Conditions, simulated oral

Carbamate pesticides can easily be converted to A-nitroso derivatives in the presence of sodium nitrite under acidic conditions. The A-nitroso form of carbofuran could possibly be formed in the human stomach (Nelson et al. 1981). Since carbofuran is used routinely on a variety of crops and nitrite is a common component of the human diet and present in human saliva, nitrosation of carbamates under conditions simulating those in the human stomach is possible. Lijinsky and Schmal (1978) tested nitrosocarbofuran and five other nitrosated carbamate pesticides for carcinogenicity in rats. Nitrosocarbofuran, at 16.5 mg/kg BW administered orally once weekly for 23 weeks, was the most toxic compound tested and caused the death of several animals by liver damage early in the experiment. Among survivors, nitrosocarbofuran was the most carcinogenic,... 

The strategy for the development of the oral absorption model at pION is illustrated in Fig. 7.58. The human jejunal permeabilities reported by Winiwarter et al. [56] were selected as the in vivo target to simulate by the in vitro model. In particular, three acids, three bases and two nonionized molecules studied by the University of Uppsala group were selected as probes, as shown in Fig. 7.58. They are listed in the descending order of permeabilities in Fig. 7.58. Most peculiar in the ordering is that naproxen, ketoprofen, and piroxicam are at the top of the list, yet these three acids are ionized under in vivo pH conditions and have lipophilicity (log Kj) values near or below zero. The most lipophilic molecules tested, verapamil and carbamazepine... 

The evaluation of the contribution on relative efficacy by cathartic agents to the overall management of oral drug overdoses is often difflcult because of limitations of human volunteer studies that do not simulate clinical conditions, because of multiple therapies employed, because the dosage for cathartics used were not comparable, and because the expected theoretical effects were not observed. 

The biotransformation of 1,1,2,2-tetrachloroethane was studied in rats and mice using [ C]l,l,2,2-tetrachloroethane. The metabolic disposition study was conducted after oral administration of the unlabelled compound on five days per week for four weeks, followed by a single dose of the radiolabelled compound to simulate conditions of a bioassay for carcinogenicity testing. After oral administration of 0.59 mmol/kg bw (98.5 mg/kg bw) [ C]l,l,2,2-tetrachloroethane to rats and 1.19 mmol/kg bw (198.7 mg/kg bw) to mice, 7% and 9.7% of the administered radioactivity were recovered in the expired air of rats and... 

The model was developed from several data sets in which rats were dosed with chromium(VI) or chromium(III) intravenously, orally, or by intratracheal instillation, because depending on route of administration, different distribution and excretion patterns occur. In cases where parameters were not available (absorption rates, tissue affinity, biotransformation), estimates were obtained by fitting. This was done by duplicating the initial conditions of published experiments in the model, varying the unknown parameters and comparing the results of the simulation to the reported results. Tissue affinity constants were estimated using reported chromium levels in tissues at various times after exposure. 

Tricker, A.R., R. Haubner, B. Spiegelhalder, and R. Preussmann The occurrence of tobacco-specific nitro-samines in oral tobacco products and their potential formation under simulated gastric conditions Food Chem. Toxicol. 26 (1988) 861-865. 

Dissolution is a very important CQA of the ASD and can be used in setting QTPP of the product. Although dissolution does not simulate the actual in vivo conditions the dosage form would encounter after oral ingestion, it can be used as an in vitro quality... 

The biomaterial must also demonstrate special abrasion properties that stand up to the oral environment. The most favorable properties are those demonstrated by natural teeth. If the surface of a glass-ceramic is too hard for example, it could dam e the antagonist tooth. However, if the biomaterial is too soft compared with natural dentition, it would wear too easily. Comprehensive tests simulating the actual oral conditions have been conducted in a mastication simulator. Heinzmann et al. (1990) and Krecji et al. (1993) were the first to show that the IPS EMPRESS glass-ceramic demonstrates favorable abrasion properties corresponding to those of natural teeth. Subsequent studies have confirmed these findings. It is very likely that this... 

Schematics of the oral cavity from mouth to pharynx, larynx, and trachea are shown in Fig. 55. A computational grid of 3,36,000 structured cells was used by Zahmatkesh et al. for the simulations of airflow conditions in the oral cavity.

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