| 1. |
- Aasa, Jenny, et al.
(författare)
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Internal dose of glycidol in children and estimation of associated cancer risk
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Children are more susceptible to exposures to harmful compounds compared to adults. Monitoring of the actual exposures in vivo is important to enable risk mitigation actions. The general population, including children, is exposed to the carcinogen glycidol through food. A possible exposure source to glycidol is food containing refined cooking oils where it is present as a process-induced contaminant in the form of fatty acid esters.In the present study internal (in vivo) doses of the genotoxic and carcinogenic compound glycidol have been determined in a cohort of 50 children and in a reference group of 12 adults (non-smokers and smokers). The lifetime in vivo doses of glycidol have been calculated from the levels of the hemoglobin (Hb) adduct N-(2,3-dihydroxypropyl)-valine in blood samples from the subjects, demonstrating about a 5-fold variation between the children (71–322 µMh). This variation is likely due to different dietary habits and/or different genotypes/phenotypes of the enzymes involved in the detoxification of glycidol. Data from the adults indicate that the non-smoking subjects are exposed to about the same level as the children, whereas the smoking subjects have about double levels, likely due to the presence of glycidol in tobacco smoke. The estimated exposure to glycidol in the children is higher than those estimated by European Food Safety Authority.The calculated relative cancer risk increment due to glycidol exposure demonstrated an unacceptable risk for all subjects. The excess lifetime risk based on the estimated lifetime in vivo doses of glycidol exceeded 1/1000, which should be compared to a generally applied acceptable lifetime risk level of 1/100 000. A small contribution to the internal dose of glycidol from other precursors to the measured Hb adduct, and corresponding contribution to estimated risks from intake of glycidol from food cannot though be excluded.
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| 2. |
- Aasa, Jenny, et al.
(författare)
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Internal Doses of Glycidol in Children and Estimation of Associated Cancer Risk
- 2019
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Ingår i: Toxics. - : MDPI AG. - 2305-6304. ; 7:1
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Tidskriftsartikel (refereegranskat)abstract
- The general population is exposed to the genotoxic carcinogen glycidol via food containing refined edible oils where glycidol is present in the form of fatty acid esters. In this study, internal (in vivo) doses of glycidol were determined in a cohort of 50 children and in a reference group of 12 adults (non-smokers and smokers). The lifetime in vivo doses and intakes of glycidol were calculated from the levels of the hemoglobin (Hb) adduct N-(2,3-dihydroxypropyl)valine in blood samples from the subjects, demonstrating a fivefold variation between the children. The estimated mean intake (1.4 mu g/kg/day) was about two times higher, compared to the estimated intake for children by the European Food Safety Authority. The data from adults indicate that the non-smoking and smoking subjects are exposed to about the same or higher levels compared to the children, respectively. The estimated lifetime cancer risk (200/10(5)) was calculated by a multiplicative risk model from the lifetime in vivo doses of glycidol in the children, and exceeds what is considered to be an acceptable cancer risk. The results emphasize the importance to further clarify exposure to glycidol and other possible precursors that could give a contribution to the observed adduct levels.
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| 3. |
- Aasa, Jenny, et al.
(författare)
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Measurement of micronuclei and internal dose in mice demonstrates that 3-monochloropropane-1,2-diol (3-MCPD) has no genotoxic potency in vivo
- 2017
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Ingår i: Food and Chemical Toxicology. - : Elsevier BV. - 0278-6915 .- 1873-6351. ; 109, s. 414-420
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Tidskriftsartikel (refereegranskat)abstract
- In this study 3-monochloropropane-1,2-diol (3-MCPD), a compound that appears as contaminant in refined cooking oils, has been studied with regard to genotoxicity in vivo (mice) with simultaneous measurement of internal dose using state-of-the-art methodologies. Genotoxicity (chromosomal aberrations) was measured by flow cytometry with dual lasers as the frequency of micronuclei in erythrocytes in peripheral blood from BalbC mice intraperitoneally exposed to 3-MCPD (0, 50, 75, 100, 125 mg/kg). The internal doses of 3-MCPD in the mice were calculated from N-(2,3-dihydroxypropyl)-valine adducts to hemoglobin (Hb), quantified at very low levels by high-resolution mass spectrometry.Convincing evidence for absence of genotoxic potency in correlation to measured internal doses in the mice was demonstrated, despite relatively high administered doses of 3-MCPD. The results are discussed in relation to another food contaminant that is formed as ester in parallel to 3-MCPD esters in oil processing, i.e. glycidol, which has been studied previously by us in a similar experimental setup. Glycidol has been shown to be genotoxic, and in addition to have ca. 1000 times higher rate of adduct formation compared to that observed for 3-MCPD. The conclusion is that at simultaneous exposure to 3-MCPD and glycidol the concern about genotoxicity would be glycidol.
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| 4. |
- Aasa, Jenny, et al.
(författare)
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The genotoxic potency of glycidol established from micronucleus frequency and hemoglobin adduct levels in mice
- 2017
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Ingår i: Food and Chemical Toxicology. - : Elsevier BV. - 0278-6915 .- 1873-6351. ; 100, s. 168-174
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Tidskriftsartikel (refereegranskat)abstract
- Glycidol is a genotoxic animal carcinogen that has raised concern due to its presence in food, as glycidyl fatty acid esters. Here we investigated the genotoxicity of glycidol in BalbC mice (0-120 mg/kg) by monitoring the induction of micronuclei in peripheral blood as a marker of chromosomal damage. The scoring of the micronuclei was assessed by flow cytometry. In the treated mice, the internal dose of glycidol, expressed as area under the concentration-time curve, AUC (mol x L-1 x h; Mh), was measured by dihydroxypropyl adducts to hemoglobin (Hb). The study showed that glycidol induced linear dose dependent increases of Hb adducts (20 pmol/g Hb per mg/kg) and of micronuclei frequencies (12 parts per thousand per mMh). Compared to calculations based on administered dose, an improved dose-response relationship was observed when considering internal dose, achieved through the applied combination of sensitive techniques used for the scoring of micronuclei and AUC estimation of glycidol in the same mice. By comparing with earlier studies on micronuclei induction in mice exposed to ionizing radiation we estimated the radiation dose equivalent (rad-eq.) of glycidol to be ca 15 rad-eq./mMh.
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| 5. |
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| 6. |
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| 7. |
- Abramsson-Zetterberg, Lilianne
(författare)
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Strongly heated carbohydrate-rich food is an overlooked problem in cancer risk evaluation
- 2018
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Ingår i: Food and Chemical Toxicology. - : Elsevier BV. - 0278-6915 .- 1873-6351. ; 121, s. 151-155
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Tidskriftsartikel (refereegranskat)abstract
- A cascade of compounds is produced when foodstuffs are heated at high temperatures but only a few of these compounds have been identified and quantified. In this study data are evaluated regarding differences in the micronucleus frequency of human erythrocytes (fMNs) in peripheral blood (a known biomarker of genotoxicity) in individuals that consumed either high- or low-heated food during a 4-day period. Concomitantly, acrylamide (aa) levels were measured in the food that the participants consumed. The obtained fMNs in this human study are compared with the fMNs in mice after comparable exposure levels of pure aa. The results of this comparison showed several hundred times higher fMNs in humans compared with mice. With an assumed linear correlation between an increased genotoxic effect and cancer, our data suggest that aa only represents a fraction of all carcinogenic compounds produced in heated carbohydrate-rich food. Consequently, our daily intake of carbohydrate-rich food heated at high temperatures might be responsible for one-fifth of the rate of the total cancer risk. One sentence summary: A biomarker of genotoxicity indicates the risk of cancer to be some hundred-fold greater in heated carbohydrate-rich food than the risk calculated from animal studies on pure acrylamide.
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| 8. |
- Abramsson-Zetterberg, Lilianne, et al.
(författare)
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The impact of folate status and folic acid supplementation on the micronucleus frequency in human erythrocytes
- 2006
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Ingår i: Mutation Research. - : Elsevier BV. - 1383-5742 .- 1388-2139. ; 603:1, s. 33-40
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Tidskriftsartikel (refereegranskat)abstract
- Folic acid has a well-documented stabilising effect on chromosomes. A correlation between folate status and chromosome stability in humans has been reported in studies that were restricted to certain subpopulations, e.g., folate-deficient persons. The goal of the present investigation was to clarify if there also is a correlation between folate status and chromosome stability among individuals without any folate deficiency. The method used here is the recently developed flow cytometry-based micronucleus assay in human transferrin-positive reticulocytes (MN-Trf-Ret). In a blood sample, separation of the very young reticulocytes from the mature erythrocytes makes this micronucleus assay possible. This investigation comprises three studies (cross-sectional, giving baseline data), two of which are connected to an intervention study. In the three cross-sectional studies (total number of subjects, 99) the frequency of MN-Trf-Ret (fMN-Trf-Ret) was measured and compared with the serum folate status. In two of the studies also serum homocysteine and Vitamin B12 were measured and compared with the baseline fMN-Trf-Ret. Combining the results from the three cross-sectional studies, a negative correlation between folate status and fMN-Trf-Ret was obtained (p < 0.05). The goal of the intervention studies was to clarify if different nutritional supplementations had any effect on the fMN-Trf-Ret and the cell proliferation (percentage polychromatic erythrocytes, PCE). Each of the two studies involved two groups, one placebo and one supplemented group. In one of the studies the supplementation was folic acid, 1000 μg/day during 1 week (n = 30, both sexes); in the other intervention study, folic acid (800 μg/day), B12 (20 μg/day) and B6 (4 mg/day) were taken during 1 week (n = 29, both sexes). No significant difference in %PCE or fMN-Trf-Ret between the two groups was found in either of the two intervention studies.
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| 9. |
- Abramsson-Zetterberg, Lilianne, et al.
(författare)
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The synthetic food colouring agent Allura Red AC (E129) is not genotoxic in a flow cytometry-based micronucleus assay in vivo
- 2013
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Ingår i: Food and Chemical Toxicology. - : Elsevier BV. - 0278-6915 .- 1873-6351. ; 59, s. 86-89
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Tidskriftsartikel (refereegranskat)abstract
- The safety of several azo colouring agents, used as food additives, has during the years been questioned. Allura Red AC (E129) has in some publications been classified as genotoxic. In fact, in the European Union, Allura Red is permitted as a food additive in human food, but, surprisingly, it was not acceptable as an additive for use in animal feed. In this study we have evaluated whether Allura Red is genotoxic using a flow cytometer-based micronucleus assay in peripheral blood of mice. Male FVB mice were given a single intra-peritoneal injection of various doses of Allura Red and sacrificed at 46 h after treatment. The tested doses were 0, 100, 200, 400, 600, 800, 1000, 1500, and 2000 mg/kg body weight (b.w.). Each dose group constituted three mice, except for in the dose group of 1000 mg/kg b.w., which constituted four mice. Blood samples were collected and the frequency of micronucleated polychromatic erythrocytes (fMNPCE) and the cell proliferation (%PCE) was determined. The analyses did not show any significant difference in the %PCE or in the fMNPCE. Consequently, under the testing circumstances one can conclude that Allura Red is not genotoxic.
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| 10. |
- Andersson, Maria A., et al.
(författare)
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Evaluation of the potential genotoxicity of chromium picolinate in mammalian cells in vivo and in vitro
- 2007
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Ingår i: Food and Chemical Toxicology. - : Elsevier BV. - 0278-6915 .- 1873-6351. ; 45:7, s. 1097-1106
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Tidskriftsartikel (refereegranskat)abstract
- Chromium picolinate (CrPic) is a synthetic nutritional supplement primarily used for weight loss and muscle building. Recent studies have indicated that CrPic might be genotoxic and these findings together with the wide-spread consumer use, have increased the concern about its safety. In the present study we investigated the potential genotoxicity of CrPic in mice given a single intraperitoneal injection (up to 3 mg/kg b.wt.) by evaluating the frequency of micronucleated polychromatic erythrocytes (fMNPCE) in peripheral blood, and DNA damage in lymphocytes and hepatocytes. The fMNPCE was evaluated after 42 h and DNA damage after 16 h. Using the Comet assay DNA damage was also monitored in extended-term cultures of human lymphocytes and in L5178Y mouse lymphoma cells that had been exposed for 3 h to 500 μM CrPic under different exposure conditions.A slight, but significant CrPic-induced increase in DNA damage (P < 0.001) was observed in the human lymphocytes, but only when these cells were exposed in the absence of serum. In all other experiments CrPic was found to be without genotoxic effects, both in vivo and in vitro. Taken together, our results suggest that a high concentration of CrPic might be DNA damaging, but only under non-physiological conditions.
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