In vivo toxicity of nitroaromatics: A comprehensive quantitative structure-activity relationship study.
The toxicity data of 90 nitroaromatic compounds related to their 50% lethal dose concentration for rats (LD50) were analyzed to develop quantitative structure-activity relationship (QSAR) models. Quantum-chemically calculated descriptors together with molecular descriptors generated by DRAGON, PaDEL, and HiT-QSAR software were utilized to build QSAR models. Quality and validity of the models were determined by internal and external validation techniques. The results show that the toxicity of nitroaromatic compounds depends on various factors, such as the number of nitro-groups, the topological state, and the presence of certain structural fragments. The developed models based on the largest (to date) dataset of nitroaromatics in vivo toxicity showed a good predictive ability. The results provide important input that could be applied in a preliminary assessment of nitroaromatic compounds' toxicity to mammals. Environ Toxicol Chem 2017;36:2227-2233. © 2017 SETAC.
Department of Chemistry and Biochemistry, Jackson State University, Jackson, Mississippi, USA.
Aminah
A
Gooch
Department of Chemistry and Biochemistry, Jackson State University, Jackson, Mississippi, USA.
Natalia
N
Sizochenko
Department of Chemistry and Biochemistry, Jackson State University, Jackson, Mississippi, USA.|Department of Coatings and Polymeric Materials, North Dakota State University, Fargo, North Dakota, USA.
Bakhtiyor
B
Rasulev
Department of Chemistry and Biochemistry, Jackson State University, Jackson, Mississippi, USA.|HX5, Vicksburg, Mississippi, USA.
Leonid
L
Gorb
Department of Chemistry and Biochemistry, Jackson State University, Jackson, Mississippi, USA.
Jerzy
J
Leszczynski
D000818:Animals; D004785:Environmental Pollutants / Q000737:chemistry / Q000633:toxicity; D007928:Lethal Dose 50; D008962:Models, Theoretical; D009578:Nitrobenzenes / Q000737:chemistry / Q000633:toxicity; D011237:Predictive Value of Tests; D021281:Quantitative Structure-Activity Relationship; D051381:Rats; D012984:Software
D004785:Environmental Pollutants; D009578:Nitrobenzenes
Molecular descriptor; Nitroaromatic; Quantitative structure-activity relationships; Toxic effects; Toxicity mechanisms