Alternative methods for regulatory toxicology – a state-of-the-art review

This state-of-the art review is based on the final report of a project carried out by the European Commission’s Joint Research Centre (JRC) for the European Chemicals Agency (ECHA). The aim of the project was to review the state of the science of non-standard methods that are available for assessing the toxicological and ecotoxicological properties of chemicals. Non-standard methods refer to alternatives to animal experiments, such as in vitro tests and computational models, as well as animal methods that are not covered by current regulatory guidelines. This report therefore reviews the current scientific status of non-standard methods for a range of human health and ecotoxicological endpoints, and provides a commentary on the mechanistic basis and regulatory applicability of these methods. For completeness, and to provide context, currently accepted (standard) methods are also summarised. In particular, the following human health endpoints are covered: a) skin irritation and corrosion; b) serious eye damage and eye irritation; c) skin sensitisation; d) acute systemic toxicity; e) repeat dose toxicity; f) genotoxicity and mutagenicity; g) carcinogenicity; h) reproductive toxicity (including effects on development and fertility); i) endocrine disruption relevant to human health; and j) toxicokinetics. In relation to ecotoxicological endpoints, the report focuses on non-standard methods for acute and chronic fish toxicity. While specific reference is made to the information needs of REACH, the Biocidal Products Regulation and the Classification, Labelling and Packaging Regulation, this review is also expected to be informative in relation to the possible use of alternative and non-standard methods in other sectors, such as cosmetics and plant protection products.JRC.I.5-Systems Toxicolog

First detection of two superoutbursts during rebrightening phase of a WZ Sge-type Dwarf Nova : TCP J21040470+4631129

We report on photometric and spectroscopic observations and analysis of the 2019 superoutburst of TCP J21040470+4631129. This object showed a 9 mag superoutburst with early superhumps and ordinary superhumps, which are the features of WZ Sge-type dwarf novae. Five rebrightenings were observed after the main superoutburst. The spectra during the post-superoutburst stage showed Balmer, He I, and possible sodium doublet features. The mass ratio is derived as 0.0880(9) from the period of the superhump. During the third and fifth rebrightenings, growing superhumps and superoutbursts were observed, which have never been detected during a rebrightening phase among WZ Sge-type dwarf novae with multiple rebrightenings. To induce a superoutburst during the brightening phase, the accretion disk needs to have expanded beyond the 3 : 1 resonance radius of the system again after the main superoutburst. These peculiar phenomena can be explained by the enhanced viscosity and large radius of the accretion disk suggested by the higher luminosity and the presence of late-stage superhumps during the post-superoutburst stage, plus by more mass supply from the cool mass reservoir and/or from the secondary because of the enhanced mass transfer than those of other WZ Sge-type dwarf novae.peer-reviewe

First Detection of Two Superoutbursts during Rebrightening Phase of a WZ Sge-type Dwarf Nova: TCP J21040470+4631129

We report photometric and spectroscopic observations and analysis of the 2019 superoutburst of TCP J21040470+4631129. This object showed a 9-mag superoutburst with early superhumps and ordinary superhumps, which are the features of WZ Sge-type dwarf novae. Five rebrightenings were observed after the main superoutburst. The spectra during the post-superoutburst stage showed the Balmer, He I and possible sodium doublet features. The mass ratio is derived as 0.0880(9) from the period of the superhump. During the third and fifth rebrightenings, growing superhumps and superoutbursts were observed, which have never been detected during a rebrightening phase among WZ Sge-type dwarf novae with multiple rebrightenings. To induce a superoutburst during the brightening phase, the accretion disk was needed to expand beyond the 3:1 resonance radius of the system again after the main superoutburst. These peculiar phenomena can be explained by the enhanced viscosity and large radius of the disk suggested by the higher luminosity and the presence of late-stage superhumps during the post-superoutburst stage, plus by more mass supply from the cool mass reservoir and/or from the secondary because of the enhanced mass transfer than those of other WZ Sge-type dwarf novae.Comment: 13 pages, 10 figures, accepted for publication in PAS

EVALUATION OF ACCIDENTS AND COMPLICATIONS OF MAXILLARY THIRD MOLAR EXTRACTION

Aim and objectives: The present study aims is to observe and analyse the frequency of occurrence of accidents and complications of wisdom tooth extraction in a group of 60 patients, and the impact of the choice of different extraction techniques. Material and methods: This observational study analyses the statistical data obtain from 60 patients that presented for the extraction of the upper third molar. Demographic data, type of extraction techniques, occurrence of accidents during teeth extraction and the complications after the extractions were evaluated. Conclusions: Following this study, we can affirm that the intraoperative accidents occur in 33% of the cases and the complications of the wisdom teeth extractions appears in 15% of the patients

THE EVALUATION OF LOCO-REGIONAL ANESTHESIA ACCIDENTS AND COMPLICATIONS IN ORAL AND MAXILLOFACIAL SURGERY

Current medical concerns lead to painless and anxiety-free surgical treatment from the time of anesthesia to the completion of therapeutic surgery. Loco-regional anesthesia is widely used for oral and maxillofacial surgical procedures due to the advantages com-pared to the general anesthesia: the collaboration with the patient is maintained during the surgical procedure, the localized anesthesia in the operatory field, the general side-effects and allergic risks are maintained on a minimum level the resumption of patient feeding as soon as the anesthesia is metabolized. On the other hand, the accidents, and the complications of the loco-regional anesthesia in oral and maxillofacial surgery were insufficient studied. Our study is the first one which highlights these aspects and brings a new point of view for understanding the most common and the rarest ones. In this prospective observational study were included 100 patients which presented for different oral and maxillofacial surgical interventions under loco-regional anesthesia. All the anesthesia accidents and complications were noted and discussed. Loco-regional anesthesia remains the safest and most used type of anesthesia in oral and maxillofacial surgery. The accidents and complications can be prevented by knowing local anatomy, pharmacological properties of anesthetic substances and patient comorbidities

Mesenchymal Stem Cells Derived from Human Periapical Cysts and Their Implications in Regenerative Medicine

Mesenchymal stem cells currently play an important role in the tissue engineering field in developing new regenerative approaches. The oral cavity is a rich source of mesenchymal stem cells, and introducing the use of dental stem cells, characterized by a multilineage differentiation potential, immunomodulatory activity and repair capacity, offers a good perspective for clinical dentistry. Human periapical cyst mesenchymal stem cells (hPCy-MSCs) represent a new category of dental stem cells, being collected from pathological tissue and exhibiting MSCs-like properties. As studies have described, these new identified cells possess the same characteristics as those described in MSCs, exhibiting plasticity, a high proliferation rate and the potential to differentiate into osteogenic, adipogenic and neural lineages. Reusing the biological tissue that is considered pathologic offers a new perspective for the development of further clinical applications. The identification and characterization of MSCs in the human periapical cysts allows for a better understanding of the molecular interactions, the potential healing capacity and the mechanisms of inducing the local osteogenic process, integrated in the microenvironment. Although their involvement in regenerative medicine research is recent, they exhibit important properties that refer them for the development of clinical applications in dentistry

Retromolar Triangle Anesthesia Technique: A Feasible Alternative to Classic?

Anesthetic techniques play an important role in the outcome of the therapeutic procedures in dentistry. Although inferior alveolar nerve block (IANB) anesthesia is currently the most often used, there are situations that imply the need of an alternative anesthesia technique to overcome the potential risks and complications. The aim of the study was to evaluate the efficacy of the retromolar triangle anesthesia technique in achieving the desired nerve block, while evaluating the duration of the anesthesia for the included cases. Methods: The present prospective study included 50 subjects that had indication of inferior molar extraction. The performed anesthesia technique for these cases was the retromolar triangle approach, and the analyzed parameters for evaluating the efficacy of this anesthesia technique were the positive nerve block of the branches involved in the area (inferior alveolar, buccal, and lingual nerves) and the duration of the anesthesia. Results: The efficiency of the retromolar triangle anesthesia technique was positive in 64% of the cases for the inferior alveolar nerve, 46% of the cases for the lingual nerve, and 22% of the cases for the buccal nerve. The duration of the anesthesia revealed a mean value of 72.4 min, suggesting that the duration is an essential factor in its effectiveness. Conclusions: Retromolar triangle anesthesia can be a viable option for clinicians, offering a simple and easy approach for the management of clinical cases

The Implications of Titanium Alloys Applied in Maxillofacial Osteosynthesis

Titanium alloys are known for their biological, mechanical and chemical properties, which have successfully expanded their use in the maxillofacial field. The internal fixation using titanium miniplates and screws offer a new perspective for the treatment of trauma and in orthognathic surgery and maxillofacial oncology. Although, titanium is highly recommended for its excellent biocompatibility, recent research has focused on identifying the potential local and general implications of the interactions between the human tissue and the metallic particles. This present review aims to outline the existing tissue changes, cellular alterations and future perspectives regarding the use of titanium-based alloys as osteosynthesis materials, taking into consideration the existing present debate whether the routinely removal of these materials should be an indication

The Influence of Salivary pH on the Prevalence of Dental Caries

Dental caries is the most prevalent chronic oral disease, influencing the oral and systemic health of the individuals, being the result of the interaction of multiple factors, such as microbial agents, the oral environment, the salivary pH, and the host response. The main process that occurs in dental caries is the demineralization of the tooth enamel, process that is directly influenced by the salivary pH, exposing the dental structures to the action of pathological agents. The role of saliva in the etiology of dental caries is a major one, by influencing the homeostasis through the altering of its buffer capacity. The properties of saliva are influenced either by local pathogens or through a general mechanism with direct implications upon the salivary components. The alteration of the salivary pH, flow rate, and composition will further have repercussions upon the cariogenic activity, through a change of its physiochemical properties. Nevertheless, the salivary pH is strongly linked to the incidence of dental caries, any persistent imbalance due to various causes can be assessed as an indicator of the oral health status

The Challenges of OSCC Diagnosis: Salivary Cytokines as Potential Biomarkers

Fast, economic, and noninvasive, molecular analysis of saliva has the potential to become a diagnostic tool of reference for several local and systemic diseases, oral cancer included. The diagnosis of Oral Squamous Cell Carcinoma (OSCC) can be performed using high specificity and sensibility biomarkers that can be encountered in the biological fluids. Recent advances in salivary proteomics have underlined the potential use of salivary biomarkers as early diagnosis screening tools for oral neoplasia. In this respect, over 100 salivary molecules have been described and proposed as oral cancer biomarkers, out of which cytokines are among the most promising. Besides being directly involved in inflammation and immune response, the role of salivary cytokines in tumor growth and progression linked them to the incidence of oral malignant lesions. This review summarizes the existing studies based on the use of salivary cytokines as potential oral cancer biomarkers, their involvement in the malignant process based on their type, and ther influence upon prognostic and metastatic rates