts).
PC is used for manufacturing food and liquid containers, such as tableware (plates
and mugs), microwave ovenware, cookware and reservoirs for water dispensers, as
well as for non-food applications, such as toys and pacifiers with PC shields.
BPA-based epoxyphenolic resins are used as protective linings for food and
beverage cans and as a coating on residential drinking water storage tanks and
supply systems. Additionally, BPA may be used upstream in the process of
manufacturing of some raw materials, which are then used to produce food contact
materials. BPA is also used in the manufacturing of a number of non-foodrelated
39
applications, e.g. epoxy resin-based paints, medical devices, surface coatings,
printing inks and flame retardants.
The general population can be exposed to BPA via food/drinking water and/or via the
use of non-food consumer products such as thermal paper, toys, etc.. Environmental
sources can include surface water (during swimming) and outdoor air (inhalation of
aerosols). In addition, BPA from epoxy-based floorings, adhesives, paints, electronic
equipment and printed circuit boards may be released into indoor air (including
airborne dust) and dust. Environmental sources can potentially contribute to oral and
dermal exposure, as well as inhalation to BPA. (Opinion on BPA: Executive
summary, EFSA Journal 2015;13(1):NNNN 7 ).
At relatively high concentrations above those normally experienced by consumers of
foods containing very small concentrations of BPA, BPA has been shown to cause
some damage to the kidney in animal models.
The issue on the possible toxicity of BPA has been, and continues to be, an
extremely controversial issue amongst the world’s consumers, especially dietary
exposure in infants and young children from migration of BPA into infant formula,
leading to unprecedented, strong reactions from anti-chemical groups.
Consequently, BPA is probably one of the most studied chemicals in the history of
toxicology, and exposure to BPA via the various sources has been
implicated/associated in a wide number human epidemiological and animal models
of disease states, including reproductive problems (BPA is a “so-called” Endocrine
Disruptor”), cardiovascular disease, cancer, diabetes, and obesity amongst others.
Due to the inordinate amount of concern generated by BPA in the diet, governments
around the world have been pressured to work to obtain more certainty regarding the
real risk to the community, reacting in various different ways and making different
risk management decisions that reflect their community’s appetite for risk.
Risk management actions by governments have included legislating removal of BPA
from various products on the one hand (EU), to consumer advisory statements on
potential hazards and uncertainties(China, Hong Kong) , to advising that the
presence of low levels of BPA do not present any food safety risk to consumers
(Australia, New Zealand, USA).
Furthermore, consumer pressure has motivated the food and packaging industry
have taken their own measures to effectively remove the use of BPA from food
containing products, costing many hundreds of millions of dollars worldwide.
However, the body of evidence for many of the associations at the very small
concentrations humans are exposed to is considered weak and unlikely.
Many of the studies conducted by academic groups purporting to show associations
between BPA and human disease have been considered to be flawed or wanting in
relation to study numbers and execution, or the results have been over interpreted or
misinterpreted, or have used concentrations of BPA that are not realistic in relation to
the very small levels of dietary and environmental exposure in all human populations
(adults, children, elderly).
40
This has led many governments around the world to undertake risk assessments on
BPA, and has resulted in major, tightly controlled and costly studies being
commissioned by the USFDA and the US NIEHS over the last 3-4 years in order to
obtain more certainty on the real risk from exposure to BPA in the human population.
The most recent comprehensive risk assessment in both dietary and non-dietary
sources was completed by EFSA in January 2015. “This opinion describes the
assessment of the risks to public health associated with bisphenol A (BPA)
exposure. Exposure was assessed for various groups of the human population in
three different ways: (1) external (by diet, drinking water, inhalation, and dermal
contact to cosmetics and thermal paper); (2) internal exposure to total BPA
(absorbed dose of BPA, sum of conjugated and unconjugated BPA); and (3)
aggregated (from diet, dust, cosmetics and thermal paper), expressed as oral human
equivalent dose (HED) referring to unconjugated BPA only. The estimated BPA
dietary intake was highest in infants and toddlers (up to 0.875 µg/kg bw per day).
Women of childbearing age had dietary exposures comparable to men of the same
age (up to 0.388 µg/kg bw per day). The highest aggregated exposure of 1.449
µg/kg bw per day was estimated for adolescents. Bio-monitoring data were in line
with estimated internal exposure to total BPA from all sources. “EFSA, 2015”.
“BPA toxicity was evaluated by a weight of evidence approach. “Likely” adverse
effects in animals on kidney and mammary gland underwent benchmark dose
(BMDL10) response modelling. A BMDL10 of 8 960 µg/kg bw per day was calculated
for changes in the mean relative kidney weight in a two generation toxicity study in
mice. No BMDL10 could be calculated for mammary gland effects. Using data on
toxicokinetics, this BMDL10 was converted to an HED of 609 µg/kg bw per day. The
CEF Panel applied a total uncertainty factor of 150 (for inter- and intra-species
differences and uncertainty in mammary gland, reproductive, neurobehavioural,
immune and metabolic system effects) to establish a temporary Tolerable Daily
Intake (t-TDI) of 4 µg/kg bw per day. By comparing this t-TDI with the exposure
estimates, the CEF Panel concluded that there is no health concern for any age
group from dietary exposure or from aggregated exposure. The CEF Panel
noted considerable uncertainty in the exposure estimates for non-dietary
sources, whilst the uncertainty around dietary estimates was relatively low. “
BPA is considered as one of the most useful chemicals for a variety of industrial
uses. The overwhelming weight of scientific evidence clearly indicates that BPA, at
the levels humans are exposed to, is safe and would not lead to adverse effects.
Despite this, there is considered to be still some unanswered questions about its
safety at extremely low doses, so that safety of BPA continues to be studied and
alternative chemicals that do not have the same safety record are being substituted.
What we have learned from the BPA case study?
•
Reinforcing that chemicals in food have different effects on human health
depending on age, sex, vulnerable populations (infants and children, elderly,
pregnant women).
41
•
There is no such thing as “zero risk” regarding food, even though consumers
will expect this to be the case.
•
The dose makes the poison, and in the case of BPA exposure, the dose is
extremely low (parts per billion) and presents a very low risk to human health
•
The difference between “Hazard” and “Issue” in relation to some chemicals
like BPA, and the various other extraneous elements that have to be
considered such as social and political inputs perceptions and values.
•
Decisions where there is still some scientific uncertainty, creating very difficult
risk communication.
•
Remember from early in this Chapter under Part 1 that one of the concerns
about some stakeholder perceptions of current methodologies is that an
impression may be given that the derived risk assessment number, whether
based on extrapolation or an Acceptable Daily Intake (ADI)/Provisional
Tolerable Daily Intake (PTDI) approach, can be taken as a ‘bright line
between possible harm and safety’ (NRC 2008 p. 8) or, in other words, the
separation between safe and unsafe exposures. While it is important to
dispel this myth in the risk communication process by explaining its
inaccuracy because of variability and uncertainty, one should not lose sight of
the fact that an exceedance of a standard or guideline or other indicator of
‘safety’ by a derived risk assessment number should always trigger further
consideration of the situation being assessed. Such consideration could
include refinement of the assumptions, modelling or input values, and the
magnitude of safety factors.
Case Study 4: Acrylamide
Reference source is the US National Cancer Institute:
http://www.cancer.gov/cancertopics/causes-prevention/risk-factors/diet/acrylamidefact-sheet
Acrylamide is a good example of an unwanted chemical in food. Acrylamide is a
chemical used primarily as a building block in making polyacrylamide and acrylamide
copolymers. Polyacrylamide and acrylamide copolymers are used in many industrial
processes, such as the production of paper, dyes, and plastics, and in the treatment
of drinking water and wastewater, including sewage. They are also found in
consumer products, such as caulking, food packaging, and some adhesives. Trace
amounts of acrylamide generally remain in these products.
Acrylamide in food
Researchers in Europe and the United States have found acrylamide in certain foods
that were heated to a temperature above 120 degrees Celsius (248 degrees
Fahrenheit), but not in foods prepared below this temperature (1). Potato chips and
French fries were found to contain higher levels of acrylamide compared with other
foods (2). The World Health Organization and the Food and Agriculture Organization
42
of the United Nations stated that the levels of acrylamide in foods pose a “major
concern” and that more research is needed to determine the risk of dietary
acrylamide exposure (2).
Acrylamide and cooking
Asparagine is an amino acid (a building block of proteins) that is found in many
vegetables, with higher concentrations in some varieties of potatoes. When heated
to high temperatures in the presence of certain sugars, asparagine can form
acrylamide (known as the Maillard reaction). High-temperature cooking methods,
such as frying, baking, or broiling, have been found to produce acrylamide (3), while
boiling and microwaving appear less likely to do so. Longer cooking times can also
increase acrylamide production when the cooking temperature is above 120 degrees
Celsius (4, 5).
Is there anything In relation to the cooking process to lower dietary acrylamide
exposure, decreasing cooking time, blanching potatoes before frying, and post
drying (drying in a hot air oven after frying) have been shown to decrease the
acrylamide content of some foods (6, 7).
Acrylamide levels in food vary widely depending on the manufacturer, the cooking
time, and the method and temperature of the cooking process (8, 9). The best advice
at this time is to follow established dietary guidelines and eat a healthy, balanced
diet that is low in fat and rich in high-fiber grains, fruits, and vegetables.
Other ways humans are exposed to acrylamide
Food and cigarette smoke are the major sources of acrylamide exposure (10).
Exposure to acrylamide from other sources is likely to be significantly less than that
from food or smoking, but scientists do not yet have a complete understanding of all
sources of exposure. Acrylamide and polyacrylamide are used in some industrial and
agricultural procedures, and regulations are in place to limit exposure in those
setting.
Acrylamide and cancer
Studies in rodent models have found that acrylamide exposure poses a risk for
several types of cancer (11, 12, 13). However, the evidence from human studies is
still incomplete. The National Toxicology Program and the International Agency for
Research on Cancer consider acrylamide to be a “probable human carcinogen,”
based on studies in laboratory animals given acrylamide in drinking water. However,
toxicology studies have shown differences in acrylamide absorption rates between
humans and rodents (14).
A series of case-control studies have investigated the relationship between dietary
intake of acrylamide and the risk of developing cancers of the oral cavity, pharynx,
esophagus, larynx, large bowel, kidney, breast, and ovary. These studies generally
found no excess of tumors associated with acrylamide intake (15, 16, 17, 18, 19). In
the studies, however, not all acrylamide-containing foods were included in estimating
exposures. In addition, information in case-control studies about exposures is often
43
based on interviews (personal or through questionnaires) with the case and control
subjects, and these groups may differ in the accuracy of their recall about exposures.
One factor that might influence recall accuracy in cancer-related dietary studies is
that diets are often altered after receiving a diagnosis of cancer.
To avoid such limitations in accurately determining acrylamide exposure, biomarkers
of exposure were recently used in a Danish cohort study designed to evaluate the
subsequent risk of breast cancer in postmenopausal women (20). Among women
with higher levels of acrylamide bound to the hemoglobin in their blood, there was a
statistically significant increase in risk of estrogen receptor-positive breast cancer.
This finding suggests an endocrine hormone-related effect, which would be
consistent with the results of a questionnaire-based cohort study in the Netherlands
that found an excess of endometrial and ovarian cancer—but not of postmenopausal
breast cancer—associated with higher levels of acrylamide exposure (21). Another
cohort study from the Netherlands suggested a positive association between dietary
acrylamide and the risk of renal cell cancer, but not of prostate or bladder cancer
(22).
Other health effects of acrylamide
High levels of acrylamide in the workplace have been shown to cause neurological
damage, e.g., among workers using acrylamide polymers to clarify water in coal
preparation plants (23).
Regulation of acrylamide
The U.S. Environmental Protection Agency (EPA) regulates acrylamide in drinking
water. The EPA established an acceptable level of acrylamide exposure, set low
enough to account for any uncertainty in the data relating acrylamide to cancer and
neurotoxic effects. The U.S. Food and Drug Administration regulates the amount of
residual acrylamide in a variety of materials that come in contact with food, but there
are currently no guidelines governing the presence of acrylamide in food itself.
What research is needed?
Although studies in rodent models suggest that acrylamide is a potential carcinogen,
additional epidemiological cohort studies are needed to help determine any effects of
dietary acrylamide intake on human cancer risk. It is also important to determine how
acrylamide is formed during the cooking process and whether acrylamide is present
in foods other than those already tested. This information will enable more accurate
and comprehensive estimates of dietary exposure. Biospecimen collections in cohort
studies will provide an opportunity to avoid the limitations of interview-based dietary
assessments by examining biomarkers of exposure to acrylamide and its metabolites
in relation to the subsequent risk of cancer.
For information about acrylamide from the World Health Organization (WHO) and the
Food and Agriculture Organization of the United Nations, please visit WHO’s Food
Safety: Acrylamide page.
For information about acrylamide from the National Toxicology Program (NTP),
please visit NTP's Report on Carcinogens.
44
Selected References
1. Stadler RH, Blank I, Varga N, et al. Acrylamide from Maillard reaction
products. Nature 2002; 419(6906):449–450.
2. Food and Agriculture Organization of the United Nations. World Health
Organization. Summary report of the sixty-fourth meeting of the Joint
FAO/WHO Expert Committee on Food Additives (JECFA). Retrieved July 24,
2008, from:
http://www.who.int/entity/ipcs/food/jecfa/summaries/summary_report_64_final.
pdf .
3. Mottram DS, Wedzicha BL, Dodson AT. Acrylamide is formed in the Maillard
reaction. Nature 2002; 419(6906):448–449.
4. Gertz C, Klostermann S. Analysis of acrylamide and mechanisms of its
formation in deep-fried products. European Journal of Lipid Science and
Technology 2002; 104(11):762–771.
5. Rydberg P, Eriksson S, Tareke E, et al. Investigations of factors that influence
the acrylamide content of heated foodstuffs. Journal of Agricultural and Food
Chemistry 2003; 51(24):7012–7018.
6. Kita A, Brathen E, Knutsen SH, Wicklund T. Effective ways of decreasing
acrylamide content in potato crisps during processing. Journal of Agricultural
and Food Chemistry 2004; 52(23):7011–7016.
7. Skog K, Viklund G, Olsson K, Sjoholm I. Acrylamide in home-prepared
roasted potatoes. Molecular Nutrition and Food Research 2008; 52(3):307–
312.
8. Tareke E, Rydberg P, Karlsson P, Eriksson S, Tornqvist M. Analysis of
acrylamide, a carcinogen formed in heated foodstuffs. Journal of Agricultural
and Food Chemistry 2002; 50(17):4998–5006.
9. Mojska H, Gielecinska I, Szponar L. Acrylamide content in heat-treated
carbohydrate-rich foods in Poland. Roczniki Panstwowego Zakladu Higieny
2007; 58(1):345–349.
10. Urban M, Kavvadias D, Riedel K, Scherer G, Tricker AR. Urinary mercapturic
acids and a hemoglobin adduct for the dosimetry of acrylamide exposure in
smokers and nonsmokers. Inhalation Toxicology 2006; 18(10):831–839.
11. Dearfield KL, Abernathy CO, Ottley MS, Brantner JH, Hayes PF. Acrylamide:
Its metabolism, developmental and reproductive effects, genotoxicity, and
carcinogenicity. Mutation Research 1988; 195(1):45–77.
12. Dearfield KL, Douglas GR, Ehling UH, et al. Acrylamide: A review of its
genotoxicity and an assessment of heritable genetic risk. Mutation Research
1995; 330(1–2):71–99.
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13. Friedman M. Chemistry, biochemistry, and safety of acrylamide. A review.
Journal of Agricultural and Food Chemistry 2003; 51(16):4504–4526.
14. Fuhr U, Boettcher MI, Kinzig-Schippers M, et al. Toxicokinetics of acrylamide
in humans after ingestion of a defined dose in a test meal to improve risk
assessment for acrylamide carcinogenicity. Cancer Epidemiology Biomarkers
and Prevention 2006; 15(2):266–271.
15. Pelucchi C, Galeone C, Levi F, et al. Dietary acrylamide and human cancer.
International Journal of Cancer 2006; 118(2):467–471.
16. Mucci LA, Dickman PW, Steineck G, Adami HO, Augustsson K. Dietary
acrylamide and cancer of the large bowel, kidney, and bladder: Absence of an
association in a population-based study in Sweden. British Journal of Cancer
2003; 88(1):84–89.
17. Mucci LA, Lindblad P, Steineck G, Adami HO. Dietary acrylamide and risk of
renal cell cancer. International Journal of Cancer 2004; 109(5):774–776.
18. Mucci LA, Adami HO, Wolk A. Prospective study of dietary acrylamide and
risk of colorectal cancer among women. International Journal of Cancer 2006;
118(1):169–173.
19. Mucci LA, Sandin S, Balter K, et al. Acrylamide intake and breast cancer risk
in Swedish women. Journal of the American Medical Association 2005;
293(11):1326–1327.
20. Olesen PT, Olsen A, Frandsen H, et al. Acrylamide exposure and incidence of
breast cancer among postmenopausal women in the Danish Diet, Cancer and
Health Study. International Journal of Cancer 2008; 122(9):2094–2100.
21. Hogervorst JG, Schouten LJ, Konings EJ, Goldbohm RA, van den Brandt PA.
A prospective study of dietary acrylamide intake and the risk of endometrial,
ovarian, and breast cancer. Cancer Epidemiology Biomarkers and Prevention
2007; 16(11):2304–2313.
22. Hogervorst JG, Schouten LJ, Konings EJ, Goldbohm RA, van den Brandt PA.
Dietary acrylamide intake and the risk of renal cell, bladder, and prostate
cancer. American Journal of Clinical Nutrition 2008; 87(5):1428–1438.
23. Mulloy KB. Two case reports of neurological disease in coal mine preparation
plant workers. American Journal of Industrial Medicine 1996; 30(1):56–61.
Conclusions
This introductory chapter has attempted to cover a diverse and wide range of topics,
as a primer for the more detailed chapters that will follow. It is not possible to
elaborate comprehensively on all and every topic The content introduced in this
Chapter 1 is a mixture of topics that are considered important to reinforce basic
knowledge of food and chemical science from the very simple concepts to more
46
complicated, and includes basic information on internationally recognised chemical
risk assessment processes, chemicals that are contained in food that are “wanted”
e.g. to sustain nutritional status, and “unwanted” e.g. that occur naturally but that are
toxic at certain concentrations, introduction to toxicity and toxicology, food production
and the food processing chain, and some recent contemporary case studies on food
chemicals that pose human health and safety concerns in an attempt to highlight
how the information contained in Chapter 1 can be applied.
It is encouraged that as the student works through the module content he/she will do
their own research to explore introduced topics and concepts further in more detail.
47