The HaCaT/THP-1 Cocultured Activation Test (COCAT) for skin sensitization: a study of intra-lab reproducibility and predictivity

Main Article Content

Chantra Eskes
Jennifer Hennen
https://orcid.org/0000-0003-0243-2782
Mario Schellenberger
https://orcid.org/0000-0002-6619-3955
Sebastian Hoffmann
https://orcid.org/0000-0002-3214-7678
Sabine Frey
Daniela Goldinger-Oggier
Niklas Peter
Erwin van Vliet
https://orcid.org/0000-0001-5747-3202
Brunhilde Blömeke
https://orcid.org/0000-0002-3625-0701

Abstract

The Cocultured Activation Test (COCAT) consists of cocultured HaCaT (human keratinocyte cell line) and THP-1 cells (surrogate of antigen presenting cells). Individually, these cell lines are used to address key event 2 and 3 of the skin sensitization Adverse Outcome Pathway (AOP). Their exposure in coculture was found to have the potential to increase their response to sensitizing chemicals, enable the detection of pro-haptens and support the identification of skin sensitization potency. The present study was undertaken to assess the predictive capacity of COCAT to both skin sensitization hazard and potency and to assess the intra-laboratory reproducibility of COCAT based on the blind testing of chemicals. Results showed a reproducibility between runs of 80 % for 15 coded chemicals. 100 % sensitivity (9/9), 75 % specificity (3/4) and 92.3 % accuracy (12/13) was found for skin sensitization hazard prediction, while the tests of two chemicals were inconclusive. Including additional chemicals tested during the optimization phase in addition to the blind tested chemicals, the skin sensitization UN GHS sub-categories were correctly predicted for 85.7 % (12/14) Sub-category 1A chemicals, 83.3 % (10/12) Sub-category 1B chemicals and 92.3 % (12/13) ‘No Category’ chemicals, resulting in an overall accuracy of 87.4 % (34/39). The present study shows the COCAT to be a promising method for the identification of skin sensitization hazard and potency sub-categorization according to the UN GHS classification.

Article Details

How to Cite
Eskes, C., Hennen, J., Schellenberger, M., Hoffmann, S., Frey, S., Goldinger-Oggier, D., Peter, N., van Vliet, E. and Blömeke, B. (2019) “The HaCaT/THP-1 Cocultured Activation Test (COCAT) for skin sensitization: a study of intra-lab reproducibility and predictivity”, ALTEX - Alternatives to animal experimentation. doi: 10.14573/altex.1905031.
Section
Articles

Most read articles by the same author(s)