Harmonized approach to estimate the burden of disease of dietary exposure to four chemical contaminants - A French study.

Exposure to chemical contaminants found in foods has been associated with various adverse health effects. Burden of disease studies are increasingly used to estimate the public health impact of such exposures. The aims of this study were to estimate the burden of disease due to dietary exposure to four chemicals in France in 2019 (lead (Pb), cadmium (Cd), methylmercury (MeHg), and inorganic arsenic (i-As)), and to develop harmonized methods that can be applied for other chemicals and countries. We used national food consumption data from the third French national food consumption survey, chemical food monitoring data from the Second French Total Diet Study (TDS), dose-response data and disability weights from scientific literature, and disease incidence and demographics from national statistics. We adopted a risk assessment approach to estimate disease burden, incidence, mortality, and Disability-Adjusted Life Years (DALYs) attributable to dietary exposure to the chemicals. In all models, we harmonized food classification and exposure assessment. We propagated uncertainty through the calculations using Monte Carlo simulation. We estimated that, among these chemicals, i-As and Pb were responsible for the highest disease burden. i-As was estimated to cause 820 DALYs, or approximately 1.25 DALYs per 100,000 inhabitants. The estimated burden of Pb was 1834 to 5936 DALYs, or 2.7 (lower bound) to 8.96 (upper bound) DALYs/100,000. The burden of MeHg (192 DALYs), and Cd (0 DALY) was substantially lower. The foods contributing most to disease burden was drinks (30 %), "other foods" (mostly composite dishes) (19 %), and fish and seafood (7 %). Interpretation of estimates needs to consider all underlying uncertainties, linked with data and knowledge gaps. The harmonized models are the first to make use of data from TDS, which are available in several other countries. Thus, they can be applied to estimate the burden and to rank food-associated chemicals at national level.

Risk ranking of chemical hazards in foods: comparison of aggregating methods using infant formula as an example.

The aim of this study was to rank several chemical hazards present in one food item, namely infant formula. We first identified the substances potentially present in infant foods according to the results of the French infant Total Diet Study and to the available scientific literature. Second, we built three criteria to rank the hazards: severity, contribution to the total exposure, and risk characterisation. Each criterion was scored using quantitative or semi-quantitative scales. Third, in order to rank the chemical hazards, two approaches of aggregation of the three criteria were deployed. On the one hand, a multi-criteria decision analysis outranking method and on the other hand a semi-quantitative risk-matrix type method. We then tested these approaches on follow-on formulae for the 7-12 months population, for which contamination data from the French infant Total Diet study were available. The results of both methods showed that the six prioritised substances are the same even if not in the exact same order (acrylamide, inorganic arsenic, furan, chromium VI, lead and PCDD/Fs) demonstrating the robustness of these approaches.

Probabilistic determination of a maximum acceptable level of contaminant to reduce the risk of overexposure for a novel or emerging food: the case of cadmium in edible seaweed in the French population.

European and French populations are overexposed to cadmium (Cd) through their foods. The risk of increased cadmium exposure for consumers needs to be limited by reduced maximum limits (ML) for novel foodstuffs such as edible seaweed in France. The objective was to derive a low and protective cadmium concentration in edible seaweeds to limit cadmium overexposure in consumers. To do so, we applied a probabilistic approach to the data collected on French seaweed consumers, taking into account other sources of exposure for cadmium. This approach led to the identification of a cadmium concentration which should ensure that the seaweed-consuming population does not exceed the tolerable daily intake (TDI) of cadmium according to a probability of cases, when simultaneously exposed to other cadmium dietary sources. Considering the 5% of the population exceeding TDI, the estimated ML is equal to 0.35 mg Cd kg-1 dry matter of seaweed as an unprocessed food with a 95% confidence interval of [0.18,1.09]. The proposed approach is generic and could be applied to other relevant food/substance pairs when considering the setting of MLs in the regulatory system. It ensures better protection of consumer health.

Cr(VI) and Cr(III) in milk, dairy and cereal products and dietary exposure assessment.

Milk, dairy and cereal products are the main contributors to total chromium (Cr) dietary exposure in France (up to 42% for children), but there have been no assessments regarding dietary exposure to Cr(VI) or Cr(III) to date. To assess dietary exposure, total chromium and Cr(VI) were determined in 68 different brands and origins of milk, dairy and cereal products. Cr(VI) was not detected in these samples despite the very high sensitivity of the method used. It was therefore assumed that total chromium is only present in the Cr(III) form. Total chromium levels were quantified in 58% of milk and dairy products and 76% of cereal products. The highest mean levels were found in breakfast cereals and cheese (269 and 25 µg Cr /kg fresh weight, respectively). The findings pointed out that the dietary exposure levels of Cr(III) and Cr(VI) were well below the health-based guidance values.

Human health risks related to the consumption of foodstuffs of animal origin contaminated by bisphenol A.

Bisphenol A (BPA) is used in a wide variety of products and objects for consumers use (digital media such as CD's and DVD's, sport equipment, food and beverage containers, medical equipment). For humans, the main route of exposure to BPA is food. Based on previous estimates, almost 20% of the dietary exposure to BPA in the French population would be from food of animal origin. However, due to the use of composite samples, the source of the contamination had not been identified. Therefore, 322 individual samples of non-canned foods of animal origin were collected with the objectives of first updating the estimation of the exposure of the French population and second identifying the source of contamination of these foodstuffs using a specific analytical method. Compared to previous estimates in France, a decline in the contamination of the samples was observed, in particular with regard to meat. The estimated mean dietary exposures ranged from 0.048 to 0.050 µg (kg bw)-1 d-1 for 3-17 year children and adolescents, from 0.034 to 0.035 µg (kg bw)-1 d-1 for adults and from 0.047 to 0.049 µg (kg bw)-1 d-1 for pregnant women. The contribution of meat to total dietary exposure of pregnant women, adults and children was up to three times lower than the previous estimates. Despite this downward trend in contamination, the toxicological values were observed to have been exceeded for the population of pregnant women. With the aim of acquiring more knowledge about the origin the potential source(s) of contamination of non-canned foods of animal origin, a specific analytical method was developed to directly identify and quantify the presence of conjugated BPA (BPA-monoglucuronide, BPA-diglucuronide and sulphate forms) in 50 samples. No conjugated forms of BPAs were detected in the analysed samples, indicating clearly that BPA content in animal food was not due to metabolism but arise post mortem in food. This contamination may occur during food production. However, despite extensive sampling performed in several different shops (butcheries, supermarkets …. ) and in different conditions (fresh, prepared, frozen …), the source(s) of the contamination could not be specifically identified.

Levels of lead in foods from the first French total diet study on infants and toddlers.

Infants and toddlers are highly vulnerable to exposure to lead due to its higher absorption in small children than in adults. This study describes the optimisation and validation of a very sensitive method for the determination of low levels of lead in foods mostly consumed by infants and toddlers. This method, based on inductively coupled plasma-mass spectrometry with a programmable temperature cyclonic spray chamber, attained a limit of quantification (LOQ) of 0.6 or 0.9µgPbkg-1 for a liquid or a solid sample, that was improved by a factor 5.6-8.3 compared to the previous method (LOQ: 5µgkg-1). The analytical method was then applied to 291 food samples from the first French total diet study on infants and toddlers. Lead was detected in most samples at relatively low concentrations (range 0.0-16µgkg-1). The highest lead concentrations were mainly found in processed food products (e.g. products containing chocolate).

Perfluoroalkyl acid contamination and polyunsaturated fatty acid composition of French freshwater and marine fishes.

In this study, French marine and freshwater fish perfluoroalkyl acid (PFAA) contamination are presented along with their fatty acid (FA) composition to provide further elements for a risk/benefit balance of fish consumption to be assessed. The 29 most consumed marine fish species were collected in four metropolitan French coastal areas in 2004 to constitute composite samples. Geographical differences in terms of consumed species and contamination level were taken into account. Three hundred and eighty-seven composite samples corresponding to 16 freshwater fish species collected between 2008 and 2010 in the six major French rivers or their tributaries were selected among the French national agency for water and aquatic environments freshwater fish sample library. The raw edible parts were analyzed for FA composition and PFAA contamination. Results show that freshwater fishes are more contaminated by PFAAs than marine fishes and do not share the same contamination profile. Freshwater fish contamination is mostly driven by perfluorooctane sulfonate (PFOS) (75%), whereas marine fish contamination is split between perfluorooctanoic acid (PFOA) (24%), PFOS (20%), perfluorohexanoic acid (PFHxA) (15%), perfluoropentanoic acid (PFHpA) (11%), and perfluorobutanoic acid (PFBA) (11%). Common carp, pike-perch, European perch, thicklip grey mullet, and common roach presented the most unfavorable balance profile due to their high level of PFAAs and low level of n-3 long-chain polyunsaturated fatty acids (LC-PUFAs). These data could be used, if needed, in an updated opinion on fish consumption that takes into account PFAA contamination.

Assessment of dietary exposure to bisphenol A in the French population with a special focus on risk characterisation for pregnant French women.

Bisphenol A (BPA) is used in a wide variety of products and objects for consumers use (digital media such as CD's and DVD's, sport equipment, food and beverage containers, medical equipment). Here, we demonstrate the ubiquitous presence of this contaminant in foods with a background level of contamination of less than 5 µg/kg in 85% of the 1498 analysed samples. High levels of contamination (up to 400 µg/kg) were found in some foods of animal origin. We used a probabilistic approach to calculate dietary exposure from French individual consumption data for infants under 36 months, children and adolescents from 3 to 17 years, adults over 18 years and pregnant women. The estimated average dietary exposure ranged from 0.12 to 0.14 µg/kg body weight per day (bw/d) for infants, from 0.05 to 0.06 µg/kg bw/d for children and adolescents, from 0.038 to 0.040 µg/kg bw/d for adults and from 0.05 to 0.06 µg/kg bw/d for pregnant women. The main sources of exposure were canned foods (50% of the total exposure), products of animal origin (20%) and 30% as a background level. Based on the toxicological values set by the French Agency for Food, Environmental and Occupational Health & Safety (ANSES) for pregnant women, the risk was non negligible. Thus, we simulated scenarios to study the influence of cans and/or food of animal origin on the BPA-related risk for this specific population.

Fish and seafood consumption and omega 3 intake in French coastal populations: CALIPSO survey.

OBJECTIVE: To describe part of the results of the CALIPSO study, i.e. to provide seafood consumption data on high seafood consumers in France and its contribution to n-3 long-chain (LC) PUFA intake. DESIGN AND SUBJECTS: A total of 1011 individuals aged 18 years and over, who consumed fish and seafood at least twice weekly, were recruited. A consumption survey and a local 'total diet study' were performed to examine seafood consumption, fatty acids composition of seafood and to assess n-3 LC PUFA intake. SETTING: The CALIPSO survey was conducted in four French coastal regions (Le Havre, Lorient, La Rochelle and Toulon). METHODS: The subjects were questioned about their consumption habits, especially concerning fish and seafood, through a first validated FFQ. A sample of the most consumed seafood products (n 47) was analysed for each region for its fatty acid composition. Fatty acids and especially n-3 LC PUFA intakes in this population were then calculated. RESULTS AND CONCLUSIONS: The average consumption of fresh and frozen fish was found to be 633, 636.5 and 787.8 g/week among men aged 18-64 years, women aged 18-64 years and people over 65 years, respectively. In these population groups, the consumption of crustaceans and molluscs was 270.3, 259.9 and 279.3 g/week, respectively. The results show that, irrespective of the age group and gender, consumption of fish and seafood twice weekly without excluding oily fish allowed people to reach the national and international recommended n-3 LC PUFA intakes and demonstrates the validity of the French recommendations for fish consumption.

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).

Probabilistic modeling of young children's overall lead exposure in France: integrated approach for various exposure media.

OBJECTIVES: Emissions of lead into the environment (and thus its environmental concentrations) have decreased in recent years. We sought to estimate the overall lead exposure of children aged 6 months to 6 years (the population group most exposed and most sensitive to lead) in France through the various media (air, food, water, soils, and dust) and the respective contributions of each medium to the total dose. We have focused on the general population, leaving aside specific risk factors such as deteriorated lead paints. METHODS: We used the most recent French intake data for food and water, and a daily ingested quantity selected from the literature for soils and dust. Contamination data came from the first total diet study of contaminant levels in France (2000-2001), from regulatory testing of tap water (2004), a literature review of lead in urban soils, and a pilot study (2005) of lead in dust. Air quality monitoring measurements showed that the contribution of air could now be safely ignored. Weekly exposure doses were estimated with Monte Carlo simulations. RESULTS: Median weekly exposure dose was 7.5 microg/kg bw.week for children aged 6 months to 3 years and 4.7 for those aged from 3-6 years. 95th percentiles were 13.5 and 8.7 microg/kg bw.week. Exposure came mainly from food. The principal uncertainties are associated with quantification limits in food and water, representativeness and traceability of tap water samples, and absence of recent data about urban soil contamination. CONCLUSIONS: These results differ quite notably from earlier estimates and highlight the need, especially for policy-making purposes, to update exposure measurements for this metal.

New considerations regarding the risk assessment on Tartrazine An update toxicological assessment, intolerance reactions and maximum theoretical daily intake in France.

Tartrazine is an artificial azo dye commonly used in human food and pharmaceutical products. Since the last assessment carried out by the JECFA in 1964, many new studies have been conducted, some of which have incriminated tartrazine in food intolerance reactions. The aims of this work are to update the hazard characterization and to revaluate the safety of tartrazine. Our bibliographical review of animal studies confirms the initial hazard assessment conducted by the JECFA, and accordingly the ADI established at 7.5mg/kg bw. From our data, in France, the estimated maximum theoretical intake of tartrazine in children is 37.2% of the ADI at the 97.5th percentile. It may therefore be concluded that from a toxicological point of view, tartrazine does not represent a risk for the consumer. It appears more difficult to show a clear relationship between ingestion of tartrazine and the development of intolerance reactions in patients. These reactions primarily occur in patients who also suffer from recurrent urticaria or asthma. The link between tartrazine consumption and these reactions is often overestimated, and the pathogenic mechanisms remain poorly understood. The prevalence of tartrazine intolerance is estimated to be less than 0.12% in the general population. Generally, the population at risk is aware of the importance of food labelling, with the view of avoiding consumption of tartrazine. However, it has to be mentioned that products such as ice creams, desserts, cakes and fine bakery are often sold loose without any labelling.

Estimation of the exposure of the French population to the BSE agent: comparison of the 1980-95 consumption of beef products containing mechanically recovered meat in France and the UK, by birth cohort and gender.

Assuming that human exposure to BSE was through beef mechanically recovered meat (MRM) consumed as burgers and other meat products, we estimated the French consumption of different food items containing beef MRM, and compared these consumptions for French and British populations. To estimate consumption of meat products containing bovine MRM, we used dietary data from national individual and household food surveys conducted between 1980 and 1995. After reconciliation of consumption data between the available surveys and calendar year adjustments, we simulated consumption of one-thousandth of the French population. Consumption was estimated by birth cohort and gender, and for the periods 1980-89 and 1990-95 separately. Data showed that burgers (including manufactured minced meat) represented around 75-80% of the individual consumption of meat products containing MRM, and that consumption of burgers increased by 40% over the 1980-95 period. In all age groups, consumption was higher in males than in females. In both genders, the 1940-69 birth cohort had the highest mean consumption of burgers and other beef products containing MRM. Similar findings have been reported for the UK population. Estimated consumption of bovine MRM per calendar year increased markedly over the study period, concomitantly with an increase of bovine carcasses imported from the UK. Comparison of the 1980-1995 pattern of bovine MRM consumption in the UK and France indicated thatthis consumption peaked later in France than in the UK. This difference might result in different temporal pattern of vCJD incidence.