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Administrative data

Endpoint:
basic toxicokinetics, other
Type of information:
other: A paper-based toxicokinetics assessment by a qualified toxicologist based on summaries of studies on the substance and literature.
Adequacy of study:
key study
Study period:
5.7.2016
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
comparable to guideline study
Remarks:
In accordance with Annex VIII (point 8.8) of Regulation (EC) No 1907/2006 (REACH), a paper-based toxicokinetics assessment has been conducted by a qualified toxicologist based on summaries of studies on the substance and literature. The assessment of the likely toxicokinetic behaviour of the substance is provided to the extent that can be derived from the relevant available information at the time of the assessment. The assessment is based on the Guidance on information requirements and chemical safety assessment Chapter R.7c: Endpoint specific guidance (ECHA, November 2014).

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2016
Report date:
2016

Materials and methods

Objective of study:
absorption
distribution
excretion
metabolism
Principles of method if other than guideline:
The assessment is based on the Guidance on information requirements and chemical safety assessment Chapter R.7c: Endpoint specific guidance (ECHA, November 2014). In accordance with Annex VIII (point 8.8) of Regulation (EC) No 1907/2006 (REACH), a paper-based toxicokinetics assessment has been conducted for the substance by a qualified toxicologist.
GLP compliance:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
nonatitanium(4+) tetrasodium hydrate icosaoxidandiide
EC Number:
601-472-6
Cas Number:
117314-20-2
Molecular formula:
Sodium form: Na4Ti9O20 × n H2O Sodium/hydrogen form: 50 % Na4Ti9O20 × n H2O, 50 % Na2H2Ti9O20 × n H2O
IUPAC Name:
nonatitanium(4+) tetrasodium hydrate icosaoxidandiide
Test material form:
solid: particulate/powder
Remarks:
powder
Details on test material:
- Substance type: commercial product (pure active substance)
- Physical state: Solid powder
- Storage condition of test material: Ambient temperature, humidity and pressure. Stored in sealed containers in darkness.
- Stability under test conditions: Stable
- Purity: ca 100 %
- Particle size distribution: 2.92% <100μm
- Crystal structure: TiO6-octaedra
- Density: 2.83 x 10^3 kg/m3
- pH value: the pH value of the substance in an aqueous solution is appr. 11

Results and discussion

Any other information on results incl. tables

Toxicokinetic behaviour

The substance is a white granular solid and the molecular weight is 843 g/mol. The substance is highly insoluble in water. The substance has a low vapour pressure value (calculated as <1.2x 10^-9 Pa at 25°C), is not highly flammable and does not have explosive or oxidising properties. It is therefore considered to be of low volatility. The percentage of the test item having an inhalable particle size of less than 100 μm was determined to be 2.92%. The test item has been considered to be essentially non-inhalable.

The available repeated dose reproductive OECD 422 screening study (oral route) showed no toxicologically significant treatment-related effects. The oral administration of the substance to rate by gavage, at dose levels of 100, 300 and 1000 mg/kg bw/day was tolerated well. The study therefore showed minimal evidence of significant absorption of the substance.

The acute toxicity studies via oral and dermal routes showed no signs of systemic toxicity. The substance is not a skin sensitiser or skin irritant, but is considered to be an eye irritant. The substance gave negative results in three appropriate in vitro genotoxicity studies in either the presence or absence of an auxiliary metabolising system.

Absorption

Results of the repeated dose reproductive OECD 422 screening study (oral route) showed limited evidence of significant gastric absorption of the test item. The relatively large molecular size of the substance may also limit the amount of absorption through passive diffusion. However, the gastro-intestinal tract may provide a limited route of absorption, following oral administration, before entering the circulatory system via the blood.

It is considered that absorption via the skin will also be limited due to the molecular size of the substance. An acute dermal toxicity study showed no signs of systemic toxicity, so did not show evidence of substantial dermal absorption. As the substance is not a skin corrosive or irritant, potential dermal absorption will not be increased by damage to the skin at point of contact.

Inhalation is not considered to be a significant route of exposure based on the low volatility of the substance and particle size.

Distribution

Substantial systemic distribution of the substance is not evident from the repeated dose reproductive OECD 422 screening study and acute toxicity studies (oral and dermal) due to lack of systemic effects and lack of changes observed in hematology, blood chemistry, organ weights and histopathology.

The substance is highly insoluble and is unlikely to be absorbed unchanged. If absorbed it is likely that the substance is not distributed widely. The substance is not a skin sensitiser (based on results of a LLNA study). This suggests that the substance does not bind to carrier proteins in the circulatory system.

Metabolism

The results of the repeated dose reproduction OECD 422 screening study did not show any evidence of adaptive response in the liver of rats, so there is no evidence of enhanced metabolism. The results of the genotoxicity assays showed that genotoxicity is neither enhanced or diminished in the presence of the S9 metabolising system.

Excretion

Poorly-water soluble substances are not favourable for urinary excretion and therefore biliary excretion may well be a significant route for this substance. There is no evidence from the available studies to suggest enhanced heptatic metabolism to suggest urinary excretion is a significant route of excretion. Any substance that is not adsorbed from the gut will be excreted in the faeces.

Applicant's summary and conclusion

Conclusions:
The available information suggests that absorption of the test substance from the gastrointestinal tract will be limited. Dermal absorption is also considered to be limited. Any substance that is absorbed is unlikely to be widely distributed. Biliary excretion is likely to be the significant route of excretion. Experimental toxicokinetic studies were not available.
Executive summary:

In accordance with Annex VIII (point 8.8) of Regulation (EC) No 1907/2006 (REACH), a paper-based toxicokinetics assessment was conducted by a qualified toxicologist based on summaries of studies on the substance and literature. The assessment of the likely toxicokinetic behaviour of the substance was provided to the extent that can be derived from the relevant available information at the time of the assessment. Experimental toxicokinetic studies were not available.

The available information suggests that the substance is not readily available for absorption via the oral route but limited absorption may be possible. This is supported by the physico-chemical properties of the substance and by available toxicological data. Any substance absorbed is unlikely to be widely distributed. Biliary excretion is considered to be the significant route of excretion for the substance.

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