Bioavailability of plasticizers in dust and food after oral administration to model organism pig

For decades, phthalates are widely used as plasticizers in plenty of consumer products e.g. food packaging, toys, clothing and personal care products. They are not chemically bound to the polymer matrix, so they can easily be released into the environment for example by leaching or migration. Humans are exposed to phthalates via ingestion, inhalation or dermal uptake. They are rapidly metabolized in humans and excreted via urine, mainly within two days. Phthalates act as endocrine disruptors and target mainly the reproductive system. According to US-Environmental Protection Agency (US-EPA), infants have an unintended uptake of 60 mg dust per day. Among other things, dust contains a various amount of pollutants as e.g. phthalates. Therefore, dust could pose a potential health risk to humans. Currently there are no information’s about the bioavailability of phthalate in dust. Consequently in risk assessments the bioavailability is determined as 100 %. In the case of phthalates, in vitro digestion tests are indicating a bioaccessibility of 10 – 32 %. The aim of this study was to determine the relative oral bioavailability of certain phthalates as butyl benzyl phthalate (BBzP), bis (2-ethylhexyl) phthalate (DEHP), di-n-butyl phthalate (DnBP) and di-isononyl phthalate (DINP) in house dust after oral ingestion. Study design: Seven five week old piglets were fed five different dust samples collected from daycare centers and one food sample. Overall, 0.43 to 0.83 g of dust samples sieved to 63 µm were administered orally. The urine was collected over a period of 38 hours. The excreted metabolites were quantified using an LC-MS/MS method. Results: The mean uptake rate of the applied dust dose for BBzP, DnBP, DEHP and DINP is 28 ± 18 %, 52 ± 18 %, 43 ± 11 % and 47 ± 26 %, respectively. The bioavailability in food is 37 ± 23 % for BBzP, 39 ± 16% for DnBP, 53 ± 15 % for DEHP and 43 ± 13 % for DINP. No significant difference between the quantities of plasticizers excreted in urine after dust administration compared to food was observed. The metabolites showed their maximum concentration three to five hours post dose. Conclusion: The bioavailability of the investigated phthalates is much higher compared to the bioaccessibility reported from in vitro digestion tests. Furthermore it is noticeable that the bioavailability of DEHP does not vary between the dust samples. A dose dependent saturation process for DINP was observed. Besides other intake pathways, dust could pose a relevant source of phthalates for toddlers.Seit Jahrzenten werden Phthalate in großen Mengen als Weichmacher in (Lebensmittel-) Verpackungsmaterial, Spielzeug oder Kleidung eingesetzt und zählen daher zu einer der wichtigsten Industriechemikalien. Phthalate sind nicht an die Polymermatrix gebunden und können durch (Ab-)Nutzung relativ leicht in die Umwelt abgegeben werden. Phthalate werden als endokrin aktive Substanzen eingestuft und haben eine negative Wirkung auf das Reproduktionssystem. Kleinkinder nehmen oral täglich 60 mg unbeabsichtigt Hausstaub auf. In Hausstaub kommen teils hohe Konzentrationen an Schadstoffen, wie z.B. Phthalate, vor. Derzeit gibt es keine Kenntnisse über die orale Bioverfügbarkeit von Weichmachern in der Matrix Staub. In einem in vitro Verdauungstest konnte eine Bioverfügbarkeit von Phthalaten aus dem Staub zwischen 10,2 % (DEHP) und 32 % (DMP) nachgewiesen werden. In dieser Studie soll anhand eines Tierversuchs die orale Bioverfügbarkeit von Butylbenzylphthalat (BBzP), Bis (2-ethylhexyl)phthalat (DEHP), Di-n-butylphthalat (DnBP) und Di-isononylphthalat (DINP) in Hausstaub und Lebensmitteln untersucht werden. Studiendesign: Sieben fünf Wochen alte Schweine erhielten jeweils fünf unterschiedliche Hausstaubproben (Staub aus Kindertagesstätten auf 63 µg gesiebt; verabreicht: 0,43-0,83g) und eine Lebensmittelprobe. Der Urin wurde über 38 Stunden gesammelt. Die ausgeschiedenen Metabolite wurden mittels einer LC/MS-MS Methode bestimmt. Ergebnisse: Die durchschnittliche Aufnahme von BBzP, DnBP, DEHP und DINP im Staub lag bei 28 ± 8 %, 52 ± 18 %, 43 ± 11 % und 47 ± 26 %. Bei der Lebensmittelprobe lag sie bei 37 ± 23 % für BBzP, 39 ± 16 % für DnBP, 53 ± 15 % für DEHP und 43 ± 13 % für DINP. Es konnte kein signifikanter Unterschied bei der Aufnahme zwischen Hausstaub und Lebensmittelprobe nachgewiesen werden. Das Konzentrationsmaximum der Phthalatmetabolite im Urin konnte drei bis fünf Stunden nach der Probengabe festgestellt werden. Schlussfolgerung: In dieser Studie konnte gezeigt werden, dass die Bioverfügbarkeit - je nach Weichmacher im Hausstaub - bei ca. 40 % liegt und somit höher als in den in vitro Verdauungstests (10 – 20 %). Außerdem zeigte sich, dass die Bioverfügbarkeit von DEHP innerhalb der getesteten Staubproben stabil und reproduzierbar ist. Bei DINP konnte ein dosisabhängiger Sättigungsprozess festgestellt werden. Zusammenfassend lässt sich sagen, dass Staub eine Expositionsquelle bei Kleinkindern darstellt

Bioavailability of plasticizers in dust and food after oral administration to model organism pig

For decades, phthalates are widely used as plasticizers in plenty of consumer products e.g. food packaging, toys, clothing and personal care products. They are not chemically bound to the polymer matrix, so they can easily be released into the environment for example by leaching or migration. Humans are exposed to phthalates via ingestion, inhalation or dermal uptake. They are rapidly metabolized in humans and excreted via urine, mainly within two days. Phthalates act as endocrine disruptors and target mainly the reproductive system. According to US-Environmental Protection Agency (US-EPA), infants have an unintended uptake of 60 mg dust per day. Among other things, dust contains a various amount of pollutants as e.g. phthalates. Therefore, dust could pose a potential health risk to humans. Currently there are no information’s about the bioavailability of phthalate in dust. Consequently in risk assessments the bioavailability is determined as 100 %. In the case of phthalates, in vitro digestion tests are indicating a bioaccessibility of 10 – 32 %. The aim of this study was to determine the relative oral bioavailability of certain phthalates as butyl benzyl phthalate (BBzP), bis (2-ethylhexyl) phthalate (DEHP), di-n-butyl phthalate (DnBP) and di-isononyl phthalate (DINP) in house dust after oral ingestion. Study design: Seven five week old piglets were fed five different dust samples collected from daycare centers and one food sample. Overall, 0.43 to 0.83 g of dust samples sieved to 63 µm were administered orally. The urine was collected over a period of 38 hours. The excreted metabolites were quantified using an LC-MS/MS method. Results: The mean uptake rate of the applied dust dose for BBzP, DnBP, DEHP and DINP is 28 ± 18 %, 52 ± 18 %, 43 ± 11 % and 47 ± 26 %, respectively. The bioavailability in food is 37 ± 23 % for BBzP, 39 ± 16% for DnBP, 53 ± 15 % for DEHP and 43 ± 13 % for DINP. No significant difference between the quantities of plasticizers excreted in urine after dust administration compared to food was observed. The metabolites showed their maximum concentration three to five hours post dose. Conclusion: The bioavailability of the investigated phthalates is much higher compared to the bioaccessibility reported from in vitro digestion tests. Furthermore it is noticeable that the bioavailability of DEHP does not vary between the dust samples. A dose dependent saturation process for DINP was observed. Besides other intake pathways, dust could pose a relevant source of phthalates for toddlers.Seit Jahrzenten werden Phthalate in großen Mengen als Weichmacher in (Lebensmittel-) Verpackungsmaterial, Spielzeug oder Kleidung eingesetzt und zählen daher zu einer der wichtigsten Industriechemikalien. Phthalate sind nicht an die Polymermatrix gebunden und können durch (Ab-)Nutzung relativ leicht in die Umwelt abgegeben werden. Phthalate werden als endokrin aktive Substanzen eingestuft und haben eine negative Wirkung auf das Reproduktionssystem. Kleinkinder nehmen oral täglich 60 mg unbeabsichtigt Hausstaub auf. In Hausstaub kommen teils hohe Konzentrationen an Schadstoffen, wie z.B. Phthalate, vor. Derzeit gibt es keine Kenntnisse über die orale Bioverfügbarkeit von Weichmachern in der Matrix Staub. In einem in vitro Verdauungstest konnte eine Bioverfügbarkeit von Phthalaten aus dem Staub zwischen 10,2 % (DEHP) und 32 % (DMP) nachgewiesen werden. In dieser Studie soll anhand eines Tierversuchs die orale Bioverfügbarkeit von Butylbenzylphthalat (BBzP), Bis (2-ethylhexyl)phthalat (DEHP), Di-n-butylphthalat (DnBP) und Di-isononylphthalat (DINP) in Hausstaub und Lebensmitteln untersucht werden. Studiendesign: Sieben fünf Wochen alte Schweine erhielten jeweils fünf unterschiedliche Hausstaubproben (Staub aus Kindertagesstätten auf 63 µg gesiebt; verabreicht: 0,43-0,83g) und eine Lebensmittelprobe. Der Urin wurde über 38 Stunden gesammelt. Die ausgeschiedenen Metabolite wurden mittels einer LC/MS-MS Methode bestimmt. Ergebnisse: Die durchschnittliche Aufnahme von BBzP, DnBP, DEHP und DINP im Staub lag bei 28 ± 8 %, 52 ± 18 %, 43 ± 11 % und 47 ± 26 %. Bei der Lebensmittelprobe lag sie bei 37 ± 23 % für BBzP, 39 ± 16 % für DnBP, 53 ± 15 % für DEHP und 43 ± 13 % für DINP. Es konnte kein signifikanter Unterschied bei der Aufnahme zwischen Hausstaub und Lebensmittelprobe nachgewiesen werden. Das Konzentrationsmaximum der Phthalatmetabolite im Urin konnte drei bis fünf Stunden nach der Probengabe festgestellt werden. Schlussfolgerung: In dieser Studie konnte gezeigt werden, dass die Bioverfügbarkeit - je nach Weichmacher im Hausstaub - bei ca. 40 % liegt und somit höher als in den in vitro Verdauungstests (10 – 20 %). Außerdem zeigte sich, dass die Bioverfügbarkeit von DEHP innerhalb der getesteten Staubproben stabil und reproduzierbar ist. Bei DINP konnte ein dosisabhängiger Sättigungsprozess festgestellt werden. Zusammenfassend lässt sich sagen, dass Staub eine Expositionsquelle bei Kleinkindern darstellt

Safety assessment of titanium dioxide (E171) as a food additive

Acknowledgements: The Panel wishes to thank the following for the support provided to this scientific output: Ana Campos Fernandes, Laura Ciccolallo, Esraa Elewa, Galvin Eyong, Christina Kyrkou, Irene Munoz, Giorgia Vianello, the members of the SCER Cross-cutting WG nanotechnologies: Jacqueline Castenmiller, Mohammad Chaudhry, Roland Franz, David Gott, Stefan Weigel and the former member of the SCER Cross-cutting WG Genotoxicity Maciej Stepnik. The FAF Panel wishes to acknowledge all European competent institutions, Member State bodies and other organisations that provided data for this scientific output.Peer reviewedPublisher PD

Harmonized human biomonitoring in European children, teenagers and adults: EU-wide exposure data of 11 chemical substance groups from the HBM4EU Aligned Studies (2014–2021)

HBM4EU is co-financed under Horizon 2020 (grant agreement No 733032).As one of the core elements of the European Human Biomonitoring Initiative (HBM4EU) a human biomonitoring (HBM) survey was conducted in 23 countries to generate EU-wide comparable HBM data. This survey has built on existing HBM capacity in Europe by aligning national or regional HBM studies, referred to as the HBM4EU Aligned Studies. The HBM4EU Aligned Studies included a total of 10,795 participants from three age groups: (i) 3,576 children aged 6-12 years, (ii) 3,117 teenagers aged 12-18 years, and (iii) 4,102 young adults aged 20-39 years. The participants were recruited between 2014 and 2021 in 11-12 countries per age group, geographically distributed across Europe. Depending on the age group, internal exposure to phthalates and the substitute DINCH, halogenated and organophosphorus flame retardants, per- and polyfluoroalkyl substances (PFASs), cadmium, bisphenols, polycyclic aromatic hydrocarbons (PAHs), arsenic species, acrylamide, mycotoxins (deoxynivalenol (total DON)), benzophenones and selected pesticides was assessed by measuring substance specific biomarkers subjected to stringent quality control programs for chemical analysis. For substance groups analyzed in different age groups higher average exposure levels were observed in the youngest age group, i.e., phthalates/DINCH in children versus teenagers, acrylamide and pesticides in children versus adults, and benzophenones in teenagers versus adults. Many biomarkers in teenagers and adults varied significantly according to educational attainment, with higher exposure levels of bisphenols, phthalates, benzophenones, PAHs, and acrylamide in participants (from households) with lower educational attainment, while teenagers from households with higher educational attainment have higher exposure levels for PFASs and arsenic. In children, a social gradient was only observed for the non-specific pyrethroid metabolite 3-PBA and di-isodecyl phthalate (DiDP), with higher levels in children from households with higher educational attainment. Geographical variations were seen for all exposure biomarkers. For 15 biomarkers, the available health-based HBM guidance values were exceeded with the highest exceedance rates for toxicologically relevant arsenic in teenagers (40%), 3-PBA in children (36%), and between 11 and 14% for total DON, Σ (PFOA + PFNA + PFHxS + PFOS), bisphenol S and cadmium. The infrastructure and harmonized approach succeeded in obtaining comparable European-wide internal exposure data for a prioritized set of 11 chemical groups. These data serve as a reference for comparison at the global level, provide a baseline to compare the efficacy of the European Commission's chemical strategy for sustainability, and will give leverage to national policymakers for the implementation of targeted measures.info:eu-repo/semantics/publishedVersio

EU-wide exposure data of 11 chemical substance groups from the HBM4EU Aligned Studies (2014–2021)

Funding Information: The authors would like to thank everybody who contributed to the HBM4EU Aligned Studies: the participating children, teenagers, adults and their families, the fieldworkers that collected the samples and database managers that made the information available to HBM4EU, the HBM4EU project partners, especially those from WP7 for developing all materials supporting the fieldwork, WP9 for organizing the QA/QC scheme under HBM4EU and all laboratories who performed the analytical measurements. We would like to acknowledge Sun Kyoung Jung from the National Institute of Environmental Research of South-Korea for providing the KoNEHS Cycle III results (crt adjusted). HBM4EU is co-financed under Horizon 2020 (grant agreement No 733032). The authors thank all principal investigators of the contributing studies for their participation and contribution to the HBM4EU Aligned Studies and the national program owners for their financial support. Further details on funding for all the participating studies can be found in the Supplemental Material, Table S12.As one of the core elements of the European Human Biomonitoring Initiative (HBM4EU) a human biomonitoring (HBM) survey was conducted in 23 countries to generate EU-wide comparable HBM data. This survey has built on existing HBM capacity in Europe by aligning national or regional HBM studies, referred to as the HBM4EU Aligned Studies. The HBM4EU Aligned Studies included a total of 10,795 participants of three age groups: (i) 3,576 children aged 6–12 years, (ii) 3,117 teenagers aged 12–18 years and (iii) 4,102 young adults aged 20–39 years. The participants were recruited between 2014 and 2021 in 11–12 countries per age group, geographically distributed across Europe. Depending on the age group, internal exposure to phthalates and the substitute DINCH, halogenated and organophosphorus flame retardants, per- and polyfluoroalkyl substances (PFASs), cadmium, bisphenols, polycyclic aromatic hydrocarbons (PAHs), arsenic species, acrylamide, mycotoxins (deoxynivalenol (total DON)), benzophenones and selected pesticides was assessed by measuring substance specific biomarkers subjected to stringent quality control programs for chemical analysis. For substance groups analyzed in different age groups higher average exposure levels were observed in the youngest age group, i.e., phthalates/DINCH in children versus teenagers, acrylamide and pesticides in children versus adults, benzophenones in teenagers versus adults. Many biomarkers in teenagers and adults varied significantly according to educational attainment, with higher exposure levels of bisphenols, phthalates, benzophenones, PAHs and acrylamide in participants (from households) with lower educational attainment, while teenagers from households with higher educational attainment have higher exposure levels for PFASs and arsenic. In children, a social gradient was only observed for the non-specific pyrethroid metabolite 3-PBA and di-isodecyl phthalate (DiDP), with higher levels in children from households with higher educational attainment. Geographical variations were seen for all exposure biomarkers. For 15 biomarkers, the available health-based HBM guidance values were exceeded with highest exceedance rates for toxicologically relevant arsenic in teenagers (40%), 3-PBA in children (36%), and between 11 and 14% for total DON, Σ (PFOA + PFNA + PFHxS + PFOS), bisphenol S and cadmium. The infrastructure and harmonized approach succeeded in obtaining comparable European wide internal exposure data for a prioritized set of 11 chemical groups. These data serve as a reference for comparison at the global level, provide a baseline to compare the efficacy of the European Commission's chemical strategy for sustainability and will give leverage to national policy makers for the implementation of targeted measures.publishersversionpublishe

Adheze plazmových nanopovlaků řídí smykové vlastnosti kompozitu GF/polyester

High-performance fibre-reinforced polymer composites are important construction materials based not only on the specific properties of the reinforcing fibres and the flexible polymer matrix, but also on the compatible properties of the composite interphase. First, oxygen-free (a-CSi:H) and oxygen binding (a-CSiO:H) plasma nanocoatings of different mechanical and tribological properties were deposited on planar silicon dioxide substrates that closely mimic E-glass. The nanoscratch test was used to characterize the nanocoating adhesion expressed in terms of critical normal load and work of adhesion. Next, the same nanocoatings were deposited on E-glass fibres, which were used as reinforcements in the polyester composite to affect its interphase properties. The shear properties of the polymer composite were characterized by macro- and micromechanical tests, namely a short beam shear test to determine the short-beam strength and a single fibre push-out test to determine the interfacial shear strength. The results of the polymer composites showed a strong correlation between the short-beam strength and the interfacial shear strength, proving that both tests are sensitive to changes in fibre-matrix adhesion due to different surface modification of glass fibres (GF). Finally, a strong correlation between the shear properties of the GF/polyester composite and the adhesion of the plasma nanocoating expressed through the work of adhesion was demonstrated. Thus, increasing the work of adhesion of plasma nanocoatings from 0.8 to 1.5 mJ·m-2 increased the short-beam strength from 23.1 to 45.2 MPa. The results confirmed that the work of adhesion is a more suitable parameter to characterise the level of nanocoating adhesion in comparison with the critical normal load.Vysoce výkonné vlákny vyztužené polymerní kompozity jsou důležité konstrukční materiály založené nejen na specifických vlastnostech výztužných vláken a pružné polymerní matrici, ale také na kompatibilních vlastnostech kompozitního mezifáze. Nejprve byly na planární substráty oxidu křemičitého, které úzce napodobují E-sklo, naneseny plazmové nanopovlaky bez obsahu kyslíku (a-CSi: H) a vázající kyslík (a-CSiO: H). K charakterizaci nanopovlakové adheze vyjádřené z hlediska kritického normálního zatížení a práce adheze byl použit nanorozprašný test. Dále byly stejné nanopovlaky naneseny na vlákna E-glass, která byla použita jako výztuhy v polyesterovém kompozitu, aby se ovlivnily jeho mezifázové vlastnosti. Smykové vlastnosti polymerního kompozitu byly charakterizovány makro- a mikromechanickými zkouškami, jmenovitě zkouškou krátkým paprskem ve smyku pro stanovení pevnosti krátkého paprsku a zkouškou tlakem z jednoho vlákna pro stanovení mezifázové smykové pevnosti. Výsledky polymerních kompozitů ukázaly silnou korelaci mezi pevností krátkého paprsku a mezifázovou pevností ve smyku, což dokazuje, že oba testy jsou citlivé na změny adheze vláknových matric v důsledku odlišné povrchové úpravy skleněných vláken (GF). Nakonec byla prokázána silná korelace mezi smykovými vlastnostmi GF / polyesterového kompozitu a adhezí plazmatického nanopovlaku vyjádřenou prostřednictvím práce adheze. Zvyšování práce adheze plazmových nanopovlaků z 0,8 na 1,5 mJ · m-2 tedy zvýšilo sílu krátkého paprsku z 23,1 na 45,2 MPa. Výsledky potvrdily, že práce adheze je vhodnějším parametrem pro charakterizaci úrovně adheze nanopovlaku ve srovnání s kritickým normálním zatížením

Plazmové nanopovlaky vyvinuté pro řízení smykové pevnosti polymerních kompozitů

All reinforcements for polymer-matrix composites must be coated with a suitable material in the form of thin film to improve compatibility and interfacial adhesion between the reinforcement and the polymer matrix. In this study, plasma nanotechnology was used to synthetize such functional nanocoatings using pure tetravinylsilane (TVS) and its mixtures with oxygen gas (O2) as precursors. The plasma-coated glass fibers (GFs) were unidirectionally embedded in a polyester resin to produce short composite beams that were analyzed by a short-beam-shear test to determine the shear strength characterizing the functionality of the nanocoatings in a GF/polyester composite. The developed plasma nanocoatings allowed controlling the shear strength between 26.2 – 44.1 MPa depending on deposition conditions, i.e., the RF power and the oxygen fraction in the TVS/O2 mixture. This range of shear strength appears to be sufficiently broad to be used in the design of composites.Všechny výztuže pro polymerní kompozitymusí být potaženy vhodným materiálem ve formě tenké vrstvy, aby se zlepšila kompatibilita a adheze mezi výztuží a polymerní matricí. V této studii byla použita plazmová nanotechnologie k syntetizaci takových funkčních nanopovlaků za použití čistého tetravinylsilanu (TVS) a jeho směsí s plynným kyslíkem (O2) jako prekurzorů. Plazmová skleněná vlákna (GF) byla jednosměrně zabudována do polyesterové pryskyřice za vzniku krátkých kompozitních paprsků, které byly analyzovány zkouškou střihem s krátkým paprskem, aby se stanovila pevnost ve smyku charakterizující funkčnost nanokovin v kompozitu GF / polyester. Vyvinuté plazmové nanokovory umožnily regulovat smykovou pevnost mezi 26,2 - 44,1 MPa v závislosti na podmínkách nanášení, tj. Na vysokofrekvenčním výkonu a kyslíkové frakci ve směsi TVS / O2. Tento rozsah smykové pevnosti se zdá být dostatečně široký, aby mohl být použit při konstrukci kompozitů

Risk assessment of dietary exposure to organophosphorus flame retardants in children by using HBM-data

Due to their extensive usage, organophosphorus flame retardants (OPFRs) have been detected in humans and in the environment. Human are exposed to OPFRs via inhalation of indoor air, dust uptake or dietary uptake through contaminated food and drinking water. Only recently, few studies addressing dietary exposure to OPFRs were published. In this study, we used human biomonitoring (HBM) data of OPFRs to estimate how much the dietary intake may contribute to the total exposure. We estimated by reverse dosimetry, the daily intake of tris (2-chloroethyl) phosphate (TCEP), tris (1-chloro-2-propyl) phosphate (TCIPP), tris (1,3-dichloro-2-propyl) phosphate (TDCIPP) for children using HBM data from studies with sampling sites in Belgium, Denmark, France, Germany, Slovenia and Slovakia. For estimating the dietary exposure, a deterministic approach was chosen. The occurrence data of selected food categories were used from a published Belgium food basket study. Since the occurrence data were left-censored, the Lower bound (LB)—Upper bound (UB) approach was used. The estimated daily intake (EDI) calculated on the basis of urine metabolite concentrations ranged from 0.03 to 0.18 µg/kg bw/d for TDCIPP, from 0.05 to 0.17 µg/kg bw/d for TCIPP and from 0.02 to 0.2 µg/kg bw/d for TCEP. Based on national food consumption data and occurrence data, the estimated dietary intake for TDCIPP ranged from 0.005 to 0.09 µg/kg bw/d, for TCIPP ranged from 0.037 to 0.2 µg/kg bw/d and for TCEP ranged from 0.007 to 0.018 µg/kg bw/d (summarized for all countries). The estimated dietary intake of TDCIPP contributes 11–173% to the EDI, depending on country and LB-UB scenario. The estimated dietary uptake of TCIPP was in all calculations, except in Belgium and France, above 100%. In the case of TCEP, it is assumed that the dietary intake ranges from 6 to 57%. The EDI and the estimated dietary intake contribute less than 3% to the reference dose (RfD). Therefore, the estimated exposure to OPFRs indicates a minimal health risk based on the current knowledge of available exposure, kinetic and toxicity data. We were able to show that the dietary exposure can have an impact on the general exposure based on our underlying exposure scenarios

Safety assessment of titanium dioxide (E171) as a food additive

The present opinion deals with an updated safety assessment of the food additive titanium dioxide (E 171) based on new relevant scientific evidence considered by the Panel to be reliable, including data obtained with TiO2 nanoparticles (NPs) and data from an extended one-generation reproductive toxicity (EOGRT) study. Less than 50% of constituent particles by number in E 171 have a minimum external dimension 30 nm) up to the highest dose tested of 100 mg/kg bw per day. No effects on reproductive and developmental toxicity were observed up to a dose of 1,000 mg E 171/kg bw per day, the highest dose tested in the EOGRT study. However, observations of potential immunotoxicity and inflammation with E 171 and potential neurotoxicity with TiO2 NPs, together with the potential induction of aberrant crypt foci with E 171, may indicate adverse effects. With respect to genotoxicity, the Panel concluded that TiO2 particles have the potential to induce DNA strand breaks and chromosomal damage, but not gene mutations. No clear correlation was observed between the physico-chemical properties of TiO2 particles and the outcome of either in vitro or in vivo genotoxicity assays. A concern for genotoxicity of TiO2 particles that may be present in E 171 could therefore not be ruled out. Several modes of action for the genotoxicity may operate in parallel and the relative contributions of different molecular mechanisms elicited by TiO2 particles are not known. There was uncertainty as to whether a threshold mode of action could be assumed. In addition, a cut-off value for TiO2 particle size with respect to genotoxicity could not be identified. No appropriately designed study was available to investigate the potential carcinogenic effects of TiO2 NPs. Based on all the evidence available, a concern for genotoxicity could not be ruled out, and given the many uncertainties, the Panel concluded that E 171 can no longer be considered as safe when used as a food additive

How to use human biomonitoring in chemical risk assessment: Methodological aspects, recommendations, and lessons learned from HBM4EU.

Funding: This project received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement No 733032 HBM4EU, and co-funding from the authors’ organisations. The results presented here are based on a huge body of work performed as part of Task 5.3 of the HBM4EU in 2017–2022. First and foremost, we would like to acknowledge all our Task 5.3 colleagues for their valuable contribution to the project work, including the individual RAs and EBoD calculations. In addition, we would like to thank all our other HBM4EU colleagues, the HBM4EU-aligned study data owners, and the other stakeholders who provided support for and feedback on our work during its course.One of the aims of the European Human Biomonitoring Initiative, HBM4EU, was to provide examples of and good practices for the effective use of human biomonitoring (HBM) data in human health risk assessment (RA). The need for such information is pressing, as previous research has indicated that regulatory risk assessors generally lack knowledge and experience of the use of HBM data in RA. By recognising this gap in expertise, as well as the added value of incorporating HBM data into RA, this paper aims to support the integration of HBM into regulatory RA. Based on the work of the HBM4EU, we provide examples of different approaches to including HBM in RA and in estimations of the environmental burden of disease (EBoD), the benefits and pitfalls involved, information on the important methodological aspects to consider, and recommendations on how to overcome obstacles. The examples are derived from RAs or EBoD estimations made under the HBM4EU for the following HBM4EU priority substances: acrylamide, o-toluidine of the aniline family, aprotic solvents, arsenic, bisphenols, cadmium, diisocyanates, flame retardants, hexavalent chromium [Cr(VI)], lead, mercury, mixture of per-/poly-fluorinated compounds, mixture of pesticides, mixture of phthalates, mycotoxins, polycyclic aromatic hydrocarbons (PAHs), and the UV-filter benzophenone-3. Although the RA and EBoD work presented here is not intended to have direct regulatory implications, the results can be useful for raising awareness of possibly needed policy actions, as newly generated HBM data from HBM4EU on the current exposure of the EU population has been used in many RAs and EBoD estimations.publishersversionpublishe