Registration Dossier

Administrative data

Link to relevant study record(s)

Reference
Endpoint:
basic toxicokinetics
Type of information:
other: Paper-based toxicokinetic assessment
Adequacy of study:
key study
Study period:
The assessment was conducted in February 2013
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Summaries of studies were reviewed by a qualified toxicologist with a view to fulfilling the requirements of Annex VIII, point 8.8 of REACH.
Objective of study:
toxicokinetics
Qualifier:
no guideline required
Principles of method if other than guideline:
In accordance with REACH Annex VIII (8.8.1) as assessment has been conducted to the extent that can be derived from the relevant available information. The assessment is based on the Guidance on information requirements and chemical safety assessment Chapter R.7c: Endpoint specific guidance.
GLP compliance:
no
Remarks:
Not relevant for assessment
Details on absorption:
The water solubility (19.3 g/L at 20 + 0.5°C) could allow absorption through passive diffusion. This would suggest that the gastro-intestinal tract may provide a route of absorption, following oral administration, before entering the circulatory system via the blood.

Limited absorption may also take place via the skin due to the water solubility of the test item and the evidence of dermal irritation. Therefore damage to the skin surface may allow for increased penetration of the substance through the skin.

The low vapour pressure value (226 Pa at 25°C) shows that the substance is not available as a vapour therefore inhalation is not a significant route of exposure.
Details on distribution in tissues:
Once absorbed in the gut, the substance may be distributed in serum due to the water solubility and may therefore be distributed systemically. The water solubility would also suggest that it does not accumulate in body fat. The lack of evidence to suggest the test item is a skin sensitizer suggests that it does not bind to circulatory proteins.
Details on excretion:
There is no evidence to indicate the route of excretion but water-soluble products are not favourable for biliary excretion and therefore urinary excretion may well be a significant route for this material. Any test item that is not absorbed will be excreted in the faeces.
Metabolites identified:
no
Details on metabolites:
The results of the repeated dose reproductive screening study did not show evidence to indicate any test item influenced hepatic metabolism. The results of the genotoxicity asseys have shown that genotoxicity is neither enhanced nor diminished in the presence of the S9 metabolising system.

The low vapour pressure value (226 Pa at 25°C) and predicted negative explosive and oxidising properties shows that the substance is non volatile therefore inhalation is not a significant route of exposure. The substance has high water solubility (19.3 g/L). The available acute oral, eye/skin irritation, acute inhalation, repeated dose reproductive screening and pre-natal developmental toxicity studies showed limited evidence of absorption, metabolism and excretion.

The test item was non-mutagenic in bacteria or in the mouse and non-clastogenic in mammalian cells in vitro in the absence or presence of a liver enzyme metabolising system. The test item was not considered to be a skin sensitizer however it was considered an irritant.

Conclusions:
Interpretation of results (migrated information): other: See conclusion
The available information suggests that absorption of the test substance from the gastrointestinal tract can take place. Some absorption may also take place via the skin. Once absorbed, the substance would be distributed in the serum and thereby distributed systemically and renal elimination is likely to be the significant route of excretion. There is no evidence suggesting that the test substance may be metabolised, however no studies have been conducted to identify potential metabolites.

Description of key information

The available information suggests that absorption of the test substance from the gastrointestinal tract can take place. Some absorption may also take place via the skin. Once absorbed, the substance would be distributed in the serum and thereby distributed systemically and renal elimination is likely to be the significant route of excretion. There is no evidence suggesting that the test substance may be metabolised, however no studies have been conducted to identify potential metabolites.

Key value for chemical safety assessment

Bioaccumulation potential:
low bioaccumulation potential

Additional information

In accordance with Annex VIII (point 8.8) of Regulation (EC) No 1907/2006 (REACH), a paper-based toxicokinetic assessment has been conducted for the substance. Summaries of studies were reviewed by a qualified toxicologist with a view to fulfilling the requirements of Annex VIII, point 8.8 of REACH. 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. The assessment is based on the Guidance on information requirements and chemical safety assessment Chapter R.7c: Endpoint specific guidance (ECHA, May 2008). The available information suggests that the substance is readily available via the oral route; however absorption via the skin is also possible. This is supported by the physicochemical properties of the substance. There is no evidence to indicate the route of excretion.