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Toxicity modeling carcinogenicity

In summary, preliminary results from two animal models (rabbit and mouse) indicate that poly(N-palmitoylhydroxyproline ester) elicits a very mild, local tissue response that compares favorably with the responses observed for established biomaterials such as medical grade stainless steel or poly(lactic acid)/poly(glycolic acid) implants. At this point, additional assays need to be performed to evaluate possible allergic responses, as well as systemic toxic effects, carcinogenic, teratogenic, or mutagenic activity, and adaptive responses. [Pg.210]

Lazar (http //lazar.in silico.de/predict) is a k-nearest-neighbor approach to predict chemical endpoints from a training set based on structural fragments [43]. It derives predictions for query structures from a database with experimentally determined toxicity data [43]. Model provides prediction for four endpoints Acute toxicity to fish (lethality) Fathead Minnow Acute Toxicity (LC50), Carcinogenicity, Mutagenicity, and Repeated dose toxicity. [Pg.185]

The applicability of using these interdisciplinary approaches, which include incorporation of various physical and chemical properties of the pollutants, QSARs/QSPRs and multicomponent joint action modeling are discussed and evaluated using a group of toxic and carcinogenic pollutants, i. e., polychlorinated biphenyls (PCBs) and polycyclic aromatic hydrocarbons (PAHs). [Pg.242]

In summary, the different joint effect models of multicomponent pollutant mixtures (i.e., the toxic unit, additive and mixture toxicity indices) were presented. Using such models to analyze the joint effect of a group of toxic and carcinogenic organic compounds such as polycyclic aromatic hydrocarbons will be presented and evaluated in Sect. 3.2. [Pg.272]

This section represents different case studies to explain how physical and chemical properties, QSAR and QSPR approaches, and multicomponent toxic effect models can be used to predict the mobility and bioavailability of organic pollutants at aqueous-solid phase interfaces. Such interdisciplinary approaches are applied here to two groups of toxic and carcinogenic compounds. [Pg.273]

Comparative Toxicokinetics. No data are available to determine if there are differences in the toxicokinetics of 1,2-diphenylhydrazine among species. Toxicokinetic studies with different species could help explain observed differences in toxicity and carcinogenicity between rats and mice, and help identify the animal species that serves as the best model for extrapolating results to humans. [Pg.44]

Benigni, R., Andreoli, C., Cotta-Ramusino, M., Giogi, R, and Gallo, G., The electronic properties of carcinogens and their role in SAR studies of noncongeneric chemicals, Toxicity Modeling, 1, 157-167, 1995. [Pg.181]

In summary, in studies of chemical toxicity, pathways and rates of metabolism as well as effects resulting from toxicokinetic factors and receptor affinities are critical in the choice of the animal species and experimental design. Therefore it is important that the animal species chosen as a model for humans in safety evaluations metabolize the test chemical by the same routes as humans and, furthermore, that quantitative differences are considered in the interpretation of animal toxicity data. Risk assessment methods involving the extrapolation of toxic or carcinogenic potential of a chemical from one species to another must consider the metabolic and toxicokinetic characteristics of both species. [Pg.161]

Other enzymes associated with xenobiotic metabolism are also altered by dietary protein levels. Epoxide hydratase can hydrolyze various epoxides and appears to be important in decreasing their toxicity and carcinogenicity, although it is involved in the metabolic activation of certain carcinogens. Low dietary protein depresses epoxide hydratase activity in our dietary model (8). This may indicate both a decreased ability to detoxify epoxides and a decrease in metabolic activation of specific carcinogens, such as benzo(a)pyrene. Woodcock and Wood (19) have reported that dietary protein deficiency increases the activity of uridine diphosphate glucuronic acid (UDP6) transferase activity. This indicates that... [Pg.217]

SAFETY PROFILE Suspected carcinogen with experimental carcinogenic, tumorigenic, and neoplastigenic data. Poison by ingestion and subcutaneous routes. Mutation data reported. Used as a model carcinogenic and carcinogenic metabolite. When heated to decomposition it emits toxic fumes of NO,. See also N-NITROSO COMPOUNDS. [Pg.543]

TOPKA T Toxicity Prediction by Komputer Assisted Technology (TOPKAT) (http //www.accelrys.com/products/topkat/index.html) uses QSAR models for prediction of various toxicological properties such as mutagenicity, developmental toxicity potential, carcinogenicity, and skin/eye irritancy (see also Chapter 18). It employs the Optimum Prediction Space (OPS) technology to assess whether the query compound is well represented in its QSAR models and provides a confidence level on its prediction [85],... [Pg.230]

Calculation of electronic charges and related parameters by quick methods based on electronegativity. TOPKAT program for statistically modeling carcinogenicity, mutagenicity, skin and eye irritation, teratogenicity, and several other acute toxicity endpoints from their structures. Also runs on DEC VAX. [Pg.489]

Costa M (1997) Toxicity and carcinogenicity of Cr(VI) in animal models and humans. Crit Rev Toxicol 27 431-442. [Pg.270]

Molecular descriptors are any parameter used in the development of either a SAR or QSAR to model any type of property under investigation e.g., molecular structure, logPwith some type of biological attribute or response e.g., toxicity, LC50, carcinogenicity, etc.). A plethora of potential property response combinations exist and many have been developed with a high degree of repeatability. Some of the more common properties are listed in Table 9.1. [Pg.150]

Several model fluorescent substrates have been used withP450 2F1 [1121], but most of the interest in P450 2F1 has been in regard to its ability to activate several potential toxicants and carcinogens, including 4-ipomeanol [1121], 3-methyhn-dole [1122, 1123], styrene [1124], and naphthalene [1125],... [Pg.593]


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See also in sourсe #XX -- [ Pg.340 , Pg.341 ]




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