flash
EPAA Blue sky Workshop
1-2 October 2019, Brussels, Belgium
New Ideas for Systemic Toxicity
The EPAA organised a Blue Sky Workshop on “New Ideas for
Systemic Toxicity” from 1-2 October 2019 in Brussels, Belgium.
The Workshop was chaired by Drs George Daston and Cathe-
rine Mahony and involved 31 experts from Europe and North
America representing cross-sector industries and regulatory
agencies, the European Commission and academia. The ove-
rall goal of the Workshop was to formulate strategic research
elements to derive a list of recommended actions to identify
new ideas for repeated dose systemic toxicity. The focus was
on how specific scientific areas and new approaches might be
applied in regulatory frameworks.
The Workshop agreed that there are many technologies, or
New Approach Methodologies (NAMs), that have evolved over
the last decade and can provide an insight into the systemic
effects of chemicals as well as supporting read-across. The
NAMs discussed included computational chemistry and bio-
chemistry methods focussing on the 3D structure of potential
ligands; high throughput and content techniques; the use of
big data from omics including “deep proteomics”; the applica-
tion of microphysiological systems e.g. organoids; the role of
in silico models and virtual organs; as well a Mode of Action
ontology that can provide a framework for organising data in
a safety assessment context.
It was observed that much knowledge already exists for the
traditional tests and NAMs. A key challenge and priority is the
sharing of all types of data. There is an aspiration that data
should be made freely available and accessible from a com-
mon platform. Whilst this is currently achievable, incentives
may be required to facilitate release of more, high quality and
mechanistically relevant, information.
In addition to the present Flash report, a video with highlights from the Workshop has been produced and will be available on the
EPAA website shortly. Moreover, the main discussions and recommendations of the Workshop will be reported in a peer-reviewed
publication.
Problem formulation for the safety decision to be made
needs to be reassessed, to be fit for purpose, and the works-
hop foresaw a move from the traditional need for regulatory
requirements to that of safety-based information. This is a
large challenge, potentially disruptive in nature. The goal will
be to ensure human health protection moves away from the
reliance on traditional tests. To achieve this, solutions may
be mechanistically or knowledge (i.e. data) based. The prefe-
rence is for mechanistically-based technologies spanning the
full range of computational and in vitro methods. Integrated
systems modelling is thought to be an opportunity that can
support both read-across and ab initio alternatives to the cur-
rent paradigm.
Currently few, if any, data from NAMs are provided to agen-
cies as part of regulatory submissions. A new openness from
both sides is required in the use of NAMs. Standardisation and
validation of NAMs data will assist in this process and will un-
derpin confidence and trust building. Good communication
as well as novel concepts in understanding and quantifying
uncertainty, benchmarking technologies and case studies are
essential.
Overall, the Workshop acknowledged the significant level of
stakeholder involvement required in making better assess-
ments of systemic toxicity. The successful workflows will be
based around mechanistically derived computational and
non-animal data used in appropriate strategies. There is a
need for these new approaches to be in line with the protec-
tion goal, transparent, reproducible and accessible.
About EPAA

EPAA is a Public-Private Partnership across seven industry sectors and between European Commission and Industry
stakeholders. Launched in 2005, it gathers 37 companies, 8 European trade federations and 5 Directorates-General of
the European Commission.

Further information is available on https://ec.europa.eu/growth/sectors/chemicals/epaa_en

@EPAA3Rs

EPAA European Partnership for Alternatives