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2587. Testing of plastics for pharmaceutical use
PROCESSINGAND PACKAGINGCONTAMINANTS
917
Comparison of these results with others already obtained for EC (ibid 1972, 10, 589) indicates that while the two compounds are similar in their acute oral toxicity in rats and mice, CA is some 10-30 times more toxic than EC when injected ip. Conversely EC is more toxic than CA following application to the skin. CA is by far the more irritant of the two compounds, however. The second paper cited above reports an abrupt increase during 1969 in the incidence of tracheal stenosis in patients subjected to tracheotomy and prolonged artificial respiration, and attributes this to the inefficient removal of residues from cannulae sterilized with EO 48 hr before use. When the storage period between EO sterilization and use was increased to 15 days, the incidence of tracheal stenosis fell again to the levels recorded before EO sterilization was instituted as a routine measure. Storage of sterilized equipment of this kind for at least 8 days after exposure to EO is recommended as a safety precaution. 2587. Testing of plastics for pharmaceutical use Lefaux, R. (1972). Valeur et limites d'un contr61e analytique des mati~res plastiques b. usage pharmaceutique et m6dical. Annls pharm, fr. 30, 673. Pentelow, J. E. (1973). Practical problems in the examination and control of plastics for pharmaceutical use. Proc. Soc. analyt. Chem. 10, 41. The increasing use of plastics containers for pharmaceutical products raises the problem of the analytical testing of these materials. Two authors, one French and one English, have recently presented reviews on this subject and show some degree of accord in their general approach. The test methods for the assessment of plastics reviewed by Lefaux (first paper cited above) fall into three general categories covering tests on the plastics material itself, tests on extracts prepared by autoclaving the plastics, usually in contact with distilled water, and biological testing. The first category covers the physico-chemical properties of the plastics material (permeability to light, ultraviolet rays, air, water vapour, bacteria and viruses and absorption properties), and when these have been checked the polymer itself can be examined by a variety of methods involving extraction by various solvents, chromatographic separation and analysis by ultraviolet, infra-red, mass spectrometric and nuclear magnetic resonance methods. The polymer should be subject to routine analytical control on the basis of its infra-red spectrum and the extraction of additives. The autoclaved extract is tested for organic materials, heavy metals, tin, zinc and chromium, and can be subjected to spectrophotometric analysis. These tests may give an adequate analysis of the polymer itself, but biological testing is still very important and the author points out that there is room for improvement in current methods. He stresses the potential value of adding more sensitive procedures, such as cytotoxicity and haemolysis tests, to the acute toxicity tests in mice. The risk of accumulation of substances that are not metabolized is probably a more frequent problem than that of acute toxicity. The second paper cited above again reviews existing test procedures, laying particular stress on the testing of the final container. The testing of the physico-chemical properties of the plastics and the monitoring of extracts are described, with reference to the methods approved by those authorities who have produced monographs or guidelines on this subject. On the same basis, the author restricts his attention to the biological tests already recommended, without speculating on possible advantageous additions to the list. Consistent quality control of the plastics is again advocated.
917
Comparison of these results with others already obtained for EC (ibid 1972, 10, 589) indicates that while the two compounds are similar in their acute oral toxicity in rats and mice, CA is some 10-30 times more toxic than EC when injected ip. Conversely EC is more toxic than CA following application to the skin. CA is by far the more irritant of the two compounds, however. The second paper cited above reports an abrupt increase during 1969 in the incidence of tracheal stenosis in patients subjected to tracheotomy and prolonged artificial respiration, and attributes this to the inefficient removal of residues from cannulae sterilized with EO 48 hr before use. When the storage period between EO sterilization and use was increased to 15 days, the incidence of tracheal stenosis fell again to the levels recorded before EO sterilization was instituted as a routine measure. Storage of sterilized equipment of this kind for at least 8 days after exposure to EO is recommended as a safety precaution. 2587. Testing of plastics for pharmaceutical use Lefaux, R. (1972). Valeur et limites d'un contr61e analytique des mati~res plastiques b. usage pharmaceutique et m6dical. Annls pharm, fr. 30, 673. Pentelow, J. E. (1973). Practical problems in the examination and control of plastics for pharmaceutical use. Proc. Soc. analyt. Chem. 10, 41. The increasing use of plastics containers for pharmaceutical products raises the problem of the analytical testing of these materials. Two authors, one French and one English, have recently presented reviews on this subject and show some degree of accord in their general approach. The test methods for the assessment of plastics reviewed by Lefaux (first paper cited above) fall into three general categories covering tests on the plastics material itself, tests on extracts prepared by autoclaving the plastics, usually in contact with distilled water, and biological testing. The first category covers the physico-chemical properties of the plastics material (permeability to light, ultraviolet rays, air, water vapour, bacteria and viruses and absorption properties), and when these have been checked the polymer itself can be examined by a variety of methods involving extraction by various solvents, chromatographic separation and analysis by ultraviolet, infra-red, mass spectrometric and nuclear magnetic resonance methods. The polymer should be subject to routine analytical control on the basis of its infra-red spectrum and the extraction of additives. The autoclaved extract is tested for organic materials, heavy metals, tin, zinc and chromium, and can be subjected to spectrophotometric analysis. These tests may give an adequate analysis of the polymer itself, but biological testing is still very important and the author points out that there is room for improvement in current methods. He stresses the potential value of adding more sensitive procedures, such as cytotoxicity and haemolysis tests, to the acute toxicity tests in mice. The risk of accumulation of substances that are not metabolized is probably a more frequent problem than that of acute toxicity. The second paper cited above again reviews existing test procedures, laying particular stress on the testing of the final container. The testing of the physico-chemical properties of the plastics and the monitoring of extracts are described, with reference to the methods approved by those authorities who have produced monographs or guidelines on this subject. On the same basis, the author restricts his attention to the biological tests already recommended, without speculating on possible advantageous additions to the list. Consistent quality control of the plastics is again advocated.