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Oxidative stress (OS) can induce cell apoptosis and thus plays an important role in aging. Antioxidant foods protect tissues from OS and contribute to a healthier lifestyle. In this study, we described the used of medaka embryos (Oryzias latipes) to study the putative antioxidant capacity of dietary cocoa extract in vertebrates. A polyphenol-enriched cocoa extract regulated the expression of several genes implicated in OS, thereby protecting fish embryos from induced OS. The cocoa extract activated superoxide dismutase enzyme activity in embryos and adult fish tissues, suggesting a common mechanism for protection during embryonic development and adulthood. Furthermore, long-term feeding of the cocoa extract increased fish life span. Our study demonstrates that the polyphenol-enriched cocoa extract decreases OS and extends life span in medaka fish, validating the use of medaka embryos as an economical platform to screen the antioxidant capacity of food compounds.

This study outlines how a combination of and in vitro data can be used to define the applicability domain of selected structural alerts within the protein binding profilers of the Organisation for Economic Co-operation (OECD) Quantitative Structure-Activity Relationship (QSAR) Toolbox. Thirty chemicals containing a cyclic moiety were profiled for reactivity using the OECD and Optimised Approach based on Structural Indices Set (OASIS) protein binding profilers. The profiling results identified 22 of the chemicals as being reactive towards proteins. Analysis of the experimentally data showed 19 of these chemicals to be reactive. Subsequent analysis allowed refinements to be suggested to improve the applicability domain of the structural alerts investigated. The accurate definition of the applicability domain for structural alerts within in silico profilers is important due to their use in chemical category in predictive and regulatory toxicology.

44The desire to reduce the number of animals used in experiments has highlighted the need to 45 standardise and validate in vitro methods as alternatives to bioaccumulation studies using fish. 46The present work details a process based on five criteria to develop a list of reference 47 compounds to evaluate alternative test methods to standard assays using rainbow trout 48 (Oncorhynchus mykiss). The approach was based on: 1) inclusion of relevant chemical classes 49for bioaccumulation and supported by data on bioconcentration factor (BCF), whole body 50 biotransformation rate (Kmet) and metabolic pathways (criteria 1-2); 2) cover a broad range of 51 bioconcentration potencies, logarithmof octanol-water coefficient (Log Kow), metabolic 52 susceptibility, molecular weight and maximum molecular diameter (criteria 3-4); and 3) 53 identification of chemicals that are unsuitable for in vitro testing according to cut-off values for 54 hydrolysis, volatility in solution and lipophilicity (criterion 5). In silico techniques were 55 employed to predict maximal log BCF, Kmet and the metabolic pathway for those chemicals for 56 which in vivo data for some of these properties were not available. Of the 139 compounds 57 considered as reference compounds, 51 were supported by high quality in vivo BCF, 22 58 compounds were supported by either in vivo Kmet or metabolic biotransformation data and ten 59 chemicals did not pass volatility and lipophilicity cut-off values. The list of reference 60 compounds is anticipated to provide a transparent basis for future experimental assessment of 61 the applicability of alternative methods for bioaccumulation assessment within the larger 62 scientific community. The potential of a compound to bioaccumulate is one of many hazardous properties that needs 67 to be evaluated in risk assessment procedures. Although bioaccumulation refers to the 68 accumulation of a substance in an organism from all routes of exposure (from the environment 69 and diet), the bioaccumulation of chemicals is usually expressed by the bioconcentration factor 70 (BCF) that refers only to its accumulation from the environment in a waterborne exposure. In 71 aquatic risk assessments, BCFs have been measured in fish according to the Organisation for 72Economic Cooperation and Development (OECD) Test Guideline305 [1][2]. 73In vivo test systems for bioaccumulation are demanding in terms of resources and the use of 74 large number of animals per test substance. Coupled with this, compliance with legislation such 75 as the European Union REACH (Registration, Evaluation, Authorisation and restriction of 76 Chemicals) regulation [3] has the potential to increase the demand for animal testing to assess 77 bioaccumulation for a large number of chemicals. Other methods such as in silico (computer-78 based) and in vitro techniques have been proposed as alternatives to in vivo testing since they 79 comply better with the principles of the 3Rs (reduction, refinement and replacement) for animal 80 testing [4]. 81In silic...