Study of intra- and interlaboratory variability in the results of rabbit eye and skin irritation tests

Weil, Carrol S.; Scala, Robert A.

doi:10.1016/0041-008x(71)90112-8

Cited by 342 publications

(88 citation statements)

References 12 publications

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“…4). There was decreased cellularity of the endothelium in (11,42). Addi-tionally, differences in the response from one animal to another have been found to contribute to the variability of the scores (43).…”

Section: Microscopic Observationsmentioning

confidence: 99%

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

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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.

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Section: Microscopic Observationsmentioning

confidence: 99%

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

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“…The simulations also demonstrate why it is important to establish objective criteria to be used as the basis for judging alternative method performance. The establishment of data-based performance benchmarks will better guide reviewers of a validation study in setting realistic performance expectations given the real-world technical limitations characteristic of the current state of the art (69,71,72).…”

Section: Resultsmentioning

confidence: 99%

Validation of alternative methods for toxicity testing

Bruner

Carr

Chamberlain

et al. 1996

Toxicology in Vitro

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“…This system also provides for some additional dermal findings frequently seen in repeat-dose studies. Variability in evaluations using the Draize system was demonstrated dramatically in a classic study by Weil and Scala (1971), which compared scores for the same materials evaluated in different laboratories and found a high degree of interlaboratory variability. Providing a comprehensive training program with periodic recertification and limiting the core technical staff to a small number of technicians using similar evaluation criteria can help provide consistent results within a laboratory.…”

Section: In-life Observations and Evaluation Of Effectsmentioning

confidence: 99%

Dermatotoxicology

2016

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The minipig has long been identified as the nonrodent animal of choice for preclinical safety evaluation of topically applied materials. This article reviews types of topical applications, study designs, and practical considerations. Dermal administration to the minipig presents multiple challenges. Issues to be considered are the area of exposure, the nature of the test article, the need for covering of the dose site, preparation of the dose site, and procedures for administration. The potential for cross-contamination (exposure of control animals to test article) is very high in topical studies and appropriate safeguards to prevent this are discussed. Topical administration to the intact skin is the most commonly utilized form of safety evaluation, but procedures have also been developed for intradermal administration and for the use of nonintact/wounded skin; these will be discussed. Evaluation of local (topical) effects is critical and can become complicated. Considerations in evaluations of the skin are interobserver variability, use of different scoring systems and discrepancies between in vivo observations, necropsy observations, and microscopic pathology findings. Causes for apparent discrepancies and suggestions for practical resolution through appropriate procedures are discussed. Practical issues in necropsy and histotechnology procedures and techniques to optimize preservation of skin are also discussed.

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Study of intra- and interlaboratory variability in the results of rabbit eye and skin irritation tests

Cited by 342 publications

References 12 publications

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

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

Validation of alternative methods for toxicity testing

Dermatotoxicology

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Study of intra- and interlaboratory variability in the results of rabbit eye and skin irritation tests

Cited by 342 publications

References 12 publications

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

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

Validation of alternative methods for toxicity testing

Dermatotoxicology

Contact Info

Product

Resources

About

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

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