| 1. |
- Aasa, Jenny, et al.
(författare)
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Cancer risk estimation of glycidol based on rodent carcinogenicity studies, a multiplicative risk model and in vivo dosimetry
- 2019
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Ingår i: Food and Chemical Toxicology. - : Elsevier BV. - 0278-6915 .- 1873-6351. ; 128, s. 54-60
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Tidskriftsartikel (refereegranskat)abstract
- Here we evaluate a multiplicative (relative) risk model for improved cancer risk estimation of genotoxic compounds. According to this model, cancer risk is proportional to the background tumor incidence and to the internal dose of the genotoxic compound. Furthermore, the relative risk coefficient per internal dose is considered to be approximately the same across tumor sites, sex, and species. In the present study, we demonstrate that the relative risk model is valid for cancer risk estimation of glycidol, a common food contaminant. Published tumor data from glycidol carcinogenicity studies in mice and rats were evaluated in combination with internal dose estimates from hemoglobin adduct measurements in blood from mice and rats treated with glycidol in short-term studies. A good agreement between predicted and observed tumor incidence in responding sites was demonstrated in the animals, supporting a relative risk coefficient that is independent of tumor site, sex, and species. There was no significant difference between the risk coefficients for mice (5.1% per mMh) and rats (5.4% per mMh) when considering internal doses of glycidol. Altogether, this mechanism-based risk model gives a reliable risk coefficient, which then was extrapolated to humans considering internal dose, and background cancer incidence.
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| 2. |
- 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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| 3. |
- 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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| 4. |
- 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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| 5. |
- Bøhn, Thomas, et al.
(författare)
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Daphnia magna negatively affected by chronic exposure to purified Cry-toxins
- 2016
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Ingår i: Food and Chemical Toxicology. - : Elsevier BV. - 0278-6915 .- 1873-6351. ; 91, s. 130-140
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Tidskriftsartikel (refereegranskat)abstract
- Cry-toxin genes originating from Bacillus thuringiensis are inserted into genetically modified (GM) plants, often called Bt-plants, to provide insect resistance to pests. Significant amounts of Bt-plant residues, and thus Cry-toxins, will be shed to soil and aquatic environments. We exposed Daphnia magna to purified Cry1Ab and Cry2Aa toxins for the full life-span of the animals. We used single toxins in different doses and combinations of toxins and Roundup, another potential stressor on the rise in agricultural ecosystems. Animals exposed to 4.5 mg/L (ppm) of Cry1Ab, Cry2Aa and the combination of both showed markedly higher mortality, smaller body size and very low juvenile production compared to controls. Animals exposed to 0.75 mg/L also showed a tendency towards increased mortality but with increased early fecundity compared to the controls. Roundup stimulated animals to strong early reproductive output at the cost of later rapid mortality. We conclude that i) purified Cry-toxins in high concentrations are toxic to D. magna, indicating alternative modes-of-action for these Cry-toxins; ii) Cry-toxins act in combination, indicating that 'stacked events' may have stronger effects on non-target organisms; iii) further studies need to be done on combinatorial effects of multiple Cry-toxins and herbicides that co-occur in the environment.
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| 6. |
- Carlsson, Henrik, 1987-, et al.
(författare)
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Strategy for identifying unknown hemoglobin adducts using adductome LC-MS/MS data : Identification of adducts corresponding to acrylic acid, glyoxal, methylglyoxal, and 1-octen-3-one
- 2016
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Ingår i: Food and Chemical Toxicology. - : Elsevier BV. - 0278-6915 .- 1873-6351. ; 92, s. 94-103
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Tidskriftsartikel (refereegranskat)abstract
- Electrophilic compounds have the ability to form adducts with nucleophilic sites in proteins and DNA in tissues, and thereby constitute risks for toxic effects. Adductomic approaches are developed for systematic screening of adducts to DNA and blood proteins, with the aim to detect unknown internal exposures to electrophiles. In a previous adductomic screening of adducts to N-terminals in hemoglobin, using LC-MS/MS, 19 unknown adducts were detected in addition to seven previously identified adducts. The present paper describes the identification of four of these unknown adducts, as well as the strategy used to identify them. Using LC-MS data from the screening, hypotheses about adduct identities were formulated: probable precursor electrophiles with matching molecular weights were suggested based on the molecular weights of the modifications and the retention times of the analytes, in combination with comparisons of theoretical Log P calculations and databases. Reference adducts were generated by incubation of blood samples with the hypothesized precursor electrophiles. The four identified precursor electrophiles, corresponding to the observed unknown adducts, were glyoxal, methylglyoxal, acrylic acid and 1-octen-3-one. Possible origins/exposure sources and toxicological information concerning the electrophilic precursors are discussed. The identified adducts could be explored as possible biomarkers for exposure.
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| 7. |
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| 8. |
- Garcia, Juliana, et al.
(författare)
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Amanita phalloides poisoning : Mechanisms of toxicity and treatment
- 2015
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Ingår i: Food and Chemical Toxicology. - : Elsevier BV. - 0278-6915 .- 1873-6351. ; 86, s. 41-55
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Forskningsöversikt (refereegranskat)abstract
- Amanita phalloides, also known as 'death cap', is one of the most poisonous mushrooms, being involved in the majority of human fatal cases of mushroom poisoning worldwide. This species contains three main groups of toxins: amatoxins, phallotoxins, and virotoxins. From these, amatoxins, especially alpha-amanitin, are the main responsible for the toxic effects in humans. It is recognized that alpha-amanitin inhibits RNA polymerase II, causing protein deficit and ultimately cell death, although other mechanisms are thought to be involved. The liver is the main target organ of toxicity, but other organs are also affected, especially the kidneys. Intoxication symptoms usually appear after a latent period and may include gastrointestinal disorders followed by jaundice, seizures, and coma, culminating in death. Therapy consists in supportive measures, gastric decontamination, drug therapy and, ultimately, liver transplantation if clinical condition worsens. The discovery of an effective antidote is still a major unsolved issue. The present paper examines the clinical toxicology of A. phalloides, providing the currently available information on the mechanisms of toxicityinvolved and on the current knowledge on the treatment prescribed against this type of mushrooms. Antidotal perspectives will be raised as to set the pace to new and improved therapy against these mushrooms.
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| 9. |
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| 10. |
- Koppelman, SJ, et al.
(författare)
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Allergenicity attributes of different peanut market types
- 2016
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Ingår i: Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association. - : Elsevier BV. - 1873-6351. ; 91, s. 82-90
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Tidskriftsartikel (refereegranskat)
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