title: An in silico expert system for the identification of eye irritants.
abstract: This report describes development of an in silico, expert rule-based method for the classification of chemicals into irritants or non-irritants to eye, as defined by the Draize test. This method was developed to screen data-poor cosmetic ingredient chemicals for eye irritancy potential, which is based upon exclusion rules of five physicochemical properties - molecular weight (MW), hydrophobicity (log P), number of hydrogen bond donors (HBD), number of hydrogen bond acceptors (HBA) and polarizability (Pol). These rules were developed using the ADMET Predictor software and a dataset of 917 eye irritant chemicals. The dataset was divided into 826 (90%) chemicals used for training set and 91 (10%) chemicals used for external validation set (every 10th chemical sorted by molecular weight). The sensitivity of these rules for the training and validation sets was 72.3% and 71.4%, respectively. These rules were also validated for their specificity using an external validation set of 2011 non-irritant chemicals to the eye. The specificity for this validation set was revealed as 77.3%. This method facilitates rapid screening and prioritization of data poor chemicals that are unlikely to be tested for eye irritancy in the Draize test.
authors.affiliation: a Office of Cosmetics and Colors, Center for Food Safety and Applied Nutrition , US Food and Drug Administration , 5100 Paint Branch Parkway, College Park, MD 20740 , USA.
authors.forename: R P
authors.initials: RP
authors.lastname: Verma
authors.forename: E J
authors.initials: EJ
authors.lastname: Matthews
mesh_terms: D000826:Animal Testing Alternatives; D055598:Chemical Phenomena; D003198:Computer Simulation; D003358:Cosmetics / Q000737:chemistry / Q000633:toxicity; D005103:Expert Systems; D005128:Eye Diseases / Q000139:chemically induced*; D007509:Irritants / Q000737:chemistry* / Q000633:toxicity; D021281:Quantitative Structure-Activity Relationship; D015203:Reproducibility of Results; D014116:Toxicology / Q000379:methods
chemical_list: D003358:Cosmetics; D007509:Irritants
keywords: Draize test; decision support system; expert rule; eye irritation; hydrophobicity; in silico; molecular weight; number of hydrogen bond acceptors; number of hydrogen bond donors; physicochemical exclusion rules; polarizability