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The European Partnership for Alternative Approaches to Animal Testing (EPAA) convened a Partners' Forum Toxicokinetics and Read-Across to provide an overview on research activities to develop in vitro toxicokinetics methods and physiologically-based kinetic (PBK) models and to find synergies to enhance use of toxicokinetic data to strengthen read-across. Currently, lacking toxicokinetic data often prevent the application of read-across. Preferably, toxicokinetic data should be generated using in vitro and in silico tools and anchored towards human relevance. In certain sectors, PBK modelling is being used for risk assessment, but less so in others. Specific activities were identified to facilitate the use of in vitro and in silico toxicokinetic data to support read-across: The collation of available tools indicating the parameters and applicability domains covered; endpoint-specific guidance on toxicokinetics parameters required for read-across; case studies exemplifying how toxicokinetic data help support read-across. Activities to enhance the scientific robustness of read-across include the further user-friendly combination of read-across tools and formal guidance by the authorities specifying the minimum information requirements to justify read-across for a given toxicity endpoint. The EPAA was invited to continue dissemination activities and to explore possibilities to collate a contemporaneous list of open toxicokinetics tools that assist risk assessment.

EU regulations call for the use of alternative methods to animal testing. During the last decade, an increasing number of alternative approaches have been formally adopted. In parallel, new 3Rs-relevant technologies and mechanistic approaches have increasingly contributed to hazard identification and risk assessment evolution. In this changing landscape, an EPAA meeting reviewed the challenges that different industry sectors face in the implementation of alternative methods following a science-driven approach. Although clear progress was acknowledged in animal testing reduction and refinement thanks to an integration of scientifically robust approaches, the following challenges were identified: i) further characterization of toxicity pathways; ii) development of assays covering current scientific gaps, iii) better characterization of links between in vitro readouts and outcome in the target species; iv) better definition of alternative method applicability domains, and v) appropriate implementation of the available approaches. For areas having regulatory adopted alternative methods (e.g., vaccine batch testing), harmonised acceptance across geographical regions was considered critical for broader application. Overall, the main constraints to the application of non-animal alternatives are the still existing gaps in scientific knowledge and technological limitations. The science-driven identification of most appropriate methods is key for furthering a multi-sectorial decrease in animal testing.

Objective: The objective was to evaluate the effects of vertical key spacing on a conventional computer keyboard on typing speed, percentage error, usability, forearm muscle activity, and wrist posture for both females with small fingers and males with large fingers. Background: Part 1 evaluated primarily horizontal key spacing and found that for male typists with large fingers, productivity and usability were similar for spacings of 17, 18, and 19 mm but were reduced for spacings of 16 mm. Few other key spacing studies are available, and the international standards that specify the spacing between keys on a keyboard have been mainly guided by design convention. Method: Experienced female typists ( n = 26) with small fingers (middle finger length ≤ 7.71 cm or finger breadth of ≤ 1.93 cm) and male typists ( n = 26) with large fingers (middle finger length ≥ 8.37 cm or finger breadth of ≥ 2.24 cm) typed on five keyboards that differed primarily in vertical key spacing (17 × 18, 17 × 17, 17 × 16, 17 × 15.5, and 18 × 16 mm) while typing speed, error, fatigue, preference, forearm muscle activity, and wrist posture were recorded. Results Productivity and usability ratings were significantly worse for the keyboard with 15.5 mm vertical spacing compared to the other keyboards for both groups. There were few significant differences on usability ratings between the other keyboards. Reducing vertical key spacing, from 18 to 17 to 16 mm, had no significant effect on productivity or usability. Conclusions: The findings support the design of keyboards with vertical key spacings of 16, 17, or 18 mm. Applications: These findings may influence keyboard design and standards.

Work-related upper extremity musculoskeletal disorders, including carpal tunnel syndrome, are prevalent among dentists and dental hygienists. An important risk factor for developing these disorders is forceful pinching which occurs during periodontal work such as dental scaling. Ergonomically designed dental scaling instruments may help reduce the prevalence of carpal tunnel syndrome among dental practitioners. In this study, eight custom-designed dental scaling instruments with different handle shapes were used by 24 dentists and dental hygienists to perform a simulated tooth scaling task. The muscle activity of two extensors and two flexors in the forearm was recorded with electromyography while thumb pinch force was measured by pressure sensors. The results demonstrated that the instrument handle with a tapered, round shape and a 10 mm diameter required the least muscle load and pinch force when performing simulated periodontal work. The results from this study can guide dentists and dental hygienists in selection of dental scaling instruments.

Laroche Carlo. Les archives du Ministère de la France d'Outre-Mer. In: La Gazette des archives, n°4, 1948. pp. 15-20.

Laroche Charles. Les archives de l'expansion française outre-mer conservées en Métropole. In: La Gazette des archives, n°55, 1966. pp. 235-252.

The European Partnership for Alternative Approaches to Animal Testing (EPAA) convened a Partners' Forum on repeated dose toxicity (RDT) testing to identify synergies between industrial sectors and stakeholders along with opportunities to progress these in existing research frameworks. Although RTD testing is not performed across all industrial sectors, the OECD accepted tests can provide a rich source of information and play a pivotal role for safety decisions relating to the use of chemicals. Currently there are no validated alternatives to repeated dose testing and a direct one-to-one replacement is not appropriate. However, there are many projects and initiatives at the international level which aim to implement various aspects of replacement, reduction and refinement (the 3Rs) in RDT testing. Improved definition of use, through better problem formulation, aligned to harmonisation of regulations is a key area, as is the more rapid implementation of alternatives into the legislative framework. Existing test designs can be optimised to reduce animal use and increase information content. Greater use of exposure-led decisions and improvements in dose selection will be beneficial. In addition, EPAA facilitates sharing of case studies demonstrating the use of Next Generation Risk Assessment applying various New Approach Methodologies to assess RDT.