Journal Pre-proofs

Review

Relationships between food and diseases: what to know to ensure food safety

Monica Gallo, Lydia Ferrara, Armando Calogero, Domenico Montesano,

Daniele Naviglio

PII: S0963-9969(20)30439-7
DOI: https://doi.org/10.1016/j.foodres.2020.109414
Reference: FRIN 109414

To appear in: Food Research International

Received Date: 5 January 2020

Revised Date: 21 May 2020
Accepted Date: 4 June 2020

Please cite this article as: Gallo, M., Ferrara, L., Calogero, A., Montesano, D., Naviglio, D., Relationships
between food and diseases: what to know to ensure food safety, Food Research International (2020), doi: https://
doi.org/10.1016/j.foodres.2020.109414

This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover
page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version
will undergo additional copyediting, typesetting and review before it is published in its final form, but we are
providing this version to give early visibility of the article. Please note that, during the production process, errors
may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

© 2020 Published by Elsevier Ltd.

Relationships between food and diseases: what to know to ensure food safety

Monica Gallo1*, Lydia Ferrara2, Armando Calogero3, Domenico Montesano4, Daniele Naviglio5
1*Department of Molecular Medicine and Medical Biotechnology, University of Naples Federico II,
via Pansini, 5; 80131 Naples, Italy.
2Department of Pharmacy, University of Naples, Federico II, Via Domenico Montesano 49, 80131
Naples, Italy.
3Department of Advanced Biomedical Science, University of Naples Federico II, Via S. Pansini 5,
80131 Naples, Italy.
4Department of Pharmaceutical Sciences, Section of Food Science and Nutrition, University of
Perugia, via San Costanzo 1, 06126 Perugia, Italy.
5Department of Chemical Sciences, University of Naples Federico II, Via Cintia 4, 80126 Naples,
Italy.

*Corresponding author: Monica Gallo Tel +39 081 7463117; e-mail: mongallo@unina.it

ABSTRACT

In recent years, the concept of food has undergone a radical transformation to the point of attributing
to foods, in addition to their nutritional and sensorial properties, an important role in maintaining
health and psycho-physical well-being and in the prevention of certain diseases. However, foods can
hide many pitfalls for human health. There are many critical points in food production processes and
they can represent real risks of contamination or of unsafe food production for consumers. Proper
conservation, physico-chemical and microbiological stability, cooking methods are fundamental
control parameters to ensure the safety of food products. Generally, the development of a food-borne
disease is due to specific conditions, such as the virulence of the microorganism present, the microbial
load present in the food and the conditions of the host's immune system. Furthermore, the possible
presence of other types of contaminants, in addition to microbial ones, can have implications for the
health of consumers. Consequently, the rigorous compliance of personnel who work in contact with
food during the phases of production, processing, transport and storage with hygienic rules is essential
to guarantee food safety and prevent foodborne disease. So, in this review, major issues are addressed
such as reviewing the major food-related causes of disease. From this point of view, the relevant
microorganisms involved in food contamination (bacteria, viruses, parasites, fungi and mycotoxins),

1
are taken into account. In addition, potentially allergenic foods or foods most commonly associated
with food intolerance, are also considered. Many adverse reactions of the body towards foods are
caused by the treatments to which they are subjected in order to maintain unchanged organoleptic
characteristics as long as possible over time. This is also a critical point for food contamination that
is considered in this review. A section is reserved to food additives potentially capable of causing
disorders to the human body. In addition to biological contamination, the important issues represented
by chemical contamination caused by pesticides, heavy metals, contaminants produced involuntarily
are also considered. In conclusion, this review highlights that to protect consumers from food-borne
diseases, an integrated approach to food safety must be adopted which affects the entire food chain,
from farm to fork.

Keywords: Allergy; Chemical safety; Food hygiene; Food poisoning; Microbiological safety; Risk to
health.

1. Introduction

Food and water may be the main vectors for the dissemination of infectious diseases. In fact, for
various reasons, accidental and/or fraudulent, food can be contaminated by microorganisms or
harmful substances and cause infections, such as food poisoning and toxinfections (Tack et al., 2019).
Foods are naturally introduced into the body through the gastrointestinal tract, and it is at this level
that the first symptoms of infection are usually seen. Food contamination can occur at all stages of
the production chain, from farm to table (Nerín et al., 2016).
Some infections are endemic, while others are more common in countries with low economic
standards and with low hygienic conditions, but we must also note that the incidence of foodborne
diseases is increasing in all industrialized countries due to changes related to lifestyle and choice of
food. Current work habits have led to an increase in the number of meals eaten outside the home,
requiring more restaurants, bars, kiosks and fried food stores. For these reasons, in order to preserve
public health, more health controls are required by the competent authorities (Caswell, 2019).
Furthermore, the reduced availability of time devoted to food preparation by families has led to an
increased consumption of ready-made meals, which are based on the use of fresh or pre-cooked foods,
the safety of which is linked to compliance with the fundamental rules of hygiene both for immediate
consumption or in terms of the expiration dates, both of which require refrigeration in the packaging
in a perfectly intact state. Generally, once thawed, the part of the food not consumed should not be
frozen again because freezing does not kill all bacteria on food, especially on meat and vegetables; in

2
the cold, they enter into a state of quiescence that allows for them to survive even at low temperatures.
When a food is thawed, the bacteria resume their activities and begin to multiply, and, consequently,
the risk of poisoning increases, especially if the food is eaten raw. The development of new tastes,
such as exotic fruit or raw foods, the promotion of special diets for the control of body weight, also
useful for the prevention of cardiovascular diseases, the availability of all foods regardless of the
season, are all factors that they require intensive production methods, with high exploitation of
agricultural land and intensive livestock breeding. As a consequence of the growing consumer
demand for new products, the quantity of products imported from countries with food safety
regulatory deficiencies, has increased, with the high probability of importing infectious agents that
are not well known (Atkins and Bowler, 2016). Generally, food can be contaminated throughout
production and therefore each step of the processing chain must comply with the correct hygiene
rules. Furthermore, chemical contamination of food should not be underestimated: various foreign
materials can be present as a result of fraudulent operations, accidental causes, environmental
pollution and/or incorrect procedures at the level of production, manipulation and conservation. The
deliberate addition of toxic substances to products placed on the market is a rare event; in the past,
there have been reports of fraudulent contamination of foods that caused serious permanent damage
to consumers, even death. Much less rare is accidental contamination by containers used to contain
toxic products, such as pesticides, solvents, and detergents, which, not being cleaned in an effective
way, can be used unknowingly to contain foods and/or beverages. Even the environment should be
monitored to prevent persistent and bio-accumulative toxic substances from causing food
contamination. In terms of production, harmful substances can be present due to improper treatment,
such as the application of pesticides in periods too close to the harvest time of agricultural products,
foreign substances released from containers used for storing food and drinks with an acidic pH, a
cooked food left at high temperatures for a long time, incorrect application of cooking times required
for a given food, the use of food past its expiration date, and contamination by sick individuals or
poor hygiene; additionally, avoiding contact between raw and cooked food reduces the risk of cross
contamination (Nerín et al., 2016). Raw meat and poultry, raw seafood, raw milk, meats, pates, soft
cheeses, and packaged sandwiches are particularly sensitive to contamination during food processing.
Additives, substances with no nutritional value that are added to preserve, to colour and to flavour
foods and drinks are deliberately added as foreign substances to foodstuffs; these additives include
preservatives that serve to prevent alteration or to maintain and enhance the appearance, taste, smell
and texture of the food (Martins et al., 2019). The use of additives in food processing, both in quality
and in quantity added, must be regulated by law; currently, there are lists of authorized substances
because they are recognized as safe on the basis of experimental tests; they are well characterized

3
substances that guarantee consumer safety (Lindsay, 2017). Table 1 shows the various types of
additives that can be added to foods and their roles (Table 1).

< Insert Table 1 here >

Food additives must be used at a dose necessary to achieve the purpose, as these substances may be
toxic when they are added in excessive amounts; thus, it is necessary to establish the maximum
acceptable daily intake (ADI) and the amount of additive to be added without endangering health,
following the directives established by law (Wong, 2018).
Regarding the specific addition, it is important to evaluate whether the additives interact with each
other or with the components of food since this may result in the production of substances that are
hazardous to health, such as nitrosamines, which are produced by reactions between nitrites and
proteins and are known to be carcinogenic (Laganà et al., 2017; Linke et al., 2018).
Our way of life has profoundly changed, and, consequently, eating habits, including eating ready-to-
eat meals or foods that are pre-cooked, are long-lasting, have an excellent taste, have an excellent
consistency, have a good smell and a pleasant appearance, often lead to an unbalanced diet that is
responsible for gastrointestinal, hepatic, autoimmune and allergic reactions (Conlon and Bird, 2015).
Therefore, the prevention of foodborne illness can only be guaranteed if all rules of hygiene are
strictly observed in the preparation and preservation of food products. All steps of the food production
process must follow all the rules in the HACCP (Hazard Analysis and Critical Control Points) system
to drastically reduce the dangers of food poisoning. The HACCP system promotes the concept of
prevention and analyses the potential dangers at every stage of the production process and in
subsequent stages, such as during storage, transportation, and marketing to the consumer.

< Insert Figure 1 here >

2. Foodborne diseases caused by bacteria

Several food-borne diseases result from biological contamination. Nonetheless, this type of
contamination is also capable of producing food poisoning and causing food deterioration. Many
pathogenic microorganisms are responsible for food poisoning resulting from both the consumption
of food containing pathogenic microorganisms and from food intoxication following ingestion of a
food contaminated with a toxin produced by microorganisms that have multiplied within the food
itself (Bhunia, 2018). There are different types of microorganisms that can cause foodborne diseases,

4
such as bacteria, viruses, parasites, protozoa and fungi. In this case, the toxin, not the bacteria, is
responsible for the disease symptoms, which are generally represented by nausea, vomiting,
abdominal pain, diarrhoea, and, rarely, fever. The course is usually benign, but in people with weak
physical attributes, such as children, the elderly, and sick individuals, a serious or even lethal situation
can occur. These bacteria have their own mechanism of action and can attack the body only if they
are in a position to be able to multiply abundantly in particular foods. In Table 2, the main agents
responsible for these diseases are listed.

< Insert Table 2 here >

Food poisoning caused by Salmonellae, gram-negative bacilli and asporogenous, facultative

anaerobes, is manifested by hyperacute gastroenteritis, caused by aggression to the intestinal wall by
bacteria and begins with abdominal pain, nausea, vomiting, diarrhoea, fever, and headache. Meat can
be contaminated at the origin of the food production chain also because Salmonella infection is not
always promptly and correctly diagnosed in farm animals (Fulgione et al., 2018; Proroga et al., 2019).
Especially in poultry flocks, contamination is favoured by various factors, including cultivation in
confined spaces, which facilitates the transmission of infections (Rajan et al., 2017). For the
prevention of poisoning from Salmonella, it is necessary to store products at a low temperature until
cooking the foods, and if to the preparation of a meals in advance is required, the prepared meal
should be stored at refrigerator temperatures or temperatures below 63 °C to prevent the
multiplication of any present Salmonella. Contamination can also occur after cooking through contact
with surfaces and containers of previously contaminated cooking utensils from the uncooked meat.
Creams (mayonnaise, cream, etc.) can be contaminated, either because they are prepared with eggs
containing Salmonella or because of their manipulation by healthy carriers (Kitazawa et al., 2019).
Salmonella food contamination is determined by a variety of environmental and ecological factors,
including water activity, pH, chemical composition, the presence of natural or added antimicrobial
agents, storage, temperature factors and processes, such as heat and physical manipulation. In the
literature, there are documented cases of extraintestinal infections that are most frequently associated
with immunodeficiency and general debilitation (Chang and Shen, 2018). In a study carried out in
2015, the case of a patient with osteomyelitis caused by a bacterial strain of Salmonella enterica
Newport was reported (Weston and Moran, 2015).
Clostridium perfringens is a spore-forming and anaerobic bacillus that usually lives in the intestines
of animals and humans and is found in high abundance in faeces. The spores of this bacillus are
resistant to heat and easily survive cooking; indeed, thermal shock stimulates germination in an

5
anaerobic environment, where the vegetative forms produce a toxin similar to that of cholera, which
acts on the intestinal mucosa, stimulating the loss of liquids. Foods contaminated by spores
responsible for food poisoning include uncooked meat, broth and meat sauces, in which a anaerobic
environment favourable for enterotoxin product is present following cooking. To avoid this food
poisoning, it is necessary to consume meat, broth and meat sauce immediately after cooking, or, when
this is not possible, it is necessary to cool them quickly and preserve them constantly in the
refrigerator (Dolan et al., 2015). Clostridium perfringens appears to be a very dangerous bacterium,
accounting for two clinically distinct gastrointestinal syndromes: necrotizing enteritis and food
poisoning. Fortunately, necrotizing enteritis is rare in industrialized countries and is due to the
production of a particularly aggressive toxin by certain strains of the bacterium, which, in most cases,
presents very accentuated symptoms, leading to the death of the patient (Geetha and Palanivel, 2017).
Listeria monocytogenes is a bacterium found in soil, water and vegetation. It can contaminate various
foods, including milk, vegetables, soft cheeses, undercooked meats, and is responsible for listeriosis
(Jordan and McAuliffe, 2018).
The symptoms of food intoxication by Staphylococcus, a gram-positive microorganism belonging to
the Staphylococcaceae family, are caused by Staphylococcus enterotoxins and not by the bacteria.
The period between contaminated food consumption and the onset of symptoms is very short,
typically 3-4 hours. Creams and milk are particularly suitable for the multiplication of staphylococci,
especially if the temperature is between 20 and 40 °C. The resulting enterotoxin is heat resistant,
therefore, the eventual cooking of food, while killing the bacteria, is not able to eliminate it; only the
use of containers and refrigerators at confectioners and other preparation laboratories of sweets and
ice cream has reduced the frequency of this poisoning (Vázquez-Sánchez et al., 2018). Boiled
potatoes, potato salad, prepared foods and those ready to be consumed without cooking are frequently
subject to Staphylococcus aureus infection (Huang, 2015). Keeping the temperature in food below 6
°C is necessary to stop bacterial growth and prevent contamination.
Although Escherichia coli is a common gut symbiont and plays an important role in the digestive
process and the formation of certain vitamins, its presence in high concentrations can procure diseases
in humans and animals. Its elimination occurs via the faeces, which are the main means of
contamination for food-borne diseases in products such as meat that has been infected during the
processing steps and is not adequately cooked, unpasteurized milk, cheese derivatives, raw
vegetables, fish products and other foods contaminated with faeces (Barbosa et al., 2016). Burgers
are at risk for contamination because the bacterium, if present, is able to penetrate deeply into minced
meat and is able to resist the low cooking temperature to which burgers are normally subjected. The
absence of E. coli is required as the primary indicator of no faecal contamination in water intended

6
for human consumption, the waters of hot springs, bathing waters and in different matrices, such as
foods and cosmetics; therefore, water is considered safe to drink when the absence of this mandatory
bacterium is determined. Genetic studies have revealed that the diversity and complexity of E. coli strains
are influenced by multiple environmental factors, which affect their long-term survival (Jang et al., 2017).
E. coli produces four types of toxins, which are characterized by different sensitivities to heat treatment:
the heat-labile toxins LT-1 and LT-2 and the thermostable toxins StA StB. The heat-labile toxins are
very similar in structure and function to Shiga toxins, which are produced by other bacteria of the
genus Shigella (De Boer and Heuvelink, 2000). The mechanism of Shiga toxins consists of two
different subunits, one of which contributes to adherence and entry of the toxin into host intestinal
cells, while the other stimulates the cells to release water, causing diarrhoea. These toxins are capable
of preventing the formation of proteins and causing cell apoptosis, in addition to widespread bleeding
and damage to the intestinal epithelium.
Herman et al. (2015) reported numerous cases of infection attributed to leafy vegetables, such as
salad, caused by Shiga toxins in the United States between 1973 and 2012 (Herman et al., 2015).
In addition to intestinal diseases, some strains of E. coli are aetiologic agents of extraintestinal
diseases, such as urinary tract infections, meningitis, peritonitis, septicaemia and pneumonia. New
strains of E. coli are continuously formed through the natural biological process of mutation, and
some of these strains have several features that can be harmful to the affected guest. A particularly
virulent strain is E. coli O157: H7 of the entero-haemorrhagic type that, in addition to causing bloody
diarrhoea, can cause haemolytic uremic syndrome, characterized by acute renal failure, haemolytic
anaemia, and thrombocytopenia, which are relatively frequent in children (Cheng et al., 2016).
E. coli strains have the ability, through fimbriae, to adhere to uroepithelial cells and cause cystitis in
elderly people, patients with diabetes, patients with catheters, and patients in communities because
they are debilitated and hygiene may be less than adequate (Schreiber et al., 2017).
Vibrio parahaemolyticus is a non-invasive bacterium belonging to the genus of vibrions, being
halophilic it is generally found in waters and in marine food. Transmission occurs by ingestion of raw
or undercooked crustaceans and molluscs (Ghenem et al., 2017; Rezny and Evans, 2018).
Pork is the preferred substrate for Yersinia enterocolitica, and the main route of transmission to
humans is through the consumption of food, particularly meat and offal contaminated indirectly from
faeces during the slaughtering process, as well as eggs, milk, vegetables, and rice. The bacterium
grows well at refrigeration temperatures and thus contaminated foods, such as ready to eat or
refrigerated foods, may represent a further significant source of infection (Saraka et al, 2017).
Infection caused by Yersinia enterocolitica may occur in different clinical forms: food poisoning is
the most common, characterized by severe abdominal pain, accentuated on the right side of the body,

7
so it is often misdiagnosed as appendicitis. Other inflammations, with different localizations, are
pharyngitis, pneumonia, meningitis, splenic abscesses, arthritis, osteomyelitis, dermatitis, urinary
tract infections, erythema nodosum and blood sepsis (Zinczuk et al., 2015).
Different symptoms and morbidity are associated with food intoxication by Clostridium botulinum,
a spore-forming and anaerobic bacillus that produces a potent neurotoxin labile in foods, which is
absorbed in the intestine and acts on synapses and neuromuscular plaques, preventing the release of
acetylcholine, resulting in paralysis of the muscles. The early symptoms are dizziness and modest
intestinal disorders, without fever; subsequently, neurological symptoms arise with paralysis of the
cranial nerves, causing impaired vision and drooping eyelids, difficulty swallowing, and difficulty
speaking. The paralysis spreads in descending order in a symmetrical manner; in 10% of cases, death
occurs from respiratory or cardiac paralysis (Peck et al., 2011). The risk of botulism is high in foods
that are stored in anaerobic conditions and with a pH of approximately 4.6. At one time, the disease
was often caused by sausages and canned foods since the preparation methods did not ensure the
destruction of the spores. Currently, industrial products are subject to procedures that guarantee food
safety, and jams and home-prepared products in oil should be considered potentially dangerous
(Mazzobre et al., 2000). Oils and other products of a lipid nature are generally used for storing food,
but they are subject to oxidation and, being stored at room temperature, could favour the growth of
Clostridium botulinum and sporogenic forms, both due to environmental factors, such as oxygen and
temperature, and intrinsic factors, such as pH, salt concentration, water activity, and the chemical
structure of the lipid itself (Taylor et al., 2013).
Products infected by Clostridium botulinum incur, through multiplying, food alteration with gas
production. It is standard practice not consume sauces that display any alteration, especially if
contained in boxes with bulges or cans with deformed lids. Intoxication occurs not only in humans
but also in animals; in fact, the Clostridium genus includes several species of anaerobic and spore-
forming bacteria that produce botulinum toxin and are distributed ubiquitously in soil and aquatic
sediments (Esplelund and Klaveness, 2014). The decomposition of plants, algae and animals creates
anaerobic environments that facilitate the growth of C. botulinum, which can enter the food chain,
leading to the poisoning of animals (Anza et al., 2014).
Overall, although it is not always very simple, in order to slow down the growth of bacteria and
prevent risks to food safety, it is necessary to follow the best food safety practices, use adequate food
handling techniques, rigorous cleaning and sanitization procedures and binomial control time-
temperature of food.

3. Foodborne diseases caused by viruses

8
Acute gastroenteritis is regarded as one of the most common diseases in humans and represents a
serious public health problem worldwide, affecting individuals of all ages. Several groups of viruses
have been reported as causative agents of this disease, which has the characteristic of seasonal
appearance and includes rotavirus, norovirus, sapovirus, adenovirus, human astrovirus and many
others.
Noroviruses are single-stranded RNA viruses belonging to the family Caliciviridae and are
responsible for infectious food-borne gastroenteritis. They are very virulent and affect communities
that attend the same meal distribution centre: schools, restaurants, hospitals, prisons, hotels, and
cruise ships (Kwan et al., 2017). A great deal of time was required to identify this pathogen through
the dosage of antibodies in blood because isolation or making cultures was impossible due to its small
size. The norovirus is spread mostly in the winter and is transmitted through contagion among people
through the faecal-oral route, with vomiting, through the dispersion of droplets of saliva,
contaminated food, unsafe water, oysters, berries, vegetables, or beverages (Buckow et al., 2008).
The foods responsible for norovirus gastroenteritis are cold and undercooked (Xie & Liu, 2015), and
contamination is caused by washing with non-potable water or discharge; cooked and cold food can
be contaminated instead by infected personnel work in food preparation. Noroviruses (NoV) represent
a primary cause of both acute and chronic viral gastroenteritis and in recent times there has been a
significant increase in this disease worldwide. To date, the control of norovirus gastroenteritis is a
arduous task both because there is no vaccine to prevent infection, and because an antiviral agent is
missing for its treatment (Randazzo et al., 2018). Baert and coworkers studied the behavior of murine
Norovirus-1 (MNV-1), a type of norovirus that infects mice and which belongs to the same genus of
NoV, therefore, it is a suitable surrogate for the human virus. A low inactivation of MNV-1 were
observed in this study suggesting that the risk of NoV infection persists if mild pasteurization is used.
Instead, a heat treatment at 80 °C for 2.5 minutes was sufficient to inactivate this virus (Baert et al.,
2008). The studies performed by Buckow et al. (2008) on feline calicivirus, FCV (as surrogate of
human NoV), confirmed that the heat treatment of 75 °C for 2 minutes in cell culture medium or
mineral water, showed efficient inactivation of FCV. From the results obtained by these authors,
therefore, it is clear that a standard pasteurization process (e.g. 88 °C for 2 minutes) would be
sufficient to inactivate NoV. However, mild pasteurization processes (65-75 °C for a period of 30-15
seconds) are often applied to avoid a deterioration in the quality of the food. Therefore, during heat
treatments on food, it is necessary to take into account the ability of the virus to withstand these
temperatures.

9
Rotavirus and norovirus are common in Japan-detected viruses in children below 5 years of age and
usually do not cause severe gastrointestinal inflammation (Thongprachum et al., 2015). However,
early diagnosis and early intervention should be performed in rare cases where these viruses are
associated with serious complications, such as perforation or gastroduodenal ulcers, that could be
fatal to the children themselves (Ueda, 2016).
A gastrointestinal outbreak occurred in China during a festival in 2014 (Wang et al., 2015) following
the consumption of oysters. Forty-six strains of calicivirus were identified in the faeces of patients
who were diagnosed with a mixed infection caused by norovirus and sapovirus by molecular
epidemiological studies based on nucleotide sequencing and phylogenetic analysis (Lu et al., 2015).
The contagion of polluted food intake is, in fact, an important mode of propagation, and the faecal
contamination of water basins is an important element (Murray and Taylor, 2015).
Hepatitis A, the most common viral disease transmitted by food, is caused by the consumption of
contaminated water, foods that are raw or poorly cooked, or vegetables washed with contaminated
water. In most cases, the seafood and transmitter viruses responsible for this pathology is hepatitis A
virus (HAV), a picornavirus that is currently considered the prototype of hepatovirus. In fact, when
the virus is ingested through contaminated food and reaches the intestine and, subsequently, the liver,
it multiplies, causing necrotic degenerative lesions. This virus is able to survive the normal cooking
of food, therefore, it is always advisable to respect the elementary rules of hygiene and to buy foods
whose hygienic reliability is guaranteed.
Preventive care can play an important role in patients with chronic liver disease and is based on the
limitation of alcohol, a low-fat diet, iron supplementation, and hepatitis vaccination. The Food and
Drug Administration has approved the license of two inactivated hepatitis A vaccines that are highly
immunogenic and have been authorized in paediatric and adult formulations and are particularly
recommended for international travellers, children in communities with high infection rates from
hepatitis A virus, drug addicts, patients with chronic liver disease and people with coagulation factor
disorders (Arguedas and Fallon, 2001; Aggarwal and Goel, 2015).

4. Foodborne diseases caused by fungi and mytotoxins

Fungi are organisms that have filaments called hyphae and are perpetually present in the soil, under
the bark of trees and in different environments; their ideal habitat is the forest, and they are essential
for safeguarding the ecosystem. Fungi have different shapes, colours and sizes, and they reproduce
by means of spores.

10
Many species of fungi are harmful to humans due to the presence of toxic substances that cause slight
or allergic digestive problems and even serious liver damage, hallucinations, and death (Chan et al.,
2016; Verna et al., 2014; Lima et al., 2012). In relation to the time that elapses between the ingestion
of poisonous mushrooms and the appearance of symptoms, there are short-latency symptoms that
appear between 30 minutes and six hours after ingestion and are resolved in a couple of days with a
low risk of mortality, and long-latency symptoms, with a high risk of mortality, appear after 20 hours
of ingestion (White et al., 2019).
Gastrointestinal syndrome is the most common and can be caused by many fungi, especially
Entoloma lividum, Russula ametic, and Boletus satanas. The active ingredients responsible are
numerous, and not all are known. Symptoms subside after a couple of days, and it is necessary to
supplement water loss.
Panterinica syndrome is caused by Amanita muscaria and by Amanita pantherina, presenting, in
relation to the amount of ingested toxins, dizziness, unsteadiness, euphoria, tremors, confusion, and
seizures with hallucinations and drowsiness (Ward et al., 2013; Garcia et al., 2015).
Muscarinic toxicity is caused by muscarine, a substance isolated from Amanita muscaria and is
characterized by headaches, abdominal pain, hypersalivation, intensive sweating, watery eyes,
trembling and bradycardia (Epis et al., 2010; Marinov et al., 2018).
Psychodysleptic syndrome caused by fungi of the genus Psilocybe, Panaeolus, and Stropharia are
characterized by abnormal vision and distorted perception of colours and shapes; disorientation,
agitation and aggressiveness are often also present.
Coprinic syndrome is attributed to the toxins of Coprinus atramentarius that, with alcohol, causes
redness, hypotension, tachycardia, and headache (Hossain and Park. 2016). When the poisoning by
this fungi manifests itself as long-latency symptoms, a higher incidence of mortality occurs; the
symptoms are initially diagnosed as flu-like gastroenteritis and are underestimated by both the patient
and the treating physician, resorting to late hospitalization and irreparable compromising of health.
The most frequent fungal poisoning is Falloidea syndrome, whose toxicity is related to the presence
of amatoxin and is characterized by frequent episodes of vomiting and diarrhoea, which lead rapidly
to severe states of dehydration and electrolyte imbalances. The organ most affected is the liver, and
protein synthesis is blocked by inhibition of RNA polymerase II, leading to cell death; the extent of
liver damage can lead to the need for transplantation or death.
The syndrome Orellanica, caused by Cortinarius orellanus and speciosissimus, differs from the
others because there are no gastrointestinal manifestations, but headaches, muscle aches, chills, loss
of appetite, and decreased urine output, leading to often irreversible renal insufficiency, has been

11
reported (Frank et al., 2009; Esposito et al., 2015). For this type of intoxication, the only treatment is
dialysis, and kidney transplantation is provided in cases where renal failure is irreversible.
Gyromitra syndrome, which is very rare, characterized by drowsiness, muscle spasms, haemolytic
anaemia, liver damage and kidney after repeated ingestion of considerable amounts of toxic fungi
(Pfab et al., 2008; Saviuc et al., 2010).
Moulds are microscopic fungi that grow in the presence of humidity and a temperature of 15-30 °C,
but they can also proliferate at refrigerator temperatures. Moulds are often present on the walls of
coloured decomposition products and do not tolerate high temperatures; thus they are destroyed by
the pasteurization of foods. In some cases, moulds are useful, for example, when they are involved in
the production of antibiotics, in the ripening of cheeses such as gorgonzola and camembert, and in
the fermentation of some wines where only a few well-defined strains are used in a strictly controlled
process. Additionally, in foodstuffs in which the mould does not intervene in the production process,
it is always a sign of degradation of the product and can also cause damage. Mycotoxins are, in fact,
toxic secondary metabolites produced by fungi that, if developed in a food, can be a source of
dangerous poisoning in the liver, kidneys, nerve centres or digestive tract (Berthiller et al., 2013).
One of the most common epidemics of the Middle Ages known in Europe was ergotism, characterized
by neuroconvulsive and hallucinatory symptoms, gangrene of the extremities, and strong burning
caused by the presence of a fungus, Claviceps purpurea, which contaminated the rye that was milled
into flour to produce bread.
Mycotoxins have different types of toxicity: acute, chronic, mutagenic and teratogenic. Acute
intoxication largely causes damage to the liver or kidneys, which, in extreme cases, can lead to death,
but some mycotoxins act primarily by interfering with protein synthesis and produce effects ranging
from skin sensitivity or necrosis up to a strong immune deficiency. The effects of long-term ingestion
of low doses of toxins are variable: the major chronic effect of many mycotoxins is the induction of
especially cancer of the liver. Some toxins interfere with DNA replication, causing mutagenic and
teratogenic effects. Consequently, understanding the molecular basis of cancer can lead to the
identification of diagnostic, predictive, prognostic and therapeutic biomarkers (Carlomagno et al.,
2017). The foods most likely to be contaminated are cereals, oilseeds, dried fruit, spices, and fruits
and vegetables that are subject to contamination, as well as derivative products, such as flour,
unrefined oils, juices, spices and milk products. Many toxigenic fungi of the genera Aspergillus,
Fusarium and Penicillium are pathogenic, destructive to cereal cultivation and produce aflatoxins
before harvesting, immediately after harvesting or, more commonly, during the drying and storage of
grain commodities. The substrate on which aflatoxins grow is fundamental, and they are prevalent in
raw materials rich in carbohydrates. Patulin is the typical mycotoxin of rotten fruit and is produced

12
by the blue moulds Aspergillus and Penicillium, which most frequently cause alterations (Rahimi and
Rezapoor, 2015; Snini et al., 2015). Aspergillus flavus produces aflatoxins on peanuts, corn, barley,
peas, spices, wheat, soybeans and also on rice (Lv et al., 2019). Aflatoxins are toxic both to humans
and animals and cause acute damage to the liver, cirrhosis, cancer and teratogenic effects. There are
different types of aflatoxins, of which the most common types are: B1, B2, G1 and G2. When
aflatoxins B1 and B2 are ingested by cows in lactation, a portion is hydroxylated and excreted in
milk, thus becoming aflatoxins M1 and M2, which are less toxic than B1 and B2 but are of
significance in humans as consumers of milk (Bellio et al., 2016). Aflatoxin B1 is considered a potent
liver carcinogen (IARC, 1993). Due to the high toxicity of aflatoxins, many states have established
very low limits allowed in food. In Italy, this limit is regulated by Decree 149/2004 and Directive
2006/1881/CE.
Ochratoxins are produced by Aspergillus ochraceus and Penicillium viridicatum and are known to
have two types: ochratoxin A, the most toxic, and ochratoxin B. Ochratoxin A causes acute renal
intoxication, causing necrosis of the renal tubules and of certain types of liver cells; it can also have
an immunosuppressive effect and is probably carcinogenic. This mycotoxin is a serious issue in
veterinary health in Northern Europe because it causes severe nephritis in pigs (Bol et al., 2016). It is
fat-soluble, so it accumulates in the fat of infected animals and can be ingested by humans eating
pork. Other sources of mycotoxin ingestion by humans are bread made with contaminated barley or
grain, spices, cocoa, coffee, wine and beer.
Fumonisins are produced by Fusarium moniliforme and Fusarium proliferatum, and their toxicity has
different effects on different animal species: equine species incur a neurotoxic syndrome called
leukoencephalomalacia, liver cancer and kidney abnormalities have been observed in rats, pulmonary
oedema has been reported in pigs, and immunosuppression has been observed in ducks. The powerful
inhibitory action of fumonisins on sphingolipid synthesis appears to underlie the toxic effects caused
by these substances, and their carcinogenic activity is caused by the loss of sphingosine, an
endogenous anti-tumour agent. In humans, the consumption of contaminated cereals, especially corn,
increases the incidence of oesophageal cancer.
Trichothecenes are a family of over 200 toxins produced by genera Fusarium, Myrothecium,
Spicellum, Stachybotrys, Cephalosporium, Trichoderma, and Trichothecium. Many species
belonging to genus Fusarium, such as Fusarium sporotrichioides, F. langsethiae, F. graminearum,
F. culmorum, F. poae, and F. equiseti produce these tetracyclic sesquiterpenoid substances which
can be divided into four types (A-D) according to characteristic functional groups. In particular, the
group A includes T-2 and HT-2 toxin in addition to diacetoxyscirpenol, the group B includes
deoxynivalenol and nivalenol, and these are the main contaminants in wheat, barley, oats, maize, rye

13
and corn (McCormick et al., 2011). Symptoms of human poisoning include nausea, vomiting,
headache, and gastrointestinal disorders, but trichothecenes are not considered carcinogenic.
Zearalenones are produced by several species of Fusarium, especially F. graminearum, F. culmorum
and F. equiseti, and animals, including cattle and pigs, are the most sensitive species to these
mycotoxins, which are characterized by powerful oestrogenic effects, which causes a specific
syndrome affecting the reproductive system in animals. The products subject to zearalenone
contamination are corn, wheat, barley and oats (Jia et al., 2016). Zearalenone has been considered
responsible for some cases of precocious puberty in children. The observance of good hygiene is
crucial to protect our health (Luo et al., 2018).

5. Foodborne diseases caused by parasites

Parasites are organisms belonging to the group of protozoa, helminths, and pinworms and are
transmitted to humans by beef and pork, raw or semi-raw fish, fruits and vegetables contaminated by
sewage, and infected water. Parasites cause infections in muscle tissues and organs, causing
anaphylactic shock, amoebic dysentery and other pathologies. Many parasites are eliminated by
cooking or by very low temperatures, while others can live in the human body, sometimes for decades,
causing serious damage to health. Giardia lamblia, Cryptosporidium sp., and Entamoeba histolytica
are important pathogenic intestinal parasites and are among the leading causes worldwide of
diarrhoeal illness in humans (Di Genova and Tonelli, 2016). Giardia lamblia is a single-celled
organism belonging to the anaerobic flagellate protozoa and is a parasite responsible for giardiasis
(Adam, 2001). The parasite present in food and water contaminated by faecal material attaches by
suction cups to the wall of the small intestine of the individual, where it interferes with the normal
absorption of fat and carbohydrates. Malabsorption and indigestion resulting from a reduction of
intestinal microvilli increases intestinal permeability and apoptosis of enterocytes; these effects may
facilitate the development of chronic intestinal disease, including inflammation, irritable bowel
syndrome, and allergy, through little-known mechanisms (Cotton et al. 2011). Generally, the presence
of the parasite does not cause any disease, but after an incubation period of 10-12 days, diarrhoea,
epigastric pain, anorexia, nausea and flatulence appear; in children and in people with immune
deficiencies, these conditions can cause steatorrhea, weakness, weight loss, growth retardation and
cognitive impairment (Hassanein et al., 2017).
Cryptosporidium parvum is the species most responsible for infection in humans, both at the digestive
level by respiratory inhalation of oocysts during vomiting and can be present in water, both the
recreational type and that used in food preparation, soil, raw fruits and vegetables, unpasteurized

14
milk, veal, tripe and sausages. Some studies report that many cases of intestinal cryptosporidiosis are
combined with dependent respiratory diseases of the bronchi, lungs, and trachea and inflammation of
the turbinates (Chalmers et al., 2019). Cryptosporidiosis of the respiratory tract has been detected in
many species of birds, including turkeys, chickens, partridges, pheasants, and quail, even in birds of
prey, and can occur with or without gastrointestinal disease (Nakamura and Meireles, 2015). In
immune compromised hosts, the parasites cause prolonged infections that can be fatal; for this reason,
cryptosporidiosis is considered one of the riskiest infections for patients suffering from acquired
immune deficiency syndrome (AIDS) (Wang et al., 2018).
Entamoeba histolytica is a protozoan infectious agent able to penetrate the wall of the colon and
generate disease both locally and extraintestinally as necrotic liver abscesses. This type of amoeba,
due to its characteristic virulence factors, such as its ability to produce lectins, perfluorines, and
proteases, is, globally, a frequent cause of death. Its main action is its ability to adhere to intestinal
cells, causing bloody diarrhoea with mucus in the stool; it also produces a protease that degrades the
cell wall, allowing for its spread through the bloodstream to other organs, such as the liver, lungs, and
brain (Cavagnaro et al., 2006; Anaya-Velazquez, 2011).
Tapeworms are a multicellular parasite belonging to the family of Platyhelminthes, class Cestoda.
They are commonly known as Taenia and live in the intestines of all animals, including humans,
where they can reach a length of eight metres. Three species infect humans: Taenia saginata, Taenia
solium and Trichinella spiralis. Diphyllobothrium latum or Botriocefalo are a genus of tapeworm that
can cause diphyllobothriasis in humans through the consumption of raw fish, such as trout and perch.
Humans become infected by eating raw or poorly cooked meat from infected animals, which contain
the larvae of taenia in the muscles, called cysticerci, which, in the human gut, after two or three weeks
of ingestion of the meat, turn into adult forms, causing epigastric pain, vomiting, nausea, diarrhoea,
weight loss, and increased eosinophils in the blood. The life cycle of Taenia solium utilizes pigs and
humans as an intermediate medium that hosts cysticercosis nourishes the adult taenia. Tapeworm
eggs are the vectors of transmission of cysticercosis, a pathology that, in pigs, leads to the
development of cysts in the tissues in addition to different neurological manifestations: tremors,
spasms, paralysis of the mouth and ears, salivation, flashing eyes, and walking in a circle, and it is
necessary to put them down. In a study by Trevisan et al. (2016), after performing an autopsy of the
pigs, cysticercosis was present in their brains in a relatively large number in relation to the size of the
observed phenomena (Trevisan et al., 2016). Humans can also be infected with the larvae after the
accidental ingestion of eggs present on contaminated vegetables (Rostami et al., 2016). Taenia
saginata is relatively harmless because only the intestinal tapeworm phase occurs in humans, while

15
Taenia solium infection has important health effects due to an extraintestinal infection caused by the
larval phase or due to the presence of cysts in the central nervous system (Shafaghi et al., 2015).
Fish are foods that can easily cause intestinal parasitosis due to water pollution: the different species
of Diphyllobothrium (D), including flatworms, are responsible for diphyllobothriasis in individuals
through the consumption of raw or undercooked fish. D. latum is widespread in Scandinavia, western
Russia, and the Baltic regions of Europe and is now also present in North America, easily causing
infection. In the extreme east of Russia, D. klebanovskii was identified and utilizes salmon as an
intermediate host; other species, however, are found in herring or perch. In Japan, the most common
species responsible for human infection is D. nihonkaiense: the people at highest risk of infection are
traditionally those who regularly consume raw fish, sushi and sashimi (Kuchta et al., 2015; Hochberg
et al., 2016), fishermen who eat raw liver or eggs of the fish and those involved in the preparation
and tasting of foods that contain raw fish.
Anisakis is a trematode parasite that infests in many marine species, especially oily fish (Prester,
2016), is very resistant to raw storage processes and is destroyed by cooking and freezing. The most
affected species include herring, mackerel, cod, anchovies, sardines, and mullet. Anisakiosis is
transmitted by the intake of raw fish and can manifest itself in various forms: acute, which appears
4-6 hours after ingestion of contaminated fish, with strong stomach pain, vomiting, diarrhoea, and
fever but is not fatal; chronic, which appears as training in the gastric and intestinal mucosa of
eosinophilic granuloma, abscesses and ulceration lesions that can lead to bowel obstruction and
perforation of the stomach; additionally, chronic anisakiosis represents a risk factor for stomach and
colon cancer (Garcia-Perez et al., 2015). Allergic reactions can manifest even by the handling of
infected fish and occur with variable severity; allergic reactions include urticaria, angioedema, and
anaphylactic reactions, which are sometimes accompanied by gastrointestinal symptoms (Kolkhir et
al., 2016). Less frequent are asthmatic attacks, contact dermatitis and conjunctivitis after inhalation
or intake of fish contaminated with Anisakis larvae.
Trichinellosis is acquired by ingestion of meat containing encysted larvae of Trichinella spiralis.
After exposure to stomach acid and pepsin, the larvae emerge from the cysts and invade the intestinal
mucosa where they become adults. Through the lymphatic and circulatory systems, the larvae migrate
to the striated muscles of the host where encysts take on a spiral shape; in this stage, they are stable
and can remain in this condition for a long time. Mild infections may be asymptomatic; intestinal
invasion may be accompanied by gastrointestinal symptoms; migration in muscle tissue can cause
periorbital and facial oedema, conjunctivitis, myalgias, rash, and eosinophilia; more rarely, the heart
muscle and the central nervous system may become infected. In Italy, wild foxes act as a natural
reservoir for this parasite; some domestic animals are possible sources of infection, including pork,

16
boar and horse (Franssen et al., 2017; Cencek et al., 2018). Freezing at -15 °C to kill the larvae is not
sufficient for certain Trichinella species that are insensitive to such treatment, and it is very important
to subject the meat to a temperature of 70 °C until completely cooked.

6. Allergies and Intolerances

6.1. Food allergies

Most people can eat a variety of foods with no unpleasant phenomenon, while in some individuals,
certain foods or components of them can cause adverse reactions caused by food allergies or food
intolerance (Wang and Sampson, 2011). This phenomenon is exponentially increasing in the whole
population and can be mainly attributed to a greater intake of non-natural substances present both in
the food and in the air we breathe.
A food allergy is a negative response to food that occurs immediately or after a few minutes of taking
in a small amount and causes the appearance of skin rashes, itching, nasal congestion, coughing and
wheezing and also involves the immune system (Hamilton et al., 2010). The best-known allergenic
foods are cow's milk, eggs, soy, wheat, shellfish, fresh fruit and dried fruit.
An allergy to milk proteins, caused, in particular, by lactoglobulin, is found more often in infants and
children whose parents have a predisposition to allergies. The symptoms are usually gastrointestinal,
although negative responses vary between different individuals and can appear during the first three
months of age or later in life, between six and eighteen months. The modification of protein structure
by high-temperature treatment can eliminate the allergenicity factor: some sensitive individuals to
such food, in fact, can tolerate sterilized or evaporated milk-based products but not pasteurized milk.
These individuals can also consume "special artificial" or hypoallergenic milks that are prepared with
already fragmented proteins and are therefore more digestible and tolerable. For some children who
are allergic to cow's milk, soy milk is recommended as a substitute product, as it is a complete food
from a nutritional point of view, and its products are cost-effective. Soy allergies are very rare;
however, recent studies have shown, for very sensitive individuals, the possibility that soy is due to
cross allergies with cow's milk protein (Smaldini et al., 2011; Gomez-Andre et al., 2012; Tzifi et al.,
2014). An allergy to nuts, in particular, to peanuts, shows symptoms of a certain severity; a peanut
allergy manifests itself in childhood and lasts for life and can even be lethal (Cetinkaya et al., 2019).
Some of the potentially allergenic proteins in foods can be eliminated by cooking or industrial
processing, by which proteins are denatured: high pressure treatment, fermentation, and enzyme
treatment can help to reduce the allergenicity of proteins (Schwager et al., 2015).

17
Rare cases of allergic reactions are also caused by oils and the correlation between the onset of the
disease and the food is not always immediate for a prompt diagnosis: sometimes the adverse reaction
is due to the presence of pollen of the plant from which they were extracted (Treudler and Simon,
2017) or to inhalation of volatile substances (Kuroyama et al., 2015) or supplements of omega-3
extracted from fish fat (Howard-Thompson et al., 2014). An allergy to eggs is widespread among
children, but it represents a form of hypersensitivity bound to decrease over time: it is very likely that
a person allergic to eggs in childhood can consume them in adulthood without showing any adverse
reaction (Urisu et al., 2015). The allergy form is determined by three proteins with different
characteristics: ovalbumin and ovotransferrin are heat-sensitive, so full cooking of chicken meat,
where they are present, will not cause an allergic reaction (Claude et al., 2016); ovomucoid, a
glycosylated protein present in the albumin, is very resistant to both heat and trypsin digestion and
retains its allergenic capacity even after cooking (Bartnikas et al., 2015). Recent studies have shown
that allergies are determined by the S-S bonds in sulfur-containing amino acids. Experimentally, it
has been shown that it is possible to reduce S-S bonds by electrolysis with the loss of two peptide
fragments from both sides of molecules containing disulfide bridges, resulting in a decrease in
allergenicity (Kido and Matsumoto, 2015; Palmer et al., 2017).
Fish are a source of proteins and can also contain biologically active substances, such as
eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), and are therefore a very important
food for health. With the increased consumption of fish, however, allergic reactions have become a
worldwide problem, especially in developing coastal countries where fish is a main food. An allergy
to seafood, which is evident from early childhood, persists throughout life and involves the immune
system and the production of IgE antibodies. Although the first manifestation of an allergic reaction
to foods is in the gastrointestinal system, in the case of fish products, symptomatology occurs not
only after ingestion but also by inhalation or contact with the skin in particularly sensitive people
(Prester, 2016).
Tropomyosin is the main allergen responsible for the cross-reactivity of the ingestion of crustaceans
and shellfish and the inhalation of other invertebrates, such as dust mites (Zhang et al., 2019).
Tropomyosin is a protein composed of two sub-units folded into an alpha-helix, of filamentous form,
highly resistant to heat, and is implicated in the control of muscle contractions and prevention of, in
combination with troponin, the link between actin and myosin and, consequently, contractions.
Merluccidae belong to the Gadidae family and include very valuable fish, such as cod, hake and
Alaska pollock. Major allergens of these fishes, including parvalbumin, a calcium binding protein
present in the muscle (Kuehn et al., 2010) and collagen (Kobayashi et al., 2016) of various species,
have been detected. Contact with cod, by ingestion or inhalation of cooking fumes, can cause allergy

18
symptoms, such as oropharyngeal swelling, urticaria, facial angioedema, and anaphylaxis; in some
individuals, asthma attacks may be experienced only by exposure to the smell of fish. Collagen, as an
allergen in fish, was identified in 2000 and has been underestimated because its allergenic potential
is very low, but its use in the nutraceutical, cosmetic, and pharmacological fields has increased the
development of collagen allergies and is the subject of further research. The major allergen is
constituted, in fact, by the parvalbumins present in all species of fish, which are able to undergo cross-
reactions: almost half of the individuals allergic to fish experience an allergic reaction when
consuming several different species, while the other individuals experience an allergic reaction to
only one species, tolerating all others. It is appropriate, however, in the case of allergic reactions when
consuming the fish, to take into account other conditions that could cause the reaction, such as the
Anisakis simplex allergy and Scombroid syndrome. Anisakis simplex is a parasite of fish that can
infect humans, especially consumers of raw fish, and can easily cause allergic reactions; in this case,
the allergen is not of the fish but of its parasite (Meseguer et al., 2007; Pravettoni et al., 2012).
Scombroid syndrome is characterized by a rash and gastrointestinal symptoms and occurs without
involvement of the immune system or the presence of IgE; the allergic symptoms are due to the
exposure to biogenic amines, especially histamine, which are released in large quantities during the
rotting process of fish, particularly during that of mackerel and tuna (Tortorella et al., 2014).
Scombroid syndrome is not an allergic reaction and can affect all individuals who ingest spoiled fish
that was not conserved in a suitable manner (Bilò et al., 2019). For some individuals, peanuts are one
of the causes of food-induced anaphylaxis. The cause of the allergic phenomenon is, however,
independent of the type of cultivar because both the protein content and the quality of the present
proteins are comparable between the different species (Koppelman et al., 2016). The main allergens
are represented by seed storage proteins, including viciline, conglutin and glycinin, that have high
stability and are responsible for serious anaphylactic reactions. Allergic reactions to peanuts can be
either mild or extreme, but, compared to reactions to other food, peanut allergens are more dangerous
and are even lethal. There are reports of atopic dermatitis, angioedema, asthma, diarrhoea, nausea,
vomiting and anaphylaxis: all of these symptoms are preceded by urticaria. Although peanuts share
homologous proteins with beans and related legumes from the botanical point of view, the majority
of individuals do not show clinical reactions to other legumes; similarly, individuals allergic to
peanuts do not show a high risk of cross- or co-reactivity to soybean allergens, as evidenced by
previous experiments (Van Boxtel et al., 2008).

6.2. Food intolerances

19
Food intolerance is related to enzymatic dysfunction determined by the absence or deficiency of
certain enzymes; it can cause allergy-like symptoms but does not involve the immune system and
occurs when the body cannot properly digest a food or a component of it. Lactase deficiency, the lack
of an enzyme necessary for the digestion of milk sugar that leads to lactose intolerance, is particularly
well known. When the enzymatic activity is reduced, lactose is not broken down into its components,
glucose and galactose, and, as such reaches, the large intestine where it is fermented by bacteria,
causing symptoms such as intestinal cramps, flatulence, and diarrhoea. Lactase deficiency is a
widespread phenomenon that is acquired over time, especially if individuals no longer include milk
in their diet; it is very rare, in fact, that lactose intolerance is congenital but begins to manifest itself
at approximately 5-6 years of age, and it more commonly manifests among adults as a result of
inflammatory diseases, such as gastroenteritis, celiac disease and Crohn's disease, which cause partial
atrophy of the intestinal villi (Montgomery et al., 2018). The amount of milk and dairy products that
can cause symptom intolerance varies from individual to individual: many individuals with reduced
lactase activity can consume a glass of milk with no problem, and the consumption of aged cheeses,
which are low in lactose, and fermented milk products such as yogurt are well tolerated; thus, their
consumption has increased worldwide.

6.3. Celiac disease

Celiac disease is a pathology that involves the immune system and is characterized by a permanent
intolerance to gluten, the main protein of wheat; celiac disease manifests itself in early childhood,
after weaning, presenting chronic inflammation of the small intestine, which can causes the
disappearance of the intestinal villi (Lebwohl et al., 2018). In a healthy individual, the intestinal
mucosa is lined with tissue protrusions, villi, which have the function of absorbing essential nutrients.
In individuals with celiac, for which the ingestion of foods containing gluten is toxic to the gut, the
villi regress, and the intestinal mucosa is damaged, reducing the surface absorption of nutrients and
causing failure and malnutrition (Jiménez et al., 2016). The disease accompanies the individual for
life, and only a very restrictive diet with the elimination of all foods containing gluten improves
symptoms, which include weakness occurring from weight loss, abdominal cramps, diarrhoea, and
irritability.
In children, the consequences of weight loss and malnutrition are more clearly visible due to impeded
growth (Paul et al., 2016). Recent studies have highlighted a number of neurological manifestations
in patients with celiac disease: cerebellar ataxia, peripheral neuropathy, deafness, headache,
depression, and epilepsy (Mearns et al., 2019). Autism is considered a possible manifestation of

20
intolerance to gluten in non-celiac patients. Gluten intolerance with or without celiac disease, but
with the presence of intestinal inflammation, may also be the cause of skin disorders such as
dermatitis herpetiformis (Harries, 2014). Autoimmune diseases, allergies, and psoriasis have been
linked to gluten intolerance, and in these cases, serological screening for antibodies against gliadin,
endomysia and transglutaminase is necessary to diagnose celiac disease with certainty or to assign it
as a gluten intolerance.

6.4. Phenylketonuria

In 1934, Ivar Asbjørn Fölling examined two children with pronounced mental retardation and
diagnosed oligophrenia phenylpyruvica for the first time, observing the presence of phenylpyruvic
acid in their urine (Fölling I.A., 1934). This disease, known in later years as phenylketonuria, is a
recessive autosomal disease determined by the PAH (phenyl alanine hydroxylase) gene mutation
encoding the enzyme phenylalanine hydroxylase, which is particularly active in the liver. Blocking
the metabolism of phenylalanine and its transformation into tyrosine leads to an accumulation of
phenylalanine in the blood and in some tissues of the body. Phenylalanine accumulation is partially
converted into phenylpyruvate and acetate, and these metabolites are excreted in urine. Tyrosine
deficiency causes an insufficient production of molecules derived from it, including the
neurotransmitters adrenaline and noradrenaline, dopamine, and melanin; phenylalanine that
accumulates in the brain leads to mental retardation, growth retardation and early death (Schlegel et
al., 2016). This disease can be controlled by the intake of foods free from phenylalanine; however,
this amino acid must still be supplied in controlled amounts since it is an essential amino acid, which
is needed for the production of proteins in body tissue (Brown and Lichter-Konecki, 2015). Although
phenylketonuria occurs mainly in childhood, the first symptoms may also develop in late adulthood
as a common neurological disease characterized by progressive dementia and characteristics of
Parkinson’s disease (Vardy et al., 2020).

7. Diseases from dietary manipulations

Many adverse reactions of the body towards foods are caused by the treatments to which they are
subjected in order to maintain unchanged organoleptic characteristics as long as possible over time.
To prevent foodborne diseases and to ensure the quality and safety of products, it is necessary that
each handling operation be performed in accordance with the behavioural rules established by the
World Health Organization (WHO).

21
Unpleasant organic reactions can be caused by the indiscriminate use of insecticides, herbicides, and
pesticides in the cultivation of food. Excessive use of food additives or the excessive consumption of
exotic foods, to which the body has not developed any defence mechanisms, increase the risk of an
adverse reaction. Over the past forty years, the relentless industrialization and the spread of food on
an international scale have required treatments that were not previously implemented, of which the
main one is food handling. This process includes all the chemical and physical industrial processes
that lead to the production of food that is no longer intact from a biological point of view (Bahna and
Burkhardt, 2018; Velázquez-Sámano et al., 2019; Marion-Letellier et al., 2019).

8. Milk processing

Milk undergoes a long series of transformations both to eliminate the possibly present pathogenic
bacteria and to prolong the storage time. In addition, we must consider that the cows are subject to
treatments using hormones and antibiotics to maintain high production, and these substances may be
present both in animal meat and in milk, with possible adverse effects on consumer health, especially
in infants or elderly individuals (Baars, 2019). Additionally, fresh milk can be a dangerous pathogenic
vector: the germs that may be present in milk may come from sick animals (primary pollution) or
result from subsequent its handling (secondary pollution), causing infection. The most important
diseases transmitted by milk are tuberculosis and brucellosis; the latter can also contaminate dairy
products derived from unpasteurized milk, along with many other bacteria, including Staphylococcus,
Streptococcus, Clostridia, Salmonella, and Listeria infections. Additionally, germs can contaminate
the milk from external sources through poor hygiene during milking, transport and distribution, from
the operator if they do not observe the basic rules of hygiene or are an unconscious carrier of diseases,
from the environment if the premises on which the livestock are raised and that where milk processing
occurs are not hygienically fit, and from the food if it is contaminated with mould or bacteria.
Moreover, the size of the stables and automation and mechanization of the operations are the basis of
microbiological contamination problems in milk and its derivative products (Velázquez-Ordoñez et
al., 2019).
Most anti-dairy microbes are neutralized by disinfectants and by heat treatments of milk, but these
methods are ineffective for clostridia, whose presence causes "late blowing", a defect of both hard and
soft cheeses, characterized by the presence of holes, cracks and a spongy consistency, which is associated
with an unpleasant taste and smell. The main cause is feeding cattle with fodder stored in the absence
of air, the silage, which affects the growth of Clostridia, as they are anaerobic bacteria; instead, a
traditional diet based on fresh grass decreases the number of spores present. Even the presence of

22
aflatoxin M1 in milk is caused by contamination of the feed since it is produced by a fungus,
Aspergillus flavus, which can attack corn, the main ingredient in cow feed. The presence of the many
risks related to the consumption of raw milk makes the implementation of rehabilitation treatments
necessary to destroy pathogenic microorganisms present therein. Raw milk is channelled into closed
tanks and cooled to 4 °C to slow bacterial growth; it is then transferred through refrigerated tankers
to factories where it is subjected to various treatments, such as pasteurization, sterilization, ultra-
filtration, and homogenization, to obtain a product that can be consumed without any health hazards
(Griep et al., 2018; Moezi et al., 2019).

9. Chemical and physical agents responsible for food alteration

The organoleptic characteristics of foods exposed to air at ambient temperature undergo alterations
over time that may be to the cause of disorders and diseases most frequently affecting the digestive
system. To avoid such problems, one must know the causes of the alteration to properly implement a
different and effective processing techniques. Air, particularly, the oxygen constituent, pH,
temperature, and the presence of enzymes and micro-organisms are the main factors in food
deterioration. Preservation methods may be physical in nature: the use of low temperatures
(refrigeration, freezing), use of high temperatures (pasteurization, sterilization), elimination of water
(concentration, drying, freeze-drying), removal of air (vacuum packaging, packaging with CO2 or
N2), smoking, the use of methods of a chemical nature, and the use of food additives (Sohail et al.,
2018).

10. Food additives

Food additives are substances that are intentionally added to food with the aim of improving
technological characteristics, such as organoleptic properties or shelf life. Their use is not new: the
salting of meat for storage and adding spices to foods as a preservative, was a common practice among
Egyptians, Greeks and Romans, as well as the use of dyes. In recent decades, our lifestyle has
changed, and the use of food additives, combined with new industrial technologies, has made the
large-scale preparation of foods in various forms possible, such as powder mixes for sauces, mashed
potatoes and instant desserts and meals that are ready to eat. Such products available today may not
exist if there were no additives, but in recent decades, along with increased usage, the types of
additives on the market have also increased, thus increasing the overall amount of these substances
that are consumed daily by Western consumers. Exposure to these substances in increasingly high

23
concentrations is a risk factor for sensitive people, especially children and the elderly. The
accumulation of food additives can disrupt intestinal homeostasis, thus promoting inflammatory
responses that are damaging to tissues. It has been observed that the balance of seriously
compromised intestinal homeostasis causes an increase in inflammatory bowel diseases such as
Crohn's disease and ulcerative colitis (Laudisi et al., 2019; Velázquez-Sámano et al., 2019).
The addition of additives containing phosphorus, either in the form of salts or as a polyphosphate, for
used in pH adjustment as thickeners, and as emulsifiers, causes serious danger of death by heart attack
or kidney damage. The quantity of phosphorous in the additives, being easy to absorb, is added to the
amount that is already present in the food, resulting in increased difficulty of elimination for the
organism.
Many studies have shown that sulfites and bisulfites are a widely used in pre-packaged products as
preservatives and antioxidants, and the sulfur dioxide present in jams, juices, and wines is also used
as a spray in restaurants to prevent oxidation of salads and fruit salads. Furthermore, sulfites prevent,
among other effects, a known alteration of crustaceans that causes blackening or melanosis, by acting
as specific competitive inhibitors of polyphenol oxidase, an enzyme that converts tyrosine into
melanic pigments. In susceptible individuals, these additives can cause dermatitis, hives, hypotension,
abdominal pain and diarrhoea; moreover, in highly susceptible individuals, sulfites can cause
anaphylactic reactions and asthma attacks. The severity of the reactions varies widely, but adults with
bronchial hyperactivity and children with chronic asthma appear to be at greater risk. Exposure to
sulfites as well as acute episodes can cause chronic alterations in both the skin and chronic respiratory
symptoms (Carocho et al., 2014; Zhang et al., 2014). Even salicylates naturally present in nuts,
berries, grapes, olives, and herbs can cause chronic urticaria and bronchospasms, affect the
gastrointestinal tract with colitis and diarrhoea and have effects on the circulation or even cause
anaphylactic shock (Skypala et al., 2015). More attention should be paid to the use of monosodium
glutamate as a flavour enhancer in many food products. Some issues, such as reactions that affect the
digestive system, causing pain in the gall bladder and bouts of diarrhoea, reactions that have been
identified to interfere with the normal functioning of the sense organs, such as ringing in the ears and
possible eye damage, or increased blood pressure and asthma have been linked to the consumption
of monosodium glutamate (Sharma, 2015). Due to its widespread presence in chips, candy, biscuits,
cheese, fries, ketchup, sauces, rice and freeze-dried pasta, the exposure of children to monosodium
glutamate can be very harmful because it can be addictive, increase appetite, and have long-term
effects on obesity. The long-term consumption of glutamates may have neurotoxic effects with
degenerative changes in neurons and astrocytes in the cerebellar cortex, as has been demonstrated in
albino rats. In addition, monosodium glutamate increases the concentration of βamyloid in the

24
hippocampus region, favouring the incidence of Alzheimer's disease (Dief et al., 2014). The nitrates
added to sausages and canned meats as antimicrobials to prevent the botulinum toxin can cause
headaches, even hours after food consumption. The reduction of nitrates to nitrites by nitrate-
reductase, an enzyme present in the bacterial flora of the oral cavity and of the intestinal lumen, may
cause acute toxic effects to the methaemoglobin action of nitrites; chronic toxic effects are due to the
reactions between nitrogen oxide and amines, resulting in the formation of nitrosamines and
carcinogenic substances (Habermeyer et al., 2015; Bedale et al., 2016).

11. Synthetic sweeteners

The consumption of sugary drinks is considered one of the dietary causes of metabolic disorders such
as obesity and type 2 diabetes, diseases that are increasing in the Western population. Many studies
have been developed to evaluate the replacement of sucrose with low-calorie sweeteners to find an
effective solution for weight management (Wong, 2018). The replacement of sucrose with saccharin
and aspartame, synthetic non-caloric sweeteners, in yogurt administered to Wistar rats showed weight
gain in the rats compared to the control rats fed yogurt with added sucrose: although the mechanisms
of this effect are still not clear, it is assumed that weight gain is attributable to an increased retention
of liquids (Feijó de Matos et al., 2013). Furthermore, it was shown that the long-term consumption
of aspartame leads to hepatocellular damage and alterations of the antioxidant status of the liver,
leading to a considerable decrease in the concentration of glutathione and reduced activity of the
glutathione peroxidase and glutathione reductase enzymes. Very controversial opinions exist on the
safety of aspartame: when ingested, it is rapidly metabolized into its three components: aspartic acid,
phenyl-alanine, and methanol. For the presence of phenylalanine, this sweetener should not be taken
by patients with phenylketonuria patients; when aspartame is processed by chymotrypsin, present in
the intestines, methanol, a toxic substance that causes neurological disorders, nausea, headache, mood
disorders of balance, blurred vision, and blindness, is released; additionally, children are especially
at risk. Aspartame degrades very easily when subjected to heat and therefore is not used in baked
goods; moreover, the preservation of foods at any unsuitable temperature causes its decomposition
with harmful effects (Ardalan et al., 2017; Lebda et al., 2017). Being 200 times sweeter than sucrose,
it causes the early onset of metabolic diseases related to obesity, such as hyperlipidaemia, insulin
resistance, cardiovascular problems and even some cancers. Sucralose is a synthetic sweetener
recently obtained by the chlorination of sucrose and is used globally as a food additive. It interacts
with chemosensors that play a role in the sensation of sweet taste; it is quite stable when subjected to
heat, but chlorinepropanols, a class of potentially toxic compounds, are generated at very high

25
temperatures. In rats, sucralose alters the microbial composition of the gastrointestinal tract, with a
notable reduction of beneficial bacteria. Although early studies have shown that it is eliminated
without decomposition in the gastrointestinal tract, further analysis revealed the presence of methanol
in faecal extracts after oral administration of sucralose. Doubts about its safety have been raised about
its alleged effects on the thymus, a gland that is very important for the immune system, and its feared
carcinogenicity in the blood system (Berry et al., 2016; Magnuson et al., 2017).

12. Natural and artificial colorants

The use of colour additives is a solution that the food industry makes use of on a daily basis to restore
or revive the original colour appearance of a food, which is very important for influencing consumer
choice when they are purchasing a product.
Food additives and among them the dyes have been and are constantly monitored as toxic potentials.
In truth, just because several substances belonging to these categories can be classified as a
contaminant, this does not mean that all of them cause foodborne illness. Nevertheless, due to the
often contradictory results and insufficient data to definitively classify many substances normally
used as safe or carcinogenic, a constant evaluation of both new and already known chemical
substances is certainly necessary and desirable.
Although today all food additives are carefully regulated by federal authorities and various
international organizations to ensure that foods are safe to eat and carefully labeled, there are
nevertheless significant concerns and the problem is currently much discussed as some evidence on
the use of these substances has emerged over the years. In fact, the Food and Drug Administration
(FDA) and the European Food Safety Authority (EFSA) have published a list of approved dyes and
additives. The reports of these agencies are complete and there are guidelines for the use of agents
intended for both human and animal use. In the U.S. food landscape, the FDA (FDA 2010) is
responsible for regulating all coloring additives to ensure that foods containing coloring additives are
safe to eat, contain only approved ingredients, and are carefully labeled. In the same way, in Europe
this task is carried out by the EFSA (2016). The use of both natural and synthetic colouring substances
is widespread and sometimes presents undesirable events that can cause different types of
disturbances, from skin reactions to anaphylactic shock (Kobylewski and Jacobson, 2012; El-Wahab
and Moram, 2013; Amchova et al., 2015). Some colours are more dangerous, such as atrazine and
azodyes that may cause hypersensitivity reactions, allergies and asthma; others belonging to the
missing category are fat-soluble and can cause neurological effects; erythrosine is particularly
dangerous. It is a red dye that can cause hyperthyroidism and sensitivity to light. Finally, some dyes

26
have proven toxic to humans with high carcinogenic, mutagenic, and teratogenic properties (Amin et
al., 2010; Reza et al., 2019).
The inadequacy of most of carcinogenicity, genotoxicity and hypersensitivity tests, together with the
fact that dyes do not improve the safety or nutritional quality of food, makes it necessary to pay
greater attention to the use of the dyes currently in use; therefore, to ensure food safety, food dyes
should be present to a limited extent and possibly replaced by dyes of natural origin that have been
proven to be harmless. Recent research has shown that many food dyes and additives are responsible
for "attention deficit disorder", "hyperactivity in children" and "Feingold syndrome" (Feingold,
1977). Feingold syndrome presents is predominantly diagnosed in people of young age, and one of
the most plausible hypotheses considers the fact that their body, not yet fully developed, is not able
to adequately and sufficiently detoxify harmful substances. The typical symptoms that occur are easy
distraction, little tolerance for frustration, nervousness, anxiety, impulsivity and aggression that tend
then to be maintained with the passing years. At the base of this syndrome, various causes are assumed
that are genetic in nature, such as central nervous system dysfunction and inadequate embryonic
development, which may be related to low-molecular-weight compounds present in artificial
colouring substances; their action in this regard does not seem to be based on an immunological
mechanism but rather on toxicological/pharmacological interactions (Ramesh and Muthuraman, 2018).

< Insert Figure 2 here >

13. Pesticides, heavy metals and other contaminants

In several studies, the close correlation between natural toxins, pesticides, illegal additives in food
and health risks is evident. Many substances belonging to the above categories are known to be
carcinogenic, mutagenic, teratogenic or toxic and have often been correlated with diseases such as
colitis, metabolic dysregulation and obesity and related comorbidities (Chassaing et al., 2015; Roca-
Saavedra et al., 2018). Nevertheless, macro and microelements represent one of the qualitative
parameters of many foods such as cereals (Stein, 2010). However, it must be remembered that these
elements are not only essential for the proper functioning of plants and humans, but they can be
potentially toxic to living organisms (White and Brown, 2010). In particular potentially toxic
elements are represented by the so-called heavy metals. Generally, on the basis of their danger to
human health, these metals can be classified into different groups: (a) essential elements, such as Cu,
Zn, Mo, Cr and Se; (b) other elements that can be considered essential such as Mn, Ni and V; (c)
potentially toxic elements, such as Cd, Pb and Hg (Mehri and Marjan, 2013). Under certain

27
conditions, even the essential elements (eg Cu) can lead to toxicity both for plant species and for
those who consume them (Bost et al., 2016). In agricultural soils Hg represents a serious danger to
human health (Toth et al., 2016), in fact it is known that, like other metals, Hg can migrate from soil
to food through the intake of plants (Gall et al., 2015). Moreover, it must be taken into account that
this element is one of the most widespread metals and in particular it is present in fish products, so it
reaches the food chain influencing the health of consumers (Karagas et al., 2012). Mercury toxicity
has been extensively documented, one of the most highlighted aspects is the damage that this element
can cause at the neurological level. In this sense, it has been shown that in the preschool infant
population, prenatal exposure to mercury (through the consumption of fish during pregnancy) is
closely related to subsequent adverse neurological development (Freire et al., 2010). Nowadays it is
common opinion that the main causes of the presence of toxic elements in important plants for food
use (for example rice), is due to the accumulation of industrial waste, agricultural waste and the
uncontrolled use of chemical products (Antoniadis et al., 2019). In addition, the use of fertilizers,
such as NPK, can bring a quantity of mineral elements to the soil and therefore to the various crops.
These fertilizers are not always able to promote high levels of dangerous heavy metals, but long-term
application could cause its accumulation in the soil and increase, for example, the risk of Cd
accumulation in plants (McBride, 2003). To date, much is known about cadmium. It represents a
heavy non-essential metal scarcely present in the earth's crust. It is a toxic element naturally present
in the environment but often it is of anthropogenic derivation, in particular it can derive from mining
or from the use of fertilizers (Järup and Åkesson, 2009). Since Cd is highly toxic, it represents a
serious problem for human health and safety as it can enter the food chain (Wenzel et al., 2001;
Rodríguez-Serrano et al., 2008). Foods contaminated with an excess of Cd can damage vital organs
such as organs such as lungs and liver causing cancer and serious diseases (Zarcinas et al., 2004), as
well as causing serious kidney damage and osteoporosis (Rai et al., 2003). A very relevant topic is
represented by veterinary drugs and pesticides, in fact every year there is a considerable increase in
their use which inevitably promotes the presence of dangerous residues in food of animal origin (Deng
et al., 2011). These drug residues can present enormous dangers to human health (Desmarchelier et
al., 2018). To date, more than 1000 antiparasitic substances are used worldwide. The use of pesticides
is subject to strict legislation which guarantees correct use and the obligation not to exceed the
maximum residue limits (MRLs). Despite these restrictions, the continued exposure of consumers to
low quantities of hundreds of different pesticides throughout their lives should be taken into account,
in fact many studies on these substances have shown close correlations between them and various
pathologies such as headache and nausea but also much more serious problems such as reproductive
damage, endocrine disorders (Baldi et al., 2001; Rivas et al., 2007) and many types of cancer

28
(Alexander et al., 2012; Rusiecki et al., 2006). In particular, very aggressive forms of cancer such as
leukemia, non-Hodgkin's lymphoma and brain, bone, breast, ovarian, prostate, testicular and liver
cancers have been reported (Cantor et al., 1992). In some scientific evidence in the literature, the
increased likelihood of children living in homes where their parents use pesticides to develop brain
cancer compared to those living in residences where pesticides are not used has been highlighted
(Bradman et al., 2007). Finally, it must be considered that some compounds deriving from meat are
carcinogenic potential. These substances include both exogenous and endogenous N-nitrous
compounds (Jakszyn et al., 2004), heme iron, heterocyclic amines (HCA) and polycyclic aromatic
hydrocarbons (PAH). These last two groups of compounds are strongly influenced by cooking and
preparation methods (Iwasaki et al., 2010; Jakszyn et al., 2004), in fact HCA are generally formed
during the cooking of beef, pork, chicken or fish; PAHs can be found especially in raw foods, but
also in cooked and preserved ones of all kinds, including cereals, vegetables and meat.

14. Unintentionally produced contaminants

An important aspect to take into account is that during production and following the application of
some production techniques, non-desirable compounds can be formed unintentionally. By this
definition we mean those substances that are not naturally present in the normal raw material used
for food production nor that are added during the normal production process. These include
environmental pollutants or contaminants deriving from the agricultural production of crops or
livestock or from the inadequate manufacture of the food product itself. In some cases the production
of food involves the application of thermal processes in the production of different types of food such
as meat, coffee, cocoa, etc. In particular, heat treatment is often used as a method of cooking meat, in
fact it can be grilled, barbequing, pan-fried and smoked. Roasting represents a crucial step for the
manufacture of coffee and cocoa, but at the same time, however, this technique could produce, in
carbohydrate-rich foods, mutagenic compounds through the Maillard reaction, in which amino acids,
asparagine in particular, react with reducing sugars during thermal processing at temperatures higher
than 120°C.
These types of cooking, however, cause the involuntary generation of contaminants, as in the case of
acrylamide in fried starchy foods or benzo[α]pyrene and other PAHs during the roasting process of
coffee and cocoa beans. In fact, charcoal-cooking and grilling in meat cooking or roasting in coffee
and cacao bean treatment, can generate an high release of PAHs and acrylamide through the pyrolysis
process of organic matter at high temperature (Diggs, Harris, Rekhadevi and Ramesh, 2012),
exposing people to a significant risk.

29
Many studies on genotoxicity of acrylamide and its metabolite glycidamide have been reported
(Besaratinia & Pfeifer, 2007; Rice, 2005; Dearfield et al., 1995).
As already evident from the literature, acrylamide is biotransformed into an active form, glycidamide,
by means of one of the cytochrome P450 2E1 (CYP2E1). Subsequently, this compound reacts with
cellular DNA, causing chromosomal damage (aberrations, micronuclei, aneuploidy) and mutagenic
effects and tumor induction (Adler et al., 2000; Ghanayem et al., 2005; Rice, 2005). Bongers and co-
workers reported that acrylamide may increase the risk of multiple myeloma and follicular lymphoma
in men (Bongers et al., 2012). It is not possible to avoid the formation of acrylamide in roasting
products such as coffee, and it is difficult to control the levels of this toxic substance as it varies with
the percentage of Robusta type in the mixture and with the time-temperature parameters during the
roasting process. Instead, it is possible to control the roasting conditions to minimize the formation
of acrylamide.
Likewise, benzopyrene should also be considered as an involuntarily produced chemical. This
substance, belonging to the polycyclic aromatic hydrocarbons (PAH), to date is considered, from the
point of view of toxicity, the most important of the approximately 660 compounds of this group and
for this reason it is often used as a marker in the contamination of PAH in food samples (EU, 2011).
Overall, therefore, these compounds must be considered very dangerous for human health. EFSA
(2008) has cataloged sixteen molecules belonging to this family based on their significance for public
health. In particular, EFSA grouped PAHs into three groups based on their food training levels,
potential toxicity, mutagenic and carcinogenic activity. Benzo[α]pyrene and crisisene formed a group
called the 2-PAH group, while a group of benzo[α]pyrene, chrysene, benz[α]anthracene and
benzo[b]fluorantene indicated the 4-PAH group. The third group, group 8-PAH, included 8 priority
PAHs, namely benzo[α]pyrene, chrysene, benz[α]anthracene, benzo[b]fluoranthene, anthracene,
benzo[k]fluoranthene, benzo[ghi]perylene, and dibenz[a,h]anthracene (EFSA, 2008). Instead, IARC
had used another criterion, carcinogenicity for humans. Based on this criterion, 3 groups were
identified: Group 1, carcinogen as benzo[α]pyrene; Group 2°, probable carcinogen as
dibenz[a,h]anthracene; Group 2B, possible carcinogen as benz[α]anthracene, benzo[b]fluoranthene
and chrysene. Data from the literature report that the most toxic compounds, benzo[α]pyrene and
congeners with five or six rings, are generally found at very low concentrations in food, with the
exception of benzo[ghi]perylene. This can occur because during roasting, some classes of nutrients
such as carbohydrates and peptides give rise to new molecules generating precursors, such as the case
of naphthalene. These new molecules can be added to particular compounds, in turn generating PAHs
(Kislov, Sadovnikov and Mebel, 2013). Specifically, benzo[a]pyrene is able to activate the aryl
hydrocarbon receptor (AhR). This receptor allows regulation of a group of xenobiotic metabolizing

30
enzymes (XME) which include phase I enzymes, phase II detoxification enzymes (Darwish, Ikenaka,
Eldaly and Ishizuka, 2010). Furthermore, AhR also regulates phase III xenobiotic transporters such
as multi-drug resistance protein 1 (MDR1) and multi-drug resistance protein 2 (MRP2) which are
involved in the process of excretion of benzo[a]pyrene and its metabolites (Kranz et al., 2014).
In general, unavoidable substances considered to be genotoxic carcinogens are undesirable in food
and are usually treated through the ALARA (As low as reasonably accepted) principle.
For substances such as acrylamide or PAHs considered to be involuntary contaminants, the ALARA
principle generally applies. When considering genotoxic compounds, a thresholdless mechanism is
presumed and a "safe intake level" cannot be ascertained, so no formal risk assessment is performed
and the "ALARA" principle is applied. This principle is intended to mean that the level of these
contaminants should be the lowest reasonably achievable (Scientific Committee on Food, 2002).
In a publication of the Japanese Food Safety Commission (FSCJ) it confirms the genotoxic power of
acrylamide and glycidamide with tests both in vitro and in vivo (Food Safety Commission of Japan,
2012). At the same time, however, considering the low level of intake of these substances with the
diet, it is not possible to establish a close relationship between neoplastic risk and acrylamide due to
insufficient margins of exposure (MOE), for which the FSCJ concluded that they are ongoing efforts
are needed to reduce dietary intake of AA according to the ALARA principle for the protection of
public health.

15. Conclusions

Foodborne illnesses are caused by the consumption of food or water contaminated with various types
of agents, such as bacteria, viruses, toxins, parasites and non-conventional agents. The main route of
introduction of these organisms is the gastrointestinal route, and it is at this level that the first
symptoms are usually exhibited. Food contamination can occur at all stages in their production chain,
from primary production (farming) to the table. For consumers, the best way to be assured of food
security is to inquire about the basic principles of food production and to properly prepare food at
home without neglecting important instructions and information on the label that allows for the
detection of the presence of substances that may cause allergies or intolerances, as well as the
expiration date of the product itself, thus avoiding unpleasant consequences. The knowledge of the
various types of contaminants, the critical points where food contamination can occur, the knowledge
of the diseases deriving from them are essential weapons to correctly apply all the prevention rules
in order to guarantee public health.

31
Conflicts of Interest

The authors declare that they have no conflicts of interest regarding the publication of this paper.

Funding

This research did not receive any specific grant from funding agencies in the public, commercial, or
not-for-profit sectors.

Author Contributions

Monica Gallo, Lydia Ferrara, Armando Calogero, Domenico Montesano and Daniele Naviglio:
writing—original draft preparation, Monica Gallo, Domenico Montesano and Daniele Naviglio:
writing—review and editing, Lydia Ferrara and Daniele Naviglio: visualization, Monica Gallo:
supervision.

References

Adam, R. D. 2001. Biology of Giardia lamblia. Clinical Microbiology Reviews, 14(3), 447–475.
Aggarwal, R., & Goel, A. (2015). Hepatitis A: epidemiology in resource-poor countries. Current
Opinion in Infectious Diseases, 28, 488–496.
Adler, I. D., Baumgartner, A., Gonda, H., Friedman, M. A., & Skerhut, M. (2000). 1-
Aminobenzotriazole inhibits acrylamide-induced dominant lethal effects in spermatids of male
mice. Mutagenesis, 15, 133–136.
Alexander, D., Weed, D. L., Mink, P. J., & Mitchell, M. E. (2012). A weight-of-evidence review of
colorectal cancer in pesticide applicators: the agricultural health study and other epidemiologic
studies. International Archives Occupational Environmental Health 85, 715–45.
Amchova, P., H. Kotolova, & J. Ruda-Kucerova. (2015). Health safety issues of synthetic food
colorants. Regulatory Toxicology and Pharmacology 73, 914–922.
Amin, K. A., H. A. Hameid II, & A. A. Elsttar. (2010). Effect of food azo dyes tartrazine and
carmoisine on biochemical parameters related to renal, hepatic function and oxidative stress
biomarkers in young male rats. Food and Chemical Toxicology 48, 2994–2999.
Antoniadis, V., Shaheen S. M., Levizou, E., Shahid, M., Niazi, N. K., Vithanage, M., Ok, Y. S.,
Bolan, N., & Rinklebe, J. (2019). A critical prospective analysis of the potential toxicity of trace

32
 element regulation limits in soils worldwide: Are they protective concerning health risk
assessment? - A review. Environment International 127, 819–847.
Anza, I., D. Vidal, C. Laguna, S. Díaz-Sánchez, S. Sánchez, Á. Chicote, ... & R. Mateo. (2014).
Eutrophication and bacterial pathogens as risk factors for avian botulism outbreaks in wetlands
receiving effluents from urban wastewater treatment plants. Appl. Environ. Microbiol., 80, 4251–
4259.
Ardalan, M. R., H. Tabibi, V. E. Attari, & A. M. Mahdavi. (2017). Nephrotoxic effect of aspartame
as an artificial sweetener: a brief review. Iranian Journal of Kidney Diseases, 11, 339–343.
Arguedas, M. R., & M. B. Fallon. (2001). Prevention in liver disease. The American Journal of the
Medical Sciences, 321, 145–151.
Atkins, P., & I. Bowler. (2016). Food in society: economy, culture, geography. Routledge, Taylor &
Francis Group, London and New York.
Baars, T. (2019). Regulations and production of raw milk. In Raw Milk 65–89. Academic Press.
Baert, L., Wobus, C.E., Van Coillie, E., Thackray, L.B., Debevere, J., Uyttendaele, M., (2008).
Detection of murine norovirus 1 using plaque assay, transfection assay and real-time RT-PCR
before and after heat exposure. Appl. Environ. Microbiol. 74, 543–546.
Bahna, S. L., & J. G. Burkhardt. (2018). The dilemma of allergy to food additives. In Allergy &
Asthma Proceedings, 39, 3–8.
Baldi, I., Filleul, L., Mohammed-Brahim, B., Fabrigoule, C., Dartigues, J. F., Schwall, S., Drevet, J.
P., Salamon, R., & Brochard, P. (2001). Neuropsychologic effects of long-term exposure to
pesticides: results from the French Phytoner study. Environmental Health Perspectives, 109, 839–
844.
Barbosa, L. J., L. F., Ribeiro, L. F., Lavezzo, M. M. C., Barbosa, G. A. M. Rossi, & L. A. do Amaral.
(2016). Detection of pathogenic Escherichia coli and microbiological quality of chilled shrimp
sold in street markets. Letters in Applied Microbiology, 62, 372–378.
Bartnikas, L. M., W. J. Sheehan, K. L. Tuttle, C. R. Petty, L. C. Schneider, & W. Phipatanakul.
(2015). Ovomucoid specific immunoglobulin E as a predictor of tolerance to cooked egg. Allergy
& Rhinology, 6, e198-e204.
Bedale, W., J. J. Sindelar, & A. L. Milkowski. (2016). Dietary nitrate and nitrite: Benefits, risks, and
evolving perceptions. Meat Science, 120, 85–92.
Bellio, A., D. Bianchi, M. Gramaglia, A. Loria, D. Nucera, S. Gallina, ... & L. Decastelli. (2016).
Aflatoxin M1 in cow’s milk: Method validation for milk sampled in northern Italy. Toxins, 8, 57–
69.

33
Berry, C., D. Brusick, S. M. Cohen, J. F. Hardisty, V. L. Grotz, & G. M. Williams. (2016). Sucralose
non-carcinogenicity: a review of the scientific and regulatory rationale. Nutrition and Cancer, 68,
1247–1261.
Berthiller, F., C. Crews, C. Dall'Asta, S. D., Saeger, G., Haesaert, P., Karlovsky, ... & J. Stroka (2013).
Masked mycotoxins: A review. Molecular Nutrition & Food Research, 57, 165–186.
Besaratinia, A., & Pfeifer, G. P. (2007). A review of mechanisms of acrylamide carcinogenicity.
Carcinogenesis, 28, 519–528.
Bhunia, A. K. 2018. Foodborne microbial pathogens: mechanisms and pathogenesis. Springer,
New York, USA.
Bilò, M. B., M. Martini, C. Tontini, O. E. Mohamed, & M. T. Krishna. (2019). Idiopathic
anaphylaxis. Clinical & Experimental Allergy 49, 942–952.
Bol, E. K., L. Araujo, F. F. Veras, & J. E. Welke. (2016). Estimated exposure to zearalenone,
ochratoxin A and aflatoxin B1 through the consume of bakery products and pasta considering
effects of food processing. Food and Chemical Toxicology, 89, 85–91.
Bost, M., Houdart, S., Oberli, M., Kalonji, E., Huneau, J-F., & Margaritis, I. (2016). Dietary copper
and human health: current evidence and unresolved issues. Journal of Trace Elements in Medicine
and Biology, 35, 107–115.
Bradman, A., Whitaker, D., Quirós, L., Castorina, R., Henn, B. C., Nishioka, M., Morgan, J., Barr,
D. B., Harnly, M., Brisbin, J. A., Sheldon, L. S., Mckone, T. E. & Eskenazi, B. (2007). Pesticides
and their metabolites in the homes and urine of farmworker children living in the Salinas Valley,
CA. Journal of Exposure Science and Environmental Epidemiology 17, 331–49.
Brown, C. S., & U. Lichter-Konecki. (2016). Phenylketonuria (PKU): a problem solved?. Molecular
Genetics and Metabolism Reports, 6, 8–12.
Buckow, R., Isbarn, S., Knorr, D., Heinz, V., Lehmacher, A. (2008). Predictive model for inactivation
of feline Calicivirus, a norovirus surrogate, by heat and high hydrostatic pressure. Applied and
Environmental Microbiology 74, 1030–1038.
Cantor, K. P., Blair, A., Everett, G., Gibson, R., Burmeister, L. F., Brown, L. M., Schuman, L., &
Dick, F. R. (1992). Pesticides and other agricultural risk factors for non-Hodgkin's lymphoma
among men in Iowa and Minnesota. Cancer Research, 52, 2447–55.
Carlomagno, N., P. Incollingo, V. Tammaro, G. Peluso, N. Rupealta, G. Chiacchio, ... & M. Sabbatini.
(2017). Diagnostic, predictive, prognostic, and therapeutic molecular biomarkers in third
millennium: a breakthrough in gastric cancer. BioMed Research International 2017:Article ID
7869802. https://doi.org/10.1155/2017/7869802

34
Carocho, M., M. F. Barreiro, P. Morales, & I. C. Ferreira. (2014). Adding molecules to food, pros
and cons: A review on synthetic and natural food additives. Comprehensive Reviews in Food
Science and Food Safety, 13, 377–399.
Caswell, J. A. (2019). Valuing food safety and nutrition. Routledge, Taylor & Francis Group, London
and New York.
Cencek, T. (2018). Occurrence of Trichinella spp. in rats on pig farms. Annals of Agricultural and
Environmental Medicine, 25, 698–700.
Cetinkaya, P. G., B. Buyuktiryaki, O. Soyer, U. M. Sahiner, C. Sackesen, & B. E. Sekerel. (2019).
Phenotypical characterization of tree nuts and peanut allergies in east Mediterranean
children. Allergologia et Immunopathologia, doi.org/10.1016/j.aller.(2019).07.005.
Chalmers, R. M., A. Davies, and K. Tyler. (2019). Cryptosporidium. Microbiology 165:500–502.
Chan, C. K., H. C. Lam, S. W. Chiu, M. L. Tse, & F. L. Lau. (2016). Mushroom poisoning in Hong
Kong: a ten-year. Hong Kong Med J, 22, 124–130.
Chang, S., & B. Shen, (2018). Classification and reclassification of inflammatory bowel diseases:
from clinical perspective. In Interventional Inflammatory Bowel Disease: Endoscopic
Management and Treatment of Complications, 17–34. Academic Press.
Chassaing, B., Koren, O., Goodrich, J. K., Poole, A. C., Srinivasan, S., Ley, R. E., & Gewirtz, A. T.
(2015). Dietary emulsifiers impact the mouse gut microbiota promoting colitisand metabolic
syndrome. Nature, 519, 92–96.
Cheng, M. F., W. L. Chen, I. F. Huang, J. R. Chen, Y. H. Chiou, Y. S. Chen,... & J. L. Wang (2016).
Urinary tract infection in infants caused by extended-spectrum beta-lactamase-producing
Escherichia coli: comparison between urban and rural hospitals. Pediatric Nephrology, 31, 1305–
1312.
Claude, M., R. Lupi, G. Bouchaud, M. Bodinier, C. Brossard, & S. Denery-Papini. (2016). The
thermal aggregation of ovalbumin as large particles decreases its allergenicity for egg allergic
patients and in a murine model. Food Chemistry, 203, 136–144.
Conlon, M. A., & A. R. Bird, (2015). The impact of diet and lifestyle on gut microbiota and human
health. Nutrients, 7, 17–44.
Cornick, S., & K. Chadee. (2017). Entamoeba histolytica: host parasite interactions at the colonic
epithelium. Tissue Barriers, 5(1), e1283386. DOI: 10.1080/21688370.2017.1283386.
Cotton, J. A., J. K. Beatty, & A. G. Buret. (2011). Host parasite interactions and pathophysiology in
Giardia infections. International Journal for Parasitology, 41(9), 925–933.

35
Darwish, W. S., Ikenaka, Y., Eldaly, E., & Ishizuka, M. (2010). Mutagenic activation and
detoxification of benzo[a]pyrene in vitro by hepatic cytochrome P450 1A1 and phase II enzymes
in three meat-producing animals. Food and Chemical Toxicology, 48, 2526–2531.
Dearfield, K. L., Douglas, G. R., Ehling, U. H., Moore, M. M., Sega, G. A., & Brusick, D. J. (1995).
Acrylamide: a review of its genotoxicity and an assessment of heritable genetic risk. Mutat. Res.,
330, 71–99.
De Boer, E., & A. E. Heuvelink, (2000). Methods for the detection and isolation of Shiga
toxin‐producing Escherichia coli. Journal of Applied Microbiology, 88(S1), 133S–143S.
de Matos Feijó, F., C. R. Ballard, K. C. Foletto, B. A. M. Batista, A. M. Neves, M. F. M. Ribeiro, &
M. C. Bertoluci. 2013. Saccharin and aspartame, compared with sucrose, induce greater weight
gain in adult Wistar rats, at similar total caloric intake levels. Appetite, 60, 203–207.
Deng, X. J., Yang, H. Q., Li, J. Z., Song, Y., Guo, D. H., Luo, Y., ... & Bo, T. (2011). Multi-class
residues screening of 105 veterinary drugs in meat, milk, and egg using ultra high performance
liquid chromatography tandem quadrupole time-of-flight mass spectrometry. Journal of Liquid
Chromatography & Related Technologies, 34, 2286–2303.
Desmarchelier, A., Fan, K., Minh Tien, M., Savoy, M. C., Tarres, A., Fuger, D., ... & Mottier, P.
(2018). Determination of 105 antibiotic, anti-inflammatory, antiparasitic agents and tranquilizers
by LC-MS/MS based on an acidic QuEChERS-like extraction. Food Additives & Contaminants:
Part A 35, 646–660.
Di Genova, B. M., & R. R. Tonelli. (2016). Infection strategies of intestinal parasite pathogens and
host cell responses. Frontiers in Microbiology, 7, article 256.
Dief, A. E., E. S. Kamha, A. M. Baraka, & A. K. Elshorbagy. (2014). Monosodium glutamate
neurotoxicity increases beta amyloid in the rat hippocampus: a potential role for cyclic AMP
protein kinase. Neurotoxicology, 42, 76–82.
Diggs, D. L., Harris, K. L., Rekhadevi, P. V., & Ramesh, A. (2012). Tumor microsomal metabolism
of the food toxicant, benzo(a)pyrene, in ApcMin mouse model of colon cancer. Tumor Biology,
33, 1255–1260.
Dolan, G. P., K. Foster, J. Lawler, C. Amar, C. Swift, H. Aird, & R. Gorton. (2016). An
epidemiological review of gastrointestinal outbreaks associated with Clostridium perfringens,
North East of England, 2012–2014. Epidemiology & Infection, 144(7), 1386–1393.
EFSA (2016). Re-evaluation of food colours: EFSA completes major programme, 14 September
2016. http://www.efsa.europa.eu/en/press/news/160914-0/Accessed 15 April 2020.
EFSA (2008). http://www.efsa.europa.eu/sites/
default/files/scientific_output/files/main_documents/724.pdf. Accessed on April 5th 2020.

36
El-Wahab, H. M. F. A., & G. S. E. D. Moram. (2013). Toxic effects of some synthetic food colorants
and/or flavor additives on male rats. Toxicology and Industrial Health, 29(2), 224–232.
Epis, S., C. Matinato, G. Gentili, F. Varotto, C. Bandi, & D. Sassera. (2010). Molecular detection of
poisonous mushrooms in different matrices. Mycologia, 102(3), 747–754.
Espelund, M., & D. Klaveness. (2014). Botulism outbreaks in natural environments–an
update. Frontiers in Microbiology, 5, article 287.
Esposito, F., Fasano, E., De Vivo, A., Velotto, S., Sarghini, F., & Cirillo, T. (2020). Processing effects
on acrylamide content in roasted coffee production. Food Chemistry, 319, 126550.
Esposito, P., E. La Porta, M. Calatroni, S. Bianzina, C. Libetta, M. Gregorini, ... & A. Dal Canton.
(2015). Renal involvement in mushroom poisoning: The case of Orellanus
syndrome. Hemodialysis International, 19, E1–E5.
EU. (2011). Commission regulation (EU) No 835/2011 of 19 August 2011 amending Regulation (EC)
No 1881/2006 as regards maximum levels for polycyclic aromatic hydrocarbons in foodstuffs.
Official Journal of European Union, L215, 4–8.
FDA (2010). Overview of Food Ingredients, Additives & Colors, November 2004; revised April
2010. https://www.fda.gov/food/food-ingredients-packaging/overview-food-ingredients-
additives-colors/Accessed 15 April 2020.
Feingold, B. F. (1977). Behavioral disturbances linked to the ingestion of food additives. Delaware
Medical Journal, 49, 89–94.
Food Safety Commission of Japan. Acrylamide in Foods Generated through Heating. Food Safety
2016; Vol. 4, No. 3, 74–88 (2016013s). https://doi.org/10.14252/foodsafetyfscj.2016013s.
Frank, H., T. Zilker, M. Kirchmair, F. Eyer, B. Haberl, G. Tuerkoglu-Raach, ... & U. Heemann.
(2009). Acute renal failure by ingestion of Cortinarius species confounded with psychoactive
mushrooms: a case series and literature survey. Clinical Nephrology, 71, 557–562.
Franssen, F., Swart A., van der Giessen, J., Havelaar A. & Takumi, K. (2017). Parasite to patient: A
quantitative risk model for Trichinella spp. in pork and wild boar meat. International Journal of
Food Microbiology, 241, 262–275.
Freire, C., Ramos, R., Lopez-Espinosa, M. J., Díez, S., Vioque, J., Ballester, F., & Fernández M. F.
(2010). Hair mercury levels, fish consumption, and cognitive development in preschool children
from Granada, Spain. Environmental Research, 110, 96–104.
Fulgione, A., M. Cimafonte, B. Della Ventura, M. Iannaccone, C. Ambrosino, F. Capuano, ... & R.
Capparelli, R. (2018). QCM-based immunosensor for rapid detection of Salmonella Typhimurium
in food. Scientific Reports, 8, 16137–16145.

37
Gall, J. E., Boyd, R. S., & Rajakaruna, N. (2015). Transfer of heavy metals through terrestrial food
webs: a review. Environmental Monitoring and Assessment, 187, 201–222.
Garcia, J., V. M. Costa, A. Carvalho, P. Baptista, P. G. de Pinho, M. de Lourdes Bastos, & F.
Carvalho. (2015). Amanita phalloides poisoning: Mechanisms of toxicity and treatment. Food and
Chemical Toxicology, 86, 41–55.
Garcia-Perez, J. C., R. Rodríguez-Perez, A. Ballestero, J. Zuloaga, B. Fernandez-Puntero, J. Arias-
Díaz, & M. L. Caballero. (2015). Previous exposure to the fish parasite Anisakis as a potential risk
factor for gastric or colon adenocarcinoma. Medicine 94(40), 1699-1706.
Geetha, M., & K. M. Palanivel. (2017). Necrotic enteritis in layer chicken. Veterinary Science
Research Journal, 8(1/2), 73–76.
Ghanayem, B. I., McDaniel, L. P., Churchwell, M. I., Twaddle, N. C., Snyder, R., Fennell, T. R., &
Doerge D. R. (2005). Role of CYP2E1 in the epoxidation of acrylamide to glycidamide and
formation of DNA and hemoglobin adducts. Toxicol. Sci., 88, 311–318.
Ghenem, L., Elhadi, N., Alzahrani, F., & Nishibuchi, M. (2017). Vibrio parahaemolyticus: A review
on distribution, pathogenesis, virulence determinants and epidemiology. Saudi Journal of
Medicine & Medical Sciences, 5(2), 93–103.
Griep, E. R., Y. Cheng, & C. I. Moraru. (2018). Efficient removal of spores from skim milk using
cold microfiltration: Spore size and surface property considerations. Journal of Dairy
Science, 101(11), 9703–9713.
Habermeyer, M., A. Roth, S. Guth, P. Diel, K. H. Engel, B. Epe, ... & D. Knorr. (2015). Nitrate and
nitrite in the diet: how to assess their benefit and risk for human health. Molecular Nutrition &
Food Research, 59(1), 106–128.
Hamilton, R. G., D. W. MacGlashan, & S. S. Saini. (2010). IgE antibody-specific activity in human
allergic disease. Immunologic Research, 47(1-3), 273–284.
Harries, C. (2014). Gluten intolerance and skin diseases. Encyclopedia of Medical Immunology:
Allergic Diseases, 339–346.
Hassanein, F. I., A. I., Shehata, & R. Abdul-Ghani. (2017). G. lamblia and H. pylori infections among
mentally challenged individuals in rehabilitation centers in Alexandria, Egypt. The Journal of
Infection in Developing Countries, 11, 577–582.
Herrmann, S. S., L. Duedahl-Olesen, T., Christensen, P. T. Olesen, & K. Granby. (2015). Dietary
exposure to volatile and non-volatile N-nitrosamines from processed meat products in
Denmark. Food and Chemical Toxicology, 80, 137–143.
Hochberg, N. S., & N. Bhadelia. (2016). Infections associated with exotic cuisine: the dangers of
delicacies. In Infections of Leisure, Fifth Edition 355–374. American Society of Microbiology.

38
Hossain, M. A., and S. C. Park. (2016). 14 A Review on Mushroom Toxins. In Food Toxicology 275.
CRC Press.
Howard-Thompson, A., A. Dutton, R. Hoover, & J. Goodfred. (2014). Flushing and pruritus
secondary to prescription fish oil ingestion in a patient with allergy to fish. International Journal
of Clinical Pharmacy, 36, 1126–1129.
Huang, L. (2015). Growth of Staphylococcus aureus in cooked potato and potato salad—A one-step
kinetic analysis. Journal of Food Science 80, M2837–M2844.
International Agency for Research on Cancer (IARC). (1993). Some naturally occurring substances:
Food items and constituents, heterocyclic aromatic amines and mycotoxins, monographs on the
evaluation of carcinogenic risks to humans, vol. 56, International Agency for Research on Cancer.
Lyon.
International Agency for Research on Cancer (IARC) (2010). Monographs on the evaluation of
carcinogenic risk to humans, overall evaluation of carcinogenicity. IARC Monographs on the
Evaluation of Carcinogenic Risks to Humans, Suppl 92, 33–814.
Iwasaki, M., Kataoka, H., Ishihara, J., Takachi, R., Hamada, G. S., Sharma, S., Le Marchand, L., &
Tsugane, S. (2010). Heterocyclic amines content of meat and fish cooked by Brazilian methods.
Journal of Food Composition and Analysis, 23, 61–69.
Jakszyn, P., Agudo, A., Ibáñez, R., García-Closas, R., Pera, G., Amiano, P., & González, C.A. (2004).
Development of a food database of nitrosamines, heterocyclic amines, and polycyclic aromatic
hydrocarbons. Journal of Nutrition, 134, 2011–2014.
Jang, J., H. G. Hur, M. J. Sadowsky, M. N. Byappanahalli, T. Yan, & S. Ishii. (2017). Environmental
Escherichia coli: ecology and public health implications—a review. Journal of Applied
Microbiology, 123, 570–581.
Järup, L., & Åkesson, A. (2009). Current status of cadmium as an environmental health problem.
Toxicology and Applied Pharmacology, 238, 201–208.
Jia, R., Q. Ma, Y. Fan, C. Ji, J. Zhang, T. Liu, & L. Zhao. (2016). The toxic effects of combined
aflatoxins and zearalenone in naturally contaminated diets on laying performance, egg quality and
mycotoxins residues in eggs of layers and the protective effect of Bacillus subtilis biodegradation
product. Food and Chemical Toxicology, 90, 142–150.
Jiménez, A. O., R. G. Martínez, M. B. Quiles, J. A. N. Majid, & M. I. González. (2016). Celiac disease
and new diseases related to gluten. Nutricion Hospitalaria, 33(Suppl 4), 345.
Jordan, K., & McAuliffe, O. (2018). Listeria monocytogenes in foods. In Advances in Food and
Nutrition Research, 86, 181–213. Academic Press.

39
Karagas, M. R., Choi, A. L., Oken, E., Horvat, M., Schoeny, R., Kamai, E., Cowell, W., Grandjean,
P., & Korrick, S. (2012) Evidence on the human health effects of low-level methylmercury
exposure. Environmental Health Perspectives, 120, 799–806.
Kido, J., & T. Matsumoto. (2015). Attenuated allergenic activity of ovomucoid after
electrolysis. Allergy, Asthma & Immunology Research, 7, 599–604.
Kislov, V. V., Sadovnikov, A. I., & Mebel, A. M. (2013). Formation mechanism of polycyclic
aromatic hydrocarbons beyond the second aromatic ring. Journal of Physical Chemistry, 117,
4794–4816. http://dx.doi.org/10.1021/jp402481y.
Kitazawa, H., H. Aoki, F. Ueda, T. Morita, & M. Mochizuki. (2019). Effective countermeasures for
Salmonella contamination in actual oilmeal manufacturing plant in India. Journal of Applied
Microbiology. doi.org/10.1111/jam.14438.
Kobayashi, Y., H. Akiyama, J. Huge, H. Kubota, S. Chikazawa, T. Satoh, ... & M. Aihara. (2016).
Fish collagen is an important panallergen in the Japanese population. Allergy, 71, 720–723.
Kobylewski, S., & M. F. Jacobson. (2012). Toxicology of food dyes. International Journal of
Occupational and Environmental Health, 18, 220–246.
Kolkhir, P., G. Balakirski, H. F. Merk, O. Olisova, & M. Maurer. (2016). Chronic spontaneous
urticaria and internal parasites–a systematic review. Allergy, 71, 308–322.
Koppelman, S. J., S. Jayasena, D. Luykx, E. Schepens, D. Apostolovic, G. A. De Jong, ... & H. Cheng.
(2016). Allergenicity attributes of different peanut market types. Food and Chemical
Toxicology, 91, 82–90.
Kranz, J., Hessel, S., Aretz, J., Seidel, A., Petzinger, E., Geyer, J., & Lampen, A. (2014). The role of
the efflux carriers Abcg2 and Abcc2 for the hepatobiliary elimination of benzo[a]pyrene and its
metabolites in mice. Chemico- Biological Interactions, 224, 36–41.
Kuchta, R., M. E. Serrano-Martínez, & T. Scholz. (2015). Pacific broad tapeworm Adenocephalus
pacificus as a causative agent of globally reemerging diphyllobothriosis. Emerging Infectious
Diseases, 21, 1697-1703. doi: 10.3201/eid2110.150516.
Kuehn, A., T. Scheuermann, C. Hilger, & F. Hentges. (2010). Important variations in parvalbumin
content in common fish species: a factor possibly contributing to variable
allergenicity. International Archives of Allergy and Immunology, 153, 359–366.
Kuroyama, M., Kagawa, H., Kitada, S., Maekura, R., Mori, M., & Hirano, H. (2015). Exogenous
lipoid pneumonia caused by repeated sesame oil pulling: a report of two cases. BMC Pulmonary
Medicine, 15, 135-140. DOI 10.1186/s12890-015-0134-8
Kwan, H. S., P. K., Chan, & M. C. Chan. (2017). Overview of norovirus as a foodborne pathogen.
In The Norovirus, 21–30. Academic Press.

40
Laganà, P., E. Avventuroso, G. Romano, M. E. Gioffré, P. Patanè, S. Parisi, ... & S. Delia. (2017).
Use and Overuse of Food Additives in Edible Products: Health Consequences for Consumers.
In Chemistry and Hygiene of Food Additives, 39–46. Springer, Cham.
Laudisi, F., C. Stolfi, & G. Monteleone. (2019). Impact of food additives on gut
homeostasis. Nutrients, 11, 2334.
Lebda, M. A., H. G. Tohamy, & Y. S. El-Sayed. (2017). Long-term soft drink and aspartame intake
induces hepatic damage via dysregulation of adipocytokines and alteration of the lipid profile and
antioxidant status. Nutrition Research, 41, 47–55.
Lebwohl, B., D. S. Sanders, & P. H. Green. (2018). Coeliac disease. The Lancet, 391(10115), 70–81.
Lima, A. D., R. C. Fortes, M. G. Novaes, & S. Percário. (2012). Poisonous mushrooms; a review of
the most common intoxications. Nutricion Hospitalaria, 27, 402–408.
Lindsay, R. C. (2017). Food additives. In Fennema's Food Chemistry, 803–864. CRC Press.
Linke, B. G., T. A. Casagrande, & L. I. A. Cardoso. (2018). Food additives and their health effects:
A review on preservative sodium benzoate. African Journal of Biotechnology, 17, 306–310.
Lu, L., R. Jia, H. Zhong, M. Xu, L. Su, L. Cao, ... & J. Xu. (2015). Molecular characterization and
multiple infections of rotavirus, norovirus, sapovirus, astrovirus and adenovirus in outpatients with
sporadic gastroenteritis in Shanghai, China, 2010–2011. Archives of Virology, 160, 1229–1238.
Luo, Y., X. Liu, & J. Li. (2018). Updating techniques on controlling mycotoxins-A review. Food
Control, 89, 123–132.
Lv, C., Jin, J., Wang, P., Dai, X., Liu, Y., Zheng, M., & Xing, F. (2019). Interaction of water activity
and temperature on the growth, gene expression and aflatoxin production by Aspergillus flavus on
paddy and polished rice. Food Chemistry, 293, 472–478.
Magnuson, B. A., A. Roberts, & E. R. Nestmann. (2017). Critical review of the current literature on
the safety of sucralose. Food and Chemical Toxicology, 106, 324–355.
Marinov, P., G. Bonchev, D. Ivanov, S. Zlateva, T. Dimitrova, & K. Georgiev. (2018). Mushrooms
intoxications. Journal of IMAB–Annual Proceeding Scientific Papers, 24, 1887–1890.
Marion-Letellier, R., A. Amamou, G. Savoye, & S. Ghosh. (2019). Inflammatory bowel diseases and
food additives: To add fuel on the flames! Nutrients 11, 1111-1123. doi:10.3390/nu11051111
Martins, F. C., M. A. Sentanin, and D. De Souza. (2019). Analytical methods in food additives
determination: Compounds with functional applications. Food Chemistry, 272, 732–750.
Mazzobre, M. F., Schebor, C., Burin, L., & Chirife, J., (2000). Survey of pH and water activity in
acidified bottled vegetables and meats (home processed) in relation to the potential growth of
Clostridium botulinum. Revista Argentina de Microbiologia, 32, 63–70.

41
Mearns, E. S., A. Taylor, T. Craig, J. Kelly, S. Puglielli, A. B. Cichewicz, ... & M. Hadjivassiliou.
(2019). Neurological manifestations of neuropathy and ataxia in celiac disease: a systematic
review. Nutrients, 11, 380-394.
McBride, M. B. (2003). Toxic metals in sewage sludge-amended soils: has promotion of beneficial
use discounted the risks? Advances in Environmental Research, 8, 5–19.
McCormick, S.P., Stanley, A.M., Stover, N.A. & Alexander, N.J. (2011). Trichothecenes: From
simple to complex mycotoxins. Toxins, 3, 802–814; doi:10.3390/toxins3070802.
Mehri, A., & Marjan, R. F. (2013). Trace elements in human nutrition: a review. International Journal
of Medical Investigation, 2, 115–128.
Meseguer, J., V. Navarro, I. Sánchez-Guerrero, B. Bartolomé, & J. N. Alvarez. (2007). Anisakis
simplex allergy and nephrotic syndrome. Allergologia et Immunopathologia, 35, 216–220.
Moezi, P., M. Kargar, A. Doosti, & M. Khoshneviszadeh. (2019). Multiplex Touchdown PCR assay
to enhance specificity and sensitivity for concurrent detection of four foodborne pathogens in raw
milk. Journal of Applied Microbiology, 127, 262–273.
Montgomery, R. K., H. A. Büller, E. Η. Rings, J. Dekker, & R. J. Grand. (2018). Lactose intolerance
and regulation of small intestinal lactase activity. In Nutrition and Gene Expression 23–53. CRC
Press.
Murray, T. Y., & M. B. Taylor. (2015). Quantification and molecular characterisation of human
sapoviruses in water sources impacted by highly polluted discharged wastewater in South
Africa. Journal of Water and Health, 13, 1055–1059.
Nakamura, A. A., & M. V. Meireles. (2015). Cryptosporidium infections in birds-a review. Revista
Brasileira de Parasitologia Veterinária, 24, 253–267.
Nerín, C., M. Aznar, & D. Carrizo. (2016). Food contamination during food process. Trends in Food
Science & Technology, 48, 63–68.
Palmer, D. J., T. R. Sullivan, M. S. Gold, S. L. Prescott, & M. Makrides. (2017). Association between
family characteristics and the effect of timing of regular egg introduction in infant egg
allergy. JAMA Pediatrics, 171, 489–490.
Paul, S. P., L. McVeigh, E. Gil-Zaragozano, & D. Basude. (2016). Diagnosis and nursing
management of coeliac disease in children. Nursing Children and Young People, 28, 18–24.
Peck, M. W., S. C. Stringer, & A. T. Carter. (2011). Clostridium botulinum in the post-genomic
era. Food Microbiology, 28, 183–191.
Pfab, R., Haberl, B., Kleber, J., & Zilker, T. (2008). Cerebellar effects after consumption of edible
morels (Morchella conica, Morchella esculenta). Clinical Toxicology 46, 259–260.

42
Pravettoni, V., L. Primavesi, & M. Piantanida. (2012). Anisakis simplex: current
knowledge. European Annals of Allergy and Clinical Immunology, 44, 150–156.
Prester, L. (2016). Seafood allergy, toxicity, and intolerance: a review. Journal of the American
College of Nutrition, 35, 271–283.
Proroga, Y. T. R., Mancusi, A., Peruzy, M. F., Carullo, M. R., Montone, A. M. I., Fulgione, A. &
Capuano, F. (2019). Characterization of Salmonella Typhimurium and its monophasic variant 1,
4,[5], 12: i:-isolated from different sources. Folia Microbiologica, 64, 711–718.
Rahimi, E., & M. Rezapoor Jeiran. (2015). Patulin and its dietary intake by fruit juice consumption
in Iran. Food Additives & Contaminants: Part B, 8, 40–43.
Rai, U. N., Tripathi, R. D., Vajpayee, P., Pandey, N., Ali, M.B., & Gupta, D.K. (2003). Cadmium
accumulation and its phytotoxicity in Potamogeton pectinatus L. (Potamogetonaceae). Bullettin
of Environmental Contamination and Toxicology, 70, 566–575.
Rajan, K., Z. Shi, Z., & S. C. Ricke. (2017). Current aspects of Salmonella contamination in the US
poultry production chain and the potential application of risk strategies in understanding emerging
hazards. Critical Reviews in Microbiology, 43, 370–392.
Ramesh, M., & A. Muthuraman. (2018). Flavoring and coloring agents: Health risks and potential
problems. In Natural and Artificial Flavoring Agents and Food Dyes, 1–28. Academic Press.
Randazzo, W., D. H. D’Souza, & G. Sanchez. (2018). Norovirus: The burden of the unknown.
In Advances in Food and Nutrition Research, 86, 13–53. Academic Press.
Reza, M. S. A., M. M. Hasan, M. Kamruzzaman, M. I. Hossain, M. A. Zubair, L. Bari, ... & K. Islam.
(2019). Study of a common azo food dye in mice model: Toxicity reports and its relation to
carcinogenicity. Food Science & Nutrition, 7, 667–677.
Rezny, B. R., & Evans, D. S. (2018). Vibrio Parahaemolyticus. StatPearls Publishing, Treasure Island
(FL).
Rice, J.M. (2005). The carcinogenicity of acrylamide. Mutat. Res., 580, 3–20.
Rivas, A., Cerrillo, I., Granada, A., Mariscal-Arcas, M., & Olea Serrano, F. (2007). Pesticide
exposure of two age groups of women and its relationship with their diet. Science of the Total
Environment, 382,14–21.
Roca-Saavedra, P., Mendez-Vilabrille, V., Miranda, J. M., Nebot, C., Cardelle-Cobas, A., Franco, C.
M., & Cepeda, A. (2018). Food additives, contaminants and other minor components: Effects on
human gut microbiota – a review. Journal of Physiology and Biochemistry, 74, 69–83.
Rusiecki, J. A., Hou, L., Lee, W. J., Blair, A., Dosemeci M, Lubin JH, Bonner, M., Samanic, C.,
Hoppin, J. A., Sandler, D. P., & Alavanjaet M.C.R. (2006). Cancer incidence among pesticide

43
 applicators exposed to metolachlor in the Agricultural Health Study. International Journal of
Cancer, 118, 3118–23.
Saraka, D., C. Savin, S. Kouassi, B. Cissé, E. Koffi, N. Cabanel,... & E. Carniel, (2017). Yersinia
enterocolitica, a neglected cause of human enteric infections in Cote d’Ivoire. PLoS Neglected
Tropical Diseases, 11, e0005216.
Saviuc, P., P. Harry, C. Pulce, R. Garnier, & A. Cochet. (2010). Can morels (Morchella sp.) induce
a toxic neurological syndrome? Clinical Toxicology, 48, 365–372.
Schiffman, S. S., & K. I. Rother. (2013). Sucralose, a synthetic organochlorine sweetener: overview
of biological issues. Journal of Toxicology and Environmental Health Part B, 16, 399–451.
Schlegel, G., R. Scholz, K. Ullrich, R. Santer, & G. M. Rune. (2016). Phenylketonuria: direct and
indirect effects of phenylalanine. Experimental Neurology, 281, 28–36.
Schreiber, H. L., M. S. Conover, W. C. Chou, M. E. Hibbing, A. L. Manson, K. W. Dodson,... & J.
Livny. (2017). Bacterial virulence phenotypes of Escherichia coli and host susceptibility
determine risk for urinary tract infections. Science Translational Medicine, 9, [eaaf1283].
https://doi.org/10.1126/scitranslmed.aaf1283.
Schwager, C., S. Kull, S. Krause, F. Schocker, A. Petersen, W. M. Becker, & U. Jappe. (2015).
Development of a novel strategy to isolate lipophilic allergens (oleosins) from peanuts. PloS One,
10, e0123419.
Scientific Committee on Food, 2002. Opinion of the Scientific Committee on Food on new findings
regarding the presence of acrylamide in food, expressed on 3 July 2002.
Shafaghi, A., K. A. Rezayat, F. Mansour-Ghanaei, & A. A. Maafi. (2015). Taenia: an uninvited
guest. The American Journal of Case Reports, 16, 501.
Sharma, A. (2015). Monosodium glutamate-induced oxidative kidney damage and possible
mechanisms: a mini-review. Journal of Biomedical Science, 22, 93-99.
https://doi.org/10.1186/s12929-015-0192-5.
Skypala, I. J., M. Williams, L. Reeves, R. Meyer, & C. Venter. (2015). Sensitivity to food additives,
vaso-active amines and salicylates: a review of the evidence. Clinical and Translational Allergy, 5,
34–38.
Smaldini, P., R. Curciarello, A. Candreva, M. A. Rey, C. A. Fossati, S. Petruccelli, & G. H. Docena.
(2012). In vivo evidence of cross-reactivity between cow’s milk and soybean proteins in a mouse
model of food allergy. International Archives of Allergy and Immunology, 158, 335–346.
Snini, S. P., J. Tannous, P. Heuillard, S. Bailly, Y. Lippi, E. Zehraoui, ... & O. Puel. (2016). Patulin
is a cultivar-dependent aggressiveness factor favouring the colonization of apples by Penicillium
expansum. Molecular Plant Pathology, 17, 920–930.

44
Sohail, M., D. W. Sun, & Z. Zhu. (2018). Recent developments in intelligent packaging for enhancing
food quality and safety. Critical Reviews in Food Science and Nutrition, 58, 2650–2662.
Stein, A. J. (2010). Global impacts of human mineral malnutrition. Plant Soil, 335, 133–154.
Tack, D. M., E. P. Marder, P. M. Griffin, P. R. Cieslak, J. Dunn, S. Hurd, ... & K. Smith. (2019).
Preliminary incidence and trends of infections with pathogens transmitted commonly through
food—Foodborne Diseases Active Surveillance Network, 10 US sites, (2015)–(2018). Morbidity
and Mortality Weekly Report, 68, 369-373.
Taylor, R. H., M. L. Dunn, L. V. Ogden, L. K. Jefferies, D. L. Eggett, & F. M. Steele. (2013).
Conditions associated with Clostridium sporogenes growth as a surrogate for Clostridium
botulinum in nonthermally processed canned butter. Journal of Dairy Science, 96, 2754–2764.
Thongprachum, A., S. Takanashi, A. F. Kalesaran, S. Okitsu, M. Mizuguchi, S. Hayakawa, & H.
Ushijima. (2015). Four-year study of viruses that cause diarrhea in Japanese pediatric
outpatients. Journal of Medical Virology, 87, 1141–1148.
Tortorella, V., P. Masciari, M. Pezzi, A. Mola, S. P. Tiburzi, M.C. Zinzi, ... & M. Verre. (2014).
Histamine poisoning from ingestion of fish or scombroid syndrome. Case Reports in Emergency
Medicine, 2014, Article ID 482531.
Toth, G., Hermann, T., Da Silva, M. R., & Montanarella, L. (2016). Heavy metals in agri-cultural
soils of the European Union with implications for food safety. Environment International, 88, 299-
309.
Treudler, R., & J. C. Simon. (2017). Pollen-related food allergy: an update. Allergo Journal
International, 26, 273–282.
Trevisan, C., E. M. Mkupasi, H. A. Ngowi, B. Forkman, and M. V. Johansen. (2016). Severe seizures
in pigs naturally infected with Taenia solium in Tanzania. Veterinary Parasitology 220, 67–71.
Tzifi, F., V. Grammeniatis, and M. Papadopoulos. (2014). Soy-and rice-based formula and infant
allergic to cow's milk. Endocrine, Metabolic & Immune Disorders-Drug Targets (Formerly
Current Drug Targets-Immune, Endocrine & Metabolic Disorders) 14, 38–46.
Ueda, N. (2016). Gastroduodenal perforation and ulcer associated with rotavirus and norovirus
infections in japanese children: a case report and comprehensive literature review. In Open forum
infectious diseases 3(1). Oxford University Press.
Urisu, A., Y. Kondo, and I. Tsuge. (2015). Hen's egg allergy. In Food Allergy: Molecular Basis and
Clinical Practice 101, 124–130. Karger Publishers.
van Boxtel, E. L., L. A. van den Broek, S. J. Koppelman, and H. Gruppen. (2008). Legumin allergens
from peanuts and soybeans: effects of denaturation and aggregation on allergenicity. Molecular
Nutrition & Food Research 52, 674–682.

45
Vardy, E. R., A. MacDonald, S. Ford, and D. L. Hofman. (2020). Phenylketonuria, Co-morbidity and
Ageing: a review. Journal of Inherited Metabolic Disease 2020 43, 167-178. doi:
10.1002/jimd.12186.
Vázquez-Sánchez, D., J. A. Galvão, and M. Oetterer. (2018). Contamination sources, biofilm-
forming ability and biocide resistance of Staphylococcus aureus in tilapia-processing
facilities. Food Science and Technology International 24, 209–222.
Velázquez-Ordoñez, V., B. Valladares-Carranza, E. Tenorio-Borroto, M. Talavera-Rojas, J. A.
Varela-Guerrero, J. Acosta-Dibarrat, and L. Pareja. (2019). Microbial contamination in milk
quality and health risk of the consumers of raw milk and dairy products. In Nutrition in Health
and Disease-Our Challenges Now and Forthcoming Time. IntechOpen.
Velázquez-Sámano, G., R. Collado-Chagoya, R. Alejandro Cruz-Pantoja, A. Aída Velasco-Medina,
and J. Rosales-Guevara. (2019). Hypersensitivity reactions to food additives. Revista Alergia de
Mexico 66, 329–339.
Verma, N., A. Bhalla, S. Kumar, R. K. Dhiman, and Y. K. Chawla. (2014). Wild mushroom poisoning
in north India: case series with review of literature. Journal of Clinical and Experimental
Hepatology 4, 361–365.
Wenzel, W. W., Kirchbaumer, N., Prohaska, T., Stingeder, G., Lombi, E., Adriano, D.C., (2001).
Arsenic fractionation in soils using an improved sequential extraction procedure. Analitica
Chimica Acta 436, 309-323.
White P. J., Brown, P. H. (2010). Plant nutrition for sustainable development and global health.
Annals of Botany 105, 1073–1080.
Wang, J., and H. A. Sampson. (2011). Food allergy. The Journal of Clinical Investigation 121, 827–
835.
Wang, R. J., J. Q. Li, Y. C. Chen, L. X. Zhang, and L. H. Xiao. (2018). Widespread occurrence of
Cryptosporidium infections in patients with HIV/AIDS: Epidemiology, clinical feature, diagnosis,
and therapy. Acta Tropica 187, 257–263.
Wang, Y., J. Zhang, and Z. Shen. (2015). The impact of calicivirus mixed infection in an oyster-
associated outbreak during a food festival. Journal of Clinical Virology 73, 55–63.
Ward, J., K. Kapadia, E. Brush, and S. D. Salhanick. (2013). Amatoxin poisoning: case reports and
review of current therapies. The Journal of Emergency Medicine 44, 116–121.
Weston, N., and E. Moran. (2015). Salmonella newport causing osteomyelitis in a patient with
diabetes. BMJ Case Reports, doi:10.1136/bcr-2015-212330.
White, J., S. A. Weinstein, L. De Haro, R. Bédry, A. Schaper, B. H. Rumack, and T. Zilker. (2019).
Mushroom poisoning: a proposed new clinical classification. Toxicon 157, 53–65.

46
Wong, D. W. (2018). Additives. In Mechanism and Theory in Food Chemistry, Second Edition 361–
380. Springer, Cham.
Wong, D. W. (2018). Sweeteners. In Mechanism and Theory in Food Chemistry, Second Edition 309–
325. Springer, Cham.
Xie, Y., and X. Liu. (2015). The advances in the contamination and detection of foodborne pathogen
noroviruses in fresh produce. Bing du xue bao= Chinese Journal of Virology 31, 685–697.
Zarcinas, B. A., Pongsakul, P., McLaughlin, M. J., Cozens, G. (2004). Heavy metals in soils and
crops in Southeast Asia 2. Thailand. Environmental Geochemistry and Health 26, 359–371.
Zhang, J. B., H. Zhang, H. L. Wang, J. Y. Zhang, P. J. Luo, Z. H. U. Lei, and Z. T. Wang. (2014).
Risk analysis of sulfites used as food additives in China. Biomedical and Environmental
Sciences 27, 147–154.
Zhang, Z., H. Xiao, X. Zhang, and P. Zhou. (2019). Insight into the effects of deglycosylation and
glycation of shrimp tropomyosin on the in vivo allergenicity and mast cell function. Food &
Function 10, 3934–3941.
Zińczuk, J., P. Wojskowicz, J. Kiśluk, D. Fil, A. Kemona, and J. Dadan. (2015). Mesenteric
lymphadenitis caused by Yersinia enterocolitica. PRZ Gastroenterol. 10, 118–121.

Table and Figure captions

47
Table 1. Classification of additives and their function in food preparations.

Table 2. Pathogenic microorganisms and the main foods that can become contaminated.

Figure 1. Risk factors for food diseases.

Figure 2. Main strategies for food safety.

Table 1

48
 ADDITIVES
Sweeteners: used to give a sweet taste to foods
Dyes: impart colour to a food or return it to the original colour
Preservatives: prolong food preservation
Antioxidants: prolong food preservation against oxidation
Supports: used to dissolve, dilute or disperse additives, flavours or nutrients
Acidifiers: increase the acidity of a product
Acidity regulators: control the acidity of a product
Anti-caking agents: reduce the attachment of a product's particles
Emulsifiers: make it possible to mix two foods that are immiscible (oil + water)
Melting salts: used to disperse proteins in cheeses and obtain a more even distribution of fat
Agents of resistance, foaming, gelling, coating, humidifying, leavening, sequestering, flour
treatment, anti-foaming, and fillers
Flavour enhancers: enhance the aromaticity of the product
Packaging gases: gases, other than air, introduced before packaging a product
Propellants: gases that expel the food product from a container
Stabilizers: maintain the chemical-physical state of the product
Thickeners: increase product viscosity

Table 2
49
 Pathogenic microorganisms Main foods at risk of contamination
Aeromonas spp Raw vegetables, prepared salads, sliced meat, bivalve
molluscs
Bacillus cereus Rice, pasta, flour, vegetables, dairy products
Campylobacter Jejunii Poultry and other types of meat
Clostridium perfrigens Rolled meat or stewed, boiled, or roasted beef
E. coli verocytotoxigenic (VTEC) raw meats, foods contaminated with animal faeces, water
Escherichia coli (enterotoxigenic and Different food, water
enteropathogenic - ETEC, EPEC)
Listeria monocytogenes Unpasteurized dairy products, pate, salad
Salmonellae Poultry and meat from other farm animals, cakes and ice
cream made with eggs
Staphylococcus aureus Meat products, creams, milk, fish
Clostridium botulinum Meat, canned fish, salami, vegetables in oil
Vibrio cholerae Water, vegetables, fish products
Vibrio parahaemolyticus Raw fish, crustaceans, seafood
Norovirus, rotavirus (SVRS) Water, shellfish
Yersinia enterocolitica Pork meat, offal, vegetables

Figure 1
50
Figure 2
51
52
Highlights
Food can be a vehicle for pathogens and therefore potential sources of disease.
Microorganisms such as bacteria, viruses and parasites can be responsible for foodborne diseases.
Mycotoxins can be present in commonly used foods and pose a serious health threat.
The increase in food allergies seems related to a greater intake of non-natural substances.
Some foodborne diseases can result from dietary manipulations.

53
54
Conflict of interest form

Monica Gallo has no conflict of interest

Lydia Ferrara has no conflict of interest
Armando Calogero has no conflict of interest
Domenico Montesano has no conflict of interest
Daniele Naviglio has no conflict of interest

55