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Aldehydes’ Sources, Toxicity, Environmental Analysis, and Control in Food

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Aldehydes’ Sources, Toxicity,
Environmental Analysis, and Control
in Food

Mahmoud H. El-Maghrabey, Rania El-Shaheny, Mohamed A. El Hamd,

Lateefa A. Al-Khateeb, Naoya Kishikawa, and Naotaka Kuroda

Abstract Aldehydes are highly reactive carbonyl compounds that are widespread
in the nature. Aldehydes are broadly distributed in the indoor and outdoor environ-
ment sourced from the industrial, restaurant, and motor vehicular exhausts. Besides,
aldehydes are thought to be a major cause of the photochemical smog in the air.
Aldehydes are also present in rainwater and the surface water due to their washing
away from the atmosphere owing to their high-water solubility. In addition, micro-
bial or photochemical degradation of organic chemicals leads to the formation of
aldehydes in the surface water. Furthermore, chlorination and ozonation steriliza-
tion of drinking water lead to aldehydes’ formation. On the other hand, aldehydes
could be formed during cooking upon high-temperature frying and also could be

M. H. El-Maghrabey ()
Department of Pharmaceutical Analytical Chemistry, Faculty of Pharmacy, Mansoura
University, Mansoura, Egypt
Graduate School of Biomedical Sciences, Course of Pharmaceutical Sciences, Nagasaki
University, Nagasaki, Japan
e-mail: [email protected]
R. El-Shaheny
Department of Pharmaceutical Analytical Chemistry, Faculty of Pharmacy, Mansoura
University, Mansoura, Egypt
M. A. El Hamd
Department of Pharmaceutical Analytical Chemistry, Faculty of Pharmacy, South Valley
University, Qena, Egypt
Department of Pharmaceutical Sciences, College of Pharmacy, Shaqra University,
Al Dawadmi, Shaqra, Kingdom of Saudi Arabia
L. A. Al-Khateeb
Department of Chemistry, Faculty of Science, King Abdulaziz University,
Jeddah, Kingdom of Saudi Arabia
N. Kishikawa · N. Kuroda
Graduate School of Biomedical Sciences, Course of Pharmaceutical Sciences, Nagasaki
University, Nagasaki, Japan

© The Author(s), under exclusive license to Springer Nature Switzerland AG 2022 117
M. Vasanthy et al. (eds.), Organic Pollutants, Emerging Contaminants and Associated
Treatment Technologies, https://doi.org/10.1007/978-3-030-72441-2_5
118 M. H. El-Maghrabey et al.

sourced from cigarette smoke and/or other combustion operations. Besides, alde-
hydes are present in wine and vegetable oils, and they are formed as by-products
during deterioration, maturing, or microbial fermentation of food. Human exposure
to aldehydes from the environment or food could bring many adverse health effects
either acute or chronic ones. Aldehydes are highly reactive with biological mole-
cules; thus, they are considered highly toxic. The aldehydes’ biochemical modifica-
tion could lead to the disruption of biological functions, and consequently, cause
many diseases. Thus, aldehyde monitoring in the surrounding environmental and
food samples is vital to control the toxic aldehydes’ possible health risk on humans.
Aldehydes’ different sources in the environment, molecular toxicity mechanisms,
possible effects on human health, and recently developed analytical methods for
determination and control of aldehydes in environmental and food samples will be
summarized in this chapter.

Keywords Aldehydes’ sources · Environmental sources · Aldehydes in food ·

Human exposure · Aldehydes’ toxicity · Toxicity mechanisms · Environmental
analysis · Food analysis

1 Introduction

Aldehydes are highly reactive naturally ubiquitous carbonyl compounds that are
widespread in the surrounding indoor and outdoor environments. They are classi-
fied according to their side chain into different categories including saturated alde-
hydes (e.g., alkanals), unsaturated aldehydes (e.g., alkenals, oxo-alkenals,
hydroxy-alkenals, and dialkenals), dialdehydes (malondialdehyde (MDA) and gly-
oxal (Gly)), and aromatic aldehydes (e.g., benzaldehyde, cinnamaldehyde, vanillin,
and anisaldehyde). The chemical structures of different kinds of aldehydes are
shown in Fig. 1.
Environment aldehydes are sourced from industrial activities, and exhausts from
restaurants and stores kitchens, and motor vehicles. Additionally, most of the alde-
hydes are hydrophilic compounds; thus, they are washed away from the atmosphere
into rainwater and surface water. Another source for aldehydes in the surface water
is the microbial and photochemical degradation of some chemical compounds that
are spread in nature (Zhang et al., 1994a; Altemose et al., 2015; Kuykendall, 2010).
Besides, aldehydes are also formed inside the human body mainly through lipid
peroxidation, and to a smaller extent from autoxidation of carbohydrate and ascor-
bate, and as reaction products of oxidases, peroxidases, and some metabolic
enzymes (Kuykendall, 2010). In addition, aldehydes are present in many foods
including many fruits and vegetables (e.g., acetaldehyde), cinnamon and peas (e.g.,
cinnamaldehyde), almonds and cherries (e.g., benzaldehyde), anise extract (e.g.,
anisaldehyde), and vanilla extract (e.g., vanillin). Furthermore, aldehydes are
employed as additives in cosmetics, detergents, and food industries (e.g., C7–C13
Aldehydes’ Sources, Toxicity, Environmental Analysis, and Control in Food 119

Fig. 1 The chemical structures of different categories of aldehydes

aliphatic aldehydes, benzaldehyde, 4-hydroxybenzaldehyde, cinnamaldehyde,

anisaldehyde, vanillin, and furfural) (O’Brien et al., 2005; Feron et al., 1991).
Aliphatic and aromatic aldehydes have also been identified in drinking water
sourced from leakage from surface water. Additionally, aromatic aldehydes and
alpha ketoaldehydes were detected in many beverages (Cancho et al., 2002; Serrano
et al., 2013a; Osório & Cardeal, 2013; Lachenmeier et al., 2013). Besides, aldehy-
dic function group exists in some antibiotics such as tylosin, josamycin, streptomy-
cin, and spiramycin. Furthermore, some anticancer agents, such as cyclophosphamide
and ifosfamide, produce the reactive toxic aldehyde acrolein and crotonaldehyde,
upon their metabolism, causing neurotoxicity and hemorrhagic cystitis (O’Brien
et al., 2005; Sood & O’Brien, 1996). In the same context, the medicinal drugs
120 M. H. El-Maghrabey et al.

sudoxicam, felbamate, misonidazole, and abacavir were found to be metabolized

also into reactive aldehydes, such as Gly, atropaldehyde, or reactive aldehydes inter-
mediate, causing various side effects including hepatotoxicity and aplastic anemia
(O’Brien et al., 2005; Kapetanovic et al., 2002; Heimbrook & Sartorelli, 1986;
Walsh et al., 2002). As can be seen, aldehydes surround us everywhere, in the envi-
ronment, in food, in beverages, and even in some medicines, in addition to their
in vivo formation through various oxidative and metabolic processes. Meanwhile,
aldehydes are very reactive due to the presence of the polarized carbon-oxygen
double bond imparting them substantial dipole moments resulted from the high dif-
ference in electronegativity between the oxygen and carbon atoms. Thus, the carbon
atom possesses high electrophilicity rendering it very reactive toward nucleophilic
sites such as nucleotide bases and protein amino acids producing many toxic effects
inside the human body when present in high concentration. This reactivity and tox-
icity are augmented in α,β-unsaturated aldehyde, such as acrolein and crotonalde-
hyde, as the double bond is conjugated with the carbonyl group, employing positive
polarization for the β-carbon; thus, it becomes another site for nucleophilic attacks.
Furthermore, the presence of γ-hydroxy group substitution with electron-­
withdrawing power, such as in 4-hydroxy-2-nonenal (HNE) and 4-hydroxy-2-­
hexenal (HHE), employs more electrophilicity to the β-carbon (Feron et al., 1991;
McMurry, 1984) making these aldehydes more reactive and more dangerous. Given
these facts, the main objective of this chapter is to summarize and discuss different
sources of aldehydes in the environment and food, possible effects on human health,
their molecular toxicity mechanisms, and recently reported method for analysis and
control of aldehydes in environmental and food samples.

2 Aldehydes’ Sources in the Environment and Food

Aldehydes are emitted indoor and outdoor and released into the environment and
act as dangerous pollutants as they cause adverse health effects on humans in rural
and even in urban areas (Araki et al., 2020). They are produced either naturally or
due to industrial activity. Also, they are present in many kinds of foods. Their
sources will be discussed in detail in the following sections.

2.1 Natural Environmental Source of Aldehydes

Naturally, aldehydes are resulted from the photooxidation of volatile organic hydro-
carbons that are produced from the metabolism of the plants. They are released from
the dark reactions of ozone with any volatile organic compound (VOC), which con-
tains unsaturated carbon-carbon bonds (unsaturated VOCs), as well as organic acids
(Zhang et al., 1994b; Villanueva et al., 2015). The unsaturated VOCs include ben-
zene, ethylbenzene, limonene, p-dichlorobenzene, styrene, toluene, and xylene, and
Aldehydes’ Sources, Toxicity, Environmental Analysis, and Control in Food 121

many of them are present in paints, thinners, adhesive agents, printing inks, clean-
ing agents, and petrochemical oils such as gasoline and kerosene (Araki et al., 2020;
Kanazawa et al., 2010). According to their boiling points (BPs) and volatility,
Godish T. classified these VOCs into very volatile organic compounds that have BP
ranged from <0 °C to 50–100 °C, volatile organic compounds with BP ranged from
50–100 °C to 240–260 °C, semi-volatile organic compounds with BP ranged from
240–260 °C to 380–400 °C, and particulate organic matter with boiling points above
380 °C (Godish, 2016). Unfortunately, these compounds and their products of alde-
hydes have many adverse health impacts including irritation, wheezing, and other
common allergic symptoms, according to the World Health Organization, 2009
guidelines for indoor quality (Heseltine & Rosen, 2009).

2.2 Industrial Sources of Aldehydes

Aldehydes are also derived from urban and industrial activities such as biomass
burning, fossil fuel combustion, and household activities (Nguyen et al., 2020).
Aldehydes enter as raw materials or additives in many industrial activities including
the manufacturing of building materials, flooring wallpaper, adhesives, and furni-
ture (Zhang et al., 2020). Aldehydes are exchanged in the indoor and outdoor air;
however, their indoor levels are generally more than that of outdoor levels (Gilbert
et al., 2008). The indoor air aldehydes’ pollution has a major public health concern
due to the continued elevation in their indoor level and at the same time, general
populations spend most of their time in indoor environments. Aldehydes and other
VOCs were reported to be emitted from building materials, and they are considered
as a major source of sick building syndrome (Takeda et al., 2009; Takigawa et al.,
2010, 2012). Also, cleaning and maintenance agents, furniture, paints, particle
boards, fabrics, carpets, and others were the main sources of the increased levels of
indoor as a local emission of aldehydes more than outdoor (O’Brien et al., 2005;
Brown, 1999). Therefore, due to the known hazardous effects of aldehydes and
VOCs on humans, the World Health Organization (WHO) set a guideline to prevent
their health risks. In addition, in Japan, the Ministry of Health, Labor, and Welfare
developed air quality guidelines for formaldehyde and 12 VOCs (Araki et al., 2020;
Heseltine & Rosen, 2009).
The circulated anthropogenic aldehydes are mainly formaldehyde and acetalde-
hyde. Relatively, formaldehyde is the most abundant aldehyde in indoor air com-
pared to its presence in outdoor air, followed by acetaldehyde (Zhang et al., 1994a).
Zhang et al. (1994a), and Baez et al. (2003) reported that aldehydes are present in
high concentrations (2–10 times) in indoor than their presence in outdoor, related to
the multiple varieties in the sources of aldehydes in indoor air such as direct emis-
sions and chemical formation than their sources in outdoor air. Moreover, tempera-
ture, humidity, and the low air exchange rates in the indoor environment resulted in
high concentrations of aldehydes and total VOCs more than that of the outdoor ones
(Zhang et al., 2020; Salthammer et al., 1995; Chi et al., 2016). On the other hand,
122 M. H. El-Maghrabey et al.

the outdoor VOC concentrations are affected by season and temperature which indi-
rectly affect the presence of the total aldehydes, as well as proximity to emission
sources such as industry, traffic and gas stations, and meteorology, such as mixing
height, wind speed, and precipitation (Kwon et al., 2006; Jia et al., 2008; Cheng
et al., 1997).
The sources of aldehydes in the urban areas are motor vehicle wastes in air,
either via direct aldehydes emission, or indirect through hydrocarbon emission,
which then undergo photochemical oxidation and converts into aldehydes (Cecinato
et al., 2002; Destaillats et al., 2002). The urban areas’ vehicular fleet involved the
vehicles fueled with hydrated ethanol, gasohol (gasoline and anhydrous ethanol
mixed in a ratio of about 4:1), and diesel, as reported in a study in Londrina (Pinto
& Solci, 2007). In these fuel hydrocarbons, the oxidation and/or ring breaking of
benzene, ethylbenzene, toluene, and xylenes in the internal combustion motor or the
exhaust gave the largest carbonyl emissions, as a source for aldehydes and other
pollutants. O’Brien et al. (O’Brien et al., 2005) divided these carbonyl emissions
into four groups according to their chemical structure, namely, alkanals, alkenals,
aromatic aldehydes, and α-oxoaldehydes. The chemical structures of these types of
aldehydes are illustrated previously in Fig. 1. The crowdedness in the urban areas
allowed aldehyde to be present in residential, workplace environments, and the con-
fined spaces as spacecraft and airline cabins (National Research Council, 2002).
Modern industrial settings use aldehydes as raw materials or they are released dur-
ing the manufacturing process as a source of humans to be exposed to aldehydes. In
different synthetic products such as resins, resin coating, lubricating oils, polyure-
thane, polyester plastics, and plasticizers, formaldehyde is used in their manufac-
ture (O’Brien et al., 2005).
The sources of aldehydes in the rural areas are hydrocarbons’ photooxidation
and ozonolysis, especially for the naturally emitted one, named as nonmethane
(Rottenberger et al., 2004). For this reason, aldehydes are thought to be a major
player in the formation of air photochemical smog (Granby et al., 1997). The burn-
ing processes, such as the agriculture productions, photochemical decomposition of
hydrocarbons and other organics in the air, and incomplete combustion of oxygen-
ated fuels in engines, resulted in increased emissions of aldehydes in indoor air
(Pinto & Solci, 2007). Moreover, naturally generated through tropospheric reac-
tions of the terpenes and isopropene emitted by foliage also react with hydroxyl
radicals to contribute to the formation of aldehydes (O’Brien et al., 2005; Leikauf,
2020). The rural areas are apart from the industrial operations; therefore, they
receive minimal impact from local anthropogenic sources of aldehydes, just from
alcohols incomplete combustion or polymeric materials aldehydes leakages.
In both rural and urban areas, cooking oil fumes, which are a mixture of chemi-
cals contain aldehydes (acrolein, and t,t-2,4-decadienal), acid, alcohol, and polycy-
clic aromatic hydrocarbons (e.g., benzo(a)pyrene) (Peng et al., 2017), are suspected
as indoor pollutant carcinogens. These fumes were emitted from high-temperature
frying and classified as group 2 A by the International Agency of Research on
Cancer (IARC WHO, 2017). Aldehydes are the major components in cooking oil
fumes, as they are produced by the decomposition of the fatty acids of the cooking
Aldehydes’ Sources, Toxicity, Environmental Analysis, and Control in Food 123

oils at the cooking temperature (Fullana et al., 2004a; Lin & Liou, 2000; da Silva &
Pereira, 2008; Katsuta et al., 2008).
Another source of aldehydes is cigarette smoke which is considered a potential
risk for indoor aldehyde pollution (Baez et al., 2003). Acetaldehyde is the major
component of the cigarette smoke with a concentration of 709μg/cigarette, followed
with acrolein (82μg/cigarette), then formaldehyde (54μg/cigarette), and then cro-
tonaldehyde (15μg/cigarette) (O’Brien et al., 2005). In general, the released alde-
hydes from cigarette smokers are categorized into a mainstream (the part inhaled by
the smoker), a side-stream (a part released from the burning cigarette), and an envi-
ronmental (indoor or/and outdoor) tobacco smoke (a combination of the smoke of
aged side-stream and breathed out mainstream). It was found that acetaldehyde is
the most abundant saturated aldehydes in environmental tobacco smoke, followed
by formaldehyde and propionaldehyde. As the smokers inhale about less than 50%
of each cigarette, therefore, the side-stream smoke could be a significant contributor
to the indoor aldehyde release (Fujioka & Shibamoto, 2006; Stabbert et al., 2017).
In order to overcome this problem, alternative electronic cigarettes (e-cigarettes),
have been activated in the United States in 2007, to decrease the indoor smoking
restrictions. These were analyzed to assess their potential health impacts, compared
to the standard tobacco cigarettes. For all by-products measured in e-cigarettes, the
results revealed that they considerably lowered the level of aldehydes and they
could help in the decrease of the indoor aldehyde pollutants (McAuley et al., 2012).
Regarding the aqueous environment, the formaldehyde concentrations have been
reported to be about 1.38 mg/L, 6.8 mg/L, and less than 0.1 mg/L in rainwater, fog
water, and in drinking water, respectively (O’Brien et al., 2005). The presence of
formaldehyde in rainwater is from its scavenging from the gas phase and aerosol on
which formaldehyde is absorbed in the polluted areas and has no correlation with
rainfall.
Aldehydes are washed away from the atmosphere into the rainwater and surface
water due to their high solubility in water. Furthermore, the natural microbial and
photochemical degradation of organic chemicals could lead to the formation of
aldehydes in the surface water. An aqueous photoproduction of dissolved organic
compounds, absorption from the gas phase, transportation on the regional scale, and
degradation such as the activity of microorganisms, all resulted in the existence of
different types of aldehydes, especially formaldehyde, in rainwater (Southwell
et al., 2010).

2.3 Aldehydes’ Sources in Food and Cosmetics

The reactive aldehyde, formaldehyde, is present in the fish and seafood naturally
resulted from some oxidative enzyme reactions, such as amine oxidases and the
oxidation of lipids by some microorganism activities. Besides, formaldehyde is pro-
duced also inside the frozen fish due to the breakdown of trimethylamine into
dimethylamine and formaldehyde (Cui et al., 2007; Gram et al., 2002; Arashisar
124 M. H. El-Maghrabey et al.

et al., 2004). Furthermore, aldehydes are usually used in the form of formalin (37%
formaldehyde), as a preservative for meats and frozen fishes, to extend the shelf life
and stiffness and to preserve their fresh look for a longer time (Jaman et al., 2015;
Kibria, 2007). As fish is a favorite diet in different areas, the presence of formalin
contributes to the accumulation of formaldehyde more than the carcinogenic thresh-
old to humans (LD50 30 gm) (Jaman et al., 2015). Improper freezing and time-­
consuming transport force the sellers of fish to indulge in malpractices, as they dip
the whole fish in or inject their body cavities with formalin or spread formalin mixed
water as a preservative (Bhowmik et al., 2020; Sumon et al., 2020).
Moreover, aldehydes have a sensory relevance to be added to the most foodstuff
products (e.g., cheese, seafood, and meat), usually added in low concentration and
in limited types. Moreover, the presence of certain aldehydes could be an indication
of temperature overheating, microbial fermentation, quality deterioration, and off-­
flavor (Schultheiss et al., 2000). Alcohols (methanol, ethanol) are present in vegeta-
bles, fruits, fruit juices, and fermented beverages (a substantial amount of ethanol or
contaminated with methanol) (Ohimain, 2016). They are converted in vivo to alde-
hydes (mainly, formaldehyde and acetaldehyde) through the action of dehydroge-
nase enzymes. As well, aspartame (an artificial sweetener) undergoes intestinal
conversion forming aspartic acid-methyl ester (10% of all compounds), then upon
further hydrolysis of the methyl ester, methanol is formed and which is then trans-
ported through the portal vein to the liver (Hill & Belsito, 2003). Methanol is then
oxidized to formaldehyde and formic acid by alcohol and aldehyde dehydrogenases,
and microsomal oxidases. Regarding acetaldehyde, it is either naturally present or
added as a flavoring substance to many fluids such as vegetables and fruits, and
alcoholic products.
As we mentioned previously, the cooking of fat-containing foods or frying using
oil or fats could produce acetaldehyde, formaldehyde, and acrolein (Kundu et al.,
2020; Lynch et al., 2008; Zamora et al., 2015). Many other common foods and soft
drinks have different types of aldehydes and their derivatives, such as peas (contain
acetaldehyde), cherries and almonds (contain benzaldehyde and hexanal, during
their unripe seeds), cinnamon (contains cinnamaldehyde), anise (contains anisalde-
hyde), and vanilla extracts (contain anisaldehyde and vanillin). The environmental
aldehydes are mainly represented by formaldehyde, but the dietary aldehydes have
multiple forms and with variable concentration levels (O’Brien et al., 2005; Hellwig
et al., 2018).
Other sources of aldehyde pollution are cosmetics and hair salons, as aldehydes,
especially formaldehyde, are used there as fumigating agents. Different regulatory
practices are set for cosmetics, in which formaldehyde is used as a preservative, as
it is highly biocidal, pungent, and skin-irritant (Wu et al., 2003).
In conclusion, aldehydes in food could be classified according to their sources
and concentrations in brief into the following:
1. Aldehydes derived from phospholipid and fatty acid hydroperoxide decomposi-
tion, namely, alkanals, alkenals, hydroxyalkenals, glycolaldehyde, Gly, and
acrolein (from cooked vegetables). They are formed endogenously through lipid
Aldehydes’ Sources, Toxicity, Environmental Analysis, and Control in Food 125

peroxidation of the food products (Spiteller, 2001), mainly vegetables and fruits.
They distribute their aldehydes in vivo through the enzymatical hydrolysis of
their unsaturated fatty acids with lipoxygenase-hydroperoxide lyases (Gardner
et al., 2004).
2. Aldehydes and ketones derived from monoterpene of essential oils of some
odoriferous plants. They are mainly added to foodstuff and beverages as flavor-
ing additives (Baines & Seal, 2012). An example of these monoterpenes alde-
hydes is citral, a reactive alkenal present in all citrus fruits and forms about 3%
of lemon peel essential oil (Cimanga et al., 2002; Umano et al., 2002). Citral is
commonly used as an additive flavor agent in cosmetics, detergents, and some
sweet food industries, after its approval from the US Food and Drugs
Administration (FDA) as safe additive “generally recognized as safe, GRAS
182.10 coding” (Mori et al., 2019).
3. Aromatic aldehydes, such as benzaldehydes, cinnamaldehyde, salicylaldehyde,
vanillin, and furaldehyde. Benzaldehyde is the main component present in the
fixed essential oils of the kernels and seeds of apricots, peaches, plums, bitter
almonds, and cherries (Prabuseenivasan et al., 2006). It is believed that it has
antibacterial, antiviral, antifungal, insecticidal, and antioxidant properties
(Kordali et al., 2005). Cinnamaldehyde is commonly used in baked goods and
sweets, ice cream, and juices, chewing gums, condiments, and meat prepara-
tions, as a flavoring additive (Friedman et al., 2000; Cocchiara et al., 2005).
Salicylaldehyde and vanillin have antimicrobial properties (Petrović et al., 2015).
Furaldehyde is present in abundance in coffee and cocoa (Yang et al., 2016).
4. Dialdehydes (MDA), α-oxoaldehydes (3-deoxyglucosone, Gly, and methylgly-
oxal (MGly)), formed from advanced glycation end products and peroxidation of
lipids (O’Brien et al., 2005).
The major aldehydes that could exist in food and cosmetics are listed in Table 1
with a hint about their nature and their potential sources.

3  uman Health Risks Related to Aldehydes and Molecular

H
Mechanisms of Their Toxicity

3.1 Aldehydes’ Adverse Impacts on Human Health

Aldehydes’ adverse effects on humans are caused by their endogenous production

(i.e., bio-formation through oxidative stress or metabolic processes) and exogenous
sources (National Research Council, 2014). As we mentioned in the previous sec-
tion, the continuous contact or exposure to carbonyl aldehydes is higher in indoor
air than outdoors, and the most abundant aldehyde there is formaldehyde (Zhang
et al., 1994a; Baez et al., 2003). Formaldehyde is a widespread crucial allergen, as
well as it is reported to be toxic and irritating to the respiratory tract, eyes, and skin,
and its effects depend on its ambient levels (de Groot & Flyvholm, 2020; Clarisse
126 M. H. El-Maghrabey et al.

Table 1 Aldehydes’ sources from food and cosmetics

Aldehyde Properties Sources Ref
Formaldehyde Short-chain Environmental pollutant, Feron et al.
saturated aldehyde metabolic by-product, natural (1991) and
constituents Abraham et al.
Formed during the cooking (2011)
process of oils and fats, as well as
sugars
Fumigating agents in cosmetics
and hair salons
Nonanal Medium-chain Human and plant metabolites Omonov et al.
saturated aldehyde Present in many natural oils (e.g., (2014)
lemongrass, citrus, cinnamon,
and rose oils)
Produced from ozonolytic
processes that induce oxidative
cleavage in the unsaturated oils
from plant origin
Vanillin Aromatic aldehyde The major component of natural Walton et al.
vanilla and it is used in the food (2003)
and fragrance industry
Used as a flavoring agent in
pharmaceutics
Acrolein and α, β, unsaturated They are produced during the Woodruff et al.
crotonaldehyde aldehydes (very preparation of various foods such (2007), Leikauf
reactive and toxic) as fried potatoes, old cheese, and (2002), and
salted fish Werley et al.
They originate from (2008)
petrochemical combustion, smoke
from cigarettes, and coal and
wood incineration
Acrolein is also a lipid
peroxidation by-product in the
human body
Citral α, β, unsaturated Added as a flavoring agent in Adams et al.
branched aldehyde food and beverages (2008)
Added as an odorant to cosmetics
and detergents
Cinnamaldehyde Aromatic alkenal A component of plant essential Otoni et al.
oils, added as a preservative to (2014)
provide antimicrobial properties
against many strains
Used as a flavoring agent
HNE Very reactive α, β, A toxic aldehyde, found mainly Ma and Liu
unsaturated aldehyde in vegetable oils and oil-cooked (2017)
or derived foods
Lipid peroxidation by-product
(continued)
Aldehydes’ Sources, Toxicity, Environmental Analysis, and Control in Food 127

Table 1 (continued)
Aldehyde Properties Sources Ref
Gly and MGly Very reactive Metabolic by-product naturally O’Brien et al.
α-oxoaldehydes present in dietary foods and (2005) and
drinks such as bread, rice, yogurt, Lange et al.
soy sauce, beer, wine, tea, coffee; (2012)
as well as in oils
Formed products in smog, fog,
cigarette smoke, vehicle exhaust,
as well as some household
cleaners
Formed in vivo via carbohydrates
and ascorbate autoxidation,
glycated proteins degradation,
and peroxidation of lipids

et al., 2003). Formaldehyde contact allergy occurs frequently in women associated

with hand dermatitis, and the sensitization is caused, especially in nurses, metal-
workers, para-medical professionals, and cosmetologists. Women patients are aller-
gic to formaldehyde induced eczema by about 1.5 times more than men. In 2013,
the European community discovered a patch testing to measure the traces of form-
aldehyde in such individuals (Pontén et al., 2013). In formaldehyde-rich areas, if the
susceptible individuals are trying to avoid aldehydes or substances containing it, the
dermatitis will frequently heal entirely and constantly (de Groot & Flyvholm, 2020).
Among the domestic individuals, formaldehyde aggravates the frequent nocturnal
breathlessness, as it affects different respiratory system parameters and might cause
bronchial hyper-responsiveness, with or without smoking tobacco (Clarisse et al.,
2003; Rumchev et al., 2002).
Related to the central nervous system, there is a disease of unknown etiology
named multiple chemical sensitivity (MCS) (Kreutzer et al., 1999), resulted from
repeated exposure to the aldehydes and VOCs in an indoor environment. MCS
symptoms are termed a sick building syndrome, involving headache, nose, eyes, and
throat irritation, mental fatigue, and respiratory distress, among the new building
owners with newly constructed homes (Hayashi et al., 2004). The olfactory system
is responsible for the expression of MCS symptoms. The olfactory epithelium,
which consists of olfactory bulb neurons and higher center, receives the airborne
chemical information. Chemical signals collected by the olfactory epithelium are
transported into olfactory bulb neurons, periglomerular cells, and granule cells.
Various signaling substances are responsible for the olfactory system functioning,
such as tyrosine hydroxylase (as well responsible for dopamine synthesis), is pres-
ent in abundant in periglomerular cells (McLean & Shipley, 1988). Formaldehyde
causes the olfactory nerve threshold defect in a concentration is higher than 60μg/
m3. Long-term exposure to a low level (80 ppm) of formaldehyde in rats’ experi-
ments, resulted in a particular localized variation in the MOB in the brain and
changed its neuronal function that is caused by increases in the number of periglo-
merular cells that are immune-positive to tyrosine hydroxylase (Hayashi et al., 2004).
128 M. H. El-Maghrabey et al.

In addition to the allergic and inflammatory effects of aldehydes, some of them

possess potential carcinogenic and mutagenic properties (Pinto & Solci, 2007). The
International Agency for Research on Cancer (2008) (IARC) (Crosignani, 2008)
categorized formaldehyde as group 1 carcinogen (confirmed human carcinogen).
Regarding acetaldehyde, it was first classified as group 2B carcinogen (agents prob-
ably carcinogenic to humans) (Villanueva et al., 2015); however, this was then
revised by IARC (1999) and acetaldehyde was classified as a group I carcinogen
owing to the carcinoma risk correlated with its release after consumption of ethano-
lic beverages. Like formaldehyde and acetaldehyde, many other aliphatic (acrolein),
aromatic (benzaldehyde), and low-molecular weight aldehydes have been found to
be genotoxic to many biosystems including microbial, mammalian, and even insect
ones (Liu et al., 2007; Feng et al., 2006). Moreover, formaldehyde has an impact in
teratogenicity, embryotoxicity, gene mutations, and chromosomal abnormalities in
mammalian cells in animals (Thrasher & Kilburn, 2001; Hashim & Fatimah, 2016;
Yang et al., 2010); therefore, the US Environmental Protection Agency (EPA) deter-
mined the daily maximum dose reference of formaldehyde to be 200μg/kg human
body weight per day (Kundu et al., 2020).
The exposure to aldehydes from the surrounding environment can potentiate the
occurrence of many diseases, called collectively as the oxidative stress ailments,
namely, cardiovascular illness, diabetes, rheumatoid arthritis, Alzheimer’s illness,
cataract, Werner’s syndrome, and neurodegenerative diseases such as amyotrophic
lateral sclerosis, and Parkinson’s disease, and other hundreds of clinical disorders
that are correlated to oxidative stress ailments. Oxidative stress results from a dis-
turbance that promotes the formation of reactive oxygen species that exceeds the
organism’s antioxidant capacity, which can be significant for cancer prognosis
(O’Toole et al., 2008; LoPachin et al., 2008a, b; Bhatnagar, 2006; Fedorova
et al., 2014).
As previously discussed, aldehydes are formed upon oxidation processes of
polyunsaturated fatty acids in cooking food systems and the formed aldehydes
include Gly, acrolein, formaldehyde, acetaldehyde, pentanal, hexanal, and HNE
(Zhu et al., 2001; Fullana et al., 2004b). These aldehydes are confirmed as the main
causes of food rancidity and lead to the loss of nutritional quality in foods (Zhou &
Decker, 1999). Moreover, their presence in a concentration of 10μg/m3 is associated
with mucus and respiratory stress, headaches, nausea, dizziness, and/or lung car-
cinogen. Also, these aldehydes have caused repeated chronic symptoms in some
individuals in closed indoor areas, such as conjunctivitis, bronchitis, laryngitis, or
dry cough, and even they can provoke contact-type dermatitis and aggravate the
effect of pollens or other allergen sensitivities (Garrett et al., 1998).
As mentioned previously, fish and seafood are major sources of exposure to alde-
hydes, mainly formaldehyde, for the populations (Kuehl et al., 1994). Moreover,
fish preservation via salting or smoking, in the presence of formaldehyde, may raise
the probability of stomach carcinoma, even after cooking in high temperatures.
Epidemiologic studies confirmed the relation between high consumption of fish and
pickled vegetables with the incidence of adenocarcinoma in the stomach (Tsugane,
2005; Wu et al., 2011; Yoo et al., 2020).
Aldehydes’ Sources, Toxicity, Environmental Analysis, and Control in Food 129

3.2 Molecular Mechanism of Aldehydes’ Toxicity

Owing to their electrophilic nature, aldehydes could bond covalently with the
electron-­rich sites (nucleophiles) on the human body. These reactions potentially
impair many enzyme functions, proteins, DNA, and various macromolecules,
thereby leading to cellular process inhibitions and subsequent cellular toxicity
(Esterbauer et al., 1991; Kehrer, 2000). In vivo aldehyde toxicity through adduct
formation occurs with a second-order rate reaction kinetics. This reaction rate is
dependent on aldehyde levels and nucleophilic biological target amount, as well as,
their electronic energies that affect the rate constant (LoPachin & Gavin, 2014).
The aldehydes can be categorized to relatively soft or hard according to the elec-
tron distribution on the atoms of the molecule and subsequent polarizability. The
hard-electrophilic aldehydes such as alkanals and formaldehyde are characterized
by relative non-polarizability where their weak electron density is concentrated on
the carbonyl carbon atom. On the other hand, the soft-electrophilic aldehydes such
as α,β-unsaturated aldehydes, including acrolein and crotonaldehyde, are more
polarizable since they show several spots with weak electron density. Meanwhile,
the biological nucleophiles (e.g., lysine and histidine amino groups) are compara-
tively hard since they have a more localized charge due to their lesser atomic radii
and larger electronegativity. The hard and soft acid and base (HSAB) theory real-
ized that covalent adducts are favorably and rapidly formed between electrophiles
and nucleophiles having similar softness or hardness. On the other hand, the reac-
tions of electrophile and nucleophile with substantially different softness or hard-
ness are less favorable and slower (O’Brien et al., 2005; LoPachin & Gavin, 2014;
LoPachin et al., 2012; Schwöbel et al., 2011).
In addition to the degree of softness or hardness, the electrophilic index, an elec-
trophilicity measure that unites chemical potential with softness, is related to the
adduct reactions’ rate constant (k) and consequently directly correlates to toxicant
power (LoPachin et al., 2007a, b, 2009). The toxicity of aldehydes is also influenced
by physicochemical factors such as steric hindrance, acid-base equilibrium, and
solubility. The less hindered aldehydes, e.g., monosubstituted, reacted quicker than
the more hindered, e.g., disubstituted aldehyde (Chan & O’Brien, 2008). Meanwhile,
the solubility of the toxicant is a determining factor of tissue distribution that con-
trols its effective concentration at the target site and the overall rate of adduct forma-
tion (Mccarthy et al., 1994; Böhme et al., 2009). On the other hand, the acid-base
equilibrium has a direct influence on the electrophilic index and consequently the
toxicant potency (Schopfer et al., 2011).
Hard aldehydes such as formaldehyde and acetaldehyde are known genotoxic
compounds that trigger nasopharyngeal cancer in humans and nasorespiratory epi-
thelial carcinoma in rodent models. The cause of this toxicity is the ability of the
two aldehydes to react with amines through 1,2-addition mechanism forming ami-
nols which go then through dehydration producing imines. Therefore, formalde-
hyde and acetaldehyde react favorably with comparatively hard nucleophiles (e.g.,
deoxyguanosine N2 nitrogen). Besides, alkanals can undergo hard−hard
130 M. H. El-Maghrabey et al.

interactions with lysine residues ε-amino and DNA exocyclic amino groups induc-
ing the formation of cross-links with proteinaceous amino acids and deoxynucleo-
sides, respectively (Kuykendall & Bogdanffy, 1994; Lu et al., 2010).
Soft aldehydes can undergo Michael addition with soft nucleophiles, such as the
cysteine residues (sulfhydryl groups) present in the biological systems. Additionally,
the deprotonated cysteine thiolate (RS−), which exists in equilibrium with the pro-
teins’ sulfhydryl moiety, is characterized by softness and high nucleophilicity, and
thus, favorably interact with the soft unsaturated aldehydes. Furthermore, the histi-
dine imidazole side chain and lysine ε-amino group have nucleophilic amine groups
that are favorable to react with unsaturated aldehydes via 1,4-Michael addition
(LoPachin et al., 2012). α-Oxoaldehydes (e.g., Gly) can interact with nucleophilic
sites on proteins producing advanced glycation end products (AGEs), which are
strongly linked to diabetes pathogenesis (El-Maghrabey et al., 2018a). The favor-
able nucleophilic groups for interaction with oxoaldehyde derivatives include the
side chains of lysine and arginine that contain hard nitrogen groups (Lo et al., 1994)
as well as the cysteine thiolate sites on proteins (Zeng & Davies, 2005).
The unsaturated aldehydes belong also to the conjugated type-2 alkenes that
comprise also the α,β-unsaturated amides, esters, and ketones. Type-2 alkenes are
electrophilic compounds that have variable electrophilic properties and softness and
reveal a common toxicity mechanism. In consequence, experiencing an environ-
mental combination of unsaturated carbonyl compounds can lead to “type-2 alkene
toxicity” via combined interactions (Martyniuk et al., 2011).

4  nalysis of Aldehydes in the Surrounding Environment

A
and Food Samples

4.1  hallenges in Analytical Determination of Aldehydes

C
and How to Overcome Them

Aldehydes’ determination in environmental and food samples at trace levels is a

challenge to the analyst due to many factors. At first, most of the aldehydes are very
hydrophilic and with small molecular sizes; thus, they are not well retained in
reversed-phase columns commonly used in HPLC. Second, aldehydes, especially
aliphatic ones, have very weak absorbance in the UV region rendering their spectro-
photometric detection problematic. Despite the fact that α,β-unsaturated aldehydes
possess UV absorbance at 220 nm, due to the presence of the C=C chromophore
group conjugated with the carbonyl one, its UV detection is also limited due to the
low obtained sensitivity and repeatability. The third limiting factor for aldehyde
determination is their high polarity and hence their poor ionization and fragmenta-
tion behavior that render them nearly undetectable by mass spectrometry (Long &
Picklo, 2010). The fourth limiting factor for aldehyde determination is their high
Aldehydes’ Sources, Toxicity, Environmental Analysis, and Control in Food 131

chemical reactivity toward amines; thus, they form amide adducts with amines and
amino acids present in the sample. Hence, their recovery in intact form from a com-
plicated matrix (food samples) becomes tedious. Also, these adducts are usually
water-soluble which complicate their recovery using organic solvents. The fifth fac-
tor is their volatile nature which hinders their complete recovery from the sample
matrices (Shibamoto, 2006). Finally, the sixth property for aldehydes that render
their analysis very difficult is their poor stability and their possible degradation to
aliphatic carboxylic acids upon their treatment with harsh extraction conditions
(Eggink et al., 2010).
All these limiting factors for aldehyde determination could be partially or fully
overcome through derivatization with suitable reagents. Derivatization will help to
decrease aldehyde polarity and consequently improve their retention behavior on
LC columns and allow their recovery from aqueous samples (El-Maghrabey et al.,
2016). Moreover, derivatization forms adducts with strong UV absorption
(Gonçalves et al., 2010; de Lima et al., 2018), fluorescence (El-Maghrabey et al.,
2014, 2015), or chemiluminescence (Ali et al., 2014) properties. In the same con-
text, a new form of derivatization called dual-labeling, in which a purification tag
and a fluorophore are reacted with aldehydes at the same time, was recently reported
by El-Maghrabey et al. (2018b). Labeling of aldehydes with a purification tag such
as taurine produced an adduct that possesses a sulfonic acid group. This group is
known to be easily retained selectively on anion exchange sorbents, allowing the
easy recovery of the reaction product in a pure form free from the excess fluorescent
derivatizing reagent and other interfering matrix components (Fig. 2) (El-Maghrabey
et al., 2018b).
Additionally, aldehydes’ derivatization could improve their MS detectability by
enhancing their ionization efficiency and fragmentation properties (El-Maghrabey
et al., 2016, 2018c). Despite the fact that LC-MS is very selective, the sample coex-
isting substances could cause matrix effects that might affect the analytes’ ioniza-
tion extent leading to an error in the measurement. In order to overcome this
problem, derivatization with isotope-coded reagent has been employed. The sample
is derivatized with the reagent light form, while the standard is derivatized with its
heavy type. Afterward, both are combined in a certain ratio and then analyzed by
LC-MS/GC-MS giving relative and absolute quantification for the samples at one
LC-MS run (El-Maghrabey et al., 2020a, b; Kishikawa et al., 2019). For this pur-
pose, many isotope-coded reagents were designed for aldehydes, including the nor-
mal and deuterium (D) or 15N substituted dinitrophenyl hydrazine (Zurek & Karst,
2000; Prokai et al., 2012), D0/D3-4-(1-methyl-1H-phenanthro[9,10-d]imidazol-­2-yl)
phenylamine (D0/D3-MPIA) (Sun et al., 2014), and most recently, the commercially
available 14N/15N-ammonium acetate combined with 9,10-phenanthrenequinone
(El-Maghrabey et al., 2018c).
Another advantage gained by derivatization is the improved stability of the pro-
duced aldehyde adduct over the original aldehyde, thus facilitating their recovery
from complex matrices (Eggink et al., 2010; Kishikawa et al., 2019). At last, we can
132 M. H. El-Maghrabey et al.

Fig. 2 A diagram showing the purification tag/fluorophore dual-labeling followed by solid-phase

extraction. (Reprinted with permission from Ref. El-Maghrabey et al. (2018b) © Elsevier)

conclude that the choice of the derivatizing agent, the extraction technique, and the
applied analytical platform are crucial for obtaining a selective and sensitive detec-
tion method for aldehydes. Next, we will discuss the recent analysis techniques
applied for aldehydes’ control and determination in the surrounding environment
and food.

4.2  nalytical Methods for Aldehydes’ Monitoring

A
in Environmental Samples

Aldehydes’ monitoring in the surrounding environment is vital for the evaluation of

their exposure risk and assess their potential adverse effect on human wellbeing. As
we mentioned previously, derivatization approach is almost essential for aldehydes
prior to their determination. 2,4-Dinitrophenylhydrazine (DNPH) is the most com-
monly used reagent in this approach. DNPH reacts with the carbonyl group of the
Aldehydes’ Sources, Toxicity, Environmental Analysis, and Control in Food 133

aldehydes forming colored hydrazones that could be easily analyzed with UV detec-
tor (Kishikawa et al., 2019). Prieto-Blanco et al. derivatized different types of alde-
hydes such as the aliphatic aldehydes, formaldehyde, hexanal, decanal, and acrolein
and the aromatic aldehyde, benzaldehyde, with DNPH and then determined them in
particulates from the atmosphere utilizing HPLC-UV. A surprising data resulted
stating that the levels of aldehydes in industrial sites are not higher than their levels
in rural ones but even it is slightly lower (Prieto-Blanco et al., 2010). Rosenberger
et al. analyzed a similar group of aldehydes to those analyzed by Prieto-Blanco after
DNPH derivatization; however, Rosenberger et al.’s method was targeting determi-
nation of aldehydes in commercial aircraft cabin air (Rosenberger et al., 2016).
They used a DNPH-coated silica gel cartridge for solid-phase extraction (SPE) of
aldehydes to make simultaneous adsorption and derivatization of aldehydes present
in the cabin air. The formed colored hydrazones were monitored using
HPLC-UV. They found that the maximum highest level of aldehydes in the air of
cabin was reached at the phase of taxi-takeoff-climb. DNPH was also used for ali-
phatic aldehyde derivatization, especially those with short chains, for their analysis
in rainwater by HPLC-UV. Aldehyde extraction and derivatization were performed
simultaneously via solid-phase microextraction (μSPE) using polypropylene mem-
brane porous sheet loaded with C2-coated silica. The authors found that formalde-
hyde is present plentifully in rainwater followed by acetaldehyde and propanal and
at last pentanal (Basheer et al., 2010).
In addition, Liu et al. extracted DNPH-derivatized aldehydes using ionic liquid
via single-drop liquid-liquid microextraction (LLME) (Fig. 3). 1-Octyl-3-methyl-
imidazolium-­hexafluorophosphate was used for extraction, and the extracted hydra-
zones were analyzed using HPLC-UV. The authors stated that there were no
aldehydes found in the river water. On the other hand, they found that formaldehyde
was present in seawater and snow water in a mild and trace amount, respectively
(Liu et al., 2010).
Additionally, DNPH was used for the derivatization of aldehydes in water sam-
ples spiked with heavy metal before their analysis with HPLC-UV. This study dem-
onstrated that the formation of aldehydes was induced upon illumination of the
complex of Cu(II) with amino acids (Lin et al., 2009). At last, DNPH was used for
the derivatization of aldehydes prior to their determination with micellar electroki-
netic chromatography (MEKC). The method was applied for aldehydes’ determina-
tion in drinking water and swimming pool samples employing μSPE. According to
this study, the level of aldehydes in chlorinated swimming pool water is similar to
its level in ozonated drinking water, which highlights the danger of water ozonation
(Fernandez-Molina & Silva, 2014).
Apart from the DNPH derivatization and HPLC-UV analysis methods, GC-MS
was utilized for aldehydes’ determination in environmental matrices. Another
hydrazine reagent, namely, 2,2,2,-trifluoroethylhydrazine (TFEH) was used for
derivatization of aldehydes in drinking and surface water prior to their GC-MS anal-
ysis. TFEH is used in GC-analysis as its derivatives have high volatility; thus, they
134 M. H. El-Maghrabey et al.

Fig. 3 Illustration for

single drop LLME

provide a strong response in GC-MS. The TFEH-derivatized aldehydes were

extracted with μSPE prior to their GC-MS analysis. It was reported that the level of
aldehydes in the commercialized mineral water is surprisingly higher than that pres-
ent in the surface waters (Kim & Shin, 2011). Additionally, hydroxylamine reagents,
such as O-(2,3,4,5,6-pentafluorobenzyl)-hydroxylamine (PFBHA), were used for
aldehydes’ derivatization before their GC-MS analysis to increase their volatility
and ionization. Serrano et al. used PFBHA for the derivatization of aldehydes
employing an micro liquid–liquid extraction (MLLE) method for their extraction
from the pool and environmental water samples. The extracted formed derivatives
were then analyzed by GC-MS. The authors found that the level of aldehyde was
substantially elevated in swimming pool water than environmental samples such as
tap and well water (Serrano et al., 2013a). The same research group derivatized the
same group of aldehydes using the same reagent but instead of MLLE, they used the
classical static headspace for aldehydes’ extraction and derivatization combined in
one step and they applied their method to drinking water samples. Their study
revealed that drinking water disinfection prompted aldehydes’ formation in water.
They also stated that disinfection via ozonation forms more aldehydes than disin-
fection through chlorination and chloramination (Serrano et al., 2013b). Recently,
Zhang et al. determined acetaldehyde, hexanal, acrolein, and crotonaldehyde in
cigarette mainstream smoke gas phase by GC-MS directly in derivatization-free
approach. They found that the aldehydes’ levels are higher in the smoke of US ciga-
rettes than that of China cigarettes (Zhang et al., 2019). Collectively, the reported
Aldehydes’ Sources, Toxicity, Environmental Analysis, and Control in Food 135

methods for determination and control of aldehydes in environmental samples are

summarized in Table 2.

4.3  nalytical Methods for the Determination of Aldehydes

A
in Food Samples

In order to judge the quality and safety of food, aldehydes’ monitoring is one of the
most vital procedures. Aldehydes were found in considerable amounts in different
human consumable food and beverage products. As mentioned previously in detail,
aldehydes’ food sources include vegetable oils, cooked food, alcoholic beverages,
and even drinking water. In the next paragraphs, we will summarize the analytical
methods used for the analysis of aldehydes in each of those sources.
Aldehydes’ analyses in vegetable oils have been performed by several chromato-
graphic methods, and in most of them, the used extraction method was LLE. Butylated
hydroxytoluene was mixed with the analyzed samples during the extraction as an
antioxidant to prevent the artificial formation of aldehydes during extraction. Ma
et al. developed a chromatographic method coupled with a dual-channel photodiode
array detector for aldehydes’ determination in oil samples and French fries before
their derivatization with DNPH. The analyzed aldehydes by this method included
HHE, HNE, and MDA (Ma & Liu, 2017). Douny et al. used also DNPH for
derivatization of the same group of aldehydes; however, liquid chromatography
coupled with tandem mass spectrometry (LC-MS/MS) was used to monitor the
formed hydrazones. The role of DNPH here is to increase the ionization efficiency
of aldehydes (Douny et al., 2015). In addition, another hydrazine reagent, pentafluo-
rophenylhydrazine (PFPH) was used by Gabbanini et al. for derivatization of HNE,
and they also used LC-MS/MS instrumentation for the determination of the formed
hydrazine (Gabbanini et al., 2015).
Ramezani et al. reported a GC system linked to flame ionization detector
(GC-FID) for aldehydes’ determination without derivatization, prior to their extrac-
tion from the oil samples using a smartly designed reverse micelles technique
(Ramezani et al., 2015). When surfactants are dispensed in a non-polar organic
phase accompanied with a little volume of water, reverse micelles are formed as
nano-inverted aggregated surfactant molecules forming water cores inside the
organic phase. This water core extracts the hydrophilic analytes, such as aldehydes,
then, centrifugation is employed for achieving phase separation. The sedimented
surfactant-rich phase is then transferred to a centrifuge tube in which back extrac-
tion is performed through mixing it with chloroform and water followed by sonica-
tion of the mixture and then centrifugation. Phase separation occurs and the upper
organic layer is the surfactant-rich phase, while the lower organic layer contains the
 136

Table 2 Summation of the previously reported methods for aldehydes’ analysis in the surrounding environment
Derivatizing Recovery Detection limit
Sample Analytes Instrument agent Extraction (%) (unit) Ref.
Atmospheric particulates Acrolein, C1–C10 alkanals, HPLC-UV DNPH Ultrasonic 86–110 3–10 (ng/mL) Prieto-Blanco et al.
benzaldehyde extraction (2010)
Cabin air Acrolein, C1–C6 alkanals, HPLC-UV DNPH SPE 98–103 8–20 (ng) Rosenberger et al.
benzaldehyde (2016)
Rainwater C1–C5 alkanals HPLC-UV DNPH μSPE 85–107 0.03–0.15 (ng/ Basheer et al. (2010)
mL)
River, sea, and snow Acrolein, crotonaldehyde HPLC-UV DNPH Single drop 84–107 0.04–2.0 (ng/ Liu et al. (2010)
water C1–C5 alkanals, LLME mL)
Environmental water C1–C9 alkanals HPLC-UV DNPH None 93–115 7–121 (nM) Lin et al. (2009)
Drinking and pool water C1–C10 alkanals, MEKC-UV DNPH μSPE Not 65–775 (pg/ Fernandez-Molina
benzaldehyde mentioned mL) and Silva (2014)
Drinking water C1–C10 alkanals GC-MS TEFH μSPE Not 0.1–0.5 (ng / Kim and Shin (2011)
mentioned mL)
Swimming pool water, Gly, M Gly, C1–C5 alkanals, GC-MS PFBHA LLE 96–99 0.7–80 (pg/mL) Serrano et al. (2013a)
tap, and well water benzaldehyde
Drinking water Gly, MGly, C1–C5 alkanals, GC-MS PHBHA Headspace 97–99 2–80 (pg/mL) Serrano et al.
benzaldehyde (2013b)
Cigarette smoke Acetaldehyde, hexanal, GC-MS None Headspace 79–115 0.014–0.12 Zhang et al. (2019)
acrolein, crotonaldehyde (μg/cigarette)
M. H. El-Maghrabey et al.
Aldehydes’ Sources, Toxicity, Environmental Analysis, and Control in Food 137

targeted analytes which are then injected into the GC-FID. The scheme for the
reverse micelle technique is illustrated in Fig. 4 (Ramezani et al., 2015). Results
obtained by these methods show that aldehydes’ levels are elevated in oil samples
upon thermal treatment due to the induced lipid peroxidation. Thus, we can con-
clude that the aldehydes’ levels in oil may possibly be considered as a good monitor
for its quality and its lipid deterioration status.
Aldehydes were also determined in different types of food including cooked
meat, canned vegetables, yogurt, and baby food. Different aldehydes including
alkanals, acrolein, and benzaldehyde were determined by Gosseti et al. in different
cooked food samples by LC-MS/MS prior to their derivatization with DNPH. The
authors inspected the effect of food matrices, used frying matrices (olive oil or but-
ter), and way of cooking on the level of aldehydes in food (Gosetti et al., 2011). It
was found that the levels of some aliphatic aldehydes are increased upon cooking in
olive oil than in the case of cooking with butter. In addition, the oil cooked steak
contains most of the tested aldehydes; however, the butter or oil in which the steak
was cooked has much lower levels of aldehydes. Another LC-MS method was
developed for aldehydes’ determination in food, but this time targeting α-dicarbonlys
including Gly and its methylated and dimethylated forms. O-Phenylene diamine
(OPD) was used for the derivatization of these compounds, forming highly ioniz-
able quinoxaline derivatives easily detectable by MS. In this study, it was found that
dimethylglyoxal (DMGly) was detected in higher amounts in baby foods than Gly
and MGly (Kocadağlı & Gökmen, 2014). Donegatti et al. developed a

n-hexane modifier

Agitate Claude state Centrifuge

Oil Triton X-100 Clear Surfactant rich phase

Ultrasonic and Water 1mL

centrifugation
chloroform
300 µl

Chloroform phase inject to GC-FID

Fig. 4 Schematic illustration of the reverse micelle device. (Reprinted with permission from Ref.
Ramezani et al. (2015) © Elsevier)
138 M. H. El-Maghrabey et al.

chromatographic capillary micellar electrokinetic method coupled with UV detec-

tion for aldehydes’ determination in milk products prior to their derivatization with
benzhydrazide. As a result, acetaldehyde was the only aldehyde that could be found
in yogurt (Donegatti et al., 2017). In addition, volatile aldehydes were analyzed in
canned vegetables using headspace sample extraction prior to their derivatization
with PFBHA and and GC-MS analysis. It was found that reactive toxic aldehydes
including Gly and formaldehyde were detected only in the liquid phase of the
canned vegetable, which is a non-edible portion (Serrano et al., 2017).
Various techniques were also developed for aldehydes’ determination in differ-
ent juices and beverages. An HPLC-UV method was reported for the analysis of the
aromatic aldehydes, furfurals, in samples from fruit-based juices, using the natural
absorbance for the detection of these aromatic aldehydes. They used vortex assisted-­
salting out LLME for extracting furfurals from the juice samples prior to their anal-
ysis. In this study, they found that the concentrations of 5-hydroxymethylfurfural in
some grape and apple juice samples are higher than the maximum allowed level
stated by the Fruit Juice Producers International Federation. These could have
resulted from improper storage, or prolonged heating during the juice production
(Abu-Bakar et al., 2014).
Goncalves and coworkers have developed a novel extraction method for alde-
hydes from alcoholic beverages called gas-diffusion microextraction (GDME)
(Gonçalves et al., 2010). In GDME, an extractor device, composed of a small-sized
tube made from Teflon containing a microporous semipermeable membrane with
hydrophobic nature, is used. The rule of this semipermeable membrane is allowing
the volatile analytes’ mass transfer while preventing their solvent diffusion. This
device is then immersed inside the sample as shown in Fig. 5. Then, the extraction
solvent containing the derivatizing agent is put inside the extractor device, followed
by volatilization of the aldehydes through heating the sample with agitation, thus,
facilitating the transfer of the aldehydes from the samples to the extracting solvent
through the semipermeable membrane. The derivatization reagent in the solvent
will react with the aldehydes; hence, extraction and derivatization occur simultane-
ously. This technique allows substantial enrichment for the targeted analytes, yield-
ing high sensitivities, as the extracting solvent will not be saturated due to the
continuous draw of the analytes from the solvent through the derivatization reac-
tion. Goncalves and coworkers simultaneously DNPH derivatized and extracted a
group of versatile aldehydes, including furfural, acetaldehyde, and methyl-­
propionaldehyde, from beer samples prior to their determination with HPLC-UV. In
addition, they used LC-MS to confirm the presence of the aldehyde in beer through
detecting the masses corresponding to the DNPH derivatives (Gonçalves et al.,
2010). Furthermore, free and bound acetaldehydes in wine were simultaneously
extracted and derivatized using the same technique by the same research group, and
many more carbonyls were identified in wine using hyphenation of HPLC-DAD
and tandem MS (Cruz et al., 2012). At last, Lima et al. used the same extraction
technique, GDME, but this time coupled with newly developed aldehydes’ colori-
metric reagent, 4-hydrazinobenzoic acid, for analysis of aldehydes in wine (de Lima
Aldehydes’ Sources, Toxicity, Environmental Analysis, and Control in Food 139

Fig. 5 Illustration for GDME where (a) a magnified view of the extractor, (b) detailed diagram for
the chemical equilibria; in which the numbers from 1 to 7 represent extractor’s superior piece and
lower piece, sample solution, stir bar, heater with stirring capability, the membrane, and the accep-
tor solution, respectively, while α, β, and γ represent the analyte, the derivatizing agent, and the
formed product. (This figure is reprinted with permission from Ref. Gonçalves et al. (2010) ©
Elsevier)

et al., 2018). They stated that the GDME method necessitates the use of the standard
addition method to decrease the matrix effect (de Lima et al., 2018).
Olivero and Trujillo have designed a derivatization free GC-MS method for alde-
hydes’ determination in the wine after their headspace microextraction. Their results
indicated that the level of aldehydes is more elevated in red wines than in white ones
(Pérez Olivero & Pérez Trujillo, 2010). Besides, an HPLC-FL method was designed
by You et al. for the purpose of C1–C10 alkanals analysis in alcoholic beverages.
They used the derivatization fluorescence labeling hydrazine reagent,
2-[2-(7H-dibenzo[a,g]carbazol-7-yl)-ethoxy]ethylcarbonylhydrazine (DBCEEC),
for derivatization of aldehydes. They found that the very short-chain aldehydes,
namely, formaldehyde and acetaldehyde were the major aldehydes in these bever-
ages among the tested alkanals (You et al., 2009). The reported analytical for alde-
hydes in food and drinks is summarized in Table 3.

5 Conclusion

Human exposure to aldehydes from the surrounding environment and food forms
represents a high toxicological alert. In this chapter, different sources of aldehydes
in the environment and food are discussed in detail. Aldehydes could be formed
from the photooxidation of volatile organic hydrocarbons emitted for the plants or
from biomass burning and fossil fuel combustion. Aldehydes are also present in
rainwater and the surface water sourced from the upper atmosphere. Besides, chlo-
rination and ozonation of drinking water for sterilization purposes could lead to the
Table 3 Summation of the previously reported methods for aldehydes’ analysis in food and drinks
140

Recovery Detection
Sample Analytes Instrument Derivatizing agent Extraction (%) limit (unit) Ref.
Vegetable oil and HHE, HNE, MDA HPLC-UV DNPH LLE 96–101 9–14 (ng/ Ma and Liu (2017)
French fries mL)
Linseed oil HHE, HNE, MDA, LC-MS/MS DNPH LLE 79–101 20–140 Douny et al.
2,4-decadienal (ng/g) (2015)
Vaseline, sweet HNE LC-MS/MS PFPH LLE 91–105 7 (ng/g) Gabbanini et al.
almond, and olive (2015)
oil
Vegetable oil C3–C7 alkanals GC-FID None Reverse micelles 80 20.0–80.0 Ramezani et al.
technique (ng/g) (2015)
Smoked salmon, Acrolein, C1–C10 LC-MS/MS DNPH On-line SPE 71–100 2–272 (pg/g) Gosetti et al.
grilled or cooked alkanals, benzaldehyde (2011)
meat
Baby food Gly, MGly, DMGly LC-MS OPD Protein 89–110 3–27 (ng/g) Kocadağlı and
precipitation Gökmen (2014)
Yoghurt C1–C5 alkanals except MEKC-UV Benz-hydrazide Filtration 80–125 0.4–0.5 (μg/ Donegatti et al.
butanal mL) (2017)
Canned vegetable C1–C9 alkanals, GO, GC-MS PFBHA Headspace 89–99 0.02–0.1 Serrano et al.
MGO, benzaldehyde (ng/g) (2017)
Fruits juice Furfurals HPLC-UV None Vortex assisted 82–105 0.3–3.5 (ng/ Abu-Bakar et al.
salting-out- LLME mL) (2014)
Beer Acetaldehyde, furfural, HPLC-UV DNPH GDME Not 1.5–12 (ng/ Gonçalves et al.
and methyl propanal mentioned mL) (2010)
Wine Acetaldehyde HPLC-UV & DNPH GDME Not 0.8–1.1 (ng/ Cruz et al. (2012)
LC-MS/MS mentioned mL)
Wine Acrolein, C1−C3 HPLC-UV 4-Hydrazinobenzoic GDME Not 5–210 (ng/ de Lima et al.
alkanals, furfural, acid mentioned mL) (2018)
benzaldehyde
M. H. El-Maghrabey et al.
 Recovery Detection
Sample Analytes Instrument Derivatizing agent Extraction (%) limit (unit)Ref.
Wine Alkanals, alkenals, GC-MS None HS- μSPE 20–190 2.0–8.0 (ng/Pérez Olivero and
furfural, benzaldehyde mL) Pérez Trujillo
(2010)
Alcoholic C1–C10 alkanals HPLC-FL DBCEEC None 99–104 0.20–1.8 nM You et al. (2009)
beverage
Aldehydes’ Sources, Toxicity, Environmental Analysis, and Control in Food
141
142 M. H. El-Maghrabey et al.

abundant formation of aldehydes. In food, aldehydes could be formed during high-­

temperature frying. Besides, they are present in wine and vegetable oils, and they
are formed as by-products during food deterioration or microbial fermentation. The
adverse health effects of aldehydes are many varying from allergic and inflamma-
tory effects to carcinogenicity and mutagenicity. The molecular mechanism of alde-
hydes’ toxicity was discussed in order to make a truthful risk assessment. Aldehydes
with side short chain or with long saturated chain cause toxicity through forming
adducts with the lysine side chain amino groups (hard nucleophiles) owing to their
hard-electrophilic properties. On the other hand, aldehydes with conjugated unsatu-
rated side chain, such as alkenals and α-oxoaldehydes, possess soft electrophilic
properties; thus, their main toxic effect is due to their reaction with cysteine sulfhy-
dryl group (soft nucleophile). Other factors such as side chain steric hindrance and
aldehydes’ solubility may affect the toxicity extent of aldehydes as they might limit
their accessibility to the targeted biomolecule.
As aformenioned above, aldehydes are toxic compounds that are highly reactive
towards biological molecules leading to biochemical modifications that disturb
many biological functions. Thus, aldehydes’ determination in environmental and
food samples was heavily reported in order to control their possible health risks.
Practically, derivatization for aldehydes is essential to improve their extraction,
chromatographic behavior, stability, and detectability. The most reported aldehydes’
derivatizing agent is DNPH, and additionally, there are some recent reagents, such
as PFPH, 4-hydrazinobenzoic acid, and DBCEEC, that were developed to employ
some advantages such as increasing sensitivity or allowing fluorescence detection
of aldehydes. Owing to aldehydes’ high reactivity, polarity, instability, and volatil-
ity, their extraction from complex matrices is a challenging process. Thus, different
sample pretreatment procedures for aldehydes such as GDME, fluorophore-­
purification tag dual-labeling, μSPE, and inverse micelles extraction were recently
reported. Regarding their analysis techniques in food and the surrounding environ-
ment, various chromatographic methods were reported for this purpose including
HPLC methods coupled with UV, FL, or MS detection, in addition to GC coupled
with either FID or MS detection. At last, we can conclude that the aldehydes’ deter-
mination in the surrounding environment and heavily consumed food and drinks is
a crucial matter, and the research in this area is growing fast. For developing an
integrative aldehyde assay, the choice of appropriate derivatization and extraction
technique is very important, and it mainly depends on the targeted aldehydes and
matrices. Having the right analytical tool for aldehydes in hand, we can study and
control the possible risks and adverse effects of toxic aldehydes on human health.

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