Harmonized methodology to assess chronic dietary exposure to residues from compounds used as pesticide and veterinary drug.

Risk assessments for pesticide and veterinary drug residues in food are performed respectively by the Joint FAO/WHO Expert Meeting on Pesticide Residues (JMPR) and the Joint FAO/WHO Expert Committee on Food Additives (JECFA). The models used by the two Committees to assess chronic dietary exposure are based on different data and assumptions which may be confusing, particularly for risk managers, when the same compound is used to treat plants and animals. This publication details the results of combined chronic dietary exposure assessments for eight compounds used both as pesticide and veterinary drugs. It compares the results from models in use by JMPR and JECFA with those from national estimates performed by 17 countries. Results show that the JECFA model is better reflecting less than lifetime dietary exposure by considering consumption of children and high consumers. The JMPR model is a suitable model for estimating average chronic (lifetime) exposure to residues present in widely and regularly consumed staple commodities. However, it is suitable neither for estimating children's exposure nor more generally for assessing less than lifetime dietary exposure. In order to select the appropriate exposure model related to the occurrence of adverse effects i.e. effects occurring over less-than-lifetime or effects occurring only over lifetime, this paper proposes criteria to match the toxicological profile of the compound and the appropriate exposure scenarios. These approaches will continue to be harmonized to ensure the most scientifically sound basis for the risk assessment for pesticides and veterinary drug residues and consequently for other chemicals in food.

Characterizing chronic and acute health risks of residues of veterinary drugs in food: latest methodological developments by the joint FAO/WHO expert committee on food additives.

The risk assessment of residues of veterinary drugs in food is a field that continues to evolve. The toxicological end-points to be considered are becoming more nuanced and in light of growing concern about the development of antimicrobial resistance, detailed analysis of the antimicrobial activity of the residues of veterinary drugs in food is increasingly incorporated in the assessment. In recent years, the Joint FAO/WHO Expert Committee on Food Additives (JECFA) has refined its approaches to provide a more comprehensive and fit-for-purpose risk assessment. This publication describes in detail the consideration of acute and chronic effects, the estimation of acute and chronic dietary exposure, current approaches for including microbiological endpoints in the risk assessment, and JECFA's considerations for the potential effects of food processing on residues from veterinary drugs. JECFA now applies these approaches in the development of health-based guidance values (i.e. safe exposure levels) for residues of veterinary drugs. JECFA, thus, comprehensively addresses acute and chronic risks by using corresponding estimates for acute and chronic exposure and suitable correction for the limited bioavailability of bound residues by the Gallo-Torres model. On a case-by-case basis, JECFA also considers degradation products that occur from normal food processing of food containing veterinary drug residues. These approaches will continue to be refined to ensure the most scientifically sound basis for the establishment of health-based guidance values for veterinary drug residues.

Model averaging quantiles from data censored by a limit of detection.

In chemical risk assessment, it is important to determine the quantiles of the distribution of concentration data. The selection of an appropriate distribution and the estimation of particular quantiles of interest are largely hindered by the omnipresence of observations below the limit of detection, leading to left-censored data. The log-normal distribution is a common choice, but this distribution is not the only possibility and alternatives should be considered as well. Here, we focus on several distributions that are related to the log-normal distribution or that are seminonparametric extensions of the log-normal distribution. Whereas previous work focused on the estimation of the cumulative distribution function, our interest here goes to the estimation of quantiles, particularly in the left tail of the distribution where most of the left-censored data are located. Two different model averaged quantile estimators are defined and compared for different families of candidate models. The models and methods of selection and averaging are further investigated through simulations and illustrated on data of cadmium concentration in food products. The approach is extended to include covariates and to deal with uncertainty about the values of the limit of detection. These extensions are illustrated with (134) cesium measurements from Fukushima Prefecture, Japan. We can conclude that averaged models do achieve good performance characteristics in case no useful prior knowledge about the true distribution is available; that there is no structural difference in the performance of the direct and indirect method; and that, not surprisingly, only the true or closely approximating model can deal with extremely high percentages of censoring.

Extraction of food consumption systems by nonnegative matrix factorization (NMF) for the assessment of food choices.

In Western countries where food supply is satisfactory, consumers organize their diets around a large combination of foods. It is the purpose of this article to examine how recent nonnegative matrix factorization (NMF) techniques can be applied to food consumption data to understand these combinations. Such data are nonnegative by nature and of high dimension. The NMF model provides a representation of consumption data through latent vectors with nonnegative coefficients, that we call consumption systems (CS), in a small number. As the NMF approach may encourage sparsity of the data representation produced, the resulting CS are easily interpretable. Beyond the illustration of its properties we provide through a simple simulation result, the NMF method is applied to data issued from a French consumption survey. The numerical results thus obtained are displayed and thoroughly discussed. A clustering based on the k-means method is also achieved in the resulting latent consumption space, to recover food consumption patterns easily usable for nutritionists.

Integrating variability in half-lives and dietary intakes to predict mercury concentration in hair.

Methylmercury (MeHg) is a bioaccumulative environmental toxin that exerts its effect on fetal and infant neurodevelopment. Mercury concentration in hair is a good biomarker of MeHg accumulation in the body, with seafood being the main source of MeHg in humans. Therefore, modeling the link between food intake and mercury concentration in hair is a key step in assessing the risk of MeHg exposure. Using repeated measurements of diet and mercury concentration in hair, we studied 125 French pregnant women who consumed seafood (e.g., fish, mollusks and crustaceans) and compared their individual estimated dietary MeHg intakes with their hair mercury concentrations. We used a one-compartment toxicokinetic model for these comparisons. We integrated and estimated the between-person variability in MeHg half-life into the model. In a second model, we took into account an intra-individual MeHg intake variability to improve the performance of the toxicokinetic model.

The dilemma of pesticide residues in fruits and vegetables in the Eastern Mediterranean Region.

In the World Health Organization Eastern Mediterranean Region (EMR), over 100 million people fall ill every year from foodborne diseases, of whom an estimated 37 000 die annually (disproportionally children). A number of studies have identified a clear relationship between occupational exposure to pesticides and a number of noncommunicable diseases (NCDs). For example, respiratory symptoms were reported in 65.9% of farmers exposed to pesticides in Pakistan; lymphoproliferative disorders following exposure to pesticides in Egypt; and hepatocellular carcinoma in Yemen with 73.7% of farmers having a history of chemical contact with insecticides or fertilizers. However, a challenging task regarding the burden of foodborne disease is the attribution to chemicals in food as a source for NCDs, since this requires long-term epidemiological and exposure monitoring data.

Levels of persistent organic pollutants (POPs) in foods from the first regional Sub-Saharan Africa Total Diet Study.

For the first time, a multi-centre Total Diet Study was carried out in Benin, Cameroon, Mali and Nigeria. We collected and prepared as consumed 528 typical fatty foods from those areas and pooled these subsamples into 44 composites samples. These core foods were tested for a wide spectrum of POPs, including polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs), polychlorinated biphenyls (PCBs), brominated flame-retardants (BFRs), organochlorine compounds (OCs), perfluoro alkyl substances (PFAS) and chlorinated flame retardants (CFRs). The POPs contamination levels were similar or lower than those reported in total diet studies previously conducted worldwide. In most cases, core foods belonging to fish food group presented higher POPs concentrations than the other food groups. Interestingly, we observed a difference in both contamination profile and concentration for smoked fish compared to non-smoked fish. Such finding suggests that the smoking process itself might account for a large proportion of the contamination. Further investigation would require the assessment of combustion materials used to smoke fish as a potential vehicle, which may contribute to the dietary exposure of the studied populations to POPs.

Human dietary exposure to chemicals in sub-Saharan Africa: safety assessment through a total diet study.

BACKGROUND: Human dietary exposure to chemicals can result in a wide range of adverse health effects. Some substances might cause non-communicable diseases, including cancer and coronary heart diseases, and could be nephrotoxic. Food is the main human exposure route for many chemicals. We aimed to assess human dietary exposure to a wide range of food chemicals. METHODS: We did a total diet study in Benin, Cameroon, Mali, and Nigeria. We assessed 4020 representative samples of foods, prepared as consumed, which covered more than 90% of the diet of 7291 households from eight study centres. By combining representative dietary surveys of countries with findings for concentrations of 872 chemicals in foods, we characterised human dietary exposure. FINDINGS: Exposure to lead could result in increases in adult blood pressure up to 2·0 mm Hg, whereas children might lose 8·8-13·3 IQ points (95th percentile in Kano, Nigeria). Morbidity factors caused by coexposure to aflatoxin B1 and hepatitis B virus, and sterigmatocystin and fumonisins, suggest several thousands of additional liver cancer cases per year, and a substantial contribution to the burden of chronic malnutrition in childhood. Exposure to 13 polycyclic aromatic hydrocarbons from consumption of smoked fish and edible oils exceeded levels associated with possible carcinogenicity and genotoxicity health concerns in all study centres. Exposure to aluminium, ochratoxin A, and citrinin indicated a public health concern about nephropathies. From 470 pesticides tested across the four countries, only high concentrations of chlorpyrifos in smoked fish (unauthorised practice identified in Mali) could pose a human health risk. INTERPRETATION: Risks characterised by this total diet study underscore specific priorities in terms of food safety management in sub-Saharan Africa. Similar investigations specifically targeting children are crucially needed. FUNDING: Standards and Trade Development Facility.

Correction: Ingenbleek, L. et al. Regional Sub-Saharan Africa Total Diet Study in Benin, Cameroon, Mali, and Nigeria Reveals the Presence of 164 Mycotoxins and Other Secondary Metabolites in Foods.

The authors wish to make the following corrections to their paper [...].

Sub-Saharan Africa total diet study in Benin, Cameroon, Mali and Nigeria: Pesticides occurrence in foods.

In the framework of the first regional Total Diet Study in Sub-Saharan Africa, 3696 foodstuffs, commonly consumed in Benin, Cameroon, Mali and Nigeria were purchased, prepared as consumed and pooled into 308 composite samples. Those core foods were tested for up to 470 pesticides residues by liquid and gas chromatography coupled with tandem mass spectrometry. 39 pesticides were detected with 294 total occurrences, including 47.3% organophosphate pesticides and 35.7% pyrethroids. More specifically, 6 substances represented 75.5% of all 3 organophosphates and 3 pyrethroids: chlorpyrifos (22.4%) cypermethrin (18.0%) dichlorvos (13.6%), lambda cyhalothrin (8.2%), permethrin (7.5%) and profenofos (5.8%). One pesticide or more was detected in 45.8% of samples. Strikingly, several pesticides were quantified in 2 composite samples of smoked fish from Mali: chlorpyrifos (5236-18 084 µg/kg), profenofos (30-182 µg/kg), cypermethrin (22-250 µg/kg), cyfluthrin (16-117 µg/kg), lambda cyhalothrin (9-17 µg/kg) and permethrin (3-6 µg/kg).

Occurrence of 30 trace elements in foods from a multi-centre Sub-Saharan Africa Total Diet Study: Focus on Al, As, Cd, Hg, and Pb.

This paper reports occurrence data related to 30 trace elements in food composite samples from a multi-regional Sub-Saharan Africa Total Diet Study. Herein, 2700 samples grouped in 225 food composite samples corresponding to 13 food groups: cereals, tubers, legumes, vegetables, fruits, nuts/seeds, meat, eggs, fish, milk/dairy, oil/fats, and beverages from eight locations in four countries, namely Benin (Littoral/Borgou), Cameroon (Duala/North), Mali (Bamako/Sikasso), and Nigeria (Lagos/Kano) were prepared as consumed, pooled, and analysed using a validated method based on inductively coupled plasma-mass spectrometry. The occurrence data for Al, As, Cd, Hg, and Pb as regulated by the Codex Alimentarius are discussed herein. Although the levels of As, Cd, Hg, and Pb were above the limit of quantification, they were below the maximum limits set by the Codex in most samples analysed. A distinct feature was observed for cereals and tubers, as they were mostly contaminated with Al and Pb. A pilot study regarding the impact of using artisanal cookware (made from recycled aluminium) on the contamination of food samples was performed. Relevant contamination with Al and Pb when cooking tomato samples from Cameroon and Nigeria using artisanal aluminium cookware was compared to that when cooked using stainless-steel.

Regional Sub-Saharan Africa Total Diet Study in Benin, Cameroon, Mali and Nigeria Reveals the Presence of 164 Mycotoxins and Other Secondary Metabolites in Foods.

In the framework of the first multi-centre Sub-Saharan Africa Total Diet Study (SSA-TDS), 2328 commonly consumed foods were purchased, prepared as consumed and pooled into 194 composite samples of cereals, tubers, legumes, vegetables, nuts and seeds, dairy, oils, beverages and miscellaneous. Those core foods were tested for mycotoxins and other fungal, bacterial and plant secondary metabolites by liquid chromatography, coupled with tandem mass spectrometry. The highest aflatoxin concentrations were quantified in peanuts, peanut oil and maize. The mean concentration of the sum of aflatoxins AFB1, AFB2, AFG1 and AFG2 (AFtot) in peanut samples (56.4 µg/kg) exceeded EU (4 µg/kg) and Codex (15 µg/kg) standards. The AFtot concentration (max: 246.0 µg/kg) was associated with seasonal and geographic patterns and comprised, on average, 80% AFB1, the most potent aflatoxin. Although ochratoxin A concentrations rarely exceeded existing Codex standards, it was detected in unregulated foods. One palm oil composite sample contained 98 different metabolites, including 35.4 µg/kg of ochratoxin A. In total, 164 different metabolites were detected, with unspecific metabolites like asperglaucide, cyclo(L-pro-L-val), cyclo (L-pro-L-tyr), flavoglaucin, emodin and tryptophol occurring in more than 50% of composite samples. Aflatoxin B1 (AFB1), fumonisin B1 (FB1), sterigmatocystin (STC), ochratoxin A (OTA), citrinin (CIT) and many other secondary fungal metabolites are frequent co-contaminants in staple foods, such as maize and sorghum. Populations from North Cameroon and from Benin may, therefore, suffer chronic and simultaneous exposure to AFB1, FB1, STC, OTA and CIT, which are prevalent in their diet.

Mycotoxin contamination of sorghum and its contribution to human dietary exposure in four sub-Saharan countries.

This research aimed at evaluating the safety, and the type, level and prevalence of mycotoxins in grain sorghum of four sub-Saharan African (SSA) countries (Burkina Faso, Ethiopia, Mali and Sudan). A multi-analyte LC-MS/MS method for quantification of 23 mycotoxins (nivalenol, deoxynivalenol, fusarenon X, neosolaniol, 3-acetyl deoxynivalenol, 15-acetyl deoxynivalenol, diacetoxyscirpenol, roquefortine C, HT-2 toxin, alternariol, T-2 toxin, FB1, FB2, FB3, zearalenone, aflatoxin G1, aflatoxin G2, aflatoxin B1, aflatoxin B2, sterigmatocystin, OTA, altenuene, alternariol monomethylether) was applied to different sorghum matrices. Of the 1533 analysed samples, 33% were contaminated with at least one of the following mycotoxins: aflatoxins, fumonisins, sterigmatocystin, Alternaria toxins, OTA and zearalenone. Country of origin, colour, source and collection period of sorghum samples significantly influenced the type, level and prevalence of mycotoxins. Sterigmatocystin (15%), fumonisins (17%) and aflatoxins (13%) were the most prevalent. FB1 (274 ± 585 µg/kg) had the highest mean concentration followed by FB2 (214 ± 308 µg/kg) while diacetoxyscirpenol (8.12 ± 19.2 µg/kg) and HT-2 (11.9 ± 0.00 µg/kg) had the lowest concentrations. Neosolaniol, fusarenon-X, 3-acetyl deoxynivalenol, 15-acetyl deoxynivalenol, T-2 toxin, nivalenol and roquefortine C were not detected in any of the samples. Sudan had the lowest prevalence and mean concentration of all mycotoxins. Pink sorghum had the highest concentrations of fumonisins and aflatoxins. Mycotoxins from Aspergillus spp. and Alternaria spp. are the mycotoxins of concern in SSA grain sorghum with regard to prevalence, concentration and possible health risk from exposure. Based on the performed risk characterisation, daily consumption of sorghum containing aflatoxins, alternariol, alternariol monomethyl ether, sterigmatocystin and OTA could result in exceeding the established health-based guidance values for these toxins.

Methodology design of the regional Sub-Saharan Africa Total Diet Study in Benin, Cameroon, Mali and Nigeria.

The core food model was described more than three decades ago, and has been used ever since to identify main food contributors to dietary intakes for both nutrients and other food chemicals. The Sub-Saharan Africa Total Diet Study (SSA-TDS) uses this model to describe the food consumption habits of some selected populations of Benin, Cameroon, Mali, and Nigeria, prior to use in the completion of quantitative risk assessments with regard to food chemicals. Food consumption data were derived from food expenditure data contained in national household budget surveys that were provided by the national institutes of statistics in each country. A classification of African foods was established for the purpose of the study and core foods were selected, so as to reflect 96 ± 1% of the average national total diet expressed in weight. Populations from eight study centers were selected by national stakeholders. This approach involves the purchase of 4020 individual foods, prepared as consumed and pooled into 335 food composite samples, for analysis of mycotoxins, PAHs, PCBs and dioxins, pesticides, metals and trace elements, PFAs, and BFRs. This sampling plan aims to provide a representative, cost effective, and replicable approach for deterministic dietary exposure assessments in developing countries.

World Health Organization estimates of the global and regional disease burden of four foodborne chemical toxins, 2010: a data synthesis.

Background Chemical exposures have been associated with a variety of health effects; however, little is known about the global disease burden from foodborne chemicals. Food can be a major pathway for the general population's exposure to chemicals, and for some chemicals, it accounts for almost 100% of exposure.  Methods and Findings Groups of foodborne chemicals, both natural and anthropogenic, were evaluated for their ability to contribute to the burden of disease.  The results of the analyses on four chemicals are presented here - cyanide in cassava, peanut allergen, aflatoxin, and dioxin.  Systematic reviews of the literature were conducted to develop age- and sex-specific disease incidence and mortality estimates due to these chemicals.  From these estimates, the numbers of cases, deaths and disability adjusted life years (DALYs) were calculated.  For these four chemicals combined, the total number of illnesses, deaths, and DALYs in 2010 is estimated to be 339,000 (95% uncertainty interval [UI]: 186,000-1,239,000); 20,000 (95% UI: 8,000-52,000); and 1,012,000 (95% UI: 562,000-2,822,000), respectively.  Both cyanide in cassava and aflatoxin are associated with diseases with high case-fatality ratios.  Virtually all human exposure to these four chemicals is through the food supply.  Conclusion Chemicals in the food supply, as evidenced by the results for only four chemicals, can have a significant impact on the global burden of disease. The case-fatality rates for these four chemicals range from low (e.g., peanut allergen) to extremely high (aflatoxin and liver cancer).  The effects associated with these four chemicals are neurologic (cyanide in cassava), cancer (aflatoxin), allergic response (peanut allergen), endocrine (dioxin), and reproductive (dioxin).

New approach for the assessment of cluster diets.

Dietary risk assessment is a major public health concern, positioned in the context of establishing overall food safety policy. It requires some understanding of population food choices although geographical location and social-cultural environment are variable. Several years ago, a cluster analysis based on FAO consumption data, ranging from 1990 to 1994, was at the origin of the 13, so called, GEMS/Food cluster diets. This analysis required the initial identification of 19 food markers based on geographical and cultural differences. This paper proposes a new modelling of FAO food consumption database in order to define new cluster diets based on updated consumption data from 2002 to 2007 and better adapted statistical methods. Two statistical methods were combined to extract, consumption systems that generate a substructure from the initial food consumption database and then by deriving a clustering of countries according to their consumption system profiles. The clustering resulted in 17 cluster diets composed of 2 up to 30 countries. The few discrepancies between these new clusters and former ones may be due to more recent data, and to the fact that the new approach is based on another mathematical modelling which does not require any initial identification of food markers.

Population effects and variability.

Chemical risk assessment for human health requires a multidisciplinary approach through four steps: hazard identification and characterization, exposure assessment, and risk characterization. Hazard identification and characterization aim to identify the metabolism and elimination of the chemical (toxicokinetics) and the toxicological dose-response (toxicodynamics) and to derive a health-based guidance value for safe levels of exposure. Exposure assessment estimates human exposure as the product of the amount of the chemical in the matrix consumed and the consumption itself. Finally, risk characterization evaluates the risk of the exposure to human health by comparing the latter to with the health-based guidance value. Recently, many research efforts in computational toxicology have been put together to characterize population variability and uncertainty in each of the steps of risk assessment to move towards more quantitative and transparent risk assessment. This chapter focuses specifically on modeling population variability and effects for each step of risk assessment in order to provide an overview of the statistical and computational tools available to toxicologists and risk assessors. Three examples are given to illustrate the applicability of those tools: derivation of pathway-related uncertainty factors based on population variability, exposure to dioxins, dose-response modeling of cadmium.

Human risk assessment of heavy metals: principles and applications.

Humans are exposed to a number of "heavy metals" such as cadmium, mercury and its organic form methylmercury, uranium, lead, and other metals as wel as metalloids, such as arsenic, in the environment, workplace, food, and water supply. Exposure to these metals may result in adverse health effects, and national and international health agencies have methodologies to set health-based guidance values with the aim to protect the human population. This chapter introduces the general principles of chemical risk assessment, the common four steps of chemical risk assessment: hazard identification, hazard characterization, exposure assessment, risk characterization, and toxicokinetic and toxicity aspects. Finally, the risk assessments performed by international health agencies such as the World Health Organisation, the Environmental Protection Agency of the United States, and the European Food Safety Authority are reviewed for cadmium, lead, mercury, uranium, and arsenic.

Use of advanced cluster analysis to characterize fish consumption patterns and methylmercury dietary exposures from fish and other sea foods among pregnant women.

On account of the interspecies variability in contamination and nutrient contents, consumers must balance the risks and benefits of fish consumption through their choice of species, meal size and frequency. The objectives of this study were to better characterize the risk of methylmercury (MeHg) exposure in a sample of 161 French pregnant women consuming sea food, including fish, molluscs and crustaceans, and to explore the use of unsupervised statistical learning as an advanced type of cluster analysis to identify patterns of fish consumption that could predict exposure to MeHg and the coverage of the Recommended Daily Allowance for n-3 polyunsaturated fatty acid (PUFA). The proportion of about 5% of pregnant women exposed at levels higher than the tolerable weekly intake for MeHg is similar to that observed among women of childbearing age in earlier French studies. At the same time, only about 50% of the women reached the recommended intake of 500 mg/day n-3 PUFA. Cluster analysis of the fish consumption showed that they could be grouped in five major clusters that are largely predictable of the intake of both MeHg and n-3 PUFA. This study shows that a global increase in seafood consumption could lead to MeHg exposure above the toxicological limits for pregnant women, thereby questioning the overall balance between this potential risk and potential beneficial effects of n-3 PUFA intakes. Only pregnant women consuming a high proportion of fatty fish meet the n-3 PUFA intake requirements without exceeding the toxicological limit for MeHg. The clusters identified suggest that different intervention strategies may be needed to address the dual purpose of ensuring high PUFA intakes at acceptable MeHg exposures.