Toxicity quantitative structure-activity

Hansch C, Hatheway GJ, Quinn FR, Greenberg N. Antitumor l-(X-aryl)-3,3-dialkyltriazenes 2. On the role of correlation analysis in decision making in drug modification. Toxicity quantitative structure-activity relationships of l-(X-phenyl)-3,3-dialkyltriazenes in mice. J Med Chem 1978 21 574-577. 

Narcosis represents the most fundamental mechanism of the toxicity of nonelectrolyte organic compounds, and corresponds to minimum or baseline toxicity. Quantitative structure-activity relationships for chemicals acting by this mechanism for various organisms and routes of exposure provide a valuable probe for determining whether or not a candidate chemical acts via narcosis or by an electrophile, proelectrophile, cyanogenic, or other more specific molecular mechanism. 

Roberts, D. W. (1989) Acute lethal toxicity quantitative structure-activity relationships for electrophiles and pro-electrophiles mechanistic and toxicokinetic principles, in Aquatic Toxicology and Environmental Fate (eds G. W. Suter II and M. A. Lewis), STP 1007, ASTM, Philadelphia, PA. 

Safety/Toxicity Toxic quantitative structure-activity relationships, toxicity to aqnatic microbial... 

The fundamental assumption of SAR and QSAR (Structure-Activity Relationships and Quantitative Structure-Activity Relationships) is that the activity of a compound is related to its structural and/or physicochemical properties. In a classic article Corwin Hansch formulated Eq. (15) as a linear frcc-cncrgy related model for the biological activity (e.g.. toxicity) of a group of congeneric chemicals [37, in which the inverse of C, the concentration effect of the toxicant, is related to a hy-drophobidty term, FI, an electronic term, a (the Hammett substituent constant). Stcric terms can be added to this equation (typically Taft s steric parameter, E,). 

The QSAR (quantitative structure-activity relationship) approach has been considered for the identification of toxicants that bind to steroid and aryl... 

QSARs (quantitative structure-activity relationships) Relationships between structural parameters of chemicals and their toxicity. 

In 1868 two Scottish scientists, Crum Brown and Fraser [4] recognized that a relation exists between the physiological action of a substance and its chemical composition and constitution. That recognition was in effect the birth of the science that has come to be known as quantitative structure-activity relationship (QSAR) studies a QSAR is a mathematical equation that relates a biological or other property to structural and/or physicochemical properties of a series of (usually) related compounds. Shortly afterwards, Richardson [5] showed that the narcotic effect of primary aliphatic alcohols varied with their molecular weight, and in 1893 Richet [6] observed that the toxicities of a variety of simple polar chemicals such as alcohols, ethers, and ketones were inversely correlated with their aqueous solubilities. Probably the best known of the very early work in the field was that of Overton [7] and Meyer [8], who found that the narcotic effect of simple chemicals increased with their oil-water partition coefficient and postulated that this reflected the partitioning of a chemical between the aqueous exobiophase and a lipophilic receptor. This, as it turned out, was most prescient, for about 70% of published QSARs contain a term relating to partition coefficient [9]. 

Wang YW, Liu HX, Zhao CY, Liu HX, Cai ZW, Jiang GB. Quantitative structure-activity relationship models for prediction of the toxicity of polybrominated diphenyl ether congeners. Environ Sci Technol 2005 39 4961-6. 

The Danish EPA has developed an advisory list for self-classification of dangerous substances including 20 624 substances. The substances have been identified by means of QSAR models (Quantitative Structure-Activity Relationship) as having acute oral toxicity, sensitization, mutagenicity, carcinogenicity, and/or danger to the aquatic environment. 

ADMET absorption, distribution, metabolism, excretion and toxicity BLW-ED block-localized wave function energy decomposition hERG human ether-a-go-go-related gene QSAR quantitative structure-activity relationship... 

In a study by Andersson et al. [30], the possibilities to use quantitative structure-activity relationship (QSAR) models to predict physical chemical and ecotoxico-logical properties of approximately 200 different plastic additives have been assessed. Physical chemical properties were predicted with the U.S. Environmental Protection Agency Estimation Program Interface (EPI) Suite, Version 3.20. Aquatic ecotoxicity data were calculated by QSAR models in the Toxicity Estimation Software Tool (T.E.S.T.), version 3.3, from U.S. Environmental Protection Agency, as described by Rahmberg et al. [31]. To evaluate the applicability of the QSAR-based characterization factors, they were compared to experiment-based characterization factors for the same substances taken from the USEtox organics database [32], This was done for 39 plastic additives for which experiment-based characterization factors were already available. 

The prediction of the properties of molecules from a knowledge of their structure (quantitative structure-property relationships [QSPRs] or quantitative structure-activity relationships [QSARs]). ANNs can be used to determine QSPRs or QSARs from experimental data and, hence, predict the properties of a molecule, such as its toxicity in humans, from its structure. 

Quantitative Structure-Activity Relationship studies search for a relationship between the activity/toxicity of chemicals and the numerical representation of their structure and/or features. The overall task is not easy. For instance, several environmental properties are relatively easy to model, but some toxicity endpoints are quite difficult, because the toxicity is the result of many processes, involving different mechanisms. Toxicity data are also affected by experimental errors and their availability is limited because experiments are expensive. A 3D-QSAR model reflects the characteristics of... 

Shigeoka, T., Sato, Y., Takeda, Y. (1988) Acute toxicity of chlorophenols to green algae, Selenastrum capricomutum and Chlorella vulgaris, and quantitative structure-activity relationships. Environ. Toxicol. Chem. 7, 847-854. 

Passino, D.R.M., Smith, S.B. (1987) Quantitative structure-activity relationships (QSAR) and toxicity data in hazard assessment. In QSAR in Environmental Toxicology-II. Kaiser, K.L.E., Editor, D. Reidel Publishing Co., Dordrecht, Holland, pp. 261-270. 

Govers, H., Ruepert, C., Aiking, H. (1984) Quantitative structure-activity relationships for polycyclic aromatic hydrocarbons Correlation between molecular connectivity, physico-chemical properties, bioconcentration and toxicity in Daphnia pulex. Chemosphere 13, 227-236. 

Development of quantitative structure activity relations for use in evaluating toxicity of organotin compounds (Hall and Pinkney 1985 Laughlin and Linden 1985 Laughlin et al. 1985 Laughlin 1987). 

Hodson, P.V., R. Parisella, B. Blunt, B. Gray, and K.L.E. Kaiser. 1991. Quantitative structure-activity relationships for chronic toxicity of phenol, p-chlorophcnol, 2,4-dichlorophenol, pentachlorophenol, p-nitro-phenol and 1,2,4-trichlorobenzene to early life stages of the rainbow trout (Oncorhynchus mykiss). Canad. Tech. Rep. Fish. Aquat. Sci. 1784. 56 pp. 

The octanol-water partition coefficient, Kow, is the most widely used descriptor of hydrophobicity in quantitative structure activity relationships (QSAR), which are used to describe sorption to organic matter, soil, and sediments [15], bioaccumulation [104], and toxicity [105 107J. Octanol is an amphiphilic bulk solvent with a molar volume of 0.12 dm3 mol when saturated with water. In the octanol-water system, octanol contains 2.3 mol dm 3 of water (one molecule of water per four molecules of octanol) and water is saturated with 4.5 x 10-3 mol dm 3 octanol. Octanol is more suitable than any other solvent system (for) mimicking biological membranes and organic matter properties, because it contains an aliphatic alkyl chain for pure van der Waals interactions plus the alcohol group, which can act as a hydrogen donor and acceptor. 

Besides the applications of the electrophilicity index mentioned in the review article [40], following recent applications and developments have been observed, including relationship between basicity and nucleophilicity [64], 3D-quantitative structure activity analysis [65], Quantitative Structure-Toxicity Relationship (QSTR) [66], redox potential [67,68], Woodward-Hoffmann rules [69], Michael-type reactions [70], Sn2 reactions [71], multiphilic descriptions [72], etc. Molecular systems include silylenes [73], heterocyclohexanones [74], pyrido-di-indoles [65], bipyridine [75], aromatic and heterocyclic sulfonamides [76], substituted nitrenes and phosphi-nidenes [77], first-row transition metal ions [67], triruthenium ring core structures [78], benzhydryl derivatives [79], multivalent superatoms [80], nitrobenzodifuroxan [70], dialkylpyridinium ions [81], dioxins [82], arsenosugars and thioarsenicals [83], dynamic properties of clusters and nanostructures [84], porphyrin compounds [85-87], and so on. 

Benigni, R., Andreoli, C., Conti, L., Tafani, P., Cotta-Ramusino, M., Carere, A., Crebelli, R. Quantitative structure-activity relationship models correctly predict the toxic and aneuploidizing properties of halogenated methanes in Aspergillus nidulans. Mutagenesis 1993, 8, 301-305. 

Three-dimensional quantitative structure activity relationship (3D-QSAR) analysis for in vitro toxicity of chlorophenols to HepG2 cells Y. Liu, J.N. Chen, J.S. Zhao, H.X. Yu, X.D. Wang, J. Jiang, H.J. Jin, J.F. Zhang and L.S. Wang... 

Accordingly, sorption has received a tremendous amount of attention and any method or modeling technique which can reliably predict the sorption of a solute will be of great importance to scientists, environmental engineers, and decision makers (references herein and in Chaps. 2 and 3). The present chapter is an attempt to introduce an advanced modeling approach which combines the physical and chemical properties of pollutants, quantitative structure-activity, and structure-property relationships (i. e., QSARs and QSPRs, respectively), and the multicomponent joint toxic effect in order to predict the sorption/desorp-tion coefficients, and to determine the bioavailable fraction and the action of various organic pollutants at the aqueous-solid phase interface. 

Deneer, J.W., Sinnige, T.L., Seinen, W., and Hermens, J.L.M. Quantitative structure-activity relationships for the toxicity and... 

Hermens, J., Canton, H., Janssen, P., and de Jong, R. Quantitative structure-activity relationships and toxicity studies of mixtures of chemicals with an anaesthetic potency acute lethal and sublethal toxicity to Daphnia magna, Aquat. Toxicol, 5(2) 143-154, 1984. 

Ikemoto, Y., Motoba, K., Suzuki, T., and Uchida, M. Quantitative structure-activity relationships of nonspecific and specific toxicants in several organism species, Environ. Toxicol Chem., ll(7) 931-939,1992. 

Konemann, H. Quantitative structure-activity relationships in fish toxicity studies. Part 1 relationship for 50 industrial pollutants, Toxicology, 19(3) 209-221, 1981. 

Marchini, S., Passerini, Hoglund, M.D., Pino, A., and Nendza, M. Toxicity of aryl- and benzylhalides to Daphnia magna and classification of their mode of action based on quantitative structure-activity relationship, Environ. Toxicol Chem., 18(12) 2759-2766, 1999. 

Altenburger R, Nendza M, Schuurmann G (2003) Mixture toxicity and its modeling by quantitative structure-activity relationships. Environ Toxicol Chem 22 1900-1915... 

---