title: The mucosal toxicity of different benzalkonium chloride analogues evaluated with an alternative test using slugs.
abstract: OBJECTIVE
  The objective of this study was to evaluate the mucosal toxicity of different benzalkonium chloride (BAC) analogues using slugs as the alternative test organism.
  
  
  METHODS
  The effect of different BAC analogues on the mucosal tissue of slugs was determined from the protein, lactate dehydrogenase, and alkaline phosphatase released from the foot mucosa after treatment. Additionally, mucus production and reduction in body weight of the slugs were measured. The eye irritation potency of the molecules was evaluated with the Bovine Corneal Opacity and Permeability (BCOP) assay. The antimicrobial activity of the different BAC analogues was also assessed.
  
  
  RESULTS
  All BAC analogues induced severe damage to the mucosal epithelium of the slugs, and the irritation increased with decreasing alkyl chain length: BAC-C16 < BAC-C14 < BAC-C12 approximately BAC-mix. A similar ranking was obtained with the BCOP assay for eye irritation. The relative order of activities among the three BAC analogues was the same, i.e., BAC-C14 > or = BAC-C16 > BAC-C12. The BAC-C14 exhibited higher activity than the BAC-mix.
  
  
  CONCLUSIONS
  The toxicity and activity of BAC analogues depend on the alkyl chain length. The use of BAC-C14 as a conservative agent in pharmaceutical preparations instead of the BAC-mix should be considered.
authors.affiliation: Laboratory of Pharmaceutical Technology, University of Gent, Belgium.
authors.forename: E
authors.initials: E
authors.lastname: Adriaens
authors.forename: K
authors.initials: K
authors.lastname: Dierckens
authors.forename: T G
authors.initials: TG
authors.lastname: Bauters
authors.forename: H J
authors.initials: HJ
authors.lastname: Nelis
authors.forename: F
authors.initials: F
authors.lastname: van Goethem
authors.forename: P
authors.initials: P
authors.lastname: Vanparys
authors.forename: J P
authors.initials: JP
authors.lastname: Remon
mesh_terms: D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D000890:Anti-Infective Agents / Q000633:toxicity; D001548:Benzalkonium Compounds / Q000737:chemistry / Q000633:toxicity*; D002417:Cattle; D003315:Cornea / Q000187:drug effects / Q000378:metabolism; D004353:Drug Evaluation, Preclinical / Q000379:methods; D007509:Irritants / Q000633:toxicity; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008826:Microbial Sensitivity Tests; D008974:Mollusca / Q000187:drug effects* / Q000378:metabolism; D009092:Mucous Membrane / Q000187:drug effects / Q000378:metabolism; D009093:Mucus / Q000187:drug effects / Q000378:metabolism; D011310:Preservatives, Pharmaceutical / Q000737:chemistry / Q000633:toxicity*
chemical_list: D000890:Anti-Infective Agents; D001548:Benzalkonium Compounds; D007509:Irritants; D011310:Preservatives, Pharmaceutical; D007770:L-Lactate Dehydrogenase; D000469:Alkaline Phosphatase