Methods for the determination of the hazardous properties - TSAR

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ECB/TM/18(97) rev.1 If a pre-selection process is used or the bulk fibres used are produced by a non-commercial production method, a validation must be included in the study report which shows that the fibre has similar chemical and surface characteristics as compared to that produced commercially. The suspensions of test fibre in saline should be prepared freshly immediately before the start of the injections in order to minimise possible dissolution of the fibres. Suspensions should not be reused on subsequent days. The suspensions should be stirred continuously (e.g. magnetic stirrer) from the time of preparation through sampling and until all injections of that fibre are completed. The pH of each saline fibre suspension should be measured from the time of preparation until the injection is complete. If the pH of the saline/fibre suspension increases above a pH of 9, then the saline/fibre suspension should be buffered using TRIS buffer. 1.4.3.2 Intraperitoneal Injection The selected volume of the test material in suspension should be removed from a glass vessel (under constant stirring using a magnetic stirrer) using a syringe and gently injected through a needle inserted into the lower part of the abdominal cavity of the rat. All apparatus used in preparing and injecting the suspensions should be previously sterilised or disinfected. 1.4.3.3 Control Analysis of the Test Material - Vehicle Suspensions 1.4.3.3.1 SAMPLING INSTRUMENTS, SPECIFICATIONS AND CONTROL All sampling of the suspension for the physical characterisation should be performed with a needle fitted to a syringe of an identical size as that used for injection. During the technical preparation of the experiment, for each fibre type, suspensions identical to that used for intraperitoneal injection should be prepared. Sampling should be performed according to a technique identical to that planned for the experiment. The tip of the needle should be observed under a binocular microscope to assure that there is no accumulation of fibres at the tip. 1.4.3.3.2 PHYSICAL CHARACTERISATION OF THE SUSPENSION All samples described below should be taken within 30 seconds of vortex mixing. Immediately after preparation of each suspension: • At least one sample from the middle of the container should be taken for control of concentration and homogeneity in all groups treated with the test fibre by gravimetric evaluation. - 46 -
ECB/TM/18(97) rev.1 • At least one sample (from the middle of the flask) should be taken for characterisation of fibre size by SEM in each group and for evaluation of the fibre concentration in the suspension (fibres/ml). Immediately after the end of injection of each fibre type: • One sample from the middle of the flask should be taken for control by gravimetry of conservation of suspension characteristics during the administration session. 1.4.3.3.3 MICROBIOLOGICAL CHARACTERISATION OF THE SUSPENSION Immediately prior to each daily administration, 1 ml of each fibre suspension should be sampled with a sterile pipette and inoculated into Thioglycolate-Broth appropriate for supporting and growth of all major bacterial rat pathogens (aerobic, microaerophile, anaerobic). 1.4.3.4 General observations 1.4.3.4.1 MORTALITY All animals should be observed for mortality/moribundity at least once each day. 1.4.3.4.2 CLINICAL SIGNS Each animal should have a detailed clinical observation for signs of toxicity, including time of onset, intensity and duration: • at least once during acclimatisation phase • at least once weekly during the study phase. 1.4.3.4.3 BODY WEIGHT All animals should be weighed at least • once at the beginning of acclimatisation period, • on the day of first injection, prior to the injection, • once weekly thereafter through week 13, • once every second week thereafter. 1.4.3.4.4 GROSS NECROPSY - 47 -
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Methods for the determination of the hazardous properties - TSAR

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