Showing papers by "Christer Hogstrand published in 2019"

Guidance on harmonised methodologies for human health, animal health and ecological risk assessment of combined exposure to multiple chemicals

Abstract: This Guidance document describes harmonised risk assessment methodologies for combined exposure to multiple chemicals for all relevant areas within EFSA's remit, i.e. human health, animal health and ecological areas. First, a short review of the key terms, scientific basis for combined exposure risk assessment and approaches to assessing (eco)toxicology is given, including existing frameworks for these risk assessments. This background was evaluated, resulting in a harmonised framework for risk assessment of combined exposure to multiple chemicals. The framework is based on the risk assessment steps (problem formulation, exposure assessment, hazard identification and characterisation, and risk characterisation including uncertainty analysis), with tiered and stepwise approaches for both whole mixture approaches and component-based approaches. Specific considerations are given to component-based approaches including the grouping of chemicals into common assessment groups, the use of dose addition as a default assumption, approaches to integrate evidence of interactions and the refinement of assessment groups. Case studies are annexed in this guidance document to explore the feasibility and spectrum of applications of the proposed methods and approaches for human and animal health and ecological risk assessment. The Scientific Committee considers that this Guidance is fit for purpose for risk assessments of combined exposure to multiple chemicals and should be applied in all relevant areas of EFSA's work. Future work and research are recommended.

Scientific opinion on the risks for animal and human health related to the presence of quinolizidine alkaloids in feed and food, in particular in lupins and lupin-derived products.

Abstract: The European Commission asked EFSA for a scientific opinion on the risks for animal and human health related to the presence of quinolizidine alkaloids (QAs) in feed and food. This risk assessment is limited to QAs occurring in Lupinus species/varieties relevant for animal and human consumption in Europe (i.e. Lupinus albus L., Lupinus angustifolius L., Lupinus luteus L. and Lupinus mutabilis Sweet). Information on the toxicity of QAs in animals and humans is limited. Following acute exposure to sparteine (reference compound), anticholinergic effects and changes in cardiac electric conductivity are considered to be critical for human hazard characterisation. The CONTAM Panel used a margin of exposure (MOE) approach identifying a lowest single oral effective dose of 0.16 mg sparteine/kg body weight as reference point to characterise the risk following acute exposure. No reference point could be identified to characterise the risk of chronic exposure. Because of similar modes of action for QAs, the CONTAM Panel used a group approach assuming dose additivity. For food, the highest mean concentration of Total QAs (TotQAs) (i.e. the 6 most abundant QAs) was found in lupin seed samples classified as ‘Lupins (dry) and similar-’. Due to the limited data on occurrence and consumption, dietary exposure was calculated for some specific scenarios and no full human health risk characterisation was possible. The calculated margin of exposures (MOEs) may indicate a risk for some consumers. For example, when lupin seeds are consumed without a debittering step, or as debittered lupin seeds high in QA content and when ‘lupin-based meat imitates’ are consumed. For horses, companion and farm animals, other than salmonids, the available database on adverse effects was too limited to identify no-observed-adverse-effect levels and/or lowest-observed-adverse-effect levels and no risk characterisation was possible. For salmonids, the CONTAM Panel considers the risk for adverse effects to be low.

Evaluation of the health risks related to the presence of cyanogenic glycosides in foods other than raw apricot kernels

Abstract: In 2016, the EFSA Panel on Contaminants in the Food Chain (CONTAM) published a scientific opinion on the acute health risks related to the presence of cyanogenic glycosides (CNGs) in raw apricot kernels in which an acute reference dose (ARfD) of 20 μg/kg body weight (bw) was established for cyanide (CN). In the present opinion, the CONTAM Panel concluded that this ARfD is applicable for acute effects of CN regardless the dietary source. To account for differences in cyanide bioavailability after ingestion of certain food items, specific factors were used. Estimated mean acute dietary exposures to cyanide from foods containing CNGs did not exceed the ARfD in any age group. At the 95th percentile, the ARfD was exceeded up to about 2.5-fold in some surveys for children and adolescent age groups. The main contributors to exposures were biscuits, juice or nectar and pastries and cakes that could potentially contain CNGs. Taking into account the conservatism in the exposure assessment and in derivation of the ARfD, it is unlikely that this estimated exceedance would result in adverse effects. The limited data from animal and human studies do not allow the derivation of a chronic health-based guidance value (HBGV) for cyanide, and thus, chronic risks could not be assessed.

The Use of Molecular Descriptors To Model Pharmaceutical Uptake by a Fish Primary Gill Cell Culture Epithelium.

Abstract: Modeling approaches such as quantitative structure–activity relationships (QSARs) use molecular descriptors to predict the bioavailable properties of a compound in biota. However, these models have mainly been derived based on empirical data for lipophilic neutral compounds and may not predict the uptake of ionizable compounds. The majority of pharmaceuticals are ionizable, and freshwaters can have a range of pH values that affect speciation. In this study, we assessed the uptake of 10 pharmaceuticals (acetazolamide, beclomethasone, carbamazepine, diclofenac, gemfibrozil, ibuprofen, ketoprofen, norethindrone, propranolol, and warfarin) with differing modes of action and physicochemical properties (pKa, log S, log D, log Kow, molecular weight (MW), and polar surface area (PSA)) by an in vitro primary fish gill cell culture system (FIGCS) for 24 h in artificial freshwater. Principal component analysis (PCA) and partial least-squares (PLS) regression was used to determine the molecular descriptors that influ...

ZnT8 Haploinsufficiency Impacts MIN6 Cell Zinc Content and β-Cell Phenotype via ZIP-ZnT8 Coregulation.

Abstract: The zinc transporter ZnT8 (SLC30A8) localises to insulin secretory granules of β-cells where it facilitates zinc uptake for insulin crystallisation. ZnT8 abundance has been linked to β-cell survival and functional phenotype. However, the consequences of ZnT8 haploinsufficiency for β-cell zinc trafficking and function remain unclear. Since investigations in human populations have shown SLC30A8 truncating polymorphisms to decrease the risk of developing Type 2 Diabetes, we hypothesised that ZnT8 haploinsufficiency would improve β-cell function and maintain the endocrine phenotype. We used CRISPR/Cas9 technology to generate ZnT8 haploinsufficient mouse MIN6 β-cells and showed that ZnT8 haploinsufficiency is associated with downregulation of mRNAs for Slc39a8 and Slc39a14, which encode for the zinc importers, Znt- and Irt-related proteins 8 (ZIP8) and 14 (ZIP14), and with lowered total cellular zinc content. ZnT8 haploinsufficiency disrupts expression of a distinct array of important β-cell markers, decreases cellular proliferation via mitogen-activated protein (MAP) kinase cascades and downregulates insulin gene expression. Thus, ZnT8 cooperates with zinc importers of the ZIP family to maintain β-cell zinc homeostasis. In contrast to the hypothesis, lowered ZnT8 expression reduces MIN6 cell survival by affecting zinc-dependent transcription factors that control the β-cell phenotype.

Evaluation of calcium lignosulfonate as a acceptable previous cargo for edible fats and oils.

Abstract: Shipping of edible fats and oils into Europe is permitted in bulk tanks, provided that the previous cargo is included in a positive list. The European Commission requested EFSA to evaluate the acceptability of calcium lignosulfonate as previous cargo for fats and oils. The evaluation was based on the same criteria as those used for the evaluation of the substances currently on the list in the Annex to Commission Directive 96/3/EC as a acceptable previous cargoes for edible fats and oils. In 2017, the EFSA Panel on Contaminants in the Food Chain (CONTAM Panel) concluded that calcium lignosulfonate did not meet the acceptability criteria, due to uncertainties as regards the composition and toxicity of its low-molecular weight fraction (LMWF) below 1,000 Da. In the current evaluation, new information, showing lack of genotoxicity of the LMWF isolated from a technical grade of calcium lignosulfonate was provided. Due to uncertainties regarding the presence of lignosulfonate components below 200 Da in this LMWF tested for genotoxicity, the CONTAM Panel concluded that the information provided was insufficient to assess the acceptability of calcium lignosulfonate as previous cargo. The Panel recommends a better analysis of the LMWF and a new genotoxicity test using this LMWF, including components < 200 Da, and evidence that the tested material is representative of the LMWF in products intended to be shipped as previous cargo for edible fat and oils.