title: Development of structure-activity relationship for metal oxide nanoparticles.
abstract: Nanomaterial structure-activity relationships (nano-SARs) for metal oxide nanoparticles (NPs) toxicity were investigated using metrics based on dose-response analysis and consensus self-organizing map clustering. The NP cellular toxicity dataset included toxicity profiles consisting of seven different assays for human bronchial epithelial (BEAS-2B) and murine myeloid (RAW 264.7) cells, over a concentration range of 0.39-100 mg L(-1) and exposure time up to 24 h, for twenty-four different metal oxide NPs. Various nano-SAR building models were evaluated, based on an initial pool of thirty NP descriptors. The conduction band energy and ionic index (often correlated with the hydration enthalpy) were identified as suitable NP descriptors that are consistent with suggested toxicity mechanisms for metal oxide NPs and metal ions. The best performing nano-SAR with the above two descriptors, built with support vector machine (SVM) model and of validated robustness, had a balanced classification accuracy of ~94%. An applicability domain for the present data was established with a reasonable confidence level of 80%. Given the potential role of nano-SARs in decision making, regarding the environmental impact of NPs, the class probabilities provided by the SVM nano-SAR enabled the construction of decision boundaries with respect to toxicity classification under different acceptance levels of false negative relative to false positive predictions.
authors.affiliation: California Nanosystems Institute, University of California, Los Angeles, CA 90095, USA.
authors.forename: Rong
authors.initials: R
authors.lastname: Liu
authors.forename: Hai Yuan
authors.initials: HY
authors.lastname: Zhang
authors.forename: Zhao Xia
authors.initials: ZX
authors.lastname: Ji
authors.forename: Robert
authors.initials: R
authors.lastname: Rallo
authors.forename: Tian
authors.initials: T
authors.lastname: Xia
authors.forename: Chong Hyun
authors.initials: CH
authors.lastname: Chang
authors.forename: Andre
authors.initials: A
authors.lastname: Nel
authors.forename: Yoram
authors.initials: Y
authors.lastname: Cohen
mesh_terms: D000818:Animals; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D006801:Humans; D053768:Metal Nanoparticles / Q000737:chemistry* / Q000633:toxicity; D008670:Metals / Q000737:chemistry; D051379:Mice; D010087:Oxides / Q000737:chemistry; D013329:Structure-Activity Relationship; D060388:Support Vector Machine
chemical_list: D008670:Metals; D010087:Oxides