Impact of food processing and detoxification treatments on mycotoxin contamination.

Mycotoxins are fungal metabolites commonly occurring in food, which pose a health risk to the consumer. Maximum levels for major mycotoxins allowed in food have been established worldwide. Good agricultural practices, plant disease management, and adequate storage conditions limit mycotoxin levels in the food chain yet do not eliminate mycotoxins completely. Food processing can further reduce mycotoxin levels by physical removal and decontamination by chemical or enzymatic transformation of mycotoxins into less toxic products. Physical removal of mycotoxins is very efficient: manual sorting of grains, nuts, and fruits by farmers as well as automatic sorting by the industry significantly lowers the mean mycotoxin content. Further processing such as milling, steeping, and extrusion can also reduce mycotoxin content. Mycotoxins can be detoxified chemically by reacting with food components and technical aids; these reactions are facilitated by high temperature and alkaline or acidic conditions. Detoxification of mycotoxins can also be achieved enzymatically. Some enzymes able to transform mycotoxins naturally occur in food commodities or are produced during fermentation but more efficient detoxification can be achieved by deliberate introduction of purified enzymes. We recommend integrating evaluation of processing technologies for their impact on mycotoxins into risk management. Processing steps proven to mitigate mycotoxin contamination should be used whenever necessary. Development of detoxification technologies for high-risk commodities should be a priority for research. While physical techniques currently offer the most efficient post-harvest reduction of mycotoxin content in food, biotechnology possesses the largest potential for future developments.

Assessing the safety of cosmetic chemicals: Consideration of a flux decision tree to predict dermally delivered systemic dose for comparison with oral TTC (Threshold of Toxicological Concern).

Threshold of Toxicological Concern (TTC) aids assessment of human health risks from exposure to low levels of chemicals when toxicity data are limited. The objective here was to explore the potential refinement of exposure for applying the oral TTC to chemicals found in cosmetic products, for which there are limited dermal absorption data. A decision tree was constructed to estimate the dermally absorbed amount of chemical, based on typical skin exposure scenarios. Dermal absorption was calculated using an established predictive algorithm to derive the maximum skin flux adjusted to the actual 'dose' applied. The predicted systemic availability (assuming no local metabolism), can then be ranked against the oral TTC for the relevant structural class. The predictive approach has been evaluated by deriving the experimental/prediction ratio for systemic availability for 22 cosmetic chemical exposure scenarios. These emphasise that estimation of skin penetration may be challenging for penetration enhancing formulations, short application times with incomplete rinse-off, or significant metabolism. While there were a few exceptions, the experiment-to-prediction ratios mostly fell within a factor of 10 of the ideal value of 1. It can be concluded therefore, that the approach is fit-for-purpose when used as a screening and prioritisation tool.

Towards microbial fermentation metabolites as markers for health benefits of prebiotics.

Available evidence on the bioactive, nutritional and putative detrimental properties of gut microbial metabolites has been evaluated to support a more integrated view of how prebiotics might affect host health throughout life. The present literature inventory targeted evidence for the physiological and nutritional effects of metabolites, for example, SCFA, the potential toxicity of other metabolites and attempted to determine normal concentration ranges. Furthermore, the biological relevance of more holistic approaches like faecal water toxicity assays and metabolomics and the limitations of faecal measurements were addressed. Existing literature indicates that protein fermentation metabolites (phenol, p-cresol, indole, ammonia), typically considered as potentially harmful, occur at concentration ranges in the colon such that no toxic effects are expected either locally or following systemic absorption. The endproducts of saccharolytic fermentation, SCFA, may have effects on colonic health, host physiology, immunity, lipid and protein metabolism and appetite control. However, measuring SCFA concentrations in faeces is insufficient to assess the dynamic processes of their nutrikinetics. Existing literature on the usefulness of faecal water toxicity measures as indicators of cancer risk seems limited. In conclusion, at present there is insufficient evidence to use changes in faecal bacterial metabolite concentrations as markers of prebiotic effectiveness. Integration of results from metabolomics and metagenomics holds promise for understanding the health implications of prebiotic microbiome modulation but adequate tools for data integration and interpretation are currently lacking. Similarly, studies measuring metabolite fluxes in different body compartments to provide a more accurate picture of their nutrikinetics are needed.

A framework to determine the effectiveness of dietary exposure mitigation to chemical contaminants.

In order to ensure the food safety, risk managers may implement measures to reduce human exposure to contaminants via food consumption. The evaluation of the effect of a measure is often an overlooked step in risk analysis process. The aim of this study was to develop a systematic approach for determining the effectiveness of mitigation measures to reduce dietary exposure to chemical contaminants. Based on expert opinion, a general framework for evaluation of the effectiveness of measures to reduce human exposure to food contaminants was developed. The general outline was refined by application to three different cases: 1) methyl mercury in fish and fish products, 2) deoxynivalenol in cereal grains, and 3) furan in heated products. It was found that many uncertainties and natural variations exist, which make it difficult to assess the impact of the mitigation measure. Whenever possible, quantitative methods should be used to describe the current variation and uncertainty. Additional data should be collected to cover natural variability and reduce uncertainty. For the time being, it is always better for the risk manager to have access to all available information, including an assessment of uncertainty; however, the proposed methodology provides a conceptual framework for addressing these systematically.

Establishing the level of safety concern for chemicals in food without the need for toxicity testing.

There is demand for methodologies to establish levels of safety concern associated with dietary exposures to chemicals for which no toxicological data are available. In such situations, the application of in silico methods appears promising. To make safety statement requires quantitative predictions of toxicological reference points such as no observed adverse effect level and carcinogenic potency for DNA-reacting chemicals. A decision tree (DT) has been developed to aid integrating exposure information and predicted toxicological reference points obtained with quantitative structure activity relationship ((Q)SAR) software and read across techniques. The predicted toxicological values are compared with exposure to obtain margins of exposure (MoE). The size of the MoE defines the level of safety concern and should account for a number of uncertainties such as the classical interspecies and inter-individual variability as well as others determined on a case by case basis. An analysis of the uncertainties of in silico approaches together with results from case studies suggest that establishing safety concern based on application of the DT is unlikely to be significantly more uncertain than based on experimental data. The DT makes a full use of all data available, ensuring an adequate degree of conservatism. It can be used when fast decision making is required.

Markers for nutrition studies: review of criteria for the evaluation of markers.

INTRODUCTION: Markers are important tools to assess the nutrition status and effects of nutrition interventions. There is currently insufficient consensus in nutrition sciences on how to evaluate markers, despite the need for properly evaluating them. OBJECTIVES: To identify the criteria for the evaluation of markers related to nutrition, health and disease and to propose generic criteria for evaluation. METHOD: The report on "Evaluation of Biomarker and Surrogate Endpoints in Chronic Disease" from the Institute of Medicine was the starting point for the literature search. Additionally, specific search strategies were developed for Pubmed. RESULTS: In nutrition, no set of criteria or systematic approach to evaluate markers is currently available. There is a reliance on the medical area where statistical methods have been developed to quantify the evaluation of markers. Even here, a systematic approach is lacking-markers are still evaluated on a case-by-case basis. The review of publications from the literature search resulted in a database with definitions, criteria for validity and the rationale behind the criteria. It was recognized that, in nutrition, a number of methodological aspects differ from medical research. CONCLUSIONS: The following criteria were identified as essential elements in the evaluation of markers: (1) the marker has a causal biological link with the endpoint, (2) there is a significant association between marker and endpoint in the target population, (3) marker changes consistently with the endpoint, e.g., in response to an intervention, and (4) change in the marker explains a substantial proportion of the change in the endpoint in response to the intervention.

Critical appraisal of the assessment of benefits and risks for foods, 'BRAFO Consensus Working Group'.

BRAFO, Benefit-Risk Analysis for Foods, was a European Commission project funded within Framework Six as a Specific Support Action and coordinated by ILSI Europe. BRAFO developed a tiered methodology for assessing the benefits and risks of foods and food components, utilising a quantitative, common scale for health assessment in higher tiers. This manuscript reports on the implications of the experience gained during the development of the project for the further improvement of benefit-risk assessment methodology. It was concluded that the methodology proposed is applicable to a range of situations and that it does help in optimising resource utilisation through early identification of those benefit-risk questions where benefit clearly outweighs risk or vice versa. However, higher tier assessments are complex and demanding of time and resources, emphasising the need for prioritisation. Areas identified as requiring further development to improve the utility of benefit-risk assessment include health weights for different populations and endpoints where they do not currently exist, extrapolation of effects from studies in animals to humans, use of in vitro data in benefit-risk assessments, and biomarkers of early effect and how these would be used in a quantitative assessment.

Application of the BRAFO tiered approach for benefit-risk assessment to case studies on heat processing contaminants.

The aim of the European Funded Project BRAFO (benefit-risk analysis of foods) project was to develop a framework that allows quantitative comparison of human health risks and benefits of foods based on a common scale of measurement. This publication describes the application of the BRAFO methodology to three different case studies: the formation of acrylamide in potato and cereal based products, the formation of benzo(a)pyrene through smoking and grilling of meat and fish and the heat-treatment of milk. Reference, alternative scenario and target population represented the basic structure to test the tiers of the framework. Various intervention methods intended to reduce acrylamide in potato and cereal products were evaluated against the historical production methods. In conclusion the benefits of the acrylamide-reducing measures were considered prevailing. For benzo(a)pyrene, three illustrated alternative scenarios were evaluated against the most common smoking practice. The alternative scenarios were assessed as delivering benefits, introducing only minimal potential risks. Similar considerations were made for heat treatment of milk where the comparison of the microbiological effects of heat treatment, physico-chemical changes of milk constituents with positive and negative health effects was assessed. In general, based on data available, benefits of the heat treatment were outweighing any risks.

Application of the BRAFO tiered approach for benefit-risk assessment to case studies on dietary interventions.

The respective examples, described in this paper, illustrate how the BRAFO-tiered approach, on benefit-risk assessment, can be tested on a wide range of case studies. Various results were provided, ranging from a quick stop as the result of non-genuine benefit-risk questions to continuation through the tiers into deterministic/probabilistic calculations. The paper illustrates the assessment of benefits and risks associated with dietary interventions. The BRAFO tiered approach is tested with five case studies. In each instance, the benefit-risk approach is tested on the basis of existing evaluations for the individual effects done by others; no new risk or benefit evaluations were made. The following case studies were thoroughly analysed: an example of food fortification, folic acid fortification of flour, macronutrient replacement/food substitution; the isocaloric replacement of saturated fatty acids with carbohydrates; the replacement of saturated fatty acids with monounsaturated fatty acids; the replacement of sugar-sweetened beverages containing mono- and disaccharides with low calorie sweeteners and an example of addition of specific ingredients to food: chlorination of drinking water.

Application of the BRAFO-tiered approach for benefit-risk assessment to case studies on natural foods.

There is evidence that consumption of fish, especially oily fish, has substantial beneficial effects on health. In particular an inverse relationship of oily fish intake to coronary heart disease incidence has been established. These beneficial effects are ascribed to fish oil components including long chain ω-3 polyunsaturated fatty acids. On the other hand it should be noted that oily fish also contains hazardous substances such as dioxins, PCBs and methylmercury. Soy consumption has been associated with potential beneficial and adverse effects. The claimed benefits include reduced risk of cardiovascular disease; osteoporosis, breast and prostate cancer whereas potential adverse effects include impaired thyroid function, disruption of sex hormone levels, changes in reproductive function and increased breast cancer risk The two cases of natural foods highlight the need to consider both risks and benefits in order to establish the net health impact associated to the consumption of specific food products. Within the Sixth Framework programme of the European Commission, the BRAFO project was funded to develop a framework that allows for the quantitative comparison of human health risks and benefits in relation to foods and food compounds. This paper describes the application of the developed framework to two natural foods, farmed salmon and soy protein. We conclude that the BRAFO methodology is highly applicable to natural foods. It will help the benefit-risk managers in selecting the appropriate dietary recommendations for the population.

BRAFO tiered approach for Benefit-Risk Assessment of Foods.

BRAFO stands for Benefit-Risk Analysis for Foods. This European Commission funded project aims at developing a framework that allows quantitative comparison of human health risks and benefits of foods and food compounds based on a common scale of measurement. A methodology group brought together methodologies from several disciplines relevant to the evaluation of risks and benefits in food. This group reviewed and assembled the methodologies available. They produced this guidance document that describes a tiered ('stepwise') approach for performing a risk and benefit assessment of foods. This process starts with pre-assessment and problem formulation to set the scope of the assessment. This includes defining two scenarios, the reference and an alternative that are compared in the assessment. The approach consists of four tiers. In many cases, a lower tier assessment in which risks and benefits are qualitatively evaluated may be sufficient to show a clear difference between the health impacts of the two scenarios. In other cases, increasingly sophisticated methods to integrate risks and benefits quantitatively are used at higher tiers to assess the net health impact.

Results of the monitoring program of pesticide residues in organic food of plant origin in Lombardy (Italy).

Organic agriculture, with its restrictions on the use of synthetic chemical inputs, seems to offer a low-residue alternative to conventional methods. In Europe, the Council Regulation n. 2092/91/EEC regulates the production and trade of organic products and foodstuffs; national and regional legislation in Italy gives specific guidance on the surveillance of organic agriculture. However, monitoring of specific chemical residues in organic foodstuffs is part of the regular controls on food, aiming to safeguard consumer's health. Monitoring programs are coordinated at the national level by the Ministry of Health and at local level by Regional authorities. In Lombardy, in accordance with the provisions of the General Directorate of Health of the Region and under the supervision of the 15 Local Health Units, a monitoring program of pesticide residues in food of plant origin is undertaken every year. The International Centre for Pesticides and Health Risk Prevention (ICPS), on behalf of the General Directorate of Health of the Region of Lombardy, has been collecting and elaborating the data resulting from the analysis of food samples, carried out by the local laboratories. During the period 2002-2005, a total of 3508 samples food of plant origin were analyzed for pesticide residues, among which were 266 samples of organic farming products. Commodities were classified into groups (citrus fruits, legumes, vegetables, potatoes, processed products, cereals, and fruit other than citrus) and the outcomes of the analyses were reported by year, origin of the sample and presence/absence of pesticide residues. Results showed that the vast majority of organic farming products were in conformity with the relevant legislation and did not contain detectable pesticide residues. A limited amount of samples had residues at concentration below the Maximum Residue Limit (MRL). Only in one sample the residue level was above the MRL, however it did not pose a concern for public health, as demonstrated by the outcomes of dietary risk assessment. Organic fruits and vegetables can be expected to contain fewer agrochemical residues than conventionally grown alternatives. There is a widespread belief that organic agriculture products are safer and healthier than conventional foods. It is difficult to come to conclusions, but what should be made clear to the consumer is that "organic" does not automatically equal "safe". In the absence of adequate comparative data, additional studies in this area of research are required.

Ochratoxin a contents in wine: comparison of organically and conventionally produced products.

Ochratoxin A (OTA) content was determined in 44 organically and conventionally produced wines originating from different geographical regions. Wine samples were extracted using a series of C18 and mixed-bed solid-phase cartridges and analyzed by HPLC with fluorescence detection. The identity of the mycotoxin was confirmed using liquid chromatography-tandem mass spectrometry. Recoveries were in excess of 90%, intraday precisions were better than 6%, and the interday variation was 15%. Limit of detection was 0.05 microg/L (HPLC). All sampled wines contained OTA below the level permitted by the European Union of 2 microg/L, ranging from not detectable (nd) to 0.75 microg/L for red wines (n = 26), from nd to 0.092 microg/L for rosé wines (n = 2), and from nd to 0.22 microg/L for white wines (n = 16). The concentration of OTA in organically produced wines (nd to 0.72 microg/L, median 0.092 microg/L, n = 19) was not significantly different from that in conventional products (nd to 0.75 microg/L, median 0.066 microg/L, n = 25) as assessed by a Mann-Whitney statistical test (p = 0.54).