Test No. 467: Defined Approaches for Serious Eye Damage and Eye Irritation

,

doi:10.1787/28fe2841-en

Cited by 6 publications

(2 citation statements)

References 12 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Hence, our method combines the advantageous features of STE (i.e., simplicity and high throughput) with the predictive potential of more complex organotypic eye models to differentiate category 1 and 2 eye irritants. The probability-based eye irritation testing approach presented here is closely aligned with the principles outlined in the newly established OECD Test Guideline 467, "Defined Approaches for Serious Eye Damage and Eye Irritation" [29,30]. This guideline underscores the challenge of identifying eye irritation potential due to the often unknown modes of action for many chemicals, which renders single tests insufficient.…”

Section: Combined Probability Of Digitized Readouts From Apoptosis An...mentioning

confidence: 97%

Development of a Probability-Based In Vitro Eye Irritation Screening Platform

Arora,

Goralczyk,

Andra

et al. 2024

Bioengineering

View full text Add to dashboard Cite

Traditional eye irritation assessments, which rely on animal models or ex vivo tissues, face limitations due to ethical concerns, costs, and low throughput. Although numerous in vitro tests have been developed, none have successfully reconciled the need for high experimental throughput with the accurate prediction of irritation potential, attributable to the complexity of irritation mechanisms. Simple cell models, while suitable for high-throughput screening, offer limited mechanistic insights, contrasting with more physiologically relevant but less scalable complex organotypic corneal tissue constructs. This study presents a novel strategy to enhance the predictive accuracy of screening-compatible simple cell models in eye irritation testing. Our method combines the results of two in vitro assays—cell apoptosis and nociceptor (TRPV1) activation—using micropatterned chips to partition human corneal epithelial cells into numerous discrete small populations. Following exposure to test compounds, we measure apoptosis and nociceptor activation responses. The large datasets collected from the cell micropatterns facilitate binarization and statistical fitting to calculate a mathematical probability, which assesses the compound’s potential to cause eye irritation. This method potentially enables the amalgamation of multiple mechanistic readouts into a singular index, providing a more accurate and reliable prediction of eye irritation potential in a format amenable to high-throughput screening.

show abstract

Section: Combined Probability Of Digitized Readouts From Apoptosis An...mentioning

confidence: 97%

Development of a Probability-Based In Vitro Eye Irritation Screening Platform

Arora,

Goralczyk,

Andra

et al. 2024

Bioengineering

View full text Add to dashboard Cite

show abstract

“…in silico , in chemico , and/or in vitro data) with fixed data interpretation procedures, has facilitated the use of in vitro methods or NAMs-based approaches within a regulatory context. DAs for serious eye damage and eye irritation, and for skin sensitisation, have been outlined within their own OECD test guidelines (TGs) (for example, OECD TG 467, 6 497 7 ) and are now widely used and referred to in many regulations worldwide. Here, the historical animal tests addressed very specific chemically induced adverse health effects seen in humans (corrosion, irritation or skin sensitisation) and the data from the animal tests were subsequently used to determine whether the NAMs approaches were fit-for-purpose 8–11 ).…”

Section: Technical and Scientific Barriersmentioning

confidence: 99%

New approach methodologies (NAMs): identifying and overcoming hurdles to accelerated adoption

Sewell,

Alexander-White,

Brescia

et al. 2024

Toxicology Research

View full text Add to dashboard Cite

New approach methodologies (NAMs) can deliver improved chemical safety assessment through the provision of more protective and/or relevant models that have a reduced reliance on animals. Despite the widely acknowledged benefits offered by NAMs, there continue to be barriers that prevent or limit their application for decision-making in chemical safety assessment. These include barriers related to real and perceived scientific, technical, legislative and economic issues, as well as cultural and societal obstacles that may relate to inertia, familiarity, and comfort with established methods, and perceptions around regulatory expectations and acceptance. This article focuses on chemical safety science, exposure, hazard, and risk assessment, and explores the nature of these barriers and how they can be overcome to drive the wider exploitation and acceptance of NAMs. Short-, mid- and longer-term goals are outlined that embrace the opportunities provided by NAMs to deliver improved protection of human health and environmental security as part of a new paradigm that incorporates exposure science and a culture that promotes the use of protective toxicological risk assessments.

show abstract

Evolution of the Use of Toxicological Data for Evaluating Chemical Safety and Occupational Exposure Limits

Tyshenko,

Willhite,

Levy

et al. 2023

Patty's Toxicology

View full text Add to dashboard Cite

Conventional approaches to setting occupational exposure limits (OELs) by regulatory agencies are reviewed. Example OEL derivations show how guidance values are developed in practice. OEL values from various agencies may differ. We present a framework to help select the most appropriate OELs in practice. Use of the framework is demonstrated by OELs for n ‐hexane, a data‐rich chemical and methamphetamine, a data‐poor chemical. Looking forward, “New Approach Methodologies” (NAMs) continue to develop generating chemical toxicological data via high‐throughput in vitro screening assays, computational toxicology, and other methods. NAMs for chemical risk assessment have received support from organizations such as the Organization for Economic Cooperation and Development (OECD), which has validated a number of alternative test methods. Seven NAMs case studies for chemical screening and priority‐setting are presented. Future applications of NAMs in toxicological risk assessment and occupational environments are reviewed using a four‐level tiered testing framework previously proposed by Andersen and colleagues. The use of NAMs provides increased throughput, improved mechanistic understanding in toxicological testing and reduced costs compared to traditional mammalian toxicity testing. The formal application of NAMs in setting OELs is an area of ongoing development, and more widespread application of NAMs in deriving OELs is expected in the future.

show abstract

Test No. 467: Defined Approaches for Serious Eye Damage and Eye Irritation

Cited by 6 publications

References 12 publications

Development of a Probability-Based In Vitro Eye Irritation Screening Platform

Development of a Probability-Based In Vitro Eye Irritation Screening Platform

New approach methodologies (NAMs): identifying and overcoming hurdles to accelerated adoption

Evolution of the Use of Toxicological Data for Evaluating Chemical Safety and Occupational Exposure Limits

Contact Info

Product

Resources

About