Quantitative structure—activity relationships for the toxicity of chlorophenols to mammalian submitochondrial particles

The toxicity of a series of chlorophenols, determined by a short-term in vitro assay utilizing mammalian submitochondrial particles, was related to the physicochemical and structural properties of these compounds. Quantitative Structure-Activity Relationships were defined by correlating EC50 values...

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Bibliographic Details
Published in:Chemosphere (Oxford) 1999-04, Vol.38 (10), p.2281-2292
Main Authors: Argese, Emanuele, Bettiol, Cinzia, Giurin, Gianumberto, Miana, Paola
Format: Article
Language:English
Subjects:
Animal, plant and microbial ecology
Animals
Applied ecology
Biological and medical sciences
Cattle
Cell Membrane - drug effects
chlorophenols
Chlorophenols - toxicity
Ecotoxicology, biological effects of pollution
Effects of pollution and side effects of pesticides on vertebrates
Fundamental and applied biological sciences. Psychology
Lethal Dose 50
Mammalia
Models, Theoretical
QSAR
Structure-Activity Relationship
submitochondrial particles
Submitochondrial Particles - drug effects
toxicity
uncouplers
Uncoupling Agents - metabolism
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Summary:The toxicity of a series of chlorophenols, determined by a short-term in vitro assay utilizing mammalian submitochondrial particles, was related to the physicochemical and structural properties of these compounds. Quantitative Structure-Activity Relationships were defined by correlating EC50 values with six molecular descriptors, chosen to represent lipophilic, electronic and steric effects: the n-octanol/water partition coefficient (log K OW), the constant of Hammett (Σσ), the acid dissocidtion constant (pK a), the first order valence molecular connectivity index ( 1 ζ v ), the perimeter of the efficacious section (ΣD) and the melting point (m.p.). The results of regression analysis showed that log K ow is the most successful descriptor, indicating that the ability of chlorophenols to partition into the lipid bilayer of the mitochondrial membrane has an important role in determining their toxic effects. These results are consistent with a molecular mechanism of uncoupling action based on the chemiosmotic theory and on the protonophoric properties of chlorophenols. The quality of the QSAR models confirms the suitability of the SNIP assay as a short-term prediction tool for aquatic toxicity of environmental pollutants acting on respiratory functions.
ISSN:0045-6535
1879-1298
DOI:10.1016/S0045-6535(98)00446-9