The sensitivity of metabolomics versus classical regulatory toxicology from a NOAEL perspective.

Abstract:

:The identification of the no observed adverse effect level (NOAEL) is the key regulatory outcome of toxicity studies. With the introduction of "omics" technologies into toxicological research, the question arises as to how sensitive these technologies are relative to classical regulatory toxicity parameters. BASF SE and metanomics developed the in vivo metabolome database MetaMap®Tox containing metabolome data for more than 500 reference compounds. For several years metabolome analysis has been routinely performed in regulatory toxicity studies (REACH mandated testing or new compound development), mostly in the context of 28 day studies in rats (OECD 407 guideline). For those chemicals for which a toxicological NOAEL level was obtained at either high or mid-dose level, we evaluated the associated metabolome to investigate the sensitivity of metabolomics versus classical toxicology with respect to the NOAEL. For the definition of a metabolomics NOAEL the ECETOC criteria (ECETOC, 2007) were used. In this context we evaluated 104 cases. Comparable sensitivity was noted in 75% of the cases, increased sensitivity of metabolomics in 8%, and decreased sensitivity in 18% of the cases. In conclusion, these data suggest that metabolomics profiling has a similar sensitivity to the classical toxicological study (e.g. OECD 407) design.

journal_name

Toxicol Lett

journal_title

Toxicology letters

authors

van Ravenzwaay B,Montoya GA,Fabian E,Herold M,Krennrich G,Looser R,Mellert W,Peter E,Strauss V,Walk T,Kamp H

doi

10.1016/j.toxlet.2014.03.004

subject

Has Abstract

pub_date

2014-05-16 00:00:00

pages

20-8

issue

1

eissn

0378-4274

issn

1879-3169

pii

S0378-4274(14)00119-2

journal_volume

227

pub_type

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