United States regulatory requirements for skin and eye irritation testing

Abstract

Purpose: Eye and skin irritation test data are required or considered by chemical regulation authorities in the United States to develop product hazard labeling and/or to assess risks for exposure to skin-and eye-irritating chemicals. The combination of animal welfare concerns and interest in implementing methods with greater human relevance has led to development of nonanimal skin-and eye-irritation test methods. To identify opportunities for regulatory uses of nonanimal replacements for skin and eye irritation tests, the needs and uses for these types of test data at U.S. regulatory and research agencies must first be clarified. Methods:We surveyed regulatory and non-regulatory testing needs of U.S. Interagency Coordinating Committee on the Validation of Alternative Methods (ICCVAM) agencies for skin and eye irritation testing data. Information reviewed includes the type of skin and eye irritation data required by each agency and the associated decision context: hazard classification, potency classification, or risk assessment; the preferred tests; and whether alternative or non-animal tests are acceptable. Information on the specific information needed from non-animal test methods also was collected.Results: A common theme across U.S. agencies is the willingness to consider non-animal or alternative test methods. Sponsors are encouraged to consult with the relevant agency in designing Choksi et al.

Strategies to Develop a Suitable Formulation for Inflammatory Skin Disease Treatment

“…Normally, researchers select the dorsal skin of untreated normal healthy mice as the material. After at least three consecutive days of applying the selected formulation, researchers examine the skin color and histology results to clarify whether the selected formulation induced an irritation response [ 87 , 91 , 92 ]. However, the barrier function between untreated normal healthy skin and inflammatory skin is quite different.…”

In vitro reconstructed 3D corneal tissue models for ocular toxicology and ophthalmic drug development

“…It is largely accepted that in the foreseeable future, no single in vitro test method will fully replace the in vivo Draize eye irritation test to predict the full range of eye damage and irritation responses for different chemical classes (Balls et al 1999). However, combinations of alternative test methods within a tiered testing strategy such as the bottom-up and top-down approach may be able to fully replace the Draize eye test (Scott et al 2010;Choksi et al 2019). The top-down approach is used to identify severe irritants, and the bottom-up approach is used for the identification of non-irritating materials (Engelke et al 2013).…”

“…Eye irritation testing of all manufactured consumer products and their ingredients is an international regulatory requirement to ensure consumer safety (NIEHS and NIH 2007;UN 2017). An assessment of eye irritation is also a requirement for complying with regulatory legislation in the USA and abroad including the Registration, Evaluation, Authorization, and Restriction of Chemicals (REACH) regulation for the labeling of ingredients, the Classification, Labelling and Packaging (CLP) regulation, the EU Cosmetics Directive for the transport of chemicals, and the labeling of pesticides and household products (EC 2006;EU 2008;Barroso et al 2016;Choksi et al 2019).…”

Workshop on the validation and regulatory acceptance of innovative 3R approaches in regulatory toxicology – Evolution versus revolution

“…As mentioned, a survey on needs with respect to the various decision contexts would be helpful, and work is ongoing in that area (e.g. (Strickland et al, 2018), (Daniel et al, 2018), (Choksi et al, 2018) (Piersma et al 2018a), and focus on reliability.…”