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DOI: 10.1093/toxsci/kfg165
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Risk Assessment of Acrylamide in Foods
E. Dybing* ,1 and T. Sanner
Exposure Assessment
The Norwegian Food Agency (2002) has conducted analysis
of 30 different food products plus eight brands of coffee (seven
lter coffee, one instant coffee) bought on the Norwegian
market. The sampling was chiey based on results from Sweden, such that priority was given to food items (potato crisps,
French fries) that were shown to have a high content of
acrylamide in the Swedish analysis. The analysis was performed on pooled samples of three identical products from the
same producer, but with different production dates. The analyses were carried out by the same accredited laboratory
(AnalyCen, Lidkoping, Sweden) that had conducted the Swedish analyses using LC-MS-MS methodology.
Data on intake in the adult population has been taken from
the national food survey NORKOST 1997 (Johansson et al.,
1997) based on a quantitative frequency questionnaire answered by 1291 males and 1381 females aged 16 79 years.
*Division of Environmental Medicine, Norwegian Institute of Public Health, P.O. Box 4404 Nydalen, NO-0403 Oslo, Norway,
and Institute of Cancer Research, Norwegian Radium Hospital, Montebello, NO-0310 Oslo, Norway
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TABLE 1
Estimated Intake of Acrylamide
Parameter
Males
g/day
Females
g/day
Males
g/kg bw/day
Females
g/kg bw/day
Mean
Median
90-percentile
97.5-percentile
38
29
77
125
29
24
55
88
0.49
0.41
1.01
1.62
0.46
0.42
0.86
1.45
Hazard Identication
Acrylamide is oxidized to glycidamide, a reactive epoxide, and undergoes conjugation with glutathione (Calleman
et al., 1990; Sumner et al., 1992). DNA adducts from
glycidamide have been reported following administration of
acrylamide to rodents (Segerback et al., 1995). Hemoglobin
adducts from direct reaction of acrylamide and from reaction with glycidamide have been detected in rodents administered acrylamide, in exposed humans, and in cigarette
smokers (Bailey et al., 1986; Bergmark, 1997; Bergmark et
al., 1991, 1993; Calleman et al., 1990, 1994; Fennel et al.,
2003). The relationship between the acrylamide and glyci-
TABLE 2
Contribution of Various Food Items to Estimated
Intake of Acrylamide
Food item
Males
Mean intake 38 g/day %
Females
Mean intake 29 g/day %
Soft bread
Bread, other
Biscuits
Potatoes, fried
French fries
Potato crisps
Other snacks
Coffee
Other
13.0
7.7
5.0
7.5
8.0
17.6
5.0
28.0
8.2
11.9
12.2
5.9
6.3
6.3
17.4
4.6
28.6
6.8
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TABLE 3
Estimated Intake of Acrylamide in Children Aged 9 and 13 Years
Parameter
Boys 9 years
(n 1299)
g/kg/day
Girls 9 years
(n 1658)
g/kg/day
Boys 13 years
(n 1711)
g/kg/day
Girls 13 years
(n 2068)
g/kg/day
Mean
Median
90-percentile
97.5-percentile
0.36
0.23
0.72
1.50
0.32
0.25
0.61
1.10
0.52
0.30
1.35
2.85
0.49
0.28
1.20
2.07
TABLE 4
Male Rats: Tumor Incidence after Exposure of 344 Male Rats to Various Doses of Acrylamide in the Drinking Water for 2 Years
Tumor type
Thyroid adenomas
Trend test p 0.001**
Trend test p 0.001
Testicular mesotheliomas
Trend test p 0.01
Trend test p 0.001
Adrenal pheochromocytomas
Trend test p 0.06
Oral focal hyperplasia
Trend test p 0.01
Control
0.01
0.1
0.5
2.0
1/60
(2%)
3/204
(1%)
3/60
(5%)
8/204
(4%)
3/60
(5%)
0/60
(0%)
0/58
(0%)
0/60
(0%)
7/59
(12%)
1/60
(2%)
2/59
(3%)
9/203
(4%)
7/60
(12%)
9/204
(4%)
7/60
(12%)
1/60
(2%)
1/59
(2%)
5/101
(5%)
11/60
(18%)*
8/102
(8%)
5/60
(8%)
4/60
(7%)
7/59
(12%)
12/75
(16)*
10/60
(17%)*
13/75
(17%)*
10/60
(17%)*
5/60
(8%)
Note. Acrylamide doses in mg/kg bw/day. The upper lines represent the study by Johnson et al. (1984, 1986), and the lower lines represent the study by
American Cyanamid Co. (1989) and Friedman et al. (1995).
*Signicant increase in tumor incidence (p 0.05), Fischers exact test; **Mantel-Haenszel trend test.
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TABLE 5
Female Rats: Tumor Incidence after Exposure of 344 Male Rats to Various Doses of Acrylamide in the Drinking Water for 2 Years
Tumor type
Thyroid adenomas
Trend test p 0.01**
Trend test p 0.001
Thyroid adenocarcinomas
Trend test p 0.01
0.01
0.1
0.5
2.0
0/58
(0%)
0/100
(0%)
1/58
(2%)
2/100
(2%)
10/60
(17%)
9/96
(9%)
2/60
(3%)
2/96
(2%)
1/60
(2%)
0/60
(0%)
0/59
(0%)
0/59
(0%)
11/60
(18%)
1/60
(2%)
2/60
(3%)
3/60
(5%)
1/59
(2%)
0/59
(0%)
9/60
(15%)
1/60
(2%)
1/60
(2%)
2/60
(3%)
1/58
(2%)
7/100
(7%)*
0/58
(0%)
3/100
(3%)
19/58
(33%)*
20/94
(21%)*
2/58
(3%)
2/94
(2%)
0/59
(0%)
1/60
(2%)
3/60
(5%)
16/100
(16%)*
3/60
(5%)
7/100
(7%)
23/61
(38%)*
26/95
(27%)*
6/61
(10%)
4/95
(4%)
5/60
(8%)
7/61
(11%)*
Note. Acrylamide doses in mg/kg bw/day. The upper lines represent the study by Johnson et al. (1984, 1986) and the lower lines represent the study by
American Cyanamid Co. (1989) and Friedman et al. (1995).
*Signicant increase in tumor incidence (p 0.05), Fischers exact test; **Mantel-Haenszel trend test.
had occurred from the end of the 1950s and the beginning of
the 1960s. A total of 29 deaths were observed up to 1982 (38.0
expected). There were 11 cancer deaths, compared to 7.9
expected. The increased number of cancer cases was due to
cancer of the digestive tract and the respiratory organ in a
subgroup that had previous exposure to organic dyes. Among
the employees who had no exposure to organic dyes, four
deaths were observed compared to 6.5 expected.
Collins and coworkers (1989) investigated causes of death in
four factories, three in the United States and one in the Netherlands, in order to assess possible cancer risks after exposure
to acrylamide. The investigation included 8,854 males employed in the factories between 1925 and 1976, and exposure
to acrylamide was dened as cumulative exposure 0.001
mg/m 3-years. A total of 2,293 males were identied as being
exposed. Information on smoking habits was available from
approximately 1/3 of the group. Among the exposed workers,
a signicantly reduced mortality from all causes was found
(Standardised Mortality Ratio [SMR] 81), but a weak indication of increased cancer incidence was revealed for pancreatic cancer (eight cases; SMR 203) (95% CI 87 400) as
well as for Hodgkins disease (ve cases; SMR 129 (95%
CI 42300). No increased trend was found in cancer deaths
when higher-exposed workers were compared to lower-exposed workers.
Marsh and coworkers (1999) have presented an update for
the period 1984 1994 of the same cohort of Collins and
coworkers (1989). For the period 19251994 the following
Control
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TABLE 6
Comparison of LED10 andT25 Values Estimated from the Two Acrylamide Drinking Water Studies
Experiment
LED10
Males
(testicular mesotheliomas)
Females
(mammary gland adenomas)
T25
Males
(testicular mesotheliomas)
Females
(mammary gland adenomas)
0.66
0.84
0.40
0.86
0.89
3.7
0.64
1.9
TABLE 7
Lifetime Cancer Hazards after Exposure to Acrylamide in Humans
Model
LED10 0.40 mg/kg bw/d
LED10 5 0.040 g/kg bw/d
HLED10 5 is estimated by dividing by 4.1
T25 0.64 mg/kg bw/d
T10 5 0.0256 g/kg bw/d
HT10 5 is estimated by dividing by 4.1
0.0098 g/kgbw/day
1.0 10 3
0.0062 g/kgbw/day
1.6 10 3
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TABLE 8
Lifetime Cancer Risks Related to Acrylamide in Food
Calculation basis
Lifetime risk
0.49
0.41
1.01
1.62
0.610 3
0.510 3
1.310 3
2.110 3
0.46
0.42
0.86
1.45
0.610 3
0.510 3
1.110- 3
1.910 3
Males
mean
median
90-percentile
97.5-percentile
Females
mean
median
90-percentile
97.5-percentile
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FORUM
Conclusion
In a limited exposure assessment of acrylamide in food
conducted in Norway, mean intakes were estimated to 38 and
29 g acrylamide per day in males and females, respectively,
corresponding to intake doses of 0.49 and 0.46 g per kg body
weight and day. The 97.5-percentiles of adults had intakes that
were approximately 3-fold higher than the mean intakes.
In 2-year drinking water cancer studies with acrylamide
(Friedman et al., 1995; Johnson et al., 1986), testicular mesotheliomas and mammary gland adenomas were consistently
found. Since acrylamide is converted to a mutagenic metabo-
14
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Bailey, E., Farmer, P. B., Bird, I., Lamb, J. H., and Peal, J. A. (1986).
Monitoring exposure to acrylamide by the determination of S-(2-carboxyethyl)cysteine in hydrolyzed hemoglobin by gas chromatography-mass
spectrometry. Anal. Biochem. 157, 241248.
Johansson, L., Solvoll, K., Bjrneboe, G. E., and Drevon, C. A. (1997). Dietary
habits among Norwegian men and women. Scand. J. Nutr. 2, 6370.
Johnson, K., Gorzinski, S., Bodner, K., and Campbell, R. (1984). Acrylamide:
A two-year drinking water chronic toxicity-oncogenicity study in Fischer
344 rats. Dow Chemical USA, Midland, MI.
Bergmark, E., Calleman, C. J., and Costa, L. G. (1991). Formation of hemoglobin adducts of acrylamide and its epoxide metabolite glycidamide in the
rat. Toxicol. Appl. Pharmacol. 111, 352363.
Johnson, K. A., Gorzinski, S. J., Bodner, K. M., Campbell, R., Wolf, C. H.,
Friedman, M. A., and Mast, R. W. (1986). Chronic toxicity and oncogenicity
study on acrylamide incorporated in the rinking water of Fischer 344 rats.
Toxicol. Appl. Pharmacol. 85, 154 168.
Bull, R. J., Robinson, M., Laurie, R. D., Stoner, G. D., Greisiger, E., Meier,
J. R., and Stober, J. (1984a). Carcinogenic effects of acrylamide in Sencar
and A/J mice. Cancer Res. 44, 107111.
Bull, R. J., Robinson, M., and Stober, J. A. (1984b). Carcinogenic activity of
acrylamide in the skin and lung of Swiss-ICR mice. Cancer Lett. 24,
209 212.
Butterworth, B. E., Eldrigde, S. R., Sprankle, C. S., Working, P. K., Bentley,
K. S., and Hurtt, M. E. (1992). Tissue-specic genotoxic effects of acrylamide and acrylonitrile. Environ. Mol. Mutagen. 20, 148 155.
Calleman, C. J. (1996). The metabolism and pharmacokinetics of acrylamide:
Implications for mechanisms of toxicity and human risk estimation. Drug
Metab. Rev. 28, 527590.
Calleman, C. J., Bergmark, E., and Costa, L. G. (1990). Acrylamide is
metabolized to glycidamide in the rat: Evidence from hemoglobin adduct
formation. Chem. Res. Toxicol. 3, 406 412.
Calleman, C. J., Wu, Y., He, F., Tian, G., Bergmark, E., Zhang, S., Deng, H.,
Wang, Y., Crofton, K. M., Fennell, T., and Costa, L. G. (1994). Relationships between biomarkers of exposure and neurological effects in a group of
workers exposed to acrylamide. Toxicol. Appl. Pharmacol. 126, 361371.
Collins, J. J., Swaen, G. M. H., Marsh, G. M., Utidjian, H. M. D., Caporossi,
J. C., and Lucas, L. J. (1989). Mortality patterns among workers exposed to
acrylamide. J. Occup. Med. 31, 614 617.
Dybing, E., Sanner, T., Roelfzema, H., Kroese, D., and Tennant, R. W. (1997).
T25: A simplied carcinogenic potency index: Description of the system
and study of correlations between carcinogenic potency and species/site
specicity and mutagenicity. Pharmacol. Toxicol. 80, 272279.
European Commission (2002). Opinion of the Scientic Committee on Food
on new ndings regarding the presence of acrylamide in food. http://
europa.eu.int/comm/food/fs/sc/scf/out131_en.pdf
Segerback, D., Calleman, C. J., Schroeder, J. L., Costa, L.G., and Faustman,
E. M. (1995). Formation of N-7-(2-carbamoyl-2-hy7droxyethyl)guanine in
DNA of the mouse and the rat following intraperitoneal administration of
[ 14C]acrylamide. Carcinogenesis 16, 11611165.
Generoso, W.M., Sega, G. A., Lockhart, A. M., Hughes, L. A., Cain, K. T.,
Cacheiro, N. L., and Shelby, M. D. (1996). Dominant lethal mutations,
heritable translocations, and unscheduled DNA synthesis induced in male
mouse germ cells by glycidamide, a metabolite of acrylamide. Mutat. Res.
371, 175183.
Sobel, W., Bond, G. G., Parsons, T. W., and Brenner, F. E. (1986). Acrylamide
cohort mortality study. Brit. J. Ind. Med. 43, 785788.
Stadler, R. H., Blank, I., Varga, N., Robert, F., Hau, J., Guy, P. A., Robert,
M. C., and Riediker, S. (2002). Acrylamide from Maillard reaction products.
Nature 419, 449.
Bergmark, E., Calleman, C. J., He, F., and Costa., L. G. (1993). Determination
of hemoglobin adducts in humans occupationally exposed to acrylamide.
Toxicol. Appl. Pharmacol. 120, 4554.
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using 13C nuclear magnetic resonance spectroscopy. Chem. Res. Toxicol. 5,
81 89.
Swedish National Food Agency. Press conference. Uppsala, 24 April 2002.
Available at http://www.slv.se.
Tareke, E., Rydberg, P., Karlsson, P., Eriksson, S., and Tornqvist, M. (2000).
Acrylamide: A cooking carcinogen? Chem. Res. Toxicol. 13, 517522.
Tyl, R. W., Friedman, M. A., Losco, P.E., Fisher, L. C., Johnson, K. A.,
Strother, D. E., and Wolf, C. H. (2000). Rat two-generation reproduction
and dominant lethal study of acrylamide in drinking water. Reprod. Toxicol.
14, 385 401.
15
U.S. Environmental Protection Agency [U.S. EPA] (1996). Proposed guidelines for carcinogen risk assessment. Fed. Reg. 61, 17960 18011.
U.S. Environmental Protection Agency [U.S. EPA] (1999). Draft Revised
Guidelines for Carcinogen Risk Assessment. USEPA, Washington, DC.
Wogan, G. N., Paglialunga, S., and Newberne, P. M. N. (1974). Carcinogenic
effects of low dietary levels of aatoxin B 1 in rats. Food Cosmet. Toxicol.
12, 681 685.
World Health Organization [WHO] (1996). Guidelines for Drinking-Water
Quality. 2nd ed., Vol. 2. Health criteria and other supporting information.
International Programme on Chemical Safety, Geneva.