Elucidating the relationships between the toxicity-based-toxicokinetic (TBTK)/toxicodynamic (TD) properties of engineered nanomaterials and their nanotoxicity is crucial for human health-risk analysis. Zerovalent iron (Fe
0
) nanoparticles (NPs) are one of the most prominent NPs applied in remediating contaminated soils and groundwater. However, there are concerns that Fe
0
NP application contributes to long-term environmental and human health impacts. The nematode
Caenorhabditis elegans
is a surrogate in vivo model that has been successfully applied to assess the potential nanotoxicity of these nanomaterials. Here we present a TBTK/TD approach to appraise bioaccumulation and nanotoxicity of Fe
0
NPs in
C. elegans
. Built on a present
C. elegans
bioassay with estimated TBTK/TD parameters, we found that average bioconcentration factors in
C. elegans
exposed to waterborne and food-borne Fe
0
NPs were ~50 and ~5×10
−3
, respectively, whereas 10% inhibition concentrations for fertility, locomotion, and development, were 1.26 (95% CI 0.19–5.2), 3.84 (0.38–42), and 6.78 (2.58–21) μg·g
−1
, respectively, implicating that fertility is the most sensitive endpoint in
C. elegans
. Our results also showed that biomagnification effects were not observed in waterborne or food-borne Fe
0
NP-exposed worms. We suggest that the TBTK/TD assessment for predicting NP-induced toxicity at different concentrations and conditions in
C. elegans
could enable rapid selection of nanomaterials that are more likely to be nontoxic in larger animals. We conclude that the use of the TBTK/TD scheme manipulating
C. elegans
could be used for rapid evaluation of in vivo toxicity of NPs or for drug screening in the field of nanomedicine.