Dose-response assessment of four genotoxic chemicals in a combined mouse and rat micronucleus (MN) and Comet assay protocol

Recio, Leslie; Hobbs, Cheryl A.; Caspary, William J.; Witt, Kristine L.

doi:10.2131/jts.35.149

Cited by 98 publications

(62 citation statements)

References 30 publications

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“…Induction of DNA damage by AA as measured by the Comet assay has been reported in several tissues of mice or rats (Manière et al, 2005;Dobrzynska, 2007;Recio et al, 2010;Rothfuss et al, 2010) (Table 22). …”

Section: Genotoxicitymentioning

confidence: 93%

Scientific Opinion on acrylamide in food

Publication¹

2015

EFS2

328

170

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EFSA was asked to deliver a scientific opinion on acrylamide (AA) in food. AA has widespread uses as an industrial chemical. It is also formed when certain foods are prepared at temperatures above 120 °C and low moisture, especially in foods containing asparagine and reducing sugars. The CONTAM Panel evaluated 43 419 analytical results from food commodities. AA was found at the highest levels in solid coffee substitutes and coffee, and in potato fried products. Mean and 95th percentile dietary AA exposures across surveys and age groups were estimated at 0.4 to 1.9 µg/kg body weight (b.w.) per day and 0.6 to 3.4 µg/kg b.w. per day, respectively. The main contributor to total dietary exposure was generally the category 'Potato fried products (except potato crisps and snacks)'. Preferences in home-cooking can have a substantial impact on human dietary AA exposure. Upon oral intake, AA is absorbed from the gastrointestinal tract and distributed to all organs. AA is extensively metabolised, mostly by conjugation with glutathione but also by epoxidation to glycidamide (GA). Formation of GA is considered to represent the route underlying the genotoxicity and carcinogenicity of AA. Neurotoxicity, adverse effects on male reproduction, developmental toxicity and carcinogenicity were identified as possible critical endpoints for AA toxicity from experimental animal studies. The data from human studies were inadequate for dose-response assessment. The CONTAM Panel selected BMDL 10 values of 0.43 mg/kg b.w. per day for peripheral neuropathy in rats and of 0.17 mg/kg b.w. per day for neoplastic effects in mice. The Panel concluded that the current levels of dietary exposure to AA are not of concern with respect to non-neoplastic effects. However, although the epidemiological associations have not demonstrated AA to be a human carcinogen, the margins of exposure (MOEs) indicate a concern for neoplastic effects based on animal evidence. © European Food SUMMARYFollowing a request from the European Commission, the Panel on Contaminants in the Food Chain (CONTAM Panel) was asked to deliver a scientific opinion on acrylamide (AA) in food. The Panel developed the draft scientific opinion which underwent a public consultation from 1 July 2014 to 15 September 2014. The comments received and how they were taken into account when finalising the scientific opinion were published in an EFSA Technical Report (EFSA, 2015).AA is a low molecular weight, highly water soluble, organic compound. It is used inter alia as an industrial chemical and in the production of polyacrylamides. Heightened concerns about exposure to AA arose in 2002 when it was discovered that it forms when certain foods are prepared at temperatures usually above 120 °C and low moisture. It forms, at least in part, due to a Maillard reaction between certain amino acids, such as asparagine, and reducing sugars. However, several other pathways and precursors have also been proposed to contribute to AA formation. AA forms in numerous baked or fried carbohydrate-rich f...

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Section: Genotoxicitymentioning

confidence: 93%

Scientific Opinion on acrylamide in food

Publication¹

2015

EFS2

328

170

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“…Another example is single cell gel electrophoresis (also known as the comet assay), which is a rapid, sensitive, and simple method that measures DNA damage induced by chemicals at the level of individual cells (Recio et al, 2010). These assays are based on cell proliferation, chromosome breakage, and DNA strand breaks, which are parameters related to DNA replication.…”

Section: -Can Be Performed In Human or Rodent Cells (In Vitro) Or LIVmentioning

confidence: 99%

An RNA synthesis inhibition assay for detecting toxic substances using click chemistry

2014

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-Biological risk assessment studies of chemical substances that induce DNA lesions have been primarily based on the action of DNA polymerases during replication. However, DNA lesions interfere not only with replication, but also with transcription. There is no simple method for the detection of the DNA lesion-induced inhibition of transcription. Here, we report an assay for estimating the toxicity of chemical substances by visualizing transcription in mammalian cells using nucleotide analog 5-ethynyluridine (EU) and its click chemistry reaction. Ultraviolet light and representative chemical substances (camptothecin, 4-nitroquinoline-1-oxide, mitomycin C, and cisplatin, but not etoposide) of DNAdamaging agents show toxicity, as indicated by RNA synthesis inhibition in response to DNA damage in HeLa cells. Using titanium dioxide, we observed RNA synthesis inhibition in response to the rutile form, but not the anatase form, indicating that rutile titanium dioxide is a toxic substance. Because this method is based on the transcriptional response to DNA lesions, we can use terminally differentiated neuronlike PC12 cells, the differentiation of which can be induced by nerve growth factors, for evaluating chemical substances. Ultraviolet light and some chemicals (camptothecin, 4-nitroquinoline-1-oxide, mitomycin C, and cisplatin, but not etoposide) inhibited RNA synthesis in non-differentiated PC12 cells. Conversely, camptothecin and cisplatin did not inhibit RNA synthesis in differentiated PC12 cells, but 4-nitroquinoline-1-oxide, mitomycin C, and etoposide did. And using titanium dioxide, we did not observed any RNA synthesis inhibition. These data suggest that this method might be used to estimate the potential risk of chemical substances in differentiated mammalian cells, which are the most common cell type found in the human body.

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“…Glycidamide was found to induce N-7-(2-carbamoyl-2-hydroxy-ethyl)guanine Fu et al (2000) (35) Neonatal mouse tumorigenicity bioassay Glycidamide showed 5-to 7-fold higher DNA adduct levels than when treated with acrylamide, indicating lower levels of CYP450 enzymes in immature tissues Gamboa de Costa et al (41) Micronucleus assay on hens' eggs Acrylamide increased micronucleus frequencies Recio et al (2010) (42) Micronucleus/comet assays on rats and mice Acrylamide was found to induce micronucleated reticulocytes in rats Mei et al (2010) (43) Micronucleus and Hprt assays on rats Neither acrylamide nor glycidamide increased the frequency of micronucleated reticulocytes. In contrast, both compounds produced small (approximately 2-to 3-fold above background) but significant increases in lymphocyte Hprt mutant frequency Neurotoxic effects of acrylamide …”

Section: Reproductive and Developmental Toxicity Of Acrylamidementioning

confidence: 99%

Toxicity of acrylamide and evaluation of its exposure in baby foods

Erkekoğlu

Baydar

2010

Nutr. Res. Rev.

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Contaminants are a vast subject area of food safety and quality and can be present in our food chain from raw materials to finished products. Acrylamide, an α,β-unsaturated (conjugated) reactive molecule, can be detected as a contaminant in several foodstuffs including baby foods and infant formulas. It is anticipated that children will generally have intakes that are two to three times those of adults when expressed on a body-weight basis. Though exposure to acrylamide is inevitable, it is necessary to protect infant and children from high exposure. The present review focuses on the several adverse health effects of acrylamide including mutagenicity, genotoxicity, carcinogenicity, neurotoxicity and reproductive toxicity, and the possible outcomes of childhood exposure from baby foods and infant formulas.

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Dose-response assessment of four genotoxic chemicals in a combined mouse and rat micronucleus (MN) and Comet assay protocol

Cited by 98 publications

References 30 publications

Scientific Opinion on acrylamide in food

Scientific Opinion on acrylamide in food

An RNA synthesis inhibition assay for detecting toxic substances using click chemistry

Toxicity of acrylamide and evaluation of its exposure in baby foods

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