Natural and synthetic organic compounds in the environment - a symposium report.

In March 2000, an international two-day symposium was organized in Noordwijkerhout, The Netherlands, on 'Natural and synthetic organic compounds in the environment'. The emphasis of the symposium was on the following classes of compounds: polycyclic aromatic hydrocarbons, xeno-estrogens, phyto-estrogens, and veterinary drugs. Sources, environmental distribution, uptake, biotransformation and toxic effects from the molecular to the population level were discussed. Other important aspects were the development of biomarkers, analytical methods, bioassays, molecular modelling and other research tools. Finally, the implications of the findings for government policies were discussed. In this paper, a summary is given of the most important facts and views presented at the symposium. © 2001 Elsevier Science B.V. All rights reserved

Current approaches and challenges of sample preparation procedures for the safety assessment of paper and cardboard food contact materials: A comprehensive review

In the European Union (EU), Regulation (EC) 1935/2004 provides a harmonized legal EU framework and sets out the general principles for safety and inertness for all Food Contact Materials (FCMs) and Food Contact Articles. From a food safety point of view, however, specific EU legislation for paper and cardboard FCMs is lacking, while at Member State level, national legislation differs among countries. More than 11,000 chemicals have been identified in all types of FCMs, most of them without any information on toxicity or migration potential from FCM to food. The present review shows a wide variability of protocols, approaches, and conditions used in scientific studies, which are difficult to compare. In this regard, procedures and conditions laid down in EU legislation for plastics and European Standards (EN protocols) may serve as a good basis for the future sample preparation procedures in the framework of paper and cardboard FCMs safety assessment. Challenges on sample preparation procedures are presented involving the interlinked steps of sample preparation, conditions used and their impact in chemical analysis and in vitro bioassay testing. Currently, there is no general consensus on the criteria for structuring, evaluating, and tuning sample preparation procedures for paper and cardboard FCMs. For this purpose, a set of modified criteria and a decision tree are proposed based on the literature. Along this, mass transfer processes occurring in paper and cardboard FCMs and parameters affecting chemical migration need to be accounted for prior to reaching general consensus on criteria for sample preparation procedures

The impact of legacy and novel perfluoroalkyl substances on human cytochrome P450: An in vitro study on the inhibitory potential and underlying mechanisms

Per- and polyfluomalkyl substances (PFASs) are a group of synthetic compounds with a wide range of industrial applications. PFOA and PFOS have been the most extensively studied and have been associated with hepatotoxicity. Recently, the interaction with cytochrome P450 (CYP) has been proposed as a potential key molecular event leading to PFAS-induced hepatotoxicity. In the present study, we aimed to determine a structure-activity relationship between thirteen PFASs and their inhibitory potential on the activities of four CYPs (CYP2E1, CYP2D6, CYP3A4 and CYP2C19).The influence of PFASs (5-3200 mu M) on CYP enzyme activities was measured using the Vivid (R) P450 metabolism assays. Using the same assays, Michaelis-Menten saturation curves were determined to explore the type of PFAS-induced CYP inhibition.Most PFASs were capable of inhibiting activity of the tested CYPs, as shown by their IC50 values. CYP2E1 is particularly inhibited by 3:1 FTOH, PFOA, and PFOS, whereas CYP2D6 is inhibited by PFHxS, PFHpA, PFOA, PFOS, PFNA, and PFDA. Additionally, CYP3A4 is most strongly inhibited by PFHxS, PFOA, PFOS, PFNA, and PFDA. Finally, CYP2C19 is inhibited by PFBS, PFHxS, PFHpA, PFOA, PFOS, PFNA, and PFDA. Interestingly, PFHxA and PFHxS induced an increase in CYP2E1 activity, whereas 4:2 FTOH strongly induced CYP2D6 activity. The mechanism of inhibition of CYPs by PFASs differed per CYP isoenzyme. CYP3A4 was competitively inhibited by PFBS, PFHxS, PFOS, PFNA and PFDA and non-competitively by PFOA. Additionally, CYP2C19 was competitively inhibited by PFHxA, PFOS and PFNA, whereas PFBS and PFHxS induced a mixed inhibition. Inhibition of CYP2C19 by PFHpA was atypical with an increased Vmax and a decreased Km. Finally, PFHxS competitively inhibited CYP2D6, whereas PFBS, PFOA, PFOS, PFDA and PFNA induced an atypical inhibition.Our results show that CYP inhibition by PFASs appears to be structure-dependent as well as CYP dependent. Inhibition of CYP2D6, CYP2C19 and CYP3A4 increased with increasing chain-lengths between six and nine carbons. The PFTOHs were only able to inhibit CYP2E1 and did not affect any of the other CYPS. Some PFASs remarkably induced the enzyme activity of CYPs. These results indicate that in addition to PFOA and PFOS, multiple novel PFASs may alter drug metabolism by the interference with CYPs

A vision on the 'foodture' role of dietary exposure sciences in the interplay between food safety and nutrition

Background: In this paper, the European chapter of the International Society for Exposure Science (ISES Europe) provides a vision on how dietary exposure sciences can contribute to address the challenges in the field of food safety and nutrition due to changes in food systems by answering the following question: How can we assess timely and accurately changes in dietary exposure to hazardous chemicals (and mixtures thereof) or intake of nutrients due to changes in food production, food consumption and food composition? Scope and approach: We first describe the current role of dietary exposure sciences and the instruments that are being used to assess dietary exposure in food safety and nutrition. This is followed by an analysis of current changes and developments, primarily at the European level, relevant for food safety and nutrition. This results in a list of identified challenges for dietary exposure sciences. Key findings and conclusions: We thus focus on the timely and accurate assessment of the impact of changes and developments on consumer's and public health, from the perspective of dietary exposure sciences. This includes making better use of chemical analysis, dietary exposure assessment and human biomonitoring, providing increased insight in food composition and nutrients, taking into account the impact of new technologies on human exposure, and making better use of risk-benefit assessment

Possible Adverse Effects of Food Additive E171 (Titanium Dioxide) Related to Particle Specific Human Toxicity, Including the Immune System

Titanium dioxide (TiO2) is used as a food additive (E171) and can be found in sauces, icings, and chewing gums, as well as in personal care products such as toothpaste and pharmaceutical tablets. Along with the ubiquitous presence of TiO2 and recent insights into its potentially hazardous properties, there are concerns about its application in commercially available products. Especially the nano-sized particle fraction (<100 nm) of TiO2 warrants a more detailed evaluation of potential adverse health effects after ingestion. A workshop organized by the Dutch Office for Risk Assessment and Research (BuRO) identified uncertainties and knowledge gaps regarding the gastrointestinal absorption of TiO2, its distribution, the potential for accumulation, and induction of adverse health effects such as inflammation, DNA damage, and tumor promotion. This review aims to identify and evaluate recent toxicological studies on food-grade TiO2 and nano-sized TiO2 in ex-vivo, in-vitro, and in-vivo experiments along the gastrointestinal route, and to postulate an Adverse Outcome Pathway (AOP) following ingestion. Additionally, this review summarizes recommendations and outcomes of the expert meeting held by the BuRO in 2018, in order to contribute to the hazard identification and risk assessment process of ingested TiO2