title: Assessment of chloroaniline toxicity by the submitochondrial particle assay.
abstract: The effects on mitochondrial respiration of 15 chloroanilines were recorded by using the in vitro response of submitochondrial particles (SMP) from beef heart mitochondria. The bioassay procedure for SMP is based on the process of reverse electron transfer, which can be negatively affected by inhibitors of electron transport, by uncouplers, and by chemicals that impair membrane integrity. The EC50 values, determined for the tested chloroanilines, indicate a general tendency of increasing toxicity with increasing chlorine substitution. In order to validate the results obtained and to evaluate the capability of the SMP assay to reproduce the toxic effects of the examined compounds on different freshwater species, the EC50 values were compared with literature data from other biological assays regarding both in vitro systems and whole organisms. A good correlation was found in particular with two widely used testing systems, the Microtox and the Tetrahymena assays. In addition, quantitative structure-activity relationships (QSARs) were established between the EC50 values and various molecular descriptors for hydrophobic, steric, and electronic interactions. The results obtained were utilized to elucidate the mechanism of toxic action of chloroanilines, which are commonly reported to act by the polar narcosis mode of action. Moreover, they confirmed that the SMP assay can be a useful tool for studying the toxicity of chemicals that act nonspecifically by impairing membrane structure and functions.
authors.affiliation: Department of Environmental Sciences, Università Ca' Foscari di Venezia, Italy. argese@unive.it
authors.forename: E
authors.initials: E
authors.lastname: Argese
authors.forename: C
authors.initials: C
authors.lastname: Bettiol
authors.forename: F
authors.initials: F
authors.lastname: Agnoli
authors.forename: A
authors.initials: A
authors.lastname: Zambon
authors.forename: M
authors.initials: M
authors.lastname: Mazzola
authors.forename: A V
authors.initials: AV
authors.lastname: Ghirardini
mesh_terms: D000814:Aniline Compounds / Q000633:toxicity*; D000818:Animals; D002417:Cattle; D004579:Electron Transport / Q000187:drug effects; D015386:Hazardous Substances / Q000633:toxicity; D008929:Mitochondria, Heart / Q000187:drug effects* / Q000378:metabolism; D009243:NAD / Q000378:metabolism; D011036:Poecilia; D012044:Regression Analysis; D013329:Structure-Activity Relationship; D013367:Submitochondrial Particles / Q000187:drug effects* / Q000378:metabolism; D013769:Tetrahymena pyriformis / Q000187:drug effects
chemical_list: D000814:Aniline Compounds; D015386:Hazardous Substances; D009243:NAD