J.D. van Klaveren

Cumulative risk assessment of the exposure to organophosphorus and carbamate insecticides in the dutch diet

We report the acute cumulative exposure to organophosphorus insecticides (OPs) and carbamates in the Dutch population and young children (1-6 years) via the diet. Residue data were derived from Dutch monitoring programmes performed during 2003-2005, and food consumption levels from the Dutch National Food Consumption Survey 1997/1998. The relative potency factor (RPF) approach was used to cumulate the exposure to OPs and carbamates using acephate and oxamyl as index compound respectively. The exposure was estimated using the probabilistic approach, including unit variability and processing effects. We demonstrate that about 3% of the composite samples analysed for OPs and 0.2% for carbamates contain combinations of these pesticides. The P99.9 of exposure to OPs and carbamates in the total Dutch population equals 23 and 0.64microg/kg BW/d respectively. For young children the corresponding exposure levels are 57 and 1.47microg/kg BW/d. When comparing the P99.9 of exposure with the ARfD, 50 and 9microg/kg BW/d for acephate and oxamyl respectively, there is only a possible health risk for young children. Spinach contributed most to the exposure to OPs in both age groups, followed by orange and mandarin. For carbamates apple (sauce) was the main product determining the exposure.

Validation of a probabilistic model of dietary exposure to selected pesticides in Dutch infants

A probabilistic model for dietary exposure to pesticides was validated. For this, we evaluated the agreement of dietary exposure to six pesticides as estimated with the model with exposures measured in duplicate diet samples (=‘real intake’) and those calculated with the point estimate. To calculate the exposure with the model and point estimate, consumption data of the duplicate diet survey and pesticide residue measurements from Dutch monitoring programmes in 2000 and 2001 were used. The model was considered validated when the outcome was both higher than the real intake and lower than the point estimate. Results showed that exposures estimated with the model were closer to the real intake than those of the point estimate, and that the model outcome was lower than the point estimate. Furthermore, it was shown that the probabilistic approach can address the exposure to a pesticide via the consumption of different food products, while the point estimate only estimates the exposure through the consumption of one product. The model validated is a valuable asset when estimating the dietary exposure to pesticides in both the authorization of new pesticides and the evaluation of exposures using monitoring data.

Determination of trichothecenes in duplicate diets of young children by capillary gas chromatography with mass spectrometric detection.

Trichothecenes are mycotoxins produced by several fungal genera, mainly Fusarium species, that can contaminate a wide range of cereals used for human and animal consumption. They are associated with various adverse health effects in animals and humans such as feed refusal, vomiting and immunotoxic effects. A method based on capillary gas chromatography with mass spectrometric detection was developed and validated in-house for the determination of nine trichothecenes in duplicate diets of young children. The trichothecenes were extracted from the sample matrix by water/ethanol (90/10). The extracts were cleaned by means of ChemElut® and Mycosep® columns. The cleaned extracts were evaporated to dryness and derivatized to trimethylsilyl ethers at room temperature. The residues were dissolved in iso-octane and washed with water. The final extracts were analysed for trichothecenes by GC-MS. The response was linear in the range tested (1–10 μg kg−1). Recoveries for the trichothecenes were between 70 and 111%, with the exception of nivalenol, which had a low recovery (34%). The limit of quantification for all trichothecenes was below 0.4 μg kg−1. Seventy-four food samples from young children collected by 74 respondents in a duplicate diet study were analysed for trichothecenes with the developed method. The mean levels of deoxynivalenol, nivalenol, HT-2 toxin and T-2 toxin were 5.8, 0.3, 0.3 and 0.1 μg kg−1, respectively. Based on the individual results, dietary intake calculations were made. For deoxynivalenol, the tolerable daily intake of 1 μg kg−1 body weight was exceeded by nine respondents. For the combined intake of T-2 and HT-2 toxin, the temporary tolerable daily intake of 0.06 μg kg−1 body weight was exceeded by nine respondents.

Risk-Benefit Considerations of Mitigation Measures on Acrylamide Content of Foods - A Case Study on Potatoes, Cereals and Coffee

This report produced by an independent Expert Group is the second commissioned by the ILSI Europe Task Force on Process-related Compounds. The first report, which reviewed human exposure and internal dose assessments of acrylamide in foods, stressed the need for comparison of added risks or reduced benefits ν. the benefit of acrylamide reduction. This second Expert Group was established to examine and report on the considerations for risk-benefit analysis of the mitigation measures on acyrylamide in commodities which contribute significantly to acrylamide exposure, and their impact on safety, quality, nutritional and organoleptic parameters; to position the relevance of the suspected side effects and to quantify their potential impact. The Expert Group was asked to focus on the impact of mitigation on exposure scenarios and the risk to human health using multidimensional risk assessment approaches. The report has four main objectives: 1. To summarise the impact of pre-harvest, post-harvest and processing conditions on acrylamide formation in potatoes, cereals and coffee. 2. To evaluate the impact of pre-harvest, post-harvest and processing conditions on the formation of acrylamide in these commodities. 3. To consider the nutritional value and beneficial health impact of consuming these commodities. 4. To calculate the impact of mitigation using probabilistic risk-benefit modelling to demonstrate the principle of this approach. Animal studies have shown that acrylamide is a genotoxic carcinogen. Under the premise that for genotoxic carcinogens no threshold levels of effect exists, exposure is to be minimized as far as possible. Minimization strategies therefore have been and consistently are developed, although direct evidence of carcinogenic effects in humans as a result of acrylamide intake is not available. The margin of exposure (MOE), representing the ratio between a defined point on the relevant dose-response curve, the bench mark dose lower limit (BMDL, 300 μg/kg body weight (bw) per day) and average (1 μg/kg bw per day) or high (4 μg/kg bw per day) consumer exposure has been estimated at 300 and 75, respectively. According to the European Food Safety Authority (EFSA) and the Joint FAO/WHO Expert Committee on Food Additives (JECFA) a MOE of ≥ 10 000 would indicate low concern, underlining that the relatively low MOE for acrylamide calls for rapid and effective mitigation measures in order to lower consumer exposure. Acrylamide production in foods is a consequence of the Maillard reaction between asparagine and reducing sugars. Therefore, factors affecting the concentration of these precursors in food, together with processing conditions during food preparation and storage will affect the final concentration of acrylamide in food. The commodities giving the highest exposure to acrylamide in the western diet are potatoes, cereals and coffee. The first two of these are staple foods providing for the majority of carbohydrate and some protein in the diet. Coffee is not an essential food, but has a high level of intake as a beverage, chosen not only for its flavour and hedonic value but also as a provider of caffeine. Acrylamide formation in foodstuffs depends on the concentrations and availability of the precursor molecules asparagine and reducing sugar(s).

Probabilistic modelling of exposure doses and implications for health risk characterization: Glycoalkaloids from potatoes

Potatoes are a source of glycoalkaloids (GAs) represented primarily by alpha-solanine and alpha-chaconine (about 95%). Content of GAs in tubers is usually 10-100 mg/kg and maximum levels do not exceed 200 mg/kg. GAs can be hazardous for human health. Poisoning involve gastrointestinal ailments and neurological symptoms. A single intake of >1-3 mg/kg b.w. is considered a critical effect dose (CED). Probabilistic modelling of acute and chronic (usual) exposure to GAs was performed in the Czech Republic, Sweden and The Netherlands. National databases on individual consumption of foods, data on concentration of GAs in tubers (439 Czech and Swedish results) and processing factors were used for modelling. Results concluded that potatoes currently available at the European market may lead to acute intakes >1 mg GAs/kg b.w./day for upper tail of the intake distribution (0.01% of population) in all three countries. 50 mg GAs/kg raw unpeeled tubers ensures that at least 99.99% of the population does not exceed the CED. Estimated chronic (usual) intake in participating countries was 0.25, 0.29 and 0.56 mg/kg b.w./day (97.5% upper confidence limit). It remains unclear if the incidence of GAs poisoning is underreported or if assumptions are the worst case for extremely sensitive persons.

Exposure to domoic acid through shellfish consumption in Belgium.

A main known culprit causing amnesic shellfish poisoning in humans is domoic acid (DA). The toxin appearance in sea waters (by counting the toxin producing algae) and consequently in shellfish is closely monitored to prevent acute intoxications with gastrointestinal symptoms and neurological signs. However it is assumed that there might be some chronic problems with repetitive exposures to the toxin in animals. In humans this is greatly unknown and it is mostly assessed by relating reported toxin episodes and representative consumption data. Although in Belgium no alarming outbreaks have been reported in recent years, different concentrations of DA have been found in shellfish samples. In this study the human acute and chronic exposure to DA through shellfish consumption was evaluated by linking the data of DA concentrations in samples collected in the scope of the National Food control program in the period 2004-2009 and consumption data obtained from the National Belgian Food Consumption Survey including 3245 adults. The found level of toxin was highest in scallops while lowest in mussels. The mean usual long-term intake of molluscs such as scallops, mussels and oysters for the whole Belgian population was from 0.10 g/day for scallops to 1.21 g/day for mussels. With average portion size estimated to be 56-108 g/day depending on the shellfish source it was calculated that less than 1% of the population would be at risk of acute intoxication. Using a medium bound approach, 5-6% of the population shows chronic exposure exceeding the tolerable daily intake of 0.075 μg/kg bw per day with scallops being the most probable toxin vector when using lower (68.5%) and medium (45.6%) bound concentrations.

Long-term dietary exposure to lead in young European children: comparing a pan-European approach with a national exposure assessment

Long-term dietary exposures to lead in young children were calculated by combining food consumption data of 11 European countries categorised using harmonised broad food categories with occurrence data on lead from different Member States (pan-European approach). The results of the assessment in children living in the Netherlands were compared with a long-term lead intake assessment in the same group using Dutch lead concentration data and linking the consumption and concentration data at the highest possible level of detail. Exposures obtained with the pan-European approach were higher than the national exposure calculations. For both assessments cereals contributed most to the exposure. The lower dietary exposure in the national study was due to the use of lower lead concentrations and a more optimal linkage of food consumption and concentration data. When a pan-European approach, using a harmonised food categorisation system and “European” concentration data, results in a possible health risk related to the intake of an environmental chemical for a certain country, it is advisable to refine this assessment, as part of a tiered approach, using national occurrence data, including an optimised linkage between foods analysed and consumed for that country. In the case of lack of occurrence data, these data can be supplemented with data from the “European” concentration database or by generating additional concentration data at country level.

Estimation of the acute dietary exposure to pesticides using the probabilistic approach and the point estimate methodology

Aim: This report deals with the generation of work examples using food consumption data from the Netherlands and Sweden to facilitate the understanding of probabilistic modeling of dietary exposure to pesticides by risk managers. Imaginary field trial residue data were invented to be as useful as possible to show the potential of probabilistic modeling. Via seven work examples different aspects of acute dietary exposure assessment to pesticides and the use of the probabilistic approach were addressed. Approach and Results: In work example 1 the point estimate approach was compared with the probabilistic approach using the same input data. This work example showed that the point estimate resulted in higher estimations of exposure compared to the probabilistic approach, resulting from the conservative assumptions underlying the point estimate (one high level for both consumption and residue and a high default variability factor). It was demonstrated that with the probabilistic approach all consumption levels and field trial residue levels available could be used in one analysis, resulting in a better use of the Grey Literature European Journal of Nutrition & Food Safety, 4(1): 1-3, 2014 2 available data. Also all foods contributing to the exposure could be addressed simultaneously in one analysis, as opposed to only one food at a time in the point estimate. In this way a more holistic approach to risk is possible. Work example 2 addressed the concept of ‘consumers only’. The example showed that, when exposure could occur via the consumption of more than one food, this concept could result in risk estimates that are difficult to interpret in probabilistic modeling, because the underlying database contains both consumers and non-consumers of the specific food items. This may hamper a clear risk management decision. It was also shown, when addressing only the consumers, that the exposure was influenced by the percentage of the population that consumes such a product. When that percentage was very low the exposure increased more compared to the situation where the whole population (consumers and non-consumers) was considered (e.g. kiwi fruit) than when the food was consumed by a large majority of the population (e.g. apple in The Netherlands or apple/pear in Sweden). The effect of processing on the acute exposure assessment was demonstrated in work example 3, showing clearly that processing influenced the level of exposure. It was demonstrated that with the probabilistic approach the risk assessor can address different types of food processing simultaneously with each food item being linked to the correct variability factor (e.g. variability applied when addressing apples and pears eaten whole, but not when addressing apples and pears mixed in juices and nectars). This is not possible with the point estimate. In work example 4 the effect of introducing variability in different ways into the probabilistic exposure assessment was studied. This resulted in different outcomes. The beta assumption on distribution reflects best what happens in real life (residue levels of individual units can be lower, equal or higher than the corresponding composite sample level) and the maximum residue level to be sampled is bounded at an upper level. The meaning of different endpoints in the acute exposure distribution created by probabilistic assessment was addressed in work example 5. It was argued that when a certain critical percentile of exposure exceeds the acute reference dose (ARfD) a critical examination of the exposures contributing to this, by studying for example the highest ten exposure levels with their corresponding consumption and residue levels, would be very useful, giving the risk manager an insight in the reliability of the upper percentiles. Related to this it was argued that the uncertainty factors used to derive an ARfD should be considered in relation to the occurrence probability of the exposure exceeding the ARfD. When this probability is very low (e.g. lower than 10-4 or 10-5) one can argue whether such a risk is acceptable or not. In the last two work examples the stability of the tail of the distribution was examined. In work example 6 this was done by examining the effect of the number of iterations on the upper percentiles of the exposure distribution. The results showed that the number of iterations should be sufficient for making a confident estimation of a certain percentile. The number of iterations depends on the amount of consumption data and residue levels available, and on the percentile of interest. The more data available the more combinations will be possible of food consumption and residue levels, resulting in a need for a higher number of iterations to describe the exposure within a population adequately. Also more iterations will be necessary to reliably estimate higher percentiles of the exposure distribution (≥ P99.9). In work example 7 the stability of the tail was examined by studying the effect of the presence in the food consumption database of consumers with an extreme food consumption pattern (e.g. an infant consuming 2 kg of apples) or the presence of an outlier in the residue database. It was evident that an outlier (high consumption or residue level) affected the result of an exposure assessment depending on the magnitude of the European Journal of Nutrition & Food Safety, 4(1): 1-3, 2014 3 outlier compared to the other data present in the data set and on the largeness of the data set available. The effect was more evident on the P99.99 and maximum exposure level simulated than on the P99.9. It was argued that when outliers are present in the data, it is always important to visualise them (quality check on the data, for example related to reporting mistakes in the food consumption database), and to discuss the meaning of these outliers on a possible decision about the compound addressed. For example, it can be argued to what extent individuals with extreme dietary habits should be protected or that general advices concerning healthy eating habits should suffice. Conclusion: This report demonstrates clearly the potential of the probabilistic approach when dealing with acute dietary exposure assessment of pesticide residues compared to the current methodology used. The probabilistic approach to assess dietary exposure is also applicable to data from other countries, and, more importantly, others can be trained to perform risk assessments with the same model using their own data. Different aspects of an exposure assessment were addressed to help risk managers to understand better how exposures are calculated and to interpret the results of a probabilistic exposure assessment. The complete report can be downloaded for free from http://edepot.wur.nl/28647. Full report is also available as ‘Supplementary File’.

Dietary habits and exposure to pesticides in Dutch infants

Background: Children are known to have higher dietary exposure levels to pesticide residues than adults due to higher consumption levels per kilogram bodyweight. Also social concern exists on the effects of these residues in young children, who are growing rapidly. To assess whether a certain compound may pose a risk for young children, it is important to have consumption levels of the foods that may contain the compound of interest in this age group. In the Netherlands food consumption data are available of children from 1 year onwards. However, the majority of children (if not all) already consume solid foods before age 1. Aims: Performance of a food consumption survey among Dutch infants aged 8 12 months gathering data on food consumption levels, and measuring and estimating the dietary exposure to selected pesticide residues Approach: Food consumption data were collected using a 1-daydietary record method. Weighing scales were provided, so that the amount consumed could be quantified accurately. During the study also duplicate portions of all the foods consumed by the Grey Literature European Journal of Nutrition & Food Safety, 4(1): 4-5, 2014 5 children during the study day were collected. These duplicate portions were analysed for 19pesticides at the RIKILT Institute of Food Safety to estimate the real intake of pesticides. Results: In total 373 infants (186 girls and 187 boys) were included. The fruit most eaten by this age group was banana (58%), followed by apple (34%), pear (28%) and kiwi (20%). Carrot (18%) was the most favorite vegetable, followed by broccoli (9%) and green beans (8%). Potato was also consumed frequently (49%). Of all the fruits and vegetables consumed by the children large portion sizes (LPs) were calculated at the level of the raw agricultural commodity. These LPs can be used in the point estimate approach to assess the acute dietary intake of toxic pesticide residues in the field of pesticide regulation. The infant food consumption database can also be used for probabilistic modelling of acute dietary exposure. Of 250 infants the duplicate portions were analysed for 19 pesticides. Of these samples a significant percentage (11%) had a low exposure to one or more pesticides. None of the exposures exceeded the toxicological reference level (acceptable daily intake (ADI) or acute reference dose (ARfD)). Conclusion: This study among infants resulted in a first impression of actual intake levels of pesticide residues by this age group in the Netherlands via the diet, an estimate of the LPs of fruits and vegetables consumed by young children for use in the point estimate approach and a database with consumption levels useful for probabilistic exposure assessments. Furthermore the duplicate portions collected can be used for the analysis of other compounds that may affect the development of young growing children (e.g. deoxynivalenol (DON), acrylamide, heavy metals). The complete report can be downloaded for free from http://edepot.wur.nl/44408. Full report is also available as ‘Supplementary File’.

Harmonisation of food categorisation systems for dietary exposure assessments among European children

Within the European project called EXPOCHI (Individual Food Consumption Data and Exposure Assessment Studies for Children), 14 different European individual food consumption databases of children were used to conduct harmonised dietary exposure assessments for lead, chromium, selenium and food colours. For this, two food categorisation systems were developed to classify the food consumption data in such a way that these could be linked to occurrence data of the considered compounds. One system served for the exposure calculations of lead, chromium and selenium. The second system was developed for the exposure assessment of food colours. The food categories defined for the lead, chromium and selenium exposure calculations were used as a basis for the food colour categorisation, with adaptations to optimise the linkage with the food colour occurrence data. With this work, an initial impetus was given to make user-friendly food categorisation systems for contaminants and food colours applicable on a pan-European level. However, a set of difficulties were encountered in creating a common food categorisation system for 14 individual food consumption databases that differ in the type and number of foods coded and in level of detail provided about the consumed foods. The work done and the problems encountered in this project can be of interest for future projects in which food consumption data will be collected on a pan-European level and used for common exposure assessments.