Tox News: Issue 17, September 2024

• Earlier this year Natalie Burden took on a new role in the Tox Team as Head of New Approach Methodologies (NAMs) Strategy to lead our work in accelerating the uptake and implementation of NAMs for safety assessment.
• Our Programme Manager for Drug Development, Elisa Passini, has returned from parental leave. Her main focus will be analysing data from our most recent survey to review opportunities for expanding the use of a single species in long-term toxicity studies (see Two Species Phase II survey below).
• Mark Blee joined the Tox Team last month as Programme Manager for Acute Toxicity. His focus will be on exploring opportunities to apply the 3Rs in acute toxicity testing.

We have led an analysis to inform discussions on new endocrine disruption testing requirements in the EU and minimise the potential impact on animal use. Proposals to include new endocrine disruptor-specific testing in the EU’s Registration, Evaluation, Authorisation and Restriction of Chemicals (REACH) Regulation could use tens of millions of animals and would not be feasible in practice. 

The working group identified several areas for further consideration and clarification, including where new approach methodologies could be more widely used to replace or waive animal testing.

Earlier this year we launched a new data-sharing project to review the use of two species in regulatory toxicology studies for the development of pharmaceutical molecules following ICH M3(R2).

We are collecting information on studies carried out to support development of these molecules, to better understand:

• How often similar toxicities are identified in short-term studies across different species.
• How often new or unexpected toxicities manifest in long-term studies, and the differences between rodents and non-rodents.
• The theoretical risk to human safety if using only a single species for long-term studies.

If your company is working with molecules following ICH M3(R2) and you would like to contribute to our data collection, please get in touch: elisa passini@nc3rs.org.uk.

An in vitro assay to test follicle-stimulating hormone potency developed by Dr Francesco Nevelli at Merck has been recognised in the annual NC3Rs Prize, co-funded by GSK. Dr Lorna Ewart, Emulate Inc was highly commended for a paper analysing the predictability of an organ-on-a-chip device to determine liver toxicity.

3Rs Prize webinar
Wednesday 11 September, 13.30 – 14.30 (BST)
Register for the 3Rs Prize webinar to hear more about the winning research. Professor Julia Buckingham, NC3Rs Board Chair, will present the Prize followed by presentations from the winning and highly commended paper authors.

We are challenging UK and EU based innovators to develop new approach methodologies (NAMs) that replace some of the large numbers of birds used in acute and chronic avian toxicity studies. These studies are carried out for internal chemical screening and to meet regulatory requirements for the registration of new pesticides. 

The Wings of Change Challenge is sponsored by BASF, Bayer Crop Science, Corteva and Syngenta, and supported by the American Chemistry Council and the Health and Environmental Sciences Institute. This Challenge will benefit from expertise across disciplines including in silico and in vitro approaches (e.g. QSARs, exposure and effects modelling, cell lines etc) and those working in different fields that could be applied to avian toxicity are encouraged to apply.

Wings of Change launch webinar
Tuesday 17 September 14.00 – 15.30 (BST)
Register for the launch webinar to learn more about the competition, ask the Sponsors questions and find out how to submit a competitive application.

This blog explores the rising interest in and potential of new approach methodologies (NAMs). Hear from our NAMs Advisory Group as they discuss their recent paper on opportunities to embed NAMs in chemical and drug safety assessment and share their perspective on the steps needed to make NAM-based approaches the default starting position for safety decision-making.

8 – 11 September
Copenhagen, Denmark
We are participating in a satellite workshop session at EUROTOX 2024, focusing on dose level selection for Developmental and Reproductive Toxicology studies on Wednesday 11 September. Fiona Sewell will take part alongside representatives from Charles River Laboratories and the European Chemicals Agency.

16 – 17 September
Berlin, Germany
Natalie Burden will be attending the Chem-Academy 9^th International Conference on Endocrine Disruptors and will deliver a presentation on “New Approach Methodologies and Applying the 3Rs” on Tuesday 17 September.

Our latest impact stories feature three replacement approaches developed through NC3Rs funding that were the first in vitro models validated to replace animal use for specific experiments in their research areas. One article explores the development of in vitro cell-based assays to detect the activity of Botulinum B, replacing animal testing in the manufacture of clostridial toxin-based medical products.

We are looking for researchers who are preparing a manuscript for publication that includes in vitro models, to participate in user testing of the RIVER (Reporting In Vitro Experiments Responsibly) recommendations. The RIVER recommendations detail the minimum information necessary for a reader to assess the methodological rigour and reliability of an in vitro study.

Participants will receive expert feedback on their manuscript from members of the RIVER working group, improve the transparency of their work and its chances of successful publication, and receive a £50 (Euro/USD equivalent) voucher upon completing the study.

Thursday 3 October, 10.30 – 12.45 (BST)
Delivered by Health and Safety Executive (HSE) regulatory specialists, this online session will cover how Great Britain Biocidal Products Regulation (GB BPR) information requirements can be met without vertebrate testing. The session aims to support attendees improve the quality of their submissions and understand how these will be reviewed by the regulator.

• Sewell F, Alexander-White C, Brescia S, Currie RA, Roberts R, Roper C, Vickers C, Westmoreland C, Kimber I (2024). New approach methodologies (NAMs): identifying and overcoming hurdles to accelerated adoption. Toxicol Res 13(2):tfae044. doi:10.1093/toxres/tfae044.
• Prior H, Baldrick P, Clarke DO, Passini E, Sewell F, van Meer P (2024). Exploring Greater Flexibility for Chronic Toxicity Study Designs to Support Human Safety Assessment While Balancing 3Rs Considerations. Int J Toxicol. 31:10915818241255885. doi:10.1177/10915818241255885.
• Burden N, Brown RJ, Smith R, Brescia S, Goodband T, Guerrero-Limón G, Kent L, Marty S, Pearson A, van der Mescht M, Saunders LJ, Sewell F, Wang N, Wheeler JR (2024). Resource and animal use implications of the proposed REACH information requirements for endocrine disruptor assessment. Regul Toxicol Pharmacol. 151:105671. doi:10.1016/j.yrtph.2024.105671.
• Constantine LA, Burden N, Davidson T, Dolan DG, Janer G, Häner A, Lee MR, Maynard SK, Nfon E, Nimrod Perkins A, Ryan JJ, Tell J (2024). Evaluation of the EMA log kow trigger for fish BCF testing based on data for several human pharmaceuticals. Regul Toxicol Pharmacol. 151:105651. doi:10.1016/j.yrtph.2024.105651.
• Brown RJ, Panter GH, Burden N, Weltje L, Wheeler JR, Salinas ER, Wolf Y, Lagadic L (2024). A Decision Logic for the Reliability Assessment and Interpretation of Vitellogenin Measurements. Environ Toxicol Chem. Epub ahead of print. doi:10.1002/etc.5946.