Assessment of Short-Term Toxicity of Titanium Dioxide Nano Fiber (TDNF) in Sprague Dawley Rats

Nanotechnology is easily becoming one of the fastest growing markets around the globe. Synthetic nanomaterials have many unique chemical and physical properties, mainly due to their huge specific surface area and chemical makeup. Specifically, titanium dioxide (TiO2) nanomaterials have high stability, anticorrosive and photocatalytic properties. These nanomaterials have applications for semiconductor photocatalysis, treatment of water, as a photoactive material in nanocrystalline solar cells, and medicine. However, not much is known about the toxicity of TiO2 in the nanofiber form. The objective of the present study is to investigate the adverse effects associated with acute ingestion of TiO2 nanofiber (TDNF). TDNF was fabricated via an electrospinning method, followed by dispersion in water. Six to seven week old male Sprague Dawley rats were exposed to a total of 0, 40 and 60 ppm of TDNF for two weeks via oral gavage. Weight gain and cumulative weight eaten was tracked during the course of the study, displaying statistically insignificant concentration-dependent alterations among the three treatment groups. Differences in organ weights were not statistically significant among treatment groups. Blood serum was tested for Albumin, Alanine aminotransferase, and Lactase dehydrogenase to detect tissue damage in the lungs, liver, and kidney. Results from the blood serum indicated possible damage with respect to the kidney and liver. These findings were followed by global gene expression analysis to identify which transcripts might be responsive to TNDF toxicity. Differentially expressed mRNA levels among the liver, kidney, and lung yielded interesting results. Further analysis is needed to interpret what is being done to the tissue. One theory is the fact that TNDF is unable to penetrate the cell as a result; it forms a phagocytosis site and thus triggers inflammatory and immune response. All results taken together, short-term ingestion of titanium dioxide nano fiber (TNDF) produced marginal effects indicative of toxicity

THE POTENTIAL MODULATORY EFFECT OF RUTIN ON TITANIUM DIOXIDE NANOPARTICLES-INDUCED RENAL INJURY IN MALE MICE

Objective: This study aimed to investigate the possible protective effect of rutin in management of TiO2NPs-induced renal injury in mice. Methods: Forty male Swiss albino mice were randomly divided into four groups (n=10). Group (I) served as a control group, group (II) received 100 mg/kg body weight (b. wt) of rutin (orally), group (III) received 70 mg/kg b. wt of TiO2NPs,injected intraperitoneally (i. p.), Group (IV) received 70 mg/kg b. wt of TiO2NPs plus 100 mg/kg b. wt of rutin; for 14 successive days. The renal toxicity was determined through evaluating the renal function biomarkers (serum creatinine, urea, and uric acid) and the levels of malondialdehyde (MDA), reduced glutathion (GSH), nuclear factor kappa B (NF-kB), tumor necrosis factor-α (TNF)-α, B-cell lymphoma (BCL)-2 and caspase-3 in renal tissues. Results: Administration of TiO2NPs plus rutin prevented the deleterious effect of TiO2NPs on mice kidneys through improving the renal functions, and alleviating the increase in MDA, NF-kB, TNF-α, and caspase-3 levels, as well as the decrease in GSH andBCL-2 levels, in renal tissues. Conclusion: Taken together, these findings suggested that rutin plays a role in alleviating TiO2NPs-induced oxidative stress, inflammation, and apoptosis, and exerts renal protective effects

Physiological and Hormonal Effects of Titanium Dioxide Nanoparticles on Thyroid and Kidney Functions

 تُستخدم الجسيمات النانوية لثاني أكسيد التيتانيوم (TiO2 NPs) بشكل عام في أنواع مختلفة من التطبيقات مثل صناعة البلاستيك، وصناعة الورق، والدهانات، ومعجون الأسنان، ومستحضرات التجميل، واقيات الشمس، وفي أنماط الحياة المختلفة، بسبب النطاق الواسع من التطبيقات وتعرضنا اليومي لهذه الجسيمات النانوية ونقص المعلومات عن صحة الحيوان والأنسان ، صُممت هذه الدراسة للكشف عن الآثار التي تعتمد على الجرعة والوقت من TiO2-NPs على وظائف الغدة الدرقية والكلى في ذكور الجرذان. لهذا الغرض تم استخدام   54 ذكر من الجرذان البيض وتم تصنيفها الى ثلاثة مجاميع رئيسية  ( 3,2,1) كل مجموعه تتضمن 18 جرذ عوملت بثلاث  فترات زمنية مختلفة  (1 ,2 ,4)  أسابيع  على التوالي. وتم تقسيم هذه المجاميع الى ثلاث مجاميع فرعية كل منها تتضمن ست  حيوانات تمت معاملتها على النحو التالي : (1) سيطرة , المجموعة (2 ,3) حقنت بالتجويف البروتوني بجرعات متزايدة من دقائق التيتانيوم النانوية (50 ,200) ملغ  /  كغم على التوالي.  , في نهاية  التجربة  شرحت الجرذان وتم حساب وزن الغدة ووزن الكلى اليمنى واليسرى . النتائج اظهرت انخفاض معنوي عالي (p≤ 0.01) في وزن الغدة الدرقية وارتفاع معنوي عالي (p≤ 0.01) في وزن الكلى وفي مستوى هرمون TSH ويوريا الدم والكرياتين   ومعدل البروتين الكلي , بينما انخفاض معنوي عالي في مستويات هرمون  T3  و  T4  المعاملة بجرعات مختلفة من 50- 200  ملغم / كغم TiO2في جميع الفترات الزمنية (1،2،4)  اسابيع . توضح نتائج الدراسة الحالية انخفاضًا كبيرًا في مستوى مصل T4 و T3 مع التعرض لـ TiO2 NPS الذي يعطل وظيفة الغدة الدرقية ، بينما يرفع TiO2 NPS مستوى اليوريا والبروتين الكلي والكرياتينين. يمكن أن يكون هذا مرتبطًا بالجرعة العالية من TiO2-NPs ومدة الدراسة ، مما تسبب في تنكس ونخر خلايا الكلى وتلف في الحويصلات مما أدى إلى منع الإفراز الذي رفع مستويات اليوريا في الدم ، كما أدى إلى مستويات عالية من الكرياتينين والبروتين الكلي في المصل بسبب الخلل الذي حدث في وظائف الكلى.           Titanium dioxide nanoparticles (TiO2 NPs) are generally used in different types of applications such as the industry of plastics, paper industry, paints, toothpaste, cosmetics, sunscreens, and in various lifestyles, because of the vast range of applications and our daily exposure to these nanoparticles and a lack of information on animal and human health this study was designed to reveal dose and time-dependent effects of TiO2-NPs on the thyroid gland and kidney functions in male rats. For this study 54, Sprague-Dawley albino adult male rats were classified into three main groups each of 18 rats treated for a particular duration (1,2, and 4) weeks respectively. Each group was subdivided into three subgroups each of six rats treated as follows; group (1) serve as normal control, group (2, and 3) intra-peritoneal treated with TiO2NPs (50,200) mg/kg respectively, rats are dissected at the end of each experiment and the weights of thyroid and kidney is measured. The result showed a highly significant decrease (p<0.01) in the thyroid gland and a highly significant increase (p<0.01) in kidney weights and TSH, blood urea, creatinine, and total protein, while a highly significant decrease (p<0.01) inT3 and T4 in all different doses (50,200) mg/kg at durations 1, 2 and 4 weeks. The outcomes of the present study illustrate a significant decrease in serum levels of T4 and T3 with exposure to TiO2 NPS which disrupts thyroid function, while TiO2 NPS raises the level of urea, total protein, and creatinine. This could be related to the high dose of TiO2-NPs and duration of the study, which caused degeneration and necrosis of kidney cells and damage to peritubules that led to the prevention of secretion which raised urea levels in the blood, also led to high levels of creatinine and total protein in serum because of the imbalance that occurred in the kidney functions

Adverse Outcome Pathways Associated with the Ingestion of Titanium Dioxide Nanoparticles—A Systematic Review

Funding Information: This research was funded by the Portuguese Foundation for Science and Technology FCT/MCTES through national funds (PIDDAC), PTDC/SAU-PUB/29481/2017 and co-funded by UIDB/00009/2020 (Centre for Toxicogenomics and Human Health—ToxOmics (UIDP/00009/2020; UIDB/00009/2020), iMed.ULisboa (UIDB/04138/2020+UIDP/04138/2020), CESAM (UIDP/50017/2020+UIDB/50017/2020+LA/P/0094/2020), and BioISI (UID/MULTI/04046/2019). N.V. thanks the Fundação para a Ciência e a Tecnologia/Ministério da Ciência, Tecnologia, e Ensino Superior, for her PhD grant 2020.07168.BD. L.G. was supported by FCT Individual CEEC as a Principal Researcher Grant (CEECIND/03143/2017) and R.A. as an Assistant Researcher Grant (CEECIND/01570/2018). Publisher Copyright: © 2022 by the authors.Titanium dioxide nanoparticles (TiO2-NPs) are widely used, and humans are exposed through food (E171), cosmetics (e.g., toothpaste), and pharmaceuticals. The oral and gastrointestinal (GIT) tract are the first contact sites, but it may be systemically distributed. However, a robust adverse outcome pathway (AOP) has not been developed upon GIT exposure to TiO2-NPs. The aim of this review was to provide an integrative analysis of the published data on cellular and molecular mechanisms triggered after the ingestion of TiO2-NPs, proposing plausible AOPs that may drive policy decisions. A systematic review according to Prisma Methodology was performed in three databases of peer-reviewed literature: Pubmed, Scopus, and Web of Science. A total of 787 records were identified, screened in title/abstract, being 185 used for data extraction. The main endpoints identified were oxidative stress, cytotoxicity/apoptosis/cell death, inflammation, cellular and systemic uptake, genotoxicity, and carcinogenicity. From the results, AOPs were proposed where colorectal cancer, liver injury, reproductive toxicity, cardiac and kidney damage, as well as hematological effects stand out as possible adverse outcomes. The recent transgenerational studies also point to concerns with regard to population effects. Overall, the findings further support a limitation of the use of TiO2-NPs in food, announced by the European Food Safety Authority (EFSA).publishersversionpublishe

Adverse Outcome Pathways Associated with the Ingestion of Titanium Dioxide Nanoparticles - A Systematic Review

This article belongs to the Special Issue New Insights in Toxicity and Cytotoxicity of NanomaterialsReviewTitanium dioxide nanoparticles (TiO2-NPs) are widely used, and humans are exposed through food (E171), cosmetics (e.g., toothpaste), and pharmaceuticals. The oral and gastrointestinal (GIT) tract are the first contact sites, but it may be systemically distributed. However, a robust adverse outcome pathway (AOP) has not been developed upon GIT exposure to TiO2-NPs. The aim of this review was to provide an integrative analysis of the published data on cellular and molecular mechanisms triggered after the ingestion of TiO2-NPs, proposing plausible AOPs that may drive policy decisions. A systematic review according to Prisma Methodology was performed in three databases of peer-reviewed literature: Pubmed, Scopus, and Web of Science. A total of 787 records were identified, screened in title/abstract, being 185 used for data extraction. The main endpoints identified were oxidative stress, cytotoxicity/apoptosis/cell death, inflammation, cellular and systemic uptake, genotoxicity, and carcinogenicity. From the results, AOPs were proposed where colorectal cancer, liver injury, reproductive toxicity, cardiac and kidney damage, as well as hematological effects stand out as possible adverse outcomes. The recent transgenerational studies also point to concerns with regard to population effects. Overall, the findings further support a limitation of the use of TiO2-NPs in food, announced by the European Food Safety Authority (EFSA).This research was funded by the Portuguese Foundation for Science and Technology FCT/MCTES through national funds (PIDDAC), PTDC/SAU-PUB/29481/2017 and co-funded by UIDB/00009/2020 (Centre for Toxicogenomics and Human Health—ToxOmics (UIDP/00009/2020; UIDB/00009/2020), iMed.ULisboa (UIDB/04138/2020+UIDP/04138/2020), CESAM (UIDP/50017/ 2020+UIDB/50017/2020+LA/P/0094/2020), and BioISI (UID/MULTI/04046/2019). N.V. thanks the Fundação para a Ciência e a Tecnologia/Ministério da Ciência, Tecnologia, e Ensino Superior, for her PhD grant 2020.07168.BD. L.G. was supported by FCT Individual CEEC as a Principal Researcher Grant (CEECIND/03143/2017) and R.A. as an Assistant Researcher Grant (CEECIND/01570/2018)info:eu-repo/semantics/publishedVersio

Safety assessment of titanium dioxide (E171) as a food additive

Acknowledgements: The Panel wishes to thank the following for the support provided to this scientific output: Ana Campos Fernandes, Laura Ciccolallo, Esraa Elewa, Galvin Eyong, Christina Kyrkou, Irene Munoz, Giorgia Vianello, the members of the SCER Cross-cutting WG nanotechnologies: Jacqueline Castenmiller, Mohammad Chaudhry, Roland Franz, David Gott, Stefan Weigel and the former member of the SCER Cross-cutting WG Genotoxicity Maciej Stepnik. The FAF Panel wishes to acknowledge all European competent institutions, Member State bodies and other organisations that provided data for this scientific output.Peer reviewedPublisher PD

Safety of titanium dioxide nanoparticles in cosmetics

Titanium dioxide (TiO2) is widely used in a variety of products including cosmetics. TiO2 in its nanoparticle form (nano-TiO2) is now the only form used as an ultraviolet (UV) filter in sunscreens, but also in some day creams, foundations and lip balms. While its efficacy as a UV filter is proven in the prevention of skin cancers and sunburns, some concerns have been raised about its safety. Indeed, considering its small size, nano-TiO2 is suspected to penetrate dermal, respiratory or gastrointestinal barriers, disseminate in the body and therefore constitute a potential risk to the consumer. At the skin level, most studies performed in humans or animals showed that nano-TiO2 did not penetrate beyond the outer layers of stratum corneum to viable cells and did not reach the general circulation, either in healthy or in compromised skin. The Scientific Committee on Consumer Safety (SCCS) considers nano-TiO2 as a non-sensitizer and as mild- or non-irritant to skin and concludes in no evidence of carcinogenicity (supported by the European Chemicals Agency), mutagenicity or reproductive toxicity after dermal exposure to nano-TiO2. According to the SCCS, nano-TiO2 from sunscreens does not present any health risk when applied on the skin at a concentration up to 25%. However, the SCCS does not recommend the use of nano-TiO2 in formulations that may lead to exposure of the consumer's lungs by inhalation (sprayable products and powders). Indeed, even if human data are sparse and inconsistent, lung inflammation was reported in animals. In 2016, the EU Cosmetic Regulation made nano-TiO2 as an authorized UV filter, except in products that could lead to exposure of the lungs. After oral exposure, nano-TiO2 absorption and toxicity are limited. The incidental oral exposure to nano-TiO2 contained in lip balms is thus not expected to induce adverse health effects

Studi Toksisitas Nanopartikel Organ Limpa pada Hewan Percobaan, Tinjauan Scoping Review

Nanotechnology has been developing in the medical field, but some nanoparticles have toxic effects on the body, including the spleen. This scoping review represents an attempt to take stock of existing research results related to the presence or absence of toxicity to the spleen caused by nanoparticles involving experimental animals. A scoping review was conducted to synthesize and map the toxicity of nanoparticles. It has been searched on PubMed databases for spleen or lien and toxic or toxicity, and nanoparticles or dendrimers or "metal nanoparticles" or “magnetite nanoparticles” or nanoshells or “multifunctional nanoparticles” or nanocapsules or nanoconjugates or nanodiamonds or nanogels or nanospheres. Seventeen studies met our inclusion criteria. In conclusion, it showed that 13 nanoparticles could cause toxicity in rodent spleen and as many as 4 nanoparticles did not cause toxicity in rodent spleen.Nanoteknologi telah berkembang di bidang medis, namun beberapa nanopartikel memiliki efek toksik pada tubuh seperti limpa. Tinjauan scoping review ini merupakan upaya untuk mengambil hasil-hasil penelitian yang sudah ada terkait dengan ada tidaknya toksisitas pada limpa yang disebabkan oleh partikel nano yang melibatkan hewan percobaan. Tinjauan scoping review dilakukan untuk mensintesis dan memetakan toksisitas nanopartikel. Hasil penelitian di cari melalui PubMed dengan kata kunci: spleen OR lien AND toxic OR toxicity AND nanoparticles OR dendrimers OR metal nanoparticles OR magnetite nanoparticles OR nanoshells OR multifunctional nanoparticles OR nanocapsules OR nanoconjugates OR nanodiamonds OR nanogels OR nanospheres. Tujuh belas studi memenuhi kriteria inklusi. Kesimpulannya, menunjukkan bahwa 13 nanopartikel dapat menyebabkan toksisitas pada limpa hewan pengerat dan sebanyak 4 nanopartikel tidak menyebabkan toksisitas pada limpa hewan pengerat

Titanium dioxide nanoparticles oral exposure to pregnant rats and its distribution

Background: Titanium dioxide (TiO2) nanoparticles are among the most manufactured nanomaterials in the industry, and are used in food products, toothpastes, cosmetics and paints. Pregnant women as well as their conceptuses may be exposed to TiO2 nanoparticles; however, the potential effects of these nanoparticles during pregnancy are controversial, and their internal distribution has not been investigated. Therefore, in this study, we investigated the potential effects of oral exposure to TiO2 nanoparticles and their distribution during pregnancy. TiO2 nanoparticles were orally administered to pregnant Sprague-Dawley rats (12 females per group) from gestation days (GDs) 6 to 19 at dosage levels of 0, 100, 300 and 1000 mg/kg/day, and then cesarean sections were conducted on GD 20. Results: In the maternal and embryo-fetal examinations, there were no marked toxicities in terms of general clinical signs, body weight, food consumption, organ weights, macroscopic findings, cesarean section parameters and fetal morphological examinations. In the distribution analysis, titanium contents were increased in the maternal liver, maternal brain and placenta after exposure to high doses of TiO2 nanoparticles. Conclusion: Oral exposure to TiO2 during pregnancy increased the titanium concentrations in the maternal liver, maternal brain and placenta, but these levels did not induce marked toxicities in maternal animals or affect embryo-fetal development. These results could be used to evaluate the human risk assessment of TiO2 nanoparticle oral exposure during pregnancy, and additional comprehensive toxicity studies are deemed necessary considering the possibility of complex exposure scenarios and the various sizes of TiO2 nanoparticles