Comparison of Cramer classification between Toxtree, the OECD QSAR Toolbox and expert judgment

•Assignment of Cramer class plays a significant role in setting the TTC value.•The assignment of 1016 fragrance materials by 3 different approaches was compared.•Two in silico programs differed in 16% of cases in the Cramer class assigned.•Strategies for assuring the robust assignment of a Cramer cl...

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Bibliographic Details
Published in:Regulatory toxicology and pharmacology 2015-02, Vol.71 (1), p.52-62
Main Authors: Bhatia, Sneha, Schultz, Terry, Roberts, David, Shen, Jie, Kromidas, Lambros, Marie Api, Anne
Format: Article
Language:English
Subjects:
Computer Simulation
Cramer classification
Decision Trees
in silico
OECD QSAR Toolbox
Perfume - chemistry
Perfume - classification
Perfume - toxicity
Quantitative Structure-Activity Relationship
Risk Assessment
Toxtree
TTC
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Summary:•Assignment of Cramer class plays a significant role in setting the TTC value.•The assignment of 1016 fragrance materials by 3 different approaches was compared.•Two in silico programs differed in 16% of cases in the Cramer class assigned.•Strategies for assuring the robust assignment of a Cramer class are proposed. The Threshold of Toxicological Concern (TTC) is a pragmatic approach in risk assessment. In the absence of data, it sets up levels of human exposure that are considered to have no appreciable risk to human health. The Cramer decision tree is used extensively to determine these exposure thresholds by categorizing non-carcinogenic chemicals into three different structural classes. Therefore, assigning an accurate Cramer class to a material is a crucial step to preserve the integrity of the risk assessment. In this study the Cramer class of over 1000 fragrance materials across diverse chemical classes were determined by using Toxtree (TT), the OECD QSAR Toolbox (TB), and expert judgment. Disconcordance was observed between TT and the TB. A total of 165 materials (16%) showed different results from the two programs. The overall concordance for Cramer classification between TT and expert judgment is 83%, while the concordance between the TB and expert judgment is 77%. Amines, lactones and heterocycles have the lowest percent agreement with expert judgment for TT and the TB. For amines, the expert judgment agreement is 45% for TT and 55% for the TB. For heterocycles, the expert judgment agreement is 55% for TT and the TB. For lactones, the expert judgment agreement is 56% for TT and 50% for the TB. Additional analyses were conducted to determine the concordance within various chemical classes. Critical checkpoints in the decision tree are identified. Strategies and guidance on determining the Cramer class for various chemical classes are discussed.
ISSN:0273-2300
1096-0295
DOI:10.1016/j.yrtph.2014.11.005