Skip Navigation

This Article
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrowRequest Permissions
Right arrow Disclaimer
Google Scholar
Right arrow Articles by SINA, J. F.
Right arrow Articles by MILLER, K.
Right arrow Search for Related Content
PubMed
Right arrow Articles by SINA, J. F.
Right arrow Articles by MILLER, K.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

© 1995 Oxford University Press

research-article

A Collaborative Evaluation of Seven Alternatives to the Draize Eye Irritation Test Using Pharmaceutical Intermediates

J. F. SINA*, D. M. GALER{dagger},1, R. G. SUSSMAN{dagger}, P. D. GAUTHERON{ddagger}, E. V. SARGENT§, B. LEONG, P. V. SHAH||, R. D. CURREN** and K. MILLER**,2

*Merck Research Laboratories West Point, Pennsylvania 19486 {dagger}Warner-Lambert Co. Morris Plains, NJ 07950 {ddagger}Merck Sharp and Dohme—Chibret Rion, France §Merck & Co Whitehouse Station, NJ 08889 The Upjohn Co. Kalamazoo, MI 49001 ||Hoffmann-LaRoche Nutley, NJ 07110 **Microbiological Associates Rockville, MD 20850

Received June 13, 1994; accepted November 7, 1994

Much of the data which have been generated on in vitro alternatives to the Draize eye irritation test have dealt with compounds within a specific chemical class or product category. However, in the pharmaceutical industry, it is often necessary to evaluate materials which are not related in structure or properties. It was thus decided to evaluate a diverse series of chemicals in seven in vitro methods for estimating ocular irritation. Thirtyseven test materials were chosen to represent a broad range of pH, solubility, and in vivo irritation potential. Assays were chosen to include as many different types of end points as practical. The group of assays was composed of TOPKAT (assessing structure-activity relationships), bovine corneal opacity-permeability (BCO-P; corneal opacity/toxicity), Eytex (protein coagulation), neutral red uptake (cytotoxicity), MTT in living dermal equivalent (cytotoxicity), Microtox (cytotoxicity in bacteria), and CAMVA (inflammation/toxicity). The results of the study indicated that, in general, the cytotoxicity end points did not correlate well with the in vivo data. The BCO-P, CAMVA, and Eytex assays had the best overall concordance (88.9, 75.8, and 75.0%, respectively) with this set of compounds. Estimation of irritation potential based on structure-activity (TOPKAT) was possible for only approximately 50% of the compounds; however, the assay showed 100% sensitivity (i.e., no false negatives), but low specificity (i.e., negatives correctly identified only 54.5% of the time). These data suggest that for screening of chemicals of diverse structure and properties, the more mechanism-based assays, as opposed to general cytotoxicity assays, hold more promise and should be further evaluated.


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?




Disclaimer:
Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.