Obsessive Skincare and Liver Toxicity: A Case Report on Titanium Dioxide Exposure

Yıl 2024, Cilt: 16 Sayı: 3, 81 - 85, 31.12.2024

Fatih Öner Kaya , Mohammad Jamal Abunawas , Pınar Mert

https://doi.org/10.35514/mtd.2024.116

Öz

This Case Report highlights the role of titanium dioxide (TiO2) as a perpetrator of liver toxicity when used topically. Although the European Commission has banned titanium dioxide (E171) from being used as a food additive, it is still widely used in dermatological products. Here, we describe a patient who initially presented to our clinic after experiencing a seizure. An inquiry into her history revealed that she had been suffering from generalized body aches and skin rashes for the past month. Incidentally, liver enzymes were found to be significantly elevated, and abdominal ultrasonography revealed hepatomegaly and hepatic steatosis, which was confirmed by a liver biopsy. Further investigation brought to light the patient’s obsessive skincare habits, requiring broader tests to detect any toxic exposure. Thereupon, high amounts of titanium were found in her blood results. TiO2 particles are associated with hazardous properties and pose a threat to human health and the environment; thus, its enormous usage in various products requires further studies that investigate the various ways of exposure to minimize those toxic effects.

Anahtar Kelimeler

Hepatotoxicity, Titanium dioxide, Dermatological products side effects.

Obsesif Cilt Bakımı ve Karaciğer Toksisitesi: Titanyum Dioksit Maruziyeti Üzerine Bir Olgu Sunumu

Öz

Bu Vaka Raporu, topikal olarak kullanıldığında karaciğer toksisitesinin bir sebebi olarak titanyum dioksitin (TiO2) rolünü vurgulamaktadır. Avrupa Komisyonu, titanyum dioksidin (E171) gıda katkısı olarak kullanılmasını yasaklamasına rağmen, hala geniş çapta dermatolojik ürünlerde kullanılmaktadır. Burada, bir hastanın kliniğimize nöbet geçirdikten sonra başvurduğu ve hikayesinin incelenmesi sonucu son bir aydır yaygın vücut ağrıları ve deri döküntüleri yaşadığı ortaya çıktı. Tesadüfen karaciğer enzimlerinin önemli ölçüde yüksek bulunan bu hastada karın ultrasonografisinde hepatomegali ve karaciğer yağlanması tespit edildi, bu da karaciğer biyopsisi ile doğrulandı. Detaylı araştırma hastanın obsesif cilt bakım alışkanlıklarının ortaya çıkmasına neden oldu, bu da herhangi bir toksik maruziyeti tespit etmek için geniş tarama testleri gerektirdi. Bu testlerin sonucunda anormal olarak kan testlerinde yüksek miktarda titanyum bulundu. TiO2 partikülleri tehlikeli özelliklerle ilişkilendirilmiştir ve insan sağlığı hatta çevre için bile bir tehdit oluşturur; dolayısıyla, çeşitli ürünlerdeki yaygın kullanımı olduğundan bu toksik etkileri en aza indirmek için maruz kalma yollarını araştıran daha fazla çalışmayı gerektirir.

Anahtar Kelimeler

Karaciğer Toksisitesi, Titanyum dioksit, Dermatolojik ürünlerin yan etkileri.

Kaynakça

• 1.United States Department of Agriculture, Foreign Agricultural Service; Report Category: SP2 - Prevent or Resolve Barriers to Trade that Hinder U.S. Food and Agricultural Exports. Report Name: Titanium Dioxide Banned as a Food Additive in the EU. T Belder. 2022; E42022-0011
• 2.Skocaj M, Filipic M, Petkovic J, Novak S. Titanium dioxide in our everyday life; is it safe? Radiol Oncol. 2011 Dec;45(4):227-247.
• 3.EU No 1223/2009. Commission Regulation (EU) on cosmetic products No 1223/2009 Official Journal of the European Union (30 November 2009).
• 4.FDA. Sunscreen drug products for over-the-counter human use, Final Monograph, Federal Register 64 27666, US Rockville, MD; 2000.
• 5.Newman MD, Stotland M, Ellis JI. The safety of nanosized particles in titanium dioxide and zinc oxide-based sunscreens. J Am Acad Dermatol. 2009 61:685-692.
• 6.European Association for the Study of the Liver. Electronic address: [e-mail]; Clinical Practice Guideline Panel: Chair:; Panel members; EASL Governing Board representative:. EASL Clinical Practice Guidelines: Drug-induced liver injury. J Hepatol. 2019;70(6):1222-1261.
• 7.Davern TJ. Drug-induced liver disease. Clin Liver Dis. 2012;16:231.
• 8.Zimmerman HJ. Drug-induced liver disease. Clin Liver Dis. 2000;4:73.
• 9.Alkhachroum AM, Rubinos C, Kummer BR, et al. Risk of seizures and status epilepticus in older patients with liver disease. Epilepsia. 2018;59(7):1392-1397.
• 10.Sanneerappa PB, Gul R, Nadeem M, Ramesh N. Arachnoid Cyst: An Unusual Cause for Increased Alkaline Phosphatase. Ir Med J. 2016;109(9):475.
• 11.Kleiner DE, Chalasani NP, Lee WM, Fontana RJ, Bonkovsky HL, Watkins PB, Hayashi PH, Davern TJ, Navarro V, Reddy R, Talwalkar JA, Stolz A, Gu J, Barnhart H, Hoofnagle JH; Drug-Induced Liver Injury Network (DILIN). Hepatic histological findings in suspected drug-induced liver injury: systematic evaluation and clinical associations. Hepatology. 2014 Feb;59(2):661-670.
• 12.Liver Injury Caused by Drugs - Hepatic and Biliary Disorders - Merck Manuals Professional Edition; 2023. https://www.merckmanuals.com/professional/hepatic-and-biliary-disorders/drugs-and-the-liver/liver-injury-caused-by-drugs
• 13.Tyner KM, Wokovich AM, Godar DE, Doub WH, Sadrieh N. The state of nano-sized titanium dioxide (TiO2) may affect sunscreen performance. Int J Cosmetic Sci. 2010;33:234-244.
• 14.Lademann J, Weigmann H, Rickmeyer C, Barthelmes H, Schaefer H, Mueller G, et al. Penetration of titanium dioxide microparticles in a sunscreen formulation into the horny layer and the follicular orifice. Skin Pharmacol Appl Skin Physiol. 1999;12:247-256.
• 15.Pflucker F, Wendel V, Hohenberg H, Gartner E, Will T, Pfeiffer S, et al. The human stratum corneum layer: an effective barrier against dermal uptake of different forms of topically applied micronised titanium dioxide. Skin Pharmacol Appl Skin Physiol. 2001; 14: 92-97.
• 16.Schulz J, Hohenberg H, Pflucker F, Gartner E, Will T, Pfeiffer S, et al. Distribution of sunscreens on skin. Adv Drug Deliv Rev. 2002;54:157-163.
• 17.Schilling K, Bradford B, Castelli D, Dufour E, Nash JF, Pape W, et al. Human safety review of “nano” titanium dioxide and zinc oxide. Photochem Photobiol Sci. 2010;9: 495-509.
• 18.Senzui M, Tamura T, Miura K, Ikarashi Y, Watanabe Y, Fujii M. Study on penetration of titanium dioxide (TiO2) nanoparticles into intact and damaged skin in vitro. J Toxicol Sci. 2010;35:107-113.
• 19.Tan MH, Commens CA, Burnett L, Snitch PJ. A pilot study on the percutaneous absorption of microfine titanium dioxide from sunscreens. Australas J Dermatol. 1996;37:185-187.
• 20.Walter Brand, Ruud J. B. Peters, Hedwig M. Braakhuis, Lidka Maślankiewicz & Agnes G. Oomen. Possible effects of titanium dioxide particles on human liver, intestinal tissue, spleen and kidney after oral exposure, Nanotoxicology. 2020;14:7,985-1007,
• 21.Osmond-McLeod MJ, Oytam Y, Rowe A et al. Long-term exposure to commercially available sunscreens containing nanoparticles of TiO2 and ZnO revealed no biological impact in a hairless mouse model. Part Fibre Toxicol. 2016;13:44.
• 22.Dunford R, Salinaro A, Cai LZ, Serpone N, Horikoshi S, Hidaka H, et al. Chemical oxidation and DNA damage catalysed by inorganic sunscreen ingredients. Febs Lett. 1997;418:87-90.
• 23.Gurr JR, Wang ASS, Chen CH, Jan KY. Ultrafine titanium dioxide particles in the absence of photoactivation can induce oxidative damage to human bronchial epithelial cells. Toxicology. 2005;213:66-73.
• 24.Long TC, Tajuba J, Sama P, Saleh N, Swartz C, Parker J, et al. Nanosize titanium dioxide stimulates reactive oxygen species in brain microglia and damages neurons in vitro. Environ Health Persp. 2007;115:1631-1637.
• 25.Lu N, Zhu Z, Zhao X, Tao R, Yang X, Gao Z. Nano titanium dioxide photocatalytic protein tyrosine nitration: a potential hazard of TiO2 on skin. Biochem Biophys Res Commun. 2008;370:675-680.
• 26.Park EJ, Yi J, Chung YH, Ryu DY, Choi J, Park K. Oxidative stress and apoptosis induced by titanium dioxide nanoparticles in cultured BEAS-2B cells. Toxicol Lett. 2008;180:222-229.
• 27.Sayes CM, Wahi R, Kurian PA, Liu Y, West JL, Ausman KD, et al. Correlating nanoscale titania structure with toxicity: a cytotoxicity and inflammatory response study with human dermal fibroblasts and human lung epithelial cells. Toxicol Sci. 2006;92:174-185.
• 28.Wang JX, Chen CY, Liu Y, Jiao F, Li W, Lao F, et al. Potential neurological lesion after nasal instillation of TiO2 nanoparticles in the anatase and rutile crystal phases. Toxicol Lett. 2008;183:72-80.
• 29.Cichoż-Lach H, Michalak A. Oxidative stress as a crucial factor in liver diseases. World J Gastroenterol. 2014;20(25):8082-8091.
• 30.Petković J, Žegura B, Stevanović M, Drnovšek N, Uskoković D, Novak S et al. DNA damage and alterations in expression of DNA damage responsive genes induced by TiO2 nanoparticles in human hepatoma HepG2 cells. Nanotoxicology. 2011;5:341-353.
• 31.Kang JL, Moon C, Lee HS, Lee HW, Park EM, Kim HS, et al. Comparison of the biological activity between ultrafine and fine titanium dioxide particles in RAW 264.7 cells associated with oxidative stress. J Toxicol Environ Health, Part A. 2008;71:478-485.
• 32.Rahman Q, Lohani M, Dopp E, Pemsel H, Jonas L, Weiss DG, et al. Evidence that ultrafine titanium dioxide induces micronuclei and apoptosis in Syrian hamster embryo fibroblasts. Environ Health Persp. 2002;110:797-800.
• 33.Wang JJ, Sanderson BJS, Wang H. Cyto- and genotoxicity of ultrafine TiO2 particles in cultured human lymphoblastoid cells. Mutat Res-Gen Tox En. 2007;628:99-106.
• 34.Xu A, Chai YF, Nohmi T, Hei TK. Genotoxic responses to titanium dioxide nanoparticles and fullerene in gpt delta transgenic MEF cells. Part Fibre Toxicol. 2009;6:3.