Tox News: Issue 8, December 2020

 

Despite this year being anything but usual we have still been busy writing papers, attending virtual conferences and spending a lot of time on Zoom! We hope that we can travel again in 2021 and see many of you in person next year. We hope you all have an enjoyable Christmas and we wish you a Happy New Year!

 
 

 
 

New survey launched: help us understand how microsampling is used within studies for drug and (agro)chemical development

We have launched a survey to gather information on current approaches and opinions on the use of microsampling. If you use a microsampling technique within any research or safety study for new drugs or (agro)chemicals, we are interested to learn the 3Rs impacts you have achieved. If you do not (yet) use microsampling, please let us know your concerns and/or the barriers to help us guide future strategy in this area.

 

The survey can be downloaded in .XLSX format from our website and should take no longer than 15 minutes to complete. Thank you – we very much value your participation.

 
 

 
 

NC3Rs collaboration leads to reduction in animal use for regulatory fish bioconcentration testing

Recommendations from a project led by the NC3Rs have been incorporated into guidance published by the US Environmental Protection Agency (EPA) to reduce the number of treatment concentrations required for fish bioaccumulation studies.

 

The NC3Rs has led an active programme of work and has published several papers on applying the one concentration approach in fish bioaccumulation studies. Despite this approach being an option in the OECD test guideline (TG 305), differences in the national guidelines published by the USA and Japan mean that testing at two concentrations may be required in order to facilitate worldwide registration of chemicals. Analysis carried out by the NC3Rs to support the use of a single concentration has been acknowledged within new guidance published by the US EPA in July 2020, stating the Office of Pesticide Programs will accept a single treatment level concentration under specified conditions.

 

 
 

 
 

New publication: Justification for species selection for pharmaceutical toxicity studies

Further results from our recent data-sharing collaboration with the pharmaceutical industry have been published in Toxicology Research. The paper summarises presentations from a symposium organised by the NC3Rs at the British Toxicology Society (BTS) Annual Congress in Cambridge, UK (April 2019). The review provides insights into decisions made by pharmaceutical companies to justify scientific relevance of the selected rodent and non-rodent species for toxicology testing.

 

 
 

 
 

New publication: Key Opportunities to Replace, Reduce and Refine Regulatory Fish Acute Toxicity Tests

The NC3Rs Ecotoxicology working group have published a paper on the fish acute toxicity test, one of the most frequently conducted vertebrate ecotoxicology tests and one of the few which uses death as the intended endpoint. This paper questions the value of this test, reviews opportunities to apply the 3Rs and makes recommendations on how these can be applied.

 

 
 

 
 

Promoting the 3Rs internationally

The Society of Environmental Toxicology and Chemistry Europe 30th Meeting was held virtually this year. Dr Briony Labram received a BTS travel award to attend virtually and gave a presentation on ‘Reducing, refining and replacing fish acute toxicity tests’. A blog post about Briony’s experience of attending a virtual conference can be found on the BTS website (under "BTS Travel Awards"). Dr Natalie Burden gave a presentation at the Endocrine Disrupters Interest Group on ‘The application of the 3Rs principles in Endocrine Disruptor testing’.

 

The HESI PBPK Committee, U.S. Environmental Protection Agency Office of Pesticide Programs, and National Toxicology Program (NTP) Interagency Center for the Evaluation of Alternative Toxicological Methods (NICEATM) co-sponsored a symposium on 'Opportunities and Challenges in Using the Kinetically Derived Maximum Dose (KMD) Concept to Refine Risk Assessment'. Dr Fiona Sewell gave a presentation on 'Dose selection and the 3Rs'.

 

Drs Helen Prior and Fiona Sewell ‘attended’ ACT, where Helen co-chaired and presented in the session ‘Exploring the Definition of Similar Toxicities: Case Studies Illustrating Industry and Regulatory Interpretation of ICH S6(R1) for Long-Term Toxicity Studies in One or Two Species’ devised by the NC3Rs as part of the two species project, which included speakers from Lilly, Genentech, FDA and the MHRA.

 
 

 
 

Guest Lectures and Courses

Helen recently gave lectures as part of the INSPIRE European summer school on the ethics and regulation of animal research, the 3Rs and their application within cardiovascular safety pharmacology assessments. NC3Rs is a partner organisation for this Horizon 2020-funded project with 15 PhD projects investigating new technologies and approaches for cardiovascular safety pharmacology.

 

The BTS held its Continuous Education Programme (CEP) and Virtual Lectures 2020. Briony gave a presentation on the 3Rs in Environmental Toxicology.

 

 

Visit our website events calendar for more details of upcoming virtual events.

 
 

 
 

Assessing Carcinogenicity: Hazard Identification, Classification, and Risk Assessment (A Toxicology Forum State-of-the-Science Workshop)

7-11 December 2020

 

As our understanding of chemical carcinogenesis has grown significantly over the last several decades, it is appropriate to look at whether long-standing test methods and risk assessment approaches should be updated. The US EPA is now in the process of updating its guidelines for risk assessment, which includes the 2005 Guidelines for Carcinogen Risk Assessment. These guidelines are used throughout the US EPA, as well as by numerous other federal and state agencies, to aid regulatory decision-making and set research priorities. This workshop will provide an opportunity for national/international experts and stakeholders to engage in an information exchange regarding these revisions, which will be of great value to guide next steps towards the modernization of carcinogenicity identification and risk assessment. Fiona is a participating in the discussion panel for session 4: New Approach Methodologies.

 

 
 

The NC3Rs are regularly delivering webinars hosted by NC3Rs staff members and grant holders on different 3Rs topics. Recordings of past webinars can be found on the NC3Rs website. To receive regular updates on upcoming webinars and other new learning resources, subscribe to the NC3Rs newsletter.

 
 

 
 

Recording: Scientific validity and EURL ECVAM recommendations for the replacements for animal-derived antibodies

This webinar, originally presented in July 2020, provided an overview of the scientific and welfare benefits of moving to the use of animal-free antibodies and affinity reagents and highlighted the recent Recommendation on Non-Animal-Derived Antibodies from the EU Reference Laboratory for alternatives to animal testing (EURL ECVAM). The webinar is delivered by Dr Alison Gray, School of Veterinary Medicine, University of Nottingham and Afability.

 

 
 

A list of all NC3Rs publications in Toxicology and Regulatory Sciences can be found in our bibliography.

  • Burden N, Benstead R, Benyon K et al. (2020). Key Opportunities to Replace, Reduce and Refine Regulatory Fish Acute Toxicity Tests. Environmental Toxicology and Chemistry. doi:10.1002/etc.4824

  • Sewell F, Kimber I, Boobis AR. (2020). Use of the kinetically-derived maximum dose: Opportunities for delivering 3Rs benefits. Regulatory Toxicology and Pharmacology 116:104734. doi: 10.1016/j.yrtph.2020.104734

  • Guns PJ, Guth B, Braam S et al. (2020). INSPIRE: A European training network to foster research and training in cardiovascular safety pharmacology. Journal of Pharmacological and Toxicological Methods, in press. doi: 10.1016/j.vascn.2020.106889

  • Luijten M, Corvi R, Mehta J et al. (2020). A comprehensive view on mechanistic approaches for cancer risk assessment of non-genotoxic agrochemicals. Regulatory Toxicology and Pharmacology 118: 104789. doi: 10.1016/j.yrtph.2020.104789

  • Prior H, Haworth R, Labram B et al. (2020). Justification for species selection for pharmaceutical toxicity studies. Toxicology Research 9(6): 758-770. doi: 10.1093/toxres/tfaa081

  • Wheeler JR, Gao Z, Lagadic L et al. (2020). Hormone data collection in support of endocrine disruption (ED) assessment for aquatic vertebrates: Pragmatic and animal welfare considerations. Environment International 146: 106287. doi: 10.1016/j.envint.2020.106287
 

 

New ARRIVE guidelines published in PLOS Biology

The ARRIVE guidelines have been revised to further support researchers in improving the reliability and reproducibility of their work through better reporting. Items within the guidelines, now published in PLOS Biology, have been organised into two sets to help researchers include the most important information within their manuscript. ARRIVE 2.0 is accompanied by an Explanation and Elaboration document, as well as a new website, www.arriveguidelines.org, which features information and resources for researchers, journals, funders and other stakeholders.

 

 
 

 
 

A new NC3Rs project to reduce animal use in the batch release and quality control testing of biologicals

We have been funded by the Bill & Melinda Gates Foundation to review animal use in World Health Organization guidelines for the quality control and batch release testing of biologics and vaccines. The project aims to identify how non-animal approaches can accelerate access to vaccines globally.

 

 
 

 
 

Announcing a new collaboration to showcase 3Rs technologies

Do you have a great 3Rs idea or technology you want to share with the biosciences research community? Are you looking for partners to help further develop, validate or adopt your 3Rs model or approach? Are you horizon scanning for the next 3Rs technology breakthrough to support your toxicology needs?

 

We have teamed up with konfer to provide a platform for small companies and academics to share 3Rs technologies and maximise their impact through forming new partnerships.

 

 
 

 
 

European Commission Call for data for fish toxicity studies

The European Commission is currently running a project reviewing the use of controls in aquatic toxicity testing in fish. This project will focus on whether it is appropriate to use only one control when a solvent is used in aquatic toxicity tests. Currently both a water and solvent control are required when a solvent is used which has a significant impact on the number of animals used and the resources required to conduct the test. The data are needed to assess which controls should be used in the study and the impact of using only one control on the power of the study.

 

Data that are of particular relevance to the project include:

  • TG 210 full study data using fathead minnow and dimethylformamide (DMF) as the solvent (i.e. concentration-response data and respective water-only control and solvent control data).

  • TG 210 control data where the solvent was DMF (i.e. solvent and water-only control data.

  • TG 210 using other species or solvents.

If you could share TG 210 data from studies using other species or solvents, or data from other TGs, this may still be of use.

 

To contribute data or for more information about the project or how the data will be used, please contact John Green (John@JohnWGreen-ecostats.com), who is leading the data collection and statistical analysis, also copying in Marlies Halder (Marlies.HALDER@ec.europa.eu), the project lead.

 

The deadline for responding is Tuesday 15 December, although there is some flexibility.