title: Identifying toxic degradation products in cellulose acetate dialyzers.
abstract: In September 1996, seven patients at Hospital A suffered conjunctivitis, hearing loss, diminished vision, and headaches 7-24 h after hemodialysis treatment. Eleven-year-old dialysis modules were identified as a common link between these patients. Degradation of the cellulose acetate (CA) material was identified as the cause of this incident. Degradation products were characterized from retrieved CA dialysis membranes. A series of synthesized CA degradation products was tested in vitro to assess toxicity. Based on the toxicity of the material preparations to the cells, animal tests were performed on selected CA degradation extracts and compared to extracts from actual dialysis membranes. Rabbits were IV-injected with extracts from a 13-year-old dialyzer, synthesized model compounds, and compared to controls. Ophthamological evaluation of the rabbits showed eye injury (iritis/ciliary flush) when the animals were treated with the old dialyzer or synthesized model compounds. Isolation and characterization of a toxic fraction from both of these extracts strongly indicated that oxidative stress at some point in the storage or manufacture of CA dialyzers created degradation products that reproduced some of the patient symptoms identified at Hospital A.
authors.affiliation: U.S. Food and Drug Administration, CDRH/OST, Rockville MD 20852, USA. adl@cdrh.fda.gov
authors.forename: A D
authors.initials: AD
authors.lastname: Lucas
authors.forename: J A
authors.initials: JA
authors.lastname: Kalson
authors.forename: J C
authors.initials: JC
authors.lastname: Hutter
authors.forename: R R
authors.initials: RR
authors.lastname: Wallis
mesh_terms: D000818:Animals; D001672:Biocompatible Materials / Q000737:chemistry / Q000633:toxicity; D002470:Cell Survival / Q000187:drug effects; D002482:Cellulose / Q000031:analogs & derivatives* / Q000737:chemistry / Q000633:toxicity; D003231:Conjunctivitis / Q000209:etiology; D003638:Deafness / Q000209:etiology; D004868:Equipment Failure; D005260:Female; D006261:Headache / Q000209:etiology; D006801:Humans; D019169:Jurkat Cells; D008567:Membranes, Artificial; D011817:Rabbits; D006435:Renal Dialysis / Q000295:instrumentation* / Q000592:standards; D014786:Vision Disorders / Q000209:etiology
chemical_list: D001672:Biocompatible Materials; D008567:Membranes, Artificial; C005062:acetylcellulose; D002482:Cellulose