Adjustment of a no expected sensitization induction level derived from Bayesian network integrated testing strategy for skin sensitization risk assessment.

Adjustment of a no expected sensitization induction level derived from Bayesian network integrated testing strategy for skin sensitization risk assessment. J Toxicol Sci. 2020;45(1):57-67 Authors: Otsubo Y, Nishijo T, Mizumachi H, Saito K, Miyazawa M, Sakaguchi H Abstract Skin sensitization is a key adverse effect to be addressed during hazard identification and risk assessment of chemicals, because it is the first step in the development of allergic contact dermatitis. Multiple non-animal testing strategies incorporating in vitro tests and in silico tools have achieved good predictivities when compared with murine local lymph node assay (LLNA). The binary test battery of KeratinoSensTM and h-CLAT could be used to classify non-sensitizers as the first part of bottom-up approach. However, the quantitative risk assessment for sensitizing chemicals requires a No Expected Sensitization Induction Level (NESIL), the dose not expected to induce skin sensitization in humans. We used Bayesian network integrated testing strategy (BN ITS-3) for chemical potency classification. BN ITS-3 predictions were performed without a pre-processing step (selecting data from their physic-chemical applicability domains) or post-processing step (Michael acceptor chemistry correction), neither of which necessarily improve prediction accuracy. For chemicals within newly defined applicability domain, all under-predictions fell within one potency class when compa...
Source: Journal of Toxicological Sciences - Category: Toxicology Tags: J Toxicol Sci Source Type: research