In Vitro Toxicology Models for Acute Eye and Skin Irritation Assessment

Abstract

Among the first in vitro methods to be developed were those targeted at replacing the Draize eye and skin tests. Public sentiment against the use of animals in research, pressure from animal welfare groups, and leadership by key cosmetics and personal care companies to meet corporate animal welfare mandates drove the development of these non-animal methods. Since acute irritation effects in the eye and skin are relatively simple in comparison to the complex toxicological effects observed in organ system responses after systemic exposures, the development of alternative assays for eye and skin irritation was relatively straightforward. The development of alternative test methods to predict eye and skin irritation included a number of common features and endpoints. In vivo, ocular and dermal epithelia are directly exposed to neat chemicals or undiluted formulations, and thus many of the in vitro test systems were designed model these exposures. Irritation responses typically occur locally at the site of chemical exposure in vivo resulting in cell damage and cell death. Accordingly, many of the in vitro methods are cell-based and rely on cell viability endpoints. In general, these alternative test methods fall into four categories; simple in vitro monolayer cell systems, ex vivo tissue or organ systems, complex in vitro reconstructed cell-based three dimensional tissue models, and a variety of artificial non-cell-based eye or skin models. Each assay has its special application and uses, and applicability domain, but also is limited in some manner from the in vivo experience. Overall, these in vitro and ex vivo assays may be used to predict eye or skin irritation, and some have been validated for regulatory classification and labeling purposes, but to date none of the assays provide adequate demonstrations of recovery. Furthermore, due to the specialization and limited applicability of each of the assays, current consensus suggests that no single in vitro method is likely to generate all of the required safety information needed. Thus, a combination of methods providing distinct endpoints may be utilized to meet industry needs for eye and skin irritation safety assessments. This chapter provides a review of current non-animal test methods used for regulatory classification and labeling purposes.