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Yamazoe Y.,Food Safety Commission | Mitsumori K.,Food Safety Commission
Thresholds of Genotoxic Carcinogens: From Mechanisms to Regulation | Year: 2016

Chemicals show carcinogenicity in rodent assays through genotoxic and nongenotoxic mechanisms. No threshold levels are defined for genotoxic carcinogens, and thus genotoxic carcinogens are tightly restricted. Nongenotoxic carcinogens often evoke tumorigenicity after chronic administration of high doses and show a threshold when testing multiple doses. However, verification of genotoxic and nongenotoxic carcinogens is not readily achievable in most cases. This is mainly because of overlapping of biological effects. Therefore, mechanistic support is of importance in the assessment of chemicals with tumorigenic potentials.From pathological and pharmaco (toxico) kinetic points of view, quinoids and precursors may be a category of genotoxicants different from those acting through a direct electrophilic reaction with DNA. Many food additives are capable of producing free radicals, and many food additives are able to act as free-radical scavengers. Free- and oxygen-radical scavenging mechanisms also function in the body, whereas such mechanisms are generally not present in tests of genotoxicity in vitro. Detailed investigations of in vivo pathological examinations and pharmaco (toxico) kinetic profiles on quinoid-related chemicals offer us clear assessments with regard to human safety. © 2016 Elsevier Inc. All rights reserved.


PubMed | Kasetsart University, Food safety Commission and University of Pisa
Type: Controlled Clinical Trial | Journal: Journal of veterinary pharmacology and therapeutics | Year: 2016

To evaluate the toxicokinetics and persistence of residues of melamine (MEL) in ducks, MEL was administered intravenously (i.v.) or orally (p.o.) to ducks at a dosage of 5.5 mg/kg body weight. The concentration of MEL in the plasma and various tissues was detected using HPLC equipped with an ultraviolet detector. The plasma concentration of MEL in ducks was determined up to 12 h after both i.v. and p.o. administrations. The average value of elimination half-life (t/) of MEL was 2.16 0.37 and 2.01 0.56 h after i.v. and p.o. administration, respectively. The absolute p.o. bioavailability was 90.79%. MEL was measurable in the liver and kidney after p.o. administration with maximum levels of 15.80 1.81 and 15.49 2.12 g/g at 6 h, respectively. The results suggest that most of the administered MEL is efficiently absorbed from the gastro intestinal tract, and it has the ability to distribute into various tissues of the duck.


PubMed | College Park, Ishihara Sangyo Kaisha Ltd., Food Safety Commission, Hoffmann-La Roche and 15 more.
Type: Journal Article | Journal: Toxicologic pathology | Year: 2016

The identification of adverse health effects has a central role in the development and risk/safety assessment of chemical entities and pharmaceuticals. There is currently a need for better alignment regarding how nonclinical adversity is determined and characterized. The European Society of Toxicologic Pathology (ESTP) therefore coordinated a workshop to review available definitions of adversity, weigh determining and qualifying factors of adversity based on case examples, and recommend a practical approach to define and characterize adversity in toxicology reports, to serve as a valuable prerequisite for future organ- or lesion-specific workshops planned by the ESTP.


News Article | February 2, 2016
Site: news.yahoo.com

Alexandra Clark is a sustainable-food campaigner at Humane Society International. She recently presented HSI's meat reduction work at the COP21 in Paris. Prior to joining HSI, Clark worked for the vice president of the European Parliament and was responsible for a number of high-profile parliamentary initiatives on sustainable food systems. She contributed this article to Live Science's Expert Voices: Op-Ed & Insights. Global leaders in Paris accomplished much with the climate change agreement they reached late last year, but it had its shortcomings — including a failure to specifically mitigate the emissions of climate-changing gases from animal agriculture. However, outside of the Paris talks, policymakers in the European Union (EU) are beginning to advance that discussion, pushing for a shift away from diets heavy in meat, egg and dairy products, in an effort to clear the air. There is extensive research showing the outsize impacts of animal agriculture on the environment. The Food and Agriculture Organization of the United Nations (FAO) has concluded that "the livestock sector emerges as one of the top two or three most significant contributors to the most serious environmental problems, at every scale from local to global." It's not hard to see why. The process of converting energy and protein in animal feed into meat calories and protein for humans is highly inefficient: For example, a 2014 study led by Henk Westhoek for the PBL Netherlands Environmental Assessment Agency, and appearing in Global Environmental Change, found a 50 percent reduction in all EU consumption of meat, dairy and eggs would cut agricultural greenhouse gas emissions by 19 to 42 percent. Similar research that year in the journal Climatic Change found that, in the U.K., vegetarian and vegan diets had 32 percent and 49 percent lower greenhouse gas emissions , respectively, than medium-meat diets. Compared to high-meat diets, the difference was even starker, with vegan diets emitting 60 percent less greenhouse gasses. Yet, reductions aren't the projected future we face. One 2010 study by Nathan Pelletier and Peter Tyedmers at Dalhousie University, published in the Proceedings of the National Academy of Sciences, projected a 39 percent rise in emissions from animal agriculture by 2050 over year-2000 levels, accounting for more than two-thirds of the amount of greenhouse gases considered safe by 2050. Given the threats that climate change and other environmental impacts from farm animal production pose to long-term food security, there is a need for a global shift away from meat-heavy diets. Less meat for the wealthy, food security for the poor Eggs, meat and milk can continue to serve as sources of nutrition — particularly in rural areas of developing countries, which sometimes exhibit higher rates of undernutrition. Farm animals can provide a variety of supports to pastoralists, mixed farmers and landless peoples in rural areas. In rural communities around the world, people use farm animals as a means of acquiring cash income, a way to save and accumulate assets, as a food source, and as insurance against health or other financial crises. Integrated into a broader rural landscape of small farms, animals provide inputs and services for crop production. However, most farm animal production (and growth in production) is taking place in polluting and inhumane industrial farm animal production systems. These industrial systems are feeding middle- and higher-income consumers who could benefit from more plant-based diets. According to the World Health Organization (WHO), approximately 40 percent of adults across the globe are overweight, and noncommunicable diseases linked to the overconsumption of fats and energy-dense foods (such as meat, eggs and milk) are now a leading cause of illness and death worldwide. The WHO has called for an increase in the consumption of plant-based foods — specifically fruits, vegetables, legumes, whole grains and nuts — as part of the solution. Developed countries like the United States still have the highest per-capita meat consumption. However, according to the FAO, developing and emerging economies already account for the majority of meat production overall, and are projected to account for the majority of growth in animal consumption in the coming years. Developing countries where farm animal production is expanding may no longer require an overall increase in the consumption of animal source foods among all segments of their populations, as a significant proportion of their populations are already meeting or exceeding their energy requirements.  Ironically, many developing countries with high levels of hunger and malnutrition now simultaneously bear the burden of an obesity-related public health crisis, with the number of overweight women already exceeding the number of underweight women in most developing countriesby 2005, according to research published in the American Journal of Clinical Nutrition.  To allow for a more equitable distribution of agricultural resources and to ensure long-term food security and health for all communities around the world, society should place greater emphasis on small-scale, multipurpose, more animal-welfare-friendly and environmentally sustainable farm animal production led by small farmers. Middle- and higher-income populations should also reduce their consumption of animal products.  A side event held within the U.N. climate conference — entitled "Meat: The Big Omission from the Talks on Emissions," hosted by leading international organizations such as the Royal Institute of International Affairs (Chatham House) and Humane Society International — brought together policymakers, scientists and civil society groups, and emphasized the need to reduce the number of animals raised for food. The event highlighted successful efforts around the world to achieve this goal by encouraging people to consume more plants and less meat. Jo Leinen, a German member of the European Parliament, spoke at the event, emphasizing nations' inability to mitigate climate change without shifting away from meat-centric diets. His comments came on the heels of a recently published report by Chatham House, "Changing Climate, Changing Diets: Pathways to Lower Meat Consumption," which specifically addresses potential government interventions to encourage meat and dairy reduction, ranging from public-awareness-raising campaigns to a carbon tax. Even Arnold Schwarzenegger agreed with the event premise — the former California governor, actor and bodybuilder made waves during the climate conference by calling on people to keep meat off their plates one or two days a week to address climate change, according to the BBC. And, a growing number of food service providers, educational institutions, environmental groups and other stakeholders are embracing meat-reduction initiatives such as Meatless Monday.  In October, HSI launched Green Monday South Africa and a Meatless Monday campaign in Mexico with events attended by media, celebrities and other stakeholders. There are also thriving humane eating campaigns in India, China and other emerging economies where meat consumption is rapidly rising, along with problems relating obesity and chronic disease.  The growing middle- and upper-class consumers in these countries are becoming increasingly sensitive to animal welfare, health and environmental issues, as exhibited by the increasing number of food companies in these regions adopting animal welfare policies, and the growth in the market for organic and other sustainable products.  HSI advocates what it calls compassionate eating, or the three R's: "reducing" or "replacing" consumption of animal products, and "refining" diets by choosing products from sources that adhere to higher animal welfare standards. In the EU, those goals are gaining popularity, and there is growing public support for meeting the target of a 30 percent reduction in animal product consumption by 2030 through a variety of policy mechanisms. HSI launched this formal call in September 2015 at The Free Lunch, one of the largest food events ever held outside the European Parliament, where approximately 1,000 people, including politicians, attended in support of reducing the consumption of animal-based foods in the EU. The event featured cross-party members of the European Parliament, including the Parliament's vice president, civil society representatives and a representative of the EU Health and Food Safety Commission. Pathways to the 30 percent goal include incorporating sustainable food consumption into the EU and its member states' climate action plan; revising the European Commission's Green Public Procurement guidelines; and developing guidelines for healthy and sustainable diets.  In early 2015, more than 60 cross-party members of the European Parliament wrote to European Commission President Jean-Claude Juncker and others to demand the publication of the blocked Communication on Building a Sustainable System, as well as EU sustainable dietary guidelines including a reduction in consumption of animal-based foods. The communication has been held up by a "principle of political discontinuity," practically ensuring that this important document never sees the light of day. Yet science demands more work to move this issue forward. With its overall goal and its recognition of the importance of people's consumption choices, the Paris Agreement provides a signal at the global level.  The preamble of the document states that "sustainable lifestyles and sustainable patterns of consumption and production, with developed country Parties taking the lead, play an important role in addressing climate change." The parties should elaborate this at the national and subnational level. Research increasingly shows the benefits of moving toward more plant-based diets — to improve the welfare of farm animals, promote environmental sustainability and protect human health. It is time to really get to the meat of the matter and stop avoiding the elephant — or chicken or pig — in the room.  Follow all of the Expert Voices issues and debates — and become part of the discussion — on Facebook, Twitter and Google+. The views expressed are those of the author and do not necessarily reflect the views of the publisher. This version of the article was originally published on Live Science. Why Does Less Meat Mean Less Heat? (Op-Ed) Copyright 2016 LiveScience, a Purch company. All rights reserved. This material may not be published, broadcast, rewritten or redistributed.


Miyauchi Y.,Kyushu University | Nagata K.,Tohoku Pharmaceutical University | Yamazoe Y.,Food Safety Commission | Mackenzie P.I.,Flinders University | And 2 more authors.
Molecular Pharmacology | Year: 2015

There is a large discrepancy between the interindividual difference in the hepatic expression level of cytochrome P450 3A4 (CYP3A4) and that of drug clearance mediated by this enzyme. However, the reason for this discrepancy remains largely unknown. Because CYP3A4 interactswith UDP-glucuronosyltransferase 2B7 (UGT2B7) to alter its function, the reverse regulation is expected to modulate CYP3A4-catalyzed activity. To address this issue, we investigated whether protein-protein interaction between CYP3A4 and UGT2B7 modulates CYP3A4 function. For this purpose, we coexpressed CYP3A4, NADPH-cytochrome P450 reductase, and UGT2B7 using a baculovirus-insect cell system. The activity of CYP3A4 was significantly suppressed by coexpressing UGT2B7, and this suppressive effect was lost when UGT2B7 was replaced with calnexin (CNX). These results strongly suggest that UGT2B7 negatively regulates CYP3A4 activity through a protein-protein interaction. To identify the UGT2B7 domain associated with CYP3A4 suppression we generated 12 mutants including chimeras with CNX. Mutations introduced into the UGT2B7 carboxylterminal transmembrane helix caused a loss of the suppressive effect on CYP3A4. Thus, this hydrophobic region is necessary for the suppression of CYP3A4 activity. Replacement of the hydrophilic end of UGT2B7 with that of CNX produced a similar suppressive effect as the native enzyme. The data using chimeric protein demonstrated that the internal membrane-anchoring region of UGT2B7 is also needed for the association with CYP3A4. These data suggest that 1) UGT2B7 suppresses CYP3A4 function, and 2) both hydrophobic domains located near the C terminus and within UGT2B7 are needed for interaction with CYP3A4. Copyright © 2015 by The American Society for Pharmacology and Experimental Therapeutics.


News Article | February 23, 2017
Site: www.techtimes.com

The European Food Safety Authority (EFSA) along with the European Centre for Disease Prevention and Control (ECDC) declared that superbug bacteria found across the European Union (EU), are acting as potential threats for both animal and human health. Bacteria, which is typically found in animals, foods and humans has developed resistance against widely-used antibiotics warned the health officials on Feb. 22 . Per the reports shared by EFSA and ECDC, around 25,000 people die from these superbugs every year in the EU. "Antimicrobial resistance is an alarming threat putting human and animal health in danger," said the Commissioner of EU for Health and Food Safety, Vytenis Andriukaitis. Though substantial efforts have put to stop the rise of these superbugs, the implementation was not quick enough to cover all fronts. However, Andriukaitis also stated that to prevent the further onset of the antimicrobial resistance in the near future, the Health and Food Safety Commission will be launching the new Action Plan very soon. Per the report, the Salmonella bacteria, which causes the common food-borne disease called Salmonellosis, is said to have to higher multi-drug resistance throughout EU. According to Mike Catchpole, the chief Scientists at ECDC, monophasic Salmonella Typhimurium, one of the most prevalent types of Salmonella in human, exhibits highest multi-drug resistance capability. Drug resistance in the bacterium takes place due to misuse and overuse of antibiotics, which encourages the bacterium to find other ways of survival and with time develop ways to resist the effect of antibiotics. The antimicrobial resistance levels vary based on the geographical location. The Western and Northern Europe, have lower resistance than the Southern and Eastern Europe. According to Marta Hugas, the head of the Biological Hazards and Contaminants Units at EFSA, these geographical variations are highly based on the use and overuse of antimicrobials or in layman terms antibiotic medicines. She further added that countries who have taken efforts to reduce, replace and re-think the use of antibiotic medicines in animals, have shown a decreasing trend and lower levels of antimicrobial resistance. Thus it is clear that overuse of medicines not only harms our body but also gives the bacteria a way to adapt to the effects of the medicine and create resistance to it. Carbapenem antibiotics is the last source of treatment used for treating patients infected with the superbugs resistant to multiple drugs. As a part of EU's annual monitoring report, the resistance to Carbapenem antibiotics was first detected in very low levels among animals and food sources like pigs and their meat. Apart from Carbapenem, Colistin another antibiotic was also found to show resistance in lower levels in E. coli in pigs and pig's meat. © 2017 Tech Times, All rights reserved. Do not reproduce without permission.


Wei M.,Osaka City University | Wanibuchi H.,Osaka City University | Nakae D.,Japan National Institute of Public Health | Tsuda H.,Nagoya City University | And 5 more authors.
Cancer Science | Year: 2011

The carcinogenicity of the low amounts of genotoxic carcinogens present in food is of pressing concern. The purpose of the present study was to determine the carcinogenicity of low doses of the dietary genotoxic carcinogen 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) and to investigate mechanisms by which IQ exerts its carcinogenic effects. A total of 1595 male F344 rats were divided into seven groups and administered with IQ at doses of 0, 0.001, 0.01, 0.1, 1, 10 and 100 p.p.m. in the diet for 16 weeks. We found that IQ doses of 1 p.p.m. and below did not induce preneoplastic lesions in either the liver or the colon, while IQ doses of 10 and 100 p.p.m. induced preneoplastic lesions in both of these organs. These results demonstrate the presence of no-effect levels of IQ for both liver and colon carcinogenicity in rats. The finding that p21Cip/WAF1 was significantly induced in the liver at doses well below those required for IQ mediated carcinogenic effects suggests that induction of p21Cip/WAF1 is one of the mechanisms responsible for the observed no-effect of low doses of IQ. Furthermore, IQ administration caused significant induction of CYP1A2 at doses of 0.01-10 p.p.m., but administration of 100 p.p.m. IQ induced CYP1A1 rather than CYP1A2. This result indicates the importance of dosage when interpreting data on the carcinogenicity and metabolic activation of IQ. Overall, our results suggest the existence of no-effect levels for the carcinogenicity of this genotoxic compound. © 2010 Japanese Cancer Association.


Saegusa Y.,Tokyo University of Agriculture and Technology | Saegusa Y.,Gifu University | Woo G.-H.,Japan National Institute of Health Sciences | Fujimoto H.,Japan National Institute of Health Sciences | And 10 more authors.
Reproductive Toxicology | Year: 2010

To detect molecular evidence reflecting a permanent disruption of neuronal development due to hypothyroidism, distribution of Reelin-producing cells that function in neuronal migration and positioning was analyzed in the hippocampal dentate hilus using rats. From gestation day 10, maternal rats were administered either 6-propyl-2-thiouracil (PTU) at 3 or 12. ppm (0.57 or 1.97. mg/kg body weight/day) or methimazole (MMI) at 200. ppm (27.2. mg/kg body weight/day) in the drinking water and male offspring were immunohistochemically examined at the end of exposure on weaning (postnatal day 20) and at the adult stage (11-week-old). Offspring with MMI and 12. ppm PTU displayed evidence of growth retardation lasting into the adult stage. On the other hand, all exposure groups showed a sustained increase in Reelin-expressing cells in the dentate hilus until the adult stage in parallel with Calbindin-D-28K-expressing cells at weaning and with glutamic acid decarboxylase 67-positive cells in the adult stage, confirming an increase in γ-aminobutyric acid (GABA)ergic interneurons. At the adult stage, NeuN-positive postmitotic mature neurons were also increased in the hilus in all exposure groups, however, the increased population of Reelin-producing cells at this stage was either weakly positive or negative for NeuN, indicative of immature neurons. At weaning, neuroblast-producing subgranular zone of the dentate gyrus showed increased apoptosis and decreased cell proliferation suggestive of impaired neurogenesis. The results suggest that sustained increases of immature GABAergic interneurons synthesizing Reelin in the hilus could be a signature of compensatory regulation for impaired neurogenesis and mismigration during the neuronal development as a hypothyroidism-related brain effect rather than that secondary to systemic growth retardation. © 2010 Elsevier Inc.


Asakura H.,Japan National Institute of Health Sciences | Momose Y.,Japan National Institute of Health Sciences | Ryu C.-H.,Japan National Institute of Health Sciences | Kasuga F.,Japan National Institute of Health Sciences | And 3 more authors.
Food Additives and Contaminants - Part A Chemistry, Analysis, Control, Exposure and Risk Assessment | Year: 2013

Providencia alcalifaciens is a member of the Enterobacteriaceae family that occasionally causes diarrheagenic illness in humans via the intake of contaminated foods. Despite the epidemiological importance of P. alcalifaciens, little is known about its pathobiology. Here we report that P. alcalifaciens causes barrier dysfunction in Caco-2 cell monolayers and induces apoptosis in calf pulmonary artery endothelial cells. P. alcalifaciens infection caused a 30% reduction in transepithelial resistance in Caco-2 cell monolayers, which was greater than that for cells infected with Shigella flexneri or non-pathogenic Escherichia coli. As with viable bacteria, bacterial lysates treated with heat, benzonase or proteinase, but not with polymixin B, were also involved in the cellular response. TLR4 antibody neutralisation significantly restored the P. alcalifaciens-induced transepithelial resistance reduction in Caco-2 cells, suggesting that lipopolysaccharides (LPSs) might play a central role in this cellular response. Western blotting further indicated that P. alcalifaciens LPSs reduced occludin levels, whereas LPSs from Shigella or E. coli did not. Although the viability of Caco-2 cells was not altered significantly, the calf pulmonary artery endothelial cell line was highly sensitive to P. alcalifaciens infection. This sensitivity was indeed dependent on LPS, which induced rapid apoptosis. Together, these data show that P. alcalifaciens LPSs participate in epithelial barrier dysfunction and endothelial apoptosis. The findings give insight into the LPS-dependent cell signal events affecting diarrheagenicity during infection with P. alcalifaciens. © 2013 Copyright Taylor and Francis Group, LLC.


Hara-Kudo Y.,Japan National Institute of Health Sciences | Kumagai S.,Food Safety Commission
Epidemiology and Infection | Year: 2014

Consumption of seafood contaminated with Vibrio parahaemolyticus causes foodborne infections, which are on the rise owing to increased consumption of raw seafood in Asia, Europe, North America, and other regions. V. parahaemolyticus infections have been common in Japan since the 1960s. Following an epidemic in 1997, the Japanese Ministry of Health, Labour, and Welfare instituted regulations for seafood in 1999, which appear to be reducing V. parahaemolyticus infections. In this review, we describe the scientific findings for these regulations. Analyses of the V. parahaemolyticus serotypes and isolate characteristics in samples from infected patients and contaminated seafood are discussed. In addition, based on the results of a survey, we show that new food safety regulations have led to improvements in food hygiene at many seafood retail shops, food service facilities, and restaurants. This example from Japan could be of immense help to control foodborne infections in other countries. Copyright © Cambridge University Press 2014.

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