Inflammatory and Oxidative Stress Responses of an Alveolar Epithelial Cell Line to Airborne Zinc Oxide Nanoparticles at the Air-Liquid Interface: A Comparison with Conventional, Submerged Cell-Culture Conditions

Table 1

Comparison of the lowest observed effect levels (LOELs) for nanoparticles exposure of cells exposed at ALI and submerged conditions.

Reference	Particle type	Human epithelial cell type	Time at ALI prior to exposure	Exposure; time	Postincubation; time	Exposure; time	Postincubation; time	Biological parameter	Dose for the lowest observed effect level (LOEL)^1
				ALI	ALI	Submerged	Submerged		Submerged; (𝜇g/cm^2)	ALI; (μg/cm^2)	ALI more sensitive than submerged
								IL-8 (mRNA)	12.5–25	≤2.0	yes
[26]	Coarse urban PM	Bronchial; (primary)	3 d	3 h	0 h	0 h	1 h	HOX-1 (mRNA)	25–65	≤2.0	yes
								COX-2 (mRNA)	≤7.0	≤2.0	unclear
[24]	Diesel soot	Bronchial (16HBE14o)	?^2	6 h	20 h	6 h	20 h	IL-8 (protein)	0.25–1.88	>0.1	unclear
								IL-8 (mRNA)	0.7–2.5	<0.7	yes
								GM-CSF; (mRNA)	>2.5	0.7^3	yes
This study	Agglomerated ZnO nanoparticles	Alveolar type II (A549)	1 h	3 h	0 h	1 h	0 h	IL-6 (mRNA)	>2.5	<0.7	yes
								HMOX1 (mRNA)	>2.5	>2.2	unclear
								SOD-2 (mRNA)	>2.5	>2.2	unclear
								GCS; (mRNA)	>2.5	0.7–2.5	yes

¹LOEL: lowest dose in μg/cm² at which a statistically significant effect (𝑃<0.05) was observed relative to the control.
²Not stated in publication.
³Here: 0.7 μg/cm² showed a significant effect, while 2.2 μg/cm² was not statistically significant due to larger variability in the data. Hence, we assume that 0.7 μg/cm² is a good estimate for LOEL.