CON4EI: CONsortium for in vitro Eye Irritation testing strategy

This paper presents some results of a joint research project, sponsored by Defra and conducted by FRAME and Liverpool John Moores University, on the status of alternatives to animal testing with regard to the European Union REACH (Registration, Evaluation and Authorisation of Chemicals) system for the safety testing and risk assessment of chemicals. The project covered all the main toxicity endpoints associated with REACH. This paper focuses on the use of alternative (non-animal) methods (both in vitro and in silico) for eye irritation testing. The manuscript reviews numerous in vitro tests and their possible collation into test batteries, in silico models and a refined in vivo method (the low volume eye test), before combining the use of all these methods into an integrated testing strategy. The aim of this strategy is a reduction in the number of animal tests which would need to be performed in the process of fulfilling the REACH system criteria; this would also lead to a lowering of the number of animals required in compliance with the REACH system requirements.

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An Integrated Decision-tree Testing Strategy for Eye Irritation with Respect to the Requirements of the EU REACH Legislation

Alternatives to Laboratory Animals ◽

10.1177/026119290803601s09 ◽

2008 ◽

Vol 36 (1_suppl) ◽

pp. 111-122 ◽

Cited By ~ 2

Author(s):

Christina Grindon ◽

Robert Combes ◽

Mark T.D. Cronin ◽

David W. Roberts ◽

John F. Garrod

Keyword(s):

In Silico ◽

In Vitro Tests ◽

The European Union ◽

Testing Strategy ◽

Animal Testing ◽

Joint Research ◽

Eye Irritation ◽

Joint Research Project

This paper presents some results of a joint research project, sponsored by Defra and conducted by FRAME and Liverpool John Moores University, on the status of alternatives to animal testing with regard to the European Union REACH (Registration, Evaluation and Authorisation of Chemicals) system for the safety testing and risk assessment of chemicals. The project covered all the main toxicity endpoints associated with REACH. This paper focuses on the use of alternative (non-animal) methods (both in vitro and in silico) for eye irritation testing. The manuscript reviews numerous in vitro tests and their possible collation into test batteries, in silico models and a refined in vivo method (the low volume eye test), before combining the use of all these methods into an integrated testing strategy. The aim of this strategy is a reduction in the number of animal tests which would need to be performed in the process of fulfilling the REACH system criteria; this would also lead to a lowering of the number of animals required in compliance with the REACH system requirements.

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Skin and Eye Irritation Assessment of Oil Palm (Elaeis guineensis) Leaf Extract for Topical Application

International Journal of Toxicology ◽

10.1177/1091581818773979 ◽

2018 ◽

Vol 37 (4) ◽

pp. 335-343 ◽

Cited By ~ 1

Author(s):

Nor Zuliana Yusof ◽

Siti Salwa Abd Gani ◽

Zafarizal Aldrin Azizul Hasan ◽

Zainab Idris

Keyword(s):

Oil Palm ◽

Safety Assessment ◽

Leaf Extract ◽

Elaeis Guineensis ◽

Dermal Fibroblasts ◽

Hazard Identification ◽

Eye Irritation ◽

Test Guideline ◽

Oecd Test Guideline

Many types of phytochemicals have been found to be present in oil palm leaf and could potentially be used as functional ingredients for skincare product. However, as of today, there is no published report on hazard identification and safety assessment of oil palm ( Elaeis guineensis) leaf extract (OPLE), particularly on skin and eye irritation. In this study, potential hazard of OPLE on skin and eye irritation was evaluated as an initial step to the safety assessment of OPLE. In vitro cell viability study of OPLE on normal human dermal fibroblasts showed that OPLE was nontoxic to the cells with percentage viability more than 90% after 24 and 48 hours of incubation. Skin irritation potential of OPLE was evaluated using in vitro SkinEthic reconstructed human epidermis (RHE) model (Organization for Economic Cooperation and Development [OECD] Test Guideline 439, 2015), while eye irritation potential was evaluated using in vitro SkinEthic Human corneal epithelium (HCE) model (OECD test guideline 492, 2017). Hazard identification results showed that OPLE at 1%, 5%, and 10% (wt/wt) was classified as nonirritant to the skin and eye where mean tissue viabilities of SkinEthic RHE and SkinEthic HCE were more than 50% and 60%, respectively. Therefore, we recommend a further safety assessment, such as human patch testing, to confirm the nonirritant of OPLE.

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Human induced pluripotent stem cell (iPSC)-derived cardiomyocytes as an in vitro model in toxicology: strengths and weaknesses for hazard identification and risk characterization

Expert Opinion on Drug Metabolism & Toxicology ◽

10.1080/17425255.2021.1894122 ◽

2021 ◽

Author(s):

Sarah D. Burnett ◽

Alexander D. Blanchette ◽

Weihsueh A. Chiu ◽

Ivan Rusyn

Keyword(s):

Stem Cell ◽

Pluripotent Stem Cell ◽

In Vitro Model ◽

Induced Pluripotent Stem Cell ◽

Hazard Identification ◽

Risk Characterization ◽

Vitro Model ◽

Induced Pluripotent

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Application of the EYTEX™ System to the Evaluation of Cosmetic Products and their Ingredients

Alternatives to Laboratory Animals ◽

10.1177/026119299202000120 ◽

1992 ◽

Vol 20 (1) ◽

pp. 146-163

Author(s):

Francis H. Kruszewski ◽

Laura H. Hearn ◽

Kyle T. Smith ◽

Janice J. Teal ◽

Virginia C. Gordon ◽

...

Keyword(s):

Double Blind ◽

Eye Irritation ◽

Ocular Irritation ◽

Rabbit Eye ◽

Wide Range ◽

High Concentrations ◽

Alkaline Membrane ◽

Positive Agreement

465 cosmetic product formulations and raw ingredients were evaluated with the EYTEX™ system to determine the potential of this in vitro alternative for identifying eye irritation potential. The EYTEX™ system is a non-animal, biochemical procedure developed by Ropak Laboratories, Irvine, CA, that was designed to approximate the Draize rabbit eye irritation assay for the evaluation of ocular irritation. Avon Products Inc. provided all the test samples, which included over 30 different product types and represented a wide range of eye irritancy. All the EYTEX™ protocols available at the time of this study were used. Samples were evaluated double-blind with both the membrane partition assay (MPA) and the rapid membrane assay (RMA). When appropriate, the standard assay (STD) and the alkaline membrane assay (AMA) were used, as well as specific, documented protocol modifications. EYTEX™ results were correlated with rabbit eye irritation data which was obtained from the historical records of Avon Products Inc. A positive agreement of EYTEX™ results with the in vivo assay was demonstrated by an overall concordance of 80%. The assay error was 20%, of which 18% was due to an overestimation of sample irritancy (false positives) and 2% was attributed to underestimation (false negatives). Overestimation error in this study was due in part to the inability of the protocols to accurately classify test samples with very low irritation potential. Underestimation of sample irritancy was generally associated with ethoxylated materials and high concentrations of specific types of surfactants. 100% sensitivity and 85% predictability were described by the data, indicating the efficiency of EYTEX™ in identifying known irritants. A specificity rate of 39% showed the EYTEX™ assay to be weak in discerning non-irritants. However, the EYTEX™ protocols used in this study were not designed to identify non-irritants. A compatibility rate of 99% proved the effectiveness of the EYTEX™ assay in accommodating a diversity of product types. The EYTEX™ system protocols, when used appropriately, can provide a conservative means of assessing the irritant potential of most cosmetic formulations and their ingredients.

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The EYTEX™ System and the Neutral Red Uptake Inhibition Assay in Cultured Hep G2 Cells as Alternative Methods for In Vivo Eye Irritation Following the EEC Protocol

Alternatives to Laboratory Animals ◽

10.1177/026119299001700406 ◽

1990 ◽

Vol 17 (4) ◽

pp. 325-333

Author(s):

Paul J. Dierickx ◽

Virginia C. Gordon

Keyword(s):

Neutral Red ◽

Alternative Methods ◽

Inhibition Assay ◽

Hep G2 ◽

Hep G2 Cells ◽

Eye Irritation ◽

Uptake Inhibition ◽

In Vitro Methods ◽

Neutral Red Uptake

The neutral red uptake inhibition assay and the EYTEX™ system were investigated as alternative methods for the assessment of eye irritation, determined according to the EEC protocol. The 17 test chemicals used were mainly organic solvents. The xenobiotics were applied to Hep G2 cells for 24 hours at different concentrations. Neutral red uptake inhibition was then measured. The results are expressed as the NI50 value, which is the concentration of test compound required to induce a 50% reduction in neutral red uptake. The same chemicals were also tested as coded samples by the EYTEX™ test according to the manufacturer's directions. A nearly identical quantitative correlation was found for both in vitro methods with corneal opacity scores: r = 0.84 for EYTEX™ scores and r = 0.83 for log NI50, expressed in μg/ml. Whilst these correlations are certainly not perfect, it is clear that both in vitro methods can be used as valuable prescreening methods.

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