Table 4.

Extraction of data from selected articles.

Authors	Park et al. (2011)	Choi et al. (2014)	Kato et al. (2014)	Horie et al. (2016)	Miyani and Hughes (2016)	Kim et al. (2016)	Tang et al. (2018)
Year	2011	2014	2014	2016	2016	2016	2018
DOI	10.1016/ j.tiv.2011.05.022	10.5620/ eht.2014.29.e2014004	10.1166/ jnn.2014.8719	10.1080/15376516. 2016.1175530	10.1080/15569527. 2016.1211671	10.5487/ TR.2016.32.4.311	10.1016/j.tox. 2018.05.010
Type of skin model	EpiDerm™	KeraSkin™	Developed in own laboratory	EpiDerm™	EpiDerm™	EpiDerm™	EpiKuitis™
Test substance	Polystyrene and Titanium dioxide nanoparticles	Zinc oxide nanoparticles, Titanium dioxide nanoparticles and Mixture (Zinc oxide/Titanium dioxide nanoparticles)	Polyvinylpyrrolidone-entrapped fullerene-C60 and Titanium dioxide nanoparticles	Titanium dioxide nanoparticles	Silver nanoparticles, Titanium dioxide nanoparticles and Cerium dioxide nanoparticles	Iron nanoparticles, Aluminum oxide nanoparticles, Titanium oxide nanoparticles and Silver nanoparticles	Titanium dioxide nanoparticles
Crystalline structure of TiO2	Mixture	Rutile	Rutile	Anatase and Rutile	Anatase, Rutile and Mixture	Mixture	Anatase, Rutile and Mixture
Primary particle size	25 nm	21 nm	10 nm	Anatase: 6 nm and 7 nm; Rutile: 15 nm	Anatase: 25 nm and 142 nm; Rutile: 214 nm; Mixture: 22 nm, 31 nm and 59 nm	21 nm	Anatase: 23 nm and 108 nm, Rutile: 21 nm and Mixture: 31 nm, 52 nm and 55 nm
Size of the TiO2 after dispersion (aggregate)	± 200 nm	39.4 ± 28.6 nm	Not described	Anatase: 252.1 nm and 323.2 nm; Rutile: 276.4 nm and 318.4 nm	Not described	Several hundred nm in size	Anatase: 912 nm and 410 nm, Rutile: 121nm and Mixture: 2312 nm, 246 nm and 249 nm
Analysis method	Skin irritation test; skin phototoxicity test	Skin Corrosion Test; Skin Irritation Test; Cytokine Assay and Histopathology	Intracellular ROS-Generation and Lipid Hydroperoxides	Lactate dehydrogenase assay, IL-8 enzyme-linked immunosorbent assay and relative HO-1 gene expression; Skin Irritation Test	Skin irritation test	Skin Corrosion Test; Skin Irritation Test; IL-1α assay and histopathology	Phototoxicity test
Substance concentration of TiO2	100 μg/mL	25% in deionized water	15 μg/mL	100 μg/mL	1 mg/ml	The epidermis surface was moistened with deionized water and 25 mg of the test substance was added	100 μg/mL
Exposure time	1 h	3 min and 1 h	3 h	4 h	1 h	3 min and 1 h	2 h
The expected outcome of the positive and negative controls was observed?	Yes	Yes	Yes	Yes	Yes	Yes	Yes
Results evaluation of corrosion and/or irritation and phototoxicity	Cytotoxicities and phototoxicity were assessed as a percentage of the negative control. However, the negative control exhibits the viability > 50%.	Corrosion: The article uses OECD TG431 as a reference, which says that the test material is considered to be corrosive to the skin if the viability is <50% after 3 min exposure. However, although the viability after 3 min exposure is ≥ 50%, it is corrosive if the viability is <15% after 60 min exposure. Therefore, the material is non-corrosive if the viability is ≥ 50% after 3 min exposure and ≥ 15% after 60 min exposure. Irritation: The article uses OECD TG439 as a reference, which says that test material is considered to be irritant to skin if the tissue viability after exposure/post-incubation is ≤ 50%, and is non-irritant if the viability is > 50%.	Evaluation of the induction of ROS-generation around the outside of nuclei and peroxidation of cell membrane in the epidermis by electron microscopy.	Irritation: The article uses OECD TG439 as a reference, which says that test material is considered to be irritant to skin if the tissue viability after exposure/post-incubation is ≤ 50%, and is non-irritant if the viability is > 50%.	Regarding the irritation test, the test material is considered to be irritant to skin if the tissue viability after exposure/post-incubation is less than or equal to 50%. It would be non-irritant if the viability is more than 50%.	Corrosion: The article uses OECD TG431 as a reference, which says that the test material is considered to be corrosive to the skin if the viability is <50% after 3 min exposure. However, although the viability after 3 min exposure is ≥ 50%, it is corrosive if the viability is <15% after 60 min exposure. Therefore, the material is non-corrosive if the viability is ≥ 50% after 3 min exposure and ≥ 15% after 60 min exposure. Irritation: The article uses OECD TG439 as a reference, which says that test material is considered to be irritant to skin if the tissue viability after exposure/post-incubation is ≤ 50%, and is non-irritant if the viability is > 50%.	The test substance was considered phototoxic if the UVA exposed tissues revealed a decrease in viability exceeding 25% when compared with the dark control.
Main conclusion	Polystyrene and Titanium dioxide nanoparticles did not exhibit skin irritation and phototoxicity	For all the test materials used in this study were found to be non-corrosive and non-irritant; The results were confirmed by IL-1α and histopathological analysis	Was observed that UV irradiation of 8 J/cm2 in the presence of 15 ppm TiO2 induced ROS-generation around the outside of nuclei and lipid peroxidation of cell membrane in the epidermis. However, the treatment with C60/PVP or C60/Sqn suppressed intracellular ROS and lipid peroxidation, and thereafter TiO2-catalyzed phototoxic potency was repressed in a dose-dependent manner of C60.	The UVA irradiation did not affect LDH leakage or IL-8 secretion in the culture medium, as no increase in HO-1 expression was observed, regardless of the type of TiO2 nanoparticle	The silver, cerium and titanium nanoparticles tested can be classified as non-irritants	For all the test materials used in this study were found to be non-corrosive and non-irritant; The results were confirmed by IL-1α and histopathological analysis	For all the test materials used in this study, there was no phototoxicity at test concentration in the studied skin model