Limits...
Nanotitanium dioxide toxicity in mouse lung is reduced in sanding dust from paint.

Saber AT, Jacobsen NR, Mortensen A, Szarek J, Jackson P, Madsen AM, Jensen KA, Koponen IK, Brunborg G, Gützkow KB, Vogel U, Wallin H - Part Fibre Toxicol (2012)

Bottom Line: We also compared the effects of the same paint with and without NanoTiO2.Pulmonary inflammation and DNA damage and hepatic histopathology were not changed in mice instilled with sanding dust from NanoTiO2 paint compared to paint without NanoTiO2.However, pure NanoTiO2 caused greater inflammation than NanoTiO2 embedded in the paint matrix.

View Article: PubMed Central - HTML - PubMed

Affiliation: The National Research Centre for the Working Environment, Lersø Parkallé 105, Copenhagen, Denmark. ats@nrcwe.dk

ABSTRACT

Background: Little is known of how the toxicity of nanoparticles is affected by the incorporation in complex matrices. We compared the toxic effects of the titanium dioxide nanoparticle UV-Titan L181 (NanoTiO2), pure or embedded in a paint matrix. We also compared the effects of the same paint with and without NanoTiO2.

Methods: Mice received a single intratracheal instillation of 18, 54 and 162 μg of NanoTiO2 or 54, 162 and 486 μg of the sanding dust from paint with and without NanoTiO2. DNA damage in broncheoalveolar lavage cells and liver, lung inflammation and liver histology were evaluated 1, 3 and 28 days after intratracheal instillation. Printex 90 was included as positive control.

Results: There was no additive effect of adding NanoTiO2 to paints: Therefore the toxicity of NanoTiO2 was reduced by inclusion into a paint matrix. NanoTiO2 induced inflammation in mice with severity similar to Printex 90. The inflammatory response of NanoTiO2 and Printex 90 correlated with the instilled surface area. None of the materials, except of Printex 90, induced DNA damage in lung lining fluid cells. The highest dose of NanoTiO2 caused DNA damage in hepatic tissue 1 day after intratracheal instillation. Exposure of mice to the dust from paints with and without TiO2 was not associated with hepatic histopathological changes. Exposure to NanoTiO2 or to Printex 90 caused slight histopathological changes in the liver in some of the mice at different time points.

Conclusions: Pulmonary inflammation and DNA damage and hepatic histopathology were not changed in mice instilled with sanding dust from NanoTiO2 paint compared to paint without NanoTiO2. However, pure NanoTiO2 caused greater inflammation than NanoTiO2 embedded in the paint matrix.

Show MeSH

Related in: MedlinePlus

Correlation between surface area and neutrophil influx. The threshold for inflammatory response for nanoparticles is shown as the correlation between instilled particle surface area and neutrophil cell numbers. The dashed line indicates baseline-level of inflammation in control mice. NOAEL: No observed adverse effects level LOAEL: Lowest observed adverse effect level.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC3298479&req=5

Figure 5: Correlation between surface area and neutrophil influx. The threshold for inflammatory response for nanoparticles is shown as the correlation between instilled particle surface area and neutrophil cell numbers. The dashed line indicates baseline-level of inflammation in control mice. NOAEL: No observed adverse effects level LOAEL: Lowest observed adverse effect level.

Mentions: There is much evidence that the inflammatory response induced by low-toxicity low-solubility particles correlates well with the instilled surface area of the particles [14,23-26]. We found that the specific surface area of NanoTiO2 and Printex 90 correlated strongly with the influx of neutrophils (Figure 5). The results show that the NOEL is 19 cm2 and the LOEL is 53 and 58 cm2 (Printex 90 and NanoTiO2, respectively). Our results are in line with a previous study by Stöger and colleagues demonstrating the existence of a threshold for the particle surface area at an instilled dose of approximately 20 cm2, below which no inflammatory responses could be detected in mice 1 day after intratracheal instillation [27]. In the present study, the effects were reversible over time. The neutrophilic response declined over time from day 1 to 3 and to 28 days after intratracheal instillation. BET analysis was not possible for the paint dust particles due to insufficient amounts of materials. However, estimations from the total airborne particle surface areas and volumes in Koponen et al. [7], suggest that the volume specific surface areas of the sanding dust particles were in the order of 2.8 to 3.5 m2/cm3. The specific surface area of NanoTiO2 and Printex 90 were 107.7 and 295 m2/g, respectively. Hence, assuming a density of 1 g/ml, the instilled paint surface area will only be on the order of 1 to 3% of the specific surface area for the same dose of the pure nanomaterials. This suggests that other factors such as particle chemistry are also important for the toxicity.


Nanotitanium dioxide toxicity in mouse lung is reduced in sanding dust from paint.

Saber AT, Jacobsen NR, Mortensen A, Szarek J, Jackson P, Madsen AM, Jensen KA, Koponen IK, Brunborg G, Gützkow KB, Vogel U, Wallin H - Part Fibre Toxicol (2012)

Correlation between surface area and neutrophil influx. The threshold for inflammatory response for nanoparticles is shown as the correlation between instilled particle surface area and neutrophil cell numbers. The dashed line indicates baseline-level of inflammation in control mice. NOAEL: No observed adverse effects level LOAEL: Lowest observed adverse effect level.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3298479&req=5

Figure 5: Correlation between surface area and neutrophil influx. The threshold for inflammatory response for nanoparticles is shown as the correlation between instilled particle surface area and neutrophil cell numbers. The dashed line indicates baseline-level of inflammation in control mice. NOAEL: No observed adverse effects level LOAEL: Lowest observed adverse effect level.
Mentions: There is much evidence that the inflammatory response induced by low-toxicity low-solubility particles correlates well with the instilled surface area of the particles [14,23-26]. We found that the specific surface area of NanoTiO2 and Printex 90 correlated strongly with the influx of neutrophils (Figure 5). The results show that the NOEL is 19 cm2 and the LOEL is 53 and 58 cm2 (Printex 90 and NanoTiO2, respectively). Our results are in line with a previous study by Stöger and colleagues demonstrating the existence of a threshold for the particle surface area at an instilled dose of approximately 20 cm2, below which no inflammatory responses could be detected in mice 1 day after intratracheal instillation [27]. In the present study, the effects were reversible over time. The neutrophilic response declined over time from day 1 to 3 and to 28 days after intratracheal instillation. BET analysis was not possible for the paint dust particles due to insufficient amounts of materials. However, estimations from the total airborne particle surface areas and volumes in Koponen et al. [7], suggest that the volume specific surface areas of the sanding dust particles were in the order of 2.8 to 3.5 m2/cm3. The specific surface area of NanoTiO2 and Printex 90 were 107.7 and 295 m2/g, respectively. Hence, assuming a density of 1 g/ml, the instilled paint surface area will only be on the order of 1 to 3% of the specific surface area for the same dose of the pure nanomaterials. This suggests that other factors such as particle chemistry are also important for the toxicity.

Bottom Line: We also compared the effects of the same paint with and without NanoTiO2.Pulmonary inflammation and DNA damage and hepatic histopathology were not changed in mice instilled with sanding dust from NanoTiO2 paint compared to paint without NanoTiO2.However, pure NanoTiO2 caused greater inflammation than NanoTiO2 embedded in the paint matrix.

View Article: PubMed Central - HTML - PubMed

Affiliation: The National Research Centre for the Working Environment, Lersø Parkallé 105, Copenhagen, Denmark. ats@nrcwe.dk

ABSTRACT

Background: Little is known of how the toxicity of nanoparticles is affected by the incorporation in complex matrices. We compared the toxic effects of the titanium dioxide nanoparticle UV-Titan L181 (NanoTiO2), pure or embedded in a paint matrix. We also compared the effects of the same paint with and without NanoTiO2.

Methods: Mice received a single intratracheal instillation of 18, 54 and 162 μg of NanoTiO2 or 54, 162 and 486 μg of the sanding dust from paint with and without NanoTiO2. DNA damage in broncheoalveolar lavage cells and liver, lung inflammation and liver histology were evaluated 1, 3 and 28 days after intratracheal instillation. Printex 90 was included as positive control.

Results: There was no additive effect of adding NanoTiO2 to paints: Therefore the toxicity of NanoTiO2 was reduced by inclusion into a paint matrix. NanoTiO2 induced inflammation in mice with severity similar to Printex 90. The inflammatory response of NanoTiO2 and Printex 90 correlated with the instilled surface area. None of the materials, except of Printex 90, induced DNA damage in lung lining fluid cells. The highest dose of NanoTiO2 caused DNA damage in hepatic tissue 1 day after intratracheal instillation. Exposure of mice to the dust from paints with and without TiO2 was not associated with hepatic histopathological changes. Exposure to NanoTiO2 or to Printex 90 caused slight histopathological changes in the liver in some of the mice at different time points.

Conclusions: Pulmonary inflammation and DNA damage and hepatic histopathology were not changed in mice instilled with sanding dust from NanoTiO2 paint compared to paint without NanoTiO2. However, pure NanoTiO2 caused greater inflammation than NanoTiO2 embedded in the paint matrix.

Show MeSH
Related in: MedlinePlus