สารบัญ

Contents
MENU

8.1 ABNORMAL TOXICITY TEST

APPENDIX 8 BIOLOGICAL TESTS AND METHODS

Test Animals​

      Healthy animals of different species and unquestioned strains are required for biological tests. They should not have previously been used for any test purpose, unless otherwise specified.

ANIMAL ROOM Unless otherwise specified, animal room should be maintained at the temperature of 25º to 30º and the relative humidity within a range of 30 to 70 per cent. Air-conditioning is highly recommended since it promotes environmental stability. If air-conditioning is not available, alternative methods of providing for heat dissipation must be sought.

FEED Bulk supplies for food and bedding should not be stored in animal rooms. Commercially preparedlaboratory animal feeds are preferred, if available. The special daily requirement for vitamin C for guinea-pigs may be met by the use of 50 mg per litre of ascorbic acid daily in the drinking water. Great care must be taken to ensure against contamination in foods with antibiotics or other harmful substances which may have been used in the preparation of livestock feeds, since such contaminations may confuse the results. Food and drinking water should be given ad libitum.

CAGE AND BEDDING Cages are made up of appropriate material which can be cleaned easily and permit free ventilation. Cleaning and disinfecting facilities should be adequately provided. Animal colonies should not be crowded.

      Care should be ensured that animal colonies are not contaminated by field rodents or other vermins. If available, heat sterilization of bedding before and/or after the use is preferred. Bedding should be changed at least once a week.

Diluents

DILUENT A: PYROGEN-FREE WATER Prepare pyrogen-free water by collecting freshly distilled water and sterilizing it in an autoclave at 121º for not less than 20 minutes. Pyrogen-free water meets the requirements for the absence of pyrogens as described in the “Pyrogen Test” (Appendix 8.2).

DILUENT B: PYROGEN-FREE SALINE SOLUTION Prepare an isotonic solution of sodium chloride by dissolving 9.0 g of pyrogen-free sodium chloride (prepared by heating sodium chloride at 200º for 2 hours) in pyrogen-free distilled water to make 1000 ml. Sterilize in an autoclave at 121º for not less than 20 minutes. Pyrogen-free saline solution meets the requirements for the absence of pyrogens as described in the “Pyrogen Test” (Appendix 8.2).

DILUENT C: STERILE DISTILLED WATER Prepare freshly distilled water. Sterilize in an autoclave at 121º for 20 minutes.

DILUENT D: STERILE SALINE SOLUTION Dissolve 9.0 g of sodium chloride in distilled water to make 1000 ml. Sterilize in an autoclave at 121º for 20 minutes.

DILUENT E: PYROGEN-FREE SODIUM CARBONATE SOLUTION Dissolve 25.6 g of pyrogen-free anhydrous sodium carbonate (prepared by heating anhydrous sodium carbonate at 170º for 4 hours) in pyrogen-free distilled water to make 1000 ml. Sterilize in an autoclave at 121º for not less than 20 minutes. Pyrogen-free sodium carbonate solution meets the requirements for the absence of pyrogens as described in the “Pyrogen Test” (Appendix 8.2).

8.1 ABNORMAL TOXICITY TEST

The test is designed to reveal the presence of toxicity not inherited, unexpected or unacceptable biological reactivity

Test for General Products

      Select five healthy mice not previously used for testing, weighing between 17 and 24 g. During the testing period, the animals should be housed in a suitable container and given adequate food and water. A constant temperature environment is desirable at all times. 

      Prepare the solution of the test substance as specified in the monograph. Select the route of administration and proceed as directed. If the product is packaged for dispensing in a combination package with a diluent, dilute the product as directed in the labelling.

      Use sterile glassware, syringes and needles. To each of five mice, administer the appropriate test dose by one of the following routes of administration as specified in the monograph:

      (a) Intravenous Use a 26-gauge needle, threequarter inch in length. Inject the test dose into a tail vein of each mouse. The injection should be made at the rate of 0.1 ml per second.

      (b) Intraperitoneal Use a 26-gauge needle, onequarter inch or one-half inch in length. Inject the test dose through the abdominal wall into the peritoneal cavity of each animal.

      (c) Subcutaneous Use a 26-gauge needle, one-half inch in length. Inject the test dose subcutaneously at a site on the abdominal or dorsal surface.

      (d) Oral By means of a cannula or other suitable device, administer a test dose orally.

      Observe the animals over the 48 hours following the injection. If, at the end of 48 hours, all of the animals survive and not more than one of the animals shows outward symptoms of a reaction not normally expected of the level of toxicity related to the tested material, the requirements of this test are met. If one or more animals die or if more than one of the animals shows signs of abnormal or untoward toxicity of the tested material under test, repeat the test using at least another 10 mice similar to those used in the initial test, but weighing 19 to 21 g. In either case, if all of the animals survive for 48 hours and show no symptoms of a reaction indicative of an abnormal or undue level of toxicity of the tested material, the requirements of the test are met. 

Tests for Biological Products (Immunosera and Vaccines)

      Unless otherwise prescribed, inject intraperitoneally one human dose but not more than 1.0 ml of liquid product or of the reconstituted product, into each of five healthy mice, weighing 17 to 24 g and one human dose but not more than 5.0 ml of the liquid product or of the reconstituted product, into each of two guinea-pigs, weighing 250 to 400 g. (The human dose is that stated on the label of the product to be examined or on the accompanying leaflet.)

      The requirements of this test are met if none of the animals shows signs of ill health within 7 days following the inoculation. If more than one of the animals die during the time specified, the product fails the test. If one of the animals dies or shows signs of ill health during the time specified, repeat the test with a new group of unused one or both species in which the requirements were not met. The product passes the test if none of the animals in the second group dies or shows signs of ill health within the time interval specified.

APPENDICES • 8.1 ABNORMAL TOXICITY TEST
view 1,802 ผู้เข้าชม / View
หมายเหตุ / Note : TP II 2011 PAGE 520-521