Prevalidation of a new in vitro reconstituted human cornea model to assess the eye irritating potential of chemicals

Goethem, Freddy Van; Adriaens, Els; Alépée, Nathalie; Sträube, Frank; Wever, Bart De; Cappadoro, Marina; Catoire, Sophie; Hansen, Erik W.; Wolf, Armin; Vanparys, Philippe

doi:10.1016/j.tiv.2005.05.002

Cited by 97 publications

(56 citation statements)

References 14 publications

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“…The CVs of some chemicals could not be calculated due to a negative mean relative viability value obtained for one or more of the labs; however, the resulting CVs were less than 103%. The values obtained in this study were equivalent to other cytotoxicity based validation studies (4 to 124%) Van Goethem et al, 2006). In addition, correlation of relative viability between labs was analyzed by Spearman's rank-correlation test (Table 5).…”

Section: Discussionsupporting

confidence: 71%

“…Though the number of test chemicals was different between Van Goethem et al (2006) and our STE study, almost similar values were obtained. Therefore, the STE method has a high predictive capacity for predicting irritation category of chemicals.…”

Section: Discussionsupporting

confidence: 68%

“…Although a CV for SLS could not be calculated due to negative values of the relative viability, CVs of calcium thioglycolate and Tween 80 were less than 0.13 among three labs (Table 3). Van Goethem et al (2006) reported that CVs for 0.5% and 0.1% SLS as positive controls in a reconstituted human cornea model were 11% and 12%, respectively, among the four laboratories involved in the study. Our CVs for calcium thioglycolate and Tween 80 as standard chemicals were similar to those reported by Van Goethem et al (2006).…”

Section: Discussionmentioning

confidence: 99%

“…Van Goethem et al (2006) reported that CVs for 0.5% and 0.1% SLS as positive controls in a reconstituted human cornea model were 11% and 12%, respectively, among the four laboratories involved in the study. Our CVs for calcium thioglycolate and Tween 80 as standard chemicals were similar to those reported by Van Goethem et al (2006). Moreover, estimated eye irritation rankings of each standard chemical were completely consistent between the three labs.…”

Section: Discussionmentioning

confidence: 99%

“…These statistical values indicate a high correspondence between all laboratories at two concentrations. In the prevalidation efforts of the reconstituted human corneal model, Van Goethem et al (2006) found 1.000 (when relative viability cut-off value was 50%) or 0.880-1.000 (when relative viability cut-off value was 60%). Also, Brantom et al (1997) in a COLIPA internaevaluation of red blood cell viability among 7 laboratoreported in these prevalidation studies are comparable to the values we obtained in our STE study.…”

Section: Discussionmentioning

confidence: 99%

See 4 more Smart Citations

Inter-laboratory study of short time exposure (STE) test for predicting eye irritation potential of chemicals and correspondence to globally harmonized system (GHS) classification

et al. 2009

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-Short time exposure (STE) test using rabbit corneal cell line (SIRC) cells was developed as an alternative eye irritation test. STE test uses relative viability as the endpoint after cells are exposed to the test material at constant concentrations for 5 min. In this inter-laboratory study with 3 laboratories, 44 chemicals with a wide range of classes were evaluated for the transferability, between-lab reproducibility and predictive capacity of the STE test as an alternative eye irritation test. Globally harmonized sysin vivo data. Transferability was assessed using standard chemicals (sodium lauryl sulfate, calcium thioglycolate, andThe irritation category (Irritant or Non irritant) at each test concentration (5% and 0.05%) in STE test was --el (PM) based on the relative viability at two concentrations (5% and 0.05%) were highly correlated with the GHS ranks of non-irritant, category 1, and category 2, respectively (accuracy was 75.0% at all laboratories). These results suggest that the STE test possessed easy transferability, reproducibility, good predictive performance.

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Section: Discussionsupporting

confidence: 71%

Section: Discussionsupporting

confidence: 68%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Inter-laboratory study of short time exposure (STE) test for predicting eye irritation potential of chemicals and correspondence to globally harmonized system (GHS) classification

et al. 2009

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Contribution of the WNK1 kinase to corneal wound healing using the tissue‐engineered human cornea as an in vitro model

Desjardins

Couture

Germain

et al. 2019

J Tissue Eng Regen Med

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Damage to the corneal epithelium triggers important changes in the extracellular matrix (ECM) to which basal human corneal epithelial cells (hCECs) attach. These changes are perceived by integrin receptors that activate different intracellular signalling pathways, ultimately leading to re‐epithelialization of the injured epithelium. In this study, we investigated the impact of pharmacological inhibition of specific signal transduction mediators on corneal wound healing using both monolayers of hCECs and the human tissue‐engineered cornea (hTEC) as an in vitro 3D model. RNA and proteins were isolated from the wounded and unwounded hTECs to conduct gene profiling analyses and protein kinase arrays. The impact of WNK1 inhibition was evaluated on the wounded hTECs as well as on hCECs monolayers using a scratch wound assay. Gene profiling and protein kinase arrays revealed that expression and activity of several mediators from the integrin‐dependent signaling pathways were altered in response to the ECM changes occurring during corneal wound healing. Phosphorylation of the WNK1 kinase turned out to be the most striking activation event going on during this process. The inhibition of WNK1 by WNK463 reduced the rate of corneal wound closure in both the hTEC and hCECs grown in monolayer compared with their respective negative controls. WNK463 also reduced phosphorylation of the WNK1 downstream targets SPAK/OSR1 in wounded hTECs. These in vitro results allowed for a better understanding of the cellular and molecular mechanisms involved in corneal wound healing and identified WNK1 as a kinase important to ensure proper wound healing of the cornea.

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Ocular Toxicity

Eskes¹,

Vliet²,

Schäffer³

et al. 2014

Methods in Pharmacology and Toxicology

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Prevalidation of a new in vitro reconstituted human cornea model to assess the eye irritating potential of chemicals

Cited by 97 publications

References 14 publications

Inter-laboratory study of short time exposure (STE) test for predicting eye irritation potential of chemicals and correspondence to globally harmonized system (GHS) classification

Inter-laboratory study of short time exposure (STE) test for predicting eye irritation potential of chemicals and correspondence to globally harmonized system (GHS) classification

Contribution of the WNK1 kinase to corneal wound healing using the tissue‐engineered human cornea as an in vitro model

Ocular Toxicity

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