Registration Dossier

Administrative data

Endpoint:
basic toxicokinetics
Type of information:
other: In accordance with REACH Annex VIII (8.8.1) an assessment of toxicokinetic behavior has been conducted to the extent that can be derived from the relevant available information.
Adequacy of study:
key study
Study period:
The assessment was conducted in March 2013
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Relevant studies were reviewed by a qualified toxicologist with a view to fulfilling the requirements of Annex VIII (8.8.1).

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2013

Materials and methods

Objective of study:
toxicokinetics
Test guideline
Qualifier:
no guideline required
Principles of method if other than guideline:
In accordance with REACH Annex VIII (8.8) an assessment of toxicokinetic behaviour 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 R.7c: Endpoint specific guidance (ECHA, November 2012)
GLP compliance:
no
Remarks:
Not relevant for assessment

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
Details on the test material used in the studies assessed are presented in the respective endpoint study records.

Results and discussion

Any other information on results incl. tables

TOXICOKINETIC BEHAVIOUR:

The substance is composed as listed in IUCLID section 1.2. It is a white solid with a molecular weight of 90.08 g/mol. The low vapour pressure value (7.2 x 10-5 Pa at 25ºC) and predicted negative explosive and oxidising properties shows that the substance is non volatile therefore inhalation is not a significant route of exposure.

The test item has a low log octanol/water partition coefficient (log10 Pow -2.94) and high water solubility (234 g/l at 20.0°C). The available acute dermal studies and repeated dose reproductive screening study showed limited evidence of absorption however the repeated dose reproductive screening study did not show evidence of metabolism or excretion. The test item is classified as a moderate skin sensitiser and although mild dermal irritation was evident it is not classified as a dermal irritant and therefore skin penetration may be limited. The available repeated dose reproductive screening study showed limited evidence of absorption and did not show evidence of metabolism or excretion.

The test item was found to be mutagenic in bacteria in one study in either the absence or presence of metabolic activation and weakly clastogenic in mammalian cells in vitro in the absence of metabolic activation. The test item was however found to be non-mutagenic in mammalian (CHO) cells.

Absorption

Although the test item is lipophobic in nature the high water solubility (234 g/l at 20.0°C) and small molecular size of the substance should allow absorption through the gastro-intestinal tract via passive diffusion. This would suggest that the gastrointestinal tract provides a route of absorption, following oral administration, and thereby facilitating systemic distribution via the circulatory system.

Limited dermal absorption may occur via the skin due to small molecular size (less than 100 g/mol) and water solubility. There is evidence of mild dermal irritation and the test item is also considered to be a moderate skin sensitizer. Therefore damage to the skin surface may allow for increased penetration of the substance through the skin.

The proporation of the test item having an inhalable particle size of less than 100 μm was determined to be 2% and therefore the test item is considered to be essentially non-inhalable. The low vapour pressure value (7.2 x 10-5 Pa at 25ºC) shows that the substance is not available as a vapour therefore inhalation is not a significant route of exposure.

Distribution

Once absorbed, the test item may be distributed in serum due to the water solubility and may therefore be distributed systemically. The positive response in a skin sensitisation study suggests that the test item may bind to carrier proteins in the circulatory systems

, thereby facilitating systemic distribution. The low log octanol/water partition coefficient (log10 Pow -2.94) and high water solubility would also suggest that the test item is not lipophilic and would not accumulate in body fat.

Metabolism

The results of the repeated dose reproductive/developmental screening study did not show evidence to indicate the substance influenced hepatic metabolism.

The positive result in a reverse mutation assay and the negative result in a mutagenicity study using mammalian (CHO) cells in vitro showed no evidence that genotoxicity is either enhanced or diminished in the presence of a metabolising system. However, a chromosome aberration study did show the substance to be weakly clastogenic in the absence of the metabolising system. This effect however may be due to a cytotoxic mode of action of the test item rather than a true genotoxic mechanism.

Excretion

There is no evidence to indicate the route of excretion but highly water-soluble products are not favourable for biliary excretion and therefore urinary excretion may well be a significant route for this material. In addition to the high water solubility, a molecular weight of below 300 g/mol in the rat is also a characteristic favourable for urinary excretion. Any test item that is not absorbed will be excreted in the faeces.

Applicant's summary and conclusion

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

The available information suggests that the substance is readily available via the oral route, however limited absorption via the skin is also possible. This is supported by the physico-chemical properties of the substance. Once absorbed, the substance would be

distributed in the serum. Urinary excretion is considered to be significant route of elimination of the substance.