Nano -Titanium Nitride Causes Developmental Toxicity: Review

Introduction

Nano-titanium nitride is widely used for manufacturing various industrial products, including medical devices, personal care products, cosmetics, imitated jewelry, and food additives. It is a very attractive metal with excellent biocompatibility and high resistance to corrosion and wear. Therefore, this highly useable nanomaterial produces toxic consequences for human health. Nanotechnology using titanium nitride has shown some adverse effects on the health of a person exposed. It disturbs the glucose and lipid metabolism in animals as well. In addition, titanium nitride can lead to oxidative stress in the body and causes genotoxicity, poor immune responses, inflammation, and damage to cells. These nanoparticles may also enter the placenta and cause damage to fetal growth and development.

What Are the Studies Related to Nano-Titanium Nitride Causing Developmental Toxicity?

• Nano-titanium nitride (Nano-TiN) is used commercially but has toxicological effects on the environment. The fish was exposed to different levels and concentrations of nano titanium nitride for almost five days.

• The zebrafish exposed to nano-TiN started showing developmental toxicity effects after a few hours of exposure, depending upon the dose and time of nanoparticle exposure.

• It was also found that with an increase in time and concentration of exposure to titanium nitride nanoparticles, developmental deformities, and mortality also increased.

• Mortality rate and body size or growth were grossly affected due to exposure. It also affected the development of other vital organs like the liver, kidney, and nerves, increasing reactive oxygen species and poor antioxidant capacity.

• The research showed that developmental toxicity could be caused by nano-titanium nitride exposure in zebrafish due to oxidative stress.

• Another study performed on pregnant rats exposed to titanium nitride nanoparticles showed a decrease in fetal weight, and degenerative were evident in the liver, brain, and kidney. Teratogenic effects observed in pregnant rats also showed the relation between growth-stimulating hormone(GSH) levels and lipid peroxidation in the rat's body.

What Are the Modes of Nano-Titanium Nitride Exposure?

• Oral Route- Exposure to titanium nitride nanoparticles can occur via the oral route as they are present in sunscreens, toothpaste, and foods. These nanoparticles stay inside the body organs for a prolonged period and get excreted through stool. The particles that get absorbed into the kidneys, lungs, spleen, and liver tissues cause toxicity in the body and also lead to liver damage.

• Inhalation Route- This is the most common route of titanium nitride nanoparticle exposure as the particles can travel via lung tissues, airway path, and capillaries into the liver, heart, and other organs. Therefore, it causes toxicological effects on various organs of the body.

• Dermal Route- Skin is a barrier that prevents exposure to titanium nitride nanoparticles through skin penetration. Some studies show that these nanoparticles cannot cross the skin barrier, whereas others have shown that they cross the skin dermis and causes toxicity in the body.

• Intravenous Route- Titanium nitride nanoparticles are excellent medicinal and photothermal agents used to cancerous tissues from the body. Although nano-TiN produces toxicity, it can help remove or kill cancer cells completely during photothermal cancer therapy. Intravenous injection of nano-TiN can disrupt the endothelial cells despite immunogenicity and toxicity.

What Are the Health Effects Caused by Nano-Titanium Nitride Exposure?

• Neural System- Titanium nitride nanoparticles can cause neurotoxicity, increase oxidative stress and affect the brain. It can also affect the neurons in the cerebral cortex.

• Respiratory System- Lungs can be majorly affected due to nanoparticle exposure via inhalation of toxic pollution in the environment. It can cause lung dysfunction, tumor, and fibrosis development in the lungs. Titanium nitride nanoparticles can cause bronchial and alveolar genotoxicity due to high exposure.

• Urinary System- Titanium nanoparticle exposure can cause damage to kidneys due to high levels of exposure, and kidneys can be the main target site for toxicity. But human renal toxicity due to titanium nitride nanoparticle exposure needs more research.

• Digestive System- Oral ingestion of nano-TiN can affect the digestive system, and the toxic blood and pass from the stomach to the liver, thus affecting liver functioning. It can cause liver cell damage, hepatocyte dysfunction, and liver failure.

• Reproductive System- Titanium nitride nanoparticles do not affect ovaries, testis, or fetal tissues. However, they can produce pregnancy difficulties and enter the fetus's placenta, brain, and liver. The Developmental toxicity produced by exposure to nano-TiN in humans does not have specific evidence.

• Dermal System- Dermal exposure to titanium nitride nanoparticles can cause toxicity only due to prolonged exposure. It affects the keratinocyte cells in humans by damaging the cell apoptosis process. Sunscreens used on the body also have high photocatalytic activity due to titanium nitride nanoparticles, which is why it is banned now.

• Cardiovascular System- Exposure to titanium nitride nanoparticles can cause damage to DNA (deoxyribonucleic acid) due to mitochondria-mediated apoptosis and can also affect the red blood cell oxygen-carrying capacity. Genotoxicity was caused only due to high exposure to nanoparticles of titanium nitride.

What Is the Mechanism of Titanium Nitride Nanoparticle Toxicity?

• Cellular Uptake- This occurs in two ways that are by free diffusion and endocytosis in the cell.

• Genotoxicity- Nano-TiN causes genotoxicity by forming micronuclei and damaging the DNA, which strongly depends upon the form and size of the nanoparticles.

• Immunotoxicity- Titanium nitride nanoparticles are actively taken up by platelets, macrophages, leukocytes, and monocytes due to the physicochemical properties of the nanoparticles.

• Oxidative Stress- Titanium nitride-induced oxidative stress can cause an increase in reactive oxygen species, depletion of antioxidants, and production of oxidative products.

• Neurotoxicity- Titanium nitride nanoparticles can cross the blood-brain barrier in the central nervous system by inhalation route translocation and causes oxidative stress in the brain.

Conclusion

Titanium nitride nanoparticles are extensively used in various products like plastics, paints, medical devices, biomedical, and cosmetics. This reasonably increases titanium nitride exposure concerns and associated health risks. It affects the human body causing health hazards such as neurotoxicity, genotoxicity, immunotoxicity, and cytotoxicity after penetration. Studies show titanium nitride nanoparticles can cause chromosomal defects and DNA strand breaks. It also causes developmental toxicity in zebrafish, which is evident in research. But human association with developmental toxicity caused by titanium nitride nanoparticle exposure still needs more research and a strong basis for assumption.