摘要:

From an analysis of the toxicity of phenols to rat embryos and anilines to embryo fibroblast cells a new type of toxicity is postulated for these classes of compounds. Substituents which increase the electron density on the aromatic ring as estimated by σ+or εHOMOincrease potency. It is postulated that it is the radical form of the phenols and the anilines that accounts for their toxicity. The results are compared with QSAR for radical scavengers and oxidoreductases acting on phenols, anilines and carbazoles.

ISSN:1062-936X    

DOI:10.1080/10629369508029905

出版商:Taylor & Francis Group    

年代:1995

数据来源: Taylor

摘要:

Ecological risk assessments can be used to establish the likelihood that an adverse effect will result from exposure to one or more chemicals. When evaluating contaminated sites with many chemicals present, risk assessors must grapple with the problem of quickly identifying the chemicals that are most likely to be of concern, based on effect and exposure assessment information. Many times data gaps exist and the risk assessor is left with decisions on which models to use to estimate the parameter of concern. In the present paper, a procedure is presented for ranking agrichemicals, utilizing the ASTER (ASsessment Tools for the Evaluation of Risk) system. The procedure was employed to rank the relative ecological risk of forty-nine pesticides historically used in agricultural sites in the Walnut Creek watershed near Ames, Iowa, USA. Empirical data from the ASTER system were used when available in the associated data-bases, and quantitative structure-activity relationships and expert systems were invoked when data were lacking. Separate rankings were conducted based on major species taxonomic groupings. Resulting toxic effects thresholds were compared to surface water concentrations.

ISSN:1062-936X    

DOI:10.1080/10629369508029906

出版商:Taylor & Francis Group    

年代:1995

数据来源: Taylor

摘要:

In an attempt to distinguish between the mechanisms by which electrophilic and redox cycling quinones induce the cyclosporine A (CyA)-sensitive mitochondrial membrane permeability transition, the ability of a series of quinones that span a broad range of electrophilic and redox cycling reactivities has been examined. The order of potency of quinone-induced Ca2+release was 1,4-naphthoquinone (NQ) > 1,4-benzoquinone (BQ) > 2-methyl-1,4-naphthoquinone (MQ) > 2,3-dimethoxy-1,4-naphthoquinone (DiOMeNQ) > 2,3-dimethyl-1,4-naphthoquinone (DiMeNQ). Quinones with predominantly redox cycling reactivity, NQ (≤ 4 μM), MQ, DiOMeNQ and DiMeNQ, induced the CyA-sensitive membrane permeability transition. In contrast, NQ (> 4 μM) and BQ, induced rapid and complete Ca2+release and membrane depolarization, but not swelling. Furthermore, BQ and NQ (> 4 μM)-induced effects were not prevented by CyA. Therefore, we maintain that, unlike MQ, DiOMeNQ, DiMeNQ and NQ (≤ 4μM), effects of BQ and NQ(> 4μM) on calcium flux and membrane potential are manifestviaa mechanism independent of altering the regulation of the cyclosporine A-sensitive PTP. These findings suggest that stereoelectronic descriptors for soft electrophilicity and one electron reduction potential may be useful in differentiating and predicting mechanisms of quinone toxicity.

ISSN:1062-936X    

DOI:10.1080/10629369508029907

出版商:Taylor & Francis Group    

年代:1995

数据来源: Taylor

摘要:

Benzoquinones, naphthoquinones and aziridinylbenzoquinones, can be reduced by flavoproteins to semiquinones that react with molecular oxygen to form superoxide anion with the subsequent regeneration of the parent compounds. This redox cycling, a form of futile metabolism, produces reactive oxygen species and depletes the reducing equivalents of cells without concomitant energy production. The ability of a toxicant to redox cycle is related to its one-electron reduction potential, and this study attempted to estimate reduction potential from structure using semi-empirical quantum chemical models for a diverse set of chemicals. The results of this study suggest that one-electron reduction potentials, within structural classes of benzoquinones, naphthoquinones, phenols and nitrobenzenes, can be estimated from local and global electronic indices that are related to delocalization. Smaller absolute charge on the carbonyl carbon in the quinone moiety correlated with more positive one-electron reduction potentials of 1,4-benzoquinones, naphthoquinones and two-electron reduction potentials of aziridinylbenzoquinones. The energy of frontier orbitals of the quinones, phenols and nitrobenzenes also co-varied with reduction potential. More positive reduction potentials of 1,4-benzoquinones, 1,4-naphthoquinones and phenols were correlated with more negative values of EHOMO, while more negative values of ELUMOwere correlated with more positive potentials of nitrobenzenes and aziridinylbenzoquinones. Delocalization of electron density also correlated with reduction potentials within individual classes.

ISSN:1062-936X    

DOI:10.1080/10629369508029908

出版商:Taylor & Francis Group    

年代:1995

数据来源: Taylor

摘要:

Computational chemistry provides a means for the calculation or estimation of three-dimensional chemical structure, organization and analysis of chemical data, classification of industrial chemicals by structure and properties, prediction of toxicity, and identification of chemical structure. The development of the EPA National Environmental Supercomputer Center (NESC) in Bay City, Michigan, makes available to scientists in EPA Headquarters, the ability to perform advanced QSAR modeling. This provides the means to develop and apply QSAR models for chemicals acting by a variety of molecular mechanisms. The work makes possible improved programmatic support to the Office of Pollution Prevention and Toxics under the Toxic Substances Control Act and the Pollution Prevention Act.

ISSN:1062-936X    

DOI:10.1080/10629369508029909

出版商:Taylor & Francis Group    

年代:1995

数据来源: Taylor

摘要:

A flow-through test system to perform bioconcentration experiments with tubificids was evaluated. First results were obtained for the hexachlorocyclohexane (HCH) isomers α-HCH,β−HCH, γ-HCH, and δ-HCH. Bioconcentration factors (BCFs) for these compounds were calculated from the ratio of the rate constants of uptake (k1) and clearance (k2) as: BCF = k1/k2. The BCFs of the 4 isomers increased with αfa;-HCH (32) γ-HCH (47) < δ-HCH (120) <β−HCH (190) [BCFs on fresh weight basis]. The differences in BCFs were mainly caused by different k1−values ranging form 5.4 (1/h) for α-HCH to 21.4 (1/h) forβ−HCH. A comparison of the BCFs for tubificids with BCFs already known for zebrafish and juvenile rainbow trout showed nearly the same ranking for the isomeric HCHs. The absolute values of the BCFs however were about a factor of 10 lower for tubificids compared to the two fish species, even when associating them to the fat content.

ISSN:1062-936X    

DOI:10.1080/10629369508029910

出版商:Taylor & Francis Group    

年代:1995

数据来源: Taylor

摘要:

This paper reviews the results of a series of efforts to develop QSAR models for aromatic chemicals whose toxicity is enhanced by the ultraviolet radiation present in sunlight. Photoinduced toxicity of polycyclic aromatic hydrocarbons (PAHs) was found to be a result of competing factors: structural (such as molecular stability and light absorbance) and external (irradiation energy and intensity). These two factors interact, producing a complex, multilinear relationship between toxicity and electronic structure. The HOMO-LUMO gap provided a useful ground-state index to explain the persistence, light absorption, and eventually, the photoinduced toxicity of PAHs. The derived QSAR clearly distinguished phototoxic differences between pairs of structurally similar PAHs, such as phenanthrene and anthracene, benzo [a] anthracene and tetracene, et cetera. Those PAHs exhibiting photoinduced toxicity were consistently within a specific range of the electronic parameter. Further modeling revealed a significant correlation between molecular electronic structure of excited-state PAHs and toxicity. The effect of substituents on photoinduced acute toxicity of PAHs also was investigated. Some substituents such as alkyl and hydroxy moieties do not significantly reduce the HOMO-LUMO gap of parent PAHs. Nitro- and chloro- moieties cause more significant variations of the HOMO-LUMO gap. It is concluded that photoinduced toxicity of PAHs is mainly dictated by the electronic structure of the parent chemicals. Evaluation of the phototoxicity of flexible aromatic molecules (α-terthienyls), generally supported the PAH models.

ISSN:1062-936X    

DOI:10.1080/10629369508029911

出版商:Taylor & Francis Group    

年代:1995

数据来源: Taylor

摘要:

Two methods for measuring the effect of organic toxicants on the marine macroalgaEnteromorpha intestinaliswere compared. EC50data for the effect of C1−C8n−alcohols on neutral red dye retention and ion leakage were used to construct QSARs with log Kowas the only physicochemical parameter. The two QSARs were statistically indistinguishable suggesting that both procedures reflect the same non-specific narcotic effect on membrane integrity. The effect on ion leakage of compounds with more specific modes of action was also investigated. The herbicides diuron and diquat had no effect at concentrations which inhibit photosynthesis, the uncoupler 2,4-dichlorophenol was no more toxic than a narcotic of similar polarity, but the known high toxicity of the antifouling compound tributyltin was clearly reflected by the ion leakage response.

ISSN:1062-936X    

DOI:10.1080/10629369508029912

出版商:Taylor & Francis Group    

年代:1995

数据来源: Taylor

摘要:

Two general problems of QSAR studies are discussed. The first is related to the fact that, in general, the studied property is an integral result of multistage interactions carried out at various solvent environments with different polarity under which different conformers should be prevalent. In contrast with the conventional QSAR methodologies which provide a single 3-D molecular model for each 2-D structure in the modeling process, the newly introduced dynamic QSAR method is aiming to mimic the multiplicity of 3-D molecular shapes taken from the chemicals at the different stages of the processes conditioning the endpoint under investigation. The second QSAR problem concerns the proliferation of molecular descriptors used for QSAR studies. Hoping to account for any structural factors that may affect the property under investigation, the QSAR studies often generate a large set of topological, steric, and electronic parameters. This problem can be handled by two different approaches. One can incorporate purely statistical methods, such as the multiple regression analysis, principle component analysis (PCA), partial least square (PLS), etc. In addition to the combinatorial complexity in model derivation, the large dimensionality of the initial data matrix can increase the risk for a chance correlation. The drawback of PCA, PLS and related methods is the loss of physical meaning of the resulted orthogonal regressors. We turn user's attention on QSAR methods based on physico-chemical principles used for parameter screening. In fact, one selects potentially significant factors for the studied property by creating hypotheses on interaction mechanism. The larger the knowledge for interaction mechanism the smaller the number of hypotheses created.

ISSN:1062-936X    

DOI:10.1080/10629369508029913

出版商:Taylor & Francis Group    

年代:1995

数据来源: Taylor

摘要:

Ethoxylated alcohols are the most extensively used nonionic surfactants in detergent products. The application of QSAR to their aquatic toxicity is complicated by the fact that they are multicomponent mixtures, the parent alcohols being often mixtures of isomers and homologues, each one being ethoxylated to varying degrees. A spreadsheet method for calculation of aquatic toxicity of such nonionic surfactant mixtures is presented. The method is based on a combination of the Könemann narcosis QSAR and mixture toxicity equations based on the principle of concentration addition. Log P values used in the spreadsheet calculations are themselves calculated by spreadsheet formulae based on the Leo and Hansch method modified by incorporation of the position dependent branching factor originally applied to linear alkylbenzene sulphonates. Close agreement between calculated and experimental EC50 values (48 hrDaphniatests) is obtained for a range of ethoxylated alcohols having a diversity of branching patterns, carbon numbers and degrees of ethoxylation. The effects of increasing carbon number (decreasing EC50), branching (increasing EC50) and increasing degree of ethoxylation (increasing EC50) are all quantified.

ISSN:1062-936X    

DOI:10.1080/10629369508029914

出版商:Taylor & Francis Group    

年代:1995

数据来源: Taylor