There is an increasing requirement for innovative toxicity test systems that are translational to humans yet allow reduction, refinement and replacement (3Rs) of animal use.It has been shown that "stand alone test models" are not sufficient for hazard assessment and combinatorial testing with multiple models (especially for Developmental and reproductive toxicology (DART)) is required to improve the potential hazard identification.Whereas cell culture systems have predictive value, they lack the multicellular or multi organ complexity and the complete life cycle of whole organisms, factors essential for prediction of DART.We introduce combinatorial strategy using zebra fish (Daniorerio) larvae, and nematodes (Caenorhabditiselegans) that enables identification of adverse outcome pathways (AOP) and Molecular initiating events (MIE) relevant for humans hazard identification and characterization.The test system has been applied in industry in the product development pipeline.Three novel gas treatment compounds have been assessed against an existing gas treatment compound, with known DART data in rodents.Reproductive toxicity effects in both C.elegans and zebrafish were only observed at high concentrations (100 μM and above) of the gas treatment compounds assessed in this study.These concentrations are unlikely to be reached in vivo in humans under conditions of use and therefore developmental effects are expected to be insignificant (if present at all) in humans.From the compounds tested, the existing gas treatment compound, which showed reproductive effects at high concentration only, was the most potent reproductive toxicant to nematodes and zebrafish.These results are in alignment with the reported test data for rodents,where indications of reproductive effects were only observed at high test concentrations.Furthermore observed responses are considered to be a consequence of maternal toxicity rather than a direct reproductive effect per se.Therefore, it is concluded that the other gas treatment compounds tested are unlikely to be developmental toxicants.