Metabolomics as read-across tool: An example with 3-aminopropanol and 2-aminoethanol

Read-across and grouping is one of the most commonly used alternative approaches for data gap filling in registrations submitted under the REACH Regulation as defined by the European Chemicals Agency (ECHA) in their ‘Read-Across Assessment Framework’ (RAAF, 2017). At the same time, the application o...

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Bibliographic Details
Published in:Regulatory toxicology and pharmacology 2019-11, Vol.108, p.104442, Article 104442
Main Authors: Sperber, S., Wahl, M., Berger, F., Kamp, H., Lemke, O., Starck, V., Walk, T., Spitzer, M., Ravenzwaay, B.v
Format: Article
Language:English
Subjects:
Animals
Ethanolamine - toxicity
Female
Male
Metabolome - drug effects
Metabolomics
Propanolamines - toxicity
Rats, Wistar
Read across
Risk Assessment
Toxicity Tests
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Summary:Read-across and grouping is one of the most commonly used alternative approaches for data gap filling in registrations submitted under the REACH Regulation as defined by the European Chemicals Agency (ECHA) in their ‘Read-Across Assessment Framework’ (RAAF, 2017). At the same time, the application of read-across is rejected by ECHA frequently due to various reasons. As a major reason hereof, applicants fail to reduce the level of ‘remaining uncertainty’ intrinsical to every read-across approach compared to testing a substance experimentally. Recently, the use of metabolomics to support read-across cases with biological information has been reported in a case study with phenoxy herbicides (Ravenzwaay et al., 2016). In the present case-study a ‘weight-of-evidence’ read-across approach from 2-aminoethanol (MEA = ‘source’) to 3-aminopropanol (3AP = ‘target’) with metabolomics as ‘supporting evidence’ reducing the remaining uncertainties is reported. We demonstrate the high structural similarity of the two analogous substances based on the available data and we report how metabolome data add confidence concerning mechanistic similarity in this read-across approach. Finally, the herein described read-across case supported by metabolomics is used to cover the data gaps in repeated dose and reproductive toxicity endpoint of 3AP via weight of evidence for the REACH-registration. •A read across from 2-aminoethanol (MEA) to 3-aminopropanol (3AP) is presented.•Metabolomics is used to add biological information to support the read across case.•BASF's MetaMap®Tox database was used to identify the best read across option.
ISSN:0273-2300
1096-0295
DOI:10.1016/j.yrtph.2019.104442