Title
Improvement of the Cramer classification for oral exposure using the database TTC RepDose - A strategy description
Author
Tluczkiewicz, I.
Buist, H.E.
Martin, M.T.
Mangelsdorf, I.
Escher, S.E.
Publication year
2011
Abstract
The present report describes a strategy to refine the current Cramer classification of the TTC concept using a broad database (DB) termed TTC RepDose. Cramer classes 1-3 overlap to some extent, indicating a need for a better separation of structural classes likely to be toxic, moderately toxic or of low toxicity.Groups of structurally similar compounds of high toxicity in Cramer class 1 and of moderate to low toxicity in Cramer class 3 were identified and reassigned to the appropriate Cramer class according to their observed toxicological potency in in vivo studies. This refinement results in a better discrimination of Cramer classes 1 and 3 and an increased number of substances in Cramer class 2. The TTC values are 8.7 µmol/person/d (class 1), 6.72 µmol/person/d (class 2) and 0.28µmol/person/d (class 3). Assuming a median molecular weight of 220. g/mol for the compounds of the TTC RepDose DB, the corresponding TTC values are 1930, 1478 and 63 µg/person/d for classes 1, 2 and 3 respectively. The derived thresholds are close to the TTC values initially proposed by Munro with 1800, 540 and 90 µg/person/d for classes 1, 2 and 3 respectively. Additional structural classes are discussed with a view to further refinement of the current Cramer classification scheme. © 2011 Elsevier Inc.
Subject
Life
QS - Quality & Safety
EELS - Earth, Environmental and Life Sciences
Nutrition
Cramer classification
Database
Oral exposure
Refinement
RepDose
Risk assessment
SAR
Structure activity relationship
Threshold of toxicological concern
Toxicology
TTC concept
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http://resolver.tudelft.nl/uuid:2ac69e31-e77f-4dff-b208-4d2bc706a67e
DOI
https://doi.org/10.1016/j.yrtph.2011.09.005
TNO identifier
442930
ISSN
0273-2300
Source
Regulatory Toxicology and Pharmacology, 61 (3), 340-350
Document type
article