Applying Adverse Outcome Pathways (AOPs) to support Integrated Approaches to Testing and Assessment (IATA)

This paper is the result of an international initiative and is a first attempt to develop guidelines for the care and welfare of cephalopods (i.e. nautilus, cuttlefish, squid and octopus) following the inclusion of this Class of ∼700 known living invertebrate species in Directive 2010/63/EU. It aims to provide information for investigators, animal care committees, facility managers and animal care staff which will assist in improving both the care given to cephalopods, and the manner in which experimental procedures are carried out. Topics covered include: implications of the Directive for cephalopod research; project application requirements and the authorisation process; the application of the 3Rs principles; the need for harm-benefit assessment and severity classification. Guidelines and species-specific requirements are provided on: i. supply, capture and transport; ii. environmental characteristics and design of facilities (e.g. water quality control, lighting requirements, vibration/noise sensitivity); iii. accommodation and care (including tank design), animal handling, feeding and environmental enrichment; iv. assessment of health and welfare (e.g. monitoring biomarkers, physical and behavioural signs); v. approaches to severity assessment; vi. disease (causes, prevention and treatment); vii. scientific procedures, general anaesthesia and analgesia, methods of humane killing and confirmation of death. Sections covering risk assessment for operators and education and training requirements for carers, researchers and veterinarians are also included. Detailed aspects of care and welfare requirements for the main laboratory species currently used are summarised in Appendices. Knowledge gaps are highlighted to prompt research to enhance the evidence base for future revision of these guidelines.

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Guidelines for the Care and Welfare of Cephalopods in Research -A consensus based on an initiative by CephRes, FELASA and the Boyd Group.

Regulation (EC) 1107/2009 lays down the main instruments for placing effective plant protection products (using pesticide substances) on the market that are safe for humans, animals and the environment, while at the same time ensuring effective functioning of the internal market and improved agricultural production. This European Implementation Assessment found that the above objectives, while largely relevant to real needs, are not being achieved in practice. In particular, the day to day implementation of the main instruments of the regulation – substance approval, plant protection product authorisation and enforcement of the regulatory decisions taken in the frame of the approvals and authorisations – is problematic, which also affects other related EU policies. Nevertheless, despite the implementation challenges observed, stakeholders including national competent authorities, health/environment NGOs, manufacturers of substances and plant protection products and their users (farmers), agree that the EU is the appropriate level at which regulatory action in the field of pesticides (used in plant protection products) should continue to take place. European Implementation Assessment AUTHORS (INTRODUCTION) European Implementation Assessment written by Alina DINU and Ekaterina KARAMFILOVA from the Ex-Post Evaluation Unit, Directorate for Impact Assessment and European Added Value, European Parliamentary Research Service. To contact the Unit, please email: EPRS-ExPostEvaluation@ep.europa.eu The authorship of the annexed studies, commissioned by EPRS, is set out in the following pages, and in each annex. RESPONSIBLE ADMINISTRATORS Alina DINU and Ekaterina KARAMFILOVA, Ex-Post Evaluation Unit. To contact the Unit, please e-mail EPRS-ExPostEvaluation@ep.europa.eu

The placing of plant protection products on the market

https://bura.brunel.ac.uk/bitstream/2438/12452/1/Fulltext.pdf

OECD validation study to assess intra- and inter-laboratory reproducibility of the zebrafish embryo toxicity test for acute aquatic toxicity testing

Originally designed as an alternative for the acute fish toxicity test according to, e.g., OECD TG 203, the fish embryo test (FET) with the zebrafish (Danio rerio) has been optimized, standardized, and validated during an OECD validation study and adopted as OECD TG 236 as a test to assess toxicity of embryonic forms of fish. Given its excellent correlation with the acute fish toxicity test and the fact that non-feeding developmental stages of fish are not categorized as protected stages according to the new European Directive 2010/63/EU on the protection of animals used for scientific purposes, the FET is ready for use not only for range-finding but also as a true alternative for the acute fish toxicity test, as required for a multitude of national and international regulations. If—for ethical reasons—not accepted as a full alternative, the FET represents at least a refinement in the sense of the 3Rs principle. Objections to the use of the FET have mainly been based on the putative lack of biotransformation capacity and the assumption that highly lipophilic and/or high molecular weight substances might not have access to the embryo due to the protective role of the chorion. With respect to bioactivation, the only substance identified so far as not being activated in the zebrafish embryo is allyl alcohol; all other biotransformation processes that have been studied in more detail so far were found to be present, albeit, in some cases, at lower levels than in adult fish. With respect to larger molecules, the extension of the test duration to 96 h (i.e., beyond hatch) has—at least for the substances tested so far—compensated for the reduced access to the embryo; however, more research is necessary to fully explore the applicability of the FET to substances with a molecular weight >3 kDa as well as substances with a neurotoxic mode of action. An extension of the endpoints to also cover sublethal endpoints makes the FET a powerful tool for the detection of teratogenicity, dioxin-like activity, genotoxicity and mutagenicity, neurotoxicity, as well as various forms of endocrine disruption.

Mauricio García-Franco

Papers

A European perspective on alternatives to animal testing for environmental hazard identification and risk assessment

Anaesthetics for the squid Sepioteuthis sepioidea (mollusca: cephalopoda)