Manufactured nanoparticles (MNP) rapidly undergo aging processes once released from products. Silver sulfide (Ag2S) is the major transformation product formed during the wastewater treatment process for Ag-MNP. We examined toxicogenomic responses of pristine Ag-MNP, sulfidized Ag-MNP (sAg-MNP), and AgNO3 to a model soil organism, Caenorhabditis elegans. Transcriptomic profiling of nematodes which were exposed at the EC30 for reproduction for AgNO3, Ag-MNP, and sAg-MNP resulted in 571 differentially expressed genes. We independently verified expression of 4 genes (numr-1
, and grl-20
) using qRT-PCR. Only 11% of differentially expressed genes were common among the three treatments. Gene ontology enrichment analysis also revealed that Ag-MNP and sAg-MNP had distinct toxicity mechanisms and did not share any of the biological processes. The processes most affected by Ag-MNP relate to metabolism, while those processes most affected by sAg-MNP relate to molting and the cuticle, and the most impacted processes for AgNO3 exposed nematodes was stress related. Additionally, as observed from qRT-PCR and mutant experiments, the responses to sAg-MNP were distinct from AgNO3 while some of the effects of pristine MNP were similar to AgNO3, suggesting that effects from Ag-MNP is partially due to dissolved silver ions.