Registration Dossier

Administrative data

Link to relevant study record(s)

Reference
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:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Remarks:
Relevant studies were reviewed by a qualified toxicologist with a view to fulfilling the requirements of Annex VIII (8.8.1).
Objective of study:
toxicokinetics
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

TOXICOKINETIC BEHAVIOUR

The substance is composed as described in Section 1.2. It is a pale yellow crystalline solid and the molecular weight is ≥542 - ≤ 716 g/mol.The low vapour pressure value (7.9 x 10-6 Pa at 25°C and predicted negative explosive and oxidizing 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 partition coefficient value (Log10 Pow -4.33) and high water solubility (60.0 –61.8% w/w at 20°C + 0.5°C). The available acute dermal studies showed limited evidence of absorption, however the repeated dose reproductive screening study did not show evidence of metabolism or excretion.

 

The test item was non-mutagenic in bacteria, non-clastogenic in mammalian cells in vitro and non-mutagenic in mammalian (CHO) cells in vitro in either the absence or presence of an auxiliary metabolising system. The test item is not a skin sensitizer however it is considered a mild irritant (from the results of a dermal irritation study).

 

Absorption

 

Although the test item is lipophobic in nature the high water solubility (60.0 – 61.8% w/w at 20°C) and small molecular size of the substance should 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. Therefore damage to the skin surface may allow for increased penetration of the substance through the skin.

 

The low vapour pressure value (7.9 x 10-6 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 genotoxicity assays have shown that genotoxicity is neither enhanced or diminished in the presence of the S9 metabolising system.

 

Excretion

 

There is no evidence to indicate the route of excretion but high 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.

Conclusions:
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 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.

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 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.

Key value for chemical safety assessment

Bioaccumulation potential:
no bioaccumulation potential

Additional information