Cinzia Bettiol

Modeling and prediction by using WHIM descriptors in QSAR studies: submitochondrial particles (SMP) as toxicity blosensors of chlorophenols

Abstract New 3-dimensional molecular indices (WHIM descriptors) contain information about the whole molecular structure in terms of size, shape, symmetry and atom distribution. These indices are calculated from (x,y,z)-coordinates of a molecule within different weighting schemes in a straightforward manner and represent a very general approach to describe molecules in a unitary conceptual framework. The obtained models confirm the high modeling power of the WHIM descriptors. In this work WHIM descriptors are used for modeling chlorophenols toxicity measured by other not previously considered biosensors. In particular, the attention is stressed on submitochondral particles (SMP) as toxicity biosensors recently proposed and their relationships with other biosensors are further investigated.

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 with six molecular descriptors, chosen to represent lipophilic, electronic and steric effects: the n-octanol/water partition coefficient (log Kow), the constant of Hammett (sigma sigma), the acid dissociation constant (pKa), the first order valence molecular connectivity index (1 chi v), the perimeter of the efficacious section (sigma D) and the melting point (m.p.). The results of regression analysis showed that log Kow 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 SMP assay as a short-term prediction tool for aquatic toxicity of environmental pollutants acting on respiratory functions.

Pollutant Exchange at the Water/Sediment Interface in the Venice Canals

The space-time distribution of some pollutants (Cu, Pb, Zn, Cd, Fe, Mn, V, Ni, Cr) in the sludge of the canals of Venice was studied. The contamination levels were comparable to, or higher, than those measured in the most polluted sediments of the Lagoon of Venice. Sediments were collected by two different sampling techniques: 1) collection of sediment cores (upper 5 cm) by a syringe-type corer; 2) collection by traps, placed on the bottom of the canal. Traps permitted the sampling of sediments essentially resuspended by overlying water turbulence. This sediment fraction is subjected to variations of its physicochemical parameters (principally change of redox conditions) and therefore to pollutant exchange at the water/sediment interface.The metals principally exchanged during sediment resuspension were Cd, Pb, Zn and Cu. These metals have principally an anthropogenic origin and are bound to the most labile geochemical phases of the sediment (such as sulphides), which can be oxidised during sediment resuspension, releasing metals into the water. Fe, Cr and Ni were only partially exchanged, while Mn and V were generally not exchanged; a significant fraction of these metals is of natural origin and is bound to the most refractory phases of the sediment.

Assessment of phenolic herbicide toxicity and mode of action by different assays

A phytotoxicity assay based on seed germination/root elongation has been optimized and used to evaluate the toxic effects of some phenolic herbicides. The method has been improved by investigating the influence of experimental conditions. Lepidium sativum was chosen as the most suitable species, showing high germinability, good repeatability of root length measurements, and low sensitivity to seed pretreatment. DMSO was the most appropriate solvent carrier for less water-soluble compounds. Three dinitrophenols and three hydroxybenzonitriles were tested: dinoterb, DNOC, 2,4-dinitrophenol, chloroxynil, bromoxynil, and ioxynil. Toxicity was also determined using the Vibrio fischeri Microtox® test, and a highly significant correlation was found between EC50 values obtained by the two assays. Dinoterb was the most toxic compound. The toxicity of hydroxybenzonitriles followed the order: ioxynil >bromoxynil >chloroxynil; L. sativum exhibited a slightly higher sensitivity than V. fischeri to these compounds. A QSAR analysis highlighted the importance of hydrophobic, electronic, and hydrogen-bonding interactions, in accordance with a mechanism of toxic action based on protonophoric uncoupling of oxidative phosphorylation. The results suggest that the seed germination/root elongation assay with L. sativum is a valid tool for the assessment of xenobiotic toxicity and can be recommended as part of a test battery.

H. diversicolor, N. succinea and P. cultrifera (Polychaeta: Nereididae) as bioaccumulators of cadmium and zinc from sediments: Preliminary results in the Venetian lagoon (Italy)

A field investigation was performed to evaluate the suitability of three nereid polychaetes species as biomonitors for sediment contamination by Cd and Zn in the Venetian lagoon (Italy). With regard to the treatment and subsequent chemical analysis of the animals, a specific methodology was set up. Metal concentrations in sediments and tissues were compared for 20 stations. Cd bioaccumulation was detected in all species, although bioaccumulation factors and the concentration trends were different. This finding could be explained by a difference in the metal bioavailability or in the accumulation strategy of species. Zn results have confirmed the presence of a regulation strategy in the nereid polychaetes, as previously reported.

Substituted aniline interaction with submitochondrial particles and quantitative structure–activity relationships

The toxic effects of eighteen substituted anilines were determined by means of a short-term in vitro assay, using submitochondrial particles (SMP) as biosensors. The assay allows for the quantification of the effects of toxicants that act specifically on mitochondrial respiratory functions, like uncouplers and inhibitors, or non-specifically, by disturbing the structure and functioning of the inner mitochondrial membrane. The obtained EC(50) values range from 72.5 to 1910 micromol/l. The type and position of the substituents are of fundamental importance in determining the toxic potency. In general, the presence of electron-withdrawing substituents produces higher toxic effects, whereas electron-donating groups seem to reduce the toxicity. Quantitative structure-activity relationships (QSAR) showed that toxicity values were correlated with the Hammett sigma constant and with hydrogen bonding capacity descriptors, such as E(LUMO), E(HOMO) and Q(+). The results indicate that toxicity increases with increasing the hydrogen bonding donor capacity of the NH(2) group and support the hypothesis of a mechanism of action based on hydrogen bonding formation between the amino group of anilines and polar groups at the membrane/water interface. Such an interaction would cause a derangement of the membrane structure and, as a consequence, a disturbance of its functioning.

Heavy metal partitioning in sediments from the Lagoon of Venice (Italy)

In this study heavy metal pollution in surface sediments of the Lagoon of Venice (Italy) was investigated. Attention was focused on the evaluation of the amounts of heavy metals that can potentially be released into the overlying water column, under particular environmental conditions, thus becoming bioavailable. To this end, the partitioning of heavy metals among different geochemical phases was determined by a procedure of sequential selective extractions. This approach can provide useful information for assessing the risk posed to the Lagoon ecosystem by metal contaminated sediments and for estimating the anthropogenic heavy metal content. In general, higher levels of contamination were found in sediments sampled in areas situated in the proximity of sources of pollutants and in degraded sites, which presented limited water circulation and prevailing anoxic conditions. The results of the sequential extraction procedure showed that partitioning is dependent on the metal considered: in particular, Pb, Cu, Zn and Cd were bound mainly to the most labile phases of sediments, whereas Cr and Ni were found prevalently in the residual fraction.