Tox News: Issue 3, March 2018


Fixed Concentration Procedure (FCP) now accepted at OECD


After almost a decade, efforts led by Dr Fiona Sewell (NC3Rs Programme Manager for Toxicology and Regulatory Sciences) have resulted in the adoption of the Fixed Concentration Procedure (FCP) by the OECD as Test Guideline (TG) 433. The FCP is a refined test guideline for acute inhalation toxicity studies which uses fewer animals and does not require death as an endpoint. We are currently working with our OECD National Coordinator to update the Harmonised Template (OHT) for reporting acute inhalation toxicity data so that it covers data generated using FCP.


A substantial amount of work has been conducted by the NC3Rs FCP working group (which included representatives from Public Health England, the Health and Safety Executive, academia and contract research organisations) to support the adoption of TG 433. Most recently this has included further analysis of historic inhalation toxicity data to support the robustness of ‘evident toxicity’ to predict death would occur in the next highest dose group and comparison of classifications made using FCP and existing methods. These latest analyses, and a summary of previously published data are now available in the recent publication by Sewell et al. ‘An evaluation of the fixed concentration procedure for assessment of acute inhalation’.




NC3Rs/Unilever workshop on Applying exposure science to increase the utility of non-animal data in efficacy and safety testing


Last year we jointly hosted a scientific workshop with Unilever to explore the role of exposure science in increasing the use of non-animal data for safety and efficacy testing. It was well attended, with over 80 international scientists from a range of backgrounds. A workshop report summarising the main themes discussed, along with the slides presented, is available on our website.


We were invited to present a poster on our workshop at the International Council of Chemical Associations’ Long-Range Research Initiative (ICCA-LRI) Workshop 2017 which was themed around ‘Fit-for-purpose exposure assessments for risk-based decision making’. Fiona will also be presenting outputs of the workshop and the potential for exposure-driven approaches to benefit the 3Rs at the Society of Toxicology (SOT) 2018 Annual Meeting (see also the ‘Events’ section below).




NC3Rs Cardiovascular Showcase


We have a number of ongoing activities relating to cardiotoxicity. Last year we sponsored a workshop ('Towards widespread application of mechanistic approaches for identifying cardiotoxicity') at EUROTOX 2017. Dr Helen Prior (NC3Rs Programme Manager for Toxicology and Regulatory Sciences) co-chaired and spoke during this session, and Dr Luigi Margiotta-Casaluci (Brunel University) presented his plans for the NC3Rs strategic award ‘Development of an adverse outcome pathway (AOP) for cardiotoxicity’. Helen also attended the Safety Pharmacology Society (SPS) 2017 Annual Meeting in Berlin, where she presented a poster ('Why are non-rodents not socially housed during cardiovascular telemetry recordings on safety pharmacology studies?').


There will be an opportunity to hear updates from these projects and more during a Cardiovascular Showcase event hosted by the NC3Rs on 23 March in central London. This event will bring together scientists working to advance application of the 3Rs across a range of cardiovascular topics and highlight the diversity of NC3Rs funded projects and CRACK IT challenges in this area. During the afternoon, there will be the opportunity to participate in one of three breakout sessions: 1) Funding workshop: NC3Rs/ British Heart Foundation co-funded PhD studentships; 2) Development of an adverse outcome pathway (AOP) for cardiotoxicity; and 3) Increasing the adoption of social-housing during telemetry study recordings.


Registration for the event closes on 8 March.




Professor Ian Kimber OBE – NC3Rs Toxicology Ambassador


We are delighted to announce that Professor Ian Kimber has been appointed NC3Rs Toxicology Ambassador. In this role he will act as an international ambassador for our 3Rs in toxicological and safety science programmes to ensure we maintain and build on our connections with other relevant activities, particularly those in the USA.



Opportunities to meet members of the NC3Rs toxicology team and find out more about our work at conferences and events over the upcoming months.

Find a full list of NC3Rs events on our website calendar.



Society of Toxicology (SOT) 57th Annual Meeting and ToxExpo

11-15 March 2018 (San Antonio, USA)

Fiona will be speaking during the Scientific Session ‘Toxicology’s Next Grand Challenge: Embracing Exposure Science for Effective Public Health’ on Monday March 12, 9.15am-12pm, on ‘How Exposure-Based Refinements Can Benefit the 3Rs’. We will also have a stand within the ToxExpo (booth number 452). Two posters on CRACK IT Challenge 15: NephroTube will be presented during the ‘Understanding Kidney Damage’ session on Monday March 12 9.15am-4.30pm.




British Toxicology Society (BTS) Annual Congress 2018

16-18 April 2018 (Gateshead, UK)

Registration is now open to attend the BTS Annual Congress 2018. The programme includes sessions on advanced in vitro models for inhalation toxicity testing and the role of stem cells in toxicology testing.




Society of Environmental Toxicology and Chemistry (SETAC) Europe 28th Annual Meeting

13-17 May 2018 (Rome, Italy)

Dr Luigi Margiotta-Casaluci (Brunel University) will be presenting results from the NC3Rs strategic award ‘Development of an adverse outcome pathway (AOP) for cardiotoxicity’ during the invited session ‘Advancing the adverse outcome pathway framework – an international horizon scanning approach’ on Thursday 17 May 2018 8.30am-10:05am, Room P.



We have had a busy year for publications, and have recently updated our Toxicology and Regulatory Sciences bibliography.




New ICHS3A Q&A adopted


The ICH Harmonised Guideline – Questions and Answers to ICH S3A: Note for Guidance on Toxicokinetics: The Assessment of Systemic Exposure in Toxicity Studies – Focus on Microsampling was adopted late last year.


Since the S3A Guideline was successfully implemented in 1994, sensitivity of analytical methods has improved, enabling microsampling techniques to be widely used in toxicokinetic (TK) studies. This supporting Q&A document, covers points to consider before incorporating microsampling into TK studies, benefits and some limitations of assessing TK in main study animals, and the important contribution of microsampling to the 3Rs through reduction or elimination of the need for satellite animals. The NC3Rs microsampling working group was actively involved in the consultation phase for this guideline.