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Epidemiological findings on health risks associated with dietary acrylamide
Abstracts / Toxicology Letters 229S (2014) S22–S39
evaluated not to be a tool to reduce acrylamide levels at this stage, but will be further investigated. Overall, the food industry has achieved clear reductions in several product categories, and can expect more pronounced reduction through new product development. 3-MCPD and glycidol esters are present mainly in refined edible oils and are generated during the deodorization process. In particular, 3-MCPD diesters are found in high abundance in refined palm oil. Through the use of mass defect filtering of isotope signatures, the existence of a plethora of chlorinated substances – potential precursors of MCPD esters – have been identified. Several breakthroughs in the area of mitigation of 3-MCPD-ester and glycidol-ester levels during refined palm oil production have been reported, and effort continue to further improve the quality of refined vegetable oils. http://dx.doi.org/10.1016/j.toxlet.2014.06.128 PS3.4-O2 Carcinogenicity and genotoxicity of furan in rats in vivo Angela Mally Department of Toxicology, University of Würzburg, Würzburg, Germany
S27
From 3-MCPD, it is known that it induces hyperplasia in renal tubules (in mice and rats), infertility in rats and it is possibly carcinogenic in a nongenotoxic manner. The main toxicological targets organs are kidney, testis, and liver. In order to obtain insights into toxicity mechanisms of 3-MCPD and its esters, a proteomic approach was initiated in a 28-days repeated-dose feeding study with male Wistar rats using state to the art “omics” techniques. The proteomic analysis could identify major mechanistic toxicological informations regarding the target tissue. In the liver, in all treatment groups characteristic toxicologically relevant processes and pathways were induced, including fatty acid metabolism, or NRF2-mediated oxidative stress. General results indicate a similar toxicity of 3-MCPD and its dipalmitate. Bioinformatic network analysis of effects in testicular tissue revealed that in all treatment groups multiple proteins were deregulated which are associated with genital tumor and reproductive system disease. Bioinformatic analysis of effects in the kidney tissue revealed that in all treatment groups several proteins controlling cell survival and cell death were deregulated, including an increased expression of glutathione S-transferase P1, a well-known marker of preneoplastic or neoplastic tissue. Taken together, risk assessment of 3-MCPD ester could be supported substantial by the new mechanistic “omics” data. http://dx.doi.org/10.1016/j.toxlet.2014.06.130
Furan is formed in a variety of heat-treated foods through thermal degradation of natural food constituents. European exposure estimates suggest that mean dietary exposure to furan may be as high as 1.23 g/kg bw/d and 1.01 g/kg bw/d for adults and three-to-twelve-month-old infants, respectively. Data on furan carcinogenicity indicate that furan may induce liver tumors in rats at doses 2 mg/kg bw. There is therefore a relatively low Margin of Exposure (MoE) between estimated human exposure and doses which cause tumors in rodents, raising concern that dietary exposure to furan may present a risk to human health and indicating a need to clarify the role of genetic and non-genetic mechanisms in furan risk. The presentation will summarize recent data on furan genotoxicity in vivo, including DNA binding of furan in rat liver, mutagenicity in the transgenic Big Blue rat model, liver DNA damage and changes in the expression of genes involved in DNA damage response. Particular consideration will be given to dose–response. The importance of non-genotoxic events, i.e. toxicity, inflammation and regenerative cell proliferation, in furan carcinogenicity will also be discussed. http://dx.doi.org/10.1016/j.toxlet.2014.06.129 PS3.4-O3 Use of “omics” information in risk assessment of new food risks: Proteomic investigations into mechanism of liver, kidney, and testicular toxicity induced by 3-MCPD and its dipalmitate ester in rats Alfonso Lampen Federal Institute for Risk Assessment, Berlin, Germany Recently, the German BfR calculated the potential health risk of the intake of 3-monochloro-1,2-propandiol (3-MCPD) esters which represents a new class of heat-induced contaminates. A biokinetic study using rats have shown that 3-MCPD is highly bioavailable after oral administration of 3-MCPD esters.
PS3.4-O4 Epidemiological findings on health risks associated with dietary acrylamide Janneke Hogervorst Maastricht University, Maastricht, Netherlands In 2002, the world was alarmed by the discovery of acrylamide in food. In 1994, acrylamide, widely used as an industrial chemical, was classified as a probable human carcinogen by the International Agency for Research on Cancer, owing to its carcinogenicity in rodents. Several frequently consumed foods produced at >120 ◦ C, such as French fries, cookies and coffee, contain high acrylamide levels. In this presentation, I will give an overview of the epidemiological findings on health risks of dietary acrylamide exposure. Recently, dietary acrylamide was linked inconsistently in epidemiological studies to the risk of some cancers, among which were endometrial, ovarian, and breast cancers. In addition, acrylamide was associated with decreased breast cancer survival in a prospective cohort study. In newborns, a biomarker of acrylamide exposure (acrylamide hemoglobin adducts) was inversely associated with fetal growth in two cohort studies. These findings are intriguing, but observational studies such as the mentioned ones, cannot establish causal relationships. Therefore, I will also discuss the scarce epidemiological evidence to support the biological plausibility of the observed associations, such as the observed association between an acrylamide metabolite and 8-OHdG in urine in adolescents and between potato crisps intake and markers for oxidative stress and inflammation. Lastly, I will discuss data gaps in epidemiological research on acrylamide and health risks and give suggestions for future epidemiological research. http://dx.doi.org/10.1016/j.toxlet.2014.06.131
evaluated not to be a tool to reduce acrylamide levels at this stage, but will be further investigated. Overall, the food industry has achieved clear reductions in several product categories, and can expect more pronounced reduction through new product development. 3-MCPD and glycidol esters are present mainly in refined edible oils and are generated during the deodorization process. In particular, 3-MCPD diesters are found in high abundance in refined palm oil. Through the use of mass defect filtering of isotope signatures, the existence of a plethora of chlorinated substances – potential precursors of MCPD esters – have been identified. Several breakthroughs in the area of mitigation of 3-MCPD-ester and glycidol-ester levels during refined palm oil production have been reported, and effort continue to further improve the quality of refined vegetable oils. http://dx.doi.org/10.1016/j.toxlet.2014.06.128 PS3.4-O2 Carcinogenicity and genotoxicity of furan in rats in vivo Angela Mally Department of Toxicology, University of Würzburg, Würzburg, Germany
S27
From 3-MCPD, it is known that it induces hyperplasia in renal tubules (in mice and rats), infertility in rats and it is possibly carcinogenic in a nongenotoxic manner. The main toxicological targets organs are kidney, testis, and liver. In order to obtain insights into toxicity mechanisms of 3-MCPD and its esters, a proteomic approach was initiated in a 28-days repeated-dose feeding study with male Wistar rats using state to the art “omics” techniques. The proteomic analysis could identify major mechanistic toxicological informations regarding the target tissue. In the liver, in all treatment groups characteristic toxicologically relevant processes and pathways were induced, including fatty acid metabolism, or NRF2-mediated oxidative stress. General results indicate a similar toxicity of 3-MCPD and its dipalmitate. Bioinformatic network analysis of effects in testicular tissue revealed that in all treatment groups multiple proteins were deregulated which are associated with genital tumor and reproductive system disease. Bioinformatic analysis of effects in the kidney tissue revealed that in all treatment groups several proteins controlling cell survival and cell death were deregulated, including an increased expression of glutathione S-transferase P1, a well-known marker of preneoplastic or neoplastic tissue. Taken together, risk assessment of 3-MCPD ester could be supported substantial by the new mechanistic “omics” data. http://dx.doi.org/10.1016/j.toxlet.2014.06.130
Furan is formed in a variety of heat-treated foods through thermal degradation of natural food constituents. European exposure estimates suggest that mean dietary exposure to furan may be as high as 1.23 g/kg bw/d and 1.01 g/kg bw/d for adults and three-to-twelve-month-old infants, respectively. Data on furan carcinogenicity indicate that furan may induce liver tumors in rats at doses 2 mg/kg bw. There is therefore a relatively low Margin of Exposure (MoE) between estimated human exposure and doses which cause tumors in rodents, raising concern that dietary exposure to furan may present a risk to human health and indicating a need to clarify the role of genetic and non-genetic mechanisms in furan risk. The presentation will summarize recent data on furan genotoxicity in vivo, including DNA binding of furan in rat liver, mutagenicity in the transgenic Big Blue rat model, liver DNA damage and changes in the expression of genes involved in DNA damage response. Particular consideration will be given to dose–response. The importance of non-genotoxic events, i.e. toxicity, inflammation and regenerative cell proliferation, in furan carcinogenicity will also be discussed. http://dx.doi.org/10.1016/j.toxlet.2014.06.129 PS3.4-O3 Use of “omics” information in risk assessment of new food risks: Proteomic investigations into mechanism of liver, kidney, and testicular toxicity induced by 3-MCPD and its dipalmitate ester in rats Alfonso Lampen Federal Institute for Risk Assessment, Berlin, Germany Recently, the German BfR calculated the potential health risk of the intake of 3-monochloro-1,2-propandiol (3-MCPD) esters which represents a new class of heat-induced contaminates. A biokinetic study using rats have shown that 3-MCPD is highly bioavailable after oral administration of 3-MCPD esters.
PS3.4-O4 Epidemiological findings on health risks associated with dietary acrylamide Janneke Hogervorst Maastricht University, Maastricht, Netherlands In 2002, the world was alarmed by the discovery of acrylamide in food. In 1994, acrylamide, widely used as an industrial chemical, was classified as a probable human carcinogen by the International Agency for Research on Cancer, owing to its carcinogenicity in rodents. Several frequently consumed foods produced at >120 ◦ C, such as French fries, cookies and coffee, contain high acrylamide levels. In this presentation, I will give an overview of the epidemiological findings on health risks of dietary acrylamide exposure. Recently, dietary acrylamide was linked inconsistently in epidemiological studies to the risk of some cancers, among which were endometrial, ovarian, and breast cancers. In addition, acrylamide was associated with decreased breast cancer survival in a prospective cohort study. In newborns, a biomarker of acrylamide exposure (acrylamide hemoglobin adducts) was inversely associated with fetal growth in two cohort studies. These findings are intriguing, but observational studies such as the mentioned ones, cannot establish causal relationships. Therefore, I will also discuss the scarce epidemiological evidence to support the biological plausibility of the observed associations, such as the observed association between an acrylamide metabolite and 8-OHdG in urine in adolescents and between potato crisps intake and markers for oxidative stress and inflammation. Lastly, I will discuss data gaps in epidemiological research on acrylamide and health risks and give suggestions for future epidemiological research. http://dx.doi.org/10.1016/j.toxlet.2014.06.131