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Regul Toxicol Pharmacol. 2018 Nov;99:5-21. doi: 10.1016/j.yrtph.2018.08.006. Epub 2018 Aug 23.

Finding synergies for 3Rs - Toxicokinetics and read-across: Report from an EPAA partners' Forum.

Author information

1
The International Fragrance Association (IFRA), Belgium.
2
Dow AgroSciences, United Kingdom.
3
Bonn, Germany.
4
Henkel AG & Co KGaA, Germany.
5
BASF SE, Germany.
6
European Partnership for Alternative Approaches to Animal Testing (EPAA) Industry Secretariat, Belgium.
7
GlaxoSmithKline, United Kingdom.
8
European Commission, the Directorate-General (DG) for Internal Market, Industry, Entrepreneurship and SMEs (GROW), Belgium.
9
European Commission, The Directorate-General (DG) for Research and Innovation (RTD), Belgium.
10
SIMCYP, United Kingdom.
11
Hubesch Consult BVBA, Belgium.
12
The International Fragrance Association (IFRA), Belgium. Electronic address: airizar@ifraorg.org.
13
Animal Health Europe, Belgium.
14
University of Rovira i Virgili, Spain.
15
European Commission, The Directorate-General (DG) Joint Research Centre (JRC), Italy.
16
Janssen Pharmaceuticals, Belgium.
17
Symrise AG Holzminden, Germany.
18
European Federation of Pharmaceutical Industries and Associations (EFPIA), Belgium.
19
EPAA Consultant, United Kingdom.
20
Organisation for Economic Cooperation and Development (OECD), France.
21
European Commission, the Directorate-General (DG) Environment (ENV), Belgium.
22
Zoetis Ltd, United Kingdom.
23
Cosmetics Europe, Belgium.
24
Medicines Evaluation Board, the Netherlands.
25
Scientific Consultancy - Animal Welfare, Germany.

Abstract

The European Partnership for Alternative Approaches to Animal Testing (EPAA) convened a Partners' Forum Toxicokinetics and Read-Across to provide an overview on research activities to develop in vitro toxicokinetics methods and physiologically-based kinetic (PBK) models and to find synergies to enhance use of toxicokinetic data to strengthen read-across. Currently, lacking toxicokinetic data often prevent the application of read-across. Preferably, toxicokinetic data should be generated using in vitro and in silico tools and anchored towards human relevance. In certain sectors, PBK modelling is being used for risk assessment, but less so in others. Specific activities were identified to facilitate the use of in vitro and in silico toxicokinetic data to support read-across: The collation of available tools indicating the parameters and applicability domains covered; endpoint-specific guidance on toxicokinetics parameters required for read-across; case studies exemplifying how toxicokinetic data help support read-across. Activities to enhance the scientific robustness of read-across include the further user-friendly combination of read-across tools and formal guidance by the authorities specifying the minimum information requirements to justify read-across for a given toxicity endpoint. The EPAA was invited to continue dissemination activities and to explore possibilities to collate a contemporaneous list of open toxicokinetics tools that assist risk assessment.

KEYWORDS:

Absorption; And elimination; Distribution; Excretion (ADME); Hazard and risk assessment; In vitro to in vivo extrapolation (IVIVE); Integrated approach for testing and assessment (IATA); Metabolism; Physiologically-based kinetic (PBK) modelling; Threshold of toxicological concern (TTC); Weight-of-evidence (WoE)

PMID:
30144470
DOI:
10.1016/j.yrtph.2018.08.006
[Indexed for MEDLINE]
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