title: Risk assessment of dithiocarbamate accelerator residues in latex-based medical devices: genotoxicity considerations.
abstract: The Medical Devices Agency (MDA) has investigated potential human health hazards arising from the presence of dithiocarbamate vulcanization accelerators in latex products (mainly gloves). After collection of manufacturer's data on usage and residues of these accelerators, an independent investigation of solvent extractable residues and dithiocarbamate migration into aqueous simulants was commissioned, to complement equivalent "in-house" test data from two major manufacturers. The presence of extractable accelerator residues in commercial products was confirmed. Potential human health hazards associated with dithiocarbamates include genotoxicity and possible carcinogenicity: a review of published data was conducted to evaluate the evidence for this, with particular reference to three zinc dithiocarbamates with significant commercial usage (ZDMC, ZDEC and ZDBC: see Fig. 1). Data gaps were identified, and mutagenicity studies commissioned to fill these. These studies comprised tests both in vitro (bacterial and L5178Y cell gene mutation, cultured lymphocyte chromosome aberration) and in vivo (mouse bone marrow micronucleus, rat liver UDS). It is concluded that ZDMC must be considered a genotoxin (and thus a probable carcinogen): residues of this substance in latex medical devices should be minimized. ZDEC proved genotoxic in vitro but was not clearly genotoxic in vivo, and may have activity intermediate between that of ZDMC and that of ZDBC, which showed at most weak activity in a single in vitro (chromosome aberration) test. It is proposed that the use of ZDBC as a vulcanization accelerator in the manufacture of latex gloves, rather than ZDEC, ZDMC or their precursors, would reduce or remove the health concerns arising from accelerator residues.
authors.affiliation: Medical Devices Agency, UK Department of Health, London.
authors.forename: J
authors.initials: J
authors.lastname: Tinkler
authors.forename: D
authors.initials: D
authors.lastname: Gott
authors.forename: J
authors.initials: J
authors.lastname: Bootman
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D002869:Chromosome Aberrations; D004050:Ditiocarb / Q000633:toxicity; D004350:Drug Residues / Q000032:analysis*; D004869:Equipment Safety; D005028:Ethylenebis(dithiocarbamates) / Q000032:analysis / Q000633:toxicity*; D017575:Gloves, Protective; D015386:Hazardous Substances / Q000032:analysis / Q000633:toxicity*; D006801:Humans; D007840:Latex; D051379:Mice; D015162:Micronucleus Tests; D009153:Mutagens / Q000032:analysis / Q000633:toxicity*; D011358:Product Surveillance, Postmarketing; D051381:Rats; D018570:Risk Assessment; D012486:Salmonella typhimurium / Q000187:drug effects / Q000235:genetics; D013329:Structure-Activity Relationship; D013601:T-Lymphocytes / Q000187:drug effects / Q000648:ultrastructure; D013859:Thiocarbamates / Q000633:toxicity; D015039:Ziram / Q000633:toxicity
chemical_list: D005028:Ethylenebis(dithiocarbamates); D015386:Hazardous Substances; D007840:Latex; D009153:Mutagens; D013859:Thiocarbamates; D015039:Ziram; D004050:Ditiocarb; C017801:zinc dibutyldithiocarbamate