Update of the Progress

Biocides are a specific group of chemicals used in the treatment of damaging biological growth. However, not only do they kill pathogens, they also kill non-pathogens, meaning they may have undesirable side effects harming human health and/or the environment.

The use of non-animal alternative test methods has been foreseen in the Biocides Product Regulation, Regulation (EU) 258/2012 (BPR). The widespread use of non-testing methods (NTM) would help SMEs identifying, amongst other, the so called metabolites of ecotoxicological concern whereas facilitating the approval of Biocidal Active Substances (BASs) within the BPR and reducing animal testing.

Chemoinformatics, consists in the ensemble of computational tools for the management of chemical information in order to generate knowledge from data, thus facilitating faster and better decisions. Usual chemoinformatic tasks include the transformation of chemical information into numerical data and the consequent application of mathematical methods to infer chemical knowledge related to the similarity/diversity of compounds, or the predictions of physicochemical, pharmacokinetic and/or toxicological properties.

The LIFE-COMBASE Project promotes the sustainable use of BASs from a life cycle perspective by means of computational tools.

The outputs of the preparatory actions are described next.

Within Action A.1. Selection of main substances and target groups of pesticides, BASs that are currently approved or under review for all product types (PTs) have been reviewed. Critical data have been retrieved in relation to the nature of the substance and on its ecotoxicological potential including also environmental fate parameters. Trophic levels considered include: fish, invertebrate, algae and microorganisms. Whenever available, information related to the environmentally relevant metabolites has also been retrieved. It has been noted that information concerning metabolites is rather limited both from substance identification perspective but also in relation to their ecotoxicological potential.

In the frame of Action A.2. Critical studies on existing modelling approaches with risk assessment purposes, a series of literature references have been screened in order to identify available QSAR models for the prediction of the ecotoxicological potential of BAS. Subsequently, a detailed analysis of their performance/quality in agreement with the OECD standard protocols has been performed. Furthermore, programs for the prediction of degradation products of chemicals and their corresponding toxicity have been identified and critically reviewed. Finally, the data sets for the optimization of the models have been prepared, having selected for models optimization only chemicals with a well-defined structure.

Preparatory action A.3.Requirements and specifications of the COMBASE software platform has consisted in generating a database integrating stakeholders pertaining to the complete value chain of biocidal products including regulators, industrial stakeholders, academia, biocidal product formulators and consumer associations since COMBASE intends to address stakeholders of the complete value chain. For the identification and analysis of the needs of the identified stakeholders’ different approaches have been undertaken including surveys, telephone and face to face interviews.

The description of the outputs of the implementation actions is hereby introduced.

Action B.1. Optimization and experimental assessment of chemoinformatic models implies the development and optimization of models for the prediction of the acute in vivo toxicity of fish, invertebrate (Daphnia magna), algae and microorganisms. A series of models have been developed for all trophic levels and have been statistically evaluated in terms of their performance. Of main relevance for COMBASE is the experimental validation of developed models in order to optimize them. To such target, in vivo assays have been conducted on fish, Daphnia, algae and microorganisms following the OECD TG 203, OECD TG 202, OECD TG 201 and OECD TG 209 tests, respectively. Complementing in vivo assays, in vitro experiments on fish cell lines have also been carried out. 

Out of the different developed models, those performing best have been implemented in VEGA and ToxREAD in the frame of Action B.2. Implementation of the in silico models within VEGA and integration with read across models.

In relation to the action B.3. Development and implementation of the COMBASE software platform, the COMBASE webtool has been developed and is freely accessible via registration in http://webtool.life-combase.com. The tool includes:

       A database containing experimental data for BAS and their corresponding metabolites and a proposal for substances categorization in agreement with the EU Regulation (EC) No 1272/2008 on classification, labeling and packaging.

       A predictive tool for the identification of metabolites generated within the life cycle of chemical substances with special focus on reactions taking place in the freshwater compartment.

       A set of models predicting the acute effects of chemical substances for fish, Daphnia, algae and Sewage Treatment Plant (STP) microorganisms.

       A tool proposing alternative chemical substances with biocidal potential but decreased environmental impacts.

Also within action B.3. a mobile application has been developed. The APP mainly targets professional users of biocidal products and consumers, amongst other, providing instructions for their sustainable use. Data are limited to biocidal products that pertain to product type (PT) 18 (Insecticides, acaricides and products to control other arthropods) and that are commercially available in Spain.

Both software tools have been validated by entities of academic, industrial and regulatory nature not pertaining to the project. Comments retrieved have been carefully analyzed and taken into consideration whenever appropriate.

Finally, for what refers to action B.4. Tool transferability – Training for the sustainable use of biocides, a total of four E-Learning Modules have been produced and specific training sessions describing the tools developed within the project have been organized with master students at the University of Valencia. Additionally, three seminars have been conducted in order to assure the uptake of project’s results at institutional level. A transference plan of the approach implemented within the project for alternative chemical substances (Plant Protection Products) has been produced. The possible integration of health related issues into future versions of the tool has been evaluated too, having optimized a model for mutagenicity specifically for biocides that has later been implemented into VEGA and ToxRead. Also in the area of human health impacts, in vitro studies using human cell lines have been carried out.

In relation to monitoring actions, data have been provided for the Key Project Indicators (KPI) on line database. A full package of dissemination actions has been carried out including three publications in international journals, the organization of three workshops, the participation in eight international congresses in areas relevant to the project and the definition of an after-life dissemination plan in order to assure the long term impact of the project, amongst other. Management actions complete the work done.