Showing papers in "Sar and Qsar in Environmental Research in 1996"

Estimating the sensory irritating potency of airborne nonreactive volatile organic chemicals and their mixtures.

Abstract: This article describes the possibility of estimating whether or not a mixture of nonreactive volatile organic chemicals (NRVOC) is likely to elicit complaints of sensory irritation in humans. For this estimation we rely on: a) the sensory irritating potency of individual NRVOC can be estimated from a variety of physicochemical properties of these chemicals, b) at low exposure concentrations, the additivity rule can be applied using the potency of each chemical in a mixture and c) a threshold concentration exists below which no sensory irritation will occur. We used this estimating approach and we compared the results obtained with those obtained experimentally in humans exposed to a well defined mixture. The approach presented can be used to arrive at a decision as to whether or not exposure to a mixture of NRVOC is likely to result in sensory irritation complaints by humans, either in the general indoor air situation or for industrial workers.

A novel QSAR approach for estimating toxicity of phenols.

Abstract: Toxicity values (log IGC−1 50) for 60 phenols tested in the 2-d static population growth inhibition assay with the ciliate Tetrahymena pyriformis were tabulated. Each chemical was selected so the series formed uniform coverage of the hydrophobicity/ionization surface. A high quality hydrophobicity-dependent (log K ow) structure-toxicity relationship (log IGC−1 50 = 0.741 (log Kow) −1.433; n = 17; r2 = 0.970; s = 0.134; F = 486.55; Pr > F = 0.0001) was developed for phenols with pKa values > 9.8. Similarly, separate hydrophobicity-dependent relationships were developed for phenols with pKa values of 4.0, 5.1, 6.3, 7.5, and 8.7. Comparisons of intercepts and slopes, respectively, revealed phenols with pKa values of 6.3 to be the most toxic and the least influenced by hydrophobicity. These relationships were reversed for the more acidic and basic phenols. Plots of toxicity versus pKa for nitro-substituted phenols and phenols with log Kow values of either 1.75 or 2.50 further demonstrated bilinearity...

Analysis of Structure-Toxicity Relationships for A Series of Amide Herbicides Using Statistical Methods and Neural Network

Abstract: Structure-toxicity relationships were studied for a set of 44 herbicides by means of principal component analysis (PCA), multiple regression analysis (MRA), and neural network (NN). The values of log LD50 (lethal dose 50, acute, oral, rat) of the studied compounds were well correlated with the descriptors encoding the chemical structures. Considering the pertinent descriptors, a correlation coefficient of 0.90 (n = 41) was obtained for the NN model with a configuration of 4-3-1 (and 0.92 (n = 41) with a configuration of 4-5-1). To evaluate the contribution of each descriptor on the activity, log LD50 was calculated by removing each descriptor a part. This approach provides the tendency of a descriptor to be favourable (or not) to the activity.

On the Usefulness and Reliability of Existing QSBRs for Risk Assessment and Priority Setting

Abstract: The results of a survey of quantitative structure-biodegradability relationships (QSBRs) are presented. The survey was made to evaluate the use of QSBRs for risk assessment and priority setting. It appears that few models can actually be used for legislative purposes. The major reason for this is that many models are either based on biodegradation end-points that are inconvenient for legislative purposes, or are not reproducible, or are based on too few data. It is concluded that single descriptor models cannot accurately predict the biodegradability of a broad range of chemicals. Most of these models therefore apply to narrow subclasses of chemicals only. The development of multiple descriptor models is still rather modest. More generally applicable models are based on molecular fragment contributions to biodegradability. However, for most of these models the chemical domain is uncertain. Despite the fact that none of the models in the survey meet the criteria set for judging a model to be usefu...

A mechanistic approach to deriving quantitative structure-activity relationship models for microbial degradation of organic compounds.

Abstract: Quantitative Structure-Biodegradability Relationships (QSBRs), relate the molecular structure of an organic chemical to its biological degradability. The high complexity of the microbial degradation process as well as great variety of the interactions between organism, organic pollutant and the environment make it difficult to interpret the results from biodegradability experiments. Literature concerning the various approaches applied in Structure-Biodegradability Relationship modeling is reviewed and the reliability and applicability of the results obtained from different biodegradation tests is discussed. A mechanistic approach, based on comparison of the data measured at different organization levels, will hopefully contribute to a better understanding of mechanisms taking place during the biodegradation. Their description and quantification may lead to improvement of existing QSBR models.

Multilayered dermal subcompartments for modeling chemical absorption.

Abstract: Dermal penetration of chemicals and drugs is of concern to both toxicologists and pharmacologists. Environmental professionals try to limit exposure to chemicals using protective clothing and gloves or barrier creams to trap chemicals. Drug developers try to enhance penetration of chemicals through the skin for medical purposes. Both can use predictive biologically-based mathematical models to assist in understanding the processes involved. These models are especially useful when they are based on physiological and biochemical parameters which can be measured in the laboratory. Appropriately validated models based on conservation of mass, diffusion and chemical transport by flow can be predictive of human exposures. In this paper we develop two new physiologically-based pharmacokinetic (PBPK) skin models to predict blood concentrations of dibromomethane in rats after skin-only vapor exposures. These new models improve the predictions of the blood concentrations especially at the beginning of the ...

Nonlinear Dependence of Bioconcentration Factors on n-Octanol-Water Partition Coefficients of Chlorinated Dibenzofurans and Dibenzo-p-Dioxins

Abstract: A nonlinear thermodynamic model is applied to the prediction of both the bioconcentration factor (Kbw) in the guppy (Poecilia reticulata) and the n-octanol-water partition coefficient (Kow) of chlorinated dibenzofurans and dibenzo-p-dioxins. To this end molar liquid volumes, heats of vaporization and empirically fitted parameters of the pertinent solute and solvents are used. Calculated log Kbw and log Kow values are obtained with correlation coefficients (r = 0.85 and 0.992) and mean deviations ( = 0.19 and 0.17), which compare favourably with experimental data. In addition the model enables an explanation of the well-known nonlinear log-log relationship between the two properties for compounds with high Kow values on the basis of differences between the properties of biotic lipid and n-octanol. It is suggested that the breakdown of the linear relationship is caused by entropic effects related to the number of chlorine atoms in the solute molecules and to the structures of the lipid and n...

Impact of biodegradation test methods on the development and applicability of biodegradation QSARs.

Abstract: The biodegradability of a substance depends on the structure and physical form of the substance, the time that has been available for acclimation, and the environmental conditions. Importantly, these later factors can be just as important as structure in determining the outcome of a biodegradation test. The development of appropriate QSARs for biodegradation and the ultimate value of the final QSAR depends on understanding these factors. This paper will describe what is known about the effect of test conditions on the results of biodegradation tests. The ability of these tests to reflect real environmental conditions will also be examined. Finally, we will discuss what we believe, in the light of this information, should be the goal of biodegradation QSARs and how these QSARs can be most appropriately used in fate assessments.

The Use of Cluster Significance Analysis to Identify Asymmetric QSAR Data Sets in Toxicology. An Example With Eye Irritation Data

Abstract: Cluster significance analysis is a tool that allows the identification of ‘embedded clusters’ in QSAR datasets. It is successfully applied to an eye irritation data set to show that these data are indeed asymmetric. The method identifies five parameters that form an embedded cluster of eye irritants amongst non irritants, although full separation is not achieved. This method has considerable potential to identify potential non-linearity in toxicology data sets and for parameter reduction. It is shown also that this can be obtained relatively quickly with an analysis performed on 100,000 subsets containing the same information as an analysis on 1,000,000 subsets.

Application of Structural Concepts to Evaluate the Potential Carcinogenicity of Natural Products

Abstract: The expert structure-activity relational system CASE/MULTICASE was used to obtain an assessment of the possible carcinogenicity of selligueain A, a plant-derived sweetener. Based upon a series of authoritative data bases it was predicted that this chemical had some marginal potential for being a ‘non-genotoxic’ rodent carcinogen. The relevance of this potential to possible human health risks is problematic. Still, given the fact that successful sweetener may be widely consumed, should this chemical be developed further, experimental determinations of its potential carcinogenicity appear in order.

Qsar Study of the Toxicity of Benzothiazolium Salts Against Euglena Gracilis: The Free-Wilson Approach

Abstract: The Free-Wilson QSAR model in the Fujita–Ban modification was used to calculate the quantitative substituent activity contributions to the toxicity against Euglena gracilis in a series of 91 benzothiazolium salts. An important increase of activity was found for R = styryl or SCH2C6H5 group and for R2 = propargyl or allyl group. The substituentd on benzene ring also enhance the activity. The possible relations between structure of active groups and their electronic or physicochemical properties are discussed. By using the calculated values it is possible to predict toxicity for 1300 compounds. New compounds with assumed high or low toxicity are predicted.

Identification of Phototoxic Polycyclic Aromatic Hydrocarbons in Sediments Through Sample Fractionation and QSAR Analysis

Abstract: The toxicity of certain polycyclic aromatic hydrocarbons (PAHs) can be greatly increased by simultaneous exposure of test organisms to ultraviolet (UV) wavelengths present in sunlight. This phenomenon, commonly termed photoinduced toxicity, had been evaluated extensively in laboratory settings where only one chemical of concern was present. However, more recent studies have demonstrated that complex mixtures of PAHs present, for example in sediments, also can cause phototoxicity to a variety of aquatic species when the samples are tested in simulated sunlight. Unfortunately, because these types of samples can contain thousands of substituted and unsubstituted PAHs it is difficult, if not impossible, to use conventional analytical techniques to identify those responsible for photoinduced toxicity. The objective of the present study was to link two powerful ecotoxicology tools, toxicity-based fractionation techniques and QSAR models, to identify phototoxic chemicals in a sediment contaminated with ...

Comparison of Structure-Activity Relationships Derived from Two Methods for Estimating Octanol-Water Partition Coefficients

Abstract: This study examines several established linear relationships between 96-hour acute toxicity to fish (as log LC50) and octanol-water partition coefficient (as log Kow) with regard to the effect of using a different method of calculating log Kow. For all seven classes of compounds examined here, the linear equation parameters, viz., slope, intercept, r2, and standard error of the estimated log LC50, were about the same for the two methods. As expected, the accuracies of predictions for individual compounds were often different for the two methods, but seldom remarkably so.

Descriptors and Techniques for Quantitative Structure –Biodegradability Studies

Abstract: Biodegradation occurs mainly through microbial enzyme attack, and enzyme-catalysed reactions are known to depend on hydrophobic, electronic and steric effects. However, most QSBR studies involve correlation with a single parameter, but there is no consistency regarding the class of parameter. This suggests that biodegradation occurs through a range of different mechanisms. A few QSBR studies have reported the need to include more than one class of parameter in correlations. As well as linear regression analysis, other correlation methods have been used in QSBR investigations. These include discriminant analysis, neural networks and comparative molecular field analysis (CoMFA).

Modelling of the biological activity for a set of ceramic fibre materials: a QSAR study.

Abstract: The objective was to develop quantitative structure-activity relationships (QSARs) for a set of nine ceramic raw materials. The samples were characterized by a chemical analysis (both X-ray fluorescence and neutron activation analysis) and the morphology was determined by electron microscopy in combination with automated image analysis. Further, the fibre samples were subjected to two biological activity assays, measuring cytotoxicity and hydroxyl radical production. To investigate the produced data structures, principal component analysis (PCA) and partial least squares (PLS) were applied together with rigorous validation techniques. Significant QSARs were found for both biological activity assays. The morphology of the fibres plays an important role for the cytotoxicity and their trace element background is related to the hydroxyl radical production.

A Mathematical Model of Bronchial Absorption of Vapors in the Human Lung and its Significance in Pharmacokinetic Modeling

Abstract: This work formulates a model description of moderately soluble gas and vapor uptake in the bronchial region of the lung during initial inhalation exposure. The mass transport problem is solved using an iterative-analytical approach in which inhaled chemical is partitioned to alveolar blood-gas exchange, bronchial wall absorption, and exhalation. Results of 109 simulations allowed regression analysis to provide simple algebraic equations to describe the fraction of total inhaled mass taken up by the two alternative absorption pathways. These fractions are dependent on the chemical s solubility and liquid di usivity. The derived relationships are then used in a modi ed physiologically based pharmacokinetic (PBPK) model which accounts for bronchial uptake. The results are compared to identical results from a traditional (unmodi ed) PBPK model to draw conclusions concerning the e ect of bronchial uptake on systemic chemical distribution in addition to elevated bronchial tissue concentrations.

Synergy Between Deltamethrin and Prochloraz in Bees: Different Mechanisms of Action Tested by Modeling

Abstract: The aim of this work was to propose methods to test mechanisms of synergistic effects of toxic agents in bees. We assumed that the fungicide prochloraz acts synergistically on deltamethrin by increasing the penetration of deltamethrin and/or inhibiting the oxidative metabolism of deltamethrin. These hypotheses were tested by using a pharmacokinetic box model. A previous experimental work showed that there was a synergy between deltamethrin and prochloraz in bees, and allowed to compare the effects of the treatment with 0.25 g ha−1 deltamethrin in the presence of 25 g ha−1 (Δ0.25 + P) prochloraz and the treatment with 1 g ha−1 deltamethrin alone (Δ1). We postulated that cumulated mortality was proportional to the cumulated internal deltamethrin (ID 2). To be consistent with the experimental data, ID 2 of treatment (Δ0.25 + P) had to be greater than ID 2 of treatment (Δ1) during the period from 2 to 8 hours. We studied in the most favourable conditions if the different hypotheses could be consisten...

Estimating one-electron Reduction Potentials of Quinones

Abstract: The one-electron reduction potential ∗ E1 7 of benzo-, naphtho-and anthracenequinones is related to their ability to undergo redox cycling and elicit cytotoxicity through oxidative stress To evaluate a general approach to estimate the E1 7 of benzo-, naphtho-and anthracenequinones, QSAR approaches based on gas phase and solvation based methods were employed Stereoelectronic descriptors of ground state quinones, respective intermediates of the redox cycle, and the di erences in parameters for the transition between intermediates were evaluated The variation of E1 7 was correlated with descriptors of the parent quinones and speci c transition parameters The energy of the highest occupied molecular orbital (the inverse of the ionization potential) and the energy of the lowest unoccupied molecular orbital of the parent benzoquinones were signi cantly correlated to E1 7 With the exclusion of ortho-hydroxy-substituted compounds, the reaction enthalpies for the quinone-semiquinone couple, in combin

Use of Quantitative Structure Activity Relationship Methods in Predicting Activated Carbon Adsorption Isotherms for Hazardous Air Pollutants

Abstract: A quantitative structure activity relationship (QSAR) approach is presented to predict gas phase activated carbon adsorption capacities and isotherms for several organic chemicals and their binary mixtures. F,x peri menial adsorption data reported in the literature for various binary mixtures on two di ercnt carbons were used to validate this predictive approach. The QSAR-predicted and experimental adsorption capacities for di erent chemical mixtures of small apolar hydrocarbons at di erent temperatures on two di erent carbons under a range of total pressures and gas phase compositions agreed well with r2 = 0.85 for a total of 338 data points.