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Table 4 Urea concentration per HepG2 spheroid following both acute (24 h) and prolonged (120 h) exposure to increasing concentrations (0.2–10.0 µg/mL) of ENMs

From: Understanding the impact of more realistic low-dose, prolonged engineered nanomaterial exposure on genotoxicity using 3D models of the human liver

3D HepG2 liver spheroid liver functionality Urea per spheroid (ng/µL) following
Acute (24 h) exposure (95% CI)
Urea per spheroid (ng/µL) following
Prolonged (120 h) exposure (95% CI)
ENM concentration (µg/mL) TiO2 ZnO Ag BaSO4 CeO2 TiO2 ZnO Ag BaSO4 CeO2
Untreated negative control 0.690 (0.625–0.754) 0.937 (0.786–1.088) 0.455 (0.217–0.693) 0.394 (0.235–0.553) 0.675 (0.564–0.785) 1.021 (0.981–1.061) 0.744 (0.365–1.123) 0.389 (0.188–0.589) 0.292 (0.126–0.459) 0.927 (0.746–1.107)
0.2 0.813 (0.676–0.950) 1.245 (1.097–1.393) 0.520 (0.337–0.703) 0.498 (0.379–0.618) 0.724 (0.697–0.752) 1.108 (0.902–1.314) 0.832 (0.565–1.098) 0.523 (0.431–0.615) 0.402 (0.276–0.527) 0.968 (0.812–1.124)
0.5 0.889 (0.809–0.970) 1.036 (0.969–1.103) 0.550 (0.307–0.793) 0.505 (0.312–0.698) 0.762 (0.649–0.874) 1.273 (0.811–1.725) 0.769 (0.563–0.974) 0.563 (0.440–0.686) 0.409 (0.207–0.611) 0.920 (0.761–1.078)
1.0 0.859 (0.693–1.025) 1.145 (1.056–1.234) 0.539 (0.414–0.664) 0.638 (0.571–0.706) 0.775 (0.735–0.816) 1.213 (1.092–1.334) 0.794 (0.675–0.914) 0.490 (0.264–0.716) 0.549 (0.478–0.621) 0.940 (0.710–1.170)
2.0 0.930 (0.783–1.076) 1.120 (0.873–1.366) 0.567 (0.423–0.771) 0.573 (0.376–0.771) 0.717 (0.549–0.885) 1.197 (0.902–1.492) 0.795
(0.502–1.089)
0.521 (0.428–0.615) 0.481 (0.274–0.688) 0.971 (0.706–1.236)
5.0 0.699 (0.565–0.834) 0.793 (0.668–0.919) 0.596 (0.324–0.869) 0.643 (0.487–0.799) 0.782 (0.645–0.919) 0.805* (0.636–0.974) 0.832 (0.729–0.935) 0.703 (0.595–0.811) 0.781 (0.515–1.047) 0.955 (0.672–1.238)
10.0 0.628 (0.371–0.885) 0.728* (0.635–0.821) 0.571 (0.518–0.624) 0.618 (0.214–1.021) 0.792 (0.617–0.967) 0.846 (0.771–0.921) 0.737 (0.532–0.942) 0.726 (0.367–1.085) 0.899 (0.735–1.063) 0.909 (0.755–1.064)
Aflatoxin B1 Positive Control 0.773 (0.718–0.828) 0.881 (0.729–1.033) 0.515 (0.332–0.698) 0.423 (0.330–0.517) 0.755 (0.500–1.010) 0.846 (0.771–0.921) 0.488* (0.212–0.763) 0.516 (0.432–0.600) 0.323 (0.224–0.422) 0.953 (0.878–1.029)
  1. Mean data of three biological replicates, analysed in triplicate (n = 9) are presented with 95% confidence intervals. Significance is indicated in relation to the negative control, where * = p ≤ 0.05