Carcinogenic parameters

Principles for drinking water directives Types of water covered by the DWD Parameters and parametric values Parameters in DWD 98/83/EC Basis of parametric values Microbiological parameters Carcinogenic parameters Other considerations Sampling and monitoring Quality control and assurance... 

Kitchin KT, Brown JL, Kulkami AP. 1992. Predictive assay for rodent carcinogenicity using in vivo biochemical parameters Operational characteristics and complementarity. Mutat Res 266 253-272. 

Data adequacy The key study was well designed and conducted and documented a lack of effects on heart and lung parameters as well as clinical chemistry. Pharmacokinetic data were also collected. The compound was without adverse effects when tested as a component of metered-dose inhalers on patients with COPD. Animal studies covered acute, subchronic, and chronic exposure durations and addressed systemic toxicity as well as neurotoxicity, reproductive and developmental effects, cardiac sensitization, genotoxicity, and carcinogenicity. The values are supported by a study with rats in which no effects were observed during a 4-h exposure to 81,000 ppm. Adjustment of the 81,000 ppm concentration by an interspecies and intraspecies uncertainty factors of 3 each, for a total of 10, results in essentially the same value (8,100 ppm) as that from the human study. ... 

M. Funk, I. Ponten, A. Seidel, B. Jemstrom, Critical Parameters for Adduct Formation of the Carcinogen (+)-a t/-Benzo[a]pyrene-7,8-dihydrodiol 9,10-Epoxide with Oligonucleotides , Bioconjugate Chem. 1997, 8, 310 - 317. 

The T25 should be expressed in mg/kg body weight per day. To enable a conversion of feed, drinking water, or air concentrations of carcinogens to the T25, physiological parameters should be... 

Other evidence judged to be relevant to an evaluation of carcinogenicity and of sufficient importance to affect the overall evaluation is then described. This may include data on preneoplastic lesions, tumour pathology, genetic and related effects, structure-activity relationships, metabolism and pharmacokinetics, physicochemical parameters and analogous biological agents. 

Fifth, chemicals often undergo metabolism to yield carcinogenic derivatives, the concentration of which is the relevant dose parameter. 

Mechanism-based SAR analysis of different classes and subclasses of chemical carcinogens has revealed some general and specific molecular parameters that can have significant effects on the carcinogenic potential of electrophilic compounds. 

General Molecular Parameters Affecting the Carcinogenic and Mutagenic Potential of Chemicals... 

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