Genotoxicity carcinogen

However, for some type of adverse effects, such as genotoxicity, carcinogenicity, and respiratory sensitization, it may not be possible from present knowledge to define this threshold of activity, so we may conclude that any level of exposure might carry some finite risk. In this case, OELs should be established at levels sufficiently low to avoid risks these are called pragmatic OELs. 

Nie AY, McMillian MK, Leone AM, Parker JB, Piechta L-A, Bryant S, et al. A gene signature for non-genotoxic carcinogens. Society of Toxicology, 2005. 

In contrast, the calculation of human risk for genotoxic carcinogens from... 

Ethylene oxide is used in the manufacture of raw materials and can be used to sterilize the surface of finished products and containers. Unfortunately, ethylene oxide is a genotoxic carcinogen and its use is not accepted without justification. In any event, tight controls are required on residues of ethylene oxide and its halohydrin-related substances. For raw materials the amount of these residues is limited to 1 and 50 pig/g, respectively for finished products 1 and 50 pg/g, respectively (with any affected ingredients subject to the control limits for raw materials) and for containers, based on simulated use, 1 and 50 pg/mL container volume, respectively. 

Compared to animal assays, CTA is faster and cheaper. In vitro CTAs have been shown to involve a multistage process that closely resembles some stages of in vivo carcinogenesis and have the potential to detect both genotoxic and non-genotoxic carcinogens. 

Harwood M, Danielewska-Nikiel B, Borselleca JF, Flamm GW, Williams GM and Lines TC. 2007. A critical review of the data related to the safety of quercetin and lack of evidence of in vivo toxicity, including lack of genotoxic/carcinogenic properties. Food Chem Toxicol 45 2179-2205. 

Experimental studies with human subjects and several mammalian species (monkey, dog, rat, mouse, and rabbit) were located. Animal studies addressed neurotoxicity, genotoxicity, carcinogenicity, and cardiac sensitization and were conducted over acute, subchronic, and chronic exposure durations. 

The data base for HCFC-141b is extensive and contains studies with human subjects as well as several mammalian species. The study with human subjects was well conducted and addressed clinical symptoms, respiratory effects, cardiotoxicity, hematology and clinical chemistry effects, and pharmacokinetics. The study with humans established a no-effect level (AEGL-1) that may be conservative, because a lowest-observed-effect level was not attained. The AEGL-1 of 1,000 ppm is supported by the animal data, which show an absence of effects at concentrations that are higher by a factor of 10. Animal studies addressed both acute and chronic exposure durations as well as neurotoxicity, genotoxicity, carcinogenicity, and cardiac sensitiza... 

Data adequacy The key study was well designed, conducted, and documented. Exercise takes into consideration some of the stress that humans might experience under emergency conditions. Animal studies addressed both acute and chronic exposure durations as well as neurotoxicity, genotoxicity, carcinogenicity, and cardiac sensitization. In animal studies, concentrations up to 11,000 ppm for up to 6 h did not produce adverse effects. Adjustment of the 11,000-ppm concentration by interspecies and intraspecies uncertainty factors of 3 each, for a total of 10, results in essentially the same concentration (1,100 ppm) as that derived from the human data. 

Ashby, J. and Tennant, R.W. (1988). Chemical structure, Salmonella mutagenicity and extent of carcinogenicity as indices of genotoxic carcinogens among 222 chemicals tested in rodents by the US NCI/NTP. Mutation Res. 204 17-115. 

Clay son, D.B. (1989). ICPEMC publication No. 17 Can a mechanistic rationale be provided for non-genotoxic carcinogens identified in rodent hioassays Mutation Res. 221 53-67. 

ISO (1993). Biological Evaluation of Medical Devices. Part 3 Tests for Genotoxicity, Carcinogenicity, and Reproductive Toxicity. ISO 10993-3. 

McGregor, D. (2000). Carcinogenicity and Genotoxic Carcinogens, in General and Applied Toxicology, 2nd ed. (Ballantyne, B., Marrs, T. and Syversen, T. Eds.). MacMillan, London. 

Some chemicals are believed to have no threshold above which toxic effects are observed. In other words, a single molecule has the potential to induce an adverse effect. The most common group of hazards in this respect are genotoxic carcinogens. Chemical carcinogens are not normally approved as food additives because an acceptable daily intake cannot be established. 

DEREK Expert system for the prediction of toxicity (genotoxicity, carcinogenicity, skin sensitization, etc.)... 

Mirsalis JC, Tyson CK, Butterworth BE. 1982. Detection of genotoxic carcinogens in the in vivo-in vitro hepatocyte DNA repair assay. Environ Mutagen 4 553-562. 

W. K. Lutz and A. Kopp-Schneider, Threshold dose response for tumor induction by genotoxic carcinogens modeled via cell-cycle delay. Toxicological Sciences, 1999,49(1), 110-115. 

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