1H-Imidazole-1-ethanol, 4,5-dihydro-, 2-nortall-oil alkyl derivs.

Endpoint summary

Link to relevant study record(s)

Reference

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:

June 2012

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).

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 listed in the Section 1.2 of IUCLID. It is an amber coloured viscous liquid and the molecular weight is 86.35-109.78 g/mol. The low vapour pressure value (5.1 x 10^-4 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 high log octanol/water partition coefficient value (Log10 Pow 5.4) and low water solubility 2.0 E-15⁵ – 1.7 E-4). The available acute oral and dermal studies as well as the repeated dose reproductive screening study showed evidence for potential absorption; however it did not show any 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.

Absorption

Results of the acute oral study and repeated dose reproductive screening study in rats showed evidence to support the potential gastric absorption of the test item. This is supported by the lipophilic nature of the substance (log10 Pow of 5.4). This would suggest that the gastro-intestinal tract provides a route of absorption, following oral administration, before entering the circulatory system via the blood. The small molecular size of the substance may allow absorption through passive diffusion.

Absorption may also take place via the skin, the lipophilicity of the test item may allow penetration of the dermal membrane and absorption may also take place via the skin due to small molecular size. The substance is considered to be corrosive and there is evidence of dermal irritation however it is not considered to be a skin sensitizer. Therefore damage to the skin surface may allow for increased penetration of the substance through the skin.

The low vapour pressure value (maximum 5.1 x E-04 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 potentially accumulate in the adipose tissue due to the high log octanol/water partition coefficient value (Log10 Pow 5.4).

Metabolism

The results of the reproductive screening study and teratogenicity 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 poor water-soluble products are not favourable for urinary excretion and therefore biliary 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 may take place, primarily as a consequence of the high log octanol/ water coefficient of the test item. Some absorption may also take place via the skin. Once absorbed, the substance would result in accumulation in the adipose tissues. Biliary excretion may well be significant route for the substance. There is no evidence to suggest 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 could accumulate in the adipose tissues. Biliary excretion is considered to be the significant route for the substance.

Description of key information

Theoretical assessment based on the available information from toxicity studies and physico-chemical characteristics.

Key value for chemical safety assessment

Bioaccumulation potential:

low bioaccumulation potential

Absorption rate - oral (%):

100

Absorption rate - dermal (%):

100

Additional information

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 could accumulate in the adipose tissues. Biliary excretion is considered to be the significant route for the substance. There is no evidence to suggest that the test substance may be metabolised, however no studies have been conducted to identify metabolites..