*4.3. Exposure Dose and Time*

The dose–response relationship is an important principle in nanotoxicology [42]. The modified GQDs may induce DNA hypermethylation in a time and dose dependent manner [53]. The high-dose (50 mg/L) GO induces more serious DNA methylation (hypermethylation) than low-dose (10 mg/L) treatment [101]. The effective accumulation of GFNs in the nucleus is regulated by two nuclear pore complex genes (Kapβ2 and Nup98), and their cellular internalization and absorption are related to exposure time [69]. Notably, the rGO sheets with the same size or larger size, higher concentration (100 μg/mL), and longer exposure time (24 h) showed no obvious genotoxicity in the hMSCs [71]. Overall, there are few studies on the genotoxicity of GFNs doses, and especially the combination of GFNs type and dose exposure is rare.
