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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
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 (8.8.1) 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, November 2012)
GLP compliance:
no
Remarks:
Not relevant for assessment

Test material

Constituent 1
Reference substance name:
Esterification products of Fatty acids C18 unsaturated and triethanolamine
EC Number:
939-649-8
Cas Number:
1474044-69-3
Molecular formula:
Not applicable (a generic molecular formula cannot be provided for this specific UVCB substance)
IUPAC Name:
Esterification products of Fatty acids C18 unsaturated and triethanolamine
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 in section 1.2 of IUCLID. It is an amber coloured slightly viscous liquid and the molecular weight of the constituents range from 149.19 - 942.53 g/mol. The low vapour pressure value (2.2 x 10-3 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 -2.48 – 23.1) and low water solubility 1.42 x 10-5– 6.92 x 10-5 g/l). The test item is considered not to be a skin sensitiser however mild/moderate dermal irritation was evident therefore skin penetration may be possible. The available acute oral study as well as the repeated dose reproductive screening study did not show any evidence of absorption, 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

The lipophilic nature of the substance (log10 Pow of -2.48 – 23.1) would suggest that the gastro-intestinal tract provides a route of absorption, following oral administration, before entering the circulatory system via the blood. The molecular size of the substance may also allow absorption through passive diffusion. One rate limiting factor is the extreme value for log Pow which may in fact serve as an inhibitor of significant absorption or reduce the rate of passage.

 

Absorption may also take place via the skin; the lipophilicity of the test item may allow penetration of the dermal membrane. The substance is considered not to be corrosive or a skin sensitizer however there is 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 (2.2 x 10-3 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, under normal circumstances a high log octanol/water partition coefficient value (Log10 Pow -2.48 - 23.1) would suggest an affinity to accumulate in the adipose tissue, however at extreme values (>10) then this may well not happen.

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 poorly 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.

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 may take place but may be limited by water solubility and molecular size, 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 may 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. If absorbed, the substance may result in accumulation in the adipose tissues. Biliary excretion is considered to be the significant route for the substance.

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