Risk Assessment Paradigm for Glutamate.

BACKGROUND: Re-evaluation of the use of glutamic acid and glutamate salts (referred to as glutamate hereafter) by the European Food Safety Authority (EFSA) proposed a group acceptable daily intake (ADI) of 30 mg/kg body weight (bw)/day. SUMMARY: This ADI is below the normal dietary intake, while even intake of free glutamate by breast-fed babies can be above this ADI. In addition, the pre-natal developmental toxicity study selected by EFSA, has never been used by regulatory authorities worldwide for the safety assessment of glutamate despite it being available for nearly 40 years. Also, the EFSA ignored that toxicokinetic data provide support for eliminating the use of an uncertainty factor for interspecies differences in kinetics. Key Messages: A 3-generation reproductive toxicity study in mice that includes extensive brain histopathology, provides a better point of departure showing no effects up to the highest dose tested of 6,000 mg/kg bw/day. Furthermore, kinetic data support use of a compound-specific uncertainty factor of 25 instead of 100. Thus, an ADI of at least 240 mg/kg bw/day would be indicated. In fact, there is no compelling evidence to indicate that the previous ADI of "not specified" warrants any change.

Critical review of the safety assessment of nano-structured silica additives in food.

The development of nano-materials is viewed as one of the most important technological advances of the 21st century and new applications of nano-sized particles in the production, processing, packaging or storage of food are expected to emerge soon. This trend of growing commercialization of engineered nano-particles as part of modern diet will substantially increase oral exposure. Contrary to the proven benefits of nano-materials, however, possible adverse health effects have generally received less attention. This problem is very well illustrated by nano-structured synthetic amorphous silica (SAS), which is a common food additive since several decades although the relevant risk assessment has never been satisfactorily completed. A no observed adverse effect level of 2500 mg SAS particles/kg body weight per day was derived from the only available long-term administration study in rodents. However, extrapolation to a safe daily intake for humans is problematic due to limitations of this chronic animal study and knowledge gaps as to possible local intestinal effects of SAS particles, primarily on the gut-associated lymphoid system. This uncertainty is aggravated by digestion experiments indicating that dietary SAS particles preserve their nano-sized structure when reaching the intestinal lumen. An important aspect is whether food-borne particles like SAS alter the function of dendritic cells that, embedded in the intestinal mucosa, act as first-line sentinels of foreign materials. We conclude that nano-particles do not represent a completely new threat and that most potential risks can be assessed following procedures established for conventional chemical hazards. However, specific properties of food-borne nano-particles should be further examined and, for that purpose, in vitro tests with decision-making cells of the immune system are needed to complement existing in vivo studies.

Quantitative risk assessment on the dietary exposure of Finnish children and adults to nitrite.

Nitrite intake from the consumption of cured meat and tap water was estimated for Finnish children of 1, 3 and 6 years as well as Finnish adults of 25-74 years. Nitrite content in the foods was measured by capillary electrophoresis, and was then used together with individual food consumption data from the FINDIET 2007 and DIPP studies in a stochastic exposure assessment by a Monte Carlo Risk Assessment (MCRA) program. Nitrite intake from additive sources and tap water was assessed, and more than every 10th child between the ages 3 and 6 years was estimated to have a nitrite intake exceeding the acceptable daily intake (ADI) of nitrite. The high exposure levels were caused by frequent consumption of large portions of sausages, up to 350 g day(-1) or 750 g in 3 days, among the children. Median nitrite intake from cured meat was 0.016, 0.040, 0.033 and 0.005 mg kg(-1) body weight day(-1) for children of 1, 3 and 6 years and adults, respectively. Bayesian estimation was employed to determine safe consumption levels of sausages and cold cuts for children, and these results gave rise to new national food consumption advice.

Estimation of the dietary intake of 13 priority additives in France, Italy, the UK and Ireland as part of the FACET project.

The aim of this study was to assess the dietary exposure of 13 priority additives in four European countries (France, Italy, the UK and Ireland) using the Flavourings, Additives and Contact Materials Exposure Task (FACET) software. The studied additives were benzoates (E210-213), nitrites (E249-250) and sulphites (E220-228), butylated hydroxytoluene (E321), polysorbates (E432-436), sucroses esters and sucroglycerides (E473-474), polyglycerol esters of fatty acids (E475), stearoyl-lactylates (E481-482), sorbitan esters (E493-494 and E491-495), phosphates (E338-343/E450-452), aspartame (E951) and acesulfame (E950). A conservative approach (based on individual consumption data combined with maximum permitted levels (Tier 2)) was compared with more refined estimates (using a fitted distribution of concentrations based on data provided by the food industry (Tier 3)). These calculations demonstrated that the estimated intake is below the acceptable daily intake (ADI) for nine of the studied additives. However, there was a potential theoretical exceedance of the ADI observed for four additives at Tier 3 for high consumers (97.5th percentile) among children: E220-228 in the UK and Ireland, E432-436 and E481-482 in Ireland, Italy and the UK, and E493-494 in all countries. The mean intake of E493-494 could potentially exceed the ADI for one age group of children (aged 1-4 years) in the UK. For adults, high consumers only in all countries had a potential intake higher than the ADI for E493-494 at Tier 3 (an additive mainly found in bakery wares). All other additives examined had an intake below the ADI. Further refined exposure assessments may be warranted to provide a more in-depth investigation for those additives that exceeded the ADIs in this paper. This refinement may be undertaken by the introduction of additive occurrence data, which take into account the actual presence of these additives in the different food groups.

[Assessment of the effect of selected mixture of food additives on the protein metabolism--model studies]. / Ocena wplywu mieszaniny wybranych dodatków do zywnosci na wskazniki metabolizmu bialkowego--badania modelowe.

BACKGROUND: Contemporarily, food production without food additives is very rare. Increasingly often, however, scientific works report on adverse effects of specified, single food additives on the body. Data is, in turn, lacking on the synergistic effect of a mixture of different food additives on body functions and its main metabolic pathways. OBJECTIVE: The objective of this study, an animal model, was to evaluate if and in what way the compound of chosen and most frequently used and consumed food additives, along with the change of diet composition to processed, purified, influence the selected markers of protein metabolism. MATERIAL AND METHODS: The animals were divided into four groups, which were fed with compound of feed pellets: group I and II with basic compound, group III and IV with modified compound in which part of the full grain was replaced by isocalorie wheat flour type 500 and saccharose. Animals from groups I and III received tap water, which was standing for some time, to drink. Animals from groups II and IV received solution of chosen additives to food and next they were given water to drink. The amount of given food additives was evaluated by taking into consideration their consumption by people recalculated to 1 kg of their body mass. The experiment spanned for 7 weeks. RESULTS: It was ascertained that the applied additives caused significant changes in total protein concentration and its fractions: albumin, alpha1-globulin, alpha2-globulin, beta-globulin and gamma-globulin in the blood serum of the animals under research, which can indicate and contribute to disclosure of creation of undesirable food reaction, especially when recommended levels of consumption of those additives are being exceeded. The organism response to the applied additives and accompanying it change of diet was essentially connected to sex of the animals. Undesirable character of changes taking place under the influence of applied additives, was observed both in animals fed with basic feed and modified feed with various intensity according to the parameter under research. CONCLUSIONS: The analysis of the results achieved enabled concluding that the applied mixture of food additives caused significant changes in the concentration of total protein and its fractions: albumins, alphal-, alpha2-, beta- and gamma-globulins in blood serum of the investigated animals. These changes may indicate but also may contribute to the development or manifestation of undesirable nutritional responses, especially when recommended dietary allowances are exceeded. The body's response to the applied additives and concomitant modification of diet composition was significantly correlated with sex of the animals. The unfavorable character of changes following the administration of additives was observed in both the animals on the basal diet and these fed the modified feed mixture, yet with a different intensity that was found to depend not on the feeding group but on the parameter examined.

Assessment of dietary exposure to annatto (E160b), nitrites (E249-250), sulphites (E220-228) and tartaric acid (E334) in the French population: the second French total diet study.

The results of the assessment of the dietary exposure to annatto, nitrites, tartaric acid and sulphites within the framework of the second French total diet study (TDS) are reported. These 4 additives were selected from the Bemrah et al. study [Bemrah N, Leblanc JC, Volatier JL. 2008. Assessment of dietary exposure in the French population to 13 selected food colours, preservatives, antioxidants, stabilizers, emulsifiers and sweeteners. Food Addit Contam B. 1(1):2-14] on 13 food additives which identified a possible health risk for annatto, sulphites and nitrites and a lack of data for tartaric acid. Among the composite samples selected for the whole TDS, 524 were analysed for additives (a sample was analysed for a given additive when it was identified as a major contributor for this additive only): 130 for tartaric acid, 135 for nitrites, 59 for annatto and 200 for sulphites. Estimated concentrations (minimum lower bound to maximum upper bound) vary nationally from 0 to 9 mg/kg for annatto, 0 to 420 mg/kg for tartaric acid, 0 to 108 mg/kg for sulphites and 0 to 3.4 mg/kg for nitrites. Based on the analytical results, the dietary exposure was calculated for adults and children, separately, using lower bound and upper bound assumptions. The European ADIs for these 4 additives were not exceeded except for the dietary exposure for sulphites among 2.9% of the adult population, where the major contributors were alcoholic drinks and especially wine under both hypotheses (lower and upper bound).

Uncertainty analysis of the use of a retailer fidelity card scheme in the assessment of food additive intake.

The feasibility of using a retailer fidelity card scheme to estimate food additive intake was investigated in an earlier study. Fidelity card survey information was combined with information provided by the retailer on levels of the food colour Sunset Yellow (E110) in the foods to estimate a daily exposure to the additive in the Swiss population. As with any dietary exposure method the fidelity card scheme is subject to uncertainties and in this paper the impact of uncertainties associated with input variables including the amounts of food purchased, the levels of E110 in food, the proportion of food purchased at the retailer, the rate of fidelity card usage, the proportion of foods consumed outside of the home and bodyweights and with systematic uncertainties was assessed using a qualitative, deterministic and probabilistic approach. An analysis of the sensitivity of the results to each of the probabilistic inputs was also undertaken. The analysis identified the key factors responsible for uncertainty within the model and demonstrated how the application of some simple probabilistic approaches can be used quantitatively to assess uncertainty.

Use of retailer fidelity card schemes in the assessment of food additive intake: Sunset Yellow a case study.

The feasibility of using a retailer fidelity card scheme to estimate food additive intake was investigated using the Swiss retailer MIGROS's Cumulus Card and the example of the food colour Sunset Yellow (E 110). Information held within the card scheme was used to identify a sample of households purchasing foods containing Sunset Yellow over a 15 day period. A sample of 1204 households was selected for interview, of which 830 households were retained in the study following interview. Interviews were conducted to establish household structure, patterns of consumption by different individuals within the household, and the proportion of foods containing Sunset Yellow habitually purchased at the retailer and/or consumed outside the home. Information provided by the retailer on levels of Sunset Yellow in the foods was combined with the information obtained at interview to calculate the per-capita intake of Sunset Yellow by members of participating households. More than 99% of consumers (n = 1902) of foods containing Sunset Yellow were estimated to consume less than 1 mg Sunset Yellow kg(-1) body weight day(-1). The method proved to be a simple and resource-efficient approach to estimate food additive intake on the basis of actual consumer behaviour and thus reports results more closely related to the actual consumption of foods by individuals.

Simulação técnico-econômica da inclusão de ractopamina em dietas de suínos em terminação / Technical-economic simulation of ractopamine inclusion in diets for finishing pigs

Foi realizada simulação técnico-econômica a partir de resultados de publicações para avaliar a inclusão de ractopamina em dietas de suínos em terminação. Foram utilizados 18 artigos, que avaliaram níveis de 0, 5, 10 e/ou 20ppm de ractopamina na dieta, totalizando 2.991 animais. A partir dos resultados técnicos das publicações avaliadas, foram geradas equações que foram utilizadas na simulação do desempenho técnico-econômico. Verificou-se que os custos independem do sistema de receitas do produtor e oscilam de 3 a 6ppm de ractopamina adicionada à dieta. O lucro máximo foi obtido com os níveis de 10 e 12ppm de ractopamina, respectivamente, para os sistemas de receita por peso vivo e por bonificação. Os resultados evidenciam melhor desempenho econômico da utilização de ractopamina, na dieta dos suínos em terminação, pelo sistema de receita por bonificação. As análises de sensibilidade para a variação na receita dos produtores apresentam valores ótimos de 9 a 12ppm de ractopamina, com oscilação de até R$ 49,00/cabeça entre os cenários testados.

A technical-economic simulation was performed based on results from publications for assessing the inclusion of ractopamine in the diet of finishing pigs. Eighteen articles were used, which assessed levels of 0, 5, 10, and/or 20ppm of ractopamine in the diet, totalizing 2,991 animals. Based on the results obtained in these technical publications, equations were used for the simulation of the technical-economic performance. From this study, it was established that the costs are independent of the system of revenue of the producer and range from 3 to 6ppm of ractopamine added in the diet. The maximum profit was obtained with the levels of 10 and 12ppm of ractopamine, respectively, for the systems of revenue per body weight and per bonus. The results show a better economic performance with the use of ractopamine in the diet of finishing pigs, by the system of revenue per bonus. Analyses of sensitivity of changes in the revenue of producers presented optimal values of 9 to 12ppm of ractopamine, with a range of up to R$ 49.00 per capita between the tested scenarios.

Safety assessment of coriander (Coriandrum sativum L.) essential oil as a food ingredient.

Coriander essential oil is used as a flavor ingredient, but it also has a long history as a traditional medicine. It is obtained by steam distillation of the dried fully ripe fruits (seeds) of Coriandrum sativum L. The oil is a colorless or pale yellow liquid with a characteristic odor and mild, sweet, warm and aromatic flavor; linalool is the major constituent (approximately 70%). Based on the results of a 28 day oral gavage study in rats, a NOEL for coriander oil is approximately 160 mg/kg/day. In a developmental toxicity study, the maternal NOAEL of coriander oil was 250 mg/kg/day and the developmental NOAEL was 500 mg/kg/day. Coriander oil is not clastogenic, but results of mutagenicity studies for the spice and some extracts are mixed; linalool is non-mutagenic. Coriander oil has broad-spectrum, antimicrobial activity. Coriander oil is irritating to rabbits, but not humans; it is not a sensitizer, although the whole spice may be. Based on the history of consumption of coriander oil without reported adverse effects, lack of its toxicity in limited studies and lack of toxicity of its major constituent, linalool, the use of coriander oil as an added food ingredient is considered safe at present levels of use.

Safety assessment of diacylglycerol oil as an edible oil: a review of the published literature.

Diacylglycerol oil is an edible oil with taste and usability characteristics comparable to naturally occurring oils. The objective of this review is to examine literature on diacylglycerol oil to assess its safety-in-use. Feeding rats with unheated or heated diacylglycerol oil at levels up to 5.5% in diet for 90 days did not cause any toxic effects. In chronic studies, dietary administration of diacylglycerol oil (up to 5.3%) to rats for 2 years or at 9.5% to Beagle dogs for 1 year had no adverse effects. Genotoxicity studies of unheated and heated diacylglycerol oil did not reveal any genotoxic effects. Carcinogenicity studies in rodents demonstrate that diacylglycerol oil is non-carcinogenic. In a two-generation reproductive and developmental toxicity study, gavage administration of diacylglycerol oil at dose levels of 5.0 ml/kg body weight/day did not reveal any adverse effects. In several human clinical investigations, administration of diacylglycerol oil at levels up to 0.5 g/kg body weight/day for up to 1 year did not cause adverse effects. Collectively, there is sufficient qualitative and quantitative scientific evidence available from animal and human studies suggesting that intake of diacylglycerol oil is safe for human consumption when used in a manner similar to other edible oils.

Assessment of dietary exposure in the French population to 13 selected food colours, preservatives, antioxidants, stabilizers, emulsifiers and sweeteners.

The results of French intake estimates for 13 food additives prioritized by the methods proposed in the 2001 Report from the European Commission on Dietary Food Additive Intake in the European Union are reported. These 13 additives were selected using the first and second tiers of the three-tier approach. The first tier was based on theoretical food consumption data and the maximum permitted level of additives. The second tier used real individual food consumption data and the maximum permitted level of additives for the substances which exceeded the acceptable daily intakes (ADI) in the first tier. In the third tier reported in this study, intake estimates were calculated for the 13 additives (colours, preservatives, antioxidants, stabilizers, emulsifiers and sweeteners) according to two modelling assumptions corresponding to two different food habit scenarios (assumption 1: consumers consume foods that may or may not contain food additives, and assumption 2: consumers always consume foods that contain additives) when possible. In this approach, real individual food consumption data and the occurrence/use-level of food additives reported by the food industry were used. Overall, the results of the intake estimates are reassuring for the majority of additives studied since the risk of exceeding the ADI was low, except for nitrites, sulfites and annatto, whose ADIs were exceeded by either children or adult consumers or by both populations under one and/or two modelling assumptions. Under the first assumption, the ADI is exceeded for high consumers among adults for nitrites and sulfites (155 and 118.4%, respectively) and among children for nitrites (275%). Under the second assumption, the average nitrites dietary exposure in children exceeds the ADI (146.7%). For high consumers, adults exceed the nitrite and sulfite ADIs (223 and 156.4%, respectively) and children exceed the nitrite, annatto and sulfite ADIs (416.7, 124.6 and 130.6%, respectively).

Intake assessment for benzoates in different subgroups of the Flemish population.

An exposure assessment was performed to estimate the daily intake of benzoates for the Flemish population. Three age groups were considered: preschool children (n=697; age 2-6; 3-day estimated dietary record), adolescents (n=341; age 14-18; 7-day estimated dietary record) and women (n=641; age 18-40; 2-day estimated dietary record). In a first step in the risk evaluation process as proposed by the European Union, the individual food consumption data were multiplied with the maximum permitted use levels for benzoates per food group. The median (interquartile range) estimated daily intake is, respectively, 2.0 (1.0-3.2) mg/kg bw, 1.7 (1.1-2.7) mg/kg bw and 1.92 (1.3-3.0) mg/kg bw for preschool children, adolescents and adult women. In all age groups, the greatest potential contributor to the total estimated benzoate intake was the group of non-alcoholic flavoured drinks. At respectively the 92nd percentile (children), the 97th percentile (adolescents) and the 94th percentile (women), the accepted daily intake (ADI) of 5mg/kg bw/day is exceeded slightly. However, this approach, in which the maximum permitted use levels are used is known to overestimate the intake, since not all food items in which benzoates are allowed, contain (the maximum permitted use level of) benzoates. A more precise estimation, using actual levels, is recommended.

Método de Taguchi para optimizar calidad de postres funcionales destinados al adulto mayor y estudio de prefactibilidad técnico - económica / Taguchi method to optimize the quality of functional desserts for elderly and technical prefeasibility study

Este trabajo tuvo como objetivo principal formular, desarrollar, caracterizar y evaluar alimentos funcionales para el adulto mayor, específicamente un postre (mousse de naranja), en el que se consideraron las recomendaciones nutricionales de organismos nacionales e internacionales, así como también las limitaciones de su edad. Se desarrolló un postre, mousse sabor naranja, al que se le adicionaron los siguientes elementos funcionales: fructoligosacáridos, vitaminas y minerales, y se reemplazó en su totalidad la sacarosa por un edulcorante no metabolizable ni calórico que que fue la sucralosa. La cantidad de micronutrientes incorporados fue de un 30 por ciento de la IDR (Ingesta Diaria Recomendada) para el caso de las vitaminas y entre un 10 y 20 por ciento de la IDR para los minerales. Se tomaron estos valores considerando que existen otros alimentos más, a parte de los postres desarrollados, que también aportan nutrientes a la dieta. En el caso de los fructoligosacáridos, como no existe todavía un límite reglamentado de uso, y va más bien por sus efectos digestivos, se usaron los niveles recomendados por el fabricante para productos similares. El mousse fue optimizado usando la metodología estadística de Taguchi, donde el número de variables que intervinieron en este proceso fue de siete, las que en una etapa posterior quedaron en cuatro. Los valores de evaluación, optimizados por esta metodología estadística, se obtuvieron después de aplicar el test de Karlsruhe, con una tabla de valoración especialmente diseñada para el producto, utilizando un panel de jueces entrenados para tal efecto. Finalmente, se obtuvo una única formulación como la mejor de todas, que posteriormente fue sometida a controles físicos, químicos, microbiológicos y sensoriales, éstos últimos de aceptabilidad del producto por parte de la población objetivo que fueron adultos mayores. Respecto a la evaluación de aceptabilidad por parte de adultos mayores, se les dio a cada persona la formulación optimizada más una segunda formulación cuya única diferencia con la primera fue la concentración del edulcorante. De esta forma, además de señalar el grado de aceptación indicaron su preferencia...

Assessment of the influence of energy under-reporting on intake estimates of four food additives.

Under-reporting has been identified as an important source of uncertainty in food chemical exposure assessments. The objective of the present study was to assess the influence of under-reporting on food additive intake estimates. Dietary survey data were derived from the North-South Ireland Food Consumption Survey (2001). Data from the Republic of Ireland (n = 958) were used. Energy under-reporters were identified using a ratio of energy intakes to estimated basal metabolic rate. First, food categories (n = 26) included in an assessment of exposure of four food additives were created and patterns of food intakes (i.e. likelihood of consumption, frequency of consumption and reported portion size) between acceptable and under-reporters compared. Second, for each food additive, deterministic intake estimates for the total sample (i.e. acceptable and under-reporters), under-reporters and acceptable reporters were calculated and compared. Differential reporting of the majority of food categories between acceptable and under-reporters was recorded. Under-reporters were less likely to record the consumption of a given food and more likely to under-report the frequency of consumption and portion size compared with acceptable reporters. Food additive intake estimates amongst acceptable reporters were higher than corresponding intake estimates amongst the total sample of reporters and amongst under-reporters. With the exception of one food additive (erythrosine), ratios of upper percentile additive intakes amongst acceptable reporters to corresponding intake estimates amongst the total sample of reporters did not exceed 1.06 when results were expressed as total population or consumer-only intakes. Findings illustrated that energy under-reporting does not materially influence estimates of food additive exposure based on the four food additives studied. However, a number of situations were identified where the under-reporting might exert a more significant impact on resulting exposure estimates.

Human variability in the renal elimination of foreign compounds and renal excretion-related uncertainty factors for risk assessment.

Renal excretion is an important route of elimination for xenobiotics and three processes determine the renal clearance of a compound [glomerular filtration (about 120 ml/min), active renal tubular secretion (>120 ml/min) and passive reabsorption (<120 ml/min)]. Human variability in kinetics has been quantified using a database of 15 compounds excreted extensively by the kidney (>60% of a dose) to develop renal-excretion related uncertainty factors for the risk assessment of environmental contaminants handled via this route. Data were analysed from published pharmacokinetic studies (after oral and intravenous dosing) in healthy adults and other subgroups using parameters relating primarily to chronic exposure [renal and total clearances, area under the plasma concentration time-curve (AUC)] and acute exposure (Cmax). Interindividual variability in kinetics was low for both routes of exposure, with coefficients of variation of 21% (oral) and 24% (intravenous) that were largely independent of the renal processes involved. Renal-excretion related uncertainty factors were below the default kinetic uncertainty factor of 3.16 for most subgroups analysed with the exception of the elderly (oral data) and neonates (intravenous data) for whom renal excretion-related factors of 4.2 and 3.2 would be required to cover up to 99% of these subgroups respectively.

Introduction to the Monte Carlo project and the approach to the validation of probabilistic models of dietary exposure to selected food chemicals.

The Monte Carlo project was established to allow an international collaborative effort to define conceptual models for food chemical and nutrient exposure, to define and validate the software code to govern these models, to provide new or reconstructed databases for validation studies, and to use the new software code to complete validation modelling. Models were considered valid when they provided exposure estimates (e(a)) that could be shown not to underestimate the true exposure (e(b)), but at the same time are more realistic than the currently used conservative estimates (e(c)). Thus, validation required e(b)

Design, development and validation of software for modelling dietary exposure to food chemicals and nutrients.

The Monte Carlo computational system for stochastic modelling of dietary exposure to food chemicals and nutrients is presented. This system was developed through a European Commission-funded research project. It is accessible as a Web-based application service. The system allows and supports very significant complexity in the data sets used as the model input, but provides a simple, general purpose, linear kernel for model evaluation. Specific features of the system include the ability to enter (arbitrarily) complex mathematical or probabilistic expressions at each and every input data field, automatic bootstrapping on subjects and on subject food intake diaries, and custom kernels to apply brand information such as market share and loyalty to the calculation of food and chemical intake.