An introduction to our programme in Toxicology and Regulatory Sciences

Over the past 12 years, the NC3Rs has worked closely with the pharmaceutical and chemical industries, regulatory bodies and academia to build a large programme in Toxicology and Regulatory Sciences that addresses 3Rs challenges in (eco)toxicology and safety assessment.

We have funded new research and development in the field through our research grant funding and the CRACK IT open innovation scheme. Office-led, expert-driven projects have aimed to increase the implementation of the 3Rs in the current regulatory testing paradigm, as well as to promote best practice and stimulate change in policy and regulations.

We recently held a ‘Toxicology Showcase’ event to highlight our work in this area so far, and to inform our future strategy, bringing together over 60 of our collaborators and stakeholders. More information on this event and our programme can be found here. We have launched this regular newsletter to keep the scientific community updated on our activities in this programme.

Meet the team

We currently have three Programme Managers leading projects in this area; Dr Natalie Burden (Environmental Health), Dr Helen Prior (Drug Discovery) and Dr Fiona Sewell (Human Health). Nikki Gellatly joins our team on 1 November as a Science Manager.

L-R: Helen Prior, Nikki Gellatly, Fiona Sewell and Natalie Burden.

Launch of a new project in collaboration with the pharmaceutical industry: An ABPI/NC3Rs initiative

We recently launched a new project in collaboration with the Association of the British Pharmaceutical Industry (ABPI), to review the value of a second species in regulatory toxicology studies.

Initial activities will focus on whether data from one species could be sufficient for the progression of a potential new drug in human clinical trials. This project is overseen by a steering group, chaired by Professor Ian Kimber OBE, University of Manchester.

Complete our surveys on repetition of OECD ecotoxicology Test Guideline studies

These surveys will collect information on the most commonly conducted vertebrate ecotoxicology Test Guideline studies, the deviations to technical requirements encountered most frequently, and which deviations are currently tolerated before the results of a study are no longer deemed scientifically robust.

The surveys are open to contract research organisations conducting vertebrate ecotoxicology studies; companies sponsoring vertebrate ecotoxicology studies; and regulatory agencies assessing submissions containing data from vertebrate ecotoxicology studies. This information will form the essential precursor to establishment of an OECD expert group who will then take this project forward.

They can be completed anonymously and are open for completion until 31 December 2016. To access and complete these surveys, click here.

Call for project licence holders to join new NC3Rs forum

We are looking for (eco)toxicology project licence holders to join a new NC3Rs forum which aims to share 3Rs experiences and keep the community up to date with the latest 3Rs developments.

If you are interested in joining the forum and attending the first meeting, which will be held early in 2017, please email NC3Rs Enquiries.

Vacancies at the NC3Rs

Do you have a strong understanding of the use of animals in research and a commitment to the 3Rs?

The NC3Rs is looking to expand its dynamic team to further the development and uptake of 3Rs research tools and models. We are currently recruiting for two Programme Managers (maternity cover), two Science Managers and a Funding Support administrator. This includes a Programme Manager in Toxicology and Regulatory Sciences.

The NC3Rs offers a wide range of benefits such as a final salary pension scheme, excellent holiday entitlement and access to employee shopping/travel discounts and childcare vouchers.

The deadline date for all applications is Friday 11 November.

Opportunities to meet members of our 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.

Applying exposure science to increase the utility of non-animal data in efficacy and safety testing

15 - 16 February 2017: LONDON, UK
Registration is now open for this two-day workshop hosted in collaboration between the NC3Rs and Unilever. The event will be chaired by Professor Alan Boobis OBE, Imperial College London.

This event will bring together researchers from multiple disciplines to share their knowledge and experiences in applying exposure-driven approaches to increase the utility of in vitro and in silico data for decision-making and safety assessment. Greater incorporation of exposure considerations has the potential to increase the relevance of these non-animal models to improve safety and efficacy assessment processes, and to reduce the reliance on animal testing.

American College of Toxicology annual meeting

6 - 9 November: BALTIMORE, MARYLAND, USA
The American College of Toxicology's annual meeting aims to update attendees on emerging trends in the discipline of toxicology. This year’s meeting will include a diverse scientific programme and a traditional poster reception session for attendees and exhibitors.

The NC3Rs will be presenting work on the use of recovery animals to support human clinical trial entry in pharmaceutical development: ‘The inclusion of recovery groups in repeat-dose studies: To be or not to be?’ in Symposium 13: Current Issues in Evolving Regulatory Systemic Toxicology Study Design and Conduct on Tuesday 8 November 2-5pm.

Emerging issues in inhalation toxicology and pathology

10 - 11 November: MACCLESFIELD, UK
This is the 31st annual meeting of the British Society of Toxicological Pathology held jointly with the Association of Inhalation Toxicologists.

The NC3Rs will be presenting work on refining acute inhalation studies, towards adoption of OECD Test Guideline 433.

2016 LASA annual conference

22 - 24 November: SOUTH OF ENGLAND
NC3Rs staff members will be attending the LASA annual conference.

A poster on the NC3Rs project ‘Maximising the success of bile duct cannulation studies’ will be presented by working group member Hans van Wijk from Covance.

Fish and amphibian embryos as alternative models in toxicology and teratology

1 - 2 December: PARIS, FRANCE
The NC3Rs is co-sponsoring this symposium, which aims to promote the development of fish and frog embryo models as potential alternatives to animal testing.

The symposium will bring together scientists who use fish and frog embryo models to exchange knowledge, ideas and latest developments in the field of toxicology and teratology. Breakout sessions will identify major advantages, limitations and future research needs of the fish/amphibian embryo models and establish collaborations.

British Pharmacological Society ‘Pharmacology 2016’

13 - 15 December: LONDON, UK
The British Pharmacological Society's flagship annual meeting attracts over 1,000 scientists each year, mostly from the UK but also from elsewhere across Europe and overseas.

The NC3Rs is sponsoring and co-chairing a session: ‘Organ-on-a-chip technology – the future of physiological profiling?’ on Tuesday 13 December at 10am-12pm. This session will focus on tools that improve disease modelling and safety pharmacology.

A list of all NC3Rs publications in Toxicology and Regulatory Sciences can be found in our bibliography. Publications authored so far in 2016 by NC3Rs staff include:

The 3Rs as a framework to support a 21st century approach for nanosafety assessment

A cross-sector perspective from an NC3Rs-led expert working group on the potential to reduce and refine the use of animals in nanotoxicity tests.

• Burden N, Aschberger K, Chaudhry Q et al. (2016). The 3Rs as a framework to support a 21st century approach for nanosafety assessment. Nano Today In press. doi:10.1016/j.nantod.2016.06.007.

The utility of QSARs in predicting acute fish toxicity of pesticide metabolites: A retrospective validation approach

An NC3Rs-led working group analysis demonstrating that quantitative structure activity relationships (QSARs) have potential to be utilised in predicting whether pesticide metabolites are acutely toxic to fish.

• Burden N, Maynard SK, Weltje L et al. (2016). The utility of QSARs in predicting acute fish toxicity of pesticide metabolites: A retrospective validation approach. Regulatory Toxicology and Pharmacology 80:241-246. doi:10.1016/j.yrtph.2016.05.032.

Promoting the 3Rs to enhance the OECD fish toxicity testing framework

A commentary article written in collaboration with scientists from Plymouth University, Dow AgroSciences and the OECD promoting the implementation of the recommendations of the OECD Fish Toxicity Testing Framework.

• Hutchinson TH, Wheeler JR, Gourmelon A et al. (2016). Promoting the 3Rs to enhance the OECD fish toxicity testing framework. Regulatory Toxicology and Pharmacology 76:231-233. doi:10.1016/j.yrtph.2016.02.006.

Waiving in vivo studies for monoclonal antibody biosimilar development: National and global challenges

A publication presenting results from an NC3Rs-led expert working group activity to identify the national and global challenges for waiving in vivo studies for monoclonal antibody biosimilar development.

• Chapman K, Adjei A, Baldrick P et al. (2016) Waiving in vivo studies for monoclonal antibody biosimilar development: National and global challenges. mAbs 8(3): 427-435 doi:10.1080/19420862.2016.1145331.

Social housing of non-rodents during cardiovascular recordings in safety pharmacology and toxicology studies

This article summarises findings of a survey carried out by the NC3Rs in conjunction with a Safety Pharmacology Society expert working group to identify the barriers to refining non-rodent cardiovascular telemetry studies through social housing.

• Prior H, Bottomley A, Champeroux P et al. (2016). Social housing of non-rodents during cardiovascular recordings in safety pharmacology and toxicology studies. Journal of Pharmacological and Toxicological Methods 81: 75-87. doi 10.1016/j.vascn.2016.03.004.

CRACK IT Challenges is a challenge-led competition from the NC3Rs that funds collaborations between industry, academia and SMEs to solve business and scientific 'Challenges'. The aim of the Challenges is to (i) expedite the uptake of 3Rs approaches by providing tailored and ‘off the shelf’ solutions and (ii) support economic growth by improving business processes and developing marketable products.

CRACK IT Challenges 2016 competition now open

The 2016 CRACK IT Challenges are now open for applications. Challenges relevant to toxicology are:

• Retinal 3D: A physiologically-competent human 3D retinal model (Two Phase)
• Maximise: Reliable predictions for classifying mixtures of chemicals for acute oral toxicity, and skin and eye irritation (Single Phase)

Two Phase Challenges offer up to £1 million funding and a research contract for up to three years and the Single Phase Challenges offer up to £100k funding for up to one year.

The application deadlines are:
Two Phase Challenges: 12pm (GMT), 9 November 2016.
Single Phase Challenges: 12pm (GMT), 16 November 2016.

CRACK IT Solutions is a technology partnering hub which showcases new technologies from academia and SMEs and promotes their uptake by the wider scientific community. The scheme aims to accelerate the translation of technologies with 3Rs potential ('Solutions') by helping to identify new partners and customers to use, develop or validate the technology. Funding is available for new collaborations identified through the scheme.

We are currently showcasing a large number of technologies that are relevant to toxicology. View the Solutions in more detail, submit your own Solution or contact the CRACK IT team.

State of the art in vitro models which accurately predict human liver toxicity

A recent study resulting from the CRACK IT Solution ‘State of the art in vitro models which accurately predict human liver toxicity’ highlights the importance of incorporating physiological stimuli, such as shear stress, in cell-based models.

• Rashisi H, Alhaque S, Szkolnicka D et al. (2016). Fluid shear stress modulation of hepatocyte-like cell function. Archives of Toxicology 90: 1757. doi:10.1007/s00204-016-1689-8.

An early screen for emetic liability of new chemical entities (NCEs) using the amoeba Dictyostelium

The outcome of a highly successful Solution, ‘An early screen for emetic liability of NCEs using the amoeba Dictyostelium’ has recently been published. Professor Robin Williams, working with researchers from GlaxoSmithKline, has shown that the social amoeba Dictyostelium can provide a suitable non-animal model for early prediction of bitterness for novel tastants and drugs.

• Cocorocchio M, Ives R, Clapham D et al. (2016) Bitter tastant responses in the amoeba Dictyostelium correlate with rat and human taste assays. ALTEX 33(3):225-236. doi:10.14573/altex.1509011.

£30k award for international 3Rs prize - competition now open

Each year the NC3Rs awards a prize to recognise an outstanding original contribution to scientific and technological advances in the 3Rs, published in the last three years. The award consists of a £28k prize grant and £2k personal award.

The competition is now open for applications with a deadline of 4pm (GMT) on Friday 9 December 2016. For further information on how to apply and examples of past winners see www.NC3Rs.org.uk/3rsprize.

The prize is sponsored by GlaxoSmithKline and the NC3Rs and will be presented at an awards ceremony in London in March 2017.

Skills and Knowledge Transfer grant scheme

The NC3Rs is inviting informal outlines to our new scheme which supports the transfer of knowledge, skills and expertise between academic laboratories to encourage the adoption of alternative 3Rs models, tools and technologies.

The deadline for submission is: 4pm (GMT), 25 November 2016.

New Guidance Document from the OECD on 'Considerations for Waiving or Bridging of Mammalian Acute Toxicity Tests'

The OECD has recently published a Guidance Document (number 237) on Considerations for Waiving or Bridging of Mammalian Acute Toxicity Tests.

The aim of this document is to address animal welfare concerns in the area of acute toxicity testing by introducing considerations where a study may be waived. It provides guidance and criteria for those who are responsible for generating acute toxicity data, and to those who are reviewing the data for classification and labelling purposes.

A regulator’s opinion on the future of organ-on-chip and toxicity assessment

Dr David Jones is an Expert Pharmaco-Toxicologist within the licensing division of the Medicines and Healthcare products Regulatory Agency (MHRA). In this interview, he talks to Francesca Lake, Managing Editor of the journal Future Science OA at the Organ-on-a-chip Europe 2016 conference in Cambridge (UK), where he presented ‘A UK regulatory view on the acceptability of organ-on-a-chip data’.

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