The use of low-volume dosing in the eye irritation test

Lambert, L.A.; Chambers, Wiley A.; Green, S.; Gupta, Kailash C.; Hill, Richard N.; Hurley, Pamela M.; Lee, C.C.; Lee, J.K.; Liu, P.T.; Lowther, D.K.; Roberts, Colin; Seabaugh, V.M.; Springer, Janet A.; Wilcox, N.L.

doi:10.1016/0278-6915(93)90121-e

Cited by 23 publications

(7 citation statements)

References 11 publications

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“…LVET is a refinement of Draize testing developed by Griffith et al (1980). The primary difference to the Draize test is that lower volumes of test substances (0.01 ml/0.01 g) (Lambert et al, 1993) are applied to the right-eye of the animal (Maurer et al, 2002), with no forced eyelid closure employed (ICCVAM, 2010b). Test substances are also only applied to the corneal surface and not the conjunctival sac.…”

Section: Low-volume Eye-irritation Test (Lvet)mentioning

confidence: 99%

An overview of current techniques for ocular toxicity testing

2015

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Given the hazardous nature of many materials and substances, ocular toxicity testing is required to evaluate the dangers associated with these substances after their exposure to the eye. Historically, animal tests such as the Draize test were exclusively used to determine the level of ocular toxicity by applying a test substance to a live rabbit's eye and evaluating the biological response. In recent years, legislation in many developed countries has been introduced to try to reduce animal testing and promote alternative techniques. These techniques include ex vivo tests on deceased animal tissue, computational models that use algorithms to apply existing data to new chemicals and in vitro assays based on two dimensional (2D) and three dimensional (3D) cell culture models. Here we provide a comprehensive overview of the latest advances in ocular toxicity testing techniques, and discuss the regulatory framework used to evaluate their suitability.

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Section: Low-volume Eye-irritation Test (Lvet)mentioning

confidence: 99%

An overview of current techniques for ocular toxicity testing

2015

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“… 30 Also, studies report that low-volume method provides a better correlation to human eye irritation experience for some substances. 31 In the present study, we comprehensively evaluated the effect of volume of instillation along with concentration and pH in an in vivo setting which has not been reported so far in literature. Our study showed that volume and pH of formulation are directly related to transcorneal penetration.…”

Section: Discussionmentioning

confidence: 99%

Comprehensive evaluation of formulation factors for ocular penetration of fluoroquinolones in rabbits using cassette dosing technique

Sharma

Biswas

Ojha

et al. 2016

DDDT

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ObjectiveCorneal permeability of drugs is an important factor used to assess the efficacy of topical preparations. Transcorneal penetration of drugs from aqueous formulation is governed by various physiological, physiochemical, and formulation factors. In the present study, we investigated the effect of formulation factors like concentration, pH, and volume of instillation across the cornea using cassette dosing technique for ophthalmic fluoroquinolones (FQs).Materials and methodsSterile cocktail formulations were prepared using four congeneric ophthalmic FQs (ofloxacin, sparfloxacin, pefloxacin mesylate, and gatifloxacin) at concentrations of 0.025%, 0.5%, and 0.1%. Each formulation was adjusted to different pH ranges (4.5, 7.0, and 8.0) and assessed for transcorneal penetration in vivo in rabbit’s cornea (n=4 eyes) at three different volumes (12.5, 25, and 50 μL). Aqueous humor was aspirated through paracentesis after applying local anesthesia at 0, 5, 15, 30, 60, 120, and 240 minutes postdosing. The biosamples collected from a total of 27 groups were analyzed using liquid chromatography–tandem mass spectroscopy to determine transcorneal permeability of all four FQs individually.ResultsIncrease in concentration showed an increase in penetration up to 0.05%; thereafter, the effect of concentration was found to be dependent on volume of instillation as we observed a decrease in transcorneal penetration. The highest transcorneal penetration of all FQs was observed at pH 7.0 at concentration 0.05% followed by 0.025% at pH 4.5. Lastly, increasing the volume of instillation from 12.5 to 50 μL showed a significant fall in transcorneal penetration.ConclusionThe study concludes that formulation factors showed discernible effect on transcorneal permeation; therefore, due emphasis should be given on drug development and design of ophthalmic formulation.

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“…Topical ophthalmic anesthetics were proposed to lessen pain in test animals, but their use was not found to be entirely satisfactory (Seabaugh et al, 1993). Lessening the quantity of test material 10-fold (from the 0.1 ml required in the Draize eye irritation procedure) has also become an acceptable modification (Lambert et al, 1993). Studies with 22 test materials conducted by the Soap and Detergent Association (Bagley et al, 1994) have shown that a 93% correlation exists between results from this low-volume eye test and the Draize eye irritation test.…”

Section: S Christian and R M Dienermentioning

confidence: 98%

Soaps and Detergents: Alternatives to Animal Eye Irritation Tests

Christian

Diener

1996

Journal of the American College of Toxicology

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An extensive computer search was conducted, and a comprehensive overview of the current status of alternatives to animal eye irritation tests was obtained. A search of Medline and Toxline databases (1988 to present) was supplemented with references from sources regarding in vitro eye irritation. Particular attention was paid to soap and detergent products and related ingredients. Eighty-five references are included in the review; the in vitro assays are categorized, and their predictive values for assessing acute ocular irritation are evaluated and compared with the Draize rabbit eye irritation assay and with each other. The present review shows that the increased activity of scientists from academia, industry, and regulatory agencies has resulted in substantial progress in developing alternative in vitro procedures and that a number of large, interlaboratory evaluations and international workshops have assisted in the selection process. However, none of these methodologies has obtained acceptance for regulatory classification purposes. Conclusions drawn from this review include that (a) no single in vitro assay is considered capable of replacing the Draize eye irritation test; (b) the chorioallantoic membrane vascular assay (CAMVA) or the hen egg test-chorioallantoic membrane test (HET-CAM), the chicken or bovine enucleated eye test, the neutral red and plasminogen activation assays for cytotoxicity, and the silicon microphysiometer appear to have the greatest potential as screening tools for eye irritation: and (c) choosing a specific assay or series of assays will depend on the type of agent tested and the impact of false-negative or falsepositive results. New assays will continue to be developed and should be included in future evaluations, when sufficient data are available.

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The use of low-volume dosing in the eye irritation test

Cited by 23 publications

References 11 publications

An overview of current techniques for ocular toxicity testing

An overview of current techniques for ocular toxicity testing

Comprehensive evaluation of formulation factors for ocular penetration of fluoroquinolones in rabbits using cassette dosing technique

Soaps and Detergents: Alternatives to Animal Eye Irritation Tests

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