Marco J. Zeilmaker

Levels of perfluorinated compounds in food and dietary intake of PFOS and PFOA in the Netherlands.

This study presents concentrations of perfluorinated compounds in food and the dietary intake of perfluorooctane sulfonate (PFOS) and perfluorooctanoate (PFOA) in The Netherlands. The concentrations of perfluorinated compounds in food were analyzed in pooled samples of foodstuffs randomly purchased in several Dutch retail store chains with nation-wide coverage. The concentrations analyzed for PFOS and PFOA were used to assess the exposure to these compounds in The Netherlands. As concentrations in drinking water in The Netherlands were missing for these compounds, conservative default concentrations of 7 pg/g for PFOS and 9 pg/g for PFOA, as reported by European Food Safety Authority, were used in the exposure assessment. In food, 6 out of 14 analyzed perfluorinated compounds could be quantified in the majority of the food categories (perfluoroheptanoic acid (PFHpA), PFOA, perfluorononanoic acid (PFNA), perfluorodecanoic acid (PFDA), perfluoro-1-hexanesulfonate (PFHxS), and PFOS). The highest concentration of the sum of these six compounds was found in crustaceans (825 pg/g product, PFOS: 582 pg/g product) and in lean fish (481 pg/g product, PFOS: 308 pg/g product). Lower concentrations were found in beef, fatty fish, flour, butter, eggs, and cheese (concentrations between 20 and 100 pg/g product; PFOS, 29-82 pg/g product) and milk, pork, bakery products, chicken, vegetable, and industrial oils (concentration lower than 10 pg/g product; PFOS not detected). The median long-term intake for PFOS was 0.3 ng/kg bw/day and for PFOA 0.2 ng/kg bw/day. The corresponding high level intakes (99th percentile) were 0.6 and 0.5 ng/kg bw/day, respectively. These intakes were well below the tolerable daily intake values of both compounds (PFOS, 150 ng/kg bw/day; PFOA, 1500 ng/kg bw/day). The intake calculations quantified the contribution of drinking water to the PFOS and PFOA intake in The Netherlands. Important contributors of PFOA intake were vegetables/fruit and flour. Milk, beef, and lean fish were important contributors of PFOS intake.

Dietary exposure to dioxins and dioxin-like PCBs in The Netherlands anno 2004

In this study, representative occurrence data for PCDD/Fs and dioxin-like PCBs in food were obtained and used to estimate dietary exposure of the Dutch population. Food composite samples were analyzed as well as single fish and vegetables samples. Total dioxin concentrations in animal products ranged from 0.05 pg TEQ/g product in poultry to 2.5 pg TEQ/g product (using TEF(2006)) in fish (shrimp), with 0.12pg TEQ/g product being the lowest concentrations measured in fish (tuna). In vegetable products, concentrations ranged from 0.00002 pg TEQ/g product (white kale) to 0.19 pg TEQ/g (oils and fats). A long-term dietary exposure distribution was calculated using Monte Carlo Risk Assessment software. The lower bound median exposure of the Dutch population to PCDD/Fs and dioxin-like PCBs was estimated at 0.8 pg WHO-TEQ/kgbw/d, half of which were dioxin-like PCBs. Dairy was the main source (38%) due to its high consumption. Time-trend analysis shows that the exposure to dioxins has further decreased by 35% over the past five years. This is due to lower levels of dioxin-like compounds in most of the foods, mainly influenced by lower levels in meat and milk. The use of the new TEFs gives an exposure reduction of 10% with respect to TEF(1998). Still, 4% of the Dutch population exceeds the exposure limit of 14 pg/kgbw/week as set by the EU.

Fish, contaminants and human health: Quantifying and weighing benefits and risks

This paper describes a quantitative risk-benefit assessment of fish consumption. We compare the net health effect expressed in DALYs of two scenarios. The reference scenario is the current fish intake of the Dutch population, which is less than what is recommended by the health authorities. The alternative scenario describes the health effects if the population consumes 200g of fish per week, which is close to the recommendation. All health effects due to fish consumption for which there is convincing evidence are incorporated in the assessment. The QALIBRA software (www.qalibra.eu) is used to simulate the two scenarios. The results show there is a net benefit for the population if it consumes 200g of fish each week.

An improved model to predict physiologically based model parameters and their inter-individual variability from anthropometry.

We developed a population physiology model, physB, which provides a statistical description of the physiological characteristics in the human population, in terms of the physiological parameters that are needed in physiologically based pharmacokinetic modelling. The model predicts individual organ weights, blood flows and some respiratory parameters from anthropometric properties (body height and weight, age and gender). It draws on two existing models, PK-Pop and P3M, but various changes and improvements were made. The conceptual differences among the three models are discussed and they are quantitatively compared by running all three models for various specific combinations of anthropometric properties.

Kaolinic clay derived PCDD/Fs in the feed chain from a sorting process for potatoes

At the end of 2004, during a routine monitoring project, high levels of PCDDs in milk from two farms were found. Using a bioassay and the congener patterns obtained by HRGC/HRMS, the source was traced back to the use of kaolinic clay for sorting potatoes in a production process of French fries. Rest products, especially peelings after scrubbing, were used as feed for dairy cows. Levels of PCCD/Fs in this product amounted to 44 ng WHO(1998)-TEQ kg(-1) (88% dw). The maximum level observed in milk was 20 pg WHO(1998)-TEQ g(-1) fat. A Physiologically Based PharmacoKinetic (PB-PK) model was used to model three data obtained before eliminating the source in order to estimate the starting time of the contamination of the cows, the steady-state level after prolonged contamination and the kinetics of the decrease in the levels after removal of the source. Samples of milk were continuously collected for several months showing a decrease to levels below the product limit of 3 pg WHO(1998)-TEQ g(-1) fat within 2 months, in excellent agreement with the decrease predicted by the PB-PK model. Different batches of clay were sampled and analysed, showing varying levels of especially PCDDs. All clays were confirmed to be kaolinic clay using X-ray analysis. Other by-products used for animal feed were also contaminated and led to precautionary measures at a few hundred farms, especially pig farms. However, levels in other animal derived products like pig meat did not exceed the product limits.

Fish consumption during child bearing age: a quantitative risk-benefit analysis on neurodevelopment.

The fish ingredient N3-docosahexaenoic acid 22:6 n-3 (DHA) stimulates brain development. On the other hand methylmercury (MeHg) in fish disturbs the developing central nervous system. In this Context the IQ score in children is considered as an aggregate measure of in utero brain development. To determine the effect of DHA exposure on prenatal neurodevelopment the maternal DHA intake during pregnancy was compared with its epidemiologically observed effect on the IQ score of children. For MeHg the maternal intake was converted into its accumulation in the maternal body. The maternal body burden then was compared with its epidemiologically observed relationship with the IQ score. Taking the MeHg and DHA content of 33 fish species the net effect of these compounds on the IQ score was quantified. For most fish species the adverse effect of MeHg on the IQ score exceeded the beneficial effect of DHA. In the case of long-living predators a negative effect up to 10 points on the IQ score was found. The results of this study indicate that food interventions aiming at the beneficial effects of fish consumption should focus on fish species with a high DHA content, while avoiding fish species with a high MeHg content.

A simple steady-state model for carry-over of aflatoxins from feed to cow's milk.

A simple steady-state model is derived from two kinetic one-compartment models for the disposition of aflatoxin B1 (AFB1) and aflatoxin M1 (AFM1) in the lactating cow. The model relates daily intake of AFB1 in feed of dairy cattle and the cows lactation status to resulting concentrations of AFM1 in milk. Moreover, assuming a linear relationship between the cows lactation status and feed intake, the model relates daily milk production and AFB1 concentration in total feed to AFM1 levels in milk. The model explains similar experimental outcomes from different investigations into carry-over of aflatoxins from feed to milk. Although it is difficult to set a permanent limit for AFB1 in feed, the European Union (EU) limit of 5 µg AFB1 kg−1 concentrate has proved, thus far, to be an appropriate level in preventing the EU limit of 0.05 µg AFM1 kg−1 milk being exceeded.

Risk Assessment of N-nitrosodimethylamine Formed Endogenously after Fish-with-Vegetable Meals

The consumption of fish and nitrate-rich vegetables may lead to the formation of the genotoxic carcinogen N-nitrosodimethylamine (NDMA) in the stomach. To assess human cancer risk associated with this formation, a dynamic in vitro gastrointestinal model was used to simulate NDMA formation in the stomach after a fish + vegetable meal. The experimental results were combined with statistical modeling of Dutch food consumption data resulting in predicted exposures to endogenously formed NDMA in the population. The 95th percentile of the long-term exposure distribution was around 4 ng/kg-bw in young children and 0.4 ng/kg-bw in adults. By comparing this exposure with the Benchmark Dose Lower bound (BMDL) 10 for liver cancer in a chronic carcinogenicity study, a chronic margin of exposure (MOE) was calculated of 7000 and 73,000 for young children and adults. Furthermore, the long-term exposure distribution was combined with a dose-response analysis of the liver cancer incidence data to obtain a cancer risk distribution for the human population. The 95th percentile of that distribution was 6 x 10(-6) extra risk for 5-year-old children and 8 x 10(-7) for adults. The liver cancer data allowed for the analysis of the relationship between tumor incidence and time to tumor. For an extra risk of 10(-6), the decrease in time to tumor was conservatively estimated at 3.8 min in the rat, equivalent to 0.1 days in humans. We also combined acute exposure estimates with the BMDL10 from an acute carcinogenicity study for NDMA, resulting in an acute MOE of 110,000. We conclude that the combined consumption of fish and nitrate-rich vegetables appears to lead to marginal increases of additional cancer risk.

Qalibra: a general model for food risk-benefit assessment that quantifies variability and uncertainty.

The EU project BRAFO proposed a framework for risk-benefit assessment of foods, or changes in diet, that present both potential risks and potential benefits to consumers (Hoekstra et al., 2012a). In higher tiers of the BRAFO framework, risks and benefits are integrated quantitatively to estimate net health impact measured in DALYs or QALYs (disability- or quality-adjusted life years). This paper describes a general model that was developed by a second EU project, Qalibra, to assist users in conducting these assessments. Its flexible design makes it applicable to a wide range of dietary questions involving different nutrients, contaminants and health effects. Account can be taken of variation between consumers in their diets and also other characteristics relevant to the estimation of risk and benefit, such as body weight, gender and age. Uncertainty in any input parameter may be quantified probabilistically, using probability distributions, or deterministically by repeating the assessment with alternative assumptions. Uncertainties that are not quantified should be evaluated qualitatively. Outputs produced by the model are illustrated using results from a simple assessment of fish consumption. More detailed case studies on oily fish and phytosterols are presented in companion papers. The model can be accessed as web-based software at www.qalibra.eu.

Polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) and biphenyls (PCBs) in home-produced eggs.

Home produced eggs from 62 addresses in the Netherlands were investigated for the levels of polychlorinated dibenzo-p-dioxins, dibenzofurans (PCDD/Fs) and biphenyls (PCBs), both dioxin-like (dl) and non-dioxin-like (ndl). Compared to commercial eggs, levels were relatively high with a median of 4.6 pg TEQ g(-1) fat for the sum of PCDD/Fs and dl-PCBs, and a highest level of 18.9 pg TEQ g(-1) fat. A number of samples showed clearly elevated ndl-PCB levels with a median of 13 ng g(-1) fat and a highest level of 80 ng g(-1) fat. There were no clear regional differences, even though part of the samples were derived from the rather industrial Rotterdam/Rijnmond area. Based on the congener patterns, former backyard burning of waste seems the most likely source for most eggs, with two exceptions where other sources contributed to the contamination. Similar is true for the ndl-PCBs. The study shows that average levels are about ten-fold higher than commercial eggs and may substantially contribute to the intake of PCDD/Fs and dl-PCBs by consumers. Intervention measures to reduce the intake of these contaminants by laying hens are advised.