Tox News: Issue 18, March 2025

Dr Amy Marriott joined the Tox Team in November as Programme Manager for Chemical Safety Assessment. Amy will be leading projects to advance the 3Rs in chemical testing for environmental safety and human health. She previously completed an NC3Rs-funded PhD and postdoctoral positions at the University of Liverpool/Liverpool School of Tropical Medicine developing new approach methodologies and 3Rs-aligned in vivo models for tropical diseases, to update testing guidelines for therapeutics.

Last year we held a workshop in partnership the European Centre for Ecotoxicology and Toxicology of Chemicals (ECETOC), Charles River Laboratories and the European Chemicals Agency (ECHA), to bring together global stakeholders from a range of sectors to understand different perspectives on dose setting for Developmental and Reproductive Toxicity (DART) studies. This builds on a collaboration with industry and regulatory partners to clarify ECHA advice issued in 2022 that raised concerns about testing at very high doses, well beyond the equivalent expected human exposure. The workshop report summarises discussions on setting appropriate dose levels in DART studies to collect relevant scientific information, protect human reproductive health and maintain high standards of animal welfare with agreement from ECHA that its advice would benefit from some further clarification.

As part of our work to identify opportunities to apply the 3Rs to urinalysis assessments, we have published a summary of a workshop we hosted with the Association for Comparative Clinical Pathology (ACCP). The workshop brought experts together to discuss challenges and identify opportunities for refinement. This paper summarises discussions on the value of urinalysis data, including industry case studies where urinalysis results did not affect safety assessments and novel biomarkers that can add value to urinalysis. It also includes practical steps to address the welfare concerns associated with urine sample collection, such as avoiding or refining the use of metabolism cages and reducing collection periods.

7 – 9 October
Reykjavik, Iceland
Alongside the Health and Environmental Sciences Institute (HESI) and the International Collaboration on Cosmetics Safety (ICCS), we are co-sponsoring the inaugural Innovate EcoSafety summit. Organised by a diverse multi-sector planning committee, this meeting aims to bring together experts to advance environmental safety assessment, address scientific priorities and coordinate future work in ecotoxicology.

The 2025 summit will focus on the application and implementation of new approach methodologies to improve ecological risk assessment and hazard screening, across two themes:

• Replacing acute in vivo fish testing.
• Endocrine disruptor assessment for fish and amphibians.

16 – 20 March
Orlando, Florida, USA
If you are attending the SOT 64th annual meeting this month, please come and say hello to Fiona, Elisa and Mark at booth 1504 in the exhibition hall.

• Fiona will be giving a talk on Wednesday 19 March: Considerations for dose-level selection for Developmental and Reproductive Toxicity.
• Elisa will be presenting a poster on Monday 17 March: A review of EMA and FDA submissions highlights the importance of global harmonisation to move towards in vitro-only packages for the development of biosimilars.

7 – 9 May
Liverpool, UK
The Tox team will be attending BTS congress this year, please come and see us at our booth in the exhibition space.

Natalie will be co-chairing Symposium 1, Progress in regulatory protection of the marine/aquatic environment, and delivering a talk on The need for guidance to support vitellogenin measurements in OECD Test Guidelines in the same symposium.

11 – 15 May 
Vienna, Austria
If you are attending the 35th annual SETAC Europe meeting, come and say hello to Natalie and Amy at our booth 46 in the exhibition space.

Natalie is organising and co-chairing a meeting of the SETAC Endocrine Disruptor Testing and Risk Assessment Interest Group on Monday 12 May and co-chairing sessions on endocrine disruption assessment and in silico new approach methodologies on Tuesday 13 May.

Also in the exhibition space, you can stay updated with progress on two of our CRACK IT Challenges. KREATiS, winners of the Thyroid Tox CRACK IT Challenge, will be at booth 65 and will have a poster presentation on their QSAR models and molecular docking tools to reliably predict thyroid receptor-mediated human endocrine disruption. aQuaTox Solutions, winners of the CRACK IT SAFE Challenge will be exhibiting at booth 5 and will have a poster presentation on their work developing bioassays to replace in vivo fish studies in chemical safety screening and regulatory environmental risk assessment.

Have you published a paper in the past three years that could have, or is already having, a major 3Rs impact? Whether the 3Rs were the primary focus of your work or a secondary benefit you could be eligible for the 3Rs Prize. Sponsored by GSK and consisting of a £2k personal award and a £28k prize grant to further the 3Rs impact of the winning research, this prestigious annual award is now live. Wherever you are in the world, and whatever your field of research, scientists in academia or industry are encouraged to apply. 

Work is underway on the Wings of Change CRACK IT Challenge to develop NAMs to evaluate the potential risks that chemicals such as pesticides pose to birds. We have awarded £300k proof-of-concept funding to two teams with a further £1.5M available later this year to develop and integrate the NAMs into a framework to reduce the number of animals used for regulatory risk assessment.

Building on a successful proof-of-concept phase a team led by Dr Torsten Mayr at PyroScience AT GmbH is continuing work on the SensOoChip mega CRACK IT Challenge to remove barriers to the wider use of organ-on-a-chip (OoC) technologies to replace animals in research and safety testing. We have awarded £1.6M to support the integration of sensors into a connected heart and liver OoC system for real-time multiparametric monitoring and incorporate in silico approaches to analyse and model data.

We have published a new resource for transparent communication and ethical review of planned in vivo experiments. The ARRIVE study plan provides a structured framework to communicate the design of a prospective animal study, promoting experimental design strategies that minimise bias and maximise research reliability.

The BTS Skills Gap Initiative was launched to support an increase in skilled applicants for toxicology roles in the UK.  New training modules are now being developed, with six modules planned for 2025 and a further six for 2026. Natalie is developing an ecotoxicology module to run from late April to June 2025 which includes a session she will speak in on the use of new approach methodologies in environmental safety assessment, as well as featuring and an interactive session on environmental next generation risk assessment.

• Burden N, Mitchell CA, Dang Z, Embry MR, Glaberman S, Lagadic L, Lynn SG, Marini J, Mihaich E, McDermott E, Krzykwa J, Salinas ER, Schoenfuss H, Thorpe K, Weltje L, Wheeler JR. (2025). Evaluation of in vivo fish and amphibian endocrine test guideline assays: current status and future needs. Environmental Toxicology and Chemistry. doi:10.1093/etojnl/vgaf064. Epub ahead of print.
• Tarazona JV, Fernandez-Agudo A, Adamovsky O, Baccaro M, Burden N, Campos B, Hidding B, Jenner K, John D, Lacasse K, Lillicrap A, Lyon D, Maynard SK, Ott A, Poulsen V, Rasenberg M, Schutte K, Sobanska M, Wheeler JR. (2025). Use of alternatives to animal testing for Environmental Safety Assessment (ESA): Report from the 2023 EPAA partners' forum. Regulatory Toxicology and Pharmacology 22;156:105774. doi:10.1016/j.yrtph.2025.105774
• Passini E, Adedeji AO, Allen R, Baldrick P, Basak J, Britton L, Cotton P, Harding J, Holmes T, Ljumanovic N, McClure F, McGuire A, McInnes L, Prior H, Sewell F (2025). Applying the 3Rs to urinalysis assessments in toxicity studies: refining procedures and adopting a case-by-case approach. Comparative Clinical Pathology. doi:10.1007/s00580-025-03642-5