Abstract
This study evaluates the sensitivity, detection limits, and applicability of size measurement techniques to polyacrylate‐based polymer nanocarriers (PNCs) in a hydrated state. Dynamic light scattering (DLS), particle tracking analysis (PTA), cryo‐transmission electron microscopy (cryo‐TEM), scanning electron microscopy (SEM), and differential centrifugal sedimentation (DCS) are applied to commercial and laboratory‐scale PNCs to assess the effect of UV‐mediated crosslinking, as well as the impact of active substances (ASs) and commercial dispersants on size distribution. Polydispersity and low refractive index make DLS unreliable. PTA does not detect PNCs <50 nm and requires adapting concentrations to each PNC, challenging comparisons. DCS captures polydispersity but could not detect PNCs <50 nm either. Importantly, DLS, PTA, and DCS assume spherical geometry, but commercial PNCs are unlikely to be spherical, thus seriously challenging data interpretation. Cryo‐TEM detects PNCs <50 nm and delivers the most reliable size distribution. Large differences among the PNCs tested warn against the use of model PNCs and read across when conducting risk assessment. Our results confirm the challenges and inadequacies in existing approaches and call for more research to develop multimethod approaches and adaptation of OECD guidelines to characterize PNCs, which are increasingly used across various sectors.