title: Comparison of Cramer classification between Toxtree, the OECD QSAR Toolbox and expert judgment.
abstract: 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.
authors.affiliation: Research Institute for Fragrance Materials, Inc., 50 Tice Blvd., Woodcliff Lake, NJ 07677, USA.
authors.forename: Sneha
authors.initials: S
authors.lastname: Bhatia
authors.affiliation: The University of Tennessee, College of Veterinary, 2407 River Dr., Knoxville, TN 37996, USA.
authors.forename: Terry
authors.initials: T
authors.lastname: Schultz
authors.affiliation: Liverpool John Moores University, Liverpool L3 3AF, UK.
authors.forename: David
authors.initials: D
authors.lastname: Roberts
authors.affiliation: Research Institute for Fragrance Materials, Inc., 50 Tice Blvd., Woodcliff Lake, NJ 07677, USA.
authors.forename: Jie
authors.initials: J
authors.lastname: Shen
authors.affiliation: Research Institute for Fragrance Materials, Inc., 50 Tice Blvd., Woodcliff Lake, NJ 07677, USA. Electronic address: lkromidas@rifm.org.
authors.forename: Lambros
authors.initials: L
authors.lastname: Kromidas
authors.affiliation: Research Institute for Fragrance Materials, Inc., 50 Tice Blvd., Woodcliff Lake, NJ 07677, USA.
authors.forename: Anne
authors.initials: A
authors.lastname: Marie Api
mesh_terms: D003198:Computer Simulation; D003663:Decision Trees; D010476:Perfume / Q000737:chemistry / Q000145:classification* / Q000633:toxicity; D021281:Quantitative Structure-Activity Relationship; D018570:Risk Assessment
chemical_list: D010476:Perfume
keywords: Cramer classification; OECD QSAR Toolbox; TTC; Toxtree; in silico