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Toxicological information

Toxicity to reproduction: other studies

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Administrative data

Endpoint:
toxicity to reproduction: other studies
Remarks:
mechanistic investigations
Type of information:
experimental study
Adequacy of study:
disregarded due to major methodological deficiencies
Reliability:
other: not rated according to Klimisch
Rationale for reliability incl. deficiencies:
other:
Remarks:
The references contained in this summary entry represents in vivo experiments with mechanistic investigations on reproduction toxicity 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 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.

Data source

Reference
Reference Type:
publication
Title:
Anatase titanium dioxide nanoparticles in mice: evidence for induced structural and functional sperm defects after short-, but not long-, term exposure
Author:
Smith, M.A. et al.
Year:
2015
Bibliographic source:
Asian J. Androl. 17, 261-268

Materials and methods

Principles of method if other than guideline:
Smith, M.A. et al. (2015):
Test substance: titanium dioxide, anatase (self-synthesised)
Doses: 2.5 or 5 mg / kg BW
No. of animals per sex per dose: 3 mice (long-term exposure), 9 - 11 mice (short-term exposure), 6-8 (specific investigations e. g. ROS level, hyperactivatedmotility and apoptosis/mitochondrial membrane potential (MMP))
Exposure duration: 1, 2, 3 or 5 weeks (long-term exposure), 24, 48 or 120 h (short-term exposure)
Exposure frequency: daily for 3 consecutive days
Negative control: 0.1 ml of phosphate buffer saline (PBS)
Parameters investigated: inflammatory response (cytokines), oxidative stress (ROS), histopathology of testes and scrotal adipose tissues, sperm recovery, analysis of motility (progressive and hyperactivated) and structural defects, acrosome reactions were evaluated

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
other: solid: bulk / nanomaterial

Test animals

Species:
other: Smith, M.A. et al. (2015): mice (ICR and C57BL/6)
Sex:
male

Administration / exposure

Route of administration:
other: Smith, M.A. et al. (2015): intraperitoneal injection

Results and discussion

Effect levels

Remarks on result:
other:
Remarks:
Smith, M.A. et al. (2015): Anatase TiO2 nanoparticles (ATNP) bioaccumulate in the scrotum where they self-aggregate and lead to testicular histopathology, while severely affecting epididymalsperm maturation and function, after 4–8 days, but not 10 days to 5 weeks, postinjection. Frequencies of flagellar abnormalities, inability to acrosome-react, excess residual cytoplasm (ERCs), and reduced motility were elevated and accompanied by increased ROS levels in sperm of treated males.

Applicant's summary and conclusion

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 mechanistic investigations in reproduction toxicity 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.

Smith, M. A. et al. (2015): The methodical setup is not adequately designed for risk assessment purposes of the test substance. The non-physiological route of administration via intraperitoneal injection is not guideline conform and not suitable to assess toxicity to reproduction. Furthermore, the test material is not sufficiently characterised for hazard assessment purposes.