Beyond microbeads: Examining the role of cosmetics in microplastic pollution and spotlighting unanswered questions.

The presence of microplastics in cosmetics and personal care products (C&PCPs) has been increasingly in the public eye since the early 2010s. Despite increasing research into the potential environmental and health effects of microplastics, most research to date on microplastics in C&PCPs has investigated "rinse-off" products, while the potential impacts of "leave-on" C&PCPs have been largely neglected, despite these products being purchased in greater volumes and often having two or more microplastic ingredients in their formulations(CosmeticsEurope, 2018b). This review aims to synthesize the current knowledge of microplastic in C&PCPs, assessing the potential environmental and human health impacts of C&PCPs and discussing the regulatory implications. The lack of studies on leave-on C&PCPs is significant, suggesting a severe knowledge gap regarding microplastic presence in, and emissions from, C&PCPs. There is a noticeable lack of studies on the (eco)toxicological consequences of microplastic exposure from C&PCPs. As a result, significant aspects of microplastic contamination may be overlooked in the microplastic legislations emerging globally (including from the European Commission), which intend to restrict microplastic use in C&PCPs but focus on rinse-off C&PCPs only. This review highlights the potential consequences of microplastics in leave-on C&PCPs for regulatory decision-making, particularly as alternatives to microplastics are considered during the phase-out periods and spotlights the need for sufficient monitoring and research on these alternatives, to avoid unforeseen consequences.

Towards a more effective REACH legislation in protecting human health.

There is growing evidence indicating the substantial contribution of man-made products to an increase in the risk of diseases of civilization. In this article, the Belgian Scientific Registration, Evaluation, Authorization and Restriction of Chemicals (REACH) Committee gives a critical view on the working of REACH. The current regulatory framework needs to further evolve taking into account data generated using modern science and technology. There is a need for improved assessment process not only before but also after entering the market. Objectivity, transparency, and the follow-up after market access can be optimized. Additionally, no guidance documents exist for regulation of mixture effects. Further, the lengthiness before regulatory action is a big concern. Decision-making often takes several years leading to uncertainties for both producers and end users. A first proposed improvement is the implementation of independent toxicity testing, to assure objectivity, transparency, and check and improve compliance. A "no data, no market" principle could prevent access of hazardous chemicals to the market. Additionally, the introduction of novel testing could improve information on endpoints such as endocrine disrupting abilities, neurotoxicity, and immunotoxicity. An adapted regulatory framework that integrates data from different sources and comparing the outputs with estimates of exposure is required. Fast toxicology battery testing and toxicokinetic testing could improve speed of decision-making. Hereby, several improvements have been proposed that could improve the current REACH legislation.

The Relative Age Effect on YoungAthletes of Para-Athletics: Birth quartile analysis and performance in individual athletic events / El Efecto de la Edad Relativa en los Atletas Jóvenes de Paratlético: Análisis de cuartil denacimiento y desempeño en eventos atléticos individuales / O Efeito da Idade Relativa em Jovens Atletas de Paraatletismo: Análise do quartil de nascimento e do desempenho em eventos individuais de atletismo

El Efecto de la Edad Relativa (EER) es un fenómeno caracterizado por una sobrerrepresentación significativa de atletas nacidos en los primeros meses del año competitivo en la misma categoría deedad que se ha observado en categorías juveniles de atletismo. Sin embargo, hay una falta de investigación para investigar este fenómeno y su relación con el deporte para, y no está claro si este efectoestá presente en los jóvenes atletas. Por lo tanto, nuestro estudio examinó la existencia de EER en jóvenes atletaspara-atléticos (categorías U16, U18 y U20) y el rendimiento en eventos deportivos individuales según el cuartil denacimiento (Q1, Q2, Q3 yQ4). Las fechas de nacimiento se recogieron de 700 jóvenes atletas masculinos de deportes para que participaran en eventos deportivos individuales entre 2018 y 2019 en las categorías U16, U18 y U20. En resumen, se observó una distribución desigual de las fechas de nacimiento por cuartil cuando un mayor número de jóvenes para-atletas nació en el primer trimestre del año para U16 (χ²3= 18.785; p = .0003; Phi efecto = 0.45), U18 (χ²3= 6.846; p= .05; Phi efecto = 0.17), y U20 (χ²3= 10.156; p = .017; Phiefecto = 0.17). Sin embargo, cuando comparamos el desempeño de los atletas por evento (eventos de atletismo) y por separado por cuartil, no se encontró diferencia significativa (p> .05). En conclusión, nuestro estudio evidenció el papel influyente de laedad relativa en atletismo, pero parece que este fenómeno no está relacionado con el rendimiento en atletismo.(AU)

The Relative Age Effect (RAE) is a phenomenon characterized by a significant over-representation ofathletes born in the first months of the competitive year in the same age category that has been observed in athletics juvenile categories. However, there is a lack of research to investigate this phenomenon and its relationship with para-sport, and it isnot clear whether this effect is present in young para-athletes. Thus, the present study aims to examine the existence of RAE in young para-athletics athletes (U16, U18, and U20 categories) and the performance in individual athletic events according to the birth quartile (Q1, Q2, Q3, and Q4). Birth dates were collected from 700 young male athletes from para-sport who participated in individual athletic eventsbetween 2018 and 2019 in the U16, U18, and U20 categories. In summary, unequal distribution of birth dates per quartile was observed where a greater number of young para-athletes was born in the Q1 of the year for U16 (χ²3= 18.785; p = .0003; Phi effect = .45), U18 (χ²3= 6.846; p= .05; Phi effect = .17), and U20 (χ²3= 10.156; p= .017; Phi effect =.17). However,when we compared the performance of the athletes by event (track and field events) and separately by quartile, no significant difference was found (p> .05). In conclusion, our study evidenced the influential role of relative age in track and field para-athletes, but it seems that this phenomenon is not related to performance in track and field events.(AU)

O Efeito da Idade Relativa (EIR) é um fenômeno caracterizado por uma significativa representação de atletas nascidos nos primeiros meses do ano competitivo na mesma faixa etária que tem sido observada em categorias juvenis de atletismo. No entanto, há ainda uma lacuna em termos de investigaçãopara analisar esse fenômeno e sua relação com o para-desporto. Assim, o obejtivo do presente estudo foi analisar a existência de EIR em atletas jovens de para-atletismo (categorias Sub-16, Sub-18 e Sub-20) e sua relação com o desempenho em eventos atléticos individuais de acordo com o quartil de nascimento (Q1, Q2, Q3 e Q4). As datas de nascimento foram recolhidas de 700 jovens atletas do sexo masculino de paradesporto que participaram de eventos de atletismo individuais entre 2018 e 2019 nas categorias Sub-16, Sub-18 e Sub-20. No geral, observou-se uma distribuição desigual das datas de nascimento por quartil, onde um maior número de jovens para-atletas nasceu no Q1 do ano para Sub-16 (χ²3= 18.785; p = .0003; Phi effect = .45), Sub-18 (χ²3= 6.846; p= .05; Phi effect = .17), e Sub-20 (χ²3= 10.156; p= .017; Phi effect = .17). Entretanto, quando comparamos o desempenho dos atletas por evento (provas de atletismo) e separadamente por quartil, não houve diferenças significativas (p> .05). Em conclusão, nosso estudo evidenciou o papel influente da idade relativa em paraatletas de atletismo, mas parece que esse fenômeno não está relacionadoao desempenho em eventos desta modalidade.(AU)

The EU's Per- and Polyfluoroalkyl Substances (PFAS) Ban: A Case of Policy over Science.

The proposal by the European Chemicals Agency (ECHA) to ban over 12,000 per- and polyfluoroalkyl substances (PFAS) has sparked a debate about potential consequences for the economy, industry, and the environment. Although some PFAS are known to be harmful, a blanket ban may lead to significant problems in attempting to replace PFAS-based materials for environmental transition, as well as in medical devices and everyday products. Alternative materials may potentially be less safe, as a rush to replace PFAS would reduce the time needed for toxicological analyses. Studies have shown that PFAS exhibit a diverse range of mechanisms of action, biopersistence, and bioaccumulation potential, and should thus not be treated as a single group. This is particularly true for the class of fluoropolymers. A targeted approach that considers the specific risks and benefits of each chemical may be more effective. Moreover, the proposed ban may also have unintended consequences for the environment as PFAS use is also associated with benefits such as reducing greenhouse-gas emissions and improving energy efficiency. Policymakers must carefully weigh up the potential consequences before making a final decision on the ban.

Characteristics of Mycobacterium tuberculosis PtpA interaction and activity on the alpha subunit of human mitochondrial trifunctional protein, a key enzyme of lipid metabolism.

During Mycobacterium tuberculosis (Mtb) infection, the virulence factor PtpA belonging to the protein tyrosine phosphatase family is delivered into the cytosol of the macrophage. PtpA interacts with numerous eukaryotic proteins modulating phagosome maturation, innate immune response, apoptosis, and potentially host-lipid metabolism, as previously reported by our group. In vitro, the human trifunctional protein enzyme (hTFP) is a bona fide PtpA substrate, a key enzyme of mitochondrial ß-oxidation of long-chain fatty acids, containing two alpha and two beta subunits arranged in a tetramer structure. Interestingly, it has been described that the alpha subunit of hTFP (ECHA, hTFPα) is no longer detected in mitochondria during macrophage infection with the virulent Mtb H37Rv. To better understand if PtpA could be the bacterial factor responsible for this effect, in the present work, we studied in-depth the PtpA activity and interaction with hTFPα. With this aim, we performed docking and in vitro dephosphorylation assays defining the P-Tyr-271 as the potential target of mycobacterial PtpA, a residue located in the helix-10 of hTFPα, previously described as relevant for its mitochondrial membrane localization and activity. Phylogenetic analysis showed that Tyr-271 is absent in TFPα of bacteria and is present in more complex eukaryotic organisms. These results suggest that this residue is a specific PtpA target, and its phosphorylation state is a way of regulating its subcellular localization. We also showed that phosphorylation of Tyr-271 can be catalyzed by Jak kinase. In addition, we found by molecular dynamics that PtpA and hTFPα form a stable protein complex through the PtpA active site, and we determined the dissociation equilibrium constant. Finally, a detailed study of PtpA interaction with ubiquitin, a reported PtpA activator, showed that additional factors are required to explain a ubiquitin-mediated activation of PtpA. Altogether, our results provide further evidence supporting that PtpA could be the bacterial factor that dephosphorylates hTFPα during infection, potentially affecting its mitochondrial localization or ß-oxidation activity.

Development of adverse outcome pathways relevant for the identification of substances having endocrine disruption properties Uterine adenocarcinoma as adverse outcome.

Development of adverse outcome pathways (AOPs) for uterine adenocarcinoma can provide a practical tool to implement the EFSA-ECHA Guidance (2018) for the identification of endocrine disruptors in the context of Regulations (EU) No 528/2012 and (EC) No 1107/2009. AOPs can give indications about the strength of the relationship between an adverse outcome (intended as a human health outcome) and chemicals (pesticides but not only) affecting the pathways. In this scientific opinion, the PPR Panel explored the development of AOPs for uterine adenocarcinoma. An evidence-based approach methodology was applied, and literature reviews were produced using a structured framework assuring transparency, objectivity, and comprehensiveness. Several AOPs were developed; these converged to a common critical node, that is increased estradiol availability in the uterus followed by estrogen receptor activation in the endometrium; therefore, a putative AOP network was considered. An uncertainty analysis and a probabilistic quantification of the weight of evidence have been carried out via expert knowledge elicitation for each set of MIEs/KEs/KERs included in individual AOPs. The collected data on the AOP network were evaluated qualitatively, whereas a quantitative uncertainty analysis for weight of the AOP network certainty has not been performed. Recommendations are provided, including exploring further the uncertainties identified in the AOPs and putative AOP network; further methodological developments for quantifying the certainty of the KERs and of the overall AOPs and AOP network; and investigating of NAMs applications in the context of some of the MIEs/KEs currently part of the putative AOP network developed.

Glyphosate, Roundup and the Failures of Regulatory Assessment.

Roundup is the most widely used herbicide in agriculture. It contains glyphosate as the 'active ingredient', together with formulants. There are various versions of Roundup, with somewhat different effects depending on the formulants. Most genetically-modified crops are designed to tolerate Roundup, thus allowing spraying against weeds during the growing season of the crop without destroying it. Having been so heavily used, this herbicide is now found in the soil, water, air, and even in humans worldwide. Roundup may also remain as a residue on edible crops. Many studies have found harm to the environment and to health, making it imperative to regulate the use of Roundup and to ensure that its various formulations pose no danger when used in the long-term. Unfortunately, regulators may only assess the 'active ingredient', glyphosate, and ignore the toxicity of the formulants, which can be far more toxic than the active ingredient. This omission is in violation of a ruling by the Court of Justice of the European Union. There are close ties between the regulators and the industry they are supposed to regulate. Objectionable practices include 'revolving doors' between the regulators and the industry, heavy reliance on unpublished papers produced by the industry while dismissing papers published by independent scientists, and strong covert influence on the regulatory process by industry. Although this paper focuses on the European Union (EU), the situation is much the same in the United States.

Effects of different tea tree varieties on the color, aroma, and taste of Chinese Enshi green tea.

Green tea processed by Echa 10 was shown to have a fresh and mellow taste as well as clean aroma with a clear honeysuckle fragrance. The colors of different Enshi green teas are closely related with the content of chlorophyll and chlorophyllide. The five green teas also vary in their aroma style. Echa 10 imparts a special honeysuckle fragrance, which was further analyzed by molecular sensory analysis and the formation of this honeysuckle fragrance was attributed to the key components of dodecane, octadecane, phenethyl alcohol, and jasmonone. In aroma evaluation, Echa 10 green tea showed the best performance, which is mainly related with the content of geraniol, linalool, phenethyl alcohol, and benzyl alcohol. Additionally, Echa 10 scored the highest in taste evaluation, which is mainly determined by the contents and ratios of tea polyphenols, amino acids, caffeine, and soluble sugars.

Metabolomics Provides A Novel Interpretation of the Changes in Main Compounds during Black Tea Processing through Different Drying Methods.

This study aimed to compare the effect of hot roller (HR) drying and hot air (HA) drying on the sensory evaluation, chemical quality, antioxidant activity, and metabolic profile of Yihong Congou black tea processed from E'cha NO1. The Yihong Congou black tea dried with HA obtained higher sensory scores and better chemical qualities such as the hue of tea brew color (a and b), content of theaflavins, thearubigins, water extract, free amino acids, tea polyphenol, and the ratio of polyphenol to amino acids as well as higher antioxidant capacities compared to that dried with HR. The HA drying tea increased the contents of volatile compounds that had positive correlation with sweet and flowery flavor, while the HR drying tea increased the contents of volatile compounds related to fruity flavor. Moreover, non-targeted metabolomics data indicated that the levels of most free amino acids significantly increased, while the levels of most soluble sugars reduced in the HA drying method compared to the HR drying method. The metabolic analysis was also consistent with the above results and revealed that D-ribose and gallic acid were the main characteristic metabolites of HA drying. Our results could provide a technical reference and theoretical guide to processing a high quality of Yihong Congou black tea.

FAIRification of nanosafety data to improve applicability of (Q)SAR approaches: A case study on in vitro Comet assay genotoxicity data.

(Quantitative) structure-activity relationship ([Q]SAR) methodologies are widely applied to predict the (eco)toxicological effects of chemicals, and their use is envisaged in different regulatory frameworks for filling data gaps of untested substances. However, their application to the risk assessment of nanomaterials is still limited, also due to the scarcity of large and curated experimental datasets. Despite a great amount of nanosafety data having been produced over the last decade in international collaborative initiatives, their interpretation, integration and reuse has been hampered by several obstacles, such as poorly described (meta)data, non-standard terminology, lack of harmonized reporting formats and criteria. Recently, the FAIR (Findable, Accessible, Interoperable, and Reusable) principles have been established to guide the scientific community in good data management and stewardship. The EU H2020 Gov4Nano project, together with other international projects and initiatives, is addressing the challenge of improving nanosafety data FAIRness, for maximizing their availability, understanding, exchange and ultimately their reuse. These efforts are largely supported by the creation of a common Nanosafety Data Interface, which connects a row of project-specific databases applying the eNanoMapper data model. A wide variety of experimental data relating to characterization and effects of nanomaterials are stored in the database; however, the methods, protocols and parameters driving their generation are not fully mature. This article reports the progress of an ongoing case study in the Gov4nano project on the reuse of in vitro Comet genotoxicity data, focusing on the issues and challenges encountered in their FAIRification through the eNanoMapper data model. The case study is part of an iterative process in which the FAIRification of data supports the understanding of the phenomena underlying their generation and, ultimately, improves their reusability.

COSMOS next generation - A public knowledge base leveraging chemical and biological data to support the regulatory assessment of chemicals.

The COSMOS Database (DB) was originally established to provide reliable data for cosmetics-related chemicals within the COSMOS Project funded as part of the SEURAT-1 Research Initiative. The database has subsequently been maintained and developed further into COSMOS Next Generation (NG), a combination of database and in silico tools, essential components of a knowledge base. COSMOS DB provided a cosmetics inventory as well as other regulatory inventories, accompanied by assessment results and in vitro and in vivo toxicity data. In addition to data content curation, much effort was dedicated to data governance - data authorisation, characterisation of quality, documentation of meta information, and control of data use. Through this effort, COSMOS DB was able to merge and fuse data of various types from different sources. Building on the previous effort, the COSMOS Minimum Inclusion (MINIS) criteria for a toxicity database were further expanded to quantify the reliability of studies. COSMOS NG features multiple fingerprints for analysing structure similarity, and new tools to calculate molecular properties and screen chemicals with endpoint-related public profilers, such as DNA and protein binders, liver alerts and genotoxic alerts. The publicly available COSMOS NG enables users to compile information and execute analyses such as category formation and read-across. This paper provides a step-by-step guided workflow for a simple read-across case, starting from a target structure and culminating in an estimation of a NOAEL confidence interval. Given its strong technical foundation, inclusion of quality-reviewed data, and provision of tools designed to facilitate communication between users, COSMOS NG is a first step towards building a toxicological knowledge hub leveraging many public data systems for chemical safety evaluation. We continue to monitor the feedback from the user community at support@mn-am.com.

The threat of veterinary medicinal products and biocides on pollinators: A One Health perspective.

The One Health approach acknowledges that human health is firmly linked to animal and environmental health. It involves using animals such as bees and other pollinators as sentinels for environmental contamination or biological indicators. Beekeepers noticed intoxications of apiaries located in the vicinity of sheep and cattle farms, which led to the suspicion of bees' intoxication by the products used for livestock: veterinary medicinal products (VMPs) and Biocides, confirmed by laboratory analysis. We review the legal context of VMPs and Biocidal products considering Europe as a case study, and identify shortcomings at the environmental level. We describe the possible ways these products could intoxicate bees in the vicinity of livestock farms. We also illustrate the way they may impact non-target species. The cases of ivermectin and abamectin as VMPs, deltamethrin and permethrin as Biocides are considered as case studies. We show bees can be exposed to new and unrecognized routes of exposure to these chemicals, and demonstrate that their application in livestock farming can affect the survival of pollinators, such as bees. We conclude that: (1) figures on the marketing/use of these chemicals should be harmonized, centralized and publicly available, (2) research should be devoted to clarifying how pollinators are exposed to VMPs and Biocides, (3) toxicity studies on bees should be carried out, and (4) pollinators should be considered as non-targeted species concerning the environmental risk assessment before their marketing authorization. We propose the term "Multi-use substances" for active ingredients with versatile use.

Towards the design of organosilicon compounds for environmental degradation by using structure biodegradability relationships.

Organosilicon compounds have numerous applications in consumer products. After entering the environment most of them are resistant against microbial degradation and they persist in the environment. Accordingly, they are ubiquitously present in the environment. Therefore, better environmentally degradable organosilicon compounds are urgently needed. A systematic investigation of environmental degradability of organosilicon compounds allows to derive some general design principles, which in turn would enable chemists to reduce or better avoid environmental persistence of organosilicon compounds in the environment. Therefore, in this study, all organosilicon substances registered in the European Chemicals Agency (ECHA) database were evaluated for their environmental biodegradability. Results of own experiments with different organosilicon substances were added to extend the data basis. A dataset was generated. An assessment of all data was done and invalid data were excluded. The remaining 182 substances were grouped regarding their structure to derive general rules for the environmental biodegradability of organosilicon compounds. Non-biodegradable at all were for example cyclic, linear and branched siloxanes. Groups like ethers, esters, oximes, amines, and amides were prone to hydrolysis, which can result in readily biodegradable intermediates if they do not contain silicon functional groups anymore. This knowledge could be used for the design of better degradable organosilicon compounds as non-degradable substances should be avoided if they enter the environment after their usage.

Measuring particle size distribution and mass concentration of nanoplastics and microplastics: addressing some analytical challenges in the sub-micron size range.

HYPOTHESIS: The implementation of the proposal from the European Chemical Agency (ECHA) to restrict the use of nanoplastics (NP) and microplastics (MP) in consumer products will require reliable methods to perform size and mass-based concentration measurements. Analytical challenges arise at the nanometre to micrometre interface, e.g., 800 nm-10 µm, where techniques applicable at the nanometre scale reach their upper limit of applicability and approaches applicable at the micrometre scale must be pushed to their lower limits of detection. EXPERIMENTS: Herein, we compared the performances of nine analytical techniques by measuring the particle size distribution and mass-based concentration of polystyrene mixtures containing both nano and microparticles, with the educational aim to underline applicability and limitations of each technique. FINDINGS: Light scattering-based measurements do not have the resolution to distinguish multiple populations in polydisperse samples. Nanoparticle tracking analysis (NTA), nano-flowcytometry (nFCM) and asymmetric flow field flow fractionation hyphenated with multiangle light scattering (AF4-MALS) cannot measure particles in the micrometre range. Static light scattering (SLS) is not able to accurately detect particles below 200 nm, and similarly to transmission electron microscopy (TEM) and flow cytometry (FCM), is not suitable for accurate mass-based concentration measurements. Alternatives for high-resolution sizing and concentration measurements in the size range between 60 nm and 5 µm are tunable resistive pulse sensing (TRPS) and centrifugal liquid sedimentation (CLS), that can bridge the gap between the nanometre and micrometre range.

Assessment of exposure determinants and exposure levels by using stationary concentration measurements and a probabilistic near-field/far-field exposure model.

Background: The Registration, Evaluation, Authorization and Restriction of Chemicals (REACH) regulation requires the establishment of Conditions of Use (CoU) for all exposure scenarios to ensure good communication of safe working practices. Setting CoU requires the risk assessment of all relevant Contributing Scenarios (CSs) in the exposure scenario. A new CS has to be created whenever an Operational Condition (OC) is changed, resulting in an excessive number of exposure assessments. An efficient solution is to quantify OC concentrations and to identify reasonable worst-case scenarios with probabilistic exposure modeling. Methods: Here, we appoint CoU for powder pouring during the industrial manufacturing of a paint batch by quantifying OC exposure levels and exposure determinants. The quantification was performed by using stationary measurements and a probabilistic Near-Field/Far-Field (NF/FF) exposure model. Work shift and OC concentration levels were quantified for pouring TiO 2 from big bags and small bags, pouring Micro Mica from small bags, and cleaning. The impact of exposure determinants on NF concentration level was quantified by (1) assessing exposure determinants correlation with the NF exposure level and (2) by performing simulations with different OCs. Results: Emission rate, air mixing between NF and FF and local ventilation were the most relevant exposure determinants affecting NF concentrations. Potentially risky OCs were identified by performing Reasonable Worst Case (RWC) simulations and by comparing the exposure 95 th percentile distribution with 10% of the occupational exposure limit value (OELV). The CS was shown safe except in RWC scenario (ventilation rate from 0.4 to 1.6 1/h, 100 m 3 room, no local ventilation, and NF ventilation of 1.6 m 3/min). Conclusions: The CoU assessment was considered to comply with European Chemicals Agency (ECHA) legislation and EN 689 exposure assessment strategy for testing compliance with OEL values. One RWC scenario would require measurements since the exposure level was 12.5% of the OELV.

Worldwide actions against plastic pollution from microbeads and microplastics in cosmetics focusing on European policies. Has the issue been handled effectively?

Microbeads are solid primary microplastics < 5 mm in diameter that are added to cosmetic products for cleansing and/or exfoliation of the skin. After use, they are discharged into the drain and end up in Wastewater Treatment Plants (WWTPs), from which they can escape into waters. Once disposed, there is no efficient method of recovery and the environmental conditions do not allow full biodegradation. Focusing mainly on the possible effect of microbeads on the environment and the human health, and taking into account that there have always been alternatives with similar cost, scientists suggested banning microbeads from cosmetic products. Despite the increasing knowledge on the microplastics' effects, the pressure from non-governmental organizations (NGO's) and the increasing public concern, few European and other countries worldwide have taken legislative steps against microbeads, and even fewer against other microplastics used in cosmetic products, mainly because it is a common belief that cosmetic industries responded massively to the call for a phase-out. Although EU acted soon after scientists focused on microbeads' effects by restricting cosmetics with microbeads to bare the EU Ecolabel in 2014, there is still no European-wide ban, which will probably take place as of 2022. Present study offers a thorough literature review on the presence of microbeads in cosmetics up to date, focusing primarily on the actions against their use, and questioning whether future pollution from microbeads or/and microplastics in cosmetics has been successfully handled.

Analysis and reflection on the role of the 90-day oral toxicity study in European chemical risk assessment.

The 90-day toxicity study is one of the studies used in the safety assessment of food ingredients, medicines or other chemical substances. This paper reviews the current role of the 90-day oral toxicity study in European regulatory dossiers of chemicals by reviewing EU legislation and EU and OECD guidance documents. Regulatory provisions with regard to necessity, objectives and design of such 90-day toxicity studies vary between the different sectors addressed in this review. Most often the 90-day study is expected to be part of the standard test battery used for chemical risk assessment, without necessarily being a legal requirement and its objectives may vary between regulatory domains. Exceptions, when a 90-day study is not required are spelled out in the chemicals legislation and for food contact materials. The sectorial study design requirements of the 90-day toxicity study are very often embedded in the OECD TG 408 protocol. Differences in study objectives are not necessarily reflected in specific study designs. Considering the call for the reduction of using experimental animals for scientific purposes and the fact that a 90-day study may serve different purposes, consistency between the necessity to conduct such a study, its objectives and the study design to achieve these objectives may improve judicious use of laboratory animals. Thus there may be an opportunity to reflect and further optimise the design of in vivo toxicology studies, such as the 90-day study. This should be based on a systematic analysis of past studies and risk assessments.

Predicting PBT and CMR properties of substances of very high concern (SVHCs) using QSAR models, and application for K-REACH.

Quantitative structure-activity relationship (QSAR) models have been applied to predict a variety of toxicity endpoints. Their performance needs to be validated, in a variety of cases, to increase their applicability to chemical regulation. Using the data set of substances of very high concern (SVHCs), the performance of QSAR models were evaluated to predict the persistence and bioaccumulation of PBT, and the carcinogenicity and mutagenicity of CMR. BIOWIN and Toxtree showed higher sensitivity than other QSAR models - the former for persistence and bioaccumulation, the latter for carcinogenicity. In terms of mutagenicity, the sensitivities of QSAR models were underestimated, Toxtree was more accurate and specific than lazy structure-activity relationships (LAZARs) and Computer Assisted Evaluation of industrial chemical Substances According to Regulations (CAESAR). Using the weight of evidence (WoE) approach, which integrates results of individual QSAR models, enhanced the sensitivity of each toxicity endpoint. On the basis of obtained results, in particular the prediction of persistence and bioaccumulation by KOWWIN, a conservative criterion is recommended of log Kow greater than 4.5 in K-REACH, without an upper limit. This study suggests that reliable production of toxicity data by QSAR models is facilitated by a better understanding of the performance of these models.

Indicators for lack of systemic availability of organic pigments.

Experimental data of all 143 organic pigments registered with the European Chemicals Agency, of which 88 were listed in a nanomaterial inventory, was retrieved from the registered substance fact sheets. Availability of the data was 93% for solubility, 82% for bacterial mutagenicity, 79% for acute oral toxicity, 75% for irritation, 59% for skin sensitisation, 36% for repeated dose toxicity and 34% for each clastogenicity and mutagenicity in mammalian cells and 23% for toxicity to reproduction. Pigments mostly had a water and octanol solubility of significantly below 0.1 mg/L, but fourteen were found to be of higher solubility. None were irritating to skin and eyes. Except for the metal salt and the ß-naphthol pigments, none of the insoluble pigments showed adverse effects up to limit doses indicating that poor solubility prevents systemic uptake of toxicologically relevant amounts. The few available toxicokinetic data shows absence of metabolism or significant uptake and is in support of this. Occasional effects observed on bacterial mutagenicity and skin sensitisation are attributed to impurities. There is no indication that for organic pigments other particle characteristics such as surface area or morphology have an impact on the investigated toxicological endpoints.

Marine Polyhydroxynaphthoquinone, Echinochrome A: Prevention of Atherosclerotic Inflammation and Probable Molecular Targets.

The effect of low doses of echinochrome A (EchA), a natural polyhydroxy-1,4-naphthoquinone pigment from the sea urchin Scaphechinus mirabilis, has been studied in clinical trials, when it was used as an active substance of the drug Histochrome® and biologically active supplement Thymarin. Several parameters of lipid metabolism, antioxidant status, and the state of the immune system were analyzed in patients with cardiovascular diseases (CVD), including contaminating atherosclerosis. It has been shown that EchA effectively normalizes lipid metabolism, recovers antioxidant status and reduces atherosclerotic inflammation, regardless of the method of these preparations' administrations. Treatment of EchA has led to the stabilization of patients, improved function of the intracellular matrix and decreased epithelial dysfunction. The increased expression of surface human leukocyte antigen DR isotype (HLA-DR) receptors reflects the intensification of intercellular cooperation of immune cells, as well as an increase in the efficiency of processing and presentation of antigens, while the regulation of CD95 + expression levels suggests the stimulation of cell renewal processes. The immune system goes to a different level of functioning. Computer simulations suggest that EchA, with its aromatic structure of the naphthoquinone nucleus, may be a suitable ligand of the cytosolic aryl cell receptor, which affects the response of the immune system and causes the rapid expression of detoxification enzymes such as CYP and DT diaphorase, which play a protective role with CVD. Therefore, EchA possesses not only an antiradical effect and antioxidant activity, but is also a SOD3 mimetic, producing hydrogen peroxide and controlling the expression of cell enzymes through hypoxia-inducible factors (HIF), peroxisome proliferator-activated receptors (PPARs) and aryl hydrocarbon receptor (AhR).