title: Towards AOP application--implementation of an integrated approach to testing and assessment (IATA) into a pipeline tool for skin sensitization.
abstract: Since the OECD published the Adverse Outcome Pathway (AOP) for skin sensitization, many efforts have focused on how to integrate and interpret nonstandard information generated for key events in a manner that can be practically useful for decision making. These types of frameworks are known as Integrated Approaches to Testing and Assessment (IATA). Here we have outlined an IATA for skin sensitization which focuses on existing information including non testing approaches such as QSAR and read-across. The IATA was implemented into a pipeline tool using OASIS technology to provide a means of systematically collating and compiling relevant information which could be used in an assessment of skin sensitization potential. A test set of 100 substances with available skin sensitization information was profiled using the pipeline IATA. In silico and in chemico profiling information alone was able to correctly predict skin sensitization potential, with a preliminary accuracy of 73.85%. Information from other relevant endpoints (e.g., Ames mutagenicity) was found to improve the accuracy (to 87.6%) when coupled with a reaction chemistry mechanistic understanding. This pipeline platform could be useful in the assessment of skin sensitization potential and marks a step change in how non testing approaches can be practically applied.
authors.affiliation: DuPont Haskell Global Centers for Health and Environmental Sciences, 1090 Elkton Road, Newark, DE 19711, USA. Electronic address: patlewig@hotmail.com.
authors.forename: Grace
authors.initials: G
authors.lastname: Patlewicz
authors.affiliation: Laboratory of Mathematical Chemistry, University "Prof As Zlatarov", 1 Yakim Street, Bourgas, Bulgaria.
authors.forename: Chanita
authors.initials: C
authors.lastname: Kuseva
authors.affiliation: Laboratory of Mathematical Chemistry, University "Prof As Zlatarov", 1 Yakim Street, Bourgas, Bulgaria.
authors.forename: Antonia
authors.initials: A
authors.lastname: Kesova
authors.affiliation: Laboratory of Mathematical Chemistry, University "Prof As Zlatarov", 1 Yakim Street, Bourgas, Bulgaria.
authors.forename: Ioanna
authors.initials: I
authors.lastname: Popova
authors.affiliation: Laboratory of Mathematical Chemistry, University "Prof As Zlatarov", 1 Yakim Street, Bourgas, Bulgaria.
authors.forename: Teodor
authors.initials: T
authors.lastname: Zhechev
authors.affiliation: Laboratory of Mathematical Chemistry, University "Prof As Zlatarov", 1 Yakim Street, Bourgas, Bulgaria.
authors.forename: Todor
authors.initials: T
authors.lastname: Pavlov
authors.affiliation: Liverpool John Moores University, School of Pharmacy and Biomolecular Sciences, Byrom Street, Liverpool L3 3AF, UK.
authors.forename: David W
authors.initials: DW
authors.lastname: Roberts
authors.affiliation: Laboratory of Mathematical Chemistry, University "Prof As Zlatarov", 1 Yakim Street, Bourgas, Bulgaria.
authors.forename: Ovanes
authors.initials: O
authors.lastname: Mekenyan
mesh_terms: D000485:Allergens / Q000737:chemistry* / Q000276:immunology*; D045744:Cell Line, Tumor; D017449:Dermatitis, Allergic Contact / Q000209:etiology / Q000276:immunology; D006801:Humans; D066150:Organisation for Economic Co-Operation and Development; D011485:Protein Binding / Q000276:immunology; D021281:Quantitative Structure-Activity Relationship; D018570:Risk Assessment; D012867:Skin / Q000276:immunology*; D018417:Th1 Cells; D020298:U937 Cells
chemical_list: D000485:Allergens
keywords: (Q)SAR; Adverse Outcome Pathway (AOP); Expert systems; Integrated Approaches to Testing and Assessment (IATA); Read-across; TIMES-SS