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Ocular toxicity of benzalkonium chloride homologs compared with their mixtures.

Okahara A, Tanioka H, Takada K, Kawazu K - J Toxicol Pathol (2013)

Bottom Line: In addition, the antimicrobial activities of C12-BAK and C14-BAK against A. niger, S. aureus and P. aeruginosa were assessed.C12-BAK showed antimicrobial activities at a concentration of 0.003%.These results suggest that the use of C12-BAK to replace BAK mixture as a preservative in ophthalmic solutions should be considered in order to reduce the incidence of the corneal epithelial cell injury induced clinically by BAK.

View Article: PubMed Central - PubMed

Affiliation: Nara Research & Development Center, Santen Pharmaceutical Co., Ltd., 8916-16 Takayama-cho, Ikoma, Nara 630-0101, Japan.

ABSTRACT
This study was performed to assess the in vivo ocular toxicity of benzalkonium chloride (BAK) homologs compared with commercially available BAK (BAK mixture) and to assess the ocular toxicity of BAK homolog after repeated ocular application. Rabbit eyes were examined by ophthalmology and scanning electron microscopy (SEM) after 10 applications of BAK homologs with C12 (C12-BAK) and C14 (C14-BAK) alkyl chain lengths and a BAK mixture at concentrations of 0.001% (w/v), 0.003% (w/v), 0.005% (w/v), 0.01% (w/v) and 0.03% (w/v). The ocular toxicity of C12-BAK to rabbit eyes was examined by ophthalmology and histopathology after repeated ocular application for 39 weeks. In addition, the antimicrobial activities of C12-BAK and C14-BAK against A. niger, S. aureus and P. aeruginosa were assessed. Ocular toxicity of C12-BAK was less than those of the BAK mixture and C14-BAK. No ocular toxicity was noted after ocular application of 0.01% C12-BAK to rabbits for 39 weeks. C12-BAK showed antimicrobial activities at a concentration of 0.003%. These results suggest that the use of C12-BAK to replace BAK mixture as a preservative in ophthalmic solutions should be considered in order to reduce the incidence of the corneal epithelial cell injury induced clinically by BAK.

No MeSH data available.


Related in: MedlinePlus

Scanning electron microscopy of the corneal epithelium after 10 applications of 0.005% BAK homologs and BAK mixture. C12-BAK (A-1) induced no damage. The BAK mixture (B-1) and C14-BAK (C-1) induced exfoliation of a small number of cells. Original magnification ×500. Photos A-2, B-2 and C-2 are high-magnification versions of photos A-1, B-1 and C-1, respectively. Bar = 10 μm.
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fig_001: Scanning electron microscopy of the corneal epithelium after 10 applications of 0.005% BAK homologs and BAK mixture. C12-BAK (A-1) induced no damage. The BAK mixture (B-1) and C14-BAK (C-1) induced exfoliation of a small number of cells. Original magnification ×500. Photos A-2, B-2 and C-2 are high-magnification versions of photos A-1, B-1 and C-1, respectively. Bar = 10 μm.

Mentions: Table 3Table 3. SEM Analysis of the Cornea Epithelium after 10 Applications of BAK Homologs and BAK Mixture summarizes SEM results of the corneal epithelium following 10 applications of the drugs. The corneal epithelium surface treated with 0.9% saline consisted of irregularly-shaped polygonal cells. Epithelial cells could be separated into light, medium and dark cells on the basis of their brightness. Light cells were smaller than dark or medium cells. There were a large number of microvilli and crater-like depressions, which are called epithelial holes23, on the surface of light, medium and dark cells. No damage was detected on corneas treated with concentrations of ≤ 0.005% C12-BAK or treated with the 0.001% BAK mixture. Application of 0.01% C12-BAK, 0.005% C14-BAK and 0.003%-0.01% BAK mixture caused exfoliation of a small number of cells (Fig. 1Fig. 1.


Ocular toxicity of benzalkonium chloride homologs compared with their mixtures.

Okahara A, Tanioka H, Takada K, Kawazu K - J Toxicol Pathol (2013)

Scanning electron microscopy of the corneal epithelium after 10 applications of 0.005% BAK homologs and BAK mixture. C12-BAK (A-1) induced no damage. The BAK mixture (B-1) and C14-BAK (C-1) induced exfoliation of a small number of cells. Original magnification ×500. Photos A-2, B-2 and C-2 are high-magnification versions of photos A-1, B-1 and C-1, respectively. Bar = 10 μm.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3921916&req=5

fig_001: Scanning electron microscopy of the corneal epithelium after 10 applications of 0.005% BAK homologs and BAK mixture. C12-BAK (A-1) induced no damage. The BAK mixture (B-1) and C14-BAK (C-1) induced exfoliation of a small number of cells. Original magnification ×500. Photos A-2, B-2 and C-2 are high-magnification versions of photos A-1, B-1 and C-1, respectively. Bar = 10 μm.
Mentions: Table 3Table 3. SEM Analysis of the Cornea Epithelium after 10 Applications of BAK Homologs and BAK Mixture summarizes SEM results of the corneal epithelium following 10 applications of the drugs. The corneal epithelium surface treated with 0.9% saline consisted of irregularly-shaped polygonal cells. Epithelial cells could be separated into light, medium and dark cells on the basis of their brightness. Light cells were smaller than dark or medium cells. There were a large number of microvilli and crater-like depressions, which are called epithelial holes23, on the surface of light, medium and dark cells. No damage was detected on corneas treated with concentrations of ≤ 0.005% C12-BAK or treated with the 0.001% BAK mixture. Application of 0.01% C12-BAK, 0.005% C14-BAK and 0.003%-0.01% BAK mixture caused exfoliation of a small number of cells (Fig. 1Fig. 1.

Bottom Line: In addition, the antimicrobial activities of C12-BAK and C14-BAK against A. niger, S. aureus and P. aeruginosa were assessed.C12-BAK showed antimicrobial activities at a concentration of 0.003%.These results suggest that the use of C12-BAK to replace BAK mixture as a preservative in ophthalmic solutions should be considered in order to reduce the incidence of the corneal epithelial cell injury induced clinically by BAK.

View Article: PubMed Central - PubMed

Affiliation: Nara Research & Development Center, Santen Pharmaceutical Co., Ltd., 8916-16 Takayama-cho, Ikoma, Nara 630-0101, Japan.

ABSTRACT
This study was performed to assess the in vivo ocular toxicity of benzalkonium chloride (BAK) homologs compared with commercially available BAK (BAK mixture) and to assess the ocular toxicity of BAK homolog after repeated ocular application. Rabbit eyes were examined by ophthalmology and scanning electron microscopy (SEM) after 10 applications of BAK homologs with C12 (C12-BAK) and C14 (C14-BAK) alkyl chain lengths and a BAK mixture at concentrations of 0.001% (w/v), 0.003% (w/v), 0.005% (w/v), 0.01% (w/v) and 0.03% (w/v). The ocular toxicity of C12-BAK to rabbit eyes was examined by ophthalmology and histopathology after repeated ocular application for 39 weeks. In addition, the antimicrobial activities of C12-BAK and C14-BAK against A. niger, S. aureus and P. aeruginosa were assessed. Ocular toxicity of C12-BAK was less than those of the BAK mixture and C14-BAK. No ocular toxicity was noted after ocular application of 0.01% C12-BAK to rabbits for 39 weeks. C12-BAK showed antimicrobial activities at a concentration of 0.003%. These results suggest that the use of C12-BAK to replace BAK mixture as a preservative in ophthalmic solutions should be considered in order to reduce the incidence of the corneal epithelial cell injury induced clinically by BAK.

No MeSH data available.


Related in: MedlinePlus