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Food Additives & Contaminants: Part A
ISSN: (Print) (Online) Journal homepage: www.tandfonline.com/journals/tfac20
Food process contaminants: formation,
occurrence, risk assessment and mitigation
strategies – a review
Ahmadullah Zahir, Iftikhar Ali Khan, Maazullah Nasim, Mohammad Naeem
Azizi & Fidelis Azi
To cite this article: Ahmadullah Zahir, Iftikhar Ali Khan, Maazullah Nasim, Mohammad Naeem
Azizi & Fidelis Azi (22 Jul 2024): Food process contaminants: formation, occurrence, risk
assessment and mitigation strategies – a review, Food Additives & Contaminants: Part A, DOI:
10.1080/19440049.2024.2381210
To link to this article: https://doi.org/10.1080/19440049.2024.2381210
Published online: 22 Jul 2024.
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FOOD ADDITIVES & CONTAMINANTS: PART A
Food process contaminants: formation, occurrence, risk assessment and
mitigation strategies – a review
Ahmadullah Zahira, Iftikhar Ali Khanb, Maazullah Nasimc, Mohammad Naeem Azizid and Fidelis Azie
aFaculty of Veterinary Sciences, Department of Food Science and Technology, Afghanistan National Agricultural Sciences & Technology
University, Kandahar, Afghanistan; bShenzhen Key Laboratory of Marine Microbiome Engineering, Institute for Advanced Study, Shenzhen
University, Shenzhen, China; cFaculty of Agriculture, Department of Horticulture, Kabul University, Kabul, Afghanistan; dFaculty of
Veterinary Sciences, Department of Pre-Clinic, Afghanistan National Agricultural Sciences & Technology University, Kandahar, Afghanistan;
eDepartment of Chemical Engineering, Guangdong Technion-Israel Institute of Technology (GTIIT), Shantou, Guangdong, China
ABSTRACT
Thermal treatment of food can lead to the formation of potentially harmful chemicals, known
as process contaminants. These are adventitious contaminants that are formed in food during
processing and preparation. Various food processing techniques, such as heating, drying,
grilling, and fermentation, can generate hazardous chemicals such as acrylamide (AA),
advanced glycation end products (AGEs), heterocyclic aromatic amines (HAAs), furan, polycyclic
aromatic hydrocarbons (PAHs), N-nitroso compounds (NOCs), monochloropropane diols
(MCPD) and their esters (MCPDE) which can be detrimental to human health. Despite efforts
to prevent the formation of these compounds during processing, eliminating them is often
challenging due to their unknown formation mechanisms. It is critical to identify the potential
harm to human health in processed food and understand the mechanisms by which harmful
compounds form during processing, as prolonged exposure to these toxic compounds can
lead to health problems. Various mitigation strategies, such as the use of diverse pre- and
post-processing treatments, product reformulation, additives, variable process conditions, and
novel integrated processing techniques, have been proposed to control these food hazards.
In this review, we summarize the formation and occurrence, the potential for harm to human
health produced by process contaminants in food, and potential mitigation strategies to
minimize their impact.
Introduction
Food safety is a major concern for health agencies
and consumers globally. During food processing,
ingredients such as proteins, carbohydrates, fats,
and oils can undergo various alterations, including
hydrolysis and oxidation, which can result in the
formation of harmful substances such as acrylamide
(AA), heterocyclic aromatic amines (HAAs), furan,
polycyclic aromatic hydrocarbons (PAHs), and
advanced glycation end products (AGEs) (Khan
et al. 2022). These hazardous substances known as
process contaminants can also be formed due to
the activity of microorganisms, enzyme reactions,
and inappropriate food processing methods (Wang
et al. 2021). Thermal processing of foods results in
chemical reactions that can lead to novel
contaminants that do not occur naturally in foods.
These compounds may be carcinogenic, mutagenic,
or cytotoxic. For example, high-temperature pro-
cessing of meat and plant-based products can lead
to the production of carcinogenic compounds such
as AGEs, AA, HAAs, PAHs, and furan (Flores etal.
2019; Khan et al. 2022). AA is formed via the
Maillard reaction when the heating temperature
reaches above 120°C from the reaction of reducing
sugars with free asparagine. AA can exhibit geno-
toxicity, neurotoxicity, and reproductive toxicity.
The accumulation of AGEs in vivo resulting in the
activation of various signaling pathways is closely
linked to the occurrence of different metabolic
chronic diseases (Song etal. 2021). HAAs are com-
prised of a large group of chemical compounds
© 2024 Taylor & Francis Group, LLC
CONTACT Iftikhar Ali Khan ifti_vet@szu.edu.cn Shenzhen Key Laboratory of Marine Microbiome Engineering, Institute for Advanced Study,
Shenzhen University, Shenzhen, China.
This article has been corrected with minor changes. These changes do not impact the academic content of the article.
https://doi.org/10.1080/19440049.2024.2381210
ARTICLE HISTORY
Received 24 March 2024
Revised 10 July 2024
Accepted 14 July 2024
KEYWORDS
Hazardous compounds;
toxicity; novel methods; public
health; inhibition strategies
2 A. ZAHIR ETAL.
(over 30 HAAs), almost all of which show muta-
genic and carcinogenic properties. They are formed
due to the high degree of heat processing that can
occur in a wide variety of cooked protein-rich food
items (Koszucka and Nowak 2019). Furan is a lipo-
philic oxygen heterocyclic compound with high
volatility. It is formed through various pathways
including the thermal oxidation of lipids and the
breakdown of ascorbic acid, carbohydrates, and its
derivatives. This contaminant has been found to
occur in an extensive range of food products
(González et al. 2022).
More than 100 PAHs have been identified,
several of which are mutagenic, cytotoxic, and
carcinogenic. They are ubiquitous compounds
that are formed from the incomplete pyrolysis of
organic matter or under high temperatures in
various food items. Food contamination by
PAHs may occur through various pathways such
as from environmental pollution as well as
directly from food processing techniques (Kim
et al. 2021).
Raw foods must contain the necessary precur-
sors that on heat treatment can lead to process
contaminants. Therefore, it is important to under-
stand their formation mechanisms during food
processing, especially during thermal processing,
traditional fermentation, and storage (Nilsen etal.
2019). This is essential because even though some
of these substances can be controlled during pro-
cessing, others have unknown formation mecha-
nisms making it difficult to prevent their
formation (Papageorgiou et al. 2018; Lebelo
et al. 2021).
The expansion of food production, transporta-
tion, and distribution has heightened the need to
unify food safety and quality regulations to
uphold fair trade and safeguard consumer
well-being (Tabanelli 2020). From a food safety
point of view, the occurrence of thermal process
contaminants in foods is still one of the foremost
concerns for consumers, health authorities, and
industry (Table 1). Therefore, in this review, we
explain the production of hazardous substances
during food processing, their formation, occur-
rence, and strategies to reduce and/or pre-
vent them.
Food process contaminants
Acrylamide
Thermal treatment of food can lead to the for-
mation of acrylamide (AA), which has gained
significant scientific attention in recent years. AA
(C3H5NO; prop-2-enamide) is a polar, colorless,
and odorless compound with a low molecular
weight and high solubility in water, ethanol, ace-
tone, and methanol. AA is insoluble in non-polar
solvents such as carbon tetrachloride, and at
standard temperature and pressure, it exists in a
solid form. It is highly reactive in air and rapidly
polymerizes.
In 2002, the Swedish National Food
Administration (NFA) and Stockholm University
reported that prolonged thermal processing of
certain foods, particularly bakery products, grain
products, and potatoes (i.e. starch-rich foods),
Table 1. Showed the food process contaminants formed during the heating processing of food.
Food process contaminants
Derivatives
Full name Chemical formula Abbreviation
AA Acrylamide C3H5NOAA
AGEs Advanced glycation end products AGEs
Furan Furan C4H4OFu
PAHs Acenaphthene C12H10 ACE
Acenaphthylene C12H8Acy
Anthracene C14H10 An
Naphthalene C10H10 Naph
Phenanthrene C14H10 Phe
Benzo(a)pyrene C20H12 BaP
HAAs 2-amino-1-methyl-6-phenylimidazo[4,5 b]pyridine C13H12N4PhIP
2-amino-3-dimethylimidazo[4,5-f] quinoxaline C11H11N5MeIQx
2-amino-1-methylimidazo[4,5-b] quinoline C11H10N4IQ
2-amino-1,6- dimethylfuro[3,2-e] imidazole [4,5 b] pyridine C10H10N4O IFP
2-amino-3-methyl-3H-imidazo [4,5-f] quinoxaline C10H9N5IQ
2-amino-3-trimethylimidazo[4,5-f] quinoxaline C12H10N5DiMeIQx
1-methyl-9Hpyrido[3,4-b] indole C12H10N2Harman
9H-pyrido[3,4-b] indole C11H8N2Norharman
FOOD ADDITIVES & CONTAMINANTS: PART A 3
results in the formation of high levels of AA
(ranging from 30 µg/kg to 2300 µg/kg). The for-
mation of AA is dependent on the presence of
reducing sugars and asparagine, which are limit-
ing factors in potatoes and cereal products,
respectively. In the same year, AA was included
in the list of toxic materials found in food
(Krishnakumar and Visvanathan 2014; Tamanna
and Mahmood 2015). The discovery of AA in
food led food chemists to investigate various fac-
tors involved in its formation during food pro-
cessing. Thermally, AA undergoes breakdown to
form CO, CO2, ammonia, and nitrogen oxides
(Maan et al. 2022). The significant challenge
posed by AA is the minimization of its toxic
effects in both home-cooking and industrial food
processing. Fortunately, technological advance-
ments have enabled the effective reduction of AA
levels (Borda and Alexe 2011).
Advanced glycation end products (AGEs)
At the beginning of the twentieth century, a
group of heterogeneous macromolecules that
formed through the interaction of reducing sug-
ars with biomolecules such as protein, lipids, and
DNA collectively called advanced glycation end
products (AGEs) were discovered. These com-
pounds are produced through the classical
Maillard reaction and have certain common char-
acteristics such as fluorescence, covalent cross-link
formation (among proteins), and the effect of
changing the color of foodstuffs into yellow-brown
colors (Chaudhuri et al. 2018). They are formed
as a result of the rapid binding of reducing sugar
with the amino group of amino acids through a
sequence of non-enzymatic reactions. Under the
conformational changes, these products stabilized
into the final heterogeneous products, abbreviated
as AGEs. Based on the origins, two types of
AGEs have been reported: exogenous and endog-
enous, and over 40 AGEs have been identified
and characterized. According to the chemical
characteristics of AGEs, they are classified into 3
groups (I) non-crosslinked non-fluorescent prod-
ucts; (II) crosslinked non-fluorescent products;
and (III) crosslinked fluorescent products (Table 2).
Exogenous AGEs include processed or cooked
foods, beverages, and other food products (also
Table 2. Classication of AGEs.
Non-crosslinked nonuorescent products
N-ε-carboxymethyl lysine (CML)
N-ε-carboxyethyl
lysine (CEL) Pyrraline
N-(1-deoxy-D-fructose-1-yl)-
lysine
Hydroimidazolones
derived from glyoxal
(G-H1)
Hydroimidazolones derived
from glyoxal (G-H2)
Hydroimidazolones derived from
glyoxal (G-H3)
Hydroimidazolones derived from
methylglyoxal (MG-H1)
Hydroimidazolones
derived from
methylglyoxal
(MG-H2)
Hydroimidazolones
derived from
methylglyoxal
(MG-H3)
Imidazolone A Imidazolone B
Crosslinked non-uorescent products
Methylglyoxal-lysine dimer (MOLD) Glyoxal-lysine dimer
(GOLD)
Alkyl formyl glycosyl
pyrrole
Arginine-lysine imidazole Imidazolium cross link
derived from
glyoxal and
lysine-arginine
(GODIC)
3-deoxyglucosoneimidazolone
(DOLD)
Imidazolium cross link derived from
3-deoxyglucosoneimidazolone
and lysine-arginine (GODIC)
Glucosepane
Crosslinked uorescent products
Pentosidine Argpyrimidine Vesper lysine A Vesper lysine B Vesper lysine C FFI Pyrropyridine
Fluorolink Crossline
4 A. ZAHIR ETAL.
known as dietary AGEs (dAGEs)) (Gill et al.
2019). Endogenous AGEs (also called biological
AGEs) are produced in the body as part of nor-
mal metabolism (Sergi etal. 2021). The biological
AGEs contribute to the pathogenesis of several
chronic diseases, particularly type-2 diabetes, car-
diovascular dysfunctions, and chronic kidney dis-
eases (Zhang et al. 2020). During processing
(mostly during heat treatment) and compared to
physiological conditions, the chemical structures
of AGEs and other Maillard reaction products
formed in food items are more complex and
more heterogeneous. Because of this chemical
diversity and other matters, estimating the contri-
bution of dietary AGEs has been difficult
(Guilbaud etal. 2016). In contrast to endogenous
AGEs, dAGEs are formed to a much higher
extent (Nowotny et al. 2018).
Furan and derivatives
Furan is a highly volatile, carcinogenic heterocy-
clic ether with low molecular weight, low boiling
point, and poor water solubility (Santonicola and
Mercogliano 2016). Furan, and its naturally
occurring derivatives (2-methylfuran, 2-ethylfuran,
2-pentylfuran, 2,5-dimethylfuran, 2-butylfuran,
2,3-benzofuran), primarily occur in thermal pro-
cessed foods and drinks, contributing to their
sensory characteristics (Santonicola and
Mercogliano 2016). Furan has been reported
since the 1960s and has been studied by interna-
tional organizations like the US FDA (US Food
and Drug Administration) and EFSA. The first
outcome of furan occurrence was reported by the
FDA in 2004 from thermally processed baby
foods packaged in cans and jars. Furan can be
formed through various pathways, including ther-
mal degradation of amino acids, carbohydrates,
ascorbic acid, and oxidation of carotenoids and
PFAS. It has been classified by IARC as a group
2B, potentially carcinogenic to humans and ani-
mals, and has detrimental effects on public health
(Koszucka and Nowak 2019).
Heterocyclic aromatic amines
Heterocyclic aromatic amines (HAAs) are known
to be carcinogenic compounds that are primarily
formed from the pyrolysis of amino acids and
proteins, often in conjunction with creatinine or
creatine and hexoses, particularly at high tem-
peratures and under prolonged heating conditions
(Sheng et al. 2020; Zamora and Hidalgo 2020).
The discovery of these carcinogenic compounds
dates back to 1939 by Swedish researcher
Sugimura and colleagues when extracts of horse-
meat roasted at 275◦C were found to produce
cancer in mice. Later in 1977 similar compounds
were identified in cooked food and named het-
erocyclic amines (Shabbir etal. 2015).
Polycyclic aromatic hydrocarbons
Polycyclic aromatic hydrocarbons (PAHs) are a
group of persistent organic contaminants that
contain two or more fused benzene rings in their
chemical structure (Sun et al. 2019). They are
formed during heat treatment of foods, particu-
larly drying and smoking (by pyrolysis or
pyro-synthesis). Their presence is primarily in
smoked fish, sausage, and ham (Li et al. 2021;
Wang et al. 2021). There are hundreds of PAH
isomers and several aromatic rings including two
or more fused aromatic rings (Purcaro et al.
2013). PAHs containing more than six aromatic
rings are classified as ‘large’ or heavy PAHs, while
those with up to six fused aromatic rings are
referred to as ‘small’ or light PAHs. In the envi-
ronment, numerous PAHs and related compounds
have been detected, including PAHs with 24 or
fewer carbon atoms. PAHs are categorized as
petrogenic or pyrogenic PAHs, depending on
their origin. Petrogenic PAHs differ from PAHs
found in crude oil and contaminated water after
an oil spill, while pyrogenic PAHs are formed by
fossil fuel burning. They have a different struc-
ture that is either widely oxygenated or alkylated
to produce PAH quinones. They are complex
compounds comprising hundreds of chemicals,
including derivatives of PAHs. The two most
important anthropogenic sources are thought to
be petrogenic and pyrolytic. Following their char-
acterization, more than 100 PAHs were identified;
sixteen of them were classified as priority pollut-
ants by the US Environmental Protection Agency
(EPA) due to their toxicity (Tongo et al. 2017).
Due to their biological effects, certain PAHs such
FOOD ADDITIVES & CONTAMINANTS: PART A 5
as B [α] A, B [α] P, and DB [αh] P have been
selected as marker compounds for monitoring
the environment. Among these, B [α] P is con-
sidered a human carcinogen and is used as a
PAH exposure indicator (Diggs et al. 2011; Hu
et al. 2020). The variation in the properties of
PAHs can be attributed to differences in the con-
figuration of their constituent rings. At ambient
temperature, PAHs exist in a solid state with low
volatility, exhibiting hues ranging from colorless
to white or pale yellow-green. These compounds
display moderate water insolubility and can be
degraded and photo-oxidized into simpler sub-
stances (Huang and Penning 2014).
N-nitroso compounds
N-nitroso compounds (NOCs), which are a group of
naturally occurring compounds that are well-known
potential carcinogens produced by the reaction of
nitrosating agents, including nitrite and secondary
amines and amides. They are a major risk factor for
gastrointestinal (GI) cancer. Examples of NOCs are
nitrosamines and nitrosamides. Based on their chem-
ical structure, they are classified as N-nitrosamines
(NAs) and N-nitrosamides. They are carcinogenic
chemical substances that potentially could lead to
esophageal, lung, bladder, stomach, and colon can-
cers (Jain et al. 2020). The production of nitrosa-
mines that cause cancer is significantly aided by
nitrite. It has been determined that N-nitrosodi
methylamine (NDMA) and N-nitrosodiethylamine
(NDEA) are probably carcinogenic to humans by the
International Agency for Research on Cancer (IARC).
Other frequently occurring nitrosamines in meat
products that have been linked to a possible risk of
human cancer include N-nitrosodibutylamine
(NDBA), N-nitrosopyrrolidine (NPYR), and
N-nitrosopiperidine (NPIP) (Sallan et al. 2019).
NDMA is the carcinogenic nitrosamine most fre-
quently occurring in foods (Keszei et al. 2013).
Monochloropropane diols and their esters
Monochloropropane diols and their esters (2- and
3-) and GE are primarily detected in acid-HVP
(acid-hydrolyzed vegetable proteins), and soy
sauces (mainly during the deodorization stage)
(Kamikata et al. 2019), followed in different pro-
cessed foods including meat, smoked foods,
cereal-based foods, dairy products, malts, infant
formula, baby foods, soups, sauces, and coffee.
In contrast, edible oils are the main source of
3-MCPDE (Moravcova etal. 2012; Li et al. 2016).
Lauric acid, myristic acid, palmitic acid, stearic
acid, oleic acid, linoleic acid, and linolenic acid
are the most common fatty acids that esterify
with 3-MCPD and 2-MCPD (Silva et al. 2019).
Up to 28 distinct 3-MCPD diesters, 14 different
3-MCPD monoesters, and seven unique GE can
be found in commonly ingested refined oils
(Spungen etal. 2018). It was reported that lipases
in the gastrointestinal tract may transform them
into their free forms (including 3-MCPD,
2-MCPDE, and glycidol) during digestion, lead-
ing to renal toxicity (Zheng etal. 2021). Numerous
investigations have revealed that compared to
crude oil containing <100 µg kg−1, purified oil can
contain levels from <300–2462 µg kg−1 of
3-MCPDE (Svejkovská et al. 2006).
Mechanism of formation
Acrylamide
It was found that baked and fried starch-rich foods
and coffee were the main sources of AA in foods.
The process of AA formation during thermal pro-
cessing is not fully understood, but it is known
that AA is formed in carbohydrate-rich foods that
are subjected to thermal processing methods such
as heating, frying, or baking. Raw, non-thermally
treated, or boiled foods do not contain AA
(Mousavi Khaneghah et al. 2020). Recent studies
have identified two main pathways for AA forma-
tion: the acrolein pathway and Strecker degrada-
tion. These pathways are responsible for the brown
color, crust, and mouthwatering flavor of fried,
toasted, and baked foods. Consequently, the darker
the color of such products, the higher the content
of AA. AA production at high temperatures (120 °C
or higher) in foods is primarily linked to the
Maillard reaction. However, its formation has also
been reported in potato fries under prolonged
heating, low moisture, and temperatures below
120 °C (Krishnakumar and Visvanathan 2014;
Stojanovska and Tomovska 2015).
6 A. ZAHIR ETAL.
The Maillard reaction involves a complex series
of reactions that occur between a carbonyl source
and amino acids, particularly asparagine during
the heating of food (Stojanovska and Tomovska
2015; Rifai and Saleh 2020). However, AA can
also be formed through alternative pathways,
including deamination and decarboxylation of
asparagine, decarboxylation or dehydration of
organic acids, lipid degradation, and thermal deg-
radation of proteins and amino acids, which
release ammonia (Sarion et al. 2020). The pri-
mary mechanism for AA formation involves the
reaction of asparagine with a carbonyl compound,
preferably an α-hydroxycarbonyl. This results in
the formation of N-glycosyl conjugates and inter-
mediate products, such as decarboxylated Schiff
bases, which are subsequently converted to AA.
Mass spectral analysis using 13C-labeled and
15N-labeled asparagine glucose has confirmed that
the three carbon atoms and the nitrogen of the
amide group are derived from asparagine (Vinci
et al. 2012). Recent studies have shown that AA
formation can occur at high sterilization tem-
peratures in fat-rich foods such as ripe black
table olives (Pan etal. 2020). Additionally, during
the Maillard reaction in cereal products, cocoa
beans, and coffee, a chemical called
3-aminopropionamide can be formed and con-
verted to AA under aqueous conditions (Ghorbani
et al. 2019).
The process by which oils are heated above
their smoke point yields acrolein, a precursor to
the synthesis of AA. This process is known as the
acrolein route. At this point, glycerol undergoes
breakdown, resulting in the formation of acrolein.
In the presence of asparagine, acrolein further
oxidizes to acrylic acid, leading to the production
of AA. Asparagine provides the amino group,
while acrylic acid provides the carbon source.
Another pathway for AA formation is Strecker
degradation, which occurs in foods subjected to
very high temperatures (Maan etal. 2022).
Advanced glycation end products
Advanced glycation end products (AGEs) are
formed endogenously as well as exogenously such
as during food processing and cooking (oxidation
of fats and proteins) via the Maillard reaction.
The synthesis of AGEs is a multi-stage (com-
monly a 3-stage glycation process), complex,
non-enzymatic reaction that commences within a
few hours via a condensation/glycation process
between reducing sugars, such as glucose and
fructose, and the free amino group of proteins,
lipids, and nucleic acids resulting in the forma-
tion of reversible products know as Schiff base
such as aldimine. The glucose concentration is
the driving force of this reaction (Song et al.
2021). This reaction is relatively rapid and highly
reversible and these products are retained at an
alkaline pH, typically greater than the natural
pH. High pH promotes the formation of AGEs.
Schiff base adducts undergo spontaneous intra-
molecular re-arrangements which convert these
products to relatively irreversible, covalently
bound Amadori products also known as early
glycation products. The re-arrangement of Schiff
base depends on the number of reducing sugar
and amino groups available or attached along
with the pH being upheld above natural pH. This
stage is called the initial phase (Gill et al. 2019).
The subsequent stage is the formation of more
stable Amadori products which contribute to
covalent adducts and the accumulation of pro-
teins, as a result of the dehydration and further
re-arrangement of the Schiff base and when the
pH drops below natural, these products specifi-
cally re-arrange themselves. This phase is called
the proliferation or intermediate stage (Sergi etal.
2021). Up to this stage, all products are revers-
ible. The several rearrangements of Amadori
products, such as degradation, dehydration,
reduction, oxidation, condensation, polymeriza-
tion, epimerization, isomerization, and hydrogen
bonding, results in the formation of final irre-
versible molecules called AGEs, and this stage is
called the advanced proliferation stage of glyca-
tion or final stage (Gill et al. 2019). The alterna-
tive method of AGE formation is an incubation
of lipid peroxidation products with proteins (the
acetol pathway). In the polyol pathway (the Wolff
pathway), glucose converts into fructose which
also promotes glycation; and further conversion
of fructose may lead to the formation of very
potent non-enzymatic glycation agents such as
fructose-3-phosphate and 3-deoxyglucose (Kuzan
2021). All these pathways generate AGE reactive
FOOD ADDITIVES & CONTAMINANTS: PART A 7
precursor compounds, such as glyoxal (GO)
methylglyoxal (MGO), and α-dicarbonyl (α-DC)
compounds, resulting in the formation of irre-
versible AGEs. The reaction of a protein with a
lysine residue leads to the formation of N-ε-
carboxyethyl lysine (CEL) from MGO and N-ε-
carboxymethyl lysine (CML) from GO (Cengiz
et al. 2020). In foods, AGEs are widely distrib-
uted and can be formed during a series of
thermal-related manufacturing procedures includ-
ing processing, packaging, sterilization, and pro-
longed storage of food items. Home cooking such
as grilling, boiling, reheating, and frying also
produce AGEs in ready-to-eat foods (Zhang
et al. 2020).
Furan
Furan formation in thermally processed foods is
low, but exposure depends on its volatility. It can
be formed through (1) thermal breakdown or
re-arrangement of carbohydrates, (2) oxidation of
polyunsaturated fatty acids and carotenoids, (3)
ascorbic acid oxidation, and (4) amino acid dis-
sociation (Seok et al. 2015; Chain et al. 2017;
Eldeeb and Akih-Kumgeh 2018). Thermal pro-
cessing generates furan from carbohydrates like
lactose, glucose, and fructose. Derivatives of aldo-
tetrose are synthesized and converted to furan.
The Maillard reaction produces intermediate
compounds like 1-deoxy- and 3-deoxyosones.
Furan formation can occur from all aldotetrose
derivatives (Kettlitz et al. 2019). Its formation
from polyunsaturated fatty acids is triggered by
the formation of 4-hydroxy alk-2-enables, possi-
bly including (E)-4-hydroxy but-2-enal, produced
by the oxidation of but-2-enal. Furan production
increases with the degree of unsaturation with
linolenic acid producing four times more furan
than linoleic acid (Batool et al. 2021). Furan for-
mation in baby foods occurs from carotenoid
oxidation, with precursors being lactose and fruc-
tose. Processing methods like irradiation and
UV light contribute to furan formation. Thermal
dry conditions activate furan formation from
2-furoic acid (2FA) and 2-methyl furan (2FOL)
decarboxylation (Delatour et al. 2020). Furan
formation involves ascorbic acid, found in vari-
ous foods, forming 4-deoxy ascorbic acid and
2-deoxyaldotetrose. Rapid oxidation and break-
down of ascorbic acid in the food system result
in 2, 3-diketogulonic acid (DKG), which is
transformed into aldotetrose, 3-furanone, and
furan (Sirot et al. 2019). Amino acids can con-
vert pentose sugars into furan through heat
treatment, while certain amino acids undergo
metabolization by glycolaldehyde and acetalde-
hyde, forming intermediate 2-deoxyaldotetrose
(Troise 2019). Reducing sugar, cysteine, or ser-
ine is crucial for glycoaldehyde formation
during Strecker degradation, which produces
2-deoxyaldotetrose, furan formation intermedi-
ate, and reactive carbon-2 units like glycolal-
dehyde and acetaldehyde (Batool et al. 2021).
Shen et al. (2021) found that low pH stimu-
lates furan formation in canned strawberry
jams, with fructose producing more furan than
sucrose and glucose, and xanthan gum reducing
levels (Shen et al. 2021). This indicates that acid
regulating agents such as citric acid promote furan
formation. However, the type of added sugar had
a vital role in furan formation, thus, the addition
of glucose or sucrose would be a better choice
than fructose or high fructose corn syrup.
Heterocyclic aromatic amines
HAAs are primarily formed from heterocyclic
units and amines resulting from the Maillard
reaction. HAAs are divided into two types: amino
carbolines (Non-IQ types HAAs) which are
formed at high temperatures by pyrolytic reac-
tions of proteins and amino acids, and amino
amidazo azoarenes (IQ type HAAs) which are
formed during normal cooking temperatures
(between 150–300 °C) through the reaction
between creatinine, creatine, amino acids, and
hexose. Based on the heating temperature, HAAs
are classified as thermic HAAs (between 150 to
300 °C) or amino amidazo azoarenes (IQ type
HAAs) and pyrolytic HAAs (above 300 °C) or
amino carbolines (Non-IQ types HAAs) (Szterk
2015). Due to their chemical properties, HAAs
are further sub-divided into polar (IQ-type com-
pounds) and non-polar HAAs. Over 30 HAAs
have been identified and categorized from diverse
food sources. Among them, 10 HAAs are classi-
fied by IARC as possible human carcinogens class
8 A. ZAHIR ETAL.
2B (MeIQ, PhIP, AαC, and MeAαC) and probable
human carcinogen class 2 A (IQ) (Oz 2021).
Furthermore, HAAs are highly mutagenic, with
more than 2000-fold and over 100-fold mutagenic
potential compared to benzo[a]pyrene and afla-
toxin B1, respectively (Chen et al. 2020).
Polycyclic aromatic hydrocarbons
The investigation of the formation and inhibition
of polycyclic aromatic hydrocarbons (PAHs)
during food processing has been an area of inter-
est in the scientific community. PAHs can be
generated and released as a result of incomplete
combustion or pyrolysis of organic substances
such as gas, oil, wood, coal, or biomass, as well
as charbroiled meat and tobacco, in various
industrial, natural, or other human activities (Hu
et al. 2020; Neves et al. 2021). The breakdown
and cyclization of certain organic macromolecules
such as proteins, fats, oils, and sugars at high
temperatures (500–700 °C) have been reported as
the probable mechanism for the formation of
PAHs (Camargo et al. 2012; Duedahl-Olesen
2013). At high temperatures, smaller organic sub-
stances undergo pyrolysis, and the free radicals
generated during food combustion combine to
form larger PAH particles through pyrosynthesis
(Singh and Agarwal 2018). The commonly
involved rearrangements in PAH formation are of
the Diels–Alder type. Temperature is a significant
factor that affects both the diversity and structure
of formed PAHs. Larger PAHs are formed at
lower levels compared to smaller PAHs due to
kinetic constraints in their production via the
addition of consecutive rings (Singh et al. 2016).
N-nitroso compounds
N-nitroso compounds are formed by the reaction
of nitrosating agents with a secondary amine
(Park et al. 2015). When secondary amines com-
prising dialkyl, N-alkyl ureas, N-alkyl amides,
N-alkyl carbamates, and alkyl aryl are nitrosated
(reacted with nitrite), nitrosamines are formed
(Alaba et al. 2017). Cured meat products react in
acidic environments to form nitrous acid from
sodium nitrite, which then breaks down into
nitrous anhydride (N2O3). To produce
nitrosamines, nitrosation of N2O3 and secondary
amines occurs. Studies have shown that fat oxida-
tion is an effective procedure for producing meat
products at the same time. When fat is burned, it
produces nitroso and its derivatives, which at
high temperatures break down into N2O3. N2O3
and amines combine to produce NAs (Lu et al.
2022). It’s known that tertiary amine can scarcely
generate nitrosamine, and that secondary amine
can form stable nitrosamine while nitrosamines
derived from primary amine break down quickly.
Microorganisms have been shown to convert
nitrate in spinach, cabbage, and other vegetables
to nitrite. The nitrosating reaction can also hap-
pen in the stomach when amines in an acidic
environment combine with nitric oxide derived
from nitrite or nitrate. The production of nitro-
samines from precursors in the stomachs of
humans, cats, and rabbits has been documented;
the reaction’s ideal pH range is 3 to 4. One of the
most well-known fermentation processes is the
decarboxylation of amino acids by a microbial
enzyme, which is a crucial step in the production
of nitrosamine precursors. N-nitrosopiperidine
and N-nitrosopyrrolidine, two cyclic
N-nitrosamines, are amine precursors produced
by microbial polyamine synthesis after amino
acid decarboxylation (Park etal. 2015).
Monochloropropane diols and their esters
The formation mechanism of 3-MCPDE in edible
oils remains unclear despite a significant number
of investigations on the subject. Per one study,
the generation of 3-MCPDE was triggered by
iron ions (Zhang et al. 2015). According to a
study, the formation of the 3-MCPDE could be
considerably enhanced by Fe3+. The oil’s pH,
heating temperature, and duration all affected the
formation of 3-MCPDE. 3-MCPDE were found
to be at their maximum levels at pH 4.0
(2925.3 mg/kg), 220 °C (9509.8 mg/kg), and 8 h
(4852.4 mg/kg), in that order. 3-MCPDE was pro-
duced far more frequently in the continuous
heating model than in the intermittent one (Li
et al. 2016). The currently accepted mechanism
for the formation of 3-MCPDEs entails the direct
nucleophilic attack of the chloride ion or the
generation of a cyclic acyloxonium intermediate
FOOD ADDITIVES & CONTAMINANTS: PART A 9
to incorporate chlorine into the glycerol back-
bone of monoacylglycerols (MAGs) and diacyl-
glycerols (DAGs). Similarly, it is known that
DAGs and MAGs function as precursors of GEs
through cyclic acyloxonium intermediate, medi-
ated free radical-mediated pathways (Figure 1).
High-DAG refined oils like rice bran oil and
palm oil have high concentrations of these con-
taminants (Chen et al. 2021).
Factors aecting the formation of process
contaminants
Acrylamide
Several factors influence the formation of AA
during food processing, particularly during frying
and baking at high temperatures (>120 °C). These
factors include the type, quantity, and quality of
raw materials, product viscosity, product thick-
ness, pH, free reducing sugars (glucose and fruc-
tose), asparagine content, type of thermal
treatment (particularly temperature and time),
low moisture content (water activity), and the
ratio and concentration of asparagine and reduc-
ing sugars (Wang etal. 2021). Among these, high
temperature, time, and low food moisture content
are the main factors for AA formation, which
was also confirmed by recent studies (Martinez
et al. 2019; Žilić et al. 2020; Hu et al. 2021;
Knight et al. 2021). Therefore, it can be con-
cluded that free reducing sugars, free asparagine,
low moisture conditions at the food surface, and
high temperatures (>120 °C) are the primary
requirements for AA formation in thermally pro-
cessed foods.
Advanced glycation end products
The rate of AGEs formation in food is determined
by factors such as nutrient composition (fat > pro-
tein > carbohydrate), duration of heat treatment
and temperature, pH, humidity, and the existence
Figure 1. Formation of 3-MCPDE in the presence of chloride via various routes proposed by TAG, DAG, or MAG.
10 A. ZAHIR ETAL.
of trace elements (Figure 2). Compared to foods
with high carbohydrate content including fruit,
vegetables, legumes, and whole grains, foods con-
taining high levels of fat and protein are com-
monly rich in AGE, and also susceptible to the
formation of novel AGEs during cooking
(Inan-Eroglu et al. 2020). Generally, the highest
level of AGEs was reported with animal-based
foods cooked at high temperatures for lengthy
periods and under dry conditions (Uribarri et al.
2015). With increasing quantities of proteins and
fats, the CML content in food increases. High lev-
els of CML were reported in high-fat food prod-
ucts such as butter, olive oil, cookies, and biscuits
which contain high levels of CML.
Xie et al. (2023), determined levels of dAGEs in
commercial cow, goat, and soy protein-based infant
formulas. They found that in comparison to cow
and goat-based formulas, soy-based formulas had
significantly higher concentrations of arginine
(307 mg/100 mL milk) and arginine-derived dAGEs.
The authors also found that higher dAGEs concen-
trations were related to infant formula containing
hydrolyzed proteins (peptides) than those contain-
ing intact proteins. However, the lactose-containing
formula was more susceptible to glycation than the
formulas containing sucrose and maltodextrin (Xie
et al. 2023). The same authors found that in infant
formula, one of the factors accountable for the
high occurrence of dAGEs was a higher concentra-
tion of reducing carbohydrate, and whey proteins
(due to containing more lysine residues than
caseins). Infant formulas are usually enriched with
iron and ascorbic acid, in addition to their macro-
nutrient composition. This promotes the formation
of dAGEs and enhances glycation. This indicates
that in infant formula, the occurrence of dAGEs is
relatively high which lowers the nutritional value
of the final product (Xie et al. 2021). Cengiz et al.
(2020), reported the occurrence of the most potent
precursors of AGEs such as GO and MGO in
crackers, breakfast cereals, and chips. Since, chips
and crackers, were baked at a high cooking tem-
perature and contained high fat; consequently,
these products showed higher amounts of AGE
precursors, while low-fat-containing breakfast cere-
als showed lower quantities of AGE precursors.
The author stated high concentration of salt in
crackers may influence the increased quantity of
GO and MGO (Cengiz et al. 2020).
Furan
Various factors such as pH, temperature, raw
materials, sterilization conditions, water activity
(aw), time and storage conditions, and the absence/
presence of activators and inhibitors may affect
the formation and concentration of furan. Seok
and Lee (2020) studied the effect of roasting on
the formation and kinetics of furan in nuts. They
found that increasing roasting time and tempera-
ture led to higher furan levels in nuts, reaching
up to 348 ng/g. This increase was attributed to the
higher temperature affecting unsaturated fatty acid
Figure 2. Factors that aect the formation of AGEs.
FOOD ADDITIVES & CONTAMINANTS: PART A 11
levels and decomposing linolenic and linoleic acid
(Seok and Lee 2020). Kruszewski and Obiedziński
(2020), studied the impact of raw materials (cocoa
and non-cocoa) on furan formation in dark choc-
olate. The content of furan increased after roast-
ing of cocoa beans (25.1 − 34.8 ng g−1) (Kruszewski
and Obiedziński 2020). The effect of sterilization
on furan formation in canned foods. They found
that certain canned foods showed increased furan
levels under low-
temperature-long-time (LTLT) conditions com-
pared to high-temperature-short-time (HTST)
conditions. The most often found dormant pre-
cursor of furan is ascorbic acid, followed by
unsaturated fatty acids and sugars (Santonicola
and Mercogliano 2016). Shen et al. (2015) found
with the increasing heating temperature; the con-
tent of furan rapidly increased. However, the
highest levels of furan were observed in neutral
buffer solutions, and also in all model systems the
furan levels were related to heating time. From
PUFAs, ferric ions promoted furan formation,
whereas with an optimum concentration glutamic
acid inhibited furan formation (Shen et al. 2015).
Different substrates including ascorbic acid, fatty
acids, and sugars and pH affect furan formation.
At pH 6, the maximum formation of furan was
related to the linoleic acid, whereas at pH 3, the
maximum was recorded from ascorbic acid. In
food containing linolenic acid, at >110 ◦C and
compared to pH 4.2 and pH 9.4, a higher amount
of furan (239.7 ng/mL) was found than at pH 7.0.
In the case of home cooking, the class of cooking
may also affect the quantity of formed furan, in
which a higher concentration of furan formation
was reported from the frying method (150 to
200 °C) than other cooking methods (Batool etal.
2021; Huang etal. 2022; Zhang and Zhang 2023).
Heterocyclic aromatic amines
The formation of HAAs during cooking is influ-
enced by various factors such as processing meth-
ods and conditions, pre-treatment techniques,
time and temperature, pH, mass transfer and
heat, fat content, free amino acids, carbohydrates,
water activity (aw), type of meat, lipid and lipid
oxidation, precursors in processed meat, and the
presence of antioxidants. Among these factors,
processing methods and conditions, which are
further influenced by the cooking temperature,
heat conditions, and heat transfer, are the most
critical factors affecting the formation of HAAs
(Liao et al. 2010; Gibis 2016). The cooking
method used also plays a significant role in the
formation and type of HAAs. Khan et al. (2022)
studied pan-frying, deep-fat frying, barbecuing,
and oven-roasting methods for cooking goat
meat. The results showed that the highest levels
of HAAs were obtained with deep-fat frying and
pan-frying, followed by oven roasting and
barbecuing.
High levels of HAAs have been reported in
pan-fried beef. However, modifying cooking
methods has been suggested as a means of reduc-
ing HAA production. For example, microwaving
meat primarily generates carboline-type HAAs,
while frying produces both IQ-type and
carboline-type HAAs. The formation of HAAs is
highly dependent on cooking temperature and
duration, which directly affect both HAA forma-
tion and the sensory characteristics of foods.
Previous research indicates that only small or
undetectable amounts of HAAs are produced at
temperatures of 175 °C in fried meat, whereas
higher levels occur when the cooking tempera-
ture exceeds 220 °C. However, a recent study
revealed that the content of nine HAAs increased
significantly as the cooking temperature ranged
from 150 to 350 °C. Additionally, HAAs are
formed during prolonged cooking of meat at low
temperatures.
The presence of HAA precursors, such as free
amino acids, creatine, and hexoses, may also
impact HAA formation (Suleman et al. 2019;
Elbir and Oz 2020; Sheng et al. 2020; Oz et al.
2021). During the frying of foods, HAAs form
from their precursors, which are transferred by
water molecules (Kilic et al. 2021). To limit the
movement of precursor molecules from the inner
to the outer surface of food and reduce HAA
production, it is recommended to add water-
binding materials, such as starch or salt (Nadeem
et al. 2021). The amount of HAAs produced
during meat frying decreases with microwave
treatment. After microwave pretreatment,
water-containing substances such as amino acids,
glucose, fat, and creatine are released from the
12 A. ZAHIR ETAL.
meat (Rahman etal. 2014; Lušnic et al. 2020). To
reduce precursor molecules and result in the
reduction of HAA production, the elimination of
water-containing materials is an effective method.
Polycyclic aromatic hydrocarbons
The concentration of PAHs in food is influenced
by several factors, including cooking methods
and duration, processing levels, fuel used, and
distance from the heat source, nevertheless pro-
cesses such as conching, crushing, concentration,
reprocessing, and storage can also increase the
level of PAHs in certain food products (Singh
and Agarwal 2018). The occurrence of PAHs in
food is primarily due to food processing and
preparation techniques such as roasting, smoking,
grilling, curing, drying, frying, barbecuing, refin-
ing, and steaming, as well as environmental con-
tamination. Of these techniques, grilling and
smoking are the most significant factors contrib-
uting to the production of PAHs, resulting from
the pyrolysis of organic substances at tempera-
tures above 200 °C and the incomplete burning of
fat dripping onto the fire, respectively (Lee et al.
2016; Tongo et al. 2017). Environmental contam-
ination is another important cause of PAHs con-
tamination in vegetables and plants. The growth
of plants and crops in contaminated soils or the
presence of fish or marine life in contaminated
water provides a pathway for PAHs to enter the
food chain.
N-nitroso compounds
Numerous investigations have shown that nitroso
compound formation in meat products (e.g. roast
meat, bacon and smoked or salted fish, dried and
pickled vegetables) depends on many factors such
as cooking procedures, processing, cooking time
and temperature, precursor concentrations, the
basicity of the amine, nitrite level, water activity,
pH, nitrosation catalysts/inhibitors, microbiota,
moisture activities in different meat products,
storage conditions, preservation conditions (i.e.
temperature, time, and oxygen), fat, and protein
contents (Zhou et al. 2020). The generation of
nitrosamines is significantly influenced by cook-
ing temperature, cooking time, and cooking
methods such as grilling, roasting, and frying.
Studies have shown that the amount of fat and
protein in meat products as well as the process-
ing techniques used have significant effects on
the formation of NAs (Lu etal. 2023). Black pep-
per contains piperine and piperidine, which may
act as precursors to synthesize nitrosopiperidine
(NPIP). Because secondary amines, such as piper-
idine, can easily become nitrosatable without heat
treatment, using spices containing alkoloids and
nitrates in meat products is another way to
expose meat products to nitrosamines (De Mey
et al. 2017). The effects of varying amounts of
black pepper (5, 10, or 15 g kg−1), the use of
sodium ascorbate, and the degree of cooking
(raw, medium, medium well, and well done) were
found to have an impact on the synthesis of
nitrosamine in sucuk, a type of dry fermented
sausage. consequently, sodium ascorbate signifi-
cantly reduced the amount of leftover nitrite. The
levels of nitrosodimethylamine (NDMA), nitro-
sopyrrolidine (NPYR), and nitrosopiperidine
(NPIP) were significantly influenced by the degree
of cooking. As the cooking temperature increased,
the amount of NPIP in sucuk increased both
with and without ascorbate. The amount of NPIP
in both the raw and well-prepared samples was
reduced by a high black pepper dose. Both
NDMA and NPYR concentrations increased when
15 g kg−1 of black pepper was used without ascor-
bate. In contrast, the combination of ascorbate
and 15 g kg−1 black pepper resulted in a decrease
in NPYR (Sallan et al. 2019). Throughout food
production, it is indispensable to minimize nitrite
and nitrate levels to decrease amounts of NOCs
(Zhou et al. 2020).
Monochloropropane diols and their esters
Chen et al. (2021) investigated the formation of
thermally induced GE and 3-MCPDE in refined
oils and pressed oils using different processes.
High-temperature seed roasting was the primary
contributor that significantly increased the con-
tents of GEs and 3-MCPDEs in pressed oils,
where higher precursor levels were observed. In
contrast, the concentrations of GEs and
3-MCPDEs were found to be extremely low in
16 oilseeds that were pressed using two
FOOD ADDITIVES & CONTAMINANTS: PART A 13
commonly used mechanical methods screw
pressing and hydraulic pressing (Chen et al.
2021). However, the 3-MCPDE rates were closely
related to the moisture and lipids/sugar contents,
glycerol, NaCl, and temperature, depending on
the type of food and the processing method
used. For instance, a study showed that adding
chlorine to the thermally treated (235 °C) triolein
oils increased the formation of 3-MCPDE. Wong
et al. (2017) investigated the formation of
3-MCPDE and GE in palm olein oil mixed with
sodium chloride used to fry chicken. As a result
of NaCl being the precursor for 3-MCPDE syn-
thesis, they noticed that the formation rate of
3-MCPDE increased as NaCl levels increased
(Wong et al. 2017). The formation of 3-MCPDE
is influenced by pH, as an acidic environment
activates and promotes chloride nucleophile
attack. In the model oil study, the formation of
3-MCPDE can be reduced from 7 mg kg−1 to less
than 3 mg kg−1 by lowering the pH of the oil
using sodium bicarbonate and disodium carbon-
ate. A few other important variables were inter-
mittent heating and certain metal ions, especially
those with greater catalytic capacities such as
Fe3+ (Zhang et al. 2021).
Dietary intake and risk assessment of process
contaminants
Acrylamide
AA can be found in a diverse range of com-
monly consumed food items, including cereal
products such as cereal-based snacks, popcorn,
breakfast cereals, and cereal-based baby foods,
as well as potato-derived products like French
fries and crisps, biscuits, bread, chocolate, cof-
fee, hazelnuts, raw and processed fruits and
vegetables, meat, fish, cocoa products, condi-
ments, green tea, oilseeds, sauces, and alcoholic
beverages (Powers et al. 2021). AA is mostly
found in foods that have been heated above
160–180 °C, particularly carbohydrate-rich foods
that have been fried or baked in an oven
(Esposito et al. 2020; Lindeman et al. 2021;
Pasqualone et al. 2021). The highest levels of
AA were found in dry coffee at average
middle-bound levels of 522 µg kg−1. High levels
of AA were also found in potato crisps and
snacks (389 µg kg−1) and potato fried products
(average 308 µg kg−1). Lower levels were found
in cereal-based baby foods (average 73 µg kg−1),
soft bread (average 42 µg kg−1), and baby foods,
other than cereal-based (average 24 µg kg−1).
The groups most exposed were infants, tod-
dlers, and other children. The estimated chronic
dietary exposure of children varied depending
on the age group and survey, with the 95th
percentile being between 1.4 and 3.4 µg kg−1
b.w. per day and the average being between 0.5
and 1.9 µg kg−1b.w. The average and 95th per-
centile values for the chronic dietary exposure
of adolescents, adults, the elderly, and the very
elderly were found to be between 0.4 and 0.9 µg
kg−1 b.w. per day and 0.6 and 2.0 µg kg−1 b.w.
per day, respectively, based on the age group
and survey. The categories ‘Baby foods, other
than processed cereal-based’ and ‘Other prod-
ucts based on potatoes’ comprised the largest
portion of the infants’ total exposure, respec-
tively. Potato fried products (apart from potato
crisps and snacks) accounted for up to half of
the total exposure for toddlers, other children,
and adolescents. Soft bread, breakfast cereals,
crisp bread, biscuits, crackers, and other
cereal-based products, and other potato-based
products followed. In addition to ‘Coffee,’ these
food groups were the primary sources of expo-
sure for adults, the elderly, and the very elderly
(EFSA 2009; EFSA 2011; EFSA Panel on
Contaminants in the Food Chain (CONTAM))
2015). Benchmark levels have not been set by
the EU for AA in food, and the WHO recom-
mends a limit of 0.5 µg L−1 for drinking water.
Stockholm University researchers and Swedish
NFA have reported high (150–4000 μg kg−1)
and moderate (5–50 μg kg−1) levels in heated
carbohydrate and protein-rich foods, respec-
tively (Rifai and Saleh 2020). EFSA allows for
up to 40% dietary AA for adults, and the
European Commission recommends various
levels of AA in specific foods, such as breakfast
cereals (~149 μg kg−1), fried potatoes (~272–
570 μg kg−1), bakery products (~75–1044 μg
kg−1), and roasted coffee (450 μg kg−1).
Non-thermally processed or boiled and micro-
waved foods are typically low in AA
(Iriondo-DeHond etal. 2020).
14 A. ZAHIR ETAL.
Advanced glycation end products
Since AGEs are continuously formed endoge-
nously, a huge part of AGEs can be derived from
exogenous sources. The well-recognized and
major exogenous sources of AGEs and their pre-
cursors are intrinsic to the modern Western diet
(Delgado-Andrade 2016). In comparison to AGEs
formed during normal metabolism, dAGEs are
equally considered for health complications and
are more complex and heterogeneous. Foods that
showed the highest level of AGEs are red meat
and meat-derived products, fried eggs, certain
cheeses, margarine, butter, cream, mayonnaise,
nuts, and oils (Anwar et al. 2021).
Furan
Over the past decade, furan formation in
heat-treated food processing has gained public
attention and is well-studied by well-recognized
agencies such as EFSA, the US FDA, and the UK
FSA (Rahn et al. 2019; Rahn and Yeretzian 2019).
Furan was initially detected in most canned and
jarred foods in relatively higher amounts due to
sealed containers and heat treatment for sterility
and long shelf life (Chain et al. 2017). However,
furan has also been reported in baked, roasted,
and fried foods, as well as other products such as
pickled cucumbers, bread, oyster sauces, fruit
juice, meat, and raw pasta (Jeong et al. 2019;
Seok and Lee 2020). No data on the occurrence
of methyl furans has been reported. The highest
exposure to furan was estimated for infants, pri-
marily from ready-to-eat meals. Grain and
grain-based products contribute the most to tod-
dlers, other children, and adolescents.
For adults, the elderly, and the very elderly,
coffee is the main contributor to dietary exposure
(Chain et al. 2017). Furan has been reported in
ground and roasted coffees in the range of 0.7 to
3.45 mg kg−1 (Kettlitz et al. 2019). Kim et al.
(2021) determined furan levels in commercial
coffee products and 26 varieties of coffee beans
roasted under the same conditions. Furan was
found in coffee beans at levels of 4708–8634 ng/g
and in commercial coffee products at 11–2155 ng/g,
respectively. The study also found that after roast-
ing, the amounts of monosaccharides varied
noticeably in most samples. However, due to a
large reduction of its level during roasting, glu-
cose is assumed to be the primary contributor to
furan formation (Kim et al. 2021). Gruczyńska
et al. (2018) found that furan levels in brewed
coffee are typically around 120 μg L−1, while in
ground or roasted coffee, the quantity can reach
up to 7000 μg kg−1 (Gruczyńska et al. 2018).
Altaki et al. (2017) found that infant formula
and cereal-based food had the lowest furan levels
(<0.02–0.33 ng mL−1 and 0.15–2.1 ng g−1, respec-
tively), while baby food with fish had the highest
levels from 19–84 ng g−1.
Heterocyclic aromatic amines
Thermic HAAs are widely distributed in all
heated animal-derived foods such as grilled fish,
fried steaks, roasted meat, and boiled milk, which
contain high amounts of protein and creatine, the
precursor required for their formation (Meurillon
and Engel 2016; Buła et al. 2019). Additionally,
HAAs have also been detected in various other
food items such as coffee, alcoholic beverages,
soup cubes, and smoked cheese (Barzegar et al.
2018). For instance, 2-amino-1-methyl-
6-phenylimidazo[4,5-b] pyridine (PhIP), which is
typically found in animal-derived products, has
also been detected in beer, wine, and smoked
cheese. The most commonly occurring HAAs in
meat include PhIP, MeIQx, 4,8-DiMeIQx, IQ,
MeIQ, and AαC (Gibis 2016). The concentration
of PhIP in meat typically ranges between 1 and
70 ng/g in most studies. MeIQx has been reported
at concentrations of up to 23 ng/g, while the
lower concentrations of around 1 ng/g are related
to 4,8-DiMeIQx. Some studies have reported that
IQ cannot be detected at all (Dong et al. 2020).
Polycyclic aromatic hydrocarbons
PAHs have a ubiquitous presence in the environ-
ment, being found in water, air, soil, and conse-
quently in both processed and unprocessed foods.
Contamination of foods with PAHs can occur
through environmental contamination, and food
processing practices such as smoking, drying, and
grilling (Kim et al. 2021b). Cereals and their
products, and seafood and its products, accounted
FOOD ADDITIVES & CONTAMINANTS: PART A 15
for the two highest portions of dietary exposure.
The EFSA used a variety of statistical models to
calculate Benchmark dose lower confidence limit10
(BMDL10) values for benzo[a]pyrene, PAH2,
PAH4, and PAH8. EFSA chose the lowest BMDL10
values from the statistical models that best fit the
data. The values that corresponded were 0.07,
0.17, 0.34, and 0.49 mg/kg b.w. for each day. To
determine the dietary exposure of average and
high-level consumers to benzo[a]pyrene, PAH2,
PAH4, and PAH8, as well as the corresponding
BMDL10 values obtained from the two coal tar
mixtures utilized in the carcinogenicity experi-
ments, the EFSA employed a Margin of Exposure
(MOE) method. Benzo[a]pyrene was found to be
an unreliable indicator of PAHs in food. The
CONTAM Panel concluded that PAH4 and PAH8
are the most suitable indicators of PAHs in food,
with PAH8 providing little added value compared
to PAH4 (EFSA 2008a).
N-nitroso compounds
Compared to Western countries, more frequent
and higher concentrations of NOCs have been
reported in Asian food (Xu etal. 2015). Data on
NAs occurrence for five food categories and ten
carcinogenic NAs found in food (TCNAs) were
recently made accessible. NAs have been found in
a variety of foods and drinks, including cheese,
soy sauce, oils, processed vegetables, beer and
other alcoholic and non-alcoholic beverages, pro-
cessed seafood, and human milk. Findings mostly
focus on meat and fish products and show that
heat treatment produces as well and increases the
amounts of N-NAs in food. The primary food
group that increases an individual’s risk of acquir-
ing TCNAs is meat and meat products.
Experimental data enabled the calculation of
BMDL10 values for various TCNAs in food. Nine
carcinogenic NAs have TD50 values listed in the
Carcinogenic Potency Database, with NSAR alone
having a TD50 of 0.982. When it comes to car-
cinogenic potential, NDEA, NMEA, NDMA, and
possibly NMOR are in the top category. Meat
and meat products were the only one of the five
food categories considered in the dietary expo-
sure evaluation for which data were available for
each TCNA.
The literature provides evidence that heating
(baking, frying, grilling, or microwaving) increases
the presence of NAs in meat, even if raw or
undercooked meat may contain trace levels of
these chemicals. The availability of data on
cooked, unprocessed meat and fish is, however,
restricted. Due to this, EFSA chose to estimate
exposure using two different scenarios: either
Scenario 1 excluding cooked unprocessed meat
and fish and Scenario 2 including cooked unpro-
cessed meat and fish. The TCNA mean
middle-bound (MB) dietary exposure in scenario
1 varied from less than 0.1 ng/kg bw per day in
infants to 12.0 ng/kg bw per day in toddlers. The
dietary exposure to TCNA P95 upper bound
(UB) ranged between 0 and 54.8 ng/kg bw daily
in both infants. For scenario 2 the TCNA mean
MB dietary exposure ranged from 7.4 ng/kg bw
per day in infants to 87.7 ng/kg bw per day in
toddlers. For infants, the dietary exposure to
TCNA P95 UB varied from 34.7 ng/kg bw per
day to 208.8 ng/kg bw per day for toddlers. The
five NAs that individually contribute the most to
the highest mean TCNA exposure across surveys
and age groups (>80%) in both scenarios are
NPYR, NSAR, NDMA, NPIP, and NDEA (Chain
et al. 2023).
In 2005, the Chinese authorities mandated that
the maximum level of NDMA in meat products
should not exceed 3 µg/kg, while the United States
Department of Agriculture set a limit of 10 µg/kg
for total volatile NAs in meat products. High lev-
els of NAs were reported in pork meat (100 µg/kg
of NDMA), but lower levels found in sucuk
(0.31 µg/kg NDMA) (Sallan et al. 2020).
Monochloropropane diols and their esters
There is evidence of 3-MCPDE occurrence in a
variety of food products including grilled cheese,
meat, dairy products or malts, coffee, biscuits,
toast, bread crust, soy sauce, human breast milk,
infant formulas, and cereal-based products
(Khosrokhavar et al. 2021). Bound 3-MCPDE in
the form of both mono- and diesters were more
frequently detected in edible oils than free
3-MCPD. Compared to crude oils, refined palm
oil and palm olein samples contained higher lev-
els of 3-MCPDE and GE (EFSA 2016; Li et al.
16 A. ZAHIR ETAL.
2016). However, infant formulae have been shown
to have substantial amounts of 3-MCPDE and
GE esters, possibly because of the use of refined
vegetable oils. A theoretical preliminary exposure
assessment of infant formulae marketed in Brazil
found 3-MCPDE and GE intakes of up to 5.8
and 10.5 µg/kg body weight/day, respectively
(Arisseto et al. 2017). An investigation was car-
ried out to ascertain the levels of GE, 3-MCPDE,
and 2-2-MCPDE in baby formula products. GE
had the greatest amount (1.6 µg/kg) followed by
3-MCPDE (0.7 µg/kg), and .2-MCPDE (0.4 µg/kg)
(Nik Azmi etal. 2023). In the EU there are max-
imum levels of 3-MCPDE in specified oils rang-
ing from 0.5 mg kg−1 to 2.50 mg kg−1 with limits
as low as 15 µg kg-1 for infant formula placed on
the market as a liquid.
According to studies, refined palm oil has the
highest level of 3-MCPDE (Destaillats etal. 2012).
For 3-MCPDE, EFSA reported a Tolerable Daily
Intake (TDI) of 0.8 μg/kg body weight. Meanwhile,
for 3-MCPDE, either without or in combination
with the glycidyl esters, the Joint FAO/WHO
Expert Committee on Food Additives (JECFA)
proposed a Provisional Maximum Tolerable Daily
Intake (PMTDI) of 4 μg/kg body weight. Regarding
GE, it was revealed that these substances metab-
olize in the human body to produce glycidol, a
component that the IARC has categorized as
‘probably carcinogenic to humans’ (Group 2 A).
The amount of glycidol that is produced from
GE after digestion is still unknown.
The exposure to 3-MCPDE (as 3-MCPD equiv-
alents, assuming 100% hydrolysis was estimated by
the EFSA (2016) for infants who were solely
formula-fed for the first four months of their lives.
The estimations were calculated based on 3-MCPDE
concentrations in 70 samples examined by the
German Federal Agency for Risk Assessment (BfR).
The study determined the estimated 3-MCDE
exposures to be 2.4 μg/kg bw/day based on the
mean 3-MCPDE concentrations in infant formula
and 3.2 μg/kg bw/day based on the 95th percentile
concentrations. The latter was estimated as a
‘worst-case scenario’ to account for exposures to
products that have high concentrations of 3-MCPD
esters for infants who are ‘brand loyal.’ These expo-
sures exceed the EFSA 2 μg/kg bw/day TDI for
total dietary 3-MCPD (EFSA 2008b); however, they
fall short of the JECFA 4 μg/kg bw/day PMTDI for
total dietary 3-MCPD (JECFA 2018). According to
JECFA (2018), infants fed formula had mean expo-
sures to 3-MCPD equivalents of up to 10 μg/kg bw/
day during their first month.
Mitigation strategies
To mitigate or prevent the potential occurrence
of substances of concern in the food supply chain,
both the scientific community and the food
industry have recently focused on developing
novel reduction strategies (Gaur et al. 2020). To
ensure the safety of food products for consumers,
regulations regarding maximum limits are contin-
uously updated (Fiore et al. 2019). The reduction
of hazardous substances in various food products
during processing has been extensively studied,
with several methods currently being investigated.
These include the use of variable process condi-
tions, new and integrated processing techniques,
pre-and post-processing treatments, product
reformulation, and additives, among others.
However, the effectiveness of these methods may
vary depending on the particular food, as differ-
ent compositions and product technologies may
result in the production of neo-formed contami-
nants. For example, prolonged yeast fermentation
in bread has been shown to effectively reduce AA
concentration, but may also lead to an increase
in 3-MCPDE levels and other neo-formed con-
taminants (Capuano and Fogliano 2011). Thus, it
is crucial to identify the most suitable solution
for each specific food product (Table 3).
Acrylamide
Reducing the formation of acrylamide (AA) in
food products while maintaining their quality is a
challenging issue for the food industry. To address
this issue, physical, chemical, and biological meth-
ods have been developed to mitigate AA formation.
Physical approaches
Physical methods are commonly used in the food
industry and involve modifying processing param-
eters such as time, temperature, and humidity
(aw). Microwave treatment (for coffee), blanching
(for potatoes), vacuum-based processing (for
FOOD ADDITIVES & CONTAMINANTS: PART A 17
biscuits), and the use of high-intensity ultrasound
are examples of physical methods that can reduce
AA levels by up to 90% (Rannou etal. 2016). For
potatoes, blanching and immersion in water can
also decrease the AA content by leaching aspar-
agine and glucose molecules.
Chemical approaches
Adding non-asparagine amino acids such as ala-
nine, glutamine, glycine, cysteine, and lysine can
be effective in reducing AA formation as these
amino acids compete with asparagine for car-
bonyl group reactions. For example, adding gly-
cine and cysteine to biscuits can prevent up to
97% of AA formation. Food pre-treatments, such
as the addition of a single or double cation (e.g.
sodium hydrogen carbonate, sodium chloride, or
calcium chloride) in fried potatoes, biscuits, and
ginger bread products, have been shown to sig-
nificantly reduce AA formation. Immersing foods
in lysine, glycine, and asparaginase solutions has
also been investigated as an effective method for
reducing AA formation (Capuano and
Fogliano 2011).
To decrease the AA formation, acidic pH can
be utilized. Immersing French fries in acidic
solutions, such as citric or acetic acid, has been
evaluated by several researchers and has demon-
strated a 90% reduction in AA levels. The reduc-
tion in pH results in the transformation of the
amine –NH2 group into a non-nucleophilic pro-
tonated –NH3, which can reduce the formation
of Schiff bases. Recent studies have indicated that
adding hydrocolloids containing pectate and pec-
tin to biscuits can also reduce AA levels due to
the decrease in pH, whereas galacturonic acid
can significantly increase the amount of AA pro-
duced. During food processing, the pH of the
food not only inhibits the growth of microorgan-
isms but also influences chemical reactions
(Moosavy et al. 2017). The growth of pathogenic
bacteria is restricted by pH levels below 4.6, and
the Maillard reaction does not occur in acidic
conditions (Ou et al. 2010; Zahir et al. 2020). In
addition to pH, the moisture content of the food
is also a crucial factor in AA formation. When
exposed to thermal variation, the evaporation of
water from the food matrix can cause sugars such
as fructose and glucose to form a saturated solu-
tion and even crystallize, leading to the forma-
tion of AA.
To mitigate the formation of AA, natural anti-
oxidants derived from spices and herbs have been
utilized due to their capacity to react with AA
precursors or AA itself by donating hydrogen
from –OH groups that are linked to phenols.
This process can lead to the termination of the
oxidation chain reaction and prevent the forma-
tion of AA. A study by Tesby et al. (2018) inves-
tigated the effect of natural antioxidants on the
reduction of AA formation and found that the
addition of 0.0375% allicin led to a significant
reduction of up to 50%. Plant antioxidants such
as tea polyphenols have also been used to reduce
AA levels in wheat dough. The application of
natural or synthetic antioxidants is promising,
however, the sensory characteristics of the prod-
uct, including the presence of a garlic flavor,
should be assessed. The impact of six phenolic
compounds, including ferulic acid, gallic acid,
p-cumaric acid, caffeic acid, epicatechin, catechin,
and cinnamic acid on AA content has been
Table 3. Potential food process contaminants in dierent stages of food processing and mitigation strategies.
Food process contaminants Mitigation strategies References
Acrylamide Backing, soaking, roasting, frying, blanching, fermentation, the addition
of plant antioxidants enzymes, or additives, avoiding
high-temperature heating.
Ou et al. (2010)
AGEs Optimization of processing parameters, application of alternative
processing techniques, and addition of natural antioxidants
Li et al. (2023)
Furan optimization temperature conditions and time, application of innovative
food processing technologies, selection of precursors and
ingredients, and the addition of some scavenging agents.
Batool et al. (2023)
Heterocyclic aromatic amines Addition of natural or synthetic antioxidant compounds and natural
product extracts, modication of process conditions or heating
method, use of microwave pre-treatments, and developing
biomarkers.
Oz et al. (2023)
Polycyclic aromatic hydrocarbons Improve cooking methods, washing, peeling, proper food packing,
conduct an individual risk assessment, use natural adsorbents and
replacement grilling equipment, rening vegetable oils, mild
roasting(coee), addition activated charcoal.
Afé et al. (2020); Ciecierska et al.
(2019)
18 A. ZAHIR ETAL.
studied, and the results indicate that these com-
pounds have an antioxidant and mitigating effect
on AA production (Tesby et al. 2018).
Enzymatic approaches are another chemical
alternative for mitigating AA formation, specifi-
cally the addition of an asparaginase enzyme that
competes with the asparagine molecule by car-
bonyl groups, binding to sugars. This has suc-
cessfully reduced AA levels by 85–90% in
industrial applications. Asparaginase from
Aspergillus terreus has been studied for its effect
on AA formation control. Treatment of samples
with 4 U/mL asparaginase resulted in a reduction
in AA content. In addition, vitamins have been
identified as potential mitigators, as they can
react with free radicals thereby inhibiting peroxi-
dative chain reactions due to their nucleophilic
groups. The efficiency of vitamins and amino
acids in the reduction of AA in ripe olives was
investigated by López-López et al. (2014), who
studied the effect of five different vitamins but
found that only thiamine significantly decreased
the level of AA (López-López et al. 2014).
Other strategies include the use of
bacteriocin-like inhibitors, the substitution of
reducing sugars with sucrose, incorporation of
diverse additives such as rosemary, proteins, or
amino acids, and fermentation (dough) (Esposito
et al. 2020; Sarion et al. 2021; Maan et al. 2022).
Additionally, agronomic factors such as the sulfur
content of soil have been suggested as a means of
reducing AA formation in plant-based products
(Katsaiti and Granby 2016).
Biological approaches
Biological methods for AA reduction have also
been investigated, which involve the genetic mod-
ification of food species to identify cells that reg-
ulate sugar production and modify them
accordingly. Some studies have demonstrated that
microbial methods can be as effective as techno-
logical approaches for AA reduction. Specifically,
various lactic acid bacteria, yeast, and cell-free
extracts have demonstrated promising ability to
remove AA (Krein et al. 2020; Albedwawi et al.
2021). Probiotic supplementation is also a prom-
ising approach for reducing AA in food products,
with possible mechanisms including the binding
of AA to peptidoglycan components such as
carbohydrates and alanine, and the production of
the enzyme asparaginase, which converts asparag-
ine to L-aspartic acid and ammonia, thereby pre-
venting the formation of AA. Certain Lactobacillus
species, such as L. casei and L. reuteri, have also
been reported to possess asparaginase genes
(Khorshidian et al. 2020; Azi et al. 2021)
(Figure 3).
Despite the potential benefits of the aforemen-
tioned strategies for reducing AA formation in
food products, they also have several drawbacks,
including high costs, lengthy processing times,
negative sensory effects, and difficulties in imple-
mentation on an industrial scale. As a result, new
approaches have been investigated, such as the
use of biocontrol agents that produce asparagi-
nase (specifically, probiotics such as Lactobacillus)
and non-thermal treatments like pulsed electric
fields (PEF). These methods are effective in
decreasing AA precursors in potato tissues and
subsequently reducing AA formation (Schouten
et al. 2020).
In collaboration with the European Commission
(EU) and national authorities in the EU, European
food manufacturers have identified several mea-
sures to mitigate the presence of acrylamide (AA)
in food. The measures were compiled from aca-
demic research and industry sources, and the
resulting compilation is known as the Acrylamide
Toolbox (Pogurschi et al. 2021). The toolbox con-
siders various factors such as a recipe, agronom-
ical factors (e.g. soil sulfur levels), processing,
and final preparation (e.g. preparation guidance
on-pack to the consumer) to identify reduction
measures. Significant progress has been made by
food manufacturers, particularly in the infant/
baby food classes, mostly through measures
applied at the recipe and processing stages. As an
example, in infant cereals, the use of asparaginase
as an additional step in the processing line can
result in more than an 80% reduction in AA
compared to untreated products, while maintain-
ing acceptable organoleptic properties and con-
sumer acceptability. However, no practical
measures have been identified for ground, roast,
and soluble coffee. Regarding potato crisps,
European manufacturers have reported a leveling
off in the AA content since 2011, with the mean
level in 2016 being 412 ng/g, which is a 46%
FOOD ADDITIVES & CONTAMINANTS: PART A 19
reduction from 2002. Effective AA reduction
measures had been developed and implemented
by 2011, leading to a decrease in the occurrence
of very high levels (above 2 mg/kg) from 4.8% in
2002 to 0.6% in 2016. It should be noted that
seasonality affects AA levels in potatoes, with the
highest levels occurring in the first half of the
year when potatoes are being used from storage
and the lowest levels occurring from July to
September when potatoes are being harvested.
A more recent development in the reduction
of AA in foods is found in Regulation (EU)
2017/2158, which established the application of
mitigation measures and new benchmark levels
(Table 4), updated and released in April 2018.
The ‘ALARA’ principle (As Low As Reasonably
Achievable) underpins the Regulation and states
that the occurrence of AA should be reduced to
the minimum possible level. Based on a litera-
ture review, three key parameters, namely reduc-
tion rate, side effects, and applicability and
economic impact, are proposed as effective strat-
egies for reducing AA. The toolbox includes sev-
eral beneficial mitigation strategies, such as the
use of asparaginase in bakery products and the
selection of low-sugar varieties in potato prod-
ucts (Palermo etal. 2016; Stadler 2019; Swanston
2019; Schouten et al. 2020; Lo Faro et al. 2022;
Maan etal. 2022). Table 5 presents the indicative
values for AA, as outlined by Recommendation
2013/647/EU for the 2007–2012 period, and the
values specified by Recommendation 2017/2158/
EU (European Commission, 2017) for the 2018–
2021 period, based on EFSA monitoring data.
Table 4 displays the trend in the EU for the
exceeded indicative/benchmark levels of AA in
Figure 3. A summary of AA mitigation through physical, chemical, and biological methods.
Table 4. Evolution in the Commission Regulation (EU) 2017/2158 of the indicative/benchmark levels limit exceeded for AA in
selected foodstus.
Foodstu
*Indicative value
(ng/g) 2013
**Benchmark level (ng/g)
2017
Limit exceeded
(%) Reduction (%) References
Potato chips 1,000 750 87.5 25 Mihai et al. (2020);
Regulation (2017)Popcorn 200 150 100 25
Biscuits 500 300 100 40
Corn akes 200 150 33.3 25
Breakfast cereals 400 300 0 25
Roasted muesli 400 300 0 25
Roast coee 450 400
Instant (soluble) coee 900 850
French fries (ready-to-eat) 600 500
*Commission recommendation (2013/647/EU) – indicative values
**Commission regulation (EU) 2017/2158 – benchmark levels
20 A. ZAHIR ETAL.
selected foodstuffs from 2013 to 2017, as reported
by Bušová et al. (2020) and Sarion et al. (2021)
in their respective studies on the topic (Bušová
et al. 2020; Sarion et al. 2021).
Advanced glycation end products
Mitigation of AGEs in foods such as infant for-
mula has been reviewed by Xie et al. (2021).
Optimization of processing parameters and appli-
cation of alternative processing techniques are
suggested. During the spray-drying process, the
pump rate and inlet temperature had the utmost
effects on dAGEs formation. Others evaluated the
effects of storage conditions and different drying
techniques on the formation of Nε-(carboxymethyl)
lysine (CML) in skim milk powders. The study
showed that in comparison to freeze-dried pow-
der, a significantly higher CML concentration
was obtained from spray-dried powder, and
during storage this difference increased with time.
Under 52% relative humidity and storage tem-
perature dropped from 30° to 20 °C, the inhibi-
tion of CML was 68%, and 90% inhibited when
the relative humidity of storage decreased from
52% to 33% under 30 °C. In milk recipes, mitiga-
tion strategies are more focused on lowering the
reactivity of precursors, limiting the participation
of precursors, or adding dAGEs inhibitors into
the recipe. However, some other strategies such
as encapsulation (mitigation of the Maillard reac-
tion by slowly releasing the reactive ingredient),
or in brown fermented milk, replacing the addi-
tion of glucose with enzymatically hydrolyzed
lactose (5%) in milk is effective (Xie et al. 2023).
Recently, more attempts have been made to
mitigate the AGEs in milk by application of
dAGEs inhibitors, mainly focusing on natural
compounds complemented with polyphenols.
Application of a by-product from olive oil pro-
cessing such as olive mill wastewater phenolic
powder, effectively inhibited the formation of
43.3% (GO), 55.9% of (MGO), and 47.7% of
furosine in ultra-high temperature (UHT) milk.
In addition to polyphenols, several other types of
these compounds such as terpenoids, polysaccha-
rides, alkaloids, and vitamins, are suggested as a
good source for novel drug discovery to alleviate
AGE formation. To block the AGE formation,
their mechanisms are chelating metal ions, scav-
enging free radicals, protecting protein glycation
sites, capturing active carbonyl compounds, and
lowering blood glucose levels (Song et al. 2021).
For Baijiu (an alcoholic beverage usually dis-
tilled from fermented sorghum) production, a fer-
mentation starter called vinasse which contains
ten types of phenolic compounds, is used in the
milk model system inhibiting 43.2% of CML,
because phenolic acid compounds can trap and
scavenge GO. The milk protein glycation is miti-
gated effectively by the addition of beetroot juice,
in which the formation of furosine (>30%) is
more inhibited than that of CML (17%). This
mitigation is attributed to the existence of com-
pounds with phenolic ring structures in beetroot
juice. The trapping property in the phenolic ring
is attributed to the containing vicinal hydroxyl
groups which can trap dicarbonyls through aro-
matic electrophilic replacement, whereas; when its
structure contains a monohydroxyl group, it
Table 5. Indicative values for AA in bakery products set by the Commission Regulation (EU) for the 2007–2021 periods (2013/647/
EU; 2017/2158/EU).
Food
Benchmark Level 2013
(µg/kg)
Benchmark Level 2017
(µg/kg) References
Soft bread 501 Mihai et al. (2020);
Regulation (2017)Wheat-based bread 80 50
Soft bread other than wheat-based bread 150 100
Breakfast cereals (excl. porridge) 400 300
Bran products and whole grain cereals, gun pued grain 400 300
Wheat and rye-based products 300 300
Maize, oat, spelt, barley, and rice-based products 200 150
Biscuits and wafers 500 350
Crackers except for potato-based crackers 500 400
Crispbread 450 350
Gingerbread 1000 800
Baby foods, processed cereal-based foods for infants and young
children excluding biscuits and rusks
50 40
Biscuits and rusks for infants and young children 200 150
FOOD ADDITIVES & CONTAMINANTS: PART A 21
primarily captures the existing lysine through the
formation of a quinone ring. Likewise, the extract
of lotus seedpod and lingonberry leaf containing
oligomeric procyanidins can inhibit CML forma-
tion (due to the existence of phenolic compo-
nents) by 51% and 38%, respectively. In
comparison, extracts rich in polyphenols from
natural plants, have higher inhibitory effectiveness
on dAGEs formation by the addition of pure phe-
nolic compounds in the milk model system. For
instance, the mixture of genistein, daidzein, and
catechin, showed a good suppression of dicar-
bonyl compounds in UHT milk, principally when
the respective concentrations were 1.12, 1.12, and
0.645 mM applied. In the soy milk model system,
an 85% decrease in CML, and a 20% decrease in
Heyns products formation was observed by the
application of the mixture of glycitein, genistein,
and daidzein. Moreover, numerous researchers
have investigated the effects of chemical com-
pounds or enzymes on protein glycation in milk
model systems, which were proven as reducing
agents against AGE precursors (Xie et al. 2021).
To mitigate the formation of CML in foods,
adapting the food processing parameters, and
application of inhibitors during culinary prepara-
tion are recommended (Delgado-Andrade 2016).
A study carried out by Teng et al. (2018), eval-
uated the impact of a common flavanone called
naringenin on the formation of AGEs in a bread
crust. The author found that increasing the narin-
genin content in bread (from 0.25% to 1% w/w),
the formation of CML and total fluorescent AGEs
were significantly inhibited from 9.7% to 54.3%
and 11.8% to 35.2%, correspondingly. The author
also noted that without impacting on bread qual-
ity, fortifying bread with naringenin significantly
inhibits the formation of AA in the bread crust,
meanwhile enhancing the antibacterial and antiox-
idant activity of bread crumbs (Teng et al. 2018).
Furan
Different furan mitigation strategies have been
applied to beverages such as leaving hot bever-
ages in an open atmosphere, altering thermal
processing conditions, recipe amendment, chang-
ing precursor levels, high temperature, and pres-
sure approach, and most importantly triggering a
significant reduction in furan levels by adding
several antioxidants.
Traditionally leaving hot beverages
Considering the volatile nature of furan, leaving
hot food/beverage in the open air before con-
suming can significantly reduce furan levels,
which is the first and most simple strategy to be
applied. After food has become ready-to-eat, agi-
tation and stirring can be a further factor trigger-
ing a decrease in furan levels (Mesías and Morales
2015). However, this method has some hygienic
concerns (Batool et al. 2021).
Changing thermal processing conditions
Reducing the thermal load via optimization of
temperature (low) and time during processing or
reducing the precursor levels are generally a good
mitigation option. However, altering heat process-
ing parameters, such as time and temperature,
cannot be universally adopted as both are import-
ant in ensuring the microbiological safety of
foods. Secondly, furan is produced from a variety
of precursors such as amino acids, carbohydrates,
ascorbic acid, and PUFAs. The high volatility of
furan is another factor that affects its ultimate
concentration in food (Seok et al. 2015).
To reduce levels of furan in baby foods, inno-
vative food processing technologies such as
high-pressure thermal sterilization (HPTS), ohmic
heating, high-pressure and high-temperature
(HPHT), and high-pressure processing (HPP)
have been employed. HPP has gained more atten-
tion owing to the effective decrease of furan
because of its non-thermal mechanism. In vegeta-
ble purees, the application of HPHT has pro-
duced lower furan levels, due to pre-heating time
and fast pressure release, which may drive off
furan formed during processing. However, in
comparison to the conventional resort system, to
achieve sterilization (F0=7) the use of 600 MPa
pressure in vegetable purees achieved a reduction
of furan formation from 81% to 96% (Sevenich
et al. 2014). Without affecting the overall quality
of foods and their food sensory properties, the
application of vacuum post-treatment removed
67% of furan from meat sauce, but it was ineffec-
tive in removing furan from biscuits. Leaching
22 A. ZAHIR ETAL.
reducing sugars and ascorbic acid from potato
slices by blanching, reduced furan concentrations
by 91% in potato chips.
Recipe modication
One contributing factor toward furan formation is
the pre-treatment of different food ingredients by
drying or steaming before being used in a food rec-
ipe. Thus, regarding recipe pre-treatment diverse
phases may cause substantial influences on furan
formation. Numerous studies involving model sys-
tems in particular vegetable model systems have
found that factors favoring furan formation depend
on the complexity of the food matrix. The many
interactions make the furan mitigation highly chal-
lenging. Moreover, recipe modification is required
on a case-by-case basis for every recipe and further
simulation of thermal process conditions is needed
by optimization at the factory scale. Due to limited
information about the appropriate ingredients and
their final destiny in the finished product, recipe
modification does not seem to be an easy method
to apply even for a simple vegetable puree. Hence,
attaining a significant decrease without nutritional
loss is a challenge.
Changing precursor levels
Altering levels of furan precursors such as PUFAs,
carbohydrates, and proteins under thermal oxidative
conditions can lead to the rapid production of furan
and subsequent changes in the taste of food devel-
oped by caramelization or Maillard reaction.
Nevertheless, very cautious mitigation has been car-
ried out by some strategies in both model systems
(alanine, glucose, serine), soy sauce, precursor sys-
tem, canned coffee, and real food matrices such as
vegetable puree (Batool etal. 2021).
Additives
In a canned coffee model system, the effect of
additives (certain antioxidants) causing a delay
in lipid oxidation was investigated in terms of
mitigation of furan formation. The most signifi-
cant inhibitory effect was related to the applica-
tion numbers of polyphenolics such as
chlorogenic acid (67%), followed by epicatechin
(65%), sodium sulfite (64%), epigallocatechin
gallate (60%), ferulic acid (58%), caffeic acid
(48%), tyrosol, oleuropein, ellagic and, puni-
calagin acid, owing to their radical scavenging
activity (Mogol and Gökmen 2016; Bi et al.
2017). Lee et al. (2020), reported that the addi-
tion of hydroxycinnamic acids reduced furan
formation in canned coffee model systems (Lee
et al. 2020). The most effective method that
mitigated furan formation was found after the
addition of gallic acid and malic acid as an anti-
oxidant and during UV-C light treatment of
simulated fruit juice was shown to minimize
furan formation by ending free radical chain
reactions (Hu et al. 2018). These authors tried
to reduce furan concentrations by metal ions
including calcium sulfate, iron sulfate, magne-
sium sulfate, and zinc sulfate; and antioxidants
such as butyl hydroxyanisole (BHA), butyl
hydroxytoluene (BHT), and sodium sulfite in
food model systems. They found that the reduc-
tion occurred through the application of sodium
sulfite followed by BHA, iron sulfite, BHT, and
calcium sulfite (Batool et al. 2021).
Shen et al. (2021), investigated the effects of
thickening agents such as xanthan gum, pectin,
and κ-carrageenan on furan mitigation in canned
strawberry jams. The results showed that the
addition of xanthan gum significantly reduced
furan levels in canned strawberry jams (Shen
et al. 2021), and thus, to mitigate furan forma-
tion, adding xanthan gum could also be consid-
ered a good choice. More recently, Kim et al.
(2023) studied the formation and mitigation of
furan in pumpkin puree during the entire manu-
facturing process. The results showed the addi-
tion of precursors such as ascorbic acid, fructose,
glucose, linolenic acid, linoleic acid, glutamic
acid, β-carotene, serine and, alanine enhanced
furan formation (31–94 µg/kg) compared to con-
trol (31 µg/kg), with β-carotene resulting in the
highest level of furan. In pumpkin puree contain-
ing β-carotene, additional antioxidants (such as
chlorogenic acid, quercetin, caffeic acid, and
butylated hydroxytoluene,) significantly reduced
furan formation. The authors also reported that
the furan content was greatly affected by tem-
perature but not heating time during sterilization.
Moreover, re-heating of pumpkin puree samples
by using a water bath, microwave oven or open
pot showed that open-pot re-heating effectively
FOOD ADDITIVES & CONTAMINANTS: PART A 23
reduced furan production (10–12 µg/kg) (Kim
et al. 2023). Currently, the industry federation is
working on a catalog of measures that can influ-
ence their formation (Mesias et al. 2020).
Therefore, up-to-date, no valuable mitigation
strategies other than changing the thermal load
have been recommended that are effective at the
industrial level (Bonwick and Birch 2019).
In conclusion, the most encouraging approaches
can be the combination of an optimized tempera-
ture condition and time, application of innovative
food processing technologies, selection of precur-
sors and ingredients, the addition of some scav-
enging agents by a cautious choice of all these
factors, and working on a catalog of measures.
However, more research still needs to be con-
ducted to find more effective mitigation strategies
with fewer disadvantages.
Heterocyclic aromatic amines
To reduce the formation of HAAs when cooking
or processing foods, three strategies can be
employed: (1) modification of process conditions
or cooking methods; (2) addition of natural prod-
uct extracts such as antioxidants or other com-
pounds; (3) selection of appropriate food types.
The cooking methods and conditions significantly
affect the formation of HAAs (Liao et al. 2010).
It has been shown that different cooking methods
produce different levels of HAAs. For example,
the lowest total HAAs were found in duck meat
cooked by grilling, followed by pan-frying, roast-
ing, and deep-frying methods. Similarly, the low-
est total HAAs were found in lamb patties cooked
by pan-frying, followed by frying, roasting, and
stewing. Microwave cooking of turkey and sliced
bacon meat led to lower levels of HAAs com-
pared to other methods such as pan-frying.
Generally, ‘milder’ cooking methods such as oven
roasting and boiling tend to produce lower quan-
tities of HAAs (Dong et al. 2020).
Natural compounds
One potential and effective approach for mitigat-
ing the formation of HAAs in cooked meat
involves the addition of specific substances such
as natural product extracts, spices, antioxidants,
or other compounds that have been identified for
their inhibitory effects. More than 100 different
types of additives have been investigated for their
ability to inhibit HAAs formation in cooked meat.
These substances are believed to scavenge the
free radicals involved in all pathways of HAAs
formation, thereby exerting their inhibitory
effects. In recent years, natural product extracts
and spices have been the most employed addi-
tives for HAA inhibition (Meurillon and Engel
2016). A variety of natural product extracts,
including rosemary extract, grape seed, apple peel
polyphenol extract, pomegranate seed extract,
artichoke extract, Rosa rugosa tea extract, green
tea extract, and hawthorn extract, have been
shown to inhibit HAA formation. In experiments
utilizing these extracts, varying degrees of inhibi-
tion (occasionally up to 100% for certain HAAs)
were observed concerning the formation of dif-
ferent HAAs and total HAAs. For instance, grape
seed extract was found to inhibit PhIP and
MeIQx formation in fried beef patties by 90%
and 57%, respectively. In cooked beef and chicken
meatballs, 59% to 69% inhibition of IQ, PhIP,
norharman, and MeIQx formation in cooked beef
meatballs and 31% to 73% inhibition in cooked
chicken meatballs were reported (Keskekoglu and
Uren 2017).
In recent years, a wide range of spices, includ-
ing thyme, basil, oregano, savory, garlic, paprika,
chili pepper, Sichuan pepper, prickly ash peel,
turmeric, black pepper, ginger, paprika, red chili,
clove, cinnamon, been extensively investigated for
their inhibitory effects on HAA formation.
Flavonoids (quercetin, naringenin, rutin, and
luteolin) and phenolic compounds (chlorogenic
acid, protocatechuic acid, p-coumaric acid, and
ferulic acid) have also been employed as HAA
inhibitors, with some of these compounds exhib-
iting 100% inhibition of certain HAAs. Grape
seed oil, red wine marinades or beer, dihydro-
myricetin, cellulose, chitosan, and short-chain
amylase are other types of additives that have
been investigated for their ability to inhibit HAA
formation (Suleman etal. 2019).
Selection of food items
Different types of meat (beef, pork, chicken,
and fish) and meat portions were investigated
for the formation of MeIQx, IQx, PhIP, and
24 A. ZAHIR ETAL.
DiMeIQx. The results showed that fried pork
had higher levels of total HAAs compared to
fried beef and chicken. In another study, various
animal species (pork, beef, mutton, and chicken)
and ingredients (rock candy, soy sauce, and rice
wine) were examined for the formation of nor-
harman, harman, MeIQx, IQ, MeIQ, and PhIP
in marinated meat. The study found that chicken
had the lowest amount of total HAAs compared
to pork, mutton, and beef. The use of soy sauce
contributed more to the formation of HAAs
than rice wine and rock candy. Moreover, differ-
ent types of sugars used in marinated meat have
also been found to affect the formation of
HAAs. Honey was found to be more effective
than table sugar, resulting in inhibition rates of
70%, 66%, 78%, 78%, 46%, and 73% for MeIQ,
PhIP, DiMeIQx, IQ, IQx, and norharman,
respectively. In another study, black beer showed
three-fold inhibition for total HAAs compared
to non-alcoholic Pilsner beer (Meurillon
et al. 2020).
Polycyclic aromatic hydrocarbons
Due to the ubiquitous nature of PAHs, the com-
plete elimination of these compounds from food
is difficult. Food produced using PAH-generating
commercial processes such as drying and smok-
ing should be avoided. Fruit, cereals, grain, and
vegetables grown in contaminated soil should be
rigorously washed or peeled before consumption.
To reduce PAH intake, consumers should be pro-
vided with the proper information when prepar-
ing roasted, smoked, grilled, and barbecued foods.
Fish and seafood from contaminated seawater
should only be consumed if the levels of petro-
genic and pyrogenic PAHs are below the limits of
concern.
In the refining of curd soybean oil, the use of
activated carbon has been shown to reduce PAH
levels by up to 88% (Camargo et al. 2012). The
reduction of PAHs in meat products can also be
achieved through the treatment of fermented sau-
sage surfaces with specific Lactobacillus strains
which have been shown to significantly reduce
the concentration of PAHs such as chrysene and
benzo[a]pyrene (Vasilev et al. 2017).
N-nitroso compounds
Reduction in NOC formation is probably closely
related to changing heating approaches and con-
trolling the heating duration and temperature;
adding plant polyphenols, ascorbic acid, and
vitamins. For instance, changing from a high
degree of heating to a low degree not only
decreases the number of contaminants but also
retains nutrients (Li et al. 2021). Additionally,
through choosing appropriate food ingredients
(minimum fat content), lowering the processing
temperature, selecting the proper processing
techniques (cooking instead of frying), and
choosing low-oxygen dry storage conditions (low
oxygen, dry), the formation of NAs in meat
products can also be effectively reduced (Xie
et al. 2023). However, the use of sodium ascor-
bate and green tea polyphenol (GTP) in dry fer-
mented sausage called sucuk and western-style
smoked sausage caused a considerable reduction
in the residual nitrite, nitrosamines, and thiobar-
bituric acid reactive substances (TBARs) respec-
tively (Sallan et al. 2020; Zhou et al. 2020).
NOCs are carcinogenic compounds that are
mostly formed by endogenous nitrosation. The
most significant chemicals that inhibited the for-
mation and subsequently reduction are reported
with vitamin C, vitamin E, and different types of
plant phenols (Catsburg et al. 2014). Green tea
polyphenol (GTP), grape seed extract (GSE), and
rosemary extract all decreased the amount of
residual nitrite in sausage; however, GTP’s nitrite
scavenging activity was higher than that of GSE
and rosemary extract. The levels of
N-nitrosamines, particularly NDMA, reduced as
the concentration of additives increased. Based
on the findings, we may conclude that GTP,
GSE, and rosemary have strong antioxidant prop-
erties and may prevent the synthesis of NAs.
When it comes to improving the quality of sau-
sage and reducing NAs, GTP is the most useful
ingredient that can be used in the future to pro-
duce sausage (Zhou etal. 2020).
It has been demonstrated that the nitrogen
oxide from combustion can react with amines
like gramine and horenine in the malting process
to generate NDMA during the kilning (drying of
malt) process of producing beer. During malting,
FOOD ADDITIVES & CONTAMINANTS: PART A 25
sulfur dioxide or indirect-fired kilns are employed
to minimize nitrosation during kilning (Park
et al. 2015).
Monochloropropane diols and their esters
To reduce rates of formation of monochloropro-
pane diols and their ester formation, the optimum
conditions for purifying oils were suggested by the
American Oil Chemists Society (AOCS). For
instance, intermittent frying significantly reduces
(80%) the 3-MCPDE content of palm olein as
compared to other oils such as sunflower, soybean,
and canola oils (Abd Razak et al. 2021). This indi-
cates that the quantity of these esters in the frying
oils is significantly influenced by the frying pro-
cess. Thus, mitigation strategies, such as improving
the refining process parameters and post-refining
treatments, were developed to minimize process
contaminants (Hew et al. 2020). The addition of
carbonate, neutralizes the unneeded free fatty
acids, resulting in inhibiting the formation of
3-MCPDE (Zelinková et al. 2006). A recent study
reported that a novel deodorization method for
edible oil called low-temperature ethanol steam
deodorization is beneficial in minimizing the con-
tents of 3-MCPDE and GE in vegetable oil (Peng
etal. 2023). There are numerous methods to lower
GE and 3-MCPDE in refined oil. For instance,
chloride exclusion studies by water washing of
crude palm oil (CPO) or bleached palm oil (BPO)
remove most inorganic chlorides, lessened the pro-
duction of 3-MCPDE. 3-MCPDE has also been
lowered by up to 99% by utilizing a variety of
techniques and using alcohol-based media for
steam stripping (Lakshmanan and Yung 2021).
Activated carbon, clay, antioxidants,
potassium-based salts, and other post-refining pro-
cedures have positively decreased between 10 and
99% of the GE. It has proven possible to reduce
these process contaminants using several strategies
without compromising other quality parameters
(Yung et al. 2023). Short path distillation, alkaliza-
tion using NaOH, KOH, alkali metals, or alkaline
earth metals, and post-sparging with ethanol or
steam have demonstrated concurrent mitigation of
51–91% in 3-MCPDE and 13–99% in GE, both
contaminants reaching below 1000 µg/kg. In pro-
cessed foods, 3-MCPDE was reduced by repeated
frying in the presence of antioxidants (TBHQ,
rosemary, and phenolics) (Yung et al. 2023).
Conclusions
In this paper, we have comprehensively reviewed
the formation, occurrence, and mitigation strate-
gies of food process contaminants. The produc-
tion of hazardous substances during various food
processing steps can significantly affect human
health. Despite the challenges in identifying haz-
ardous substances introduced by food constitu-
ents, processing methods, it is imperative to
strengthen food safety regulations to attempt to
mitigate their adverse effects on human health.
While a single strategy may not be effective in
eliminating food contaminants’ toxicity, a combi-
nation of mitigation strategies targeting common
food pollutants in high-risk products can be
employed. These strategies may include the appli-
cation of variable process conditions, novel, and
integrated processing techniques, various pre-and
post-processing treatments, product reformula-
tion, and additives. Furthermore, for newly dis-
covered food contaminants, novel detection
methods should be established to ensure their
effective detection and mitigation.
Authors’ contributions
A-Z contributed to the literature review and took the lead
in writing the manuscript. IA-K, M-N and MN-A contrib-
uted to the supervision and editing of the rst dra. F-AZ
was involved in planning and supervising the work. All
authors provided the conceptualization, and critical feed-
back and helped shape the review manuscript.
Disclosure statement
No potential conict of interest was reported by the authors.
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