A proposed eye irritation testing strategy to reduce and replace in vivo studies using Bottom–Up and Top–Down approaches

Scott, Laurie; Eskes, Chantra; Hoffmann, Sebastian; Adriaens, Els; Alépée, Nathalie; Bufo, Monica; Clothier, Richard H.; Facchini, Davide; Faller, Claudine; Guest, Robert; Harbell, John W.; Hartung, Thomas; Kamp, Hennicke; Varlet, Béatrice Le; Méloni, Marisa; Maiello, Pauline; Osborne, Rosemarie; Pape, Wolfgang; Pfannenbecker, U.; Prinsen, M.K.; Seaman, Christopher; Spielmann, Horst; Stokes, William S.; Trouba, Kevin J.; Berghe, C. Van den; Goethem, Freddy Van; Vassallo, Marco; Vinardell, M. Pilar; Zuang, Valérie

doi:10.1016/j.tiv.2009.05.019

Cited by 196 publications

(140 citation statements)

References 24 publications

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“…However, no ex vivo and in vitro test methods have the performance to replace fully the Draize‐EIT that has been adopted for regulatory purposes. Therefore, a tiered approach of combining several test methods that used different complementary indicators was proposed (Scott et al ., 2010). In ex vivo test methods such as the bovine corneal opacity permeability and isolated chicken eye tests, the degree of tissue damage based on change in corneal opacity, corneal permeability of fluorescein and thickness of cornea was utilized as an indicator.…”

Section: Introductionmentioning

confidence: 99%

Predictive performance of the Vitrigel‐eye irritancy test method using 118 chemicals

Yamaguchi

Kojima²,

Takezawa

2015

J of Applied Toxicology

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We recently developed a novel Vitrigel‐eye irritancy test (EIT) method. The Vitrigel‐EIT method is composed of two parts, i.e., the construction of a human corneal epithelium (HCE) model in a collagen vitrigel membrane chamber and the prediction of eye irritancy by analyzing the time‐dependent profile of transepithelial electrical resistance values for 3 min after exposing a chemical to the HCE model. In this study, we estimated the predictive performance of Vitrigel‐EIT method by testing a total of 118 chemicals. The category determined by the Vitrigel‐EIT method in comparison to the globally harmonized system classification revealed that the sensitivity, specificity and accuracy were 90.1%, 65.9% and 80.5%, respectively. Here, five of seven false‐negative chemicals were acidic chemicals inducing the irregular rising of transepithelial electrical resistance values. In case of eliminating the test chemical solutions showing pH 5 or lower, the sensitivity, specificity and accuracy were improved to 96.8%, 67.4% and 84.4%, respectively. Meanwhile, nine of 16 false‐positive chemicals were classified irritant by the US Environmental Protection Agency. In addition, the disappearance of ZO‐1, a tight junction‐associated protein and MUC1, a cell membrane‐spanning mucin was immunohistologically confirmed in the HCE models after exposing not only eye irritant chemicals but also false‐positive chemicals, suggesting that such false‐positive chemicals have an eye irritant potential. These data demonstrated that the Vitrigel‐EIT method could provide excellent predictive performance to judge the widespread eye irritancy, including very mild irritant chemicals. We hope that the Vitrigel‐EIT method contributes to the development of safe commodity chemicals. Copyright © 2015 The Authors. Journal of Applied Toxicology published by John Wiley & Sons Ltd.

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Section: Introductionmentioning

confidence: 99%

Predictive performance of the Vitrigel‐eye irritancy test method using 118 chemicals

Yamaguchi

Kojima²,

Takezawa

2015

J of Applied Toxicology

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“…However, the use of alternative methods is still desirable no single assay being able to correctly predict the full spectrum of the UN GHS categories (Cat 1, serious, irreversible eye damage vs. Cat 2A, 2B reversible eye irritation) and thus, cannot fully replace the in vivo Draize eye irritation test (Lotz et al, 2016). Therefore, the combination of the BCOP assay with other internationally accepted test methods in a tiered testing strategy is suggested to allow the detailed and structured investigation of eye irritation potential that might be implemented in future (Kolle et al, 2016;Scott et al, 2010).…”

Section: Discussionmentioning

confidence: 99%

Biocompatibility and characterization of polyglycerol-based thermoresponsive nanogels designed as novel drug-delivery systems and their intracellular localization in keratinocytes

et al. 2017

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(2017) Biocompatibility and characterization of polyglycerol-based thermoresponsive nanogels designed as novel drug-delivery systems and their intracellular localization in keratinocytes, Nanotoxicology, 11:2, 267-277, DOI: 10.1080/17435390.2017 ABSTRACTNovel nanogels that possess the capacity to change their physico-chemical properties in response to external stimuli are promising drug-delivery candidates for the treatment of severe skin diseases. As thermoresponsive nanogels (tNGs) are capable of enhancing penetration through biological barriers such as the stratum corneum and are taken up by keratinocytes of human skin, potential adverse consequences of their exposure must be elucidated. In this study, tNGs were synthesized from dendritic polyglycerol (dPG) and two thermoresponsive polymers. tNG_dPG_tPG are the combination of dPG with poly(glycidyl methyl ether-co-ethyl glycidyl ether) (p(GME-co-EGE)) and tNG_dPG_pNIPAM the one with poly(N-isopropylacrylamide) (pNIPAM). Both thermoresponsive nanogels are able to incorporate high amounts of dexamethasone and tacrolimus, drugs used in the treatment of severe skin diseases. Cellular uptake, intracellular localization and the toxicological properties of the tNGs were comprehensively characterized in primary normal human keratinocytes (NHK) and in spontaneously transformed aneuploid immortal keratinocyte cell line from adult human skin (HaCaT). Laser scanning confocal microscopy revealed fluorescently labeled tNGs entered into the cells and localized predominantly within lysosomal compartments. MTT assay, comet assay and carboxy-H2DCFDA assay, demonstrated neither cytotoxic or genotoxic effects, nor any induction of reactive oxygen species of the tNGs in keratinocytes. In addition, both tNGs were devoid of eye irritation potential as shown by bovine corneal opacity and permeability (BCOP) test and red blood cell (RBC) hemolysis assay. Therefore, our study provides evidence that tNGs are locally well tolerated and underlines their potential for cutaneous drug delivery. ARTICLE HISTORY

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“…The tiered approach of several in vitro assays combined was proposed in order to estimate the irritation potential for a wide range of chemical classes (Hagino et al, 2008;Mc Namee et al, 2009;Scott et al, 2009). For these reasons, ECVAM conducted a retrospective validation of cytotoxicity or cell function based assays (Neutral Red Release: NRR, Red Blood Cell: RBC, Fluorescein Leakage: FL, Cytocensor Microphysiometer: CM) .…”

Section: Discussionmentioning

confidence: 99%

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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A proposed eye irritation testing strategy to reduce and replace in vivo studies using Bottom–Up and Top–Down approaches

Cited by 196 publications

References 24 publications

Predictive performance of the Vitrigel‐eye irritancy test method using 118 chemicals

Predictive performance of the Vitrigel‐eye irritancy test method using 118 chemicals

Biocompatibility and characterization of polyglycerol-based thermoresponsive nanogels designed as novel drug-delivery systems and their intracellular localization in keratinocytes

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

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