Registration Dossier

Administrative data

Endpoint:
basic toxicokinetics, other
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
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:
2012
Report Date:
2012

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 (8.8.1) 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, May 2008)
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 a UVCB. It is a pale yellow liquid and the molecular weight is >119.96 - < 521.02 g/mol. The low vapour pressure value (1.0 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 a low log octanol/water partitioncoefficient value (Log10Pow -4.23 and high water solubility (miscible at 20°C). The available acute dermal and repeated dose reproductive screening studies showed limited evidence of absorption, metabolism and excretion.

The test item was non-mutagenic in bacteria and non-clastogenic in mammalian cells in vitro, however it was mutagenic in mammalian (CHO) cells in vitro in the absence of an auxiliary metabolising system.

 

The test item is not a skin sensitizer however it is considered a mild irritant.

Absorption

Although the test item is lipophobic in nature the high water solubility (miscible at 20°C ) and small molecular size of the substance could allow absorption through

passive diffusion. This would suggest that the gastro-intestinal tract provides 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 small molecular size and water solubility. Although the substance is not a skin sensitizer there is evidence of mild dermal irritation (from dermal irritation and skin sensitization studies). Therefore damage to the skin surface may allow for increased penetration of the substance through the skin.

The low vapour pressure value (1.0 Pa at 25°C) shows that the substance is not available as a vapour therefore inhalation is not a significant route of exposure.

 

Distribution

Once absorbed, the substance may be distributed in serum due to the water solubility and may therefore be distributed systemically. The lack of evidence to suggest the test item is a sensitizer suggests that it does not bind to circulatory proteins. The high water solubility would also suggest that the test item does not accumulate in body fat.

Metabolism

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 reverse mutation assay showed no evidence that genotoxicity is either enhanced or diminished in the presence of the S9 metabolising system. On the other hand in a mutagenicity study using mammalian (CHO) cells in vitro, the elimination of the mutagenic response by the addition of a rat S9 metabolising system suggests that the test substance may undergo hepatic metabolism in the intact animal.

Excretion

There is no evidence to indicate the route of excretion but high water-soluble products are not favorable 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.

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information): other: See summary in conclusions sectionThe 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 urine is 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 metabolites.
Executive summary:

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. Once absorbed, the substance would result in distribution in the serum. Urinary excretion is considered to be the significant route for the substance.