1,3-bis[12-hydroxy-octadecamide-N-methylene]-benzene

Basic toxicokinetics

Administrative data

Endpoint:

basic toxicokinetics

Type of information:

other: 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:

March 2013

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Relevant studies were reviewed with a view to fulfilling the requirements of Annex VIII (8.8.1).

Data source

Reference

Reference Type:

other: an assessment of toxicokinetic behaviour has been conducted to the extent that can be derived from the relevant available information.

Title:

Unnamed

Year:

2013

Materials and methods

Objective of study:

toxicokinetics

Test guideline

Qualifier:

no guideline followed

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.

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

-

EC Number:

423-300-7

EC Name:

-

Cas Number:

128554-52-9

Molecular formula:

Molecular formula varies for each reaction product. See section 1.2 for the molecular formula for each identified reaction product.

IUPAC Name:

12-hydroxy-N-({3-[(12-hydroxyoctadecanamido)methyl]phenyl}methyl)octadecanamide

Results and discussion

Any other information on results incl. tables

Toxicokinetic behaviour:

The substance is a UVCB. It is an off white solid powder and the molecular weight ranges from 300 - 982 g/mol. The low vapour pressure value (2.6 x 10^-6Pa) and predicted negative explosive and oxidising properties shows that the substance is not volatile. However, the median particle size is relatively small at 1.97 µm. The substance has a high log octanol/water partition coefficient value (log Pow >6.5) and low water solubility (<0.64 mg/l based on comparable substance).

The acute toxicity tests (based on a comparable substance) showed that the LD50 of the substance was greater than 2000 mg/kg bw after oral administration and dermal application. The LC50 in an acute inhalation study was >5.08 mg/L air. The substance is not classified for acute toxicity.

A sub-acute 28-day study (based on a comparable substance gave a NOAEL of 200 mg/kg bw/day. A sub-chronic 90-day study (based on a comparable substance) gave a NOAEL of 250 mg/kg bw/day. A pre-natal developmental study (based on a comparable substance) gave a NOAEL of 1000 mg/kg bw/day.

The substance is not a skin or eye irritant, but is a skin sensitiser (based on a comparable substance).

The substance is non-mutagenic in bacteria, non-clastogenic in mammalian cells in vitro and non-mutagenic in mammalian cells in vitro (based on studies on comparable substances).

Absorption:

As the water solubility of the test substance is very low, this may be considered as a rate-limiting factor for the absorption of the substance. Results of the acute oral study and repeat dose studies (28-day) showed limited evidence to support the gastric absorption of the substance. This would be supported by the lipophilic nature of the substance (log Pow >6.5). The gastro-intestinal tract may provide a limited route of absorption following oral administration.

Absorption via the skin is expected to be very limited due to the molecular weight, log Pow and low water solubility. No signs of systemic toxicity or local irritation were observed in acute dermal and skin irritation studies.

The low vapour pressure of the substance (2.6 x 10^-6 Pa) indicates that the substance is not readily available for inhalation, although the small median particle size of 1.97 µm could result in potential uptake of the substance during inhalation exposure.

If absorbed, hydrolysis of the amide bonds may occur.

Distribution:

Significant systemic distribution was not evident from the repeat dose studies (28 -day, 90 -day and pre-natal developmental toxicity).

The positive response in a skin sensitisation study suggests the substance may bind to carrier proteins in the circulatory system, potentially facilitating distribution.

Once absorbed, the substance may potentially accumulate in fatty tissues due to the high log octanol/water partition coefficient (log Pow >6.5) and low water solubility.

Metabolism

The results of the repeat dose studies did not show evidence to indicate any substance influenced hepatic metabolism. the results of the genotoxicity assays have shown that gentoxicity is neither enhanced or diminished in the presence of metabolic activation.

Hydrolysis of amine bonds is possible in the liver.

Excretion

There is no evidence to indicate the route of excretion but poorly water soluble substances are not favourable for urinary excretion. Therefore, biliary excretion may well be a significant route for this substance.

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information): other: see summary of conclusions
The available information suggests limited absorption of the substance from the gastrointestinal tract following oral administration can occur. Dermal absorption is expected to be very limited. Once absorbed the substance may accumulate in fatty tissues. There is limited evidence of the metabolism of the substance, although hydrolysis may occur. Biliary excretion may well be the significant route of excretion for the substance.