The Bovine Corneal Opacity and Permeability Test in Routine Ocular Irritation Testing and its Improvement within the Limits of OECD Test Guideline 437

Abstract

Data on eye irritation are generally needed for the hazard identification of chemicals. As the Bovine Corneal Opacity and Permeability (BCOP) test has been accepted by many regulatory agencies for the identification of corrosive and severe ocular irritants since September 2009 (OECD Test Guideline 437, TG 437), we evaluated this alternative method for routine testing at BASF. We demonstrated our technical proficiency by testing the reference standards recommended in TG 437, and 21 additional materials with published BCOP and in vivo data. Our results matched the published in vitro data very well, but with some intentionally selected false negatives (FNs) and false positives (FPs), the concordance was 77% (24/31), with FN and FP rates of 20% (2/10) and 24% (5/21), respectively. In addition, we tested 21 in-house materials, demonstrating the utility of the BCOP assay for our own test material panel. Histopathological assessment of the corneas by light microscopy was also conducted, as this was suggested as a means of improving the identification of FNs. The histopathology corrected the classification of some FNs, but also increased the number of FPs. Parallel to the test method evaluation, we compared three new opacitometer models with the current standard device. We recommend the use of an opacitometer developed in our BASF laboratory, which has certified components and electronic data storage, resulting in what we consider to be excellent sensitivity, stability and reproducibility.

Eye irritation testing of nanomaterials using the EpiOcular™ eye irritation test and the bovine corneal opacity and permeability assay

“…In the present study, histopathological evaluation of the corneas submitted to the BCOP assay was performed to corroborate the outcome of this assay and potentially to contribute to defining mechanisms of eye irritancy of the tested NMs. In an earlier study investigating a broad spectrum of non-nanosized materials in the BCOP assay, histopathological assessment of the corneas corrected the classification of some false negatives, but also increased the overall number of false positives [ 26 ].…”

“…All 23 test materials were submitted to a 2-tier non-animal testing strategy composed of the EpiOcular™ Eye Irritation Test (EpiOcular™-EIT; OECD TG 492) and the Bovine Corneal Opacity and Permeability (BCOP; OECD TG 437) assay including histopathological evaluation of the cornea [ 25 , 26 ]. Thereby, the present study further aimed at investigating the usefulness of this testing strategy for the hazard assessment and categorization of NMs.…”

Applicability of in vitro tests for skin irritation and corrosion to regulatory classification schemes: Substantiating test strategies with data from routine studies

“…One of eight corrosive materials was underpredicted in the SCT. This alkoxylated aliphatic alcohol was however also incorrectly classified as negative in the SIT in this study, and in the Bovine Corneal Opacity and Permeability assay (BCOP) (Schrage et al, 2011), the hen's egg chorioallantoic membrane test (HET-CAM; unpublished BASF data), and the EpiOcular assay . Whether this material is corrosive in humans is not known.…”

Imprinted Contact Lenses for Ocular Administration of Antiviral Drugs

“…The tests were carried out using cornea and sclera from both the bovine and porcine source. Bovine tissues are recommended as an alternative to in vivo animal tests of ocular tolerance and permeability to new substances [59]. Nevertheless, porcine eye tissues resemble better the structure of human ones in terms of composition and thickness [60].…”