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Dissertation
An in-vitro tiered approach alternative to live animal testing for determination of ocular or dermal irritation
Doctor of Philosophy (Ph.D.), Drexel University
Mar 2002
DOI:
https://doi.org/10.17918/etd-37
Abstract
There is a continual need for information concerning the potential for chemicals, if inadvertently splashed into the eyes, to cause effects from irritation to total blindness. This information is currently generated by exposing the eyes of live rabbits to the chemical. As can be imagined, this often results in severe distress to the animal while generating information that we have shown to be discernable without putting any animals at risk. This may be accomplished by replacing the live animal tests with in vitro alternatives. This has been attempted in the past with disappointing results. The reason for this poor correlation may be that each in vitro test only mimics one of the myriad mechanisms that could result in a positive animal test (i.e., inflammation, cytotoxicity, corrosion, mechanical effects). Therefore, if the chemical happens to cause eye irritation by exactly the mechanism mimicked by the in vitro alternative then you get a corresponding positive result. However, if the chemical causes eye irritation by a different mechanism, then the in vitro test is negative while the animal test is positive. To remedy this problem, this thesis proposes to choose alternative tests that each replicate one of the mechanisms of eye damage in vivo. This challenges a previous paradigm whereby multiple in vitro tests were run but a final positive result only scored if a preponderance of tests were positive. This thesis proposes that if any one of the in vitro tests were positive, this simply indicates that the live animal test would also be positive via that specific mechanism. This change resulted in much better correspondence i.e., as soon a positive test was recorded, the chemical was determined to be a probable eye irritant. When data from 60 chemicals (tested in a previous study carried out by the British Home Office and the European Commission in the early 1990s) were reassessed using this paradigm, the resulting correspondence was excellent, with Yates Corrected Chi Square results T of 29.6 (where a score >3.84 would yield >95% confidence that the results were significant). Even more encouraging than the statistical significance is that there were absolutely no false negatives in the entire set of 60 chemicals tested utilizing the newly proposed algorithm and preferred set of alternative assas.
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Details
- Title
- An in-vitro tiered approach alternative to live animal testing for determination of ocular or dermal irritation
- Creators
- David Eherts - DU
- Contributors
- Orien Tulp (Advisor) - Drexel University (1970-)
- Awarding Institution
- Drexel University
- Degree Awarded
- Doctor of Philosophy (Ph.D.)
- Publisher
- Drexel University; Philadelphia, Pennsylvania
- Resource Type
- Dissertation
- Language
- English
- Academic Unit
- Bioscience and Biotechnology [Historical]; College of Arts and Sciences; Drexel University
- Other Identifier
- 37; 991014632293904721