Toxicity relationships

Product Toxicology. The stmcture—toxicity relationships of organophosphoms compounds have been extensively researched and are relatively well understood (138—140). The phosphoms-based flame retardants as a class exhibit only moderate-to-low toxicity. NIOSH or EPA compilations and manufacturers safety data sheets show the following LD q values for rats, for representative commercial phosphoms flame retardants ... 

Dose—response evaluation is used in describing the quantitative relationship between the amount of exposure to a substance and the extent of toxic injury or disease. Data may be derived from animal studies or from studies in exposed human populations. Dose—response toxicity relationship for a substance varies under different exposure conditions. The risk of a substance can not be ascertained with any degree of confidence unless... 

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. 

Keller DA, Heck HD. 1988. Mechanistic studies on chloral toxicity Relationship to trichloroethylene carcinogenesis. Toxicol Lett 42 183-191. 

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. 

Sparks TC, Pavloff AM, Rose RL et al (1983) Temperature-toxicity relationships of pyrethroids on Heliothis virescens (F.) (Lepidoptera Noctuidae) and Anthonomus grandis grandis Boheman (Coleoptera Curculionidae). J Econ Entomol 76 243-246... 

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... 

Bailey, H.D., Liu, D.H.W., and Javitz, H.A. Time/toxicity relationships in short-term static, dynamic and plug-flow bioassays, in Aquatic Toxicology and Hazard Assessment Eighth Symposium, ASTM Special Technical Publication 891, Bahner, R.C. and Hansen, D.J., Eds. (Philadelphia, PA American Society for Testing and Materials, 1985), pp. 193-212. 

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

Veith, G.D., Call, D.J., and Brooke, L.T. Stmcture-toxicity relationships for the fathead minnow PhnepAaiesprome/as narcotic industrial chemicals. Can. J. Fish. Aquat Sci, 40(6) 743-748, 1983. 

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. 

Lennard L, Lilleyman JS. Variable mercaptopurine metabolism and treatment outcome in childhood lymphoblastic leukemia. J Clin Oncol 1989 7 1816-1823. Erratum itv.JClin Oncol 1990 8 567. Lennard L, Lewis IJ, Michelagnoli M et al. Thiopurine methyltransferase deficiency in childhood lymphoblastic leukaemia 6-mercaptopurine dosage strategies. MedPediatr Oncol 1997 29 252-255. Lennard L, Van Loon JA, Weinshilboum RM. Pharmaeogenetics of acute azathioprine toxicity relationship to thiopurine methyltransferase genetic polymorphism. Clin Pharmacol Ther 1989 46 149-154. 

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... 

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