The PD-Utility Function for Prospect Behavior and Related Researches

Based on Partial Distribution [11],[12], we put forward a PD-utility function of prospect behavior for the first time, the profiting utility function and losing utility function. The PD-utility function can reflect sufficiently the human¡¯s risk preferences properties to profiting or losing, describe and bring to light availably the important relations between profiting utility and losing utility, and interpret many conclusions in Daniel Kahneman¡¯s prospect theory in analytic way. Also we present the concepts and analytic expressions of essential indexes of realized level for prospect behavior, the limit value, the balanced value, and focus value, especially the method of calculating them. The limit level is beneficial to judge the reversal position of reality movement trend, and the latter is beneficial to judge that the focus of current reality is reasonableness or not. And we give out the calculating formula for the optimal value of realized level for prospect with its appearing probability.partial distribution, PD-utility function, prospect behavior, essential indexes, optimal value

EURL ECVAM Recommendation on the use of non-animal approaches for skin sensitisation testing

Considerable progress has been made in non-animal methods and approaches for skin sensitisation assessment since the publication in 2013 of the EURL ECVAM strategy for this endpoint. This report illustrates EURL ECVAM views on the regulatory use of individual test methods, including two in vitro methods peer reviewed by ESAC, the LuSens and the U-SENS™ and on defined approaches and provides EURL ECVAM recommendations on future work to be undertaken in the area.JRC.F.3-Chemicals Safety and Alternative Method

EURL ECVAM Recommendation on the Zebrafish Embryo Acute Toxicity Test Method (ZFET) for Acute Aquatic Toxicity Testing

Acute fish toxicity testing is an important component of the environmental hazard assessment of chemicals. Since many years, (zebra-)fish embryo-based methods have been proposed as alternatives to the acute fish toxicity test carried out with juvenile or adult fish. On behalf of the Organisation for Economic Cooperation and Development (OECD), the European Union Reference Laboratory for Alternatives to Animal Testing (EURL ECVAM) coordinated during 2008-2012 the validation of the zebrafish embryo acute toxicity test method (ZFET) to evaluate its reproducibility in support to the development of an OECD Test Guideline. In parallel to this study, Belanger and colleagues continued to collect acute fish embryo toxicity and acute fish toxicity data to assess the relevance, predictive capacity and applicability of the ZFET and submitted their report to EURL ECVAM in July 2012. Following independent scientific peer review by EURL ECVAM's Scientific Advisory Committee (ESAC) of both studies and having considered input from regulators, stakeholders, international partners and the general public, EURL ECVAM concluded that the ZFET - being available as OECD TG236 since 2013 – should be used for generating information on acute fish toxicity, where appropriate. Its use would result in an overall reduction of the numbers of juvenile and adult fish for aquatic toxicity testing. It is recognised that further guidance on the use of OECD TG236 across the various regulatory frameworks and regions should be developed addressing in particular the possible use of the ZFET to generate information on acute fish toxicity and its potential limitations.JRC.I.5-Systems Toxicolog

ECVAM Technical Report on the Status of Alternative Methods for Cosmetics Testing (2008-2009)

The ECVAM technical report presents the progress made in the development and validation of alternative methods for the human health effects relevant to the Cosmetics Directive. It provides an update on the activities described by ECVAM in 2005 , 2006 and 2007 . The report intends to present the latest scientific and technical developments in the field during 2008-2009. As required by Directive 2003/15/EC, the seventh amendment to Directive 76/768/EEC, developments in refinement and reduction methods are also described (EU, 2003). Most successes in the development of alternative methods are in acute local toxicity and short-term testing, such as e.g. skin and eye irritation/corrosion, phototoxicity and skin penetration The test methods consuming a high number of animals, however, are in long-term testing and systemic toxicity, such as e.g. reproductive toxicity and repeated dose toxicity. In these complex fields, several research initiatives are ongoing. However full replacement approaches are still lacking.JRC.DG.I.3-In-vitro method

Warm stellar matter with deconfinement: application to compact stars

We investigate the properties of mixed stars formed by hadronic and quark matter in $\beta$-equilibrium described by appropriate equations of state (EOS) in the framework of relativistic mean-field theory. We use the non- linear Walecka model for the hadron matter and the MIT Bag and the Nambu-Jona-Lasinio models for the quark matter. The phase transition to a deconfined quark phase is investigated. In particular, we study the dependence of the onset of a mixed phase and a pure quark phase on the hyperon couplings, quark model and properties of the hadronic model. We calculate the strangeness fraction with baryonic density for the different EOS. With the NJL model the strangeness content in the mixed phase decreases. The calculations were performed for T=0 and for finite temperatures in order to describe neutron and proto-neutron stars. The star properties are discussed. Both the Bag model and the NJL model predict a mixed phase in the interior of the star. Maximum allowed masses for proto-neutron stars are larger for the NJL model ($\sim 1.9$ M$_{\bigodot}$) than for the Bag model ($\sim 1.6$ M$_{\bigodot}$).Comment: RevTeX,14 figures, accepted to publication in Physical Review

The EURL ECVAM - Cosmetics Europe prospective validation study of Reconstructed human Cornea-like Epithelium (RhCE)-based test methods for identifying chemicals not requiring classification and labelling for serious eye damage/eye irritation: Validation Study Report

A prospective validation study of two Reconstructed human Tissue-based in vitro test methods (EpiOcular™ EIT and SkinEthic™ HCE) was conducted by EURL ECVAM and Cosmetics Europe to evaluate their usefulness to identify chemicals as either not classified for serious eye damage/eye irritation (No Category) or as classified (Category 1/Category 2) within UN GHS, in the framework of a Bottom-Up/Top-Down test strategy [1]. The study assessed the validity of two EpiOcular™ EIT protocols for liquids and solids, two independent SkinEthic™ HCE protocols based on short-time (SE) and long-time (LE) exposures and a test strategy combining SE and LE. The results and conclusions of this study will be presented. Briefly, over 100 chemicals were tested and both methods showed high reproducibility (>90%). The EpiOcular™ EIT liquids protocol met all the study acceptance criteria for predictive capacity [2], but not all of these criteria were met by the solids protocol nor by any of the SkinEthic™ HCE protocols/strategy. This led to optimisation of the EpiOcular™ EIT solids protocol and further validation being conducted. With final sensitivity of 96%, specificity of 63% and accuracy of 80%, the EpiOcular™ EIT met all the study acceptance criteria and is considered valid for the proposed study objective.JRC.I.5-Systems Toxicolog

Retrospective analysis of the Draize test for serious eye damage/eye irritation: importance of understanding the in vivo endpoints under UN GHS/EU CLP for the development and evaluation of in vitro test methods

For more than two decades, scientists have been trying to replace the regulatory in vivo Draize eye test by in vitro methods, but so far only partial replacement has been achieved. In order to better understand the reasons for this, historical in vivo rabbit data were analysed in detail and resampled with the purpose of (1) revealing which of the in vivo endpoints are most important in driving United Nations Globally Harmonized System/European Union Regulation on Classification, Labelling and Packaging (UN GHS/EU CLP) classification for serious eye damage/eye irritation and (2) evaluating the method’s within-test variability for proposing acceptable and justifiable target values of sensitivity and specificity for alternative methods and their combinations in testing strategies. Among the Cat 1 chemicals evaluated, 36–65 % (depending on the database) were classified based only on persistence of effects, with the remaining being classified mostly based on severe corneal effects. Iritis was found to rarely drive the classification (<4 % of both Cat 1 and Cat 2 chemicals). The two most important endpoints driving Cat 2 classification are conjunctiva redness (75–81 %) and corneal opacity (54–75 %). The resampling analyses demonstrated an overall probability of at least 11 % that chemicals classified as Cat 1 by the Draize eye test could be equally identified as Cat 2 and of about 12 % for Cat 2 chemicals to be equally identified as No Cat. On the other hand, the over-classification error for No Cat and Cat 2 was negligible (<1 %), which strongly suggests a high over-predictive power of the Draize eye test. Moreover, our analyses of the classification drivers suggest a critical revision of the UN GHS/EU CLP decision criteria for the classification of chemicals based on Draize eye test data, in particular Cat 1 based only on persistence of conjunctiva effects or corneal opacity scores of 4. In order to successfully replace the regulatory in vivo Draize eye test, it will be important to recognise these uncertainties and to have in vitro tools to address the most important in vivo endpoints identified in this paper.JRC.I.5-Systems Toxicolog

EURL ECVAM Status Report on the Development, Validation and Regulatory Acceptance of Alternative Methods and Approaches (2013-April 2014)

The EURL ECVAM status report provides an update on the progress made in the development, validation and regulatory acceptance of alternative methods and approaches since the last report published in April 2013. It is informing on ongoing research and development activities, validation studies, peer reviews, recommendations, strategies and international acceptance of alternative methods and approaches. R&D activities are ongoing for the complex endpoints where the toxicological processes and the mechanistic understanding have not been sufficiently elucidated yet and for which 3Rs solutions are more difficult to find. On the other hand, good progress In the validation and regulatory acceptance is made in areas where non-animal alternative methods have been developed and validated and where the focus lies in an intelligent combination/ integration of the various non-animal approaches.JRC.I.5-Systems Toxicolog

Stochastic Model of Tsc1 Lesions in Mouse Brain

Tuberous sclerosis complex (TSC) is an autosomal dominant disorder due to mutations in either TSC1 or TSC2 that affects many organs with hamartomas and tumors. TSC-associated brain lesions include subependymal nodules, subependymal giant cell astrocytomas and tubers. Neurologic manifestations in TSC comprise a high frequency of mental retardation and developmental disorders including autism, as well as epilepsy. Here, we describe a new mouse model of TSC brain lesions in which complete loss of Tsc1 is achieved in multiple brain cell types in a stochastic pattern. Injection of an adeno-associated virus vector encoding Cre recombinase into the cerebral ventricles of mice homozygous for a Tsc1 conditional allele on the day of birth led to reduced survival, and pathologic findings of enlarged neurons, cortical heterotopias, subependymal nodules, and hydrocephalus. The severity of clinical and pathologic findings as well as survival was shown to be dependent upon the dose and serotype of Cre virus injected. Although several other models of TSC brain disease exist, this model is unique in that the pathology reflects a variety of TSC-associated lesions involving different numbers and types of cells. This model provides a valuable and unique addition for therapeutic assessment