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Improved basis for cancer risk assessment of acrylamide from food: Determination of glycidamide in vivo doses
Stockholm University, Faculty of Science, Department of Materials and Environmental Chemistry (MMK).
2010 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Acrylamide is formed in heat processing of many common foods. According to animal cancer tests acrylamide is a carcinogen. To estimate the cancer risk from exposure via food, the response at high doses in the cancer tests with rats has to be extrapolated to the exposure levels in humans. Acrylamide is biotransformed to the epoxide glycidamide, which is assumed to be the cancer-risk increasing agent. Therefore in vivo doses of both acrylamide and glycidamide should be measured in rats and humans and related to the acrylamide intake. In vivo doses (area under the time-concentration curve, AUC) of reactive compounds can be determined from measured reaction products, adducts, to hemoglobin (Hb).

A study in mice showed that the food matrix does not have an influence on the absorbed amount of acrylamide from food. There was a linear dose-response of Hb-adduct levels from acrylamide and glycidamide.

For cancer risk assessment it is important to describe variations between individuals in intake and in AUC. Hb-adduct levels of acrylamide and glycidamide were studied in two large groups. In non-smokers the acrylamide and glycidamide-adduct levels varied with a factor of 5 and 8, respectively. The influence of other compounds in the diet on metabolic formation/elimination of glycidamide was demonstrated by associations between the ratio of glycidamide-to-acrylamide-adduct levels and alcohol intake. Furthermore, a non-linearity between glycidamide and acrylamide-adduct levels was shown at low exposure levels. AUCs from acrylamide and glycidamide in rats exposed as in the cancer tests were measured and compared with AUCs in humans exposed to acrylamide through food. The AUC of glycidamide per given dose of acrylamide was somewhat higher in humans than in the rats. Altogether the generated data could be used to improve the cancer risk estimate of acrylamide in food. The obtained data strengthen earlier preliminary cancer risk estimates of acrylamide.

Place, publisher, year, edition, pages
Stockholm: Department of Materials and Environmental Chemistry (MMK), Stockholm University , 2010. , 44 p.
National Category
Environmental Sciences
Research subject
Environmental Chemistry
Identifiers
URN: urn:nbn:se:su:diva-37757ISBN: 978-91-7447-012-3 (print)OAI: oai:DiVA.org:su-37757DiVA: diva2:305122
Public defence
2010-04-16, Magnélisalen, Kemiska övningslaboratoriet, Svante Arrhenius väg 16 B, Stockholm, 10:00 (English)
Opponent
Supervisors
Note
At the time of the doctoral defense, the following papers were unpublished and had a status as follows: Paper 4: Manuscript. Paper 5: Manuscript.Available from: 2010-03-25 Created: 2010-03-22 Last updated: 2010-05-17Bibliographically approved
List of papers
1. Internal doses of acrylamide and glycidamide in mice fed diets with low acrylamide contents
Open this publication in new window or tab >>Internal doses of acrylamide and glycidamide in mice fed diets with low acrylamide contents
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2008 (English)In: Molecular Nutrition & Food Research, ISSN 1613-4125, E-ISSN 1613-4133, Vol. 52, no 8, 974-980 p.Article in journal (Refereed) Published
Abstract [en]

The formation of acrylamide during heating of certain foodstuffs constitutes a potential health hazard. The health risk assessment should be based on knowledge about the relation between dietary exposure to acrylamide and internal doses of acrylamide and its genotoxic metabolite glycidamide. The primary aim of this study in mice was to measure these relationships at low levels of acrylamide intake through the diet. A secondary aim was to clarify which extraction method should be used when analyzing acrylamide in food in order to obtain a correct measure of the acrylamide that is available for absorption. In the analysis procedure, alkaline extraction has earlier shown much higher measured acrylamide levels in certain foods compared to water extraction. In this subcronic study the administered diets were composed to give five levels of acrylamide intakes between 3 and 50 mug/kg body weight per day (calculated on figures obtained after water extraction). Internal doses of acrylamide and glycidamide were measured through hemoglobin (Hb)-adducts. The results showed linear relationships between the exposure of acrylamide and Hb-adduct levels from both acrylamide and glycidamide at these low exposure levels. The study also showed that the "extra" acrylamide measured with alkaline extraction does not correspond to bioavailable acrylamide.

Keyword
Acrylamide, Diet, Glycidamide, Hemoglobin adducts, Internal dose
Identifiers
urn:nbn:se:su:diva-14310 (URN)10.1002/mnfr.200700341 (DOI)000258965300015 ()18496815 (PubMedID)
Available from: 2008-08-22 Created: 2008-08-22 Last updated: 2010-03-23Bibliographically approved
2. Approach for cancer risk estimation of acrylamide in food on the basis of animal cancer tests and in vivo dosimetry
Open this publication in new window or tab >>Approach for cancer risk estimation of acrylamide in food on the basis of animal cancer tests and in vivo dosimetry
2008 (English)In: Journal of Agricultural and Food Chemistry, ISSN 0021-8561, E-ISSN 1520-5118, Vol. 56, no 15, 6004-6012 p.Article in journal (Refereed) Published
Abstract [en]

The question about the contribution from acrylamide (AA) in food to the cancer risk in the general population has not yet had a satisfactory answer. One point of discussion is whether AA constitutes a cancer risk through its genotoxic metabolite, glycidamide (GA), or whether other mechanism(s) could be operating. Using a relative cancer risk model, an improvement of the cancer risk estimate for dietary AA can be obtained by estimation of the genotoxic contribution to the risk. One cornerstone in this model is the in vivo dose of the causative genotoxic agent. This paper presents an evaluation, according to this model, of published AA cancer tests on the basis of in vivo doses of GA in rats exposed in the cancer tests. The present status regarding data with importance for an improved estimation of the contribution from GA to the cancer risk of AA, such as in vivo doses measured in humans, is discussed.

Identifiers
urn:nbn:se:su:diva-14577 (URN)10.1021/jf800490s (DOI)000258270300005 ()
Available from: 2008-10-09 Created: 2008-10-09 Last updated: 2010-03-23Bibliographically approved
3. Alcohol influence on acrylamide to glycidamide metabolism assessed with hemoglobin-adducts and questionnaire data
Open this publication in new window or tab >>Alcohol influence on acrylamide to glycidamide metabolism assessed with hemoglobin-adducts and questionnaire data
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2010 (English)In: Food and Chemical Toxicology, ISSN 0278-6915, E-ISSN 1873-6351, Vol. 58, no 3, 820-824 p.Article in journal (Refereed) Published
Abstract [en]

Our purpose was to investigate whether alcohol (ethanol) consumption could have an influence on the metabolism of acrylamide to glycidamide in humans exposed to acrylamide through food. We studied a subsample from a population-based case–control study of prostate cancer in Sweden (CAPS). Questionnaire data for alcohol intake estimates was compared to the ratio of hemoglobin-adduct levels for acrylamide and glycidamide, used as a measure of individual differences in metabolism. Data from 161 non-smoking men were processed with regard to the influence of alcohol on the metabolism of acrylamide to glycidamide. A negative, linear trend of glycidamide-adduct to acrylamide-adduct-level ratios with increasing alcohol intake was observed and the strongest association (p-value for trend = 0.02) was obtained in the group of men with the lowest adduct levels (⩽47 pmol/g globin) when alcohol intake was stratified by acrylamide-adduct levels. The observed trend is likely due to a competitive effect between ethanol and acrylamide as both are substrates for cytochrome P450 2E1. Our results, strongly indicating that ethanol influence metabolism of acrylamide to glycidamide, partly explain earlier observations of only low to moderate associations between questionnaire data on dietary acrylamide intake and hemoglobin-adduct levels.

Keyword
Acrylamide, Alcohol, Glycidamide, Hemoglobin-adducts, Food frequency questionnaire
National Category
Other Basic Medicine
Research subject
Environmental Chemistry
Identifiers
urn:nbn:se:su:diva-37807 (URN)10.1016/j.fct.2009.12.014 (DOI)000275943600009 ()
Available from: 2010-03-23 Created: 2010-03-23 Last updated: 2011-12-05Bibliographically approved
4. In vivo doses from acrylamide in food – variation between and within individuals
Open this publication in new window or tab >>In vivo doses from acrylamide in food – variation between and within individuals
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(English)Manuscript (preprint) (Other academic)
Identifiers
urn:nbn:se:su:diva-37808 (URN)
Available from: 2010-03-23 Created: 2010-03-23 Last updated: 2010-03-23Bibliographically approved
5. In vivo doses of acrylamide and glycidamide in humans after intake of acrylalmide-rich food
Open this publication in new window or tab >>In vivo doses of acrylamide and glycidamide in humans after intake of acrylalmide-rich food
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2011 (English)In: Toxicological Sciences, ISSN 1096-6080, E-ISSN 1096-0929, Vol. 119, no 1, 41-49 p.Article in journal (Refereed) Published
National Category
Chemical Sciences
Identifiers
urn:nbn:se:su:diva-37810 (URN)
Available from: 2010-03-23 Created: 2010-03-23 Last updated: 2012-01-29Bibliographically approved

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