Eye irritation: Reference chemicals data bank

Bagley, Daniel M.; Botham, Philip A.; Gardner, John R.; Holland, G.; Kreiling, Reinhard; Lewis, Richard; Stringer, D.A.; Walker, A.P.

doi:10.1016/0887-2333(92)90059-z

Cited by 60 publications

(21 citation statements)

References 2 publications

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“…(1) the Eye Irritation Reference Chemicals Data Bank (ECETOC) (Bagley et al 1992a, 1999a; ECETOC 1998), (2) the database from ZEBET (Spielmann et al 1996), and (3) the database from Laboratoire National de la Santé (LNS) (Gautheron et al 1992). Before starting exploratory data analysis, a quality check of the Draize eye test data was performed.…”

Section: Methodsmentioning

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

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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.

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Section: Methodsmentioning

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

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“…Table 2 presents in vivo and in vitro information of benzalkonium chloride found in the literature. Draize scores indicate that out of the possible 110 points, 1% BAC produces 56 points, 5% BAC produces 84 points and 10% BAC produces 108 points (30,31). The reported EC 50 values evaluated by the MTT test for primary cells of rabbit corneal epithelium vary from 0.0005 to 0.0008% (w/v) (13,15,17).…”

mentioning

confidence: 96%

Comparison of an Immortalized Human Corneal Epithelial Cell Line and Rabbit Corneal Epithelial Cell Culture in Cytotoxicity Testing

Huhtala

Mannerström

Alajuuma

et al. 2002

Journal of Ocular Pharmacology and Therapeutics

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The cytotoxicity of benzalkonium chloride (BAC) and disodium edetate (EDTA) was evaluated in vitro in rabbit corneal epithelial primary cells and in the immortalized human corneal epithelial cell line SV40. Cell injury was assessed by lactate dehydrogenase (LDH) leakage and by reduction of the tetrazolium salt WST-1 to formazan by mitochondrial metabolic activity. Cell cultures were exposed to test compounds both in serum-free and in serum-containing medium. Although WST-1 and LDH tests measured different physiological endpoints, they yielded comparable results. However, the LDH test seemed less reliable due to great variation. The use of serum was found to result in lower toxicity of the compounds in both tests. The rabbit primary cell culture and the human corneal cell line were quite similar in their responses to BAC and EDTA. The human cell line is a promising in vitro alternative in oculotoxicity testing.

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“…Common chemical classes covered by this definition were hydrocarbons, alcohols, ethers, esters, ketones, amides, unreactive halogenated compounds, unreactive aromatic compounds and aprotic polar chemicals. Data on 38 neutral organics taken from the reference databank of eye irritation data published by ECETOC (European Centre for Ecotoxicology and Toxicology) (Bagley et al, 1992) together with 8 chemicals drawn from work by Jacob and Martens (1989) was analysed using principal components analysis (PCA). The mechanistic hypothesis underlying this (Q)SAR was summarized as follows.…”

mentioning

confidence: 99%

Guidance Document on the Validation of (Quantitative) Structure-Activity Relationship [(Q)SAR] Models

2014

OECD Series on Testing and Assessment

163

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Eye irritation: Reference chemicals data bank

Cited by 60 publications

References 2 publications

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

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

Comparison of an Immortalized Human Corneal Epithelial Cell Line and Rabbit Corneal Epithelial Cell Culture in Cytotoxicity Testing

Guidance Document on the Validation of (Quantitative) Structure-Activity Relationship [(Q)SAR] Models

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