Dosing procedures

Static Chemisorption. Measurements were made by two procedures. In the first, the catalyst was evacuated at ca. 250°C for at least 8 hrs and cooled to the measurement temperature under vacuum. Hydrogen was then admitted at progressively higher pressures and the amount of gas adsorbed after 15-30 min at each pressure recorded. The sample was then evacuated for 30 min and the dosing procedure repeated so as to obtain a measure of the reversibly adsorbed gas. In the second (saturation) procedure, after reduction and evacuation, the catalyst was cooled to the... 

Fixed dose procedure for acute oral toxicity testing Fixed dose procedure for acute oral toxicity testing EU... 

Fixed Dose Procedure. The fixed dose design (Figure 5.7) was proposed by the British Toxicology Society (1984). It is designed to supply the data needed for classification or labeling purposes. It is essentially a three-step limit test. 

FIGURE 5.7. British Toxicology Society fixed dose procedure. 

The fixed dose procedure is relatively new and apparently results in a large decrease in animal usage. It is also noteworthy in that it utilizes not only lethality but also evident toxicity, which, in all likelihood, refers to obvious signs of CNS effect, such as seizures or prostration. Whether or not this protocol design becomes widely accepted by various regulatory agencies remains to be established. 

TABLE 5.2. Comparison of Toxicity Classification Based on LD50 versus Fixed Dose Procedure... 

Acute Inhalation Toxicity - Fixed Dose Procedure, Draft Revised Guideline (June 2004)... 

The following draft guidelines are being developed by the OECD TG 433 (Acute Inhalation Toxicity-Fixed Concentration Procedure), TG 434 (Acute Dermal Toxicity-Fixed Dose Procedure),... 

B.lbis Acute oral toxicity - Fixed dose procedure 2004... 

As mentioned above, a NOAEL is usually not derived in acute toxicity smdies. It is more usual that the only numerical value derived is the LD50 or LC50 value. The LD50 or LC50 values (or the discriminating dose if the Fixed Dose Procedure was used or the result of the Acute Toxic Class Method) give an indication of the relative lethal potency of a substance. The slope of the dose-response curve is a particularly useful parameter as it indicates the extent to which reduction of exposure will reduce the lethality the steeper the slope, the greater the reduction in response for a particular finite reduction in exposure. 

During an on-line clean, the quality of the clean will normally be enhanced by the use of an initial chlorine dosing procedure at a pH of 7.2 to 7.6. This practice is to be recommended, irrespective of whether the current cooling system maintenance biocide program employs chlorine. With severely fouled cooling systems, it may be necessary to provide many hundreds of ppm of HOC1 in order to satisfy the oxidation demand. This in turn may require the use of a temporary, supplementary corrosion inhibitor, and almost certainly the use of some antifoam. 

It is essential to take into account a number of potential sources of experimental error in the determination of an adsorption isotherm. In the application of a volumetric technique involving a dosing procedure it must be kept in mind that any errors in the measured doses of gas are cumulative and that the amount remaining unadsorbed in the dead space becomes increasingly important as the pressure increases. In particular, the accuracy of nitrogen adsorption measurements at temperatures of about 77 K will depend on the control of the following factors ... 

The adsorption up to 50 bars was carried out by means of a Tian-Calvet type isothermal microcalorimeter built in the former CNRS Centre for Thermodynamics and Microcalorimetry. For these experiments, around 2 g of sample was used which were outgassed by Controlled Rate Thermal Analysis (CRTA) [7]. The experiments were carried out at 30°C (303 K). Approximately 6 hours is required after introduction of the sample cell into the thermopile for the system to be within 1/100 of a degree Celsius. At this point the baseline recording is taken for 20 minutes. After this thermal equilibrium was attained, a point by point adsorptive dosing procedure was used. Equilibrium was considered attained when the thermal flow measured on adsorption by the calorimeter returned to the base line. For each point the thermal flow and the equilibrium pressure (by means of a 0-70 bar MKS pressure transdueer providing a sensitivity of 0.5% of the measured value) were recorded. The area under the peak in the thermal flow, Q eas, is measured to determine the pseudo-differential... 

In a double-blind, randomized comparison of subUngual buprenorphine tablets with oral methadone in a 6-week trial in 58 patients using a flexible dosing procedure the retention rate was significantly better in those using methadone (90 versus 50%) (22). Those who completed the study had a similar number of opioid-positive urine samples, with a mean stabilization dose of 11 mg/day of buprenorphine and 70 mg/day of methadone. This study had several limitations 6 weeks is too short a period to determine any intermediate or long-term treatment outcomes, the sample size was too small, and the comparison of non-equivalent doses makes interpretation difficult. 

Holst D, Mollmaim M, Karmaim S, Wendt M. Kreislaufverhalten unter Spmalanasthesie. Kathetertechnik versus Smgle-dose-Verfahren. [Circulatory reactions under spmal anesthesia. The catheter techmque versus the single dose procedure.] Anaesthesist 1997 46(1) 38 2. 

Figure 13 Example of a (partial) Quality Assurance check-list for the inspection of the dosing procedure and other relevant activities in a toxicology study.

Zola EM, Gunkel JH, Chan RK, et al. Comparison of three dosing procedures for administration of bovine surfactant to neonates with respiratory distress syndrome. J Pediatr 1993 122 453-459. 

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