Gerhard Heinemeyer

Toxicology and risk assessment of coumarin: Focus on human data

Coumarin is a secondary phytochemical with hepatotoxic and carcinogenic properties. For the carcinogenic effect, a genotoxic mechanism was considered possible, but was discounted by the European Food Safety Authority in 2004 based on new evidence. This allowed the derivation of a tolerable daily intake (TDI) for the first time, and a value of 0.1 mg/kg body weight was arrived at based on animal hepatotoxicity data. However, clinical data on hepatotoxicity from patients treated with coumarin as medicinal drug is also available. This data revealed a subgroup of the human population being more susceptible for the hepatotoxic effect than the animal species investigated. The cause of the high susceptibility is currently unknown; possible mechanisms are discussed. Using the human data, a TDI of 0.1 mg/kg body weight was derived, confirming that of the European Food Safety Authority. Nutritional exposure may be considerably, and is mainly due to use of cassia cinnamon, which is a popular spice especially, used for cookies and sweet dishes. To estimate exposure to coumarin during the Christmas season in Germany, a telephone survey was performed with more than 1000 randomly selected persons. Heavy consumers of cassia cinnamon may reach a daily coumarin intake corresponding to the TDI.

Perfluorinated alkylated substances in vegetables collected in four European countries; occurrence and human exposure estimations

The human diet is recognised as one possible major exposure route to the overall perfluorinated alkylated substances (PFAS) burden of the human population, resulting directly from contamination of dietary food items, as well as migration of PFAS from food packaging or cookware. Most European countries carry out national monitoring programs (food basket studies) to monitor contamination with pollutants. Usually, for PFASs, non-coordinated approaches are used in Europe, since food basket studies are mainly carried out by national authorities following national requirements and questions, making comparisons between different countries difficult. A harmonised sampling campaign collecting similar food items in a uniform procedure enabling direct comparison between different regions in Europe was designed. We selected four countries (Belgium, Czech Republic, Italy and Norway), representing the four regions of Europe: West, East, South and North. In spring 2010 and 2011, 20 different types of vegetables were sampled in Belgium, Czech Republic, Italy and Norway. Perfluorinated carboxylic acids (PFCAs) were the main group of detected PFASs, with perfluorinated octanoic acid (PFOA) as the most abundant PFCA (with exception of samples from Czech Republic), followed by perfluorinated hexanoic acid and perfluorinated nonanoic acid. Dietary intake estimates for PFOA show only low human exposure due to vegetable consumption for adults and children, mostly governed by high intake of potatoes.

Estimation of dietary intake of bis(2-ethylhexyl)phthalate (DEHP) by consumption of food in the German population ☆

In the study presented here, we evaluated the exposure of the German population aged 14-80 years to bis(2-ethylhexyl)phthalate (DEHP) from consumption of food by means of deterministic and probabilistic estimations. The study was performed on the basis of an extensive review of literature from around the world reporting measured data on DEHP in food, as well as official German food control data. Only data from individual measurements were considered and used for fitting of distributions. A wide range of concentrations in non-representative samples are reported in the literature. On the basis of the available DEHP concentration data, 37 food categories were characterized which covered all major food classes. Food consumption data were taken from the diet history interviews of the German National Nutrition Survey II (Nationale Verzehrsstudie II) which was performed in 2005/2006 in a representative study population of 15,371 and is the most recent data source of this kind in Germany. Average DEHP intake was estimated deterministically using data on measured concentrations in food (medians and means) and food consumption (means). A total dietary exposure to DEHP of 3.6 (median based) and 9.3μg/kg of BW per day (based on mean values) was estimated deterministically. In addition, distributions of both concentrations and consumption figures were fitted using the @RISK best fit tool for further probabilistic estimations. This approach resulted in estimates within the same range: the estimated median DEHP intake in the whole population (both non-consumers and consumers of the foods considered) was 10.2, the arithmetic mean 14.0 and the 95th percentile 28.6μg/kg of BW per day. The respective estimates for consumers only were 12.4, 18.7 and 36.5μg/kg of BW per day. These results demonstrate that the probabilistic approach is able to estimate broader ranges of exposure even when using data representing an average intake. Moreover, it reflects the uncertainties of the estimation due to insufficient analytical data on concentrations of DEHP in food.

Regulatory toxicology in the twenty-first century: challenges, perspectives and possible solutions

Abstract The advent of new testing systems and “omics”-technologies has left regulatory toxicology facing one of the biggest challenges for decades. That is the question whether and how these methods can be used for regulatory purposes. The new methods undoubtedly enable regulators to address important open questions of toxicology such as species-specific toxicity, mixture toxicity, low-dose effects, endocrine effects or nanotoxicology, while promising faster and more efficient toxicity testing with the use of less animals. Consequently, the respective assays, methods and testing strategies are subject of several research programs worldwide. On the other hand, the practical application of such tests for regulatory purposes is a matter of ongoing debate. This document summarizes key aspects of this debate in the light of the European “regulatory status quo”, while elucidating new perspectives for regulatory toxicity testing.

Dioxin and dl-PCB exposure from food: the German LExUKon project

Polychlorinated dibenzo-p-dioxin and -furan (PCDD/F) and dioxin-like polychlorinated biphenyl (dl-PCB) exposure from food were estimated using new food consumption data from the recent German food consumption survey (Nationale Verzehrsstudie II – NVS II). Based on these comprehensive data, information on the consumption of 545 individual food items by the German population was derived. Concentrations of dioxin-like compounds in food were compiled from the German Food Monitoring Programme (GFMP), the German Dioxin Database, other German authority programmes, European countries’ authority programmes and the published literature covering the years 2000–2010. By multiplication with consumption data, estimates of intake from food were determined. The main food groups contributing most to the intake of the general public are dairy products (including milk), meat and fish (including seafood), followed – due to high consumption – by the main group vegetables. The combined intake of PCDD/F and dl-PCB (as toxic equivalents – TEQ) from food was estimated to be 2.11/1.53 pg kg–1 bw and day and 3.56/2.85 pg kg–1 bw and day (upper/lower bound) for average and high-end consumers, respectively. The estimated intake of average consumers is close to a reference value derived by the Scientific Committee on Food in 2001. Uncertainties in these estimates pertain to the influence of values below the limit of quantification (upper/lower bound ratio) and some foods not considered due to the lack of contamination data.

Cadmium exposure from food: the German LExUKon project

Cadmium is a very toxic contaminant with food being the major source of exposure for the general public. The second German food consumption survey (Nationale Verzehrsstudie II – NVS II) with about 20 000 participants (15 371 for dietary history interviews used for this study) allowed for an updated exposure assessment for the German population. Based on these comprehensive data, information on the consumption of 545 individual food items by the German population was generated. Cadmium concentrations in food were compiled from the German food monitoring programme, European countries’ authority programmes and the published literature, covering the years from 1993 to 2008, and were multiplied with consumption data to obtain estimates of cadmium intake from food. Consumption-weighted mean cadmium concentrations per main food group were highest for cereals, followed by oily seeds & fruits, and vegetables. Due to both high consumption and considerable occurrence of cadmium, cereals and vegetables contributed most to the intake of the general public, followed by the main groups beverages, fruits & nuts, and dairy products (including milk). Cadmium intake from food was estimated to be 1.46 and 2.35 µg kg–1 bw week–1 for average and high-end consumers, respectively. This corresponds to 58% for average and 95% for high-end consumers, respectively, of a reference value derived from a recent health risk evaluation performed by EFSA, using the benchmark approach. Uncertainties in these estimates pertain to the influence of values below the limit of quantification and some foods not considered due to lacking occurrence data. In conclusion, the estimated cadmium intake of the German population from food is still close to health-based reference values. Further efforts to reduce cadmium intake are required.

German database on the occurrence of food additives: application for intake estimation of five food colours for toddlers and children

To get a more realistic estimation of food additive intake for toddlers and children, a German database on the occurrence of food additives was created. It uses consumption data of two recent national nutrition surveys for toddlers and children in combination with qualitative information of food additive occurrence in the consumed food. The information on food additive occurrence is based on food labelling. A categorisation system was developed according to regulations to classify the foods consumed and to identify possible food additive use in the food groups. Two natural (E120, E160b) and three artificial food colours (E110, E124, E129) were chosen for an assessment of food additive intake. The percentage of food items containing one of the chosen food colours was calculated for every food group and the food groups with most items containing the additive were identified. Intake estimations were performed based on maximum permitted-use levels (MPLs). Firstly, additive use was assumed in all foods consumed (tier 2); and secondly, food additive use was assumed only for those items where labelling confirmed the use and for all foods with no labelling available (tier 2b). Intake estimations were then compared with the ADI. Most food items with at least one of the food colours were found in the food groups confectionary, desserts, fermented milk products, flavoured drinks and breakfast cereals. The tier 2b approach provided more realistic estimations, which were always below those of the tier 2 approach and below the ADI for mean exposure. Exposure for high-level consumers exceeded the ADI for two of the food additives in tier 2b. Keeping in mind that the database is only mirroring the current situation, it provides a good possibility to refine the estimation of food additive intake for toddlers and children in Germany. Graphical Abstract

Concepts of exposure analysis for consumer risk assessment

Risk assessment of health hazards introduced by chemicals is based on two basic elements: (i) exposure assessment and (ii) hazard identification. Risk characterisation is performed by comparing the exposure level with the NOAEL to establish the margin of exposure. If this margin is too narrow, then a concern is assumed which requires additional analyses, e.g. by refining data, or by performing additional studies. Assessment of risks by inhalation normally takes into consideration the concentrations in air that lead to toxic effects which can be compared by concentrations revealed from model assessments of measurements of concentrations of substances in room air. The key issues for exposure assessment can be separated into three parts: (i) the characterisation of the exposure scenario, (ii) the derivation of an adequate exposure model and (iii) the selection of model parameters, i.e. the determinants of the exposure. Particularly, complex evaluations need high efforts to retrieve and provide information and data. Therefore, exposure analysis should follow a tiered approach, starting with simple assumptions for exposure scenarios and models, as well as default parameters. The refinement aims at narrowing the assessment closely to reality. Therefore, due to different regulations, this approach avoids unnecessary investigations of data. The consideration of variability and uncertainty is getting more and more important in exposure evaluations, and some concepts have been recently published. The main objective of an uncertainty analysis (UA) in exposure assessment is to identify the sources of uncertainty thus providing support for decision makers which parameter is, e.g. the most critical one in an exposure scenario. An UA gives the assessor the opportunity to re-evaluate the scenario, model approaches and parameters of the analysis, and to consider their influence in the overall analysis by means of a tiered approach.

Lead exposure from food: the German LExUKon project

Lead is a highly toxic contaminant with food being the major source of exposure for the general public. The second German food consumption survey (Nationale Verzehrsstudie II – NVS II) with about 20 000 participants (15 371 for dietary history interviews used for this study) allowed for an updated exposure assessment for the German population. Based on these comprehensive data, information on consumption of 545 individual food items by the German population was generated. Lead concentrations in food were compiled from the German food monitoring programme, European countries’ authority programmes and the published literature, covering the years from 2000 to 2009, and were multiplied with consumption data to obtain estimates of lead intake from food. Average lead concentrations per main food group were highest for meat (including offal), followed by fish (including seafood), vegetables and cereals. Due to high consumption, beverages contributed most to the intake of the general public, followed by main groups vegetables, fruits & nuts and cereals. Lead intake from food was estimated to be 0.53 and 0.72 µg kg–1 bw and day for average and high-end consumers, respectively. This is close to (average consumers) respectively above (high-end consumers) a reference value derived from a recent health risk evaluation performed by EFSA, using the benchmark approach. Uncertainties in these estimates pertain to the influence of values below the limit of quantification and some foods not considered due to lacking occurrence data. In conclusion, the estimated lead intake of the German population from food is still close to health-based reference values. Further efforts to reduce lead intake are required.

Risikomanagement bei Lampenölvergiftungen in Deutschland

Seit 1954 wird in der wissenschaftlichen Literatur regelmiifgig und zunehmend a chemische Pneumonien und auch Todesfiille bei Petroleumdestillatingestionen ira Kindesalter berichtet (Ubers. 1). In den USA sind diese UnfS.lle sogar der Hauptgrund fa Krankenhausaufnahmen durch Haushaltschemikalien mit schwerwiegenden Gesundheitsst6rungen ira Kindesalter. Vergleichbare Erfahrungen gibt es auch in Afrika, Asien und Europa.