Tox News: Issue 6, October 2019


Tox Team welcomes back Dr Natalie Burden

NC3Rs Programme Manager Dr Natalie Burden has returned from maternity leave. Her main focus will be on current 3Rs challenges and opportunities in ecotoxicology, including areas such as fish acute toxicity and endocrine disruptor testing.




British Toxicology Society (BTS) Executive Committee

Fiona has joined the British Toxicology Society (BTS) Executive Committee. The BTS is an important focal point for the UK toxicology community, providing a valuable forum for early career development and sharing knowledge and best practice between colleagues and across sectors. Fiona is looking forward to contributing to the important work of the committee.




Complete these surveys and help us assess our impact

We are currently conducting surveys of the agrochemical and industrial chemical industries, as well as CROs supporting them, for two of our ecotoxicology projects. The feedback we receive will help us understand the impact of our work and inform our next steps in these areas. The surveys can be found via the following links:

The surveys should each take no longer than 15 minutes to complete. Thank you – we very much value your participation.



Applying the 3Rs in drug development: Improving delivery of innovative treatments to patients

In June we hosted a one-day workshop that brought together leaders from the international pharmaceutical community across industry, academia and regulatory authorities. The workshop report summarises how the NC3Rs supports the pharmaceutical industry as well as discussions on the future direction and potential new projects to address current challenges.




Call for data: acute oral toxicity studies

In collaboration with the European Partnership for Alternative approaches to Animal Testing (EPAA) we would like to request access to study reports from acute oral toxicity studies in order to develop a database of clinical signs observed during these studies. This will be analysed and used to develop guidance on the use of evident toxicity as an endpoint to support the use of the Fixed Dose Procedure (FDP) for acute oral toxicity studies (OECD Test Guideline 420). This test uses fewer animals than other accepted methods and does not use death as an endpoint, giving clear animal welfare benefits.


Please email for more information.



Promoting the 3Rs internationally

The Tox Team have had a busy few months travelling to scientific meetings to disseminate our work on a vast number of topics, including single species use for post-'first-in-human' (FIH) studies, justification for species selection in pharmaceutical toxicity studies, advancing the 3Rs for pharmaceuticals and in acute toxicity testing, European-standard housing and procedures and social housing telemetry. These meetings included:

  • Royal Society for the Prevention of Cruelty to Animals (RSPCA) meeting on Challenging Refinements in Stevenage
  • British Toxicology Society (BTS) Annual Congress in Cambridge
  • Society of Toxicology (SOT) Annual Meeting in Baltimore
  • Data Sciences International (DSI) European User Group Meeting in Berlin
  • Minipig Research Forum in Vienna
  • International Congress of Toxicology in Honolulu
  • EUROTOX in Helsinki
  • Safety Pharmacology Society (SPS) in Barcelona
  • Association of Inhalation Toxicologists (AIT) Conference in Brighton
  • American Association for Laboratory Animal Science (AALAS) National Meeting in Denver

You can read reports from two NC3Rs-hosted symposia via our website.



Guest Lectures and Courses

Natalie recently gave lectures as part of the TOPRA (The Organisation for Professionals in Regulatory Affairs) MSc in Regulatory Affairs course and at the TOPRA Scotland meeting.


Briony attended the Practical Application of Toxicology in Drug Development (PATDD) course, jointly organised by the BTS and ACT and held at the Møller Centre in Cambridge. This course was a brilliant opportunity to gain a comprehensive overview of non-clinical safety assessment as well as build networks with other toxicologists. A PDF of feedback from PATDD participants can be downloaded from the BTS website.


Opportunities to meet members of the NC3Rs Tox 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.



The 10th International Fresenius Conference: "Endocrine Disruptors"

12-13 November (Frankfurt, Germany)


This two day conference will bring together experts from authorities, industry and academia to discuss the new criteria and guidance for identification of endocrine disruptors and their implementation.


Natalie will be giving a presentation entitled 'Conducting aquatic vertebrate tests for investigation of endocrine disrupting properties: Challenges and 3Rs implications'.




40th Annual Meeting American College of Toxicology and Council (ACT)

17-20 November (Phoenix, USA)


Helen and Fiona will be attending ACT, where Helen is speaking in a session on 19 November on 'Safety Pharmacology for Toxicologists: Incorporating Functional Endpoints into Toxicology Studies and Highlighting Proposals for Changes in Guideline Requirements'. She will give the opening talk entitled 'Introduction and perspectives on Safety Pharmacology endpoints within toxicology studies'. We will also have a booth in the Exhibition Hall.




In Silico Toxicology Network Meeting

26 November (Cambridge, UK)


This event aims to foster the in silico toxicology community in the UK and beyond, and is supported by the BTS, the Royal Society of Chemistry (RSC) Chemical Information and Computer Applications Group (CICAG), the Cambridge Alliance on Medicines Safety (CAMS) and Lhasa Ltd.


Fiona will be giving a talk entitled 'Using In Silico Approaches to Support the 3Rs in Safety Assessment'.




The 19th International Fresenius ECOTOX Conference: Aquatic and Terrestrial Ecotoxicology and Risk Management

5-6 December (Cologne, Germany)


This conference will cover a vast range of ecotoxicology topics, from endocrine disruptor assessment and animal welfare, through to communication of complex agrochemical topics to the public.


Natalie will be giving a presentation entitled 'Applying the 3Rs in Ecotoxicology'.



A list of all NC3Rs publications in Toxicology and Regulatory Sciences can be found in our bibliography. New publications co-authored by NC3Rs staff include:

  • Prior H, Monticello T, Boulifard V et al. (2019). Integration of Consortia Recommendations for Justification of Animal Use Within Current and Future Drug Development Paradigms. International Journal of Toxicology 38(4): 319–325. doi:10.1177/1091581819852922

  • Lagadic L, Bender K, Burden N et al. (2019). Recommendations for Reducing the Use of Fish and Amphibians in Endocrine‐Disruption Testing of Biocides and Plant Protection Products in Europe. Integrated Environmental Assessment and Management 15(4): 659‑662. doi:10.1002/ieam.4156

  • Gellatly N and Sewell F (2019). Regulatory acceptance of in silico approaches for the safety assessment of cosmetic-related substances. Computational Toxicology 11: 82-89. doi:10.1016/j.comtox.2019.03.003

  • Hasselgren C, Ahlberg E, Akahori Y et al. (2019) Genetic toxicology in silico protocol. Regulatory Toxicology and Pharmacology 107: 104403. doi:10.1016/j.yrtph.2019.104403

  • Jackson SJ, Authier S, Brohmann H et al. (2019). Neurofunctional test batteries in safety pharmacology – Current and emerging considerations for the drug development process. Journal of Pharmacological and Toxicological Methods 100: 106602. doi:10.1016/j.vascn.2019.106602

  • Redfern WS, Dymond A, Strang I et al. (2019). The functional observational battery and modified Irwin test as global neurobehavioral assessments in the rat: Pharmacological validation data and a comparison of methods. Journal of Pharmacological and Toxicological Methods 98: 106591. doi:10.1016/j.vascn.2019.106591


RespiraTox: a QSAR model to predict human respiratory irritation of chemicals

Through the NC3Rs CRACK IT Challenge competition, researchers from Fraunhofer ITEM (Germany) and the University of Birmingham (UK), in collaboration with Challenge Sponsors Shell, have developed a QSAR model to predict human respiratory irritation. The model can replace the use of in vivo rodent studies in the early identification of candidate chemical toxicities and support the replacement of in vivo studies in assessing respiratory irritation in chemicals taken forward to registration.


The model is available as an open access web-based tool, allowing end-users to predict respiratory irritation by entering structural information. The tool provides a readout on the reliability of its predictions and displays a list of structurally similar neighbours within the database, supporting further investigation. The overall approach adheres to the five OECD principles for QSAR validation.