ERGO collaborated with the seven sister projects in the EURION cluster under BHC-27-2018 on specific relevant scientific topics and synergized research outputs, e.g. on the thyroid hormone system and developmental neurotoxicity.
Knowledge management, data generation & infrastructure
Initially, model chemicals were chosen to cover relevant Modes of Action (MoA) of chemicals interfering with the THS of vertebrates via intensive literature reviews to contribute to existing data. The selected chemicals were used for case studies in experimental approaches to generate a comprehensive data warehouse.
For data generation, more than 50 embryo and in vivo experiments with amphibians, fish, and mammals (mice) as well as in vitro assays and in silico model simulations were made.
ERGO has investigated in vitro cell-based assays for THS activity related to MIEs of THS active chemicals. Four were prioritized for the first phase of characterization for pre-validation, aligned with the strategy used by the EU Joint Research Center (JRC). Selection of the assays for prevalidation was based on the outputs and results of mammalian in vitro tests as well as alignment with the JRC effort to support validation of bioassays for prioritized endpoints.
For in embryo and in vivo experiments, ERGO has investigated, developed, and prevalidated more than 30 fish THS sensitive endpoints. Four endpoints (eye development, swim bladder inflation, thyroid hormone levels and thyroid histopathology) have been prevalidated and approved by OECD to enter validation. Early 2024, the validation started with two OECD Test Guidelines (TGs); TG 236 (fish embryo toxicity test) and TG 210 (fish early life-stage toxicity test), representing non-protected embryonic testing and embryo to juvenile developmental testing. The validation is ongoing with 15 international partner laboratories for four fish species. Standard operational procedures (SOPs) for the assessment of the new endpoints were developed and shared with participating organizations as annexes to the original TGs. The validation continues after the end of the ERGO project with support from other projects.
In amphibians, focus has been on new, more sensitive endpoints and comparison of sensitivities between amphibians and fish, using embryonic and in vivo assays as well as omics. New endpoints like eye development and omics outputs should be further explored. Main results indicates that sensitivities of endpoints are comparable between amphibians and fish, but more knowledge is needed before a comparison covers all relevant effects and life-stages.
ERGO investigated new mammalian endpoints and epidemiology and built a database on pollutants detected in epidemiological studies. The database was used for an AOP strategy for epidemiological and human exposure studies. Genomics data from mice, showed that transcriptome and metabolome analyses detect effects of chemicals during gestation and lactation.
Review-based data and generated data investigated cross-vertebrate classes extrapolation of assays and endpoints by AOPs and an AOP network: Single AOP development has focused on fish THS sensitive endpoints, because no endpoints have yet been validated, and they are needed for regulatory purposes.
Five AOPs linking THSD to impaired swim bladder inflation in fish have been published in the OECD Series on Adverse Outcome Pathways. An AOP linking THSD to impaired eye development has been published as AOP report and is being reviewed by OECD. A case study on THSD potential of resorcinol in fish illustrates how AOPs inform on activity and adversity of potential EDCs. A cross-species assessment of the THSD AOP network showed potential for applicability of AOPs across vertebrate taxa, supporting share of data between human and environmental health. Finally, ERGO has proposed an AOP network-based assay battery for THSD with a set of endpoints.
To support identification and prediction of THSD potential of chemicals, a decision support system (DSS) has been developed, publicly available on the ERGO webpage. It is based on experimental data and data from qualitative and quantitative structure-activity relationships (QSARs), consensus modelling and Bayesian statistics to account for conflicting input information and varying levels of information and confidence.
Examples of many Knowledge Transfer, Communication, Dissemination and Exploitation activities:
• A Dissemination and Exploitation Plan
• An ERGO Introductory Video (
https://ergo-project.eu/ergo-launches-introductory-video/(se abrirá en una nueva ventana))
• The ERGO Project website (
https://ergo-project.eu/(se abrirá en una nueva ventana))
• ERGO social media; Twitter page (
https://twitter.com/ERGO_EU(se abrirá en una nueva ventana); @ERGO_EU) & LinkedIn
• ERGO publications: 40+ peer reviewed publications and OECD endorsed AOPs
• Participation in international events
