Articles of general interest ETHYLENE
OXIDE
RESIDUES
IN STERILIZED
61
MEDICAL
DEVICES
The safety of ethylene oxide (EO) used as a sterilizrepeatedsterilization produced a slight local erything agent and the acceptability of the residues remain- ema,no productsgave positive reactionsin the aniing after such use have attracted attention fairly fre- mal tests,and the erythemawasconsideredto be of quently over the past few years. Indeed, the FDA cur- doubtful significance.The author suggeststhat redrently appears to be involved in an evaluation of the cell haemolysisis a responsiveand reproducibleindex use of EO in the sterilization of foods, cosmetics and of the EO content of sterilized equipmentfollowing medical devices. The effects of the products arising aeration. from EO, particularly ethylene chlorohydrin, ethylene In his secondpaper, Gunther (ibid 1974,31, 684) glycol and 2-mercaptoethanol have been investigated concentrateson the EO sterilizationof finishedprod(Cited in FE.?: 1972,10, 589, 592 & 719; ibid 1973, ucts, thoseinvestigatedbeing two different kinds of 11, 330; ibid 1974, 12, 275) and last year saw the rubber endotrachealtube, a gum-rubberFoley cathappearanceof two reports on a study of changesin eter and two different PVC endotracheal tubes. biocompatibility as a function of the post-exposure Sampleswere testedfor haemolysisfollowing steriliaeration time of EO-sterilized materials (Gunther, zation and aeration by proceduressimilar to those describedin the first report, but the haemolysistest Am. J. Hosp. Phnn. 1974,31, 558 & 684). The five materialsused for the first part of the was slightly modified in that all the haemoglobin study werea thin siliconerubber from an anaesthesia releasedby cell haemolysiswasacidified to haematiri face mask,a gum rubber from a catheter, and three prior to its estimationso that all formsof haemoglodifferent brandsof PVC tubing of the kind often used bin could be detectedon one wavelength(520 nm). in heart-lung machines,blood sets and catheters. Measurementshad previously beentaken at the isosMaterials for single-sterilizationtestswere placed in bestic point for oxyhaemoglobinand reduced haeindividual glassineenvelopesin Kraft paperbagsand moglobin (548.5 nm) and were not sensitiveto the were sterilized for 1 cycle (421mg EO/Iitre at 55°C presenceof methaemoglobin. for 3 hours). Samplesfor repeatedsterilization were Again, significantEO residueswere found after the treated in a similar mannerafter they had beenpre- 24-hour ambient aeration of all sterilized products. conditioned by daily sterilization (exposurefor 7.5 After the 8-hour heatedaerationonly the gum rubber hours) for 5 days. EO and its residueswere deter- catheterwas free of residues,although the remaining mined by the distillation and titration of approxi- levelswere minor in one of the PVC endotracheal mately 2-g samples,and the haemolytic activity of tubesand in one of the rubber ones.A permanent sterilizedand unsterilizedsampleswas studiedusing residuewasfound in all the products,exceptone type human blood and a calorimetric procedure.Toxicity of PVC tube, after repeatedsterilization. It is notewasassessed by iv injection of extracts into mice and worthy that the rubber products were inherently insc injection into rabbits. Sampleswere aeratedafter compatiblewith red blood cellsevenbeforethe sterilisterilization either at ambient temperature for 24 zation procedure.Control studieswith ethyleneglycol hours or by forced, heated ventilation at 50°C for and ethyl alcohol showedno haemolysisat concent8 hours. rations up to 15 mg/20ml, while Freon-12waswithSignificantquantitiesof residualEO (05-2.4 mg/g) out effect up to 32 mg/20 ml. It wasalso found that were found in all the PVC products after useof the the degreeof haemolysiscausedby 15 mg ethylene former aeration method, but heated aeration left a chlorohydrin/20 ml was similar to that producedby measurableresidue(05 mg/g) in only one. A per- 2 mg E0/20 ml. manent residuefound in the gum rubber rose from This secondstudy thus confirmedthat while there 1 to 7 mg/g after repeatedEO treatment followed is a considerablevariation in residuecontent after by the 8-hour heatedaeration,but this effect wasnot EO treatment even in similar polymers,the 8-hour observedwith the other polymerstested.Siliconerub- heatedaeration consistentlyproducesbetter results ber desorbedthe most rapidly, and producedno hae- than longeraerationat room temperature.There was, molysis.This was also the only samplethat caused however, some discrepancy between the results no haemolysisin the unsterilizedstate; it was closely obtained in the two parts of the study with regard followed by one PVC sample,which caused2% hae- to the gum-rubbercatheters.From the comparative molysis, the other unsterilized products causing investigationof the various EO derivatives,it seems 10-20x haemolysis.In general,the degreeof haemo- that EO is the most potent inducer of haemolysis lysisinducedby the sterilizedproductsparalleledthe and it is thus particularly important that EO be levelsof EO residuesretained,rangingfrom 0 to 10% desorbedfrom sterilizedproducts. in samplessubjectedto the 8-hour heatedaeration. [F. A. Charlesworth-BIBRA] With the exception of gum rubber, which after
ENZYMES FOR THE WASH It is now 10yearssinceenzymeswereintroducedinto washingpowdersto produce biological whiter-thanwhiteness.Sincethat time, many critics have berated the manufacturersof enzyme detergentsabout the
adverseeffectsof their productscomparedwith those of conventionalwashingpowders.Not only have extremely washday-redhandsbeen reported, but also washdayrhinorrhoea,sneezing,coughand other res-
OXIDE
RESIDUES
IN STERILIZED
61
MEDICAL
DEVICES
The safety of ethylene oxide (EO) used as a sterilizrepeatedsterilization produced a slight local erything agent and the acceptability of the residues remain- ema,no productsgave positive reactionsin the aniing after such use have attracted attention fairly fre- mal tests,and the erythemawasconsideredto be of quently over the past few years. Indeed, the FDA cur- doubtful significance.The author suggeststhat redrently appears to be involved in an evaluation of the cell haemolysisis a responsiveand reproducibleindex use of EO in the sterilization of foods, cosmetics and of the EO content of sterilized equipmentfollowing medical devices. The effects of the products arising aeration. from EO, particularly ethylene chlorohydrin, ethylene In his secondpaper, Gunther (ibid 1974,31, 684) glycol and 2-mercaptoethanol have been investigated concentrateson the EO sterilizationof finishedprod(Cited in FE.?: 1972,10, 589, 592 & 719; ibid 1973, ucts, thoseinvestigatedbeing two different kinds of 11, 330; ibid 1974, 12, 275) and last year saw the rubber endotrachealtube, a gum-rubberFoley cathappearanceof two reports on a study of changesin eter and two different PVC endotracheal tubes. biocompatibility as a function of the post-exposure Sampleswere testedfor haemolysisfollowing steriliaeration time of EO-sterilized materials (Gunther, zation and aeration by proceduressimilar to those describedin the first report, but the haemolysistest Am. J. Hosp. Phnn. 1974,31, 558 & 684). The five materialsused for the first part of the was slightly modified in that all the haemoglobin study werea thin siliconerubber from an anaesthesia releasedby cell haemolysiswasacidified to haematiri face mask,a gum rubber from a catheter, and three prior to its estimationso that all formsof haemoglodifferent brandsof PVC tubing of the kind often used bin could be detectedon one wavelength(520 nm). in heart-lung machines,blood sets and catheters. Measurementshad previously beentaken at the isosMaterials for single-sterilizationtestswere placed in bestic point for oxyhaemoglobinand reduced haeindividual glassineenvelopesin Kraft paperbagsand moglobin (548.5 nm) and were not sensitiveto the were sterilized for 1 cycle (421mg EO/Iitre at 55°C presenceof methaemoglobin. for 3 hours). Samplesfor repeatedsterilization were Again, significantEO residueswere found after the treated in a similar mannerafter they had beenpre- 24-hour ambient aeration of all sterilized products. conditioned by daily sterilization (exposurefor 7.5 After the 8-hour heatedaerationonly the gum rubber hours) for 5 days. EO and its residueswere deter- catheterwas free of residues,although the remaining mined by the distillation and titration of approxi- levelswere minor in one of the PVC endotracheal mately 2-g samples,and the haemolytic activity of tubesand in one of the rubber ones.A permanent sterilizedand unsterilizedsampleswas studiedusing residuewasfound in all the products,exceptone type human blood and a calorimetric procedure.Toxicity of PVC tube, after repeatedsterilization. It is notewasassessed by iv injection of extracts into mice and worthy that the rubber products were inherently insc injection into rabbits. Sampleswere aeratedafter compatiblewith red blood cellsevenbeforethe sterilisterilization either at ambient temperature for 24 zation procedure.Control studieswith ethyleneglycol hours or by forced, heated ventilation at 50°C for and ethyl alcohol showedno haemolysisat concent8 hours. rations up to 15 mg/20ml, while Freon-12waswithSignificantquantitiesof residualEO (05-2.4 mg/g) out effect up to 32 mg/20 ml. It wasalso found that were found in all the PVC products after useof the the degreeof haemolysiscausedby 15 mg ethylene former aeration method, but heated aeration left a chlorohydrin/20 ml was similar to that producedby measurableresidue(05 mg/g) in only one. A per- 2 mg E0/20 ml. manent residuefound in the gum rubber rose from This secondstudy thus confirmedthat while there 1 to 7 mg/g after repeatedEO treatment followed is a considerablevariation in residuecontent after by the 8-hour heatedaeration,but this effect wasnot EO treatment even in similar polymers,the 8-hour observedwith the other polymerstested.Siliconerub- heatedaeration consistentlyproducesbetter results ber desorbedthe most rapidly, and producedno hae- than longeraerationat room temperature.There was, molysis.This was also the only samplethat caused however, some discrepancy between the results no haemolysisin the unsterilizedstate; it was closely obtained in the two parts of the study with regard followed by one PVC sample,which caused2% hae- to the gum-rubbercatheters.From the comparative molysis, the other unsterilized products causing investigationof the various EO derivatives,it seems 10-20x haemolysis.In general,the degreeof haemo- that EO is the most potent inducer of haemolysis lysisinducedby the sterilizedproductsparalleledthe and it is thus particularly important that EO be levelsof EO residuesretained,rangingfrom 0 to 10% desorbedfrom sterilizedproducts. in samplessubjectedto the 8-hour heatedaeration. [F. A. Charlesworth-BIBRA] With the exception of gum rubber, which after
ENZYMES FOR THE WASH It is now 10yearssinceenzymeswereintroducedinto washingpowdersto produce biological whiter-thanwhiteness.Sincethat time, many critics have berated the manufacturersof enzyme detergentsabout the
adverseeffectsof their productscomparedwith those of conventionalwashingpowders.Not only have extremely washday-redhandsbeen reported, but also washdayrhinorrhoea,sneezing,coughand other res-
