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The mucosal toxicity of different benzalkonium chloride analogues evaluated with an alternative test using slugs

Els Adriaens UGent, Kristof Dierckens UGent, Tieneke Bauters UGent, Hans Nelis UGent, Freddy Van Goethem, Philipe Vanparys and Jean Paul Remon UGent (2001) PHARMACEUTICAL RESEARCH. 18(7). p.937-942
abstract
Purpose. 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 similar to BAG-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 greater than or equal to BAC-C16 > BAC-C12. The BAC-C14 exhibited higher activity than the BAG-mix. Conclusions. The toxicity and activity of BAG analogues depend on the alkyl chain length. The use of BAC-C14 as a conservative agent in pharmaceutical preparations instead of the BAG-mix should be considered.
Please use this url to cite or link to this publication:
author
organization
year
type
journalArticle (original)
publication status
published
subject
keyword
BCOP assay, mucosal toxicity, BAC analogues, antimicrobial activity, HUMAN RESPIRATORY MUCOSA, slug, BOVINE CORNEAL OPACITY, TOPICAL NASAL STEROIDS, IN-VITRO, ABSORPTION ENHANCERS, ASSAY, DRUGS, VIVO
journal title
PHARMACEUTICAL RESEARCH
Pharm. Res.
volume
18
issue
7
pages
937 - 942
Web of Science type
Article
Web of Science id
000170027500006
JCR category
CHEMISTRY, MULTIDISCIPLINARY
JCR impact factor
2.801 (2001)
JCR rank
15/118 (2001)
JCR quartile
1 (2001)
ISSN
0724-8741
DOI
10.1023/A:1010928025753
language
English
UGent publication?
yes
classification
A1
copyright statement
I have transferred the copyright for this publication to the publisher
id
412495
handle
http://hdl.handle.net/1854/LU-412495
date created
2007-06-05 15:18:00
date last changed
2010-07-14 12:03:05
@article{412495,
  abstract     = {Purpose. 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 {\textlangle} BAC-C14 {\textlangle} BAC-C12 similar to BAG-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 greater than or equal to BAC-C16 {\textrangle} BAC-C12. The BAC-C14 exhibited higher activity than the BAG-mix.
Conclusions. The toxicity and activity of BAG analogues depend on the alkyl chain length. The use of BAC-C14 as a conservative agent in pharmaceutical preparations instead of the BAG-mix should be considered.},
  author       = {Adriaens, Els and Dierckens, Kristof and Bauters, Tieneke and Nelis, Hans and Van Goethem, Freddy and Vanparys, Philipe and Remon, Jean Paul},
  issn         = {0724-8741},
  journal      = {PHARMACEUTICAL RESEARCH},
  keyword      = {BCOP assay,mucosal toxicity,BAC analogues,antimicrobial activity,HUMAN RESPIRATORY MUCOSA,slug,BOVINE CORNEAL OPACITY,TOPICAL NASAL STEROIDS,IN-VITRO,ABSORPTION ENHANCERS,ASSAY,DRUGS,VIVO},
  language     = {eng},
  number       = {7},
  pages        = {937--942},
  title        = {The mucosal toxicity of different benzalkonium chloride analogues evaluated with an alternative test using slugs},
  url          = {http://dx.doi.org/10.1023/A:1010928025753},
  volume       = {18},
  year         = {2001},
}

Chicago
Adriaens, Els, Kristof Dierckens, TIENEKE BAUTERS, Hans Nelis, Freddy Van Goethem, Philipe Vanparys, and Jean Paul Remon. 2001. “The Mucosal Toxicity of Different Benzalkonium Chloride Analogues Evaluated with an Alternative Test Using Slugs.” Pharmaceutical Research 18 (7): 937–942.
APA
Adriaens, E., Dierckens, K., BAUTERS, T., Nelis, H., Van Goethem, F., Vanparys, P., & Remon, J. P. (2001). The mucosal toxicity of different benzalkonium chloride analogues evaluated with an alternative test using slugs. PHARMACEUTICAL RESEARCH, 18(7), 937–942.
Vancouver
1.
Adriaens E, Dierckens K, BAUTERS T, Nelis H, Van Goethem F, Vanparys P, et al. The mucosal toxicity of different benzalkonium chloride analogues evaluated with an alternative test using slugs. PHARMACEUTICAL RESEARCH. 2001;18(7):937–42.
MLA
Adriaens, Els, Kristof Dierckens, TIENEKE BAUTERS, et al. “The Mucosal Toxicity of Different Benzalkonium Chloride Analogues Evaluated with an Alternative Test Using Slugs.” PHARMACEUTICAL RESEARCH 18.7 (2001): 937–942. Print.