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Acrylamide Intake, Its Effects on Tissues and Cancer

Authors:

Abstract

Acrylamide has a toxic potential in tissues including the reproductive and urinary system. It is also a known neurotoxic compound in experimental animals. It is defined as 2A group carcinogen by International Agency of Research on Cancer. Two years studies in the rodents have shown that acrylamide leads to some tumors such as thyroid, liver, ovarian, and breast. The levels of acrylamide in food and exposure in various population have been studied extensively during the past decade. It has genotoxic potential through glycidamide which is a chemically reactive epoxide of acrylamide in animals. Both acrylamide and glycidamide bind to hemoglobin and thus occur as hemoglobin adducts that are used to measure the level of acrylamide exposure. Considering the health risk assessment of acrylamide, the margin of exposure (MoE) criterion is used as an alternative approach. European Food Safety Authority Scientific Committee has declared that there is a health concern among the local population because of the relatively low MoE values. Until now, a number of cohort studies including human exposure of acrylamide have been conducted in different countries, and the corresponding risk assessments of some cancer types are acquired. However, all these studies have not provided enough evidences concerning the risk of cancer with daily intake of dietary acrylamide in human.
CHAPTER
4
Acrylamide
I
n
tak
e
,
I
ts
Effects on
T
issues
and
C
anc
er
Ayşegül
ÇEBİ
Faculty
of Health
Sciences,
Giresun
University,
Piraziz/Giresun,Turkey
INTR
ODUC
TION
Acrylamide
is an
industrial
chemical that has been used
since
the middle of the
1950s
in the manufacturing of
polyacrylamide.
It is not known to occur
as
a natural
pr
oduct.
Acrylamide
has been
classified
by
International
Agency of Research on
Cancer
(IARC)
as
a
“2A Group”
carcinogen [1].A
person can be
exposed
to
acrylamide
from diet, drink
-
ing
w
ater
,
smoking,
secondhand
smoke, occupational
conditions and
so
on.
Acrylamide
is
also used mainly
in certain
industrial pr
ocesses,
such as
paper
manufacturing,
and drinking water and
wastewater
tr
eatment. It
is
found in
small
amounts in some consumer products, such
as
caulk, food
packaging,
and some
adhesives.
Human exposure to acrylamide is
widespread
in the
world.
In the
past
few
y
ear
s,
animal studies
have shown that acrylamide
was
a multiorgan
carcinogen
in
rodents
[2,3]
.
In
2002,
Swedish scientists first declared
that
acrylamide was
formed in
heated foods
(frying, baking,
and
roasting
of some
foods)
[4].
Acrylamide
is metabolized to reactive
glycidamide
via epoxidation. Glycidamide
is believed to have a role in the genotoxity of acrylamide by attaching itself to
DNA.
Acrylamide
and
its
metabolite
,
glycidamide,
react
readily
with a number of
biomolecules including hemoglobin [5].
There have been many studies that claimed an
association
between
acrylamide
and increased risk of cancer in
human.
The potential carcinogenic
effects
of dietary
acryl- amide are
controversial.
After
findings
of
acrylamide
intake in daily food
consumption many
epidemiological studies
have emerged
investigating
the
association
between acryl- amide intake and cancer. Food frequency questionnaire (FFQ), a
commonly used approach in the cohort
studies,
to
measure
the
daily
intake of
acrylamide has
been argu-
able. Generally, coffee,
French
fries,
and fried potato
products are the more commonly consumed food source of
acrylamide
in the world.
It
was
reported that acrylamide increased the incidence of benign and
malignant
tumor
s
in some
organs
such
as
thyroid,
adrenals,
and tunica
vaginalis.
Hence,
acrylamide induced lung and skin tumors, in a series of nonstandard carcinogenicity
bioassays
in mice [3,6].
Acrylamide
in Food
http://dx.doi.org/10.1016/B978-0-12-802832-2.00004-8
Copyright © 2016
Elsevier Inc
.
All
rights reserved.
63
64
Acrylamide
in
F
ood
A
series
of wide-ranging cohort studies have been carried out to lighten the
carci- nogenic effect of acrylamide on human in different countries including
Sweden,
the
Netherlands,
and the USA.
HUMAN EXPOSURE TO
A
CR
Y
L
AMIDE
Acrylamide
has been considered
as
a probable carcinogen and
classified as
“2A
Gr
oup”
in 1994 by IARC
[1].
People can be exposed to
acrylamide
from diet,
drinking water,
smoking,
secondhand
smoke,
occupational conditions and so
on.
Acrylamide is
used
as
a building block in making
polyacrylamide
and
acrylamide
copolymers.Therefore,
it takes part in
manufacturing
of the
water-soluble
polymer
s
which are used for paper manufac-
tur
ing,
sludge
tr
eatment,
w
aste
w
ater
,
soil
stabilization,
and so on
[7].Although
these have a wide range of area of
usage,
its
exposure to human is
limited.
Oral
feeding,
inhalation and dermal contact are the
ways
to intake of
acrylamide. Factory
and tunnel
w
ork
er
s
are at
risk
with
respect
to
acrylamide intake
by
inhalation
and
skin contact.
It
can
be absorbed through skin and
mucous
membranes.
During the
manufacture,
the
estimated
exposure of
acrylamide is
0.07
mg/kg/day. In
previous animal
studies,
dermal application
of radio- active-labeled
acrylamide resulted in AA-val adduct
levels,
which were found to be lower than
those observed following intraperitonal application in rats and mice [8]. Dermal
absorption
levels
vary from about 3% to 100% in vitro and animal studies [7]. In
vitro studies [8,9] showed that low
doses
(1.3
g/cm2) of
acrylamide
(prepared using
ethyl acetate) in
creams
and lotions had a 30%
absorption,
while higher
doses
(2000
g/
cm2) of
acrylamide (also prepared
in ethyl
acetate)
had a reduced
absorption (20%)
in
pig. They concluded that the lower absorbed dose following the
2000
g/cm2
application of acrylamide
was
attributed to a saturation in the penetration
of acrylamide. Absorption of 20–30%
was
found in low doses
(0.1
g/cm2) of
acrylamide in
poly
-
acrylamide gels in vitro [8,10]. Acrylamide is quickly
absorbed by the skin and mucosa if
inhaled.
After taken by oral way, it is well
absorbed and
distr
ibuted to
the
tissues
[11]
.
Acrylamide
can be
carcinogenic,
after
conversion to
glycidamide
which
is DNA reactive [12].
In
addition, acrylamide
is found in filtered cigarette smoke.The
levels
of
acrylamide have been
declared
to range between 1100 and
2340
ng per
cigarette
[13]
.
Indirect expo
-
sure of
acrylamide
via environment drinking water
was
presented by
European
Chemi
-
cals Bureau, a joint of European Union in
2002.
The daily
acrylamide dose
thr
ough
drinking water
was calculated
using three
parameters.These
are the maximum expected concentration of
acrylamide
in drinking water
(0.125
μg/L), the
daily
intake of drinking water
(2
L/day), and human
average
bodyweight.This equation is
expressed as
follows:
Dose
=
Concentration
Body weight
× Intake
This formula gives a dose of
0.0036
μg/kg bodyweight/day for a
70
kg
average human [7].
Oral exposure of
acrylamide is
more
effective
to the body than the
dermal
exposure
as
the skin can act
as
a
barrier.
Fir
stl
y
,
acrylamide
enter
s
the
body; after digestion
and
absorp- tion, then excreted by urine. Its half life is
3.1–3.5
h in the body. In the
liver,
acrylamide comes over conjugation by glutathione (GSH) and form mercapturic acid
to excrete.
Additionally,
epoxidation of acrylamide by cytochrome P450 2E1
(CYP2E1) enzyme
results
in the formation of
glycidamide,
which binds to DNA and
has mutagenic effects. Glycidamide
encounter
s
further biotransformation through
hydrolysis
to form glycer- amide or conjugation by GSH,
resulting
in the formation of
mercapturic acid excreted in the urine
[5]
.
Acrylamide displays biphasic
elimination
with an
initial half life
of about
5
h
and a
final half life
of
8
days
in
tissues.
In
addition,
it
does not
accumulate
in the body.
DIETARY INTAKE OF
A
CR
Y
L
AMIDE
Acrylamide
is one of the by-products of the
Maillard
reaction between reducing
sugar
s
(i.e., glucose and fructose) and free
asparag
ine
.
Thus, it
appear
s
in
starchy
foods such
as
potato
chips, crisps,
and bread treated at temperatures above
120
°C. Cooking
methods specify the formation of acrylamide. Baking, frying, deep-frying,
overcooking, and microwaving produce high amounts of
acrylamide,
but not boiling
foodstuffs.
Distribution of
acrylamide levels
in
foods has
been reported between 2007 and
2010 by European Food
Safety
Authority (EFSA) Scientific Committee. The coffee
substi- tutes, potato
crisps,
and French
fries
have high
acrylamide levels,
while other
processed
cereal-based
foods for
infants
and young children have low
levels [14].
Food categories are shown in Table 1.
The
basic sources
of
acrylamide
in
foodstuffs
depend on the national/regional food
habits.
For
example,
in the
USA,
French
fries
and other potato products are highly
con
-
sumed (the average daily acrylamide intake is
35%),
while coffee and bread are
con
-
sumed
relatively less (coffee, 7%
and toast and soft
bread, 11%)
[15].
Comparing dietary acrylamide intake
across
populations is challenging because of
procedural
variations
in the estimation of the intake. It is known that food
preparation methods change among different cultures. Using open-ended
24
h
dietary
recalls,
an
investigation
including
stratified analyses according
to the
habitual
alcohol
consumption, smoking
status, physical activity,
body
mass
index
(BMI),
and
education
was
performed to evaluate the mean dietary
acrylamide
intake and its
dietary sources in 27 center
s
in
10 countries in the EPIC
stud
y
.
The south and west of Europe take
acrylamide
mostly from
bread, crisp bread,
and
rusks (range: 24–50%), whereas
the north of Europe
takes
it from
coffee (range 33–40%),
followed
by br
ead,
cr
isp
,
and
rusks
(range:
20–
35%).Among
all
Europe
countr
ies,
these two food
groups
were
settled
at the
first
and
the
second
or
der
,
whereas potatoes and its products
(fries)
and
other
s
such
as
cooking
above
120
°C were
Acrylamide
I
ntak
e
,
I
ts
E
ff
ec
ts
on
T
issues
and Cancer
65
Table 1 Distribution of acrylamide levelsa in foods
in
Food
ca
t
egor
y
2010
n
M
edian
(
μ
g/k
g)
M
ean
(
μ
g/k
g)
P90
(
μ
g/k
g)
P95
(
μ
g/k
g)
Maximum
(
μ
g/k
g)
French fries, sold as
r
eady-to-eat
256 240 338 (336–339) 725 1024 2174
French
fries
from
fresh
potatoes 196 239 325 (325–326) 692 921 2174
French
fries
from potato
dough
1
150 150 150 150 150
Unspecified
French fries
59
240 382 1019 1377 1800
Potato crisps 242 450 675 (674–676) 1538 2080 4533
Potato
crisps
from
fresh
potatoes 173 543 758 (757–758) 1822 2193 4533
Potato
crisps
from potato
dough
19
370 435 980 1000 1000
Unspecified
potato crisps
50
313 481 (478–484) 890 1389 4039
Precooked French
fries/potato
pr
oducts
117 151 331 (329–333) 873 1159 3955
for home
cooking
Fries
baked in the oven (oven fries)b
28
410 690 1888 1991 3955
Deep-fried friesc
64
115 198 (195–201) 568 681 1155
Unspecified
potato products for home cookingd
25
179 270 707 928 1295
Soft bread 150 18 (9–24) 30 (25–35) 63 94 425
Unspecified
bread
0
– –
Breakfast
cer
eals
174 91 (91–100) 138 (132–144) 293 353 1290
Biscuits, crackers, crisp bread, and
similar
462 129 333 833 1337 5849
Crack
er
s
64
139 178 303 491 1062
Crisp bread
54
110 249 (248–250) 665 1443 1863
W
afer
s
37
225 389 880 1300 1300
Ginger bread 207 134 415 (414–415) 1187 1635 3191
Other
biscuits, crackers,
crisp
bread,
and similar 100 99 289 (288–290) 640 1061 5849
Coffee and coffee
substitutes
151 242 527 1200 2000 8044
Roast coffee 103 200 256 (255–257) 462 641 1932
Instant
(soluble)
coffee
15
520 1123 2629 8044 8044
Coffee substitutes
24
870 1350 (1349–1350) 3300 3400 4200
Unspecified
coffee
9
300 441 1800 1800 1800
Ac
ryl
am
ide
in
F
o
od
66
Baby foods (excluding cereal
based)
55 12 (0–18) 69 (64–74) 116 419 1107
Processed cereal-based foods for infants 128 24(0–30) 51 (45–57) 144 175 578
and young
childr
en
Biscuits
and
rusks
for
infants
and young children 46 57 86 (83–90) 175 250 470
Other
processed cereal-based
foods for infants 82 13 (0–24) 31 (23–39) 60 130 578
and young children
Unspecified cereal-based
foods for
infants
and
0
– –
young children
Other
foods
336 82 (82–84) 225 (221–228) 612 811 3972
Muesli and porridge 14 56 80 (77–83) 104 420 420
Pastries
and cakes 81 55 146 (144–148) 420 793 890
Nonpotato
savoury
snacks 80 115 192 (189–194) 389 618 1910
Other
unspecified
products 161 81 (81–82) 293 (289–298) 707 1330 3972
a
Values
indicate middle bound (MB) and
ranges
in
brackets
indicate lower bound
(LB)
and upper bound (UB) values.When LB and UB do not
differ
from the MB,
only the MB value is presented.
b
86%
were reported to be
analyzed as prepared, 14% analyzed as
unprepared.
c
73%
were reported to be
analyzed as prepared, 8% analyzed as unprepared, 19%
type of
preparations
were
unknown.
d
56%
were reported to be
analyzed as prepared, 44% analyzed as
unprepared [14].
A
cr
yla
mi
de
I
nt
ak
e
,
I
ts
E
ff
ec
t
s
on
T
is
sue
s
an
d
Ca
nce
r
third
(range 4–26%).
In the UK,
potatoes
were found to be higher
acrylamide
contr
ib
uto
r
s
(15%) [16]. Comparing acrylamide intake with life style
factors,
alcohol
consumption
was
found to be
associated
with
acrylamide
intake in all population
(
p
=
0.002 for men;
p
= 0.03 for women). Dietary
acrylamide
intake
was
found higher in
women who
con
-
sumed alcohol than
abstainers.
But, there were no
consistent
data
revealing
the association between
acrylamide
intake and alcohol drinking in men. It
was
found that acrylamide intake
was
related with smoking
status
in women
(
p
<
0.001),
and not in men
(
p
= 0.49). Smok
er
s
and former
smok
er
s
were more related
with acrylamide intake than never
smokers. Physical activity,
BMI, and education
were not related with dietary acrylamide intake both in women and in men [16].
RISK
ASSESSMENT
Acrylamide has
an
electrophilic
double bond, which can react with nucleophilic
groups. Thus, it covalently interacts with cellular nucleophiles such
as
the
sulfydryl
groups in reduced glutathione and in proteins
[12].
Different
approaches
are
available
for physio-
logically
based pharmacokinetic (PBPK) modeling of
acrylamide
absorption,
metabo
-
lism, and constitution for predicting human internal exposures
to acrylamide and
glycidamide
to eliminate
bias
in risk assessment.
Acrylamide
has a complex
metabolism
in
viv
o.
After
absorption,
minimum four
dif- ferent urinary acrylamide metabolites have been identified in rats [17].
N
-
acetyl-
S
-
(propionamide)-cysteine (APC) is a mercapturic acid that accounts for
48% of
the
d
o
s
e
.
To
analyze
APC in urine, a biological monitoring method has
been developed, which comprises acid hydrolysis of APC to produce S-
carboxyethyl-cysteine [18]. Hemoglobin adducts of acrylamide are used to measure
human exposure to
electr
o
-
philic compounds over the first
4
months (human red
blood
cells’
life span is
120
days). N-terminal
valine
of hemoglobin
has
the adduct
formation,
and it is used
as
a marker of in vivo exposure (internal dose) to
acrylamide
[19].
A modified Edman degradation is
processed as
an
analytical
procedure.
Measurement of hemoglobin
adducts
of glycidam- ide is
also
used
as
a
similar
analytical approach.
Hemoglobin adducts of
acrylamide
and
glycidamide
are found
three to
five
times higher in
smok
er
s
than in nonsmok
er
s
[20,21]. The average dietary
acrylamide intake of
0.8
μg/kg/day has been estimated in
non
-
smoker US
population
[21].
In
Vesper’s study,
the
levels
of hemoglobin
adducts,
that is, HbAA
and HbGA have expanded respectively between 3–910 and
4–756
pmol/g
hemoglobin. Mexican-Americans
have the
highest level
of hemoglobin
adducts,
whereas non-Hispanic
blacks
have the lowest in the US population [21]. However, in
children and
adolescents,
a higher dietary acrylamide intake has been found than
the adults because of the elevated consumption of acrylamide rich foods such
as
potato chips, French
fr
ies,
and the lower body weight
[12].After
2003,
some
mitigation
strategies
have been reported for the food types with high acrylamide
levels.
Although there are
Acrylamide
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ntak
e
,
I
ts
E
ff
ec
ts
on
T
issues
and Cancer 6868
Acrylamide
in
F
ood
preventive
studies, generally
in all
countries,
they have not been considered an
effective protection from
acrylamide
exposure but only in some population
subgroups
[22,23].
There are some studies that has shown a
relationship
between the dietary intake
of
acrylamide
and the
increased risk
of cancer in human. But, this
relationship is
considered
inconsistent.
A
meta-analysis
of some
epidemiological studies
has indicated
that dietary
acrylamide
is not
associated
with the risk of most common
cancer
s
[24].
The
J
oint
FAO/WHO
Expert Committee on Food
Additives
(JECFA) performed
the margin of exposure (MoE)
as
an
alternative
approach for the health risk
assessment
of
acrylamide.
MoE is
based
on the benchmark
dose,
derived from
dose–
response
mod
-
eling,
and a
qualitative description
for a
possible
prioritization of r
isks.
According to
the
JECFA,
dietary exposure of
acrylamide
is
calculated
to be
0.13
μg/kg bw/day and
the
value of MoE is 1385 for
average,
0.69
μg/kg bw/day, value
of MoE is 261 for high consumer. EFSA Scientific Committee has proposed that
there is a health concer
n
among the local population because of the
relatively
low
MoE
v
alues.
They have sug- gested this approach for compounds that have genotoxic
and carcinogenic
features
like
acrylamide
[25].
The 64th meeting of the
JECFA
noted that in 2005 the
average acrylamide
intake
of the general population
was
0.001
mg/kg bw/day and the BMDL (benchmark
dose lower limits for a 10% extra risk in
tumors)
of
0.30
mg/kg bw/day for
induction of mammary
tumor
s
in rats (MoE: 300), whereas high acrylamide
consumer
s
have
the
value of
0.004
mg/kg bw/day (MoE: 75) [26]. In the 72nd
meeting of JECFA,
No
changes
have been
observed
in the
average
and high dietary
acrylamide
exposure values and this remained the
same
in 2010.The
JECFA has
declared
that the BMDL10
has
been
0.18
mg/kg bw/day, and the MoE
values
of the
average
and high
exposures,
respectively,
have
been 180 and 45 for the induction of Harderian
gland
tumor
s
in mice.The
BMDL10
has
been
0.31
mg/kg bw/day, and the MoE
values
have been 310 and
78,
respectively
for the mammary
tumor
s
in
rats.
MoE
values
state human health concer
n.
Acrylamide
w
as
considered
as
both genotoxic and
carcinogenic
by
FAO/WHO
in
2010 [27].
TOXIC EFFECTS OF ACRYLAMIDE IN
TISSUES
Previous
studies
have shown the
toxicological effects
of
acrylamide
in
tissues.
In a
study, the hazardous effects of a single oral dose of
150–100
mg/kg acrylamide
were
h
i
s
t
o
-
pathologically examined on the testis in pre-pubertal and adult mice.
Acute testicular damage and
necrosis
of the late elongated
spermatids
were seen one
day after
admin
-
i
s
t
r
a
tion
of
acrylamide
in the
prepubertal
mice.The round
spermatids
had been destroyed in
stages
I–II and IV–VIII one day
after administration
of
acrylamide
in adult mice [28]. In a
stud
y
,
acrylamide was administered
to the
rats
at
Acrylamide
I
ntak
e
,
I
ts
E
ff
ec
ts
on
T
issues
and Cancer 69
doses
of 0, 5,
15,
30,
45,
and
60
mg/
kg/day for 5
consecutive days
by oral
gavage,
and
morphological changes
were shown in the testicular histology. The deterioration
was
observed in the germ cells of
the
Acrylamide
I
ntak
e
,
I
ts
E
ff
ec
ts
on
T
issues
and Cancer 70
seminiferous
epithelium of
rats administered
with
acrylamide
at a dose of
60
mg/kg/da
y
.
Furthermore, a wide range of multinucleated giant cells with sloughed
seminiferous epithelium were
seen
in the lumen of the
seminiferous
tub
ule
.
Decreased
sperm concen
-
tration and morphological defects of sperm in cauda epididymis of
the acrylamide- treated group were seen in a dose-dependent manner [29].
Numerous experiments related with
acrylamide
were done within
National
T
o
xicol
-
ogy Program (NTP) and were reported in
2002.
Administration
of 0.14, 0.35,
0.70, 1.41,
3.52,
and
7.03
mM
acrylamide
in the drinking water
corresponds
to the consumed
amount
of about 1.4, 3.8, 7.8, 15.4, 37.4, and
67.6
mg/kg bw/day for male rats and
1.7, 4.3, 8.3,
16.9, 39.4,
and
70.0
mg/kg bw/day
acrylamide
for
female rats.
Furthermore, male
rats
fed with 7.4,
18.5, 37, 74, 185,
and
370
mg
acrylamide
per kg diet.These
experiments
showed that liver weights, liver to brain weight ratios were decreased in all rats
administered
7.03
mM acrylamide in the drinking water for
14
days. Neoplastic findings were
not
detected in these
animals.
Dilation of the urinary bladder
was
determined in
several
male and female rats, and the lesion
was
determined
microscopically.
Furthermore,
hind-leg
paralysis was observed
in the
rats
which had
grossly dilation.
Germinal
epithelium
degen
-
eration in the
seminiferous
tubules of testes
was
observed
microscopically
in male rats
administered
7.03
mM
acrylamide
in the drinking
water.There were some proof that
the
lesions occurred in the reproductive
tissues.
The
n
umber
s
of germinal cells showed a
decline,
and multinucleated
spermatids
existed
in the lumens of
seminiferous
tubules [30].
Acrylamide has neurotoxic
effects
in mice,
rats,
guinea
pigs, rabbits, cats,
dogs,
and monkeys
[1,31–34]
.
The
loss
of motor function such
as
hind-limb
splay
and
wither
ed
rotarod performance is the main neurotoxic
response,
whereas the
ultrastructural and biochemical changes are the other overt
responses.
Axonal
degeneration
was
increased in a dose-dependent manner in the
sciatic
nerve of both
males
and
females following
the
administration of
acrylamide
to the
rats.
The dilation
was microscopically
observed in axons
besides
this foamy
macrophages,
and myelin
debris were
also
observed [30].
Small-diameter nerves may be damaged by acrylamide intoxication. It has been
shown that the
response
of
s
w
eat
glands
to pilocarpine which is a cholinergic
agonist
is dropped in acrylamide intoxicated mice [35]. Acrylamide can damage
unmyelinated
axons
in the
vagus
nerve and the enteric nervous
system [36,37].
Interference with axonal transport and the enhanced
calcium
input [38] are some
mechanisms
of
acrylamide
neu-
rotoxicity
[39,40]
.
Acrylamide
intoxication
leads
to
degeneration of
epidermal
nerves in the skin
[41]
.
Acrylamide
intoxication
causes
some degeneration in epidermal and
der
-
mal
nerves.Typical
epidermal nerves with a
varicose appearance
and some branching in the
suprabasal layers
are shown in Figure
1(a). Early stage
of the
acrylamide
intoxication (in
5
days)
epidermal nerves and
Acrylamide
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dermal nerves are still readily demonstrated with
the
protein gene product (PGP) 9.5.
Epidermal
and dermal nerves have the
same
mor
phol
-
ogy with the control mice but
the branching patterns of the epidermal nerves had become more elaborate at this
stage
(Figure
1(b)).
In
21
days
of the
acrylamide
intoxica- tion (in the late
stage),
the
number of
epidermal
nerves
was
reduced (Figure
1(c))
[41].
Acrylamide
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(a)
(b)
(c)
Figure 1 Skin innervation seen in
acrylamide-intoxicated
mic
e
.
This
micrograph shows the
inner
v
a
-
tion of the epidermis in control mice
(a),
in the initial stage (b), and in the late stage
(c)
of
acrylamide
intoxication.
T
he
skin of the hindfoot was
immunocytochemically
stained with the protein gene
pr
od
-
uct 9.5
(PGP 9.5).
(a)
I
n
the
subepidermal
nerve
r
eg
ions
,
PGP
9.5 (+) nerves are found and typical
vari- cose
appearance
and some branching points are found in the
epider
mis
.
(b)
T
he
initial stage
seems
after the acrylamide intoxication, the branching
patterns
of
PGP 9.5 (+)
epidermal nerves have
Acrylamide
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become
prominen
t
.
(c)
I
n
the late stage after the acrylamide intoxication, the
abundance
of
epidermal
ner
v
es
significantly
decr
eased
.
Bar
=
20
μm
[41]
.
Acrylamide
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After the
acrylamide intoxication,
the degeneration pattern of dermal nerves
resem-
bles
to
epidermal
ner
v
es.
At the light
microscopy, individual
PGP 9.5 (+)
dermal nerves have been shown with a linear pattern of
similar
axonal caliber
(Figure
2(a)
).
After
the
acrylamide intoxication (in the late
stage),
the PGP 9.5
immunoreactivity of dermal
nerves appeared as fragmented
and
globular
in mice
(Figure
2(b)
).
A
single
Schwann cell
(a) (b)
(c) (d)
Figure 2 Dermal nerves seen in
acrylamide-intoxicated
mic
e
.
Skin
sections of the control group (a
and
c) and
21
days in acrylamide intoxicated mice (the late
stage
,
b and d) seem by
immunostaining
with
protein gene product 9.5
(PGP 9.5)
(a, b) and by regular electron microscopy
(c,
d). (a)
PGP
9.5
(+)
der
-
mal nerves showing a discrete linear shape in control
g
r
oup
.
(b) Dermal nerves showing
fr
ag
men
t
ed
shape with a globular
appearance
in
acrylamide-intoxicated
mic
e
.
(c) Unmyelinated
nerves
sho
wing
as enclosed by a single Schwann
cell
in the dermis of control
g
r
oup
.
T
he
axoplasm
and organelles
sho
w
a regular
struc
tur
e
.
(d)
T
he
proportion
of intact axons is variable in
acrylamide-
intoxicated
mic
e
.
S
ome
axons seem like swollen
shape
,
the corruption has become in organelles and
the
appearance
of
v
acu
-
oles
.
Bars
=
10
μ
m
(a,
b
)
=
1
μ
m
(c,
d)
[41]
.
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enveloped the unmyelinated nerves at the ultrastructural level in the control mice
(Figure
2(c)).
Conversely, dermal axons became
s
w
ollen
with dissolution of
organelles and the
appearance
of
vacuoles
in
acrylamide-intoxicated
mice (Figure 2(d))
[41].
Acrylamide administration to F334/N rats (for male and female) caused retinal
degeneration in the
e
y
es.
The incidence of degeneration
raised
after the administra-
tion of
0.70
mM to the male
rats,
whereas it raised after the administration of 0.35
and
0.70
mM to the
females.
Some degeneration
was
recorded in the retina,
includ
-
ing the loss of
photor
eceptor
s
related with
h
ypocellular
ity and thinning in
other
retinal
layers
[30].
In preputial
glands,
the
prevalence
of duct
ectasia
had been
increased
by
administra- tion of
acrylamide (0.175,
0.35, and
0.70
mM) to the male rats.The
dilation of the k
er
-
atin-filled main ducts is a
microscopical
sign of this
lesion.
Furthermore, inflammation also usually exists in diverse
intensity.
Two non-
neoplastic lesions, which were focal hypertrophy and diffuse cytoplasmic
vacuolation, including adrenal cortex appeared with the incidence being
significantly
raised in the
0.70
mM of acrylamide-treated
female rats.
Focal
hypertrophy referred to
as
the varied
focal
expansion of cortical cells in the zona
glomerulosa
or zona
fasiculata
of
adrenal
cortex had occurred by administra- tion of
acrlamide
.
The
compression
of adjacent
tissue was
not recorded. The cytoplasm
was
mostly eosinophilic
and
granular
in natur
e
,
and some of them had
several
lipid vacu-
oles,
although lipid accumulation
was
not the first reason of cellular
enlargement.
The
cytoplasmic
lipid
vacuoles
of the zona
fasiculata
or zona
reticularis increased
in a focal
or
diffuse
type
.
In the
spleen,
the
proliferation
of hematopoietic
cells elevated
by
0.70
mM
of
acrylamide administration
to the female
rats.
A slight enlargement of the
spleen
w
as
usually recorded. The splenic enlargement derived from the increased
hematopoietic
activity
had been
microscopically shown.
Bone marrow
hyperplasia
and
ovarian
atrophy, which were known
as
nonneoplastic
lesions, significantly
increased in
the 0.35
and/or
0.70
mM groups of
female rats
[30].
Acrylamide rapidly distributed to tissues [17,42–44]. Acrylamide distribution
appeared to be the highest in the muscle
tissue
ranging between 30% and 50% of
the
administered dose in dogs and pigs, after acrylamide administration of
1
mg/kg
b
w
.
Liver
was
the next with about 14% in
dogs,
whereas the
gastrointestinal
tract
was
the
second with about
20%
in
pigs.
In
pigs,
the absorption of
acrylamide
would
be slower than dogs [45].
After administration
of
120
mg/kg (2,3-14C)
acrylamide
to the
male
and
13.5–17.5
days pregnant
female Swiss–Webster
mice
,
radioactive-labeled acrylamide was
detected
in
the
gastrointestinal
tract, liver,
pancreas, testis,
brain, and
gallbladder, as
well
as
epithelia of oral cavity,
esophagus,
and bronchi. The
13.5
days fetuses also had
uniformly labeled
acrylamide,
whereas fetal brain had slightly increased level. In the
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tissues
of
17.5
days
fetuses,
the distribution of
labeled acrylamide resembled
that in the
maternal
tissues b
ut
the
increased
level
was
reported in
fetal
skin [43].
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The blood
tissue
had the majority of the
absorbed
dose at
24
h
following
a 6-h
inha
-
lation exposure to
3
ppm
acrylamide
in
rats,
followed
by the
skin,
spleen,
and
lung.
Ho
w
-
ever, the distribution pattern
was
different although the same protocol
was
carried
out
in mice.The skin had the highest level of the
absorbed
dose followed
by the subcutane- ous
fat, testes,
and blood [44].
Acrylamide doses
less
than
15
mg/kg/day did not cause serious problems in
clinical
signs
of toxicity or neurotoxicity,
indices
of reproductive performance
(mating,
pregnancy, and
fertility)
or the number of corpora lutea and the
signs
of
histological
or
neur
opatho
-
logical changes.
However,
doses
higher than
15
mg/kg/day
resulted
in the
signs
of
neur
o
-
toxicity and
changes
in copulatory behavior.These higher
doses also
caused
a
decrease
in
fertility affecting
sperm motility and morphology in both
rats
and
mice [46,47].
CARCINOGENICITY IN ANIMAL
STUDIES
FAO/WHO
reported that acrylamide
was
carcinogenic in rats, producing
increased
incidences
of benign and
malignant
tumor
s
in some
organs
such
as thyroid,
adr
enals,
and tunica
vaginalis.
Hence,
acrylamide
induced lung and skin tumors, in a
series
of
non-
standard carcinogenicity bioassays
in
mice
.
Animal experiments have
shown that acryl- amide is a multiorgan carcinogen in mice and rats. However,
none exhibited excess cancer risk at lower
doses
of
acrylamide
[48].
Two-year
studies
were done in F-344 rats receiving
doses
of about 0, 0.01, 0.1,
0.5, or
2
mg/kg/day acrylamide in drinking
w
ater
.
The incidence of
tumor
s
in
mammary and
clitoral
glands,
uter
us,
testes,
brain and
spinal cor
d,
adrenal, pituitary,
thyroid,
and oral cavity increased according to histopathological results at the
termination stage [3,6]. Another two-year study in Fischer F344/N male and
female rats that had received drinking water at concentrations of 0.0875, 0.175,
0.35, and
0.70
mM (equivalent
to
0.33, 0.66, 1.32,
and
2.71
mg/kg bw/day for
males
and
0.44, 0.88, 1.84,
and
4.02
mg/kg
bw/day for
females) was
performed in NTP
laboratories.
At the end of the
study,
the
incidence of cancer in the
pancreatic islets
and of
malignant mesotheliomas
increased
in male
rats,
whereas the incidence of
cancer
s
in the clitoral
gland,
mammary
gland,
skin, liver, and tongue increased in female
rats.
The incidence of
thyroid gland and heart
tumor
s
increased
in both male and
female rats
receiving
acrylamide
[30].
A previous study demonstrated that acrylamide had carcinogenic properties.
A/J
mice (male and
female)
were
administered
with
acrylamide
by
gastric
intubation,
intra
-
peritoneal injection, and
topically
to the
shaved
back over
8
weeks starting from an
age of
8
weeks.The dose
levels
were 12.5 and
25
mg/kg bw applied by
gavage
three
times a week, or were 0, 1, 3, 10, 30, and
60
mg/kg bw applied three times a week by
intraperi- toneal injection. After the administration, lung adenomas appeared in both
sexes in a dose-related manner. Female SENCAR mice administered with
Acrylamide
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intraperitoneal
injec
-
tion of acrylamide and dermal application of TPA (i.e., the
skin tumor pr
omoter
,
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issues
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12-O-tetradecanoylphorbol-13-acetate) following an initiation promotion pr
otocol.
Combined
acrylamide
and
TPA
administration
exhibited
increased skin
tumor
s
in SEN
-
CAR mice
[2].
In the
same laboratory, female
Swiss-ICR mice were
administered
with
acrylamide
orally six times over
2
weeks with total
doses
of 75, 150, and
300
mg/kg.
At the end of one
year,
skin and lung
tumor
s
were observed in mice [49].
In a two-year
study,
B6C3F1 mice (96,
males
and
females)
received
acrylamide,
con
-
centrations
of
0.0875,
0.175,
0.35,
and
0.70
mM
(6.25,
12.5,
25,
and
50
ppm
acrylamide)
in the drinking water ad
libitum.
Afterward,
the incidence of the Harderian
gland adenoma and combined Harderian
gland
adenoma or
adenocarcinoma was raised
significantly
in all
acrylamide
dose groups of male B6C3F1
mice.
Furthermore, the
incidence of lung alveo- lar/bronchiolar adenoma and combined lung
alveolar/bronchiolar adenoma or carcinoma
was raised significantly
at 0.175 and
0.70
mM
acrylamide
doses.
A
significant increase
w
as
observed in the incidence of stomach
(forestomach)
squamous cell papilloma and
com
-
bined stomach
(forestomach)
squamous cell papilloma
or
carcinoma
at 0.35 and
0.70
mM
acrylamide
doses.
The
incidence of Harderian gland adenoma
was raised significantly
for all doses in
females.
The combined incidence of mammary gland adenoacanthoma
or
adenocarcinoma
was raised significantly
at 0.175, 0.35, and
0.70
mM
acrylamide,
and
the
incidence of
mammary gland adenocarcinoma
was
raised significantly at 0.175 and
0.70
mM
acrylamide.
It
was
observed that the incidences of lung
alveolar/bronchiolar adenoma, combined lung alveolar/bronchiolar adenoma or
carcinoma, and malignant mesenchymal skin
tumor
s
(fibrosarcoma, hemangiosarcoma,
liposarcoma,
myxosarcoma,
neurofibrosarcoma,
or
sarcoma)
were
raised significantly
at
0.35 and
0.70
mM acrylamide doses.The
incidences
of ovary
granulosa
cell tumor
(benign) and
mammary gland
adeno
-
carcinoma at
0.70
mM were
also significantly
increased
in
female
B6C3F1 mice
[30]
.
The
incidence of the tunica
vaginalis
mesotheliomas in Fischer 344 rats can be increased by long-term acrylamide
exposure.
The mesotheliomas of tunica
vaginalis
testis of Fischer
344
rats are
benign and
equivalent
to human benign
mesothelioma
of tunica
vaginalis
testis or adenomatoid
tumor
s
by
reason
of
cellular
uniformity
[50,51]
.
In
Beland’s
stud
y
,
F344/N
rats received 0,
0.0875,
0.175,
0.35,
and
0.70
mM
doses
of
acrylamide
in the
drinking water for
2
y
ear
s,
and it
has
been shown a
dose-related increasing
trend in
follicular cell
adenoma and carcinoma, and combined follicular cell adenoma or
carcinoma in thyroid gland. Malignant mesothelioma
was
commonly appeared in the
epididymis,
and all rats having mesothelioma on the
testicular
tunics
also
had this
neoplasm
on the
epididymis
in males. In
females,
the prevalence of fibroadenomas in
the mammary gland
was
significantly
increased
than the control group
[51]
.
In the
past
2-year
carcinogenicity study,Wistar
Han
rats received
0.5–3.0
mg/kg/day
doses
of
acrylamide
in drinking water.There are signifi- cantly
increased incidences
of thyroid
follicular neoplasms
in
males
and
females.
Increased incidence of mammary
fibroadenomas
in
females
is observed but not
statistically
signifi- cant [52].Two-year
Acrylamide
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carcinogenicity
study
results
in
animals
that received
different doses
of
acrylamide
are
shown in Table 2.
Acrylamide
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Table 2 Summary of some 2-year carcinogenicity study results in animals receiving different doses of
acrylamide
T
est
animal
G
ender
Min and max
dosage
of
acrylamide
Tumor
type
R
ef
er
enc
es
F344 rats
F344 rats
F344 rats
F344 rats
F344/N
(Nctr) rat
F344/N
(Nctr) rat
B6C3F1/
Nctr mice
B6C3F1/
Nctr mice
F344 rats
F344 rats
B6C3F1
mice
B6C3F1
mice
Wistar
Han rats
Wistar
Han rats
Female
Male
Female
Male
Female
Male
Female
Male
Female
Male
Female
Male
Female
Male
0.01–2.0
mg/kg
bw/da
y
0.01–2.0
mg/kg
bw/da
y
1.0–3.0
mg/kg
bw/
day
0.1–2
mg/kg
bw/
day
0,
0.0875–0.70
mM
0,
0.0875–0.70
mM
0,
0.0875–0.70
mM
0,
0.0875–0.70
mM
0.44–4.02
mg/kg
bw/da
y
0.33–2.71
mg/kg
bw/da
y
1.10–9.96
mg/kg
bw/da
y
1.04–8.93
mg/kg
bw/da
y
0.5–3.0
mg/kg
bw/
day
0.5–3.0
mg/kg
bw/
day
Mammary
gland adenoma, fibroadenoma,
or
fibroma,
thyroid
gland follicular
cell adenoma or
carcinoma,
oral
cavity
papilloma, uterine
adenocarcinoma, clitoral gland adenoma,
pituitary adenoma
Thyroid gland
follicular
cell
adenoma,
mesothelioma of
the
testes
tunica
albuginea, adrenal
pheochromocytoma,
benign Mammary gland
fibroadenoma,
thyroid gland
follicular
cell adenoma or carcinoma
Thyroid gland
follicular
cell
adenoma,
mesothelioma of
the
testes
tunica
Mammary gland
fibroadenoma, clitoral
gland
carcinoma,
oral
cavity papilloma
or
carcinoma,
skin fibroma or sarcoma
Thyroid
follicular
cell
carcinoma, cardiac schwannomas,
testicu-
lar
mesothelioma,
pancreatic
islet
cell adenoma
Harderian
gland adenoma,
lung alveolar/bronchiolar adenoma,
mammary
gland adenoacanthoma,
mammary
gland
adenocarci-
noma, ovarian
granulosa
cell tumor, skin
sarcoma,
hemangiosar-
coma, liposarcoma, myxosarcoma,
neurofibrosarcoma,
or sarcoma Harderian gland
adenoma,
lung
alveolar/bronchiolar adenoma,
forestomach squamous
cell
papilloma
Mammary gland
fibroadenoma,
thyroid gland
follicular
cell adenoma or carcinoma
Thyroid gland
follicular
cell adenoma or
carcinoma,
meso-
thelioma of the
epididymis
or testes tunica vaginalis
Harderian gland
adenoma,
mammary gland adenocanthoma
and
adenocarcinoma,
lung
alveolar,
bronchiolar
adenoma,
ovary
granulosa
cell
tumor
s
(benign), skin, various
types of
sarcoma,
stomach,
foretomach
squamous
cell papilloma
Lung
alveolar,
bronchiolar combined adenoma and
carcinoma, stomach
squamous
combined
papilloma
or
carcinoma
Mammary
gland fibroadenoma, adenoma,
adenocarcinoma,
adenoma and/or
adenocarcinoma,
thyroid
follicular
cell
adenoma, follicular
cell
adenocarcinoma, follicular
cell
adenoma and/or adenocarcinoma
Thyroid
follicular
cell
adenoma, follicular
cell
J
ohnson et al.
(1986) [3]
J
ohnson et al.
(1986) [3]
Friedman et al.
(1995) [6]
Friedman et al.
(1995) [6]
Beland et al.
(2013) [51]
Beland et al.
(2013) [51]
Beland et al.
(2013) [51]
Beland et al.
(2013) [51]
NTP(2012) [30]
NTP(2012) [30]
NTP(2012) [30]
NTP(2012) [30]
Maronpot et al.
(2015) [52]
Maronpot et al.
(2015) [52]
Ac
ryl
am
ide
in
F
o
od
76
In a
study,
F344 rats and B6C3F1 mice were exposed to
acrylamide
with
drinking water containing
acrylamide
by repeat dosing [53].The
daily doses
of
acrylamide
were about
2.59
±
0.69
mg/kg bw/day for mice,
1.07
±
0.28
mg/kg
bw/day for
female
rats, and
0.96
±
0.28
mg/kg bw/day for male
rats.
The
analysis
results of Hb adducts of
acrylamide
and
glycidamide
formation showed
significant
linear
relationships
betw
een the
acrylamide
and
glycidamide
Hb adduct
levels
and
the corresponding AUCs (area under the curves) [53]. In preliminary
studies,
it has
been demonstrated that acryl- amide caused fibroadenomas of the mammary
gland and thyroid gland follicular
tumor
s
in rats [3,6].
IN VITRO AND IN VIVO
GENO
T
O
XICIT
Y
In
addition,
acrylamide
and
glycidamide
are potential germ
cell mutagens
[54,55]
.
P
rev
i
-
ous
studies
have shown that
acrylamide
and its metabolite
glycidamide
induce
micr
onu
-
clei in rodents [56,57]. Furthermore, it has been shown that they are
mutagenic and induce micronuclei in big blue
mice.
Both
acrylamide
and
glycidamide
are genotoxic in mice and both of them induce the mutant
frequencies
and
types
of
mutations in the liver of mice
[58]
.
Several studies
were conducted to explore DNA
damage
induced by acryl- amide using the Comet
assay.
It
was observed
that there
was
genotoxic
effects
in
human
HepG2
cells
treated with 2.5, 5, 10, and
20
mM of
acrylamide
[59].
Acrylamide has genotoxic potential in vivo in somatic cells and germ
cells.
Thus,
acrylamide
can induce heritable damage at gene and at chromosome
level.
It has
strong
affinity
to proteins of the sperm
[54,55,58].
However, a number of
nongenotoxic mech
-
anisms
such
as
endocrine disruption and oxidative
stress
have
been proposed to
cause
at
least
some of the tumorigenicity of
acrylamide
in
rats
[60].
Glycidamide
which is a product of metabolized
acrylamide
is a reactive epoxide
and forms DNA
adducts.
This epoxide occurred in the CYP2E1 detoxification
system
and
is
a primary pathway which
is responsible
for the genotoxity of
acrylamide
in germ cells
[61,62]
.
The heritable
translocations
and
specific-locus
mutations
recovered in the off- spring of male mice exposed to
acrylamide
or
glycidamide
have
been
evaluated
in sev- eral studies. Exposure of spermatozoa or spermatids to
acrylamide or glycidamide
increases
the
frequency
of mutational
events.
Dominant
lethal mutations, heritable
trans- locations, and unscheduled DNA
synthesis
in germ
cells were
assayed
in male mice treated with
glycidamide
.
The metabolic conversion
of
acrylamide
to
glycidamide
may be responsible for the mutagenicity of acrylamide
[55,63]. Furthermore, a dominant lethal
assay
study using 1-aminobenzotriazole to
inhibit the metabolic conversion of
acrylamide
to
glycidamide
by cytochrome P450
was
performed in mice, and
tr
eatment with 1-aminobenzotriazole
decreased
the
dominant lethal
response
which occurred by
acrylamide
exposure.The
lethal effects
of
acrylamide
were inhibited in CYP2E1
knock
-
out mice
[64,65]
.
The
levels
of male
germ cell mutagenicity
[64],
micronuclei [62] and
77
Acrylamide
in
F
ood
Acrylamide
I
ntak
e
,
I
ts
E
ff
ec
ts
on
T
issues
and Cancer 77
glycidamide
DNA adducts
decreased
in CYP2E1 knockout mice after the administra-
tion of
acrylamide
[62].
The
strains
of
Salmonella typhimurium (Ames test),
Escherichia
coli
,
and
Klebsiella
pneum
o
n
i
a
are used to
assay bacterial
gene mutation induced by
acrylamide [66]
.
Acrylamide
generally did not induce reverse mutations in bacteria. Because of the
absence of CYP2E1,
capable
of
metabolizing acrylamide
to
glycidamide,
mutagenic
effects
of
acrylamide
do
not occur in some
bacterial strains.
However,
acrylamide
induced
chromosomal
aberrat
i
on
s
,
micronuclei (containing whole chromosomes or acentric
fragments),
sister chromatid
exchanges, polyploidy,
and
aneuploidy
with
lack
of
metabolic
activation
in
mammalian c
e
ll
s
[59,67–72].
HUMAN CANCER COHORT
STUDIES
A
series
of
epidemiological studies
have been carried out to
evaluate
the potential
asso- ciation between
acrylamide
intake and
cancer. Differences
in the
acrylamide
content in
foodstuffs
have caused the controversial results to estimate the actual
intake by
com
-
monly using an FFQ. These
differences
led to various debates of
accurately
classifying
persons as
low or high
acrylamide
consumers.
The CTS began in
1995–1996,
and 133,479 active and retired female
teacher
s
and
administrator
s
were recruited
as
a
large prospective
cohort. In this
large
cohort
stud
y
,
the
association
between the incidence of
breast
cancer and some air
pollutants
such
as
acryl-
amide,
carbon
tetrachloride,
and chloroprene
was
examined.The
baseline
dietary intake
was measured
using
California
State
T
eacher
s
Retirement
System
returned a completed baseline questionnaire. Some women not available for the
study conditions such
as
unknown history of prior cancer were excluded from the
study population. Thus,
the
resulting population
was
comprised of 112,378 women.
During the follow-up time of
15
years,
there has been 5676
cases
of
invasive
breast cancer, and many data from
this study present evidence for
increased
risk of
several
compounds such
as acrylamide,
car- bon tetrachloride, chloroprene, 4,4’-methylene
bis(2-chloroaniline),
propylene
oxide, and vinyl chloride. Estrogen receptor positive or progesterone receptor
positive
(ER+/
PR+)
tumor
s
have been related to higher ambient
levels
of
acrylamide benzidine,
car- bon
tetrachloride,
ethylidene
dichloride,
and vinyl chloride
[73].
A
serial
of cohort
studies
began in Sweden to lighten the
association
between
acryl- amide intake and cancer
[74,75]
.
A
prospective
cohort study in
Swedish
men
started in
1997 and
lasted
for
9.1
year;
45,306 men who were cancer-free and completed an
FFQ
were included for the
study.
Dietary intake
was assessed
using the FFQ which
had self- administered 96 food
items.
The mean of daily intake of
acrylamide was
36.1
±
9.6
μg. Through a follow-up
study,
it
was
understood that
coffee (23%),
whole-
grain
soft
bread
(17%),
whole-grain crisp bread
(8%),
white bread
(7%),
cookies/buns
78
Acrylamide
in
F
ood
(7%),
breakfast cereals
(6%),
w
afer
s/crack
er
s
(6%),
fried potato
(6%),
and potato
crisps
(4%) were
the
79
Acrylamide
in
F
ood
main
contr
ib
utor
s
to acrylamide intake. During the study, 2696 prostate cancer
cases were diagnosed and 1088 cases had localized prostate cancer, whereas 951
cases had
advanced
prostate
cancer.
Relative risk (RR):
0.88; 95%
confidence interval
(CI): 0.70–
1.09. No
significant association was
found between
acrylamide
intake and prostate
can
-
cer
[74]. Afterward,
to analyze dietary acrylamide intake and colorectal cancer
risk in Swedish men (number of
populations:
45,306), the same cohort population
data were used. RR: 0.95; 95% CI: 0.74–1.20.
Statistically significant association was
not found between the
acrylamide
intake and colorectal cancer [75].
To
evaluate
the
association
between dietary
acrylamide
intake and
epithelial
ovarian cancer, a population-based prospective study namely the Swedish
Mammography Cohort
was
conducted in
Swedish
women; 61,057 women were
enrolled for the study and dietary acrylamide intake
was
calculated by FFQ at
baseline 1987–1990, and at follow-up in
1997.
During the follow-up of
17.5
years,
368
cases
of
ovarian
cancer were
recognized.
There
was
no relationship found
between acrylamide intake and ovarian
cancer:
RR: 0.84; 95% CI:
0.62–1.14.
The
mean dietary
acrylamide
intake for Swedish women
was
24.6
±
7.6
μg/day
[76].
To
evaluate the relationship between acrylamide intake and
cancer,
the
same Swedish
cohort
was
used.Then, a total of 687 incident cases of endometrial carcinoma were
recognized from 36,369 women. The
values
of hazard ratio (HR) and
95%
CI,
r
espectiv
el
y
,
were 0.96 and 0.76–1.21.There
was
no relationship found between
endometrial carcinoma and
acrylamide
intake [76].
Breast cancer incidence
was
obtained from the Swedish Mammography
cohor
t.
During the follow-up, 2952
invasive breast
cancer
cases
were recognized and 2062
cases were
available
for information status of ER and PR from a total of 61,433
women.
Acrylamide
intake
was reversibly
correlated with
ER+PR+
and total
breast
cancer risk, but not
significant
after modification of dietary and other risk
f
actor
s
of
breast cancer. The RR of breast cancer for the highest versus the lowest quartile and
95% CI
w
er
e
,
respectively:
0.91 and 0.80–1.03 [77].
A multicenter prospective cohort study “European Prospective Investigation
into
Cancer and Nutrition (EPIC)” including 10 European countries started to
assess
the
relationship
between the dietary intake of
acrylamide
and ductal
adenocarcinoma
of
the
exocrine
pancreatic
cancer risk in
1992.
European men and women more than
500,000 were enrolled in the EPIC cohort
study.
After the exclusions from the
cohort,
Co
x
regression
modeling
was
used to
evaluate
the data including 477,308
participants.
At
the
end of the study, 856 pancreatic adenocarcinomas were
diagnosed and included for
analyses.
During a mean follow-up time of
11
years,
Denmark had the highest mean and median
dietary acrylamide
intake in men and
women.The UK and the Netherlands had,
respectively,
the second and the third
order, whereas Italy had the last for acrylamide intake. EPIC cohort study showed
that at
baseline,
the mean dietary
acrylamide
intake
was
26.22
±
14.79
μg/day, it
was
80
Acrylamide
in
F
ood
higher in men
(31.90
μg/day and
0.40
μg/kg
bw/da
y)
than in women
(23.81
μg/day–0.37
μg/kg bw/day). Furthermore, there
was
no
81
Acrylamide
in
F
ood
association
between acrylamide intake and pancreas cancer risk in EPIC (HR:
0.95% and
95%,
CI: 0.89–1.01).The
association
between
acrylamide
intake and
pancreas
cancer risk did not have
statistically significant
heterogeneity by
geographical location or by mean
acrylamide
intake (p
values
were found to be
>0.23) [78].The
same
EPIC
cohor
t
data were used to evaluate the
association
between esophageal carcinomas and acryl- amide
intake
.
After the follow-up, the
number of identified
esophageal carcinomas
w
as
341,
most of these
carcinomas was esophageal adenocarcinoma (EA
C).
An
increased
risk of
esophageal carcinomas was
observed at the second and third
quartiles.
HR for
Q2 vs Q1 were 1.75%, and 95% CI
was
1.12–2.74; HR for Q3 vs Q1
was
1.66,
95%
CI,
1.05–2.61.
No risk
was
observed at the fourth quartile which is the highest
[79].
The Netherlands Cohort Study appraised the association between several
cancer types and dietary
acrylamide
intake
[80–86].
Of 62,573 women and 58 279
men aged
55
69
years
enrolled to the Netherlands Cohort Study at
baseline
in 1986.
Breast
(2225
cases),
prostate (2246
cases),
colorectum (2190
cases),
lung (1895
cases),
lymphatic (1233
cases),
stomach (563
cases), pancreas
(349
cases),
renal cell (339
cases),
endometrium (221
cases),
brain (216
cases), esophagus
(216
cases),
ovary (195
cases),
larynx (180
cases),
oral
cavity (101
cases),
oropharynx (83
cases),
and thyroid (66
cases)
cancer
s
were detected in
t
h
i
s
prospective study.
Dutch Food and Consumer Product
Safety
Authority
was
data supplier to estimate acrylamide exposure. In women,
the mean acrylamide intake
w
as
21.1
±
11.9
μg/day, whereas
22.5
±
12.2
μg/day in
men.
The mean
acrylamide
intake
of total
study
population
was
21.8
±
12.1
μg/day
(i.e
.,
0.30
±
0.18
μg/kg bw/day).The
sources of
acrylamide
were
chiefly coffee (47%),
Dutch
spiced
cake
(15%),
cookies
(13%),
French
fries
(8%),
and potato
crisps (2%)
in the
subcohort.After
the follow-up
study
of
16.3
years, HRs for
lymphatic malignancies
were
evaluated.
HRs of multiple
myeloma
and follicular
lymphoma
were 1.14
(95%
CI:
1.01–1.27)
and 1.28
(95%
CI:
1.03–1.61)
per
10
mg acryl- amide/day increment in men.This cohort study indicated
that
acrylamide
could increase the multiple myeloma and
follicular
lymphoma in men
but not in women [85].
To determine the
association
between endometrial, ovarian, and breast cancer
risk and dietary
acrylamide
intake in the Netherlands Cohort Study, 1835, 327, and
300 of
cases
were
diagnosed
with
cancer
s
of
breast,
endometrium, and
ovary,
respectively,
at
the
end of the follow-up of
11.3
y
ear
s.
Significantl
y
,
an
increased
relation
was
found
betw
een
acrylamide
intake and
ovarian
cancer in
all
g
r
oups.
HR
value
and
95%
CI were 1.11 and
0.99–1.25, respectively,
with an increment of
acrylamide
daily intake of
10
μg.
Fur
ther
-
more,
statistically significant association was
found in the never smoker group.
HR, 95% CI: 1.17
(1.01–1.36).
No relation
was
found between
breast cancer
and
dietary
82
Acrylamide
in
F
ood
acrylamide intake. An increased risk of
postmenopausal
endometrial cancer
was
observed related with
increased dietary acrylamide
intake among nonsmoker
participants.
In
this
subcohort, the daily
acrylamide
intake
was
found to be
21.0
±
11.9
μg
(0.32
±
0.19
μ
g
/
k
g
bw/da
y).
While Dutch spiced cake
was
the main source of
diversity
in
acrylamide
intake for this population,
coffee,
French
fries,
potato
crisps,
and cookies were the next
stuffs
[80].
83
Acrylamide
in
F
ood
A case–cohort study from the Netherlands Cohort Study
was
performed to clarify
the
association
with key gen mutations in
Kirsten-ras
(KRAS) and adenomatous
pol
-
yposis
coli (APC) in the risk of colorectal carcinoma and
acrylamide
intake.The
tumor
tissues
of 733
cases
were examined to perform mutation
analysis
in codons 12–13 of
exon 1 of KRAS gene and 1286–1520 of exon 15 of APC gene. It
was
observed that
significantly
positive correlation in men between the colorectal cancer risk with an
active
mutation in KRAS gene and
acrylamide intake, whereas significantly reverse cor
-
relation were observed between tumor risk with truncating mutation in the APC
gene in women.The HR value of fourth
vs. first
quartile and
95%
CI were,
respectively,
2.12 and
1.16–3.87;
p 0.01 for KRAS mutation. HR
value
of fourth
vs.
first
quartile and 95% CI were,
respectively,
0.47 and 0.23–0.94; p 0.02 for APC
mutation [86]. In this large
prospective
cohort
stud
y
,
1986–2002,
a
positive
correlation
was
not determined
betw
een the head–neck and thyroid
cancer risk
and
dietary
acrylamide
intake in men.A decreased
risk was observed
for
oral cavity
and oro- and
hypopharynx
cancer
s
and intake of dietary
acrylamide
in
men.
An
increased
risk
was
found for oral
cavity
cancer and dietary acryl- amide intake in nonsmoker women
only (case number were not enough). The study group combined never
smok
er
s
and
former
smokers,
quit
smoking
before
10
years;
HRs
of former
smok
er
s
were higher
than the never
smok
er
s
but not
statistically
significant, and lower than the current
smok
er
s
and former
smokers,
quit smoking just before [83].
A
meta-analysis
of 25 studies on dietary acrylamide intake and colorectal, breast,
kidney, prostate,
ovarian,
bladder, and
esophageal
cancer risk has shown no
association but kidney has
increased
risk [87].
There are some
case–control studies
in
relationship
with EAC and
esophageal
squa-
mous cell carcinoma and
acrylamide
intake [87,88].
A
preliminary
cohort
study was
conducted among
w
ork
er
s
who were
occupationally exposed to
acrylamide
in the USA and the Netherlands from 1925 to
1983.The
cohor
t
consisted
of 2293 men and 6561
controls.
Data of exposure to
acrylamide
were gathered by inter
vie
ws,
after
that the
estimated
exposure
level was
found to be
0.3
mg/m3 for total work
day.
The respiratory cancer mortality
was
recorded at one plant (SMR = 1.31). However, the
author
s
did not comment any
association
with
acrylamide
exposure and cancer [89].
The
Nurses’
Health Study I (NHS I)
was
a
prospective
cohort that included
121,700
female nurses
started in
1976,
and then one more cohort
was
found
as
NHS
II in 1989 and
consisted
of 116,671
female nurses.
Usual dietary
acrylamide
intake
was
assessed b
y
a
semi-quantitative
FFQ in 1991 with a follow-up
every
4
year
in this
prospective
cohor
t
study.Wilson
and co
w
ork
er
s
recorded 1179 of
invasive breast
cancer
cases
among 90,628 of women in the premenopause phase aged
26–56
y
ear
s.
The
average acrylamide
intake of the lowest and the highest quintile were
10.8
μg/day
and
37.8
μg/day, respectively. French
fries (23%)
were the
first
contributor of
acrylamide, coffee (15%) was
the second, and
afterward
cold
breakfast
cereal
(12%),
potato chips
(9%),
and other potatoes (baked,
84
Acrylamide
in
F
ood
roasted,
and
mashed;
5%).
The
author
s
neither did nor found any
association
betw
een
dietary acrylamide
intake and
breast cancer
(RR:
0.92;
95%
CI:
0.76,
1.11)
[90]
.
In
NHS,
the
association
between the
dietary acrylamide
intake and
breast, endometrial,
and
o
v
ar
-
ian
cancer
s
was
evaluated among
premenopausal–postmenopausal
US
women; 6301
cases
of
invasive
breast cancer, 484
cases
of
invasive
endometrial
adenocarcinoma,
and
416
cases
of epithelial ovarian cancer were recorded from 1980 to 2006.
Acrylamide intake of the lowest quintile and the highest quintile ranged
9–26
μg/day, respectively. Coffee (20%)
was
the major source of acrylamide whereas
breakfast
cereal (15%) and French fries
(12%)
were the second and the third order.
An
association was
not found between acrylamide intake and breast cancer (RR:
0.95; 95% CI:
0.87–1.03).
An
ele
-
vated risk of endometrial cancer
was
found among
highest
acrylamide
consumer
s
(RR:
1.41; 95% CI,
1.01–1.97;
P
=
0.03).
There
was
no detected risk of ovarian cancer
with
acrylamide
intake (RR:
1.25; 95%
CI: 0.88–1.77) [91].
The UK
W
omen
s
Cohort Study for breast cancer occurrence including 33,731
women
was
started in 1995. It
was
adopted
as
UK arm of EPIC study to
assess
dietary information [92].The
results
of some cohort
studies
on
acrylamide
intake and
cancer are
summarized
in Table 3.
KEY
F
A
CT
S
Acrylamide was firstly classified as
a probable carcinogen by IARC in 1994
[1].
It
is determined
as a
“reasonably anticipated
to be a human
carcinogen”
by NTP in
2011 [30].
FAO/WHO
(Food and Agriculture Organization of the United
Nations/
World Health Organization) estimated the
acrylamide levels
in food
categories
and the contribution to total exposure of the
general
public.The
estimated average
intake for the general population
was
0.3–0.8
μg/kg body weight
(bw)/day [7].
Increased
tumor risk at
different sites was
found in 2-year drinking water
studies
on
experimental
animals administered
with
acrylamide
[3,6].Two
different
BMDL10 for
acrylamide
are estimated to be
0.31
mg/kg bw/day for the induction of mammary
tumor
s
in female rats and
0.18
mg/kg bw/day for Harderian gland
tumor
s
in male
mice by the
J
oint
FAO/WHO
Expert Committee on Food
Additives
[27].
Various approaches
have been
suggested
to
assess
the
quantitative risk
of
carcinogens,
and MoE (margin of exposure) approach is the most
favorite
among
them. Accord- ing to the
J
oint
FAO/WHO
Expert Committee on Food
Additives,
MoE is esti- mated to be 200 for an
average acrylamide
consumer,
whereas MoE is
estimated
to
be 50 for a high
acrylamide
consumer [26].
• Acrylamide has neurotoxic
effects
on experimental
animals
such
as
rats, mice,
and
guinea pigs
[31].
Axonal
degenerations
were observed in a dose-dependent
85
Acrylamide
in
F
ood
manner in
acrylamide-administered rats
[30]
.
Reproductive
tissues
are
particularly
vulnerable to the
administration
of
different doses
of
acrylamide
to the
rats
[30].
86
Acrylamide
in
F
ood
Table 3
R
esults
of cohort studies on dietary acrylamide intake and some cancer
t
ypes
Dietary
acrylamide
Cancer side Country Number of
cases
intake Acrylamide sources
R
ef
er
enc
es
Colorectal,
colon,
proximal colon
cancer,
distal
colon cancer
Breast
cancer
Endometrial
carcinoma
Breast
cancer
Breast
cancer
Head-neck and
thyroid cancer,
oral cavity,
larenx,
ora and
hypopharyngeal
cancer
Swedish
men
Swedish
women
Swedish
women
California
women
UK womens
Netherlends
11,326 participants
676 cases
61,433 participants
2952 cases
61,226 participants
687 cases
112,378 participants
5676 cases
33,731 participants
1084 cases
120,852 participants
36.1
±
9.6
μg
24.6
±
7.6
μg
24.6
±
7.6
μg
Mean
=
15
±
0.23
μ
g/da
y
Range =
10–21/da
y
Mean
=
21.8
±
12.1
μg
22.5
±
12.1
μg (male)
21.1
±
11.9
μg (female)
Coffee
23%,
grain
bread
17%,
crisp
bread
8%,
white bread 7%,
cookies/buns 7%,
wafers/cracker/rusks
6%,
fried potato 6%
Coffee
29%,
grain
bread
13%,
crisp
bread
8%,
white bread 7%,
cookies/buns 6%,
breakfast
cereals/muesli
7%,
fried potato 5%
BMI <25 alcohol
<20
nonsmoker
Patoto chips 23%,
bakery goods 17%,
potato
crisps
14%,
bread
10%, biscuits
9%,
coffee
8%
Coffee
15%,
Dutch
spiced
57%,
French
fries 14%.
cookies
3%, potato
crisps
5%
Larsson
et al.
(2009) [75]
Larsson
et al.
(2009) [77]
Larsson
et al.
(2009) [76]
Garcia et al.
(2015) [73]
Burley et al.
(2010) [92]
Schouten
et
al.
(2009)
[83]
Continued
A
cr
yla
mi
de
I
nt
ak
e
,
I
ts
E
ff
ec
t
s
on
T
is
sue
s
an
d
Ca
nce
r
Table 3
R
esults
of cohort studies on dietary acrylamide intake and some cancer
t
ypes—
c
on
t
d
Dietary
acrylamide
Cancer side Country Number of
cases
intake Acrylamide sources
R
ef
er
enc
es
Pancreatic 10 European 521,330 participants
26.22
± 14.79 -
Obon-
cancer countries
(Denmark,
France,
Germany,
Greece, Italy,
Norway, Spain,
Sweden,
the
Netherlands,
UK
(EPIC)
865 cases μg/day 10–90th
percentile range
w
as
10.25–45.89
μ
g/da
y
Santacana
et
al.
(2013)
[78]
Esophageal
cancer
European - Range
15.7–23.3
μ
g/
d
ay
Alcohol 3(0.3–12.3) Barrosa
(2014) [79]
Colorectal The Netherlands 120,852 participants
Coffee,
Dutch spice Hogervorst
cancer 733 cases
cake, cookies,
potato
chips,
French fries
et
al.
(2014)
[86]
Epithelial
Swedish
women 61057 participants
24.6
±
7.6
μg Coffee
29%,
grain
Larsson
et al.
ovarian cancer 368 cases bread
13%,
crip bread
8%, breakfast
cereals
7.5%, wafers
7%,
cookies/buns
6%,
fried
potato
5%,
boiled
potato
4.5%,
white
bread
4%,
bread crumbs
3.5%,
potato crisps
2.5%,
French
fries
2%,
oatmeal porridge
2.5%
(2009) [76]
Ac
ryl
am
ide
in
F
o
od
84
Lymphatic The Netherlands 120,852 participants
Coffee,
Dutch spice
Bonger
s
et al.
malignancies, 170
cases
(male),
cake, cookies,
potato
(2012) [85]
multiple 153
cases
(female)
chips,
French fries
myeloma,
diffuse for multiple
large-cell myeloma
lymphoma, 159
cases
(male),
chronic 100
cases
(female)
lymphoctic for
diffuse large
cell
leukemia, lymphoma
follicular 134
cases (male),
66
lymphoma,
cases
for chronic
waldenström lymphocytic
macrlob
u
-
leukemia
linemia- 42
cases (male),
47
immunocytoma,
cases (female)
for
mante cell
follicular
lymphoma
lymphoma, 54
cases (male),
35
T-cell
lympho
-
cases (female)
for
mas, hemato
-
Waldenström–
logical macroglobulinemia
malignancies and immunocytoma
Endometrial
ovarian,
breast
The Netherlands 62,573 participants
1835
cases
of breast
Daily:
21.0
±
11.9
μg Dutch
spices
cake Hogervorst
et
al.
(2007)
cancer
s
cancer; [80]
211
cases
of
endometrial cancer.
195
cases
of ovarian
cancer
Prostate cancer
Swedish
men
45,306 participants Mean:
23.7
= lowest
Larsson
et al.
2696 cases μg/day
49.8
μ
g/
da
y
= highest
(2009) [74]
A
cr
yla
mi
de
I
nt
ak
e
,
I
ts
E
ff
ec
t
s
on
T
is
sue
s
an
d
Ca
nce
r
Acrylamide
occurrence in
foods
and intake in
different
population
groups
have
been
studied extensively worldwide over the past decade. A few comprehensive
case– cohort
studies
such
as
“European Prospective Investigation into Cancer and
Nutr
i
-
tion
,
“Swedish Mammography Cohort,” and the “Netherlands Cohort
Study”
were performed to
define
the
relationship
between
acrylamide
intake and
cancer.Although the overall evidence is limited,
epidemiological
studies found no
direct association between
acrylamide
intake and risk of cancer except for the
renal
cell,
endometrial, and ovarian cancers.
MINI
DIC
TIONAR
Y
MoE MoE is margin of exposure and used by risk
assessors
to
evaluate
probable
safety
concerns that
stem from the food or feed of the
substances
which are genotoxic and
carcinogenic.
It
is
a ratio of two
f
actor
s
that
appraise
a population the dose at which a
small
but
measurable adverse
effect is
first
observed and the range of exposure to the matter considered.
Cohort study Cohort is a
large
group of people who are linked in some way and
share
common
features
(e.g.,
exposed to a drug,
chemical,
or
vaccine)
were born in a
particular
period.They are
followed over time for a
research. Scientists
observe these groups and uses correlations to define the
risk of subject relation.
BMDL BMDL is a
statistical
lower confidence limit on the dose at the BMD (benchmark dose) which is
described
a dose that produces a predetermined change in the
response
rate of an
adverse
effect
com
-
pared to the background. Risk
assessors
calculate the lower bound on the BMD
(typically
the 95%
lower confidence limit).This dose is
called
the Benchmark Dose Lower bound Confidence
Limit.This BMDL extended with reducing the
sample size,
resulting in a lower, more health
protective risk value, and
appropriately reflecting
uncertainty in the study.
Epoxidation Epoxidation is a reaction that
yields
an epoxide. Epoxide is a
cyclic
ether with a
thr
ee-
atom
ring which is equilateral triangle that makes it extremely
strained.
Epoxides are more reactive
by
the
strained ring than the other ethers. Epoxidation occur
s
in the P450 cytochrome
monooxygenase
sys
-
tem. For example, acrylamide is metabolized to
glycidamide,
a highly reactive
epoxide by the P450 cytochrome monooxigenase
CYP2E.
F344 rat The
Fischer
F344 inbred rats originate from a nucleus colony obtained from the National Insti-
tutes of Health,
Bethesda,
Mar
yland.
After an inbred strain has been divided into
several branches
for
a number of
years
and if this
separation
happens at the
early years
of
inbreeding,
genetic
variations
result among the branches
as
a result of new mutations. It is
called “substrains“
and remarked by a
slash
and
letter
s
or some
numbers.
For
example,
F344/N
is
the
substrain
maintained by the National
Institutes
of Health,
designated
as
“N
.
SUMMARY POINT
S
Acrylamide is a commodity chemical used in the industry and laboratory. It is
also obtained from carbon hydrate and amino acid by heating the
food, primarily
coffee,
the
products of potato, and French
fr
ies.
Acrylamide has
been proved to have
toxic
effects
in experimental
animals.
It has been shown
as
a toxic chemical to some
tissues
such
as
the
reproductive
tissues
and retina
besides
neurotoxicity in rats and
mice. It is converted
to
glycidamide which is a highly reactive epoxide by CYP2E
in humans, then acquires
Acrylamide
I
ntak
e
,
I
ts
E
ff
ec
ts
on
T
issues
and Cancer 8686
Acrylamide
in
F
ood
genotoxic and
carcinogenic properties
to
several
organs.
Epidemiological studies
did
not
indicate any
association
between occupational and dietary exposure of
acrylamide
and incidence of
cancer
.
A few
studies
have shown a
relationship
between
acrylamide
intake and the incidence of
cancer
s
in renal
cells,
endometrium, and ovary.
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... AA could induce DNA damage in the PC Cl3 and FRTL5 rat thyroid cell lines, as well as in human lymphoblastoid TK6 cells in the comet assay (Koyama et al., 2006). ÇEBİ (2016) reported that AA has a toxic potential in tissues including the reproductive and urinary system. It is also a known neurotoxic compound in experimental animals. ...
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The present work was planned to study the effects of E110 (sunset yellow) as a common synthetic in Egypt and E100 (curcumin) as a natural food-drug colorants on the testis of the male mouse. The plan of work was designed to cover six parameters: histopathological, cytochemical (involving DNA and total proteins), testis weight, sperm parameters (i.e., sperm abnormalities and sperm motility), and measuring testosterone levels in blood sera. The mice were divided into three groups, ten per each. The first group remained as controls, whilst the second orally given sunset yellow-E110 (30 mg/kg b.wt/day) as SY-group and the third one E100 'CU-group' also gavage 37 mg/kg b.wt., both fed on their acceptable daily intake (ADI) dosages for 60 days. The results detected that SY revealed distinct alterations in the desired parameters, particularly histological changes in structure of seminiferous tubules such as vacuolation, necrosis and multinucleate cells. Whilst, the cytochemical DNA and proteinic profiles of the SY-treatment mice exhibited severe damage in the DNA and total protein configurations. However, such deteriorations in the spermatogenic epithelia were also approved with changes in the other criteria after administration with E110. From such alterations, the E110 recorded a highly significant increase (P< 0.0001) in the abnormalities of sperm morphology and motility. Moreover, the testosterone levels in sera of male mice indicated the significant differences among groups. The molecular protocol manifested SY (E110) - induced DNA polymorphic changes in confrontation with control by primer OPC07, whilst CU (E100) kept on the control pattern. In conclusion, the present study explored the possibility of using the applied six parameters to assessment and differentiate between the two food flavours indicating that E100 (CU) is more biosafe than the synthetic additive E110 (SY).
... Besides this inorganic form, formation of acrylamide by heating the high carbohydrate food over 120 °C via Maillard reaction has aroused significant interest all around the world. The commonly consumed food sources containing acrylamide are coffee, French fries, fried potato products and roasted foods [5]. Roasting process not only destroys pellicle, microorganisms and food contaminants but also releases some food toxicants such as furfural, acrylamide [6]. ...
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The acrylamide content and color formation (CIE L*, a* and b*) of hazelnuts which processed at different roasting temperatures of 130 °C, 150 °C, 160 °C and 170 °C with roasting time for 15 and 30 min were evaluated. Acrylamide contents of roasted hazelnuts were measured by means of Ultra Performance Liquid Chromatography (UPLC). Acrylamide formation of roasted hazelnuts was undetectable and stayed under the instrument detection level in all treatments with an exception. The only acrylamide formation was detected in treatment of the highest heat (170 °C) and longest time (30 min) with the value of 19 ± 2.5 μg/kg which was just below the instrument’s detection limit of 20 μg/kg. Color analyses were performed using computer-aided image processing technology (CIE L*a*b*). The Euclidean distance (ΔE) and Browning index (BI) were calculated. Color L* values which show brightness and the degree of roasting ranged from 55.14 to 76.16. The lowest color L* values were calculated from the treatment that detected acrylamide. The color L* values, therefore, may be useable as a quick quality control parameter to estimate the sufficient roasting time and temperature in roasting process of hazelnuts. The roasting temperature at 170 °C and time for 30 min may be accepted as threshold values to avoid acrylamide formation in roasting process of hazelnut according to findings of the present study.
... Besides this inorganic form, formation of acrylamide by heating the high carbohydrate food over 120 °C via Maillard reaction has aroused significant interest all around the world. The commonly consumed food sources containing acrylamide are coffee, French fries, fried potato products and roasted foods [5]. Roasting process not only destroys pellicle, microorganisms and food contaminants but also releases some food toxicants such as furfural, acrylamide [6]. ...
... Nevertheless the sensory evaluation showed that improvements would be necessary. Still, the RF treated cookies were healthier, since acrylamide has been associated with disease and particularly cancer [63][64][65]. ...
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Background: Today, new lifestyles, higher incomes and consumer awareness are creating consumer demand for a year-round supply of high-quality, diverse and innovative food products. However, when it comes to innovation, the food sector is less changeable when compared to other sectors, such as high technology. Still, in the past decades much and important developments have been achieved in several areas related to foods and the food industry. Methods: A systematic review of scientific literature was conducted on Science Direct. The topics investigated were: aspects related to innovation in food development (such as the transfer of innovation, open innovation, collaborative innovation and consumer perception and its role in the developing process); the innovation in the food industry (particularly regarding the processing technologies and packaging, which are two prominent areas of innovation in this sector nowadays); the innovation in the cooking sector (particularly in regards to the molecular gastronomy and science based cooking). Results: A total of 146 articles were included in the review and the aspects focused allowed confirming that innovation has been recognized as a key driver of economic growth. Within the framework of ‘open innovation’, a number of key issues related to the acquisition of external knowledge in food technology must be taken into consideration. Food product development is highly dependent on the consumer perception and acceptance, and hence it is of utmost importance to include the consumer in the development process to minimize failure probabilities. The sectors of the food industry where important developments and innovation are registered include the processing technologies and the packaging systems, where the latest progresses have produced very significant outcomes. Conclusion: The present work allowed verifying the latest improvements and trend towards food product development from two perspectives, the product itself and the industrial processing. This sector is undoubtedly a major key for the success and competitiveness nowadays in the food industry.
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The main objectives of this study were to purify the glutathione S-transfereses (GSTs) and assess the effect of high doses of acrylamide (ACR) on male albino Wistar rat liver, kidney, testis and bran GST activities, and expression analysis of GST. ACR (50 mg/300 ml) was ingested for 40 days (20 doses) in drinking water on alternative days, on 40 day post ingestion the control and treated tissues were collected for GST purification by affinity column and biochemical characterization of GSTs by substrate specificities, and GST expression by immuno dot blots. In the analysis of the purified GSTs, we observed that liver GSTs were resolved in to three bands known as Yc, Yb and Ya; kidney GSTs were resolved in to two bands known as Yc and Ya; testis and brain GSTs were resolved as four bands known as Yc, Yb, Yβ and Yδ on 12.5% sodium dodecyl sulfate polyacrylamide gel (SDS PAGE). In the analysis of biochemical characterization, we observed a significant decrease (p < 0.05) in the specific activities of liver GST isoforms with the substrates 1-chloro 2,4-dinitrobenzene (CDNB), bromosulfophthalein (BSP), p-nitrophenyl acetate (pNPA), p-nitrobenzyl chloride (pNBC) and cumene hydroperoxide (CHP), but showed no activity with ethacrynic acid (ECA) and significant decrease (p < 0.05) in the specific activities of kidney GST isoforms with the substrates CDNB, pNPA, pNBC and CHP, but showed no activity with BSP and ECA, and a significant decrease (p < 0.05) in the specific activities of testis and brain GST isoforms with the substrates CDNB, BSP, pNPA, pNBC, ECA and CHP. In the analysis of immuno dot blots, we observed a decreased expression of liver, kidney, testis and brain GSTs. Through the affinity purification and biochemical characterization, we observed a tissue specific distribution of GSTs that is liver GSTs possess Yc, Yb and Ya sub units known as alpha (α) and mu (μ) class GSTs; kidney GSTs possess Yc and Ya sub units known as (α) alpha class GST; testis and brain GSTs possess Yc, Yb, Yβ and Yδ sub units known as alpha (α), mu (μ) and pi (π) class GSTs. Purification studies, biochemical characterization and immuno dot blot analysis were revealed the GSTs were sensitive to high doses of ACR and the high level exposure to ACR cause the damage of detoxification function of GST due to decreased expression and hence lead to cellular dysfunction of vital organs.
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