Screening and prioritization of nano- and microplastic particle toxicity studies for evaluating human health risks – development and application of a toxicity study assessment tool

Concern regarding the human health implications that exposure to nano- and microplastic particles (NMPs) potentially represents is increasing. While there have been several years of research reporting on the ecotoxicological effects of NMPs, human health toxicology studies have only recently emerged. The available human health hazard data are thus limited, with potential concern regarding the relevance and reliability for understanding the potential human health implications. In this study we develop and apply a NMP toxicity screening assessment tool (NMP-TSAT) for evaluating human health effects studies against a suite of quality assurance and quality control (QA/QC) criteria for both in vivo and in vitro studies. A total of 74 studies representing either inhalation or oral exposure pathways were identified and evaluated. Assessment categories include particle characterization, experimental design, and applicability for risk assessment; with critical and non-critical criteria organized to allow screening and prioritization. It is observed that the majority of studies evaluated using the NMP-TSAT have been performed on monodisperse particles, predominately spheres (≈60%), consisting of polystyrene (≈46%). The majority of studies have tested particles < 5 μm, with a minimal particle size of 10 nm and a maximum particle size of about 200 μm. The total assessment score (TAS) possible for in vivo studies is 52, whereas for in vitro studies it is 46, which is based on receiving a maximum score of 2 against 26 and 23 criteria, respectively. The evaluated TAS ranged from between 12 and 44 and 16–34, for in vivo and in vitro studies, respectively. Given the challenges associated with prioritizing studies based on ranking them according to their TAS we propose a Tiered approach, whereby studies are initially screened based on how they score against various critical criteria, which have been defined for their relevance for assessing the hazards and risks for human health. In this instance, studies that score a minimum of ‘1’ against each of the critical criteria, regardless of how they rank according to their TAS, are prioritized as part of a Tier 1 screening and prioritization phase, which would then be followed by an expert evaluation, representing a Tier 2 level of assessment. Using this approach we identify 10 oral ingestion and 2 inhalation studies that score at least 1 against all critical criteria. Lastly, several key observations for strengthening future effects studies are identified, these include a need for the generation and access to standard reference materials representative of human exposure to NMPs for use in toxicity test systems and/or the improved characterization and verification of test particle characteristics, and the adoption of study design guidance, such as recommended by OECD, when conducting either in vivo inhalation or oral ingestion toxicity tests.

The Biological Effects of 3D Resins Used in Orthodontics: A Systematic Review

Three-dimensional (3D) resin medical-dental devices have been increasingly used in recent years after the emergence of digital technologies. In Orthodontics, therapies with aligners have gained popularity, mainly due to the aggressive promotion policies developed by the industry. However, their systemic effects are largely unknown, with few studies evaluating the systemic toxicity of these materials. The release of bisphenol A and other residual monomers have cytotoxic, genotoxic, and estrogenic effects. This systematic review aims to analyze the release of toxic substances from 3D resins used in Orthodontics and their toxic systemic effects systematically. The PICO question asked was, “Does the use of 3D resins in orthodontic devices induce cytotoxic effects or changes in estrogen levels?”. The search was carried out in several databases and according to PRISMA guidelines. In vitro, in vivo, and clinical studies were included. The in vitro studies’ risk of bias was assessed using the guidelines for the reporting of pre-clinical studies on dental materials by Faggion Jr. For the in vivo studies, the SYRCLE risk of bias tool was used, and for the clinical studies, the Cochrane tool. A total of 400 articles retrieved from the databases were initially scrutinized. Fourteen articles were included for qualitative analysis. The risk of bias was considered medium to high. Cytotoxic effects or estrogen levels cannot be confirmed based on the limited preliminary evidence given by in vitro studies. Evidence of the release of bisphenol A and other monomers from 3D resin devices, either in vitro or clinical studies, remains ambiguous. The few robust results in the current literature demonstrate the absolute need for further studies, especially given the possible implications for the young patient’s fertility, which constitutes one of the largest groups of patients using these orthodontic devices.

Impact of food processing on postprandial glycaemic and appetite responses in normoglycaemic adults: a randomized, controlled trial

Chickpeas are among the lowest glycaemic index carbohydrate food eliciting protracted digestion and enhanced satiety responses. In vitro studies suggest that mechanical processing of chickpeas significantly increases starch digestion. However,...

Synthesis, anti-tubercular evaluation and molecular docking studies of Nitrogen-rich piperazine-pyrimidine-pyrazole Hybrid Motifs

A convenient and efficient synthesis of a series of ethyl-1-(6-(4-substitutedacetylatedpiperazin-1-yl)pyrimidin-4-yl)-5-amino-1H-pyrazole-4-carboxylate (8a-8j) has been developed by five steps which include activation of a methylene group, hydrazinolysis, cyclisation and chloro-amine coupling reactions. Moreover, our proposed mechanism was confirmed in this study demonstrating that ethyl 5-amino-1-(6-chloropyrimidin-4-yl)-1H-pyrazole-4-carboxylate is the key intermediate to fulfill the desired outcomes. In silico and in vitro studies were carried out to identify the active agents among the developed adducts against mycobacterium tuberculosis (PDB ID:4TRO). Compound 8a (Docking Score: -26.81 and MIC: 1.6 ug/mL) was found to be the most potent among the synthesized molecules. All the synthesized compounds showed acceptable drug-like properties which make them suitable for further lead modification using in silico design approaches.