Formation of hydrogen fluoride by gamma and beta sterilisation in medical devices containing perfluoroheptane.
Infusion of hexadecafluoroheptane, a liquid perfluorocarbon released from repaired Althane dialysers was found to be the most probable reason for the deaths of 53 dialysis patients reported in the year 2001. This study focuses on toxic decomposition products generated due to gamma and beta sterilisation of hexadecafluoroheptane. The responsible dialysers were sterilised with a maximum dose of 45 kGy gamma irradiation. We investigated the influence of both 20-500 kGy gamma and beta irradiation on perfluoroheptane. Analysis of the irradiated samples verified the decomposition of perfluoroheptane in dependence on the dose of irradiation. Beta irradiation resulted in a higher degree of decomposition than the same dose of gamma irradiation. As decomposition products, hydrogen fluoride, CO2, and one saturated fluorinated hydrocarbon which could not be analysed exactly were identified. Even at 20 kGy gamma irradiation hydrogen fluoride was detectable. Our results provide evidence that hydrogen fluoride is generated as a highly toxic decomposition product when perfluoroheptane is sterilised with gamma irradiation as it was applied on the affected dialysers. There is no evidence of other toxic degradation products especially perfluoroisobutylene. Therefore, hydrogen fluoride or the dissociated fluoride ions might act as a toxic agent when medical devices containing liquid perfluorocarbons are sterilised by irradiation.
Zündorf
Josef
J
Federal Institute for Drugs and Medical Devices (BfArM), Kurt-Georg-Kiesinger-Allee 3, D-53175 Bonn, Germany.
Kremer
Stefan
S
Grüger
Thomas
T
D001610:Beta Particles; D002849:Chromatography, Gas; D017523:Croatia; D015314:Dialysis Solutions / Q000737:chemistry; D004307:Dose-Response Relationship, Radiation; D004340:Drug Contamination; D004866:Equipment Contamination; D004864:Equipment and Supplies; D005466:Fluorocarbons / Q000032:analysis / Q000737:chemistry*; D005720:Gamma Rays; D006536:Heptanes; D006801:Humans; D006845:Hydrocarbons, Fluorinated / Q000138:chemical synthesis / Q000528:radiation effects / Q000633:toxicity*; D006858:Hydrofluoric Acid / Q000032:analysis / Q000737:chemistry*; D006863:Hydrogen-Ion Concentration; D010782:Photolysis / Q000528:radiation effects*; D006435:Renal Dialysis / Q000295:instrumentation; D018570:Risk Assessment / Q000379:methods; D013030:Spain; D017550:Spectroscopy, Fourier Transform Infrared; D013242:Sterilization / Q000379:methods
D015314:Dialysis Solutions; D005466:Fluorocarbons; D006536:Heptanes; D006845:Hydrocarbons, Fluorinated; C528185:perfluoroheptane; D006858:Hydrofluoric Acid