Slide 1: A non-animal toolbox informed by pulmonary toxicity AOPs for human inhalation safety
SERS - Safety, Environmental & Regulatory Science | Unilever R&D Poster #121: A non-animal toolbox informed by pulmonary toxicity adverse outcome pathways (AOPs): a next-generation risk assessment (NGRA) approach for human inhalation safety Renato Ivan de Ávila, PhD Early Investigators Flash Present
Slide 2: Human-relevant strategy for selecting NAMs for lung toxicity NGRA
SERS - Safety, Environmental & Regulatory Science | Unilever R&D 2 Human-relevant strategy for selecting NAMs for lung toxicity NGRA Broad coverage of bioactivity readouts relevant to inhalation hazards which can provide in vitro PoDs Upper respiratory tract: MucilAir -HF Lower respiratory tract: Ep
Slide 3: In vitro PoDs were lower than predicted exposure for high-risk scenarios
SERS - Safety, Environmental & Regulatory Science | Unilever R&D 3 In general, for high-risk exposure-chemical scenarios in vitro PoDs were lower than the predicted exposure • The obtained PoDs were combined with exposure estimates to calculate BER values • BER is able to separate the low- and high-
Slide 4: Defining a safe threshold: animal testing versus non-animal NAMs
SERS - Safety, Environmental & Regulatory Science | Unilever R&D 4 Defining a safe threshold: animal testing versus non-animal NAMs • Traditional Margin of Safety (MoSanimal data for local lung effects) > 25* → low risk *Uncertainty safety factor of 25 to account for uncertainties related to intersp
Slide 5: Concluding remarks
SERS - Safety, Environmental & Regulatory Science | Unilever R&D 5 Concluding remarks • Strategy of selecting non-animal NAMs informed by AOPs associated with pulmonary toxicity can provide relevant biological coverage • Benchmarking decision outcomes provides an alternative to the traditional valid