A Toxicologist's View of Cancer Risk Assessment

Rozman, Karl K.; Kerecsen, Laszlo; Viluksela, M; Österle, Doris; Deml, E.; Viluksela, Matti; Stahl, Bernhard; Greim, Helmut; Doull, John

doi:10.3109/03602539608993990

Cited by 57 publications

(35 citation statements)

References 17 publications

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“…In particular, this relation coincides with the "general law" expected by Rozman et al (1996) and Rozman (1998Rozman ( , 2000:…”

Section: Molecular Exposomics and Timesupporting

confidence: 79%

“…In particular, the first of these relations coincides with the less formal expectation of Rozman et al (1996) that:…”

Section: Molecular Exposomics and Timesupporting

confidence: 68%

“…if we identify the ratio t/κ as the index "n" of Rozman et al (1996), and replace the ambiguous notation "c" by what it actually stands for: an endpoint concentration. In our model, as well, the quantity t/κ turns out to be positive.…”

Section: Molecular Exposomics and Timementioning

confidence: 99%

“…if we identify the ratio t/k as the index "n" of Rozman et al (1996) and Doull (2000, 2001) and replace the ambiguous notation "c" by what it actually stands for an endpoint concentration. In thermodynamics, pressure p is considered as a function of temperature and volume (p0f (T,V)), and assuming energy conservation according to the first law of thermodynamics, the condition of a closed system described by the internal energy is…”

Section: Molecular Exposomics and Timementioning

confidence: 99%

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Chemical- and effect-oriented exposomics: Three Gorges Reservoir (TGR)

Schramm

Wang

et al. 2012

Environ Sci Pollut Res

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Exposomic studies of the rapidly changing environment of the Three Gorges Reservoir (TGR) after its impounding is elaborated as a novel field of human and environmental research. Molecular exposomics is focused on the measure of all exposures to molecules and especially persistent organic pollutants-like compounds are of emerging interest due to their lifetime existence in the environment and humans. Theoretical considerations in general and particular for the TGR are deduced and presented using quantitative approaches for this research field. Since exposomics is strongly time-dependent, a theory is presented to link extension of exposure, time, and related effects. Similarity to the first law of thermodynamics is outlined. On top of this, the integrated use of biomarkers is presented employing chemical analysis for biomarkers of exposure and effects, biomarkers in vivo, in vitro approaches and the link between chemical mixtures, and the onset of disease and lethality. Besides real organisms, also virtual organisms are favored to act as well-defined subcompartments such as fat of biota and with respect to time of exposure. Exposomics is the perspective of risk evaluation and chronic exposures in the running century. It needs novel theories, approaches, and integrated action between medical and environmental disciplines. The existing knowledge about molecular stressors has to be assembled and put into a context especially with respect not only to time resp. lifetime exposure of humans but also eco-toxicological findings by using highly conserved phylogenetic mechanisms to enable links between human and risks of environmental biota. The TGR is a good example not only to employ biomonitoring of real but also virtual organisms due to the lack of established ecotopes in this changing environment so far. Progress in understanding long-term risks requires a proper theory as well as novel tools such as virtual organisms. On top, multidisciplinary approaches and the utilization of existing knowledge about the exposure of the environment and humans have to be merged and directed into mutual concepts. Effect-oriented and chemical analysis must be designed time-oriented to determine lifetime exposures of mankind and nature. Perspectively, a first attempt about exposomic theory and concepts is proposed and has to be developed experimentally further enclosing virtual besides of real organisms and compartments. Environmental and human exposomics have to be considered as a Res (2013) 20:7057-7062 DOI 10.1007/s11356-012-1319 unified global issue in order to effectively utilize their mutual existing knowledge most effectively. The TGR is a challenging model system aiming this objective.

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“…In particular, this relation coincides with the "general law" expected by Rozman et al (1996) and Rozman (1998Rozman ( , 2000:…”

Section: Molecular Exposomics and Timesupporting

confidence: 79%

“…In particular, the first of these relations coincides with the less formal expectation of Rozman et al (1996) that:…”

Section: Molecular Exposomics and Timesupporting

confidence: 68%

Section: Molecular Exposomics and Timementioning

confidence: 99%

Section: Molecular Exposomics and Timementioning

confidence: 99%

See 2 more Smart Citations

Chemical- and effect-oriented exposomics: Three Gorges Reservoir (TGR)

Schramm

Wang

et al. 2012

Environ Sci Pollut Res

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“…The very logical scale for the abscissa in the publication by Rozman et al (5) apparently escaped the notice of many toxicologists. These authors plotted dose on a logarithmic scale, which is, of course, well established in pharmacology and toxicology.…”

mentioning

confidence: 99%

Thresholds in Chemical Carcinogenesis: What Are Animal Experiments Telling Us?

Waddell

2003

Toxicol Pathol

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It appears that the controversy over whether animal experiments demonstrate a threshold for carcinogenicity from chemicals was due to an error in plotting dose response. A linear (arithmetic) scale for the dose of chemicals obscures effects at doses below those used in the experiment and distorts the effect seen over the range of doses used. Gaddum (Nature 156: 463, 1946) pointed out that, empirically, dose should be on a logarithmic scale to effect a linear quantal response. It now is proposed that this logarithmic relationship of dose to effect has a sound basis in chemical thermodynamics (Waddell, Toxicol Sci 68: 275-279, 2002). When the results of major studies (e.g., ED01, etc.) done in the past were reanalyzed with this in mind using the Rozman et al scale (Drug Metab Rev 28: 29-52, 1996), which has a logarithmic scale down to one molecule (10 0 ), unequivocal thresholds were demonstrated. Many animal studies now have been reanalyzed by this procedure (e.g., Waddell, Toxicol Sci 72: 158-163, 2003; Waddell, Food Chem Toxicol, in press; Waddell, Hum Exp Toxicol, in press); these studies show thresholds for carcinogenicity at doses ranging from 10 17.1 to 10 21.92 molecules/kg/day. These results require a complete reevaluation of human risk assessment for carcinogenesis from chemicals and a redirection of basic research to discover the system, or systems, that are overwhelmed at these thresholds.

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Linear Low‐Dose Extrapolations

Dourson

Haber

2010

Cancer Risk Assessment

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A Toxicologist's View of Cancer Risk Assessment

Cited by 57 publications

References 17 publications

Chemical- and effect-oriented exposomics: Three Gorges Reservoir (TGR)

Chemical- and effect-oriented exposomics: Three Gorges Reservoir (TGR)

Thresholds in Chemical Carcinogenesis: What Are Animal Experiments Telling Us?

Linear Low‐Dose Extrapolations

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