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Description of key information

Liu, R. et al. (2010): Investigtion of intake and cellular changes in pulmonary alveolar macrophages after TiO2 exposure was conducted.

Husain, M. et al. (2015): Investigation of intake and signaling processed in mice after TiO2 exposure was conducted.

No conclusion can be drawn from the publications due to lack of quality, reliability and adequacy of the experimental data for the fulfilment of data requirements under REACH.

 

The references contained in this section represent in vitro and in vivo experiments with investigations on immunotoxicity with very limited value for risk assessment purposes. All references do not fulfil the criteria for quality, reliability and adequacy of experimental data for the fulfilment of data requirements under REACH and hazard assessment purposes (ECHA guidance R4 in conjunction with regulation (EC) 1907/2006, Annexes VII-X). The information contained therein were included for information purposes only.

Key value for chemical safety assessment

Effect on immunotoxicity: via oral route

Link to relevant study records

Referenceopen allclose all

Endpoint:
immunotoxicity, other
Remarks:
in vitro, cell culture
Type of information:
experimental study
Adequacy of study:
disregarded due to major methodological deficiencies
Reliability:
other: not rated according to Klimisch et al.
Rationale for reliability incl. deficiencies:
other:
Remarks:
The references contained in this summary entry represents in vitro experiments with investigations on immunotoxicity with very limited value for risk assessment purposes. The references do not fulfil the criteria for quality, reliability and adequacy of experimental data for the fulfilment of data requirements under REACH andhazard assessment purposes (ECHA guidance R4 in conjunction with regulation (EC) 1907/2006, Annexes VII-X). The information contained therein were included for information purposes only.
Principles of method if other than guideline:
Liu, R. et al. (2010):
Test substance: TiO2 microsized particles (obtained from Shanghai Titanium dioxide Materials Technology Company Ltd. (China) (crystalline phase anatase, primary particle size 200 nm, particle size in culture medium 287 nm, specific surface area 4 m²/g)
and three different TiO2 nanoparticles, thereof NP-1, NP-2 and NP-3:
- NP-1 from Hongsheng Materials Technology Company Ltd. (China) (crystalline phase anatase, primary particle size 5 nm, particle size in culture medium 348 nm, specific surface area 210 m²/g)
- NP-2 obtained from Degussa (crystalline phase 80 % anatase 20 % rutile, primary particle size 21 nm, particle size in culture medium 238 nm, specific surface area 50 m²/g)
- NP-3 from Hongsheng Materials Technology Company Ltd. (China) (crystalline phase rutile, primary particle size 50 nm, particle size in culture medium 212 nm, specific surface area 30 m²/g)
Test system: pulmonary alveolar macrophages (PAM) isolated from lung lavage fluid of Sprague-Dawley rats
Doses/consentrations: 300, 150, 75, 37.5, 18.75 µg/mL
Exposure conditions: single exposure for 24 h
Negative control: untreated cells
Positive control: not specified
Parameters investigated: nitric oxide (No) and cytokine assay (incl. TNF-alpha, IL-6), phagocytosis ability (uptake of neutral red dye), chemotactic ability (Transwell chamber migration assay), Fc receptor expression (rosettes formation assay), MHC class II expression (flow cytometry)
Remarks on result:
other:
Remarks:
Liu, R. et al. (2010): The study aims to identify correlations of the crystal structure, surface area and doses with immunologic alterations. Quantity of TiO2 particles inside PAMs increased dose-dependant, PAMs displayed incomplete membranes after exposure to NP-1 and NP-2. The NO level significantly increased after exposure to >18.5 µg/mL of NP-1 and NP-2 and to > 37.5 µg/mL of NP-3 and microsized TiO2. TNF-alpha levels were significantly increased after exposure to 18.5 µg/mL NP-1, but only slightly increased after exposure to 300 µg/mL NP-2, NP-3 and microsized TiO2. IL-6 levels were significantly increased after exposure to > 75 µg/mL NP-1 and > 18.75 µg/mL NP-2, as well as 300 µg/mL NP-3 and microsized TiO2. Phagocytic ability and chemotactic was significantly decreased at all doses and test substances. Decreased rosettes formation with sensitised erythrocytes was observed after exposure to TiO2, indicating a decreased Fc receptor expression. Flow cytometry indicated decreased expression of MHC class II molecules after exposure to TiO2.
Conclusions:
No conclusion can be drawn from the above publications due to lack of quality, reliability and adequacy of the experimental data for the fulfilment of data requirements under REACH.

The references contained in this summary entry represent in vitro experiments with investigations on immunotoxicity with very limited value for risk assessment purposes. All references do not fulfil the criteria for quality, reliability and adequacy of experimental data for the fulfilment of data requirements under REACH and hazard assessment purposes (ECHA guidance R4 in conjunction with regulation (EC) 1907/2006, Annexes VII-X). The information contained therein were included for information purposes only.

Liu, R. et al. (2010):
The identity of the isolated cells from rat lung lavage fluid was not analysed, the protocol merely describes the culture of adherent cells. Regarding the in vitro assays, results are questionable since there are experimental / methodical deficiencies (e.g. no data of calibration of the test system, no positive controls and insufficient documentation of data (raw data, tables)). Furthermore, an analytical verification of target concentration is missing. Number of replicates in some assays is not elusive from documentation. The results of the fluorescence activated cell sorting cannot be verified as reliable since there is a lack of data (e.g. frequency of measurements, gating, clusting / choice and differentiation between dead or alive cell populations, no positive control).
Endpoint:
immunotoxicity: inhalation
Type of information:
experimental study
Adequacy of study:
disregarded due to major methodological deficiencies
Reliability:
other: not rated according to Klimisch et al.
Rationale for reliability incl. deficiencies:
other:
Remarks:
The references contained in this summary entry represents in vivo experiments with investigations on immunotoxicity with very limited value for risk assessment purposes. The references do not fulfil the criteria for quality, reliability and adequacy of experimental data for the fulfilment of data requirements under REACH andhazard assessment purposes (ECHA guidance R4 in conjunction with regulation (EC) 1907/2006, Annexes VII-X). The information contained therein were included for information purposes only.
Principles of method if other than guideline:
Husain, M. et al. (2015):
Test substance: Titanium dioxide nanoparticles (UV-Titan L181, Kemira, Pori, Finland), surface modified with zirconium, silicon, aluminium, and polyalcohol, primary particle size 20.6 nm, surface area 107.7 m²/g, 70.8 % rutile
Dose/concentration: Exp1: 18 and 162 µg, Exp2: 162 µg
Control(s): vehicle control (0.9 % NaCl MilliQ water containing 10 % v/v acellular BAL collected from C57BL/6 mice)
No. of animals per sex per dose: Exp1: 6, Exp2: 3
Duration of treatment / exposure: not applicable
Frequency of treatment: single application
Post exposure period: Exp1: 24 hours and 28 days, Exp2: 4 hours and 24 hours
Parameters investigated:
Exp1: TiO2 content in liver and heart tissues (via hyperspectral microscopy), profile of cardiovascular and hepatic global genomic responses after TiO2 translocation
Exp2: TiO2 content in blood
Species:
other: Husain, M. et al. (2015): mouse (C57BL/6)
Sex:
female
Route of administration:
other: Husain, M. et al. (2015): intratracheal instillation
Remarks on result:
other:
Remarks:
Husain, M. et al. (2015): Exp1: Notable amounts of TiO2 were found in livers of mice exposed to the 18 and 162 µg doses sampled 24h post-exposure, decreased amount was observed at 28d post-exposure. Trace amounts of TiO2 were detected at both doses and time points. Activation of complement cascade and inflammatory processes in heart and specific activation of complement factor 3 in blood, suggesting activation of an early innate immune response essential for particle opsonisation and clearance, was observed. The liver showed a subtle response with changes in the expression of genes associated with acute phase response. Exp2: Trace amounts of TiO2 were detected at the 24h post-exposure
Conclusions:
No conclusion can be drawn from the above publications due to lack of quality, reliability and adequacy of the experimental data for the fulfilment of data requirements under REACH.

The references contained in this summary entry represent in vivo experiments with investigations on immunotoxicity with very limited value for risk assessment purposes. All references do not fulfil the criteria for quality, reliability and adequacy of experimental data for the fulfilment of data requirements under REACH and hazard assessment purposes (ECHA guidance R4 in conjunction with regulation (EC) 1907/2006, Annexes VII-X). The information contained therein were included for information purposes only.

Husain, M. et al. (2015):
Regarding the hyperspectral microscopy results, results are questionable since there are experimental / methodical deficiencies (e.g. no data of calibration or validation of the test system, no confirmation of location within cells vie z-axis analysis, no positive controls and an insufficient characterisation of test material). The health status of the animals was not documented. Furthermore, only 2 doses were tested and the vehicle used is unsuitable for risk assessment, since the identity and characteristics are not documented sufficiently.
Endpoint conclusion
Endpoint conclusion:
no study available

Effect on immunotoxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no study available

Effect on immunotoxicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Liu, R. et al. (2010):

The study aims to identify correlations of the crystal structure, surface area and doses with immunologic alterations. Quantity of TiO2 particles inside PAMs increased dose-dependant, PAMs displayed incomplete membranes after exposure to NP-1 and NP-2. The NO level significantly increased after exposure to >18.5 µg/mL of NP-1 and NP-2 and to > 37.5 µg/mL of NP-3 and microsized TiO2. TNF-alpha levels were significantly increased after exposure to 18.5 µg/mL NP-1, but only slightly increased after exposure to 300 µg/mL NP-2, NP-3 and microsized TiO2. IL-6 levels were significantly increased after exposure to > 75 µg/mL NP-1 and > 18.75 µg/mL NP-2, as well as 300 µg/mL NP-3 and microsized TiO2. Phagocytic ability and chemotactic was significantly decreased at all doses and test substances. Decreased rosettes formation with sensitised erythrocytes was observed after exposure to TiO2, indicating a decreased Fc receptor expression. Flow cytometry indicated decreased expression of MHC class II molecules after exposure to TiO2.

The identity of the isolated cells from rat lung lavage fluid was not analysed, the protocol merely describes the culture of adherent cells. Regarding the in vitro assays, results are questionable since there are experimental / methodical deficiencies (e.g. no data of calibration of the test system, no positive controls and insufficient documentation of data (raw data, tables)). Furthermore, an analytical verification of target concentration is missing. Number of replicates in some assays is not elusive from documentation. The results of the fluorescence activated cell sorting cannot be verified as reliable since there is a lack of data (e.g. frequency of measurements, gating, clusting / choice and differentiation between dead or alive cell populations, no positive control).

 

Husain, M. et al. (2015):

Exp1: Notable amounts of TiO2 were found in livers of mice exposed to the 18 and 162 µg doses sampled 24h post-exposure, decreased amount was observed at 28d post-exposure. Trace amounts of TiO2 were detected at both doses and time points.  Activation of complement cascade and inflammatory processes in heart and specific activation of complement factor 3 in blood, suggesting activation of an early innate immune response essential for particle opsonisation and clearance, was observed. The liver showed a subtle response with changes in the expression of genes associated with acute phase response. Exp2: Trace amounts of TiO2 were detected at the 24h post-exposure

Regarding the hyperspectral microscopy results, results are questionable since there are experimental / methodical deficiencies (e.g. no data of calibration or validation of the test system, no confirmation of location within cells vie z-axis analysis, no positive controls and an insufficient characterisation of test material). The health status of the animals was not documented. Furthermore, only 2 doses were tested and the vehicle used is unsuitable for risk assessment, since the identity and characteristics are not documented sufficiently.

Justification for classification or non-classification

No conclusion can be drawn from the publications due to lack of quality, reliability and adequacy of the experimental data for the fulfilment of data requirements under REACH.

 

The references contained in this section represent in vitro and in vivo experiments with investigations on immunotoxicity with very limited value for risk assessment purposes. All references do not fulfil the criteria for quality, reliability and adequacy of experimental data for the fulfilment of data requirements under REACH and hazard assessment purposes (ECHA guidance R4 in conjunction with regulation (EC) 1907/2006, Annexes VII-X). The information contained therein were included for information purposes only.