Structure/toxicity relationship

Wong PTS, Chau YK, Kramar O, Bengert GA (1982) Structure-toxicity relationship of tin compounds on algae. Canadian Journal of Fisheries and Aquatic Sciences, 39 483-488. 

Schultz TW, Moulton MR Structure-toxicity relationships of selected naphthalene derivatives. 2. Principal components analysis. Bull Environ Contam Toxicol 1985 34 1-9. 

Ridings JE, Manallack DT, Saunders MR, Baldwin JA, Livingstone DJ. Multivariate quantitative structure-toxicity relationships in a series of dopamine mimetics. Toxicol 1992 76 209-17. 

Croni MT et al. (2000) Structure-toxicity relationships for aliphatic compounds encompassing a variety of mechanisms of toxic action to Vibrio fischeri. SAR QSAR Environ Res 11(3-4) 301-312... 

Tanii H, Hashimoto K. 1984a. Structure-toxicity relationship of aliphatic nitriles. Toxicol Lett 22 267-272. 

Milbrath, D.S., J.L. Engel, J.G. Verkade, and J.E. Casida. "Structure-Toxicity Relationships of l-Substituted-4-alkyl-2,6,7-trioxabicyclo[2.2.2]octanes." Toxicology and Applied Pharmacology 47 (1979) 287-93. 

Structure-toxicity relationships of organotin compounds on algae were summarized by Wong and coworkers85. 

Gray, A.J. 1985. Pyrethroid structure-toxicity relationships in mammals. Neuro toxicology 6 127-137. 

Lawrence, L.J. and J.E. Casida. 1982. Pyrethroid toxicology mouse intracerebral structure-toxicity relationships. Pestic. Biochem. Physiol. 18 9-14. 

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. 

Such essential limitations may markedly decrease the reliability and predictive capacity of quantitative structure-toxicity relationships (STRs) in haloalkenes and all other classes of toxic xenobiotics, but recognition of limitations does not suppress the need for predictive tools. In fact, any approach, empirical or mechanistic, that is able to uncover qualitative STR trends and to assign a priori labels of potential toxicity is certainly welcome. 

A. Gallegos, D. Robert, X. Girones, R. Carbo-Dorca, Structure-Toxicity Relationships of Polycyclic Aromatic Hydrocarbons Using Molecular Quantum Similarity ,. /. Corn-put.-Aided Mol. Des. 2001, 15, 67 - 80. 

TOPKAT Quantitative structure toxicity relationship (QSTR) models for assessing various measures of toxicity... 

Tanii, H. and Hashimoto, K. Structure-toxicity relationship of acrylates and methacrylates, Toxicol. Lett., 11(1-2) 125-129, 1982. 

With increasing toxicity data of various kinds, more rehable predictions based on structure-toxicity relationships of toxic endpoints can be attempted [31-36]. Even the Internet can be used as a source for toxicity data, albeit with caution [37]. A number of predictive methods have been compared from a regulatory perspective [35]. Often traditional QSAR approaches using multiple Hnear regression are used [38]. Newer approaches include the use of neural networks in structure-toxicity relationships... 

A number of approaches are available or under development to predict metabolism, including expert systems such as MetabolExpert (Compudrug), Meteor (Lhasa), MetaFore [42] and the databases Metabolite (MDL) and Metabolism (Synopsys) [43]. Ultimately such programs may be linked to computer-aided toxicity prediction based on quantitative structure-toxicity relationships and expert systems for toxicity evaluation such as DEREK (Lhasa) (see also Chapter 8) [44]. 

Cronin, M.T.D. Schultz, T.W. Structure-toxicity relationships for phenols to Tetrahymena pyrifirmis. Chetnosphere 1999, 32, 1453-1468. 

The group recognizes that a major practical problem is lack of information of biotransformation and relevant receptor or target site of many chemicals. In such cases, the chemicals should be classified using computer-based structure-toxicity relationships and expert judgment and experience. 

If the two-center C-0 bond energies fall outside of the reactive range (-14.1 to -12.9 eV), it is expected that they will be less genotoxic. The epoxides shown below fall outside that range, and should be nongenotoxic [15,16]. It should be noted, however, that this structure-toxicity relationship has possibly not been verified by a large enough data set. 

P.J. (2005) Application of quantitative structure-toxicity relationships for acute NSAID cytotoxicity in rat hepatocytes. Chem.-Biol. Interact., 152, 177-191. 

II. Structure-toxicity relationships and mechanism. Toxicol appl Pharmacol, 80, 336-344... 

Clearly, extensive whole-animal toxicity studies have not been warranted in the development of structure-toxicity relationships. Accordingly, Wesche et al.11 and Edwards and colleagues12,13 have developed in vitro methods for assessing neurotoxicity in neuronal cells. Based on these studies, dihydroartemisinin has been found to be the most neurotoxic artemisinin analog (Figure 9.2). 

In order to examine SARs in this mechanistically and structurally novel antimalarial drug class, and to make a comparison with structure-toxicity relationships, we established a convenient synthesis of the natural product.21 Making liberal use of a key synthetic intermediate from this synthesis has provided entry to a variety of analog classes, as well as radiolabeled artemisinin22 (Figure 9.5). 

No quantitative structure-toxicity relationship could be determined, but the MOA and the mechanism of toxicity (MOT) were not identical and it, therefore, was possible to develop high-potency, low-toxicity antimalarials. 

Many of the different factors discussed in this section that together make up the observed toxicity of a chemical (e.g. acute versus chronic administration, assays in vitro versus in vivo, the effects of substituents or metabolism) will be illustrated with heterocyclic chemicals in the following section. However, as mentioned in the Introduction, they are but the tip of the iceberg with respect to the structure-toxicity relationships awaiting discovery within this subgroup of organic chemicals. 

Toxicology. The structure-toxicity relationships of organophosphorus compounds have been extensively researched and are relatively well understood. The phosphorus-hased Dame retardants as a class exhibit only moderate-to-low toxicity. 

Swenson, E.S., W.B. Milisen, and W. Curatolo. 1994. Intestinal permeability enhancement Structure-activity and structure-toxicity relationships for nonylphenoxypolyoxyethylene surfactant permeability enhancers. Pharm Res 11 1501. 

Cajina-Quezada, M. and Schultz, T.W. (1990) Structure - toxicity relationships for selected weak acid respiratory uncouplers, Aquatic Toxicology 17, 239-252. 

Veith, G.D., Call, D.J., Brooke, L.T. (1983) Structure-toxicity relationships for the fathead minnow, Pimephalespromelas Narcotic industrial chemicals. Can. J. Fish Aqua. Sci. 40, 743-748. 

Numerous studies have examined the structure-toxicity relationships for CDDs. For example, examination of lethality data in guinea pigs revealed that the fully lateral-substituted tetra- to hexachloro-substituted isomers were the most toxic congeners, and the structure-activity relationships were comparable to those observed for their AHH-induction and receptor-binding activities (Eadon et al. 

Nendza, M., Seydel, J.K. (1988) Quantitative structure-toxicity relationship for ecotoxicologically relevant biotest systems and chemicals. Chemosphere 17, 1585-1602. 

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