See discussions, stats, and author profiles for this publication at: https://www.researchgate.

net/publication/339030340

A Review on Acrylamide in Food: Occurrence, Toxicity, and Mitigation

Strategies

Article in International Journal of Toxicology · February 2020

DOI: 10.1177/1091581820902405

CITATIONS READS

208 4,027

2 authors, including:

Fatima A Saleh
Beirut Arab University
41 PUBLICATIONS 1,079 CITATIONS

SEE PROFILE

All content following this page was uploaded by Fatima A Saleh on 15 April 2020.

The user has requested enhancement of the downloaded file.

Review
International Journal of Toxicology
2020, Vol. 39(2) 93-102
A Review on Acrylamide in Food: Occurrence, ª The Author(s) 2020
Article reuse guidelines:
sagepub.com/journals-permissions
Toxicity, and Mitigation Strategies DOI: 10.1177/1091581820902405
journals.sagepub.com/home/ijt

Lubna Rifai1 and Fatima A. Saleh2

Abstract
Acrylamide (AA) is a food contaminant present in a wide range of frequently consumed foods, which makes human exposure to
this toxicant unfortunately unavoidable. However, efforts to reduce the formation of AA in food have resulted in some success.
This review aims to summarize the occurrence of AA and the potential mitigation strategies of its formation in foods. Formation
of AA in foods is mainly linked to Maillard reaction, which is the first feasible route that can be manipulated to reduce AA
formation. Furthermore, manipulating processing conditions such as time and temperature of the heating process, and including
certain preheating treatments such as soaking and blanching, can further reduce AA formation. Due to the high exposure to AA,
recognition of its toxic effect is necessary, especially in developing countries where awareness about AA health risks is still very
low. Therefore, this review also focuses on the different toxic effects of AA exposure, including neurotoxicity, genotoxicity,
carcinogenicity, reproductive toxicity, hepatotoxicity, and immunotoxicity.

Keywords
acrylamide, toxicity, food, mitigation strategies

Introduction temperature reaches 120 C or higher.8 Maximum limits for

AA in food have not been established, although the World
For thousands of years, people have used heat to cook their Health Organization (WHO) guideline for AA in drinking
food. Thermal processing has a great importance in terms of water is 0.5 mg/L.9 The SNFA and Stockholm University
microbiological safety, nutritional quality, and the desired sen- researchers reported moderate levels (5-50 mg/kg) and high
sory properties, such as color, texture, and flavor; however, levels (150-4,000 mg/kg) of AA in heated protein and
undesirable chemicals have arisen as problems associated with carbohydrate-rich foods, respectively.10 Foods that lack AA
food processing techniques.1,2 Heating of food induces chem- are those that are boiled or nonthermally treated.11
ical reactions that lead to the formation of heat-induced toxic
substances, the so-called thermal process contaminants.3 One
such compound that has received much scientific interest over
Mechanism of AA Formation in Food
the recent years is acrylamide (AA).4 Before its discovery in
food, AA was known as an industrial chemical compound used A few months following the 2002 announcement by the SNFA,
primarily as a building block in many industrial processes, such much attention became focused on the Maillard reaction after it
as in the production of plastics, glues, paper, component of was reported that AA formation in starchy foods during heating
cigarette smoke, and in the treatment of drinking water and involves 2 natural components, namely, reducing sugars and
wastewater, including sewage.1 Acrylamide was also found the amino acid asparagine.12 High temperatures and low moist-
in consumer products, such as caulking, food packaging, and ure content in food favor the formation of AA.13 Maillard
some adhesives.5 reaction is not a single reaction but a complex series of reac-
Although AA has probably been around as long as people tions that occur during the thermal processing of food. During
have been baking, roasting, toasting, or frying foods, it was
only in April 2002 when the Swedish National Food Adminis- 1
Department of Nutrition & Dietetics, Faculty of Health Sciences, Beirut Arab
tration (SNFA) announced that prolonged heat treatments of University, Beirut, Lebanon
some foods could create significant amounts of AA.6 This dis- 2
Department of Medical Laboratory Sciences, Faculty of Health Sciences,
covery by Swedish researchers resulted in the detection of AA Beirut Arab University, Beirut, Lebanon
in a wide range of foods, particularly starchy foods such as
Corresponding Author:
potato and grain products when processed at high tempera- Fatima A. Saleh, Department of Medical Laboratory Technology, Faculty of
tures.7 Acrylamide does not appear in raw foods themselves; Health Sciences, Beirut Arab University, Beirut, Lebanon.
however, it is formed during the heating process when the Email: f.saleh@bau.edu.lb
94 International Journal of Toxicology 39(2)

Figure 1. Main pathway of acrylamide formation in food.

this nonenzymatic reaction, reducing sugars (glucose and fruc- Acrylamide Exposure
tose) condense with amino acids, mainly asparagine, to pro-
Humans can be exposed to AA through oral, dermal, and
duce N-glycoside that usually rearranges to the Amadori
inhalational routes.22 Acrylamide is also present in nondietary
rearrangement product, which in turn undergoes different steps
sources such as tobacco smoke, which is, therefore, another
to produce melanoidin, where a further decarboxylation of the
source of exposure for both smokers and nonsmokers (through
Schiff base leads to AA formation (Figure 1).14-16 This reaction
passive smoking).23 For smokers, it was found that tobacco
is primarily responsible for the brown color, crust, and char-
smoking is a more prominent source of AA exposure than
acteristic tasty flavor of baked, fried, and toasted foods.17
food.24 In addition, due to its wide variety of other nonfood
Research has shown that the reducing sugars are the limiting
industrial uses, many people can be exposed to AA in the
factors in potatoes, while asparagine is the limiting factor in
workplace through dermal absorption or inhalation.25 There-
cereal products.18 Recent studies have indicated that one other
fore, AA exposure is a combination of exposures from differ-
compound called 3-aminopropionamide can also be formed
ent sources such as diet, smoking, drinking water, and
during the Maillard reaction and can be converted to AA
occupational sources.
under aqueous conditions.19 This compound has been identi-
fied in cocoa beans, coffee, and cereal products.20 Maillard
reaction is primarily a surface reaction, so AA in bread is
located mainly in the crust with very low amounts in the Dietary Exposure
crumb.21 In potato crisps, one possible reason for the high The presence of AA in heat-processed foods is a worldwide
AA content is that the crisp is essentially 2 thin surfaces with health concern, since this substance has been classified as a
very little matter between them.21 In addition, the darker in probable human carcinogen by the International Agency for
color the food product is (burnt toast, darker chips), the higher Research on Cancer (IARC).26 Acrylamide is primarily formed
the AA content.21 in food products derived from raw materials that are rich in
In conclusion, free asparagine, free reducing sugar, high carbohydrates and low in proteins.10,27 Fried, deep-fried, or
temperature (>120 C), and low moisture conditions at the sur- baked food items, such as cake, bread, French fries, and chips
face of the food are key requirements for AA formation in heat- are believed to contain the highest levels of AA as shown in
processed foods.17 Table 1.13 Despite the fact that AA concentration in coffee is
Rifai and Saleh 95

Table 1. Acrylamide Levels in Selected Food Groups.a studies and to ensure monitoring of AA levels in food prod-
ucts.34 Another Lebanese study on the amount of AA in
Minimum Maximum
acrylamide, acrylamide,
caffeinated beverages showed that caffeinated beverages
Food group Food product group mg/kg mg/kg contributed an average of 29,176 mg/kg of AA, which was
higher than the risk intake for carcinogenicity and neuro-
Potatoes Potato crisps 117 3,770 toxicity set by the WHO.35 This study shows alarming
Chips/French fries 59 5,200 results that call for the need to regulate the caffeinated
Potatoes (raw) <10 <50
Cereal Corn crisps 120 220
product industry in Lebanon by setting legislations and stan-
products Bakery products and biscuits 18 3,324 dard protocols for product preparation in order to limit the
Gingerbread <20 7,834 AA content and protect the consumers.
Bread <10 130 The Joint Expert Committee on Food Additives had reported
Bread (toast) 25 1,430 that the major foods contributing to the total AA intake for
Breakfast cereals 11 1,057 most countries are potato crisps (6%-46%), potato chips
Rice and Fried noodles 3 581 (16%-30%), coffee (13%-39%), pastry and sweet biscuits
noodles Fried rice <3 67
Rice crackers, grilled, or 17 500
(10%-20%), and bread (10%-30%). 36 Furthermore, food
fried packages that contain polyacrylamide may lead to indirect
Fruits and Canned black olives 123 1,925 exposure to AA monomer residual.37 Although nonfood expo-
vegetables Prune juice 53 267 sures may exist, the diet is assumed to be the major source of
Fried vegetables 34 34 AA exposure for the general nonsmoking population, where
Nuts Nuts 28 339 around 38% of caloric uptake is provided by food sources that
Fish and Fish and seafood products, <2 39 are known to contain AA.38
meat crumbed, or battered
Meat/poultry products, <10 64
crumbed, or battered
Cocoa-based Chocolate products <2 826 Acrylamide Metabolism
products Cocoa powder <10 909
Coffee Coffee (roasted) 45 975 After consumption, it is demonstrated that AA is rapidly and
Coffee substitute 116 5,399 completely absorbed by the gastrointestinal tract in rats via the
Coffee extract/powder 195 4,948 circulation and is distributed to the peripheral tissues.39 The
a
Adapted from Food and Agriculture Organization/World Health fate of AA in humans seems to be qualitatively similar to that in
Organization.28 rodents.39 One exploratory study in healthy volunteers have
confirmed that AA can cross the blood–placenta barrier in a
human placenta in vitro model as well as the blood–breast milk
relatively low, it is a major contributor to AA exposure in barrier in vivo in lactating mothers.40 These studies may sug-
adults because of the high amounts of coffee consumed.29 gest that AA is able to reach any human tissue. Once absorbed,
Estimates of the average intake of AA by consumers may AA is metabolized via at least 2 main pathways. It may be
differ between countries and according to dietary habits, conjugated to N-acetyl-S-(3-amino-3-oxopropyl) cysteine by
but an average mean intake can be considered to be about glutathione-S-transferase (GST), or it may be converted to gly-
0.4 mg/kg body weight per day (bw/d), and the average intake cidamide in a reaction catalyzed by the cytochrome P450
for a high-level consumer to be about 1.0 mg/kg bw/d.30 Other enzyme complex (CYP450), where this metabolite is known
researchers estimated the acceptable daily intake to be to be more reactive toward DNA and proteins than the parent
1 mg/AA/d, which is an amount exceeded in many regular AA compound (Figure 2).41,42
food products.31 The WHO states that AA has no reliably Detoxification of both AA and glycidamide can proceed
identifiable threshold of effects, meaning that exposure to low through conjugation with glutathione (GSH), mediated by GST
doses might be followed by a symptom silent period in which and the GSH adducts thereafter are excreted in urine as by-
the detrimental effects of the chemical may not be clinically products of mercapturic acids.43 The mercapturic acids of AA
apparent, but nevertheless morphological and/or biochemical and glycidamide represent the major metabolites, and their
alterations may be present.32 Tolerable daily intake for neu- urinary excretion levels are proposed to be biomarkers of AA
rotoxicity from AA was estimated to be 40 mg/kg/d while that exposure.43 Additionally, AA and glycidamide can also form
for cancer was estimated to be 2.6 and 16 mg/kg/d based on adducts with DNA and amino acids in hemoglobin, and there-
AA or glycidamide, respectively.33 fore, these adducts represent important biomarkers of AA
In a study done in Lebanon, the daily consumption of AA exposure.44 The importance of AA as a food contaminant was
from potato and corn chips was found to be 7- to 40-fold higher shown in 2002 when it was observed that feeding rats with fried
than the risk intake set by WHO but was below the neurotoxic feed showed a large increase in the level of a hemoglobin
risk threshold. The cancer risk for the Lebanese population adduct.1 Moreover, AA was found to be able to cross the
from AA exposure estimations appears to be significant, placental barrier where studies showed the presence of
highlighting the need to conduct further epidemiological AA-hemoglobin adducts in the neonatal blood.45
96 International Journal of Toxicology 39(2)

Figure 2. Proposed metabolic scheme of acrylamide.

Toxicity of AA Genotoxicity and Carcinogenicity

Neurotoxicity The genotoxicity of AA and its major metabolite glycidamide
had been investigated in several studies. A study by Alzahrani
Neurotoxicity is a major consequence of AA exposure, and
in mice showed that single doses of AA at 10, 20, and 30 mg/kg
considerable attention has been drawn to this area of investi-
and repeated doses of 10 mg/kg for 1 and 2 weeks significantly
gation. This compound is considered to be a cumulative neu-
rotoxicant in rodents as well as in humans.46 In rodent toxicity induced DNA damage compared to the control group as shown
studies, exposure to repeated doses of 10 to 50 mg/kg bw/d AA by elevation in micronuclei and chromosome aberrations in
had been reported to cause neuropathy in most laboratory ani- mice bone marrow cells.53
mal species, while exposure to single doses of 100 to 200 mg/ Moreover, prolonged exposure of animals to high concen-
kg was fatal in most animals.47 In vitro, AA was shown to trations of AA in the drinking water leads to tumor develop-
induce apoptosis in rat primary astrocytes and cause mitochon- ment at multiple sites in both male and female genders.54
drial dysfunction and apoptosis in BV-2 microglial cells.48 Although there is sufficient evidence for the carcinogenicity
Moreover, Chen and Chou showed that AA disrupted the ner- of AA in experimental animals, the few epidemiologic studies
vous system by inhibiting human neuroblastoma and glioblas- conducted to date on occupational and dietary exposure to AA
toma cellular differentiation.49 have found no consistent evidence of its carcinogenic effects in
Acrylamide neurotoxicity in occupationally exposed popu- humans.55,56 Based on the current research, AA is currently
lations has been ascertained by various epidemiological stud- classified as a “probable human carcinogen” by the IARC and
ies.50 General symptoms of neurotoxicity in humans are a as “reasonably anticipated to be a human carcinogen” by the
characteristic ataxia, skeletal muscle weakness, weight loss, US National Toxicology Program.
distal swelling, and degeneration of axons in the central and Two different cohort studies were done on factory workers
peripheral nervous systems.51,52 A case report from Sweden being exposed to high levels of AA for many years, but no
described peripheral neuropathy in tunnel workers exposed to statistically significant cancer mortality was reported.57,58
short-term but intensive doses of a grouting agent containing However, other researchers have found some association
AA and N-methylolacrylamide.52 There was a significant between AA-hemoglobin adduct levels and incidence of estro-
dose–response association between peripheral nervous symp- gen receptor-positive breast cancer as well as between AA
toms and hemoglobin adducts that were used as biomarkers.52 intake and endometrial and ovarian tumors in postmenopausal
Rifai and Saleh 97

women.59,60 Herein, it is important to note the need for further sprouts or foods that contain significant amounts of cysteine,
research on this topic to provide information about AA expo- which is an essential substrate for the synthesis of glutathione,
sure and cancer risk in humans. such as onions, garlic, cruciferous vegetables, and red pep-
pers.67,68 Foods such as poultry, yogurt, and eggs also contain
Reproductive Toxicity significant amounts of the amino acid cysteine.67

Reproductive toxicity of AA in humans has not been demon-

strated; however, in rats, the No-observed adverse effect level Mitigation Strategies for AA
for reproductive toxicity was assessed to be 2 to 5 mg/kg/d.54
Since 2002, scientists from all over the world in collaboration
The administration of 0.5 to 10 mg/kg of AA caused growth
with agencies such as FAO and WHO have been working on
retardation in rats and reduction in epididymal sperm reserves
different ways to reduce the levels of AA in foods commonly
compared to the control group.54 In addition, repeated injec-
consumed with the highest levels of AA such as potato and
tions of AA (20 mg/kg) to male rats for 20 days caused
cereal products.69,70 Although coffee is also a substantial con-
decrease in testosterone and prolactin concentrations in a
tributor to the total dietary intake of AA, which is formed
dose-dependent manner.61 In another study, reproductive toxi-
during coffee roasting, currently there are no feasible strategies
city was also revealed in AA-treated female mice, where a
to decrease AA levels in coffee. According to the Codex Code
decline in the viability of mouse granulosa cells, the number
of Practice to reduce AA in foods, it is quoted “no commercial
of corpora lutea, and progesterone production was observed.62
measures for reducing acrylamide in coffee are currently
available.”38 Nevertheless, work is presently underway to iden-
Hepatotoxicity tify new strategies for AA mitigation without significantly
Although AA is metabolized in the liver, reports of its hepato- impacting the significant organoleptic properties and accept-
toxicity in humans are still scarce. However, numerous studies ability of coffee.71,72 Thus, this review discusses strategies that
in animals have reported the harmful effects of dietary AA in have been conducted for reduction of AA in foods such as
the liver due to oxidative stress. A high dose of 25 mg/kg AA potato and cereal products that were categorized into 4 differ-
administered for 21 days resulted in significant decrease in ent groups based on the effect of raw materials, additives,
liver GSH level and total antioxidant status in experimental processing conditions as well as the effect of pH, water activity,
adult rats. Administration of AA also led to increase in serum and fermentation.
level of liver enzymes (AST, ALT, and ALK) and decrease in
superoxide dismutase and catalase activities, while total oxi- Effect of Raw Materials
dant status and malondialdehyde levels increased.63
The formation of AA in foods such as potato and cereal prod-
ucts has been widely studied. The amount of AA formed varies
Immunotoxicity greatly in the same food items due to variable food composition
Studies regarding the adverse effects of AA on the immune (ie, nutrient contents) which is affected by several factors such
system are limited compared to other end points.54 Neverthe- as the climate and storage conditions, fertilization, and manu-
less, immunotoxicity of AA was found in female BALB/c facturing.73 Reducing sugars and asparagine content of potato
mice, where AA decreased final bw, spleen, and thymus and cereal products before thermal processing play significant
weights, and lymphocyte counts in addition to causing patho- roles in the formation of AA during later processing stages.74
logical changes in lymph glands, thymus, and spleen.64 Acry- For example, since the amount of reducing sugars in potatoes is
lamide was also shown to cross the placenta and reach the fetus, much higher than that of asparagine, controlling their level in
but no significant associations were found between prenatal the initial raw material can decrease AA formation in the fin-
dietary exposure to AA and the investigated immune-related ished fried potato products. Therefore, selecting potato vari-
health outcomes or blood parameters at any age.65 eties with low content of reducing sugars may help reduce AA,
while maintaining the desirable product qualities. For instance,
potatoes with less than 1 g/kg fresh weight of reducing sugars
Mechanism of AA Detoxification should be used for frying or roasting.75 Additionally, lower
Once ingested, AA can be detoxified in the body if it is pro- levels of AA were detected in French fries made from the
cessed through CYP450 and converted into glycidamide or if it genetically modified potatoes (innate potatoes) than in fries
is bound to the sulfur-containing antioxidant glutathione as made from conventional potatoes.76 Innate potatoes were pro-
shown in Figure 2.66 However, despite the metabolic pathways duced by silencing the asparagine synthetase-1 gene (Asn1) in
assisting in AA detoxification, it is still possible to overload the the tuber resulting in lower levels of asparagine, which in turn
detoxification capability of these pathways and create health decreases the formation of AA by 52% to 78% when fried or
risks from excess exposure.67 One way to possibly help lower baked at high temperatures.77
the risk of toxicities from AA is to increase glutathione levels The reducing sugar content in potato tubers tend to decrease
by consuming sulfur-containing foods such as onions, garlic, over the course of the growing period to reach a minimum level
and cruciferous vegetables such as broccoli and brussels toward the end of the growing season which is a good indicator
98 International Journal of Toxicology 39(2)

to harvest at the right time to reduce the potential for high AA blanched prior to enzyme application.91 A study has demon-
formation during processing.78 Acrylamide content is also strated that soaking of blanched potato strips in an asparaginase
affected by climatic conditions, where warm weather condi- solution at 40 C for 20 minutes reduced AA by 60% when
tions (above 25 C-30 C) and cold climates (below 8 C-12 C) compared with blanched strips without the enzyme treatment.91
tend to increase sugar content of potato tubers and subsequently
increase AA formation upon frying.79 Therefore, it is proposed Amino acids. Inhibition of Maillard reaction, thus reducing AA
that the optimum temperature for tuber growth ranges between formation in foods, could occur by using competitive com-
15 C and 20 C.79 pounds that are able to compete with asparagine for carbonyl
Formation of AA is also related to the storage temperature groups. In fact, the addition of amino acids before heat pro-
of potato tubers. Storing potato tubers at 8 C or lower will lead cessing of foods have been proposed as a possible strategy to
to phenomenon called “low-temperature sweetening” which reduce AA formation by competing with asparagine in the
causes an increase in reducing sugar content and enhancement Maillard reaction or reacting with AA after its formation.92
of the brown pigment during frying and hence higher amounts In one study, the formation of AA was reduced by more than
of AA.80 For heat processing, potato tubers should be stored at 80% in potato slices soaked in 3% solution of either lysine or
8 C to 12 C to avoid this increase in reducing sugar content.81 glycine prior to frying.93

Vitamins. The formation of AA was reduced by more than

Effect of Additives 60% after the addition of approximately 1% of vitamin C
and vitamin B1, whereas only 20% to 30% reduction was
Plant antioxidants. The effect of antioxidants and their extracts
found after the addition of 1% vitamin B2 and vitamin B5
on the level of AA in foods has not been investigated satisfac-
in an amino acid/sugar chemical model system.94 Up to 75%
torily. Both positive and negative results had been obtained
reduction in AA formation in french fries was found by
when food researchers tried to use natural antioxidative
dipping potato cuts in 2% citric acid solutions for 1 hour
extracts to inhibit AA formation in food. Some antioxidants
before frying; however, there might be concerns about sour
were claimed to reduce AA formation, while others did not
flavors in the resulting products.95
show any effect or showed an enhancing effect.82,83
Bioactive products extracted from plants have been shown Salt solution. Some mono- and divalent cations (eg, Naþ or
to reverse AA toxicity. For example, when rosemary extract, Ca2þ) were reported to effectively mitigate AA formation in
oil, and dried leaves were added to wheat dough, AA was food.96 For example, potatoes dipped in CaCl2 solution showed
reduced by 62%, 67%, and 57%, respectively, compared to 95% reduction in the amount of AA formed in fried potatoes
wheat buns without addition of rosemary.82 On the other hand, without negatively affecting the sensory characteristics of the
grape seed extract added to baked products did not have any strips.96 These ions interact with asparagine so that the forma-
effect on AA formation.83 Similarly, other studies found that tion of the Schiff base is inhibited, and thus AA generation
the addition of sesamol, vitamin E, and antioxidants such as during heating is reduced.96
2,6-bis (1.1-dimethylethyl)-4-methylphenol to meat before
heating led to increased AA formation.84 In a model system
based on wheat flour and water, which resembled crackers, the
use of ascorbic acid and ascorbate showed a slight reduction in Effect of Processing Conditions
AA content.85 Furthermore, the addition of bamboo leaves and
Frying Time and Temperature
green tea extracts significantly reduced AA formation in an
asparagine–glucose model system.86 Generally, frying temperature and time have been shown to
In another study, chrysin, which is a natural biologically significantly affect the amount of AA formed and are consid-
active flavonoid compound found in many plants, reduced ered to be the most critical factors affecting its content in fried
AA-induced neurotoxicity in Wistar rats due to its high potato products.97 Higher temperatures and longer duration of
antioxidant power.87 Additionally, quercetin, which is a thermal processing are associated with higher AA content.97
polyphenolic flavonoid compound, contains a spectrum of
antioxidants that are able to protect against AA-induced
neurotoxicity.88 Berry juices (bilberry, black mulberry, and Soaking
raspberry) significantly restored the growth of AA-exposed
yeast cells, Saccharomyces cerevisiae, and decreased the A simple measure of presoaking potatoes before frying can
level of reactive oxygen species.89 reduce the formation of AA.98 Washing raw french fries and
soaking them in water reduced the formation of AA if they
Enzymes. The use of asparaginase enzyme is an effective strat- were fried to a lighter color.98 This is because presoaking
egy at reducing AA formation in fried potatoes, as it catalyzes causes the glucose content in the potato strips to be reduced
the hydrolysis of asparagine to aspartic acid and ammonia with increased soaking time.98 Therefore, water soaking results
without affecting the final product aspects.90 This approach in lower AA content due to the leaching of one important AA
was found to be more significant when the raw material was precursor such as glucose.
Rifai and Saleh 99

Blanching Author Contributions

Blanching is also performed in water to reduce the level of Rifai, L. and Saleh, F. contributed to conception and design, drafted
manuscript, critically revised manuscript, gave final approval, and
reducing sugars in raw potatoes, which could result in higher
agree to be accountable for all aspects of work ensuring integrity and
AA content.99 Blanching of potato strips with sunflower oil for accuracy.
43 seconds at 150 C had a greater reduction effect on the level
of AA precursors (asparagine and reducing sugars) and thus on
the final AA level, relative to soaking in water.100 Moreover, Declaration of Conflicting Interests
blanching in hot or warm water was reported to reduce the The author(s) declared no potential conflicts of interest with respect to
amount of AA in french fries.101 As the blanching temperature the research, authorship, and/or publication of this article.
and duration increased, more glucose and asparagine are being
leached out leading to french fries with lower AA levels.101
Funding
The author(s) received no financial support for the research, author-
Effect of pH, Water Activity, ship, and/or publication of this article.
and Fermentation
Acids ORCID iD
It is widely established that pH levels influence the formation Fatima A. Saleh https://orcid.org/0000-0002-3225-3673
of AA. Lowering the pH of the soaking solution has been
shown to stop the formation of the Schiff base (the nucleophilic References
amine group (NH2) is converted to the non-nucleophilic proto-
1. Tareke E, Rydberg P, Karlsson P, et al. Analysis of acrylamide, a
nated-NH3þ) that leads to AA formation.102
carcinogen formed in heated foodstuffs. J Agric Food Chem.
2002;50(17):4998-5006.
Water Content 2. Tucker G, Featherstone S. Essentials of Thermal Processing.
The total amount of water present in foods greatly influences Hoboken, NJ: Wiley-Blackwell; 2010:288.
AA content in food. It has been found that AA is formed in 3. Mogol BA, Gökmen V. Thermal process contaminants: acryla-
foods with water activity (aw) between 0.4 and 0.8. When the mide, chloropropanols and furan. Curr Opin Food Sci. 2016;7:
water activity is <0.4, the formation of AA is decreased. Water 86-92.
activity and moisture content are 2parameters that are linked 4. Hamzalıoğlu A, Mogol BA, Gökmen V.Acrylamide: an overview
together, so foods with moisture content <5% are more likely of the chemistry and occurrence in foods. Encycl Food Chem.
to follow the Maillard reaction and form AA.97 2019;492-499.
5. Sharp D. Acrylamide in food. Lancet. 2003;361(9355):361-362.
6. Arisseto AP, Toledo MC, Govaert Y, et al. Determination of
Fermentation
acrylamide levels in selected foods in Brazil. Food Addit Contam.
Formation of AA in food was also found to be affected by 2007;24(3):236-241.
fermentation.103 For instance, lactic acid fermentation was 7. Dybing E, Farmer PB, Andersen M, et al. Human exposure and
reported to be suitable in reducing AA formation in potato internal dose assessments of acrylamide in food. Food Chem
products, especially when combined with blanching.104 Toxicol. 2005;43(3):365-410.
8. Halford NG, Curtis TY, Muttucumaru N, et al. The acrylamide
problem: a plant and agronomic science issue. J Exp Bot. 2012;
Conclusion 63(8):2841-2851.
The report made by the SNFA in April 2002 about the presence 9. World Health Organization. Guidelines for Drinking-Water Qual-
of high levels of AA in carbohydrate-rich foods processed at ity. Geneva, Switzerland: World Health Organization; 1993.
high temperature (>120 C) evoked a worldwide health alarm. 10. Ahn JS, Castle L, Clarke DB, Lloyd AS, Philo MR, Speck DR.
This announcement sparked intensive investigations into AA, Verification of the findings of acrylamide in heated foods. Food
its occurrence in foods, and its adverse health effects. At pres- Addit Contam. 2002;19(12):1116-1124.
ent, AA is considered a food-borne toxicant by many interna- 11. Westney C. Food acrylamide mystery solved. Nature. 2002.
tional organizations such as the Food and Drug Administration 12. Zhang Y, Ren Y, Zhang Y. New research developments on acry-
and WHO. Many studies described the potential health risks of lamide: analytical chemistry, formation mechanism, and mitiga-
AA; however, there is paucity of information on strategies to tion recipes. Chem Rev. 2009;109(9):4375-4397.
reduce the levels of AA in processed food. This review did not 13. Krishnakumar T, Visvanathan RKT. Acrylamide in food prod-
only present the toxicity of AA including neurotoxicity, muta- ucts: a review. J Food Process Techno. 2014;5(7):1-10.
genicity, and carcinogenicity but also focused on various ways 14. Lineback DR, Coughlin JR, Stadler RH. Acrylamide in foods: a
used in mitigating AA levels in food such as soaking, blanch- review of the science and future considerations. Annu Rev Food
ing, fermentation, enzymes, or antioxidant addition. Sci Technol. 2012;3(1):15-35.
100 International Journal of Toxicology 39(2)

15. Zyzak DV, Sanders RA, Stojanovic M, et al. Acrylamide forma- 33. Tardiff RG, Gargas ML, Kirman CR, Leigh Carson M, Sweeney
tion mechanism in heated foods. J Agric Food Chem. 2003; LM. Estimation of safe dietary intake levels of acrylamide for
51(16):4782-4787. humans. Food Chem Toxicol. 2010;48(2):658-667.
16. Stadler RH, Blank I, Varga N, et al. Acrylamide from Maillard 34. Hariri E, Abboud MI, Demirdjian S, et al. Carcinogenic and neu-
reaction products. Nature. 2002;419(6906):449-450. rotoxic risks of acrylamide and heavy metals from potato and corn
17. Mottram DS, Wedzicha BL, Dodson AT. Acrylamide is formed in chips consumed by the Lebanese population. J Food Comp Anal.
the Maillard reaction. Nature. 2002;419(6906):448-449. 2015;42(2):91-97.
18. Stadler RH. The formation of acrylamide in cereal products and 35. El-Zakhem Naous G, Merhi A, Abboud MI, Mroueh M, Taleb RI.
coffee. In: Skog K, Alexander J, eds. Acrylamide and Other Hazar- Carcinogenic and neurotoxic risks of acrylamide consumed
dous Compounds in Heat-Treated Foods. England: Woodhead through caffeinated beverages among the lebanese population.
Publishing Limited; 2006;23-40. Chemosphere. 2018;208:352-357.
19. Schieberle P, Köhler P, Granvogl M. New aspects on the forma- 36. Kopp AUS, Starnberg EK. Biotransformation and Toxicokinetics
tion and analysis of acrylamide. Chem Saf Acrylamide Food. of Acrylamide in Humans; 2009.
2005;561:205-222. 37. Zhang Y, Zhang G, Zhang Y. Occurrence and analytical methods
20. Granvogl M, Schieberle P, Granvogl M, Schieberle P. Quantifi- of acrylamide in heat-treated foods. review and recent develop-
cation of 3-aminopropionamide in cocoa, coffee and cereal prod- ments. J Chromatogr A. 2005;1075(1-2):1-21.
ucts correlation with acrylamide concentrations determined by an 38. Petersen BJ, Tran N. Exposure to acrylamide: placing exposure in
improved clean-up method for complex matrices. Eur Food Res context. Adv Exp Med Biol. 2005;561:63-76.
Technol. 2007;225(5):857-863. 39. Fennell TR, Friedman MA. Comparison of acrylamide metabo-
21. Parker JK, Balagiannis DP, Higley J, et al. Kinetic model for the lism in humans and rodents. Adv Exp Med Biol. 2005;561:
formation of acrylamide during the finish-frying of commercial 109-116.
french fries. J Agric Food Chem. 2012;60(36):9321-9331. 40. Sörgel F, Weissenbacher R, Kinzig-Schippers M, et al. Acryla-
22. Dearfield KL, Douglas GR, Ehling UH, et al. Acrylamide: a mide: increased concentrations in homemade food and first evi-
review of its genotoxicity and an assessment of heritable genetic dence of its variable absorption from food, variable metabolism
risk. Mutat Res. 1995;330(1-2):71-99. and placental and breast milk transfer in humans. Chemotherapy.
23. Mojska H, Gielecińska I, Cendrowski A. Acrylamide content in 2002;48(6):267-274.
cigarette mainstream smoke and estimation of exposure to acry- 41. Miller MJ, Carter DE, Sipes IG. Pharmacokinetics of acrylamide
lamide from tobacco smoke in Poland. Ann Agric Environ Med. in fisher-334 rats. Toxicol Appl Pharmacol. 1982;63(1):36-44.
2016;23(3):456-461. 42. Sumner SC, Fennell TR, Moore TA, et al. Role of cytochrome
24. McAdam K, Kimpton H, Vas C, et al. The acrylamide content of P450 2E1 in the metabolism of acrylamide and acrylonitrile in
smokeless tobacco products. Chem Cent J. 2015;9(1):56. mice. Chem Res Toxicol. 1999;12(11):1110-1116.
25. Kim H, Lee SG, Rhie J. Dermal and neural toxicity caused by 43. Boettcher MI, Schettgen T, Kütting B, et al. Mercapturic acids of
acrylamide exposure in two Korean grouting workers: a case acrylamide and glycidamide as biomarkers of the internal expo-
report. Ann Occup Environ Med. 2017;29:50. sure to acrylamide in the general population. Mutat Res. 2005;
26. Wong KA. Screening for Acrylamide Levels in French Fries 580(1-2):167-176.
Using Portable Vibrational Spectrometers. Columbus, OH: The 44. Vesper HW, Slimani N, Hallmans G, et al. Cross-sectional study
Ohio State University; 2017. on acrylamide hemoglobin adducts in subpopulations from the
27. Fodor IK, Nita A, Felicia D, et al. Acrylamide, the health enemy European prospective investigation into cancer and nutrition
from food products that are processed at high temperatures. Ana- (EPIC) study. J Agric Food Chem. 2008;56(15):6046-6053.
lele Universitatii din Oradea, Fascicula: Ecotoxicologie, Zooteh- 45. Schettgen T, Kütting B, Hornig M, et al. Trans-placental exposure
nie si Tehnologii de Industrie Alimentara. 2015;14:157-164. of neonates to acrylamide—a pilot study. Int Arch Occup Environ
28. Food and Agriculture Organization/World Health Organization. Health. 2004;77(3):213-216.
Code of Practice for the Reduction of Acrylamide in Foods; 2009. 46. Miller MS, Spencer PS. The mechanisms of acrylamide axono-
29. Mojska H, Gielecińska I. Studies of acrylamide level in coffee and pathy. Annu Rev Pharmacol Toxicol. 1985;25(1):643-666.
coffee substitutes: influence of raw material and manufacturing 47. World Health Organization. Acrylamide levels in food should be
conditions. Rocz Panstw Zakl Hig. 2013;64(3):173-181. reduced because of public health concern says UN expert com-
30. Stadler RH, Lineback DR. Process-Induced Food Toxicants: mittee. Geneva, Switzerland: World Health Organization; 2010.
Occurrence, Formation, Mitigation, and Health Risks. Hoboken, 48. Liu Z, Song G, Zou C, et al. Acrylamide induces mitochondrial
NJ: Wiley; 2009. dysfunction and apoptosis in BV-2 microglial cells. Free Radic
31. Chuang WH, Chiu CP, Chen BH. Analysis and formation of Biol Med. 2015;84:42-53.
acrylamide in french fries and chicken legs during frying. J Food 49. Chen JH, Chou CC. Acrylamide inhibits cellular differentiation of
Biochem. 2006;30(5):497-507. human neuroblastoma and glioblastoma cells. Food Chem Toxi-
32. Adewale OO, Brimson JM, Odunola OA, et al. The potential for col. 2015;82:27-35.
plant derivatives against acrylamide neurotoxicity. Phytother Res. 50. He FS, Zhang SL, Wang HL, et al. Neurological and electroneur-
2015;29(7):978-985. omyographic assessment of the adverse effects of acrylamide on
Rifai and Saleh 101

occupationally exposed workers. Scand J Work Environ Health. 67. Ubaoji KI, Orji VU. A review on acrylamide in foods: sources and
1989;15(2):125-129. implications to health. Mgbakoigba: J Afr Stud. 2016;6(1):1-17.
51. Calleman CJ, Wu Y, He F, et al. Relationships between biomar- 68. Kraus D, Rokitta D, Fuhr U, et al. The role of human cytochrome
kers of exposure and neurological effects in a group of workers P450 enzymes in metabolism of acrylamide in vitro. Toxicol
exposed to acrylamide. Toxicol Appl Pharmacol. 1994;126(2): Mech Methods. 2013;23(5):346-351.
361-371. 69. Joint FAO/WHO Food Standards Programme Codex Committee.
52. Hagmar L, Törnqvist M, Nordander C, et al. Health effects of Food Additives and Contaminants. Thirty-sixth Session. Geneva,
occupational exposure to acrylamide using hemoglobin adducts Switzerland: WHO; 2003.
as biomarkers of internal dose. Scand J Work Environ Health. 70. Agenda Item 6 (b) Joint FAO/WHO Food Standards Programme
2001;27(4):219-226. Codex Committee. Paper presented at: Food Additives and con-
53. Alzahrani HAS. Protective effect of l-carnitine against taminants: working document for information and support to the
acrylamide-induced DNA damage in somatic and germ cells of discussion on the general standard for food additives, Thirty-
mice. Saudi J Biol Sci. 2011;18(1):29-36. eighth Session; April 24-28, 2006; The Hague, the Netherlands.
54. Exon JH. A review of the toxicology of acrylamide. J Toxicol 71. Porto ACV, Freitas-Silva O, Souza EFDE, Gottschalk LMF.
Environ Health B Crit Rev. 2006;9(5):397-412. Effect of asparaginase enzyme in the reduction of asparagine in
55. Zamani E, Shokrzadeh M, Fallah M, Shaki F. A review of acry- green coffee. Beverages. 2019;5(2):32.
lamide toxicity and its mechanism. Pharm Biomed Res. 2017; 72. Lachenmeier DW, Schwarz S, Teipel J, et al. Potential Antago-
3(1):1. nistic effects of acrylamide mitigation during coffee roasting on
56. Kumar J, Das S, Teoh SL. Dietary acrylamide and the risks of furfuryl alcohol, furan and 5-hydroxymethylfurfural. Toxics.
developing cancer: facts to ponder. Front Nutr. 2018;5:14. 2019;7(1):E1.
57. Sobel W, Bond GG, Parsons TW, et al. Acrylamide cohort mor- 73. Amrein TM, Bachmann S, Noti A, et al. Potential of acrylamide
tality study. Br J Ind Med. 1986;43(11):785-788. formation, sugars, and free asparagine in potatoes: a comparison
58. Marsh GM, Youk AO, Buchanich JM, et al. Long-term health of cultivars and farming systems. J Agric Food Chem. 2003;
51(18):5556-5560.
experience of jet engine manufacturing workers: VI: incidence
74. Olsson K, Svensson R, Roslund C-A. Tuber components affecting
of malignant central nervous system neoplasms in relation to
acrylamide formation and colour in fried potato: variation by
estimated workplace exposures. J Occup Environ Med. 2007;
variety, year, storage temperature and storage time. J Sci Food
49(1):82-95.
Agric. 2004;84(5):447-458.
59. Thonning Olesen P, Olsen A, Frandsen H, et al. Acrylamide
75. Fiselier K, Grob K. Legal limit for reducing sugars in prefabri-
exposure and incidence of breast cancer among postmenopausal
cates targeting 50 mg/kg acrylamide in French fries. Eur Food Res
women in the Danish diet, cancer and health study. Int J Cancer.
Technol. 2005;220(5-6):451-458.
2008;122(9):2094-2100.
76. Waltz E. USDA approves next-generation GM potato. Nat Bio-
60. Hogervorst JG, Schouten LJ, Konings EJ, et al. A prospective
technol. 2015;33(1):12-13.
study of dietary acrylamide intake and the risk of endometrial,
77. Plant Breeding | White Russet Potato | Innate ® Potato |
ovarian, and breast cancer. Cancer Epidemiol Biomarkers Prev.
InnatePotato.
2007;16(11):2304-2313. 78. Muttucumaru N, Powers SJ, Elmore JS, et al. Acrylamide-
61. Fatehyab Ali S, Hong JS, Wilson WE, et al. Effect of acrylamide forming potential of potatoes grown at different locations, and
on neurotransmitter metabolism and neuropeptide levels in sev- the ratio of free asparagine to reducing sugars at which free
eral brain regions and upon circulating hormones. Arch Toxicol. asparagine becomes a limiting factor for acrylamide formation.
1983;52(1):35-43. Food Chem. 2017;220:76-86.
62. Wei Q, Li J, Li X, et al. Reproductive toxicity in acrylamide- 79. Kumar D, Singh BP, Kumar P. An overview of the factors affect-
treated female mice. Reprod Toxicol. 2014;46:121-128. ing sugar content of potatoes. Ann Appl Biol. 2004;145(3):
63. Ansar S, Siddiqi J, Zargar S, et al. Hepatoprotective effect of 247-256.
Quercetin supplementation against Acrylamide-induced DNA 80. Chuda Y, Ono H, Yada H, et al. Effects of physiological changes
damage in Wistar rats. BMC Complement Altern Med. 2016; in potato tubers (Solanum tuberosum L.) after low temperature
16(1):327. storage on the level of acrylamide formed in potato chips. Biosci
64. Fang J, Liang CL, Jia XD, et al. Immunotoxicity of acrylamide in Biotechnol Biochem. 2003;67(5):1188-1190.
female BALB/c mice. Biomed Environ Sci. 2014;27(6):401-409. 81. De Wilde T, De Meulenaer B, Mestdagh F, et al. Influence of
65. Annola K, Karttunen V, Keskirahkonen P, et al. Transplacental storage practices on acrylamide formation during potato frying.
transfer of acrylamide and glycidamide are comparable to that J Agric Food Chem. 2005;53(16):6550-6557.
of antipyrine in perfused human placenta. Toxicol Lett. 2008; 82. Hedegaard RV, Granby K, Frandsen H, et al. Acrylamide in
182(1-3):50-56. bread. effect of prooxidants and antioxidants. Eur Food Res Tech.
66. Sen A, Ozgun O, Arinç E, et al. Diverse action of acrylamide on 2008;227(2):519-525.
cytochrome P450 and glutathione S-transferase isozyme activi- 83. Açar OC, Gökmen V. Investigation of acrylamide formation on
ties, mRNA levels and protein levels in human hepatocarcinoma bakery products using a crust-like model. Mol Nutr Food Res.
cells. Cell Biol Toxicol. 2012;28(3):175-186. 2009;53(12):1521-1525.
102 International Journal of Toxicology 39(2)

84. Tareke E. Identification and Origin of Potential Background 94. Wang X, Xu L. Influence factors on the formation of acrylamide
Carcinogens: Endogenous Isoprene and Oxiranes, Dietary in the amino acid/sugar chemical model system. J Food Nutr
Acrylamide. Stockholm, Sweden: Stockholm University; Res. 2014;2(7):344-348.
2003. 95. Jung MY, Choi DS, Ju JW. A novel technique for limitation of
85. Levine RA, Smith RE. Sources of variability of acrylamide acrylamide formation in fried and baked corn chips and in french
levels in a cracker model. J Agric Food Chem. 2005;53(11): fries. J Food Sci. 2003;68(4):1287-1290.
4410-4416. 96. Gökmen V, Şenyuva HZ. Acrylamide formation is prevented by
86. Zhang Y, Ying T, Zhang Y. Reduction of acrylamide and its divalent cations during the Maillard reaction. Food Chem. 2007;
kinetics by addition of antioxidant of bamboo leaves (AOB) and 103(1):196-203.
extract of green tea (EGT) in asparagine-glucose microwave heat- 97. Gökmen V, Palazoğlu TK. Acrylamide formation in foods dur-
ing system. J Food Sci. 2008;73(2):C60-C66. ing thermal processing with a focus on frying. Food Bioprocess
87. Mehri S, Veis Karami H, Vahdati Hassani F, et al. Chrysin Tech. 2008;1(1):35-42.
reduced acrylamide-induced neurotoxicity in both in vitro and 98. Pedreschi F, Kaack K, Granby K. Reduction of acrylamide for-
in vivo assessments. Iran Biomed J. 2014;18(2):101-106. mation in potato slices during frying. LWT Food Sci Tech. 2004;
88. Uthra C, Shrivastava S, Jaswal A, Sinha N, Reshi MS, Shukla 37(6):679-685.
S. Therapeutic potential of quercetin against acrylamide 99. Andersson A, Lund U. Modelling of Potato Blanching. Lund,
induced toxicity in rats. Biomed Pharmacother. 2017;86: Sweden: University of Lund; 1994.
705-714. 100. Brunton NP, Gormley R, Sinn M, Butler F, Cummins E, Keefee
89. Maslanka R, Zadrag-Tecza R, Kwolek K, et al. The effect MO. Effect of pre-treatments, frying temperature and oven
of berry juices on the level of oxidative stress in yeast cells re-heating on the acrylamide content and quality characteristics
exposed to acrylamide. J Food Biochem. 2016;40(5): of French fries from “Rooster” potato tubers. Glob Sci Books.
686-695. 2009;76-81.
90. Medeiros Vinci R, Mestdagh F, Van Poucke C, et al. Implemen- 101. Pedreschi F, Kaack K, Granby K, Troncoso E. Acrylamide
tation of acrylamide mitigation strategies on industrial production reduction under different pre-treatments in French fries. J Food
of french fries: challenges and pitfalls. J Agric Food Chem. 2011; Eng. 2007;79(4):1287-1294.
59(3):898-906. 102. Mestdagh F, Maertens J, Cucu T, et al. Impact of additives to
91. Pedreschi F, Kaack K, Granby K. The effect of asparaginase on lower the formation of acrylamide in a potato model system
acrylamide formation in French fries. Food Chem. 2008;109(2): through pH reduction and other mechanisms. Food Chem.
386-392. 2008;107(1):26-31.
92. Morales F, Capuano E, Fogliano V. Mitigation strategies to 103. Fredriksson H, Tallving J, Rosén J, Åman P. Fermentation
reduce acrylamide formation in fried potato products. Ann N Y reduces free asparagine in dough and acrylamide content in
Acad Sci. 2008;1126:89-100. bread. Cereal Chem J. 2004;81(5):650-653.
93. Heong TTTH, Tae T, Ae AE, et al. Reducing acrylamide in fried 104. Baardseth P, Blom H, Skrede G, et al. Lactic acid fermentation
snack products by adding amino acids. J Food Sci. 2005;70(5): reduces acrylamide formation and other Maillard reactions in
C354-C358. french fries. J Food Sci. 2006;71(1):C28-C33.

View publication stats