Table 4.

Comparison of Intermediate Tier Functional and Selected ToxCast HTS Assay Findings

Compound/ Descriptor		Rat Aortic Explant	Rat Whole Embryo	Zebrafish Embryo	Bioseek ToxCast HTS Assay Subset	Tanguay ZF ToxCast HTS Assay Subset	NHEERL ZF 144hpf_ TERATOSCORE_up
Assay Contribution to Embryonic Vascular Disruption MoA		3-D ex vivo primary culture, microvessel outgrowth (reflective of angiogenesis)	Intact organism, embryonic and vascular development (including placental)	Intact organism, embryonic and vascular development (chorion-on)	Human primary cell co-cultures, includes molecular regulators endpoints for vasculogenesis and angiogenesis	High throughput intact zebrafish developmental assay (dechorionated)	Medium throughput intact zebrafish developmental assay (chorion-on)
5HPP-33	Response Potency (μM)	1.28	21.2	3.41	Minimum AC50 = 2.90	Active in two assay endpoints. AC50 = 26.2 (Increased mortality), 27.1 (Activity score)	4.44
					25th Percentile = 10.87
					Median AC50 = 15.2
	Outcome Summary	Disorganized/ degenerate microvessel outgrowth	Embryo lethality	Embryo lethality	Broad activity, anti-proliferative to endothelial cells, cell-cell signaling effects	Embryo lethality, decreased activity	Embryo lethality
TNP-470	Response Potency (μM)	0.018	0.038	0.032	Minimum AC50 = 0.001	Minimum AC50 = 0.003	Not active
					25th Percentile = 0.45	25% Percentile = 0.009
					Median AC50 = 6.2	Median AC50 = 0.026
	Outcome Summary	Stunted microvessel outgrowth, otherwise normal morphology	Dysmorphogenesis, primarily caudal extension defects and abnormal somite patterning	Dysmorphogenesis, primarily caudal extension defects and abnormal somite patterning	Anti-proliferative to endothelial cells, T cells and fibroblasts. Anti-inflammatory, immunomodulatory, and tissue remodeling activity.	Dysmorphogenesis: Caudal fin, axial, pericardial edema, yolk sac defects, eye and jaw defects	Not active