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5.4 Titanium Dioxide Nanoparticles (TiO 2 Nanoparticles)
Titanium dioxide (TiO 2 ) nanoparticles are commonly used for drug delivery systems, antibacterial materials, cosmetics, sunscreens, and electronics. Nanoparticles
generally possess dramatically different physicochemical properties compared to
fine particles (FPs). Traditionally, TiO 2 FPs have been considered as poorly soluble,
low toxicity particles, so they are used as a “negative control” in toxicological studies. Rats are exposed to high concentration of TiO 2 FPs for 2 years and lung tumors
developed therefore, the International Agency for Research on Cancer (IARC) classified TiO 2 as a Group 2B carcinogen (possibly carcinogenic to humans). However,
the tumorigenic effect of TiO 2 FPs has been questioned and attributed to lung overload rather than specific carcinogenicity of fine TiO 2 (Shi et al. 2013). Sager et al.
investigated toxicity of both TiO 2 nanoparticles (80/20 anatase/rutile; 21 nm, P-25)
and TiO 2 FPs (100% rutile; 1μm) in rats. They showed that nano TiO 2 was 40-fold
more potent in inducing lung inflammation and damage at 1 and 42 days after exposure than fine TiO 2 on an equal mass burden. However, respective potencies were
not significantly different when dose was expressed on the basis of total surface area
of particles delivered to the lung (Sager et al. 2008).
Genotoxicity of titanium dioxide (TiO 2 ) nanoparticles have been investigated in
numerous studies. Comet assay and micronucleus test have been applied to show
DNA damage of TiO 2 nanoparticles in different cell cultures and animal models.
The standard comet assay, not enzyme-modified comet assay, is able to discriminate
between the genotoxicity of different types of TiO 2 . According to the standard
comet assay, anatase TiO 2 is one of the strongest genotoxic type among TiO 2
nanoparticles. It correlates with their photocatalytic activities (Møller et al. 2017).
Many studies (in vivo and in vitro) were carried out to investigate the genotoxicity
of TiO 2 FPs and nanoparticles, but results are conflicting. Some studies showed that
TiO 2 nanoparticles are genotoxic, whereas the others not. The reason for different
results may be due to the use of different nanoparticle sizes, particle dispersion,
exposure metrics, crystalline structure, and cell types may be an explanation (Shi
et al. 2013).
Anatase TiO2-NPs cause greater responses, a reduction of cell viability, an
increase of inflammatory indices (e.g., lactate dehydrogenase, LDH, interleukin-8 ,
IL-8) and an increase in Radical Oxygen Species (ROS) generation. Therefore, it
induces the cell death by an intrinsic apoptosis pathway (Iavicoli et al. 2011).
Studies have revealed that TiO2 nanoparticles are more toxic than FPs in different
animal models and multiple exposure routes such as inhalation, dermal exposure,
intratracheal instillation, oral gavage, intragastric, intraperitoneal, or intravenous
injection Oberdorster 2001; Oberdorster et al. 1994; Shakeel et al. 2016; Liu and
Yang 2013; Grissa et al. 2015). There is no information on acute toxicity for TiO2
nanoparticles in humans. A value often given in animal toxicity studies is the median
lethal dose (LD50)/median lethal concentration (LC50), which is defined as the
dosage/concentration resulting in the death of 50% of the experimental animals (Shi
et al. 2013).
5 Nanomaterials Causing Cellular Toxicity and Genotoxicity
5.4 Titanium Dioxide Nanoparticles (TiO 2 Nanoparticles)
Titanium dioxide (TiO 2 ) nanoparticles are commonly used for drug delivery systems, antibacterial materials, cosmetics, sunscreens, and electronics. Nanoparticles
generally possess dramatically different physicochemical properties compared to
fine particles (FPs). Traditionally, TiO 2 FPs have been considered as poorly soluble,
low toxicity particles, so they are used as a “negative control” in toxicological studies. Rats are exposed to high concentration of TiO 2 FPs for 2 years and lung tumors
developed therefore, the International Agency for Research on Cancer (IARC) classified TiO 2 as a Group 2B carcinogen (possibly carcinogenic to humans). However,
the tumorigenic effect of TiO 2 FPs has been questioned and attributed to lung overload rather than specific carcinogenicity of fine TiO 2 (Shi et al. 2013). Sager et al.
investigated toxicity of both TiO 2 nanoparticles (80/20 anatase/rutile; 21 nm, P-25)
and TiO 2 FPs (100% rutile; 1μm) in rats. They showed that nano TiO 2 was 40-fold
more potent in inducing lung inflammation and damage at 1 and 42 days after exposure than fine TiO 2 on an equal mass burden. However, respective potencies were
not significantly different when dose was expressed on the basis of total surface area
of particles delivered to the lung (Sager et al. 2008).
Genotoxicity of titanium dioxide (TiO 2 ) nanoparticles have been investigated in
numerous studies. Comet assay and micronucleus test have been applied to show
DNA damage of TiO 2 nanoparticles in different cell cultures and animal models.
The standard comet assay, not enzyme-modified comet assay, is able to discriminate
between the genotoxicity of different types of TiO 2 . According to the standard
comet assay, anatase TiO 2 is one of the strongest genotoxic type among TiO 2
nanoparticles. It correlates with their photocatalytic activities (Møller et al. 2017).
Many studies (in vivo and in vitro) were carried out to investigate the genotoxicity
of TiO 2 FPs and nanoparticles, but results are conflicting. Some studies showed that
TiO 2 nanoparticles are genotoxic, whereas the others not. The reason for different
results may be due to the use of different nanoparticle sizes, particle dispersion,
exposure metrics, crystalline structure, and cell types may be an explanation (Shi
et al. 2013).
Anatase TiO2-NPs cause greater responses, a reduction of cell viability, an
increase of inflammatory indices (e.g., lactate dehydrogenase, LDH, interleukin-8 ,
IL-8) and an increase in Radical Oxygen Species (ROS) generation. Therefore, it
induces the cell death by an intrinsic apoptosis pathway (Iavicoli et al. 2011).
Studies have revealed that TiO2 nanoparticles are more toxic than FPs in different
animal models and multiple exposure routes such as inhalation, dermal exposure,
intratracheal instillation, oral gavage, intragastric, intraperitoneal, or intravenous
injection Oberdorster 2001; Oberdorster et al. 1994; Shakeel et al. 2016; Liu and
Yang 2013; Grissa et al. 2015). There is no information on acute toxicity for TiO2
nanoparticles in humans. A value often given in animal toxicity studies is the median
lethal dose (LD50)/median lethal concentration (LC50), which is defined as the
dosage/concentration resulting in the death of 50% of the experimental animals (Shi
et al. 2013).
5 Nanomaterials Causing Cellular Toxicity and Genotoxicity