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Within the framework of the Health Impact Assessment Schiphol Airport, a feasibility study was conducted in primary school children. The purpose of the study was to examine the feasibility of using computerized performance tests and questionnaires to examine the behavioral effects of exposure to aircraft noise in children. The study involved 159 children aged 8-12 years, 86 attending school in Zwanenburg, a town located 8 kilometers from the airport and 73 children attending school in Uitgeest, a town located approximately 23 kilometers from the airport. Methods used to assess behavioral functioning included selected tests from the Neurobehavioral Evaluation System designed to assess attention, psychomotor performance, perceptual coding, learning and memory as well as two behavioral questionnaires. Subjective ratings of sleep quality and annoyance were also examined. Children were tested twice during school hours in the period May-June 1995 with a 4-6 week interval between testing. The results of this study indicated a high level of acceptance of computerized testing procedures by the children, teachers and parents and a high level of test-retest reliability for most tests and rating scales. Some differences in performance and behavioral ratings between the high and lower exposure groups were noted. However, no firm conclusions regarding the relationship between aircraft noise and performance can be reached because of the small number of children tested and the lack of adequate exposure information. In conclusion, the results of this study demonstrate the feasibility of applying behavioral methods in the school setting. Based on these results, it is recommended that future research designed to examine the effects of aircraft noise using these methods employ study designs involving the testing of at least 500 children from locations with known exposure levels. Further, these locations should be chosen to maximize the contrast in aircraft noise exposure and estimates of individual aircraft exposure for each child should be obtained.

In de interimrapportage wordt de huidige stand van zaken beschreven van, hoofdzakelijk, (inter)nationaal epidemiologisch onderzoek naar de relatie tussen PM10 en het optreden van gezondheidseffecten. PM10 ("particulate matter") is de afkorting van de massa van de in de lucht zwevende deeltjes (aerosol) met een diameter kleiner dan ongeveer 10 micrometer (10 mum = 0,01 mm). PM10 wordt in Nederland ook wel "fijn stof" genoemd en geldt als indicator voor de ernst van het wintersmogmengsel. Daarna wordt verslag gedaan van het onderzoek dat tot nu toe is afgerond. Uit de literatuur blijkt dat blootstelling aan wintersmog geassocieerd is met een toename van de dagelijkse sterfte, met ziekenhuisopnamen voor ademhalingsklachten, met een toename van medicijngebruik bij astmatici en met longfunctieverslechtering. Er lijkt geen drempelwaarde voor dergelijke associaties te bestaan waar beneden effecten op mortaliteit en morbiditeit niet meer voorkomen. Gelet op de moeilijkheid een drempelwaarde vast te stellen, wordt een schatting van de gezondheidseffecten uitgedrukt als procentuele toename per 100 mug/m3 verandering in de daggemiddelde concentratie van PM10. Deze toename is voor dagelijkse sterfte 10-15%, voor toename van ziekenhuisopnamen voor respiratoire aandoeningen 20-40% en voor toename van medicijngebruik bij astmatici ongeveer 30%. De longfunctieverslechtering wordt geschat op 2-4% voor 100 mug/m3 toename van de PM10 concentratie. De daggemiddelde PM10-concentraties in Nederland kunnen tijdens wintersmogepisoden oplopen tot 140 mug/m3 en hoger. Er zijn weinig toxicologische gegevens beschikbaar omtrent de gezondheidseffecten en het werkingsmechanisme van deeltjesvormige luchtverontreiniging. Enkele proefdierstudies met gecontroleerde inhalatie van verschillende (redelijk oplosbare) deeltjes suggereren dat de grootte van het oppervlak en de reactiviteit van het oppervlak van ultrafijne deeltjes (< 0,1 mum) een rol spelen in het veroorzaken van pulmonale effecten. Het grootste deel van de massa van alle deeltjes wordt veroorzaakt door deeltjes met een diameter van enige micrometers (mum) tot enige tientallen micrometers. Omdat de hoogte van de PM10-niveaus afhangt van de massa van de deeltjes worden deze PM10-niveaus vooral bepaald door deeltjes groter dan enkele micrometers in diameter. De ultrafijne deeltjes met diameters van enige honderdsten tot tienden van micrometers vormen wel de grootste aantallen deeltjes, maar dragen vrijwel niet bij aan de PM10-niveaus. Deeltjes van tussenliggende diameters bepalen voor het grootste deel het oppervlak. Zij hebben een verwaarloosbaar effect op de PM10-niveaus. Het is momenteel nog onbekend of het toxische werkingsmechanisme van de deeltjes afhangt van de massa dan wel de chemische samenstelling van de deeltjes, of afhangt van het oppervlak van de deeltjes of juist van de aantallen deeltjes. Daarom is de keuze van het juiste bestrijdingsdoel op dit moment niet eenvoudig.

De centrale vraag van deze pilot-studie is of de gekozen meetinstrumenten betrouwbaar en geschikt zijn voor toekomstig onderzoek naar de invloed van geluidsbelasting door vliegverkeer op cognitieve prestaties en gedrag van kinderen. Het pilot-onderzoek werd in de periode mei-juni 1995 uitgevoerd bij 86 kinderen (8-12 jaar oud) uit een gebied met een relatief hoge geluidsbelasting door vliegverkeer (Zwanenburg, 8 km van Schiphol) en bij 73 kinderen uit een gebied met een relatief lage geluidsbelasting (Uitgeest). De kinderen werden tweemaal onder schooltijd getest met een interval van 4 tot 6 weken. Het testinstrumentarium bestond uit een vijftal cognitieve prestatietests en twee gedragsbeoordelingslijsten ter bepaling van aandachtsvermogen, motoriek, perceptuele verwerking, geheugen, leesvaardigheid en gedragsproblemen. Daarnaast zijn korte vragenlijsten over de slaapkwaliteit en de ervaren geluidhinder afgenomen. Geconcludeerd wordt dat een veldstudie met een dergelijke omvang zowel in technische als logistieke zin goed uitvoerbaar is. Het gebruikte testinstrumentarium blijkt grotendeels betrouwbaar en geschikt voor onderzoek naar de effecten van vliegtuiggeluid op het prestatievermogen en het gedrag van kinderen, en wees voorts op enkele groepsverschillen. De hoog geluidbelaste groep scoorde slechter op een motorische en een aandachtstest. De ouders van de geluidbelaste kinderen rapporteerden meer aandachts- en sociale problemen. Anderzijds werd hyperactiviteit juist minder vaak bij de aan vliegtuiggeluid blootgestelde groep waargenomen. Voor de overige gedragskenmerken en voor (ervaren) slaapkwaliteit zijn geen verschillen tussen de twee groepen gevonden. Het percentage kinderen dat hinder van geluid ondervond was bijna twee keer zo hoog in de groep met de hoge geluidbelasting (76%) vergeleken met kinderen uit het gebied met weinig vliegtuiggeluid (40%). Vanwege het verkennend karakter is het onderzoek uitgevoerd bij een beperkt aantal kinderen. Conclusies over de relatie tussen de geluidsbelasting door vliegverkeer en het prestatievermogen en het gedrag bij kinderen zijn daarom niet mogelijk. Aanbevelingen voor eventueel verder onderzoek zijn onder meer: een steekproef van ten minste 500 kinderen, afkomstig van vergelijkbare scholen (identiteit, schoolgrootte, klassegrootte, onderwijsmethode) ; 3-5 geluidbelaste groepen met een zo groot mogelijk contrast in geluidsbelasting ; en bepaling van de individuele geluidsbelasting.

This report presents a halfway score of the research project "Winter smog and Traffic", one of the themes of the research programme "Air Pollution and Health". A state of the art is presented of the health effects associated with exposure to winter smog and of the toxicological effects caused by the inhalation of particles. A summary of the assessment of air quality and the results of epidemiological research is presented. Some policy questions are answered as far as possible at this stage of the project. Finally, an outline of a plan of activities is presented which is based on the policy needs and the most serious gaps in knowledge.

The question whether there are correlations between observed geographical differences in human health and risks due to several types of environmental contamination led to the project 'Accumulation of environmental risks'. The project aimed, firstly, at developing methods to illustrate these geographical differences and, secondly, at applying these methods. The methods are applied to map the risks due to possible severe accidents (external safety), radioactive substances and radiation, substances in air, and environmental noise. The investigation resulted in two reports. The main report contains a general description of the methods applied and the maps created. The accompanying background document (report no. 610127002) focuses on the details of the methods and on the data used. In spite of the complexity of the discussions on risk-related subjects, it appears that by applying the methods developed insight has been obtained into the geographical distribution and the proportions of risks. These methods are based on the risk concept which is implemented in the environmental policy in the Netherlands. The geographical distribution of risks differs greatly between external safety and noise on the one hand and radiation and substances on the other hand. The maps for external safety and noise show high risks on a local scale ; there are areas where risk for these two categories is equal to zero (areas without sources of danger or disturbing noise). Spatial coincidence of external safety risks rarely occurs. Especially for noise the areas of zero risk are smaller than those shown by the maps because the lack of information made a significant part of the risk incalculable. Spatial coincidence of environmental noise occurs mainly near junctions of transport lines and near (large) airports. The risks due to radiation and substances, on the contrary, cover large parts of the Netherlands, with local increases near large (industrial) sources. Peaks in risks on scales less than 500 or 100 m, e.g. near road traffic, are not visible on the maps.

This report is a practical guide for the application of probabilistic distributions of default assessment factors in human health risk assessments. RIVM and TNO developed the use of probabilistic assessment factors as a first step towards further national and international harmonisation. Consensus was reached on the nature of distributions of several human assessment factors. The proposed distributions will be applied in risk assessments of new and existing substances and pesticides, produced at RIVM and TNO. A format for this analysis is presented in this report.

A food consumption survey was conducted among 750 Dutch young adults (aged 19-30) using two independent computerized 24-hour dietary recalls. This dietary assessment method seems promising as part of a revised dietary monitoring system for the Netherlands. Dietary monitoring is an important tool for food policy evaluation and development. The methodologies for previous surveys were less optimal for answering current food policy questions. The computerized 24-hour dietary recall method has the advantage that food consumption data with a great level of detail can be collected and stored. The use of a telephone approach made it possible to collect data on two independent days in an efficient way. The resulting food consumption data are therefore able to answer more questions than previously was the case. Such questions have to do with food safety, and estimates of the fraction of the population adhering to dietary recommendations. The new approach has to be tested and developed for other population groups; calibration will also make time trend analyses possible. Response of the survey at 42% was rather low. The study population is, however, representative with regard to age, level of education and region. Subjects living in areas with high population densities were slightly underrepresented, which could be corrected for in the data. There were indications that the data in general may not be fully representative for especially Dutch young women.

Consumption of vegetables and fruits among Dutch young adults is grossly inadequate. With regard to dietary fat intake, intake of saturated fats is still too high, whereas average intake of trans fatty acids stands almost at the recommended level. A great gain in public health can be achieved by improving dietary habits to meet with recommendation levels, for example, by increasing vegetable and fruit consumption and improving the fatty acid profile in the diet. Food consumption was assessed in 750 Dutch adults 19-30 years of age. Given the recommendation of 150-200 g vegetables per day, only 2% of the research population consumed 150 g daily and none of the 750 adults assessed consumed 200 g daily. Less than 10% of the population consumed the recommended 200 g of fruit per day. Over half the respondents (53% of the women and 58% of the men) consumed a diet containing less than 35% energy fat. The recommendation to use a diet with less than 10% energy saturated fatty acids was met by few: 11% of the men and 6% of the women. Almost 60% of the men and 28% of the women used a diet that contained less than 1% energy from trans fatty acids. Based on these results we recommend that nutrition policy remain focused on increasing vegetable and fruit consumption, and decreasing intake of saturated fatty acids.

Although there is much epidemiological evidence for an interaction between diet and colorectal cancer risk, the mechanisms by which diet might protect against colorectal cancer are still unclear. Here we report the significant up-regulation of carcinogen-induced apoptosis in the colon of rats fed a diet containing low-risk factors for colon cancer, namely low fat content, high calcium and high non-digestible carbohydrate. The dose-dependent induction of apoptosis in colonic crypts by the carcinogen 1,2-dimethylhydrazine (DMH) was significantly greater in rats receiving the low-risk compared with a high-risk (high fat, low calcium, low non-digestible carbohydrate) diet (P

Over the past few years the presence of p53-like proteins in plants was frequently reported, by using the monoclonal antibody Pab240. By means of protein purification and screening a cDNA library, a Pab240 cross-reacting protein and a cDNA clone were isolated from barley. Peptide- and DNA-sequence analysis identified one and the same protein: 2-oxoglutarate dehydrogenase. Sequence analysis of 2-oxoglutarate dehydrogenase revealed that the protein contains a perfect Pab240 epitope. In barley, the 110 kDa oxoglutarate dehydrogenase was degraded during isolation to a 53 kDa Pab240 cross-reacting polypeptide, thereby mimicking curiously p53-like properties. © 2002 Federation of European Biochemical Societies. Published by Elsevier Science B.V. All rights reserved. Chemicals/CAS: Ketoglutarate Dehydrogenase Complex, EC 1.2.4.2; Plant Proteins; Tumor Suppressor Protein p53

Chemicals/CAS: Biological Products; Ethylmercury Compounds; Food Additives; Pharmaceutical Preparations; Preservatives, Pharmaceutical; Thimerosal, 54-64-8

Over the past decades the description of quantitative structure-activity relationships (QSARs) has been undertaken in order to find predictive models and/or mechanistic explanations for chemical as well as biological activities. This includes QSAR studies in toxicology. In an approach beyond the classical QSAR approaches, attempts have been made to define parameters for the QSAR studies on the basis of quantum mechanical computer calculations. The conversion of relatively small xenobiotics within the active sites of biotransformation enzymes can be expected to follow the general rules of chemistry. This makes the description of QSARs on the basis of only one parameter, chosen on the basis of insight in the mechanism, feasible. In contrast, toxicological endpoints can very often be the result of more than one physico-chemical interaction of the compound with the model system of interest. Therefore the description of quantitative structure-toxicity relationships often does not follow a one-descriptor mechanistic approach but starts from the other end, describing QSARs by multi-parameter approaches. The present paper focuses on the possibilities and restrictions of using computer-based QSAR modeling for analyzing experimental toxicological data, with emphasis on examples from the field of biotransformation and toxicity. © 2001 Elsevier Science Ltd. All rights reserved. Chemicals/CAS: Hazardous Substances

ln 2018 komt er een einde aan de aanwezigheid van TNO aan de Utrechtseweg 48 in Zeist. Duizenden TNO'ers (en bezoekers) zijn gedurende vele jaren het markante gebouw met de nog markantere trap binnengekomen en hebben gedurende die jaren daar hun beste krachten gegeven. Wanneer het gebouw kon spreken, dan zouden we wellicht versteld staan wat er zich binnen de muren allemaal heeft afgespeeld. Vreugde en verdriet, prachtig onderzoek, hartelijke collega's, vaak ruimte voor eigen initiatief, maar ook strakke werkvormen en dingen die we nooit geweten hebben en zullen weten. Het gebouw kan niet spreken en daarom is dit boekje samengesteld. Het bevat een keur aan artikelen, anekdotes en foto's die de geschiedenis doen herbeleven.

We have developed an analytical method, consisting of ion-pair liquid chromatography coupled to electrospray ionization mass spectrometry (IP-LC-ESI-MS), for the simultaneous quantitative analysis of several key classes of polar metabolites, like nucleotides, coenzyme A esters, sugar nucleotides, and sugar bisphosphates. The use of the ion-pair agent hexylamine and optimization of the pH of the mobile phases were critical parameters in obtaining good retention and peak shapes of many of the above-mentioned polar and acidic metabolites that are impossible to analyze using standard reversed-phase LC/MS. Optimum conditions were found when using a gradient from 5 mM hexylamine in water (pH 6.3) to 90% methanol/10% 10 mM ammonium acetate (pH 8.5). The IP-LC-ESI-MS method was extensively validated by determining the linearity (R2 > 0.995), sensitivity (limit of detection 0.1-1 ng), repeatability, and reproducibility (relative standard deviation

Nutrient - gene interactions are responsible for maintaining health and preventing or delaying disease. Unbalanced diets for a given genotype lead to chronic diseases such as obesity, diabetes, cardiovascular, and are likely to contribute to increased severity and/or early-onset of many age-related diseases. Many nutrition and many genetic studies still fail to properly include both variables in the design, execution, and analyses of human, laboratory animal, or cell culture experiments. The complexity ofnutrient-gene interactions has led to the realization that strategic international alliances are needed to improve the completeness of nutrigenomic studies - a task beyond the capabilities of a single laboratory team. Eighty-eight researchers from 22 countries recently outlined the issues and challenges for harnessing the nutritional genomics for public and personal health. The next step in the process of forming productive international alliances is the development of a virtual center for organizing collaborations and communications that foster resources sharing, best practices improvements, and creation of databases. We describe here plans and initial efforts of creating the Nutrigenomics Information Portal, a web-based resource for the international nutrigenomics society. This portal aims at becoming the prime source ofinformation and interaction for nutrigenomics scientists through a collaborative effort.

Objective: To determine the gastrointestinal (GI) tolerance of NUTRIOSE®FB in men. Design: A randomized, placebo-contro lled, parallel, double-blind study. Setting: The metabolic ward of TNO Quality of Life. Subjects: Forty-eight subjects started the study: 16 men participated in one of the three treatments. Subjects consumed either 22.5 g of pure maltodextrin (Glucidex®6), or 30 or 45 g of the dextrin NUTRIOSE®FB daily for 4-5 weeks. Forty-three subjects completed the study (age: 34.7±8.2 years; BMI 24.9±3.3 kg m2). Measurements: Tolerance of NUTRIOSE®FB was examined with a GI complaints questionnaire; effectiveness on colonic flora was examined by faecal analysis; fermentation by breath hydrogen excretion measurement. Furthermore, the effect on body weight (BW), energy intake and blood parameters were examined in the study. Results: Both doses of NUTRIOSE®FB were very well tolerated and GI complaints hardly differed from the placebo treatment. No diarrhoea was reported due to NUTRIOSE®FB supplementation. In the course of the study, some habituation and adaptation of GI symptoms were found. Fermentation and faecal characteristics (pH and enzyme activity) were significantly positively affected with NUTRIOSE®FB treatment. Body weight in both NUTRIOSE®FB groups remained stable over time, although the placebo-treated group showed a small increase in BW (Δday35-1 0.8±1.0 kg) (P=0.07). However, total food intake and macronutrient composition of the diet remained the same throughout the study. No significant differences were found between the three treatment groups in hunger and satiety scores and food preferences. Conclusions: Long-term supplementation of 30 or 45 g of the dextrin NUTRIOSE®FB per day was well tolerated, and may act as a pre-biotic supplement. © 2006 Nature Publishing Group. All rights reserved.

KEYWORDS - CLASSIFICATION: adverse effects;analysis;Boston;cancer epidemiology;Cholesterol;Cohort Studies;dietary modulation of cancer & cancer biomarkers;Dietary Fats;epidemiology;etiology;Eggs;Female;Food Habits;Humans;North America;Ovarian Neoplasms;Public Health;Research;Risk. Fat and cholesterol are theorized to promote ovarian carcinogenesis by increasing circulating estrogen levels. Although case-control studies have reported positive associations between total and saturated fat intake and ovarian cancer risk, two cohort studies have observed null associations. Dietary cholesterol and eggs have been positively associated with ovarian cancer risk. A pooled analysis was conducted on 12 cohort studies. Among 523,217 women, 2,132 incident epithelial ovarian cancer cases were identified. Study-specific relative risks (RR) and 95% confidence intervals (CI) were calculated by Cox proportional hazards models, and then pooled using a random effects model. Total fat intake was not associated with ovarian cancer risk (pooled multivariate RR = 1.08, 95% CI 0.86-1.34 comparing > or =45 to 30

The increased consumption of fruits and vegetables is associated with reduced cardiovascular disease. The molecular basis of this health effect is not fully understood, yet dietary flavonoids are thought to play an important role. Genetic engineering has enabled us to overexpress specific flavonoids (flavones and flavonols) in tomato fruit. Human C-reactive protein transgenic (CRPtg) mice express markers of cardiovascular risk that allow us to study of the putative health effects of wild-type tomato (wtTom) and flavonoid-enriched tomato (flTom). In this study, we analyzed whether consumption of wtTom, at a dose achievable with a human diet, has beneficial effects on cardiovascular risk markers and whether flTom may enhance such effects. CRPtg mice were fed a diet containing 4 g/kg wtTom, flTom peel, vehicle, or 1 g/kg fenofibrate, which reportedly reduces cardiovascular risk, for 7 wk. Markers of general health (bodyweight, food intake, and plasma alanine aminotransferase activities) and of cardiovascular risk (plasma CRP, fibrinogen, E-selectin, and cholesterol levels) were analyzed. All groups had comparable food intakes and body-weight gains. Plasma alanine aminotransferase activities increased significantly in vehicle and fenofibrate-treated mice. Compared with baseline, wtTom and flTom significantly reduced basal human CRP concentrations by 43 and 56%, respectively. The CRP-lowering effect of flTom significantly exceeded that of wtTom. The effects of flTom on CRP were reversed within a 2-wk washout period. WtTom and flTom did not affect fibrinogen, but comparably repressed E-selectin expression and upregulated HDL cholesterol. Tomato peel consumption improved cardiovascular risk factors in CRPtg mice, a beneficial effect that was further enhanced by enrichment of the flavonoid content. © 2006 American Society for Nutrition.

Objective: The aim of this study was to investigate the associations between meat and fish consumption and APC mutation status and hMLH1 expression in colon and rectal cancer. Methods: The associations were investigated in the Netherlands Cohort Study, and included 434 colon and 154 rectal cancer patients on whom case-cohort analyses (subcohort n = 2948) were performed. Results: Total meat consumption was not associated with the endpoints studied. Meat product (i.e. processed meat) consumption showed a positive association with colon tumours harbouring a truncating APC mutation, whereas beef consumption was associated with an increased risk of colon tumours without a truncating APC mutation (incidence rate ratio (RR) highest versus lowest quartile of intake 1.61, 95% confidence interval (CI) 0.96-2.71, p-trend = 0.04 and 1.58, 95% CI 1.10-2.25, p-trend = 0.01, respectively). Consumption of other meat (horsemeat, lamb, mutton, frankfurters and deep-fried meat rolls) was associated with an increased risk of rectal cancer without a truncating APC mutation (RR intake versus no intake 1.79, 95% CI 1.10-2.90). No associations were observed for meat consumption and tumours lacking hMLH1 expression. Conclusions: Our data indicate that several types of meat may contribute differently to the aetiology of colon and rectal cancer, depending on APC mutation status but not hMLH1 expression of the tumour. © Springer 2005.

A previously proposed explanation for the change in gluten properties on addition of pentosans to doughs was based on data for only one wheat cultivar. Using three wheat cultivars, Scipion, Soissons and Amazon, differing in technological quality from weak to strong we have obtained results that support the previous explanation. In addition to standard techniques for characterizing gluten and glutenin macropolymer (GMP) yield, composition and properties, a new technique (particle size analysis) was applied that provides further detail on GMP particle size distribution. For each of the three wheat cultivars the effect of WUS and xylanase on gluten and GMP yield, composition and properties followed the trend previously observed. However, WUS and xylanase affected gluten yield and properties more strongly for Scipion and Soissons than for Amazon. Amazon flour contains more protein and less pentosans. The analysis of GMP particles demonstrates that the volume surface average particle diameter D3,2 of GMP particles from Amazon wheat is larger than those from Scipion and Soissons. Amazon has the ability to form larger and stickier particles. These factors may explain why the effects of pentosans and xylanase on gluten yield and properties are smaller for this wheat. © 2004 Elsevier Ltd. All rights reserved.

Bacterial fructosyltransferase enzymes belonging to glycoside hydrolase family 68 (GH68) are not known to require a metal cofactor. Here, we show that Ca2+ ions play an important structural role in the Lactobacillus reuteri 121 levansucrase (Lev) and inulosucrase (Inu) enzymes. Analysis of the Bacillus subtilis Lev 3D structure [Meng, G. and Futterer, K. (2003) Nat. Struct. Biol. 10, 935-941] has provided evidence for the presence of a bound metal ion, most likely Ca2+. Characterization of site-directed mutants in the putative Ca2+ ion-binding sites of Lb. reuteri Lev and Inu revealed that the Inu Asp520 and Lev Asp500 residues play an important role in Ca2+ binding. Sequence alignments of family GH68 proteins showed that this Ca2+ ion-binding site is (largely) present only in proteins of Gram-positive origin. © 2005 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved. Molecular Sequence Numbers: GENBANK: AF459437, AF465251; Chemicals / CAS: calcium ion, 14127-61-8; fructosyltransferase, 9031-67-8; levansucrase, 9030-17-5; Calcium, 7440-70-2; Edetic Acid, 60-00-4; Hexosyltransferases, EC 2.4.1.-; inulosucrase, EC 2.4.1.9; levansucrase, EC 2.4.1.10

The effect of protein quality, protein content, bran addition, diacetyl tartaric acid ester of monoglycerides (DATEM), proving time, and their interaction on hearth bread characteristics were studied by size-exclusion fast protein liquid chromatography, Kieffer dough and gluten extensibility rig, and small-scale baking of hearth loaves. Protein quality influenced size and shape of the hearth loaves positively. Enhanced protein content increased loaf volume and decreased the form ratio of hearth loaves. The effect of protein quality and protein content was dependent on the size-distribution of the proteins in flour, which affected the viscoelastic properties of the dough. Doughs made from flours with strong protein quality can be proved for a longer time and thereby expand more than doughs made from weak protein quality flours. Doughs made from strong protein quality flours tolerated bran addition better than doughs made from weak protein quality flours. Doughs made from high protein content flours were more suited for hearth bread production with bran than doughs made from flours with low protein content. DATEM had small effect on dough properties and hearth loaf characteristics compared with the other factors.

The objective of this project was to collect and evaluate data on nutrient intake and status across Europe and to ascertain whether any trends could be identified. Surveys of dietary intake and status were collected from across Europe by literature search and personal contact with country experts. Surveys that satisfied a defined set of criteria – published, based on individual intakes, post-1987, adequate information provided to enable its quality to be assessed, small age bands, data for sexes separated above 12 years, sample size over 25 and subjects representative of the population – were selected for further analysis. In a small number of cases, where no other data for a country were available or where status data were given, exceptions were made. Seventy-nine surveys from 23 countries were included, and from them data on energy, protein, fats, carbohydrates, alcohol, vitamins, minerals and trace elements were collected and tabulated. Data on energy, protein, total fat and carbohydrate were given in a large number of surveys, but information was very limited for some micronutrients. No surveys gave information on fluid intake and insufficient gave data on food patterns to be of value to this project. A variety of collection methods were used, there was no consistency in the ages of children surveyed or the age cut-off points, but most surveys gave data for males and females separately at all ages. Just under half of the surveys were nationally representative and most of the remainder were regional. Only a small number of local surveys could be included. Apart from anthropometric measurements, status data were collected in only seven countries. Males had higher energy intakes than females, energy intake increased with age but levelled off in adolescent girls. Intakes of other nutrients generally related to energy intakes. Some north–south geographical trends were noted in fat and carbohydrate intakes, but these were not apparent for other nutrients. Some other trends between countries were noted, but there were also wide variations within countries. A number of validation studies have shown that misreporting is a major problem in dietary surveys of children and adolescents and so all the dietary data collected for this project should be interpreted and evaluated with caution In addition, dietary studies rely on food composition tables for the conversion of food intake data to estimated nutrient intakes and each country uses a different set of food composition data which differ in definitions, analytical methods, units and modes of expression. This can make comparisons between countries difficult and inaccurate. Methods of measuring food intake are not standardised across Europe and intake data are generally poor, so there are uncertainties over the true nutrient intakes of children and adolescents across Europe. There are insufficient data on status to be able to be able to draw any conclusions about the nutritional quality of the diets of European children and adolescents.

Heterologous conjugates of wheat arabinoxylan and beta-casein were prepared via enzymatic cross-linking, using sequential addition of the arabinoxylan to a mixture of beta-casein, peroxidase, and hydrogen peroxide. The maximal formation of adducts between the beta-casein and the feruloylated arabinoxylan was reached at a protein-to-arabinoxylan ratio of 10:1, in combination with a molar ratio hydrogen peroxide to substrate of 2:1 and a molar protein-to-enzyme ratio between 10(2) and 10(4). The protein-arabinoxylan adducts were separated from the arabinoxylan homopolymers by size exclusion and anion exchange chromatography. The molar ratio protein:arabinoxylan in the purified conjugates varied between 0.1 and 5.6. This is the first report on the large-scale enzymatic preparation of heterologous protein-arabinoxylan conjugates.

The effects of nonoral sensations, such as visual texture and odor, on the size of the first bite were investigated in a series of studies using specially constructed food delivery cups with lower, from which custards were ingested ("ingested custard"), and upper, from which a custard was viewed and/or smelled ("upper custard") compartments. Ingested and upper custards were either the same or different. Bite size was defined as the weight of custard sucked out of the lower compartment during a single suck through an I I -mm diameter straw. The results from the first study indicated that the recognition of oral qualities of custards via vision or olfaction determined the size of the first bite. When this recognition was favorable, e.g., when the upper custard was known to be creamy, a relatively large bite was taken, irrespective of the custard that was actually ingested. When this recognition was unfavorable, a relatively small bite was taken. The second study showed that when recognition was prevented by modifications of the upper custard's color, odor, or visual texture, bite size was determined by the oral qualities of the ingested custard. This was confirmed in a third study, where the oral characteristics of the ingested custard were varied by adding a flavorant (benzaldehyde) and/or by using nose clips to eliminate retronasal smelling. Bite sizes decreased significantly when these variations reduced creaminess. Odor and visual texture characteristics of the upper custard significantly affected the perception of creaminess and other attributes related to the food's viscosity, melting, and thickness. (C) 2004 Elsevier Inc. All rights reserved.

Background: Treatment of persons at high risk for coronary heart disease (CHD) should include nutritional counselling, but little is known about the effects of different types of education. Methods: In a quasi-experimental study design the effects of a nutritional education programme (1st year: three group sessions by a dietitian; 2nd year: one group session; 3rd year: additional focus on saturated fat; reinforcement by written nutritional messages annually) (intervention group; n=103) are compared with the effects of a posted leaflet containing standard dietary guidelines (control group; n=163). Participants had hypercholesterolemia (6-8 mmol/l) and at least two other CHD risk factors. Results: After 3 years, no significant differences existed in established CHD risk factors between intervention and control groups (adjusted mean net differences: total cholesterol (0 mmol/l), diastolic blood pressure (-1.1 mm Hg; NS), and body weight (+0.3 kg, NS)). Regarding dietary intake, the intervention group had a lower intake of total (net difference -2.0% of energy, SEM 0.9) and saturated fat (-1.2% of energy, SEM 0.4) and a higher fish (+11 g/day, SEM 4) and vegetables consumption (+21 g/day, SEM 10) during the study period (p

For human risk assessment, experimental data often have to be extrapolated for exposure duration, which is generally done by means of default values. The purpose of the present study was twofold. First, to derive a statistical distribution for differences in exposure duration that can be used in a probabilistic concept for combining assessment factors in risk characterization. Second, to obtain insight in the magnitude of the change in No-Observed-Adverse-Effect-Level (NOAEL) with exposure duration, which will lead to more science-based assessment factors for exposure duration. A large historical database, including 198 substances, was consulted. Ratios were calculated for pairs of NOAELs for systemic toxicity from oral toxicity studies with the same species (rats or mice, various strains) and different exposure duration categories. The Geometric Mean (GM), Geometric Standard Deviation (GSD), and the 90th and 95th percentile values were determined. The traditionally applied default factors for subacute to semichronic (10), for semichronic to chronic (10), and for subacute to chronic exposure (100) corresponded with the 93, 87, and 99-percentiles of the respective distributions. Options are presented for a set of default values and probabilistic distributions for assessment factors for exposure duration based on data from the consulted historical database.

Plant lignan 7-hydromatairesinol, a novel precursor of the mammalian lignan enterolactone was evaluated in a prenatal developmental toxicity study conducted in the Wistar rat. Mated female rats were fed diets containing 0, 0.25, 1, and 4% (w/w) of 7-hydroxymatairesinol in the form of potassium acetate complex (HMRlignan; potassium acetate level approximately 20% w/w within the preparation) for days 0-21 of gestation. Test substance intake was calculated to be 0.14-0.18, 0.46-0.74, and 1.19-2.93g/kg body weight/day for the low, mid, and high-dose groups, respectively. The rats were sacrificed on day 21 of the gestation period and examined for standard parameters of reproductive performance (fecundity index, gestation index, number of corpora lutea, number of implantations, pre- and post-implantation loss, number of early- and late resorptions, number of live- and dead fetuses, sex-ration and the weight of the reproductive organs). The fetuses were examined for external, visceral, and skeletal alterations. The results from this study showed no effects on reproductive performance or any treatment related findings following external, visceral, and skeletal examination of the fetuses. However, approximately half of the mated dams of the high-dose failed to thrive due to an unexpected large decrease in their food intake, and were sacrificed early. Body weights of the remaining animals of the high-dose group were decreased. Food consumption was decreased in all treatment groups during the first three days of the gestation period as a result of decreased palatability of the feed. In conclusion, the no-observed-effect level (NOEL) for maternal effects was 1%, whereas the NOEL for fetal development following daily oral HMRlignan administration throughout the gestation was equivalent to 4% in the diet. © 2004 Elsevier Inc. All rights reserved.

The embryotoxicity/teratogenicity of neohesperidin dihydrochalcone (NHDC) was examined in Wistar Crl:(WI)WU BR rats. NHDC was fed at dietary concentrations of 0, 1.25, 2.5 or 5 to groups of 28 mated female rats from day 0 to 21 of gestation. At Cesarean section 25, 22, 23, and 23 rats were found to be pregnant in the control, low-, mid-, and high-dose group, respectively. The NHDC treatment was well tolerated and all animals survived till the end of the study. Body weights (bw) and body weight gains did not differ between controls and NHDC treatment groups. The intake of NHDC was 0.8-0.9, 1.6-1.7, and 3.1-3.4g/kg bw/day for the low-, mid-, and high-dose group, respectively. Except for cecal enlargement, there were no changes observed at necropsy which could be related to the NHDC treatment. All dams had viable fetuses. The fecundity and gestation index, the number of corpora lutea, implantation sites, live and dead fetuses, early and late resorptions, pre- and post-implantation losses, and sex-ratio were not affected by the treatment. There were no differences for the mean weight of the gravid and empty uterus, ovaries, and placenta between the NHDC treatment groups and the controls. Examination of the fetuses for external, visceral, and skeletal changes did not reveal any fetotoxic, embryotoxic or teratogenic effects of NHDC. In conclusion, no adverse effects were observed at NHDC levels of up to 5% of the diet, the highest dose level tested, at which the rats consumed about 3.3g/kg body weight/day. The observed cecal enlargement is a well-known physiological, adaptive response to the ingestion of high doses of a low-digestible substance and is generally accepted to lack toxicological relevance. © 2004 Elsevier Inc. All rights reserved.

Gel network formation of pea legumin (8.4% on a protein basis, pH 7.6) was monitored via dynamic rheological measurements. Gelation was performed in the absence and presence of the thiol-blocking reagent N-ethylmaleimide, at different rates of heating and cooling. Overall, it was shown that pea legumin gel formation was not effected by changes in the heating rate, and the two differently heated samples were unaffected by the addition of 20 mM NEM, which indicated that disulfide bonds were not essential within the network strands of these legumin gels. However, slowly cooling the legumin samples caused disulfide bonds to become involved within the network; this was observed by a large increase in gel strength that was then substantially reduced when repeating the sample in the presence of NEM. These experiments were repeated with soybean glycinin in order to determine whether a common model for gel formation of legumin-like proteins could be built, based upon molecular reasoning. The two proteins were affected in the same way by changes in the conditions used, but when applying a procedure of reheating and recooling the gel networks responded differently. Pea legumin gel networks were susceptible to rearrangements that caused the gels to become stronger after reheating/recooling, yet glycinin gel networks were not. It was concluded that the same physical and chemical forces drove the processes of denaturation, aggregation, and network formation. Each process can therefore be readily targeted for modification based upon molecular reasoning. Pea legumin and soybean glycinin gel networks had structurally different building blocks, however. A model of gelation aimed at texture control therefore requires additional information.

In 2000, the thematic network ENTRANSFOOD was launched to assess four different topics that are all related to the testing or assessment of food containing or produced from genetically modified organisms (GMOs). Each of the topics was linked to a European Commission (EC)-funded large shared cost action (see http://www.entransfood.com). Since the exchange of genetic information through horizontal (lateral) gene transfer (HGT) might play a more important role, in quantity and quality, than hitherto imagined, a working group dealing with HGT in the context of food and feed safety was established. This working group was linked to the GMOBILITY project (GMOBILITY, 2003) and the results of the deliberations are laid down in this review paper. HGT is reviewed in relation to the potential risks of consuming food or feed derived from transgenic crops. First, the mechanisms for obtaining transgenic crops are described. Next, HGT mechanisms and its possible evolutionary role are described. The use of marker genes is presented in detail as a special case for genes that may pose a risk. Furthermore, the exposure to GMOs and in particular to genetically modified (GM) deoxyribonucleic acid (DNA) is discussed as part of the total risk assessment. The review finishes off with a number of conclusions related to GM food and feed safety. The aim of this paper is to provide a comprehensive overview to assist risk assessors as well as regulators and the general public in understanding the safety issues related to these mechanisms. © 2004 Elsevier Ltd. All rights reserved.

To obtain better insight into the robustness of in vitro percutaneous absorption methodology, the intra- and inter-laboratory variation in this type of study was investigated in 10 European laboratories. To this purpose, the in vitro absorption of three compounds through human skin (9 laboratories) and rat skin (1 laboratory) was determined. The test materials were benzoic acid, caffeine, and testosterone, representing a range of different physico-chemical properties. All laboratories performed their studies according to a detailed protocol in which all experimental details were described and each laboratory performed at least three independent experiments for each test chemical. All laboratories assigned the absorption of benzoic acid through human skin, the highest ranking of the three compounds (overall mean flux of 16.54±11.87μg/cm2/h). The absorption of caffeine and testosterone through human skin was similar, having overall mean maximum absorption rates of 2.24±1.43μg/cm2/h and 1.63±1.94μg/cm2/h, respectively. In 7 out of 9 laboratories, the maximum absorption rates of caffeine were ranked higher than testosterone. No differences were observed between the mean absorption through human skin and the one rat study for benzoic acid and testosterone. For caffeine the maximum absorption rate and the total penetration through rat skin were clearly higher than the mean value for human skin. When evaluating all data, it appeared that no consistent relation existed between the diffusion cell type and the absorption of the test compounds. Skin thickness only slightly influenced the absorption of benzoic acid and caffeine. In contrast, the maximum absorption rate of testosterone was clearly higher in the laboratories using thin, dermatomed skin membranes. Testosterone is the most lipophilic compound and showed also a higher presence in the skin membrane after 24h than the two other compounds. The results of this study indicate that the in vitro methodology for assessing skin absorption is relatively robust. A major effort was made to standardize the study performance, but, unlike in a formal validation study, not all variables were controlled. The variation observed may be largely attributed to human variability in dermal absorption and the skin source. For the most lipophilic compound, testosterone, skin thickness proved to be a critical variable. © 2004 Elsevier Inc. All rights reserved.

In a standard embryotoxicity/teratogenicity study, α-cyclodextrin (α-CD) was administered to groups of sixteen, artificially inseminated New Zealand White rabbits at dietary concentrations of 0, 5, 10, or 20%. An additional group received a diet containing 20% lactose. Treatment started on day 0 of gestation and ended on day 29 when the animals were killed. Except for the occurrence of transient diarrhoea in one rabbit of the 20% α-CD group for a few days, the treatment was well tolerated. A reduced food intake in the 20% α-CD group during the first week of treatment resulted in a reduced weight gain from day 0 to 12 of the study. However, the difference to the controls was not significant and at termination of the study body weights were similar in all groups. Even at the highest dose level, which corresponds to an intake of 5.9-7.5g/kg bw/day, no signs of maternal toxicity were observed. Maternal reproductive performance was not affected by the treatment. Uterine weight, placental weight, fetal weight, number of fetuses, sex ratio, number of implanation sites, resorptions, and corpora lutea did not differ among the groups. Visceral and skeletal examinations of the fetuses did not reveal any malformations, anomalies or variations that could be attributed to treatment. It was concluded that dietary α-CD is generally well tolerated by pregnant rabbits, has no adverse effect on maternal reproductive performance and is not embryotoxic, fetotoxic, or teratogenic at dietary concentrations of up to 20%, the highest dose level tested. © 2004 Elsevier Inc. All rights reserved.

Purpose of review This review summarizes selected articles on animal models of food allergy published in 2003. The research areas that are covered include mechanistic studies, the search for new therapies, as well as screening models for hazard identification of potential allergens. Recent findings Novel treatment options of both prevention and therapeutic strategies have been reported with promising results. The induction of de-sensitization to food proteins was achieved by exposure to a mixture of recombinant food allergens and T helper 1 (Th1)-skewing bacterial components. Furthermore, research in animal models has provided new insights into the role of protein structure, digestion, and gut permeability in sensitization and tolerance induction to food proteins. The Th2 hypothesis of food allergy was tested in mouse strains, linking genetic susceptibility to sensitization with differential Th1-Th2 responses. In this context, the role of the liver in development of food antigen-specific Th2 cells, and the importance of costimulatory molecules in Th2 skewing were demonstrated. Finally, rodent models to predict potential allergenicity of novel foods have been further developed using different routes of sensitization. Summary Currently, several animal models of food allergy are used, including mouse, rat, swine, and dog. Continuing research in these models may elucidate the immunological mechanisms that underlie the sensitization and challenge phase of food allergy and may result in improved therapeutic options. Furthermore, the development of animal models to predict relative allergenicity of novel foods remains an important topic.

Alpha-cyclodextrin glucosyltransferase (α-CGTase, EC 2.4.1.19) is an amylolytic enzyme used for the production of α-cyclodextrin (α-CD), a novel, soluble dietary fiber, from food-grade starch. The safety of an α-CGTase preparation obtained by batch fermentation from a recombinant strain of Escherichia coli K12 harboring the α-CGTase gene from Klebsiella oxytoca strain M5a1 was examined. In a 13-week subchronic toxicity study in rats, the administration by gavage of the α-CGTase preparation at levels of up to 20ml/kg bw/day, corresponding to a total organic solids dosage of 260mg/kg bw/day, did not cause any systemic toxic effect. Some signs of irritation were observed in the respiratory tract which occurred, however, in one sex only and/or were not dose-related. Accordingly, these changes were considered to be an unspecific consequence of the reflux and aspiration of the dosing solution. There was no evidence of a genotoxic activity in Ames tests and a chromosome aberration test in cultured human lymphocytes. It is concluded that the examined α-CGTase preparation is safe when used for the production of α-CD. © 2004 Elsevier Inc. All rights reserved. Chemicals / CAS: amylase, 9000-90-2, 9000-92-4, 9001-19-8; cyclomaltodextrin glucanotransferase, EC 2.4.1.19; Food Additives; Glucosyltransferases, EC 2.4.1.

Maillard products of beta-lactoglobulin (betaLg) and fructose oligosaccharide (FOS) were obtained in different degrees of modification depending on incubation time and pH. By use of a variety of biochemical and spectroscopic tools, it was demonstrated that the modification at limited degrees does not significantly affect the secondary, tertiary, and quaternary structure of betaLg. The consequence of the modification on the thermodynamics of the protein was studied using differential scanning calorimetry, circular dichroism, and by monitoring the fluorescence intensity of protein samples with different concentrations of guanidine-HCl. The modification leads to lowering of the denaturation temperature by 5 degrees C and a reduction of the free energy of stabilization of about 30%. Ellipsometry and drop tensiometry demonstrated that upon adsorption to air-water interfaces in equilibrium modified betaLg exerts a lower surface pressure than native betaLg (16 versus 22 mN/m). Moreover, the surface elastic modulus increased with increasing surface pressure but reached significantly smaller values in the case of FOS-betaLg. Compared to native betaLg, modification of the protein with oligofructose moieties results in higher surface loads and thicker surface layers. The consequences of these altered surface rheological properties are discussed in view of the functional behavior in technological applications.

Contains fulltext : 57316.pdf (Publisher’s version ) (Closed access) The monocyte-like human histiocytic lymphoma cell line U937 can be induced by phorbol 12-myristate 13-acetate (PMA) to undergo differentiation into a macrophage-like phenotype. We have used two-dimensional gel electrophoresis (2-DE), oligonucleotide microarrays and principal component analysis (PCA) to characterize the U937 cell line as a model system for the differentiation of monocytes into macrophages. A total of 226 differentially expressed proteins were found, of which 41 were selected by PCA for identification using matrix-assisted laser desorption/ionization tandem mass spectrometry. Based on the PCA results, three marker proteins were selected for confirmation of differential expression using Western blot and quantitative real time-PCR. The selected marker proteins were: gamma interferon inducible lysosomal thiol reductase, cathepsin D and adipocyte-fatty acid binding protein. All three proved to be good differentiation markers for macrophage maturation of U937 cells as well as peripheral blood-derived macrophages. The transcriptomics data revealed a large number of additional putative differentiation markers in U937 macrophages, many of which are known to be expressed in peripheral blood-derived macrophages. These include osteospontin, matrix metalloproteinase 9, and HC-gp39. Our results show that the characteristics of U937 macrophages resemble those of inflammatory (exudate) macrophages, exemplified by the down-regulation of 5' nucleotidase and the up-regulation of leucine aminopeptidase mRNAs. In conclusion, using the powerful combination of transcriptomics, 2-DE and PCA, our results show that U937 cells differentiated by PMA treatment are an excellent model system for monocyte derived macrophage generation from blood.