An evaluation of five potential alternatives in vitro to the rabbit eye irritation test in vivo

Bagley, Daniel M.; Bruner, Leon H.; Silva, O. de; Cottin, M.; O'Brien, K.A.F.; Uttley, Margaret; Walker, A.P.

doi:10.1016/0887-2333(92)90017-l

Cited by 57 publications

(25 citation statements)

References 8 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Although the data obtained by this test were considered encouraging, the LBT was not selected for further testing by these researchers because the biological system was not as relevant to in vivo ocular irritation as other cell culture techniques that gave better or equivalent correlations. Similar results were also obtained by Bagley et al (1992) when they tested 32 personal care and household cleaning products (predominantly surfactants) in a five-company collaborative study using the MICROTOX system as one of five in vitro tests. An average correlation coefficient of r = -0.6 was achieved when the in vitro results were compared with Draize MAS.…”

Section: Invertebrate Modelssupporting

confidence: 79%

“…The study indicated that the two NR assays were comparable to each other and produced virtually the same correlation coefficients as the low-volume eye test MAS of the Draize test ( r = -0.85 and -0.86). This conclusion was also reached by Bagley et al (1992) when 32 personal care and household cleaning products (predominantly surfactants) were tested in vitro.…”

Section: S Christian and R M Dienermentioning

confidence: 60%

“…Virtually identical results were obtained in a five-company collaborative study in which 32 personal care and household cleaning products (predominantly surfactants) were tested by the NR assays as well as by four other in vitro procedures (Bagley et al, 1992).…”

Section: S Christian and R M Dienermentioning

confidence: 74%

“…All 7-2 test products were correctly classified as irritants or nonirritants according to Federal Hazardous Substances Act criteria. This study was preceded by a five-company collaborative study in which 32 personal care and household cleaning products (predominantly surfactants) were evaluated by five different in vitro test systems (Bagley et al, 1992). Both the CAMVA and the HET-CAM procedures were evaluated in this study.…”

Section: (1985)mentioning

confidence: 99%

See 3 more Smart Citations

Soaps and Detergents: Alternatives to Animal Eye Irritation Tests

Christian

Diener

1996

Journal of the American College of Toxicology

View full text Add to dashboard Cite

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.

show abstract

Section: Invertebrate Modelssupporting

confidence: 79%

Section: S Christian and R M Dienermentioning

confidence: 60%

Section: S Christian and R M Dienermentioning

confidence: 74%

Section: (1985)mentioning

confidence: 99%

See 2 more Smart Citations

Soaps and Detergents: Alternatives to Animal Eye Irritation Tests

Christian

Diener

1996

Journal of the American College of Toxicology

View full text Add to dashboard Cite

show abstract

“…The Hen’s Egg Test–Chorioallantoic Membrane (HET-CAM) (Luepke 1985; de Silva et al 1992; Gilleron et al 1996; Spielmann et al 1996) and similar methods like the Chorioallantoic Membrane Vascular Assay (CAMVA) (Bagley et al 1994) have been proposed to provide information on conjunctiva effects in vivo due to the similarity of the CAM to the conjunctiva. Both HET-CAM and CAMVA underwent multiple international validation studies (Bagley et al 1992b, 1999b; Spielmann et al 1993, 1996, 1997; Brantom et al 1997; Ohno et al 1999; Hagino et al 1999). More recently, HET-CAM was also formally validated by the Interagency Coordinating Committee on the Validation of Alternative Methods (ICCVAM) for the UN GHS classification system, but it was not considered useful at that time to be used for regulatory purposes for the evaluation of the serious eye damage/eye irritation potential of chemicals, due to the lack of sufficient data for Cat 2 chemicals (ICCVAM 2010).…”

Section: Discussionmentioning

confidence: 99%

Retrospective analysis of the Draize test for serious eye damage/eye irritation: importance of understanding the in vivo endpoints under UN GHS/EU CLP for the development and evaluation of in vitro test methods

Adriaens¹,

Barroso

Eskes

et al. 2013

Arch Toxicol

View full text Add to dashboard Cite

For more than two decades, scientists have been trying to replace the regulatory in vivo Draize eye test by in vitro methods, but so far only partial replacement has been achieved. In order to better understand the reasons for this, historical in vivo rabbit data were analysed in detail and resampled with the purpose of (1) revealing which of the in vivo endpoints are most important in driving United Nations Globally Harmonized System/European Union Regulation on Classification, Labelling and Packaging (UN GHS/EU CLP) classification for serious eye damage/eye irritation and (2) evaluating the method’s within-test variability for proposing acceptable and justifiable target values of sensitivity and specificity for alternative methods and their combinations in testing strategies. Among the Cat 1 chemicals evaluated, 36–65 % (depending on the database) were classified based only on persistence of effects, with the remaining being classified mostly based on severe corneal effects. Iritis was found to rarely drive the classification (<4 % of both Cat 1 and Cat 2 chemicals). The two most important endpoints driving Cat 2 classification are conjunctiva redness (75–81 %) and corneal opacity (54–75 %). The resampling analyses demonstrated an overall probability of at least 11 % that chemicals classified as Cat 1 by the Draize eye test could be equally identified as Cat 2 and of about 12 % for Cat 2 chemicals to be equally identified as No Cat. On the other hand, the over-classification error for No Cat and Cat 2 was negligible (<1 %), which strongly suggests a high over-predictive power of the Draize eye test. Moreover, our analyses of the classification drivers suggest a critical revision of the UN GHS/EU CLP decision criteria for the classification of chemicals based on Draize eye test data, in particular Cat 1 based only on persistence of conjunctiva effects or corneal opacity scores of 4. In order to successfully replace the regulatory in vivo Draize eye test, it will be important to recognise these uncertainties and to have in vitro tools to address the most important in vivo endpoints identified in this paper.

show abstract

Using the Cytosensor Microphysiometer to Assess Ocular Toxicity

et al. 2014

View full text Add to dashboard Cite

Measuring in vitro cytotoxicity is one method currently used to estimate damage to the eye after chemical exposure. The Cytosensor Microphysiometer method evaluates cytotoxicity by measuring the test material-induced reduction in the metabolic rate of L929 cells. Changes in metabolic rate are measured indirectly as a function of changes in the extracellular acidification rate of the cells. During exposure to increasing concentrations of a cytotoxic material, there is a decrease in the release of acid byproducts into the surrounding medium as the cells die. These acidic metabolic byproducts cause a measurable change in the pH of a lightly buffered medium, which can be measured by the Cytosensor Microphysiometer. The change in the pH of the medium over time is then converted into a metabolic rate estimate for the cells. The endpoint measurement from the assay is the metabolic rate decline of 50%, the MRD50 value (in units of mg/ml).

show abstract

An evaluation of five potential alternatives in vitro to the rabbit eye irritation test in vivo

Cited by 57 publications

References 8 publications

Soaps and Detergents: Alternatives to Animal Eye Irritation Tests

Soaps and Detergents: Alternatives to Animal Eye Irritation Tests

Retrospective analysis of the Draize test for serious eye damage/eye irritation: importance of understanding the in vivo endpoints under UN GHS/EU CLP for the development and evaluation of in vitro test methods

Using the Cytosensor Microphysiometer to Assess Ocular Toxicity

Contact Info

Product

Resources

About