journal article·2022-07

Toxicity assessment of nanoparticles in contact with the skin

Taghrid Zaiter, Raphaël Cornu, Wassim El Basset, Hélène Martin, Mona Diab, Arnaud Béduneau

Journal of Nanoparticle Research· Volume 24· Issue 7
Publisher page

Abstract

Due to their unique physicochemical properties, engineered nanoparticles (NPs) are used in numerous skin products as sunscreen, texture agents, colorant, and drug delivery systems. While the skin is considered the first line of defense against xenobiotic entrance, the small size of NPs could promote the interaction with cutaneous cells. This review investigates the fate and the toxicological effects of organic and inorganic NPs used in cosmetic and dermatology. After direct exposure to skin cells, cytotoxicity, oxidative stress, inflammatory response, and genotoxicity were reported in a dose and time-dependent manner, especially for inorganic NPs. Despite these findings, the toxicity of nanoparticles applied to a healthy skin could be questioned due to their inability, for most of them, to reach the viable epidermis. Advanced skin models and toxicity tests validated for nanomaterials should be required for a better prediction of the dermal nanotoxicity.
Source: expertdata · Quality: candidate unverified · Source record ↗

Research context

OpenAlex topics: Skin Protection and Aging · Advancements in Transdermal Drug Delivery · Nanoparticles: synthesis and applications

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

References (95)

Show source-provided references
1. (2009) Regulation (EC) No 1223/2009 of the European Parliament and of the Council of 30 November 2009 on cosmetic products. 151
2. (2011) Guidance for industry considering whether an FDA-regulated product involves the application of nanotechnology. Biotechnology Law Report 30:613–616. https://doi.org/10.1089/blr.2011.981410.1089/blr.2011.9814 ↗
3. ISO/TC 229, Nanotechnologies (2017) ISO/TR 18401:2017 nanotechnologies — language explanation of selected terms from the ISO/IEC 80004 series
4. Liang X, Xu Z, Grice J, et al (2013) Penetration of nanoparticles into human skin. Current pharmaceutical design 19:. https://doi.org/10.2174/138161281131935001110.2174/1381612811319350011 ↗
5. Lu P-J, Huang S-C, Chen Y-P et al (2015) Analysis of titanium dioxide and zinc oxide nanoparticles in cosmetics. J Food Drug Anal 23:587–594. https://doi.org/10.1016/j.jfda.2015.02.00910.1016/j.jfda.2015.02.009 ↗
6. Hameed A, Akhtar N (2019) The skin melanin: an inhibitor of vitamin-D3 biosynthesis: with special emphasis with structure of skin. A mini review. Dermatol Case Rep 04: https://doi.org/10.35248/2684-124X.19.4.14910.35248/2684-124X.19.4.149 ↗
7. Proksch E, Brandner JM, Jensen J-M (2008) The skin: an indispensable barrier. Exp Dermatol 17:1063–1072. https://doi.org/10.1111/j.1600-0625.2008.00786.x10.1111/j.1600-0625.2008.00786.x ↗
8. Brown TM, Krishnamurthy K (2021) Histology, dermis. In: StatPearls. StatPearls Publishing, Treasure Island (FL)
9. OpenStaxCollege (2013) Layers of the skin. In: Anatomy & Physiology
10. Coates M, Lee MJ, Norton D, MacLeod AS (2019) The skin and intestinal microbiota and their specific innate immune systems. Front Immunol 10:. https://doi.org/10.3389/fimmu.2019.0295010.3389/fimmu.2019.02950 ↗
11. Harder J, Schröder J-M, Gläser R (2013) The skin surface as antimicrobial barrier: present concepts and future outlooks. Exp Dermatol 22:1–5. https://doi.org/10.1111/exd.1204610.1111/exd.12046 ↗
12. Herman A, Herman AP (2019) Antimicrobial peptides activity in the skin. Skin Res Technol 25:111–117. https://doi.org/10.1111/srt.1262610.1111/srt.12626 ↗
13. Baker LB (2019) Physiology of sweat gland function: the roles of sweating and sweat composition in human health. Temperature 6:211–259. https://doi.org/10.1080/23328940.2019.163214510.1080/23328940.2019.1632145 ↗
14. Kabashima K, Honda T, Ginhoux F, Egawa G (2019) The immunological anatomy of the skin. Nat Rev Immunol 19:19–30. https://doi.org/10.1038/s41577-018-0084-510.1038/s41577-018-0084-5 ↗
15. Clark RA (2015) Resident memory T cells in human health and disease. Sci Transl Med 7:269rv1. https://doi.org/10.1126/scitranslmed.301064110.1126/scitranslmed.3010641 ↗
16. Yan B, Liu N, Li J et al (2020) The role of Langerhans cells in epidermal homeostasis and pathogenesis of psoriasis. J Cell Mol Med 24:11646–11655. https://doi.org/10.1111/jcmm.1583410.1111/jcmm.15834 ↗
17. Bäsler K, Bergmann S, Heisig M et al (2016) The role of tight junctions in skin barrier function and dermal absorption. J Control Release 242:105–118. https://doi.org/10.1016/j.jconrel.2016.08.00710.1016/j.jconrel.2016.08.007 ↗
18. Schmid-Wendtner M-H, Korting HC (2006) The pH of the skin surface and its impact on the barrier function. Skin Pharmacol Physiol 19:296–302. https://doi.org/10.1159/00009467010.1159/000094670 ↗
19. Filipe P, Silva JN, Silva R et al (2009) Stratum corneum is an effective barrier to TiO2 and ZnO nanoparticle percutaneous absorption. Skin Pharmacol Physiol. https://doi.org/10.1159/00023555410.1159/000235554 ↗
20. Smijs TGM, Bouwstra JA (2010) Focus on skin as a possible port of entry for solid nanoparticles and the toxicological impact. J Biomed Nanotechnol 6:469–484. https://doi.org/10.1166/jbn.2010.114610.1166/jbn.2010.1146 ↗
21. Wu J, Liu W, Xue C et al (2009) Toxicity and penetration of TiO2 nanoparticles in hairless mice and porcine skin after subchronic dermal exposure. Toxicol Lett 191:1–8. https://doi.org/10.1016/j.toxlet.2009.05.02010.1016/j.toxlet.2009.05.020 ↗
22. Zvyagin AV, Zhao X, Gierden A et al (2008) Imaging of zinc oxide nanoparticle penetration in human skin in vitro and in vivo. J Biomed Opt 13:064031. https://doi.org/10.1117/1.304149210.1117/1.3041492 ↗
23. van Kuijk-Meuwissen MEMJ, Mougin L, Junginger HE, Bouwstra JA (1998) Application of vesicles to rat skin in vivo: a confocal laser scanning microscopy study. J Control Release 56:189–196. https://doi.org/10.1016/S0168-3659(98)00087-X10.1016/S0168-3659(98)00087-X ↗
24. Sonavane G, Tomoda K, Sano A et al (2008) In vitro permeation of gold nanoparticles through rat skin and rat intestine: effect of particle size. Colloids Surf, B 65:1–10. https://doi.org/10.1016/j.colsurfb.2008.02.01310.1016/j.colsurfb.2008.02.013 ↗
25. Larese FF, D’Agostin F, Crosera M et al (2009) Human skin penetration of silver nanoparticles through intact and damaged skin. chen. Toxicology 255:33–37. https://doi.org/10.1016/j.tox.2008.09.02510.1016/j.tox.2008.09.025 ↗
26. Larese Filon F, Mauro M, Adami G et al (2015) Nanoparticles skin absorption: new aspects for a safety profile evaluation. Regul Toxicol Pharmacol 72:310–322. https://doi.org/10.1016/j.yrtph.2015.05.00510.1016/j.yrtph.2015.05.005 ↗
27. Kohli AK, Alpar HO (2004) Potential use of nanoparticles for transcutaneous vaccine delivery: effect of particle size and charge. Int J Pharm 275:13–17. https://doi.org/10.1016/j.ijpharm.2003.10.03810.1016/j.ijpharm.2003.10.038 ↗
28. Wang M, Lai X, Shao L, Li L (2018) Evaluation of immunoresponses and cytotoxicity from skin exposure to metallic nanoparticles. Int J Nanomedicine 13:4445–4459. https://doi.org/10.2147/IJN.S17074510.2147/IJN.S170745 ↗
29. Fang C-L, Aljuffali IA, Li Y-C, Fang J-Y (2014) Delivery and targeting of nanoparticles into hair follicles. Ther Deliv 5:991–1006. https://doi.org/10.4155/tde.14.6110.4155/tde.14.61 ↗
30. Nanoparticles and their interactions with the dermal barrier. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2835875/. Accessed 8 Feb 2022
31. Alvarez-Román R, Naik A, Kalia YN et al (2004) Skin penetration and distribution of polymeric nanoparticles. J Control Release 99:53–62. https://doi.org/10.1016/j.jconrel.2004.06.01510.1016/j.jconrel.2004.06.015 ↗
32. Baroli B, Ennas MG, Loffredo F et al (2007) Penetration of metallic nanoparticles in human full-thickness skin. J Invest Dermatol 127:1701–1712. https://doi.org/10.1038/sj.jid.570073310.1038/sj.jid.5700733 ↗
33. Patzelt A, Richter H, Knorr F et al (2011) Selective follicular targeting by modification of the particle sizes. J Control Release 150:45–48. https://doi.org/10.1016/j.jconrel.2010.11.01510.1016/j.jconrel.2010.11.015 ↗
34. Ng KW, Lau WM (2015) Skin deep: the basics of human skin structure and drug penetration. In: Dragicevic N, Maibach HI (eds) Percutaneous penetration enhancers chemical methods in penetration enhancement: drug manipulation strategies and vehicle effects. Springer, Berlin, Heidelberg, pp 3–11
35. Sanches PL, Geaquinto LR de O, Cruz R, et al (2020) Toxicity evaluation of TiO2 nanoparticles on the 3D skin model: a systematic review. Front Bioeng Biotechnol 8:.https://doi.org/10.3389/fbioe.2020.0057510.3389/fbioe.2020.00575 ↗
36. Carrola J, Bastos V, Jarak I et al (2016) Metabolomics of silver nanoparticles toxicity in HaCaT cells: structure–activity relationships and role of ionic silver and oxidative stress. Nanotoxicology 10:1105–1117. https://doi.org/10.1080/17435390.2016.117774410.1080/17435390.2016.1177744 ↗
37. Wu Z, Yang H, Archana G et al (2018) Human keratinocytes adapt to ZnO nanoparticles induced toxicity via complex paracrine crosstalk and Nrf2-proteasomal signal transduction. Nanotoxicology 12:1215–1229. https://doi.org/10.1080/17435390.2018.153740910.1080/17435390.2018.1537409 ↗
38. O’Neill AT, Monteiro-Riviere NA, Walker GM (2008) Characterization of microfluidic human epidermal keratinocyte culture. Cytotechnology 56:197–207. https://doi.org/10.1007/s10616-008-9149-910.1007/s10616-008-9149-9 ↗
39. Zhang LW, Zeng L, Barron AR, Monteiro-Riviere NA (2007) Biological interactions of functionalized single-wall carbon nanotubes in human epidermal keratinocytes. Int J Toxicol 26:103–113. https://doi.org/10.1080/1091581070122513310.1080/10915810701225133 ↗
40. Auffan M, Rose J, Orsiere T et al (2009) CeO2 nanoparticles induce DNA damage towards human dermal fibroblasts in vitro. Nanotoxicology 3:161–171. https://doi.org/10.1080/1743539090278808610.1080/17435390902788086 ↗
41. Goenka S, Toussaint J (2020) Citrate-coated platinum nanoparticles exhibit a primary particle-size dependent effect on stimulating melanogenesis in human melanocytes. Cosmetics 7:88. https://doi.org/10.3390/cosmetics704008810.3390/cosmetics7040088 ↗
42. Tan J, Zhao C, Zhou J et al (2017) Co-culturing epidermal keratinocytes and dermal fibroblasts on nano-structured titanium surfaces. Mater Sci Eng C Mater Biol Appl 78:288–295. https://doi.org/10.1016/j.msec.2017.04.03610.1016/j.msec.2017.04.036 ↗
43. Sarkiri M, Fox SC, Fratila-Apachitei LE, Zadpoor AA (2019) Bioengineered skin intended for skin disease modeling. Int J Mol Sci 20:. https://doi.org/10.3390/ijms2006140710.3390/ijms20061407 ↗
44. Kim H, Choi J, Lee H et al (2016) Skin corrosion and irritation test of nanoparticles using reconstructed three-dimensional human skin model, EpiDerm™. Toxicol Res 32:311–316. https://doi.org/10.5487/TR.2016.32.4.31110.5487/TR.2016.32.4.311 ↗
45. Hao F, Jin X, Liu QS et al (2017) Epidermal penetration of gold nanoparticles and its underlying mechanism based on human reconstructed 3D Episkin model. ACS Appl Mater Interfaces 9:42577–42588. https://doi.org/10.1021/acsami.7b1370010.1021/acsami.7b13700 ↗
46. Suhail S, Sardashti N, Jaiswal D et al (2019) Engineered skin tissue equivalents for product evaluation and therapeutic applications. Biotechnol J 14:1900022. https://doi.org/10.1002/biot.20190002210.1002/biot.201900022 ↗
47. Ternullo S, de Weerd L, Holsæter AM et al (2017) Going skin deep: a direct comparison of penetration potential of lipid-based nanovesicles on the isolated perfused human skin flap model. Eur J Pharm Biopharm 121:14–23. https://doi.org/10.1016/j.ejpb.2017.09.00610.1016/j.ejpb.2017.09.006 ↗
48. Abd E, Yousuf SA, Pastore MN et al (2016) Skin models for the testing of transdermal drugs. CPAA 8:163–176. https://doi.org/10.2147/CPAA.S6478810.2147/CPAA.S64788 ↗
49. Samberg ME, Oldenburg SJ, Monteiro-Riviere NA (2010) Evaluation of silver nanoparticle toxicity in skin in vivo and keratinocytes in vitro. Environ Health Perspect 118:407–413. https://doi.org/10.1289/ehp.090139810.1289/ehp.0901398 ↗
50. Korani M, Rezayat SM, Arbabi Bidgoli S (2013) Sub-chronic dermal toxicity of silver nanoparticles in Guinea pig: special emphasis to heart, bone and kidney toxicities. Iran J Pharm Res 12:511–519
51. Moniz T, Costa Lima SA, Reis S (2020) Human skin models: from healthy to disease-mimetic systems; characteristics and applications. Br J Pharmacol 177:4314–4329. https://doi.org/10.1111/bph.1518410.1111/bph.15184 ↗
52. Adachi K, Yamada N, Yamamoto K et al (2010) In vivo effect of industrial titanium dioxide nanoparticles experimentally exposed to hairless rat skin. Nanotoxicology 4:296–306. https://doi.org/10.3109/1743539100379309510.3109/17435391003793095 ↗
53. Abdel-Mottaleb MMA, Moulari B, Beduneau A et al (2012) Nanoparticles enhance therapeutic outcome in inflamed skin therapy. Eur J Pharm Biopharm 82:151–157. https://doi.org/10.1016/j.ejpb.2012.06.00610.1016/j.ejpb.2012.06.006 ↗
54. Jin H, He R, Oyoshi M, Geha RS (2009) Animal models of atopic dermatitis. J Invest Dermatol 129:31–40. https://doi.org/10.1038/jid.2008.10610.1038/jid.2008.106 ↗
55. Engelhart K, El Hindi T, Biesalski H-K, Pfitzner I (2005) In vitro reproduction of clinical hallmarks of eczematous dermatitis in organotypic skin models. Arch Dermatol Res 297:1–9. https://doi.org/10.1007/s00403-005-0575-710.1007/s00403-005-0575-7 ↗
56. Crosera M, Prodi A, Mauro M et al (2015) Titanium dioxide nanoparticle penetration into the skin and effects on HaCaT cells. Int J Environ Res Public Health 12:9282–9297. https://doi.org/10.3390/ijerph12080928210.3390/ijerph120809282 ↗
57. Colombo I, Sangiovanni E, Maggio R, et al (2017) HaCaT cells as a reliable in vitro differentiation model to dissect the inflammatory/repair response of human keratinocytes. Mediators Inflamm 2017:. https://doi.org/10.1155/2017/743562110.1155/2017/7435621 ↗
58. Benameur L, Auffan M, Cassien M et al (2015) DNA damage and oxidative stress induced by CeO2 nanoparticles in human dermal fibroblasts: evidence of a clastogenic effect as a mechanism of genotoxicity. Nanotoxicology 9:696–705. https://doi.org/10.3109/17435390.2014.96888910.3109/17435390.2014.968889 ↗
59. Alarifi S, Ali D, Alakhtani S et al (2014) Reactive oxygen species-mediated DNA damage and apoptosis in human skin epidermal cells after exposure to nickel nanoparticles. Biol Trace Elem Res 157:84–93. https://doi.org/10.1007/s12011-013-9871-910.1007/s12011-013-9871-9 ↗
60. Chen L, Wu M, Jiang S et al (2019) Skin toxicity assessment of silver nanoparticles in a 3D epidermal model compared to 2D keratinocytes. Int J Nanomedicine 14:9707–9719. https://doi.org/10.2147/IJN.S22545110.2147/IJN.S225451 ↗
61. Sun T, Jackson S, Haycock JW, MacNeil S (2006) Culture of skin cells in 3D rather than 2D improves their ability to survive exposure to cytotoxic agents. J Biotechnol 122:372–381. https://doi.org/10.1016/j.jbiotec.2005.12.02110.1016/j.jbiotec.2005.12.021 ↗
62. Knudsen NØ, Rønholt S, Salte RD et al (2012) Calcipotriol delivery into the skin with PEGylated liposomes. Eur J Pharm Biopharm 81:532–539. https://doi.org/10.1016/j.ejpb.2012.04.00510.1016/j.ejpb.2012.04.005 ↗
63. Mohamed AL, Elmotasem H, Salama AAA (2020) Colchicine mesoporous silica nanoparticles/hydrogel composite loaded cotton patches as a new encapsulator system for transdermal osteoarthritis management. Int J Biol Macromol 164:1149–1163. https://doi.org/10.1016/j.ijbiomac.2020.07.13310.1016/j.ijbiomac.2020.07.133 ↗
64. Hirai T, Yoshikawa T, Nabeshi H et al (2012) Amorphous silica nanoparticles size-dependently aggravate atopic dermatitis-like skin lesions following an intradermal injection. Part Fibre Toxicol 9:3. https://doi.org/10.1186/1743-8977-9-310.1186/1743-8977-9-3 ↗
65. Ostrowski A, Nordmeyer D, Boreham A et al (2014) Skin barrier disruptions in tape stripped and allergic dermatitis models have no effect on dermal penetration and systemic distribution of AHAPS-functionalized silica nanoparticles. Nanomedicine: Nanotechnology. Biology and Medicine 10:1571–1581. https://doi.org/10.1016/j.nano.2014.04.00410.1016/j.nano.2014.04.004 ↗
66. Alarifi S, Ali D, Verma A et al (2013) Cytotoxicity and genotoxicity of copper oxide nanoparticles in human skin keratinocytes cells. Int J Toxicol 32:296–307. https://doi.org/10.1177/109158181348756310.1177/1091581813487563 ↗
67. Meyer K, Rajanahalli P, Ahamed M et al (2011) ZnO nanoparticles induce apoptosis in human dermal fibroblasts via p53 and p38 pathways. Toxicol In Vitro 25:1721–1726. https://doi.org/10.1016/j.tiv.2011.08.01110.1016/j.tiv.2011.08.011 ↗
68. Liang H, Jin C, Tang Y et al (2014) Cytotoxicity of silica nanoparticles on HaCaT cells. J Appl Toxicol 34:367–372. https://doi.org/10.1002/jat.295310.1002/jat.2953 ↗
69. Yang X, Liu J, He H et al (2010) SiO2 nanoparticles induce cytotoxicity and protein expression alteration in HaCaT cells. Part Fibre Toxicol 7:1. https://doi.org/10.1186/1743-8977-7-110.1186/1743-8977-7-1 ↗
70. Zanette C, Pelin M, Crosera M et al (2011) Silver nanoparticles exert a long-lasting antiproliferative effect on human keratinocyte HaCaT cell line. Toxicol In Vitro 25:1053–1060. https://doi.org/10.1016/j.tiv.2011.04.00510.1016/j.tiv.2011.04.005 ↗
71. Gandamalla D, Lingabathula H, Reddy Y (2017) Cytotoxicity evaluation of titanium and zinc oxide nanoparticles on human cell lines. International Journal of Pharmacy and Pharmaceutical Sciences 9:240. https://doi.org/10.22159/ijpps.2017v9i11.2192410.22159/ijpps.2017v9i11.21924 ↗
72. Sooklert K, Nilyai S, Rojanathanes R et al (2019) N-acetylcysteine reverses the decrease of DNA methylation status caused by engineered gold, silicon, and chitosan nanoparticles. Int J Nanomedicine 14:4573–4587. https://doi.org/10.2147/IJN.S20437210.2147/IJN.S204372 ↗
73. OCDE (2015) Test No. 431: in vitro skin corrosion: reconstructed human epidermis (RHE) test method
74. Park Y-H, Jeong SH, Yi SM et al (2011) Assessment of phototoxicity, skin irritation, and sensitization potential of polystyrene and TiO2nanoparticles. J Phys: Conf Ser 304:012050. https://doi.org/10.1088/1742-6596/304/1/01205010.1088/1742-6596/304/1/012050 ↗
75. Schaeublin NM, Braydich-Stolle LK, Maurer EI et al (2012) Does shape matter? Bioeffects of gold nanomaterials in a human skin cell model. Langmuir 28:3248–3258. https://doi.org/10.1021/la204081m10.1021/la204081m ↗
76. Huang Y, Lü X, Qu Y et al (2015) MicroRNA sequencing and molecular mechanisms analysis of the effects of gold nanoparticles on human dermal fibroblasts. Biomaterials 37:13–24. https://doi.org/10.1016/j.biomaterials.2014.10.04210.1016/j.biomaterials.2014.10.042 ↗
77. Leite-Silva VR, Sanchez WY, Studier H et al (2016) Human skin penetration and local effects of topical nano zinc oxide after occlusion and barrier impairment. Eur J Pharm Biopharm 104:140–147. https://doi.org/10.1016/j.ejpb.2016.04.02210.1016/j.ejpb.2016.04.022 ↗
78. Sharma V, Shukla RK, Saxena N et al (2009) DNA damaging potential of zinc oxide nanoparticles in human epidermal cells. Toxicol Lett 185:211–218. https://doi.org/10.1016/j.toxlet.2009.01.00810.1016/j.toxlet.2009.01.008 ↗
79. Shukla RK, Sharma V, Pandey AK et al (2011) ROS-mediated genotoxicity induced by titanium dioxide nanoparticles in human epidermal cells. Toxicol In Vitro 25:231–241. https://doi.org/10.1016/j.tiv.2010.11.00810.1016/j.tiv.2010.11.008 ↗
80. Kocbek P, Teskac K, Kreft ME, Kristl J (2010) Toxicological aspects of long-term treatment of keratinocytes with ZnO and TiO2 nanoparticles. Small 6:1908–1917. https://doi.org/10.1002/smll.20100003210.1002/smll.201000032 ↗
81. Browning CL, The T, Mason MD, Wise JP (2014) Titanium dioxide nanoparticles are not cytotoxic or clastogenic in human skin cells. J Environ Anal Toxicol 4:. https://doi.org/10.4172/2161-0525.100023910.4172/2161-0525.1000239 ↗
82. Ryu HJ, Seong N, So BJ et al (2014) Evaluation of silica nanoparticle toxicity after topical exposure for 90 days. IJN 9:127–136. https://doi.org/10.2147/IJN.S5792910.2147/IJN.S57929 ↗
83. Pal A, Alam S, Chauhan L, et al (2016) UVB exposure enhanced the dermal penetration of zinc oxide nanoparticles and induced inflammatory responses through oxidative stress mediated of MAPKs and NF-ĸB signaling in SKH-1 hairless mouse skin. Toxicol Res 5:. https://doi.org/10.1039/C6TX00026F10.1039/C6TX00026F ↗
84. Ilves M, Palomäki J, Vippola M et al (2014) Topically applied ZnO nanoparticles suppress allergen induced skin inflammation but induce vigorous IgE production in the atopic dermatitis mouse model. Part Fibre Toxicol 11:38. https://doi.org/10.1186/s12989-014-0038-410.1186/s12989-014-0038-4 ↗
85. Kundu J, Kim D-H, Chae IG et al (2018) Silicon dioxide nanoparticles induce COX-2 expression through activation of STAT3 signaling pathway in HaCaT cells. Toxicol In Vitro 52:235–242. https://doi.org/10.1016/j.tiv.2018.06.00810.1016/j.tiv.2018.06.008 ↗
86. Yanagisawa R, Takano H, Inoue K-I et al (2009) Titanium dioxide nanoparticles aggravate atopic dermatitis-like skin lesions in NC/Nga mice. Exp Biol Med (Maywood) 234:314–322. https://doi.org/10.3181/0810-RM-30410.3181/0810-RM-304 ↗
87. Yanagisawa R, Takano H, Ki I et al (2010) Size effects of polystyrene nanoparticles on atopic dermatitis-like skin lesions in NC/NGA mice. Int J Immunopathol Pharmacol 23:131–141. https://doi.org/10.1177/03946320100230011210.1177/039463201002300112 ↗
88. Galandáková A, Franková J, Ambrožová N et al (2016) Effects of silver nanoparticles on human dermal fibroblasts and epidermal keratinocytes. Hum Exp Toxicol 35:946–957. https://doi.org/10.1177/096032711561196910.1177/0960327115611969 ↗
89. Gao F, Ma N, Zhou H et al (2016) Zinc oxide nanoparticles-induced epigenetic change and G2/M arrest are associated with apoptosis in human epidermal keratinocytes. Int J Nanomedicine 11:3859–3874. https://doi.org/10.2147/IJN.S10702110.2147/IJN.S107021 ↗
90. Prasad RY, Chastain PD, Nikolaishvili-Feinberg N et al (2013) Titanium dioxide nanoparticles activate the ATM-Chk2 DNA damage response in human dermal fibroblasts. Nanotoxicology 7:1111–1119. https://doi.org/10.3109/17435390.2012.71065910.3109/17435390.2012.710659 ↗
91. Gong C, Tao G, Yang L et al (2010) SiO2 nanoparticles induce global genomic hypomethylation in HaCaT cells. Biochem Biophys Res Commun 397:397–400. https://doi.org/10.1016/j.bbrc.2010.05.07610.1016/j.bbrc.2010.05.076 ↗
92. Pal A, Alam S, Mittal S et al (2016) UVB irradiation-enhanced zinc oxide nanoparticles-induced DNA damage and cell death in mouse skin. Mutat Res Genet Toxicol Environ Mutagen 807:15–24. https://doi.org/10.1016/j.mrgentox.2016.06.00510.1016/j.mrgentox.2016.06.005 ↗
93. Magdolenova Z, Lorenzo Y, Collins A, Dusinska M (2012) Can standard genotoxicity tests be applied to nanoparticles? J Toxicol Environ Health A 75:800–806. https://doi.org/10.1080/15287394.2012.69032610.1080/15287394.2012.690326 ↗
94. Gong C, Yang L, Zhou J et al (2017) Possible role of PAPR-1 in protecting human HaCaT cells against cytotoxicity of SiO2 nanoparticles. Toxicol Lett 280:213–221. https://doi.org/10.1016/j.toxlet.2017.07.21310.1016/j.toxlet.2017.07.213 ↗
95. Nabeshi H, Yoshikawa T, Matsuyama K et al (2011) Amorphous nanosilica induce endocytosis-dependent ROS generation and DNA damage in human keratinocytes. Part Fibre Toxicol 8:1. https://doi.org/10.1186/1743-8977-8-110.1186/1743-8977-8-1 ↗