Ocular Irritation: Pathological Changes Occurring in the Rat with Surfactants of Unknown Irritancy

Abstract

We believe the development and validation of in vitro alternatives to eliminate the need to use animals in ocular irritation testing must be based on a thorough understanding of the mechanisms of ocular irritation. We have recently undertaken the task of developing such an understanding for a panel of surfactants. The purpose of this study was to expand our current panel of surfactants for which the microscopic changes occurring over time have been characterized. Macroscopic and microscopic findings regarding the ocular irritation of 6 surfactants of relatively unknown irritancy were compared to those of 6 surfactants of known irritancy. The right eye of each rat was treated by placing 10 μl of a surfactant directly on the cornea. Untreated left eyes served as the controls. At 3 hr and on days 1, 3, and 35, eyes and eyelids were collected for microscopic examination. Collectively, the macroscopic and microscopic findings revealed 3 surfactants to be similar to the mildly irritating surfactants previously studied, and 3 surfactants to be similar to the moderately irritating surfactant previously studied. Information such as this will be important to develop mechanistically based in vitro alternatives to replace the use of animals for ocular irritation testing.

Keywords

Cornea conjunctiva wound healing histopathology pathobiology eye testing

References

1. Bailer AJ (1988). Testing for the equality of area under the curves when using destructive measurement techniques. J. Pharmacokinet. Biopharm. 16: 303–309.

2. Bruner LH (1992). Ocular irritation. In: In Vitro Toxicity Testing. Applications to Safety Evaluation, JM Frazier (ed). Marcel Dekker, New York, pp. 149–190.

3. Daston GP and Freeberg FE (1991). Ocular irritation testing. In: Dermal and Ocular Toxicology. Fundamentals and Methods, DW Hobson (ed). CRC Press, Ann Arbor, MI, pp. 509–540.

4. Draize JH , Woodard G , and 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.

5. Freeberg FE , Nixon GA , Reer PJ , Weaver JE , Bruce RD , Griffith JF , and Sanders LW III (1986). Human and rabbit eye responses to chemical insult. Fundam. Appl. Toxicol. 7: 626–634.

6. Green S (1992). In vitro test validation and regulatory animal testing: A house built on sand versus a house of cards? ATLA, Altern. Lab. Anim. 20: 567–570.

7. Green S , Chambers WA , Gupta KC , Hill RN , Hurley PM , Lambert LA , Lee CC , Lee JK , Liu FT , Lowther DK , Roberts CD , Seabaugh VM , Springer JA , and Wilcox NL (1993). Criteria for in vitro alternatives for the eye irritation test. Food Chem. Toxicol. 31: 81–85.

8. Hey wood R and James RW (1978). Towards objectivity in the assessment of eye irritation. J. Soc. Cosmet. Chem. 29: 25–29.

9. Jester JV , Maurer JK , Petroll WM , Wilkie DA , Parker RD , and Cavanagh HD (1996). Application of in vivo confocal microscopy to the understanding of surfactant-induced ocular irritation. Toxicol. Pathol. 24: 412–428.

10.

10. Marzulli FN and Simon ME (1971). Eye irritation from topically applied drugs and cosmetics: Preclinical studies. Am. J. Optom. Arch. Am. Acad. Optom. 48: 61–79.

11.

11. Maurer JK , Li HF , Petroll WM , Parker RD , Cavanagh HD , and Jester JV (1997). Confocal microscopic characterization of initial corneal changes of surfactant-induced eye irritation in the rabbit. Toxicol. Appl. Pharmacol. 143: 291–300.

12.

12. Maurer JK and 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.

13.

13. Maurer JK , Parker RD , and Carr GJ (1998). Ocular irritation: Microscopic changes occurring over time in the rat with surfactants of known irritancy. Toxicol. Pathol. 26: 217–225.

14.

14. US Department of Health and Human Services (1985). Guide for the Care and Use of Laboratory Animals. Animal Resources Program, Division of Research Resources, National Institute of Health, Bethesda, MD.

15.

15. Weil CS and Scala RA (1971). Study of intra- and interlaboratory variability in the results of rabbit eye and skin irritation tests. Toxicol. Appl. Pharmacol. 19: 276–360.

16.

16. Williams SJ , Graepel GJ , and Kennedy GL (1982). Evaluation of ocular irritancy potential: Intralaboratory variability and effect of dosage volume. Toxicol. Lett. 12: 235–241.