Testing the effects of two different zebrafish exposure paradigms on transcriptomic-based chemical risk assessment using the flame retardant triphenyl phosphate.

In the zebrafish larval toxicity model, phenotypic changes induced by chemical exposure can potentially be explained and predicted by the analysis of gene expression changes at sub-phenotypic concentrations. The increase in knowledge of gene pathway-specific effects arising from the zebrafish transcriptomic model has the potential to enhance the role of the larval zebrafish as a component of Integrated Approaches to Testing and Assessment (IATA). In this paper, we compared the transcriptomic responses to triphenyl phosphate between 2 standard exposure paradigms, the Zebrafish Embryo Toxicity (ZET) and General and Behavioral Toxicity (GBT) assays. The ZET assay represents a developmental model with chemical exposure from 6 to 120 h post fertilization (hpf), which covers organogenesis, whereas the GBT represents a juvenile model with exposure from 72 to 120 hpf, which occurs post-organogenesis. This comparison demonstrates both similarities and differences between the 2 assays. Although both models identified similar xenobiotic metabolism pathways, the difference in exposure window length and the time of transcriptomic sampling between the 2 methods also yielded unique sets of affected pathways, demonstrating their complimentary nature. Both data sets support previously described effects of triphenyl phosphate on aquatic and mammalian systems. This work validates and strengthens the use of both exposure paradigms and continues to demonstrate that zebrafish larvae are a valuable tool in the context of IATA toward reduced reliance on the use of higher vertebrate derived data for chemical risk assessment.