Criteria for in vitro alternatives for the eye irritation test

Green, S.; Chambers, Wiley A.; Gupta, Kailash C.; Hill, Richard N.; Hurley, Pamela M.; Lambert, L.A.; Lee, C.C.; Lee, J.K.; Liu, P.T.; Lowther, D.K.; Roberts, Colin; Seabaugh, V.M.; Springer, Janet A.; Wilcox, N.L.

doi:10.1016/0278-6915(93)90118-i

Cited by 21 publications

(8 citation statements)

References 8 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Alternative in vitro tests have been broadly characterized into 2 types based on use; screens, and replacements (13,14,24). Although there are numerous screening tests available, at present there are no clearly recognized in vitro replacements for accessing ocular irritation (6,11).…”

Section: Introductionmentioning

confidence: 99%

Application of In Vivo Confocal Microscopy to the Understanding of Surfactant-Induced Ocular Irritation*^{Oryzias latipes}

et al. 1996

View full text Add to dashboard Cite

The purpose of this study was to assess the ability of in vivo confocal microscopy (CM) to provide noninvasively derived histopathologic correlates of surfactant-induced eye irritation from which specific pathologic mechanisms can be identified and later evaluated in alternative in vitro models. Rats and rabbits, divided into groups of 5, received 10 μl of an anionic or cationic surfactant in one eye with the other eye used as a control. At specified times, eyes were examined and scored for ocular irritancy using a penlight and slit-lamp. Subsequently, corneas were evaluated by in vivo CM to evaluate epithelial layer thickness and surface epithelial cell area, corneal thickness, depth of necrosis, inflammation, fibrosis, and endothelial injury. At 3 hr, the anionic surfactant produced slight irritation with peak scores of 12.4 and 8.0 out of a possible 110 in the rats and rabbits, respectively. In vivo CM revealed changes limited to the corneal epithelium that decreased in thickness to 78% in rats and 81% in rabbits at 3 hr. This decrease in the thickness correlated with a significant decrease in surface epithelial cell area from 2,061 & p l u s m n ; 395 μm 2 to 567 & p l u s m n ; 330 μm 2 in the rats and 1,523 ± 185 μm 2 to 934 ± 71 μm 2 in the rabbits (p < 0.005 and 0.005, respectively). The cationic surfactant produced severe irritation in both the rats and rabbits with peak scores of 85.4 and 80.2 occurring at day 2, respectively. In vivo CM in the rats showed complete loss of corneal epithelium, lysis of keratocytes, and loss of corneal endothelium. In the rabbits, injury appeared limited to the anterior cornea with complete loss of epithelium and loss of keratocytes extending to 52% of the corneal thickness. These findings establish the application of noninvasive, in vivo CM to qualitatively and quantitatively characterize the pathobiology of ocular irritation in situ. This information will be important in the development and evaluation of mechanistically based in vitro alternatives for ocular irritancy testing.

show abstract

Section: Introductionmentioning

confidence: 99%

Application of In Vivo Confocal Microscopy to the Understanding of Surfactant-Induced Ocular Irritation*^{Oryzias latipes}

et al. 1996

View full text Add to dashboard Cite

show abstract

“…Alternative in vitro tests have been broadly characterized as being used as either screens or replacements (20,21). Screens are used to make preliminary decisions or establish the direction for further testing (20,21).…”

Section: Introductionmentioning

confidence: 99%

“…Screens are used to make preliminary decisions or establish the direction for further testing (20,21). Screens are also used in a tier eye irritation assessment process (3).…”

Section: Introductionmentioning

confidence: 99%

“…Screens are also used in a tier eye irritation assessment process (3). The results from screens are usually confirmed by more definitive testing (20,21 (20,21). Unlike screens, replacements must provide the same answers as in vivo methods used for making definitive toxicologic assessments (20,21).…”

Section: Introductionmentioning

confidence: 99%

“…The results from screens are usually confirmed by more definitive testing (20,21 (20,21). Unlike screens, replacements must provide the same answers as in vivo methods used for making definitive toxicologic assessments (20,21). For alternative tests to be used as replacements in assessing safety, there must be some mechanistic similarity between the in vitro tests and the events occurring in vivo (20,21).…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Light Microscopic Comparison of Surfactant-Induced Eye Irritation in Rabbits and Rats at Three Hours and Recovery/Day 35*¹

Maurer

Parker

1996

Toxicol Pathol

View full text Add to dashboard Cite

Limited information exists on the pathologic changes occurring with surfactant-induced ocular irritation in the context of accidental human exposures and animal tests used to assess for such irritation. The purpose of this study was to begin to characterize the pathologic changes that occur with surfactants in the context of standard animal tests and compare the response in rats to that in rabbits. Representative anionic, cationic, and nonionic surfactants causing slight to severe ocular irritation were directly applied to the corneas of rabbits and rats at a dose of 10 μl. Eyes and eyelids of each animal were macroscopically examined for signs of irritation beginning 3 hr after dosing and periodically until recovery or day 35. Eyes and eyelids from animals in each group were collected for microscopic examination after 3 hr and at recovery or day 35. Microscopically, all of the surfactants caused erosion, denudation, and/or necrosis of the conjunctival and corneal epithelium in rabbits and rats. Necrosis of keratocytes was observed in rabbits and rats treated with the severely irritating cationic surfactant and in rats treated with anionic surfactants that were mildly irritating and moderately irritating. Corneal endothelial changes were observed in rabbits and rats with only the cationic surfactant. Changes in eyes of rabbits and rats that had not recovered by day 35 included decreased prominence of goblet cells, conjunctivalization of the corneal epithelium, neovascularization and fibrosis of the cornea, and presence of devitalized stroma. Overall, the changes in rabbits and rats were similar and suggest that the rat may be used as a surrogate for the rabbit in studies to understand better mechanisms of surfactantinduced eye irritation.

show abstract

Extent of Initial Corneal Injury as the Mechanistic Basis for Ocular Irritation: Key Findings and Recommendations for the Development of Alternative Assays

Maurer

Parker

Jester

2002

Regulatory Toxicology and Pharmacology

View full text Add to dashboard Cite

Criteria for in vitro alternatives for the eye irritation test

Cited by 21 publications

References 8 publications

Application of In Vivo Confocal Microscopy to the Understanding of Surfactant-Induced Ocular Irritation*^{Oryzias latipes}

Application of In Vivo Confocal Microscopy to the Understanding of Surfactant-Induced Ocular Irritation*^{Oryzias latipes}

Light Microscopic Comparison of Surfactant-Induced Eye Irritation in Rabbits and Rats at Three Hours and Recovery/Day 35*¹

Extent of Initial Corneal Injury as the Mechanistic Basis for Ocular Irritation: Key Findings and Recommendations for the Development of Alternative Assays

Contact Info

Product

Resources

About

Criteria for in vitro alternatives for the eye irritation test

Cited by 21 publications

References 8 publications

Application of In Vivo Confocal Microscopy to the Understanding of Surfactant-Induced Ocular Irritation*Oryzias latipes

Application of In Vivo Confocal Microscopy to the Understanding of Surfactant-Induced Ocular Irritation*Oryzias latipes

Light Microscopic Comparison of Surfactant-Induced Eye Irritation in Rabbits and Rats at Three Hours and Recovery/Day 35*1

Extent of Initial Corneal Injury as the Mechanistic Basis for Ocular Irritation: Key Findings and Recommendations for the Development of Alternative Assays

Contact Info

Product

Resources

About

Application of In Vivo Confocal Microscopy to the Understanding of Surfactant-Induced Ocular Irritation*^{Oryzias latipes}

Application of In Vivo Confocal Microscopy to the Understanding of Surfactant-Induced Ocular Irritation*^{Oryzias latipes}

Light Microscopic Comparison of Surfactant-Induced Eye Irritation in Rabbits and Rats at Three Hours and Recovery/Day 35*¹