Registration Dossier

Administrative data

Endpoint:
basic toxicokinetics, other
Remarks:
assessment of toxicokinetic behavior
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
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:
2017

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 behavior has been conducted to the extent that can be derived from the relevant available information.

Test material

Constituent 1
Chemical structure
Reference substance name:
Reaction mass of 3-[3-(1,1,1,3,5,5,5-heptamethyltrisiloxan-3-yl)propoxy]-2-hydroxypropyl methacrylate and 1-[3-(1,1,1,3,5,5,5-heptamethyltrisiloxan-3-yl)propoxy]-3-hydroxypropan-2-yl methacrylate.
EC Number:
700-334-3
Molecular formula:
C17H38O6Si3
IUPAC Name:
Reaction mass of 3-[3-(1,1,1,3,5,5,5-heptamethyltrisiloxan-3-yl)propoxy]-2-hydroxypropyl methacrylate and 1-[3-(1,1,1,3,5,5,5-heptamethyltrisiloxan-3-yl)propoxy]-3-hydroxypropan-2-yl methacrylate.
Test material form:
liquid

Results and discussion

Any other information on results incl. tables

Toxicokinetic Behaviour:

The substance is a colourless liquid and has a relatively high molecular weight.

The low vapour pressure (1.8 x 10-5 Pa at 25ºC), high flash point and predicted negative explosive and oxidising properties shows that the substance is non-volatile and therefore inhalation is not a significant route of exposure.

The substance has a high log octanal/water partition coefficient (Log Pow >6.5) and low water solubility (0.224 mg/l).

The substance is considered to be a skin sensitiser but is not a skin irritant.

A repeated dose reproductive screening study, on a structural analogue substance, showed limited evidence of absorption and did not show evidence of metabolism or excretion.

The substance was non-mutagenic in bacteria in either the absence or presence of an auxiliary metabolising system. A structural analogue substance was non-clastogenic in mammalian cells in vitro (human lymphocytes) and non-mutagenic in mammalian cells in vitro (L5178Y mouse lymphoma cell line) in either the absence or presence of an auxiliary metabolising system.

Absorption:

The results of an acute oral toxicity study in rats and repeated dose oral toxicity study in rats showed no evidence of significant absorption of the substance.

The molecular weight, high log Pow and low water solubility of the substance indicate absorption would be limitedfrom the gastrointestinal tract following oral ingestion. Any absorption that occurs for this lipohilic substance may be by micellular solubilisation.

The results of an acute dermal toxicity in rats showed no evidence of significant absorption of the substance and no systemic toxicity was observed in skin irritation and skin sensitisation studies. Absorption via the skin is expected to be low due to the molecular weight, log Pow and low water solubility of the substance.

The substance is a skin sensitiser based on LLNA study, so some uptake will have occurred although it may only have been a small fraction of the applied dose. The substance is not a skin irritant so significant damage to the skin surface should not occur to enhance penetration.

Distribution:

There is no significant evidence to suggest widespread distribution of the substance will occur. This is supported by the low water solubility of the substance.

The positive response in a skin sensitization study suggests that the substance may bind to carrier proteins in the circulatory systems, thereby facilitating potential systemic distribution.

The high partition coefficient result (log Pow >6.5) would suggest an affinity to accumulate in fatty tissues.

Metabolism:

The results of the repeated dose/reproduction screening study (conducted on a structural analogue substance) did not show evidence to indicate any substance influenced hepatic metabolism.

 

The results of the genotoxicity assays have shown that genotoxicity is neither enhanced or diminished in the presence of a 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 substance that is not absorbed will be excreted in the faeces.

Applicant's summary and conclusion

Conclusions:
The available information suggests that absorption of the test substance from the gastrointestinal tract and absorption via the skin will be limited. Any substance absorbed is likely to accumulate in fatty tissues. Biliary excretion may well be the significant route of excretion. There is no evidence to suggest that the test substance may be metabolised.