title: A practical guidance for Cramer class determination.
abstract: Expanded use of the Threshold of Toxicological Concern (TTC) methodology has brought into discussion the intent of the original questions used in the Cramer scheme or Cramer decision tree. We have analysed, both manually and by Toxtree software, a large dataset of fragrance ingredients and identified several issues with the original Cramer questions. Some relate to definitions and wording of questions; others relate to in silico interpretation of the questions. We have endeavoured to address all of these inconsistencies and misinterpretations without changing the basic structure and principles of the original decision tree. Based on the analysis of a large data set of over 2500 fragrance ingredients, we found that most of the 33 questions in the original Cramer scheme are straightforward. Through repeated examination each of the 33 questions, we found 14 where the logic underlying the development of the rule is unclear. These questions are well served by minor wording changes and/or further explanation designed to capture what we perceive to be the intent of the original decision tree. The findings reported here could be used as a guidance for conducting Cramer classification and provide advices for the improvement of the in silico tools.
authors.affiliation: School of Pharmacy and Biomolecular Sciences, Liverpool John Moores University, Liverpool, L3 3AF, United Kingdom.
authors.forename: David W
authors.initials: DW
authors.lastname: Roberts
authors.affiliation: Unilever Safety and Environmental Assurance Centre, Colworth Science Park, Sharnbrook, Bedford, MK44 1LQ, United Kingdom.
authors.forename: Aynur
authors.initials: A
authors.lastname: Aptula
authors.affiliation: The University of Tennessee, College of Veterinary, 2407 River Drive, Knoxville, TN 37996, USA.
authors.forename: Terry W
authors.initials: TW
authors.lastname: Schultz
authors.affiliation: Research Institute for Fragrance Materials, Inc., 50 Tice Boulevard, Woodcliff Lake, NJ 07677, USA. Electronic address: jshen@rifm.org.
authors.forename: Jie
authors.initials: J
authors.lastname: Shen
authors.affiliation: Research Institute for Fragrance Materials, Inc., 50 Tice Boulevard, Woodcliff Lake, NJ 07677, USA.
authors.forename: Anne Marie
authors.initials: AM
authors.lastname: Api
authors.affiliation: Research Institute for Fragrance Materials, Inc., 50 Tice Boulevard, Woodcliff Lake, NJ 07677, USA.
authors.forename: Sneha
authors.initials: S
authors.lastname: Bhatia
authors.affiliation: Research Institute for Fragrance Materials, Inc., 50 Tice Boulevard, Woodcliff Lake, NJ 07677, USA.
authors.forename: Lambros
authors.initials: L
authors.lastname: Kromidas
mesh_terms: D003198:Computer Simulation; D003661:Decision Support Techniques; D003663:Decision Trees; D006801:Humans; D008128:Logic; D015394:Molecular Structure; D010476:Perfume / Q000009:adverse effects* / Q000737:chemistry / Q000145:classification*; D018570:Risk Assessment; D012984:Software; D013329:Structure-Activity Relationship; D009626:Terminology as Topic
chemical_list: D010476:Perfume