Advanced Search

Journal Navigation

Journal Home

Subscriptions

Archive

Contact Us

Table of Contents

CiteULike is a free service for managing and discovering scholarly references - click here to get started.

Sign In to gain access to subscriptions and/or personal tools.
Toxicologic Pathology
This Article
Right arrow Abstract Freely available
Right arrow Free Full Text (Free PDF) Free
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to Saved Citations
Right arrow Download to citation manager
Right arrowRequest Permissions
Right arrow Request Reprints
Right arrow Add to My Marked Citations
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Right arrow Citing Articles via Scopus
Google Scholar
Right arrow Articles by Maurer, J. K.
Right arrow Articles by Jester, J. V.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Maurer, J. K.
Right arrow Articles by Jester, J. V.
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati   Add to Twitter  
What's this?

Pathology of Ocular Irritation with Acetone, Cyclohexanol, Parafl uoroaniline, and Formaldehyde in the Rabbit Low-Volume Eye Test

James K. Maurer

The Procter & Gamble Co, Cincinnati, Ohio

AL Molai

University of Texas Southwestern Medical Center at Dallas, Dallas, Texas

Ron D. Parker

The Procter & Gamble Co, Cincinnati, Ohio

Li Li

University of Texas Southwestern Medical Center at Dallas, Dallas, Texas

Gregory J. Carr

The Procter & Gamble Co, Cincinnati, Ohio

W. Matthew Petroll

University of Texas Southwestern Medical Center at Dallas, Dallas, Texas

H. Dwight Cavanagh

University of Texas Southwestern Medical Center at Dallas, Dallas, Texas

James V. Jester

University of Texas Southwestern Medical Center at Dallas, Dallas, Texas

The ocular irritation responses to 11 different surfactants and two concentrations of acetic acid and sodium hydroxide have been shown to depend on the extent of initial injury, despite marked differences in the processes leading to tissue damage. The purpose of these studies was to determine the extent to which this fundamental relationship applies to other nonsurfactants. Ten µl of acetone (ACT), cyclohexanol (CY), parafluoroaniline (PF), or 37% formaldehyde (FA) was directly applied to the cornea of the right eye of each rabbit. Eyes and eyelids were macroscopically scored for signs of irritation beginning 3 hours after dosing and periodically until recovery or 35 days. Tissues were obtained for light microscopic examination after 3 hours and on days 1, 3, and 35. Initial corneal injury was characterized quantitatively at 3 hours and 1 day using in vivo confocal microscopy (CM) and by postmortem quantitation of dead corneal epithelial cells and keratocytes using a Live—Dead Assay (L/D, Molecular Probes) and scanning laser CM. Corneal changes over time were characterized quantitatively using in vivo CM performed at 3 hours and 1, 3, 7, 14, and 35 days. The changes with ACT were consistent with mild irritation. Corneal injury was limited to the epithelium and superfi cial stroma, with the mean normalized depth of injury (NDI) being less than 10% with the majority of regions showing no stromal injury. Changes with CY and PF were consistent with moderate to severe irritation, and FA caused severe irritation. Specifi cally, corneal injury by CY and PF tended to involve the epithelium and anterior stroma, with the mean NDI being 10.4% to 23.8%, while injury with FA involved the epithelium, deep stroma, and at times the endothelium. Interestingly, with FA significantly less injury was observed at 3 hours with a dramatic increase in injury observed at 1 day and thereafter. In conclusion, these results continue to support and extend our hypothesis that ocular irritation is principally defined by the extent of initial injury despite clear differences in the means by which irritants cause tissue damage. We believe this approach can be applied to developing alternative assays based on injury to ex vivo eyes or injury to an in vitro corneal equivalent system.

Key Words: Animal alternatives • confocal microscopy • conjunctiva • cornea • eye testing • wound healing.

References

  • Association for Research in Vision and Ophthalmology (1994). Statement for the use of animals in ophthalmic and vision research. Invest Ophthalmol Vis Sci 35: v—vi.
  • Balls M., BothamPA, Bruner LH, Spielmann H. (1995). The EC/HO international validation study on alternatives to the Draize eye irritation test. Toxic In Vitro 9: 871—929.[CrossRef]
  • Brantom PG, Bruner LH, Chamberlain M., de Silva O., Dupuis J., Earl LK, Lovell DP, Pape WJW, Uttley M., Bagley DM, Baker FW, Bracher M., Courtellemont P., Declercq L., Freeman S., Steiling W., Walker AP, Carr GJ, Dami N., Thomas G., Harbell J., Jones PA, Pfannenbecker U., Southee JA, Tcheng M., Argembeaux H., Castelli D., Clothier R., Esdaile DJ, Itigaki H., Jung K., Kasai Y., Kojima H., Kristen U., Larnicol M., Lewis RW, Marenus K., Moreno O., Peterson A., Rasmussen ES, Robles C., Stern M. (1997). A summary report of the COLIPA international validation study on alternatives to the Draize rabbit eye irritation test. Toxic In Vitro 11: 141—179.[CrossRef]
  • Bruner LH, de-Silva O., Earl LK, Easty DL, Pape W., Spielmann H. (1998). Report on the COLIPA workshop on mechanisms of eye irritation. Altern Lab Anim 26: 811—820.
  • Chang JH, Ren H., Petroll WM, Cavanagh HD, Jester JV (1999). The application of in vivo confocal microscopy and tear LDH measurement in assessing corneal response to contact lens and contact lens solutions. Curr Eye Res 19: 171—181.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • Cormier EM, Hunter JE, Billhimer W., May J., Farage MA (1995). Correlation of animal eye data with human experience for household products. J Toxicol Cut Ocular Toxicol 14: 197—205.
  • Draize JH, Woodard G., Calvery HO (1944). Methods for the study of irritation and toxicity of substances applied topically to the skin and mucous membranes. J Pharmacol Exp Ther 82: 377—390.[Free Full Text]
  • Freeberg FE, Griffith JF, Bruce RD, Bay PHS (1984). Correlation of animal test methods with human experience for household products. J Toxicol Cutaneous Ocul Toxicol 1: 53—64.
  • Freeberg FE, Hooker DT, Griffi th JF (1986). Correlation of animal eye data with human experience for household products. J Toxicol Cutaneous Ocul Toxicol 5: 115—123.[CrossRef][Web of Science]
  • Freeberg FE, Nixon GA, Reer PJ, Weaver JE, Bruce RD, Griffith JF, Sanders III LW (1986). Human and rabbit eye responses to chemical insult. Fundam Appl Toxicol 7: 626—634.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • Grant WM (1974a). Survey of types of toxic effects involving the eyes or vision. In: Toxicology of the Eye, 2nd ed. Charles C Thomas, Springfi eld, Illinois, pp. 5—71.
  • Grant WM (1974b). Description of drugs, chemicals, plants venoms, and their effects on the eyes. In: Toxicology of the Eye, 2nd ed. Charles C Thomas, Springfi eld, Illinois, pp 75—1099.
  • Griffi th JF, Nixon GA, Bruce RD, Reer PJ, Bannan EA (1980). Dose-response studies with chemical irritants in the albino rabbit eye as a basis for selecting optimum testing condition s for predicting hazard to the human eye. Toxicol Appl Pharmacol 55: 501—513.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • Heck d'A., Casanova M., Starr TB (1990). Formaldehyde toxicity—New understanding. Crit Rev Toxicol 20: 397—426.[Web of Science][Medline] [Order article via Infotrieve]
  • Hopwood D. (1969). Fixatives and fi xation: A review. Histochem J 1: 323— 360.
  • Ichijima H., Petroll WM, Jester JV, Cavanagh HD (1992). Confocal microscopic studies of living rabbit cornea treated with benzalkonium chloride. Cornea 11: 221—225.[Web of Science][Medline] [Order article via Infotrieve]
  • Ichijima H., Petroll WM, Jester JV, Ohashi J., Cavanagh HD (1992). Effects of increasing DK with rigid contact lens extended wear on rabbit corneal epithelium using confocal microscopy. Cornea 11: 282—287.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • Imayasu M., Moriyama T., Ichijima H., Ohashi J-I., Petroll WM, Jester JV, Cavanagh HD (1994). The effects of daily wear of rigid gas permeable contact lenses treated with contact lens care solutions containing preservatives on the rabbit cornea. Contact Lens Assoc Ophthalmol J 20: 183—188.
  • Imayasu M., Petroll WM, Jester JV, Patel SK, Cavanagh HD (1994). The relationship between contact lens oxygen transmissibility and binding of Pseudomonas aeruginosa to the cornea after overnight wear. Ophthalmology 101: 371—388.[Web of Science][Medline] [Order article via Infotrieve]
  • Jester JV, Li HF, Petroll WM, Parker RD, Cavanagh HD, Carr GJ, Smith B., Maurer JK (1998). Area and depth of surfactant induced corneal injury correlates with cell death. Invest Ophthalmol Vis Sci 39: 922—936.[Abstract/Free Full Text]
  • Jester JV, Maurer JK, Petroll WM, Wilkie DA, Parker RD, Cavanagh HD (1996). Application of in vivo confocal microscopy to the understanding of surfactant-induced ocular irritation. Toxicol Pathol 24: 412—428.[Abstract/Free Full Text]
  • Jester JV, Molai A., Petroll WM, Parker RD, Carr GJ, Cavanagh HD, Maurer JK (2000). Quantitative characterization of acid and alkali induced corneal injury in the low volume eye test. Toxicol Pathol 28: 668—678.[Abstract/Free Full Text]
  • Jester JV, Moller-Pedersen T., Huang J., Sax CM, Kays WT, Cavanagh HD, Petroll WM, Piatigorsky J. (1999). The cellular basis of corneal transparency: Evidence for "corneal crystallins." J Cell Sci 112: 613—622.[Abstract]
  • Jester JV, Petroll WM, Bean J., Parker RD, Carr GJ, Cavanagh HD, Maurer JK (1998). Area and depth of surfactant-induced corneal injury predicts extent of subsequent ocular responses. Invest Ophthalmol Vis Sci 39: 2610— 2625.
  • Li H-F., Petroll WM, Maurer JK, Cavanagh HD, Jester JV (1997). Epithelial and corneal thickness measurements by in vivo confocal microscope through focusing (CMTF). Curr Eye Res 16: 214—221.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • Maurer JK, Li HF, Petroll WM, Parker RD, Cavanagh HD, Jester JV (1997). Confocal microscopic characterization of initial corneal changes of surfactant-induced eye irritation in the rabbit. Toxicol Appl Pharmacol 143:291—300.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • Maurer JK, Parker RD (1996). Light microscopic comparison of surfactant-induced eye irritation in rabbits and rats at 3 hours and recovery/day 35. Toxicol Pathol 24: 403—411.[Abstract/Free Full Text]
  • Maurer JK, Parker RD (2000). Microscopic changes occurring over time with acetic acid and sodium hydroxide in the rabbit low-volume eye test. Toxicol Pathol 28: 679—687.[Abstract/Free Full Text]
  • Maurer JK, Parker RD, Carr GJ ( 1998a). Ocular irritation: Microscopic changes occurring over time in the rat with surfactants of known irritancy. Toxicol Pathol 26: 217—225.[Abstract/Free Full Text]
  • Maurer JK, Parker RD, Carr GJ ( 1998b). Ocular irritation: Pathological changes occurring in the rat with surfactants of unknown irritancy. Toxicol Pathol 26: 226—233.[Abstract/Free Full Text]
  • Maurer JK, Parker RD, Carr GJ ( 2000). Differences in corneal cytokine levels with surfactant-induced ocular irritation in rats. J Toxicol Cut Ocul Toxicol 19: 3—20.
  • Maurer JK, Parker RD, Petroll WM, Carr GJ, Cavanagh HD, Jester JV (1999). Quantitative measurement of acute corneal injury in rabbits with surfactants of different type and irritancy. Toxicol Appl Pharmacol 158: 61—70.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • McCulley, JP (1994). Chemical agents. In: The Cornea. 3rd edition. Gilbert Smolin and Richard A. Thoft (eds). Little, Brown and Company, New York, pp 617—633.
  • Moller-Pedersen T., Cavanagh HD, Petroll WM, Jester JV (2000). Stromal wound healing explains refractive instability and haze development after photorefractive keratectomy. A one-year confocal microscopic study. Ophthalmology 107: 1235—1245.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • Moller-Pedersen T., Li H-F., Petroll WM, Cavanagh HD, Jester JV (1998). Confocal microscopic characterization of wound repair following photorefractive keratectomy. Invest Ophthalmol Vis Sci 39: 487—501.[Abstract/Free Full Text]
  • Moller-Pedersen T., Petroll WM, Cavanagh HD, Jester JV (1998). Neutralizing antibody to TGFβ modulates stromal fi brosis but not regression of photoablative effect following PRK. Curr Eye Res 17: 736—747.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • Moller-Pedersen T., Vogel M., Li H-F., Petroll WM, Cavanagh HD, Jester JV (1997). Quantification of stromal thinning, epithelial thickness, corneal haze following photorefractive keratectomy using in vivo confocal microscopy. Ophthalmology 104: 360—368.[Web of Science][Medline] [Order article via Infotrieve]
  • Nartey IN, Cavanagh HD, Jester JV, Andrews P., Petroll WM (1998). Characterization of specular `dark events' in human donor corneal endothelium by scanning and transmission electron microscopy. Cornea 17: 544—549.[Web of Science][Medline] [Order article via Infotrieve]
  • National Research Council (1996). Guide for the Care Use of Laboratory Animals. 7th ed. A Report by the Committee to Revise the Guide for the Care and Use of Laboratory Animals. Washington DC, National Academy Press.
  • Nussenblatt RB, Bron R., Chambers W., McCulley JP, Pericoi M., Ubels JL, Edelhauser HF (1998). Ophthalmologic perspectives on eye irritation testing. J Toxicol Cut Ocular Toxicol 17: 103—109.
  • Petroll WM, Cavanagh HD, Jester JV (1993). Three-dimensional imaging of corneal cells using in vivo confocal microscopy. J Microscopy 170: 213—219.[Web of Science][Medline] [Order article via Infotrieve]
  • Petroll WM, Cavanagh HD, Lemp MA, Andrews PM, Jester JV (1992). In vivo digital imaging in confocal microscopy. J Microscopy 165: 61—69.[Web of Science][Medline] [Order article via Infotrieve]
  • Petroll WM, Jester JV, Cavanagh HD (1994). In vivo confocal imaging: General principles and applications. Scanning 16: 131—149.[Web of Science][Medline] [Order article via Infotrieve]
  • Ren H., Petroll WM, Jester JV, Cavanagh HD (1997). Adherence of Pseudomonas Aeruginosa to shed rabbit corneal epithelial cells after overnight wear of contact lenses. Contact Lens Assoc Ophthalmol J 23: 63—68.
  • Ren DH, Petroll WM, Jester JV, Cavanagh HD (1999). The effect of rigid gas permeable contact lens wear on proliferation of rabbit corneal and conjunctival epithelial cells. Contact Lens Assoc Ophthalmol J 25: 136— 141.
  • Ren DH, Petroll WM, Jester JV, Ho-Fan J., Cavanagh HD (1999). Short-term hypoxia downregulates epithelial cell desquamation in vivo, but does not increase Pseudomonas aeruginosa adherence to exfoliated human corneal epithelial cells. Contact Lens Assoc Ophthalmol J 25: 73—79.
  • Ren DH, Petroll WM, Jester JV, Ho-Fan J., Cavanagh HD (1999). The relationship between contact lens oxygen permeability and binding of Pseudomonas aeruginosa to human corneal epithelial cells after overnight and extended wear. Contact Lens Assoc Ophthalmol J 25: 80—100.
  • Snedecor RW, Cochran WG (1989). Statistical Methods, Iowa University Press, Ames, IA.
  • Wagoner MD (1997). Chemical injuries of the eye: Current concept in pathophysiology and therapy. Sur Ophthalmol 41: 275—313.
  • Zesch A. (1988). Adverse reactions of externally applied drugs and inert substances. Derm Beruf Umwelt 36: 128—133.[Medline] [Order article via Infotrieve]

Toxicologic Pathology, Vol. 29, No. 2, 187-199 (2001)
DOI: 10.1080/019262301317052468
Add to CiteULike CiteULike   Add to Complore Complore   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati   Add to Twitter Twitter    What's this?


This article has been cited by other articles:


Home page
 IOVSHome page
A. Pauly, M. Meloni, F. Brignole-Baudouin, J.-M. Warnet, and C. Baudouin
Multiple Endpoint Analysis of the 3D-Reconstituted Corneal Epithelium after Treatment with Benzalkonium Chloride: Early Detection of Toxic Damage
Invest. Ophthalmol. Vis. Sci., April 1, 2009; 50(4): 1644 - 1652.
[Abstract] [Full Text] [PDF]

Home page
 International Journal of ToxicologyHome page
Annual Review of Cosmetic Ingredient Safety Assessments--2004/2005
International Journal of Toxicology, March 1, 2006; 25(2_suppl): 1 - 89.
[Full Text] [PDF]

This Article
Right arrow Abstract Freely available
Right arrow Free Full Text (Free PDF) Free
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to Saved Citations
Right arrow Download to citation manager
Right arrowRequest Permissions
Right arrow Request Reprints
Right arrow Add to My Marked Citations
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Right arrow Citing Articles via Scopus
Google Scholar
Right arrow Articles by Maurer, J. K.
Right arrow Articles by Jester, J. V.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Maurer, J. K.
Right arrow Articles by Jester, J. V.
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati   Add to Twitter  
What's this?