Alternative methods for eye irritation testing: transition in toxicological safety testing through a multi-level perspective

Abstract

Throughout the years, animal models have been used extensively for toxicological safety assessment. Alternative methods that do not require animals have been developed extensively, but are adopted scarcely in spite of scientific, economical and societal deficiencies of animal models. This is believed to be part of a transition problem, which refers to the structural reorientation of an entire sector, in this case the life sciences. One example where technological change did happen is in the field of eye irritation testing. The Draize eye irritation test using live rabbits has been (partially) replaced in OECD guidelines with the Isolated Chicken Eye (ICE) test and the Bovine Corneal Opacity and Permeability (BCOP) test. For this reason, the ICE and BCOP test serve as a case study to how and why they were successful in replacing the Draize test. The main research question is:

Which sociotechnical factors influenced the successful technological development and regulatory validation of the BCOP and ICE test methods for (partially) replacing the Draize eye irritation test in the field of toxicological safety testing?

The multi-level perspective (MLP) on transitions is employed as an analytical framework to analyze the case study according to the different levels (i.e. niche, regime and landscape) of the MLP. Data is obtained through literature review and interviews with twelve international experts in the field of toxicology. The results indicate that a globally operating, multi-actor network forms the basis of the safety-testing regime. It can be concluded that the safety-testing regime has undergone a transformation path: moderate landscape pressure in the form an effective anti-Draize campaign happened at a moment when the ICE and BCOP niche-innovations had not been sufficiently developed to fully substitute the Draize test. The safety-testing regime was disrupted enough for regime actors, industry and public authorities in particular, to pick up on the niche innovation. They responded by modifying the innovation activities that were needed to get organotypic methods validated for use in formal regulatory safety-assessment. From the moment that the first validation studies took place, the ICE and BCOP test have coexisted in symbiotic fashion next to the Draize test. Cumulative adjustments and reorientations in the safety-testing regime had to take place to validate the ICE and BCOP test: legislation was created that forced the development of alternatives methods. Industry in collaboration with public authorities and public research support actors started extensive validation programs, which have improved considerably through learning, by including prediction models, protocols and a tiered testing strategy. Under the landscape pressure of globalization, the EU and US saw increased collaboration that resulted in a retrospective validation study, which paved the way for US federal endorsement and OECD acceptance of the ICE and BCOP test.