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Administrative data

Endpoint:
basic toxicokinetics
Type of information:
other: Paper-based toxicokinetic assessment
Adequacy of study:
key study
Study period:
The assessment was conducted in February 2013
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Summaries of studies were reviewed by a qualified toxicologist with a view to fulfilling the requirements of Annex VIII, point 8.8 of REACH.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2013
Report date:
2013

Materials and methods

Test guideline
Qualifier:
no guideline required
Principles of method if other than guideline:
In accordance with REACH Annex VIII (8.8.1) as assessment 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 Chapter R.7c: Endpoint specific guidance.
GLP compliance:
no
Remarks:
Not relevant for assessment

Test material

Constituent 1
Chemical structure
Reference substance name:
1,1'-(1,1-dimethyl-3-methylene-1,3-propanediyl)bisbenzene
EC Number:
228-846-8
EC Name:
1,1'-(1,1-dimethyl-3-methylene-1,3-propanediyl)bisbenzene
Cas Number:
6362-80-7
Molecular formula:
C18H20
IUPAC Name:
(4-methyl-4-phenylpent-1-en-2-yl)benzene
Details on test material:
- Name of test material (as cited in study report): 1,1'-(1,1-dimethyl-3-methylene-1,3-propanediyl)bisbenzene
- Physical state: clear colourless liquid

Results and discussion

Toxicokinetic / pharmacokinetic studies

Details on absorption:
Results of the repeated dose reproductive screening study in rats showed evidence to support the gastric absorption of the test item. This is supported by the lipophilic nature of the substance (log10 Pow of 6.2). 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 should also allow absorption through passive diffusion.

Absorption may also take place via the skin due to small molecular size and the 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 (6.64x 10-2 Pa at 25°C) shows that the substance is not available as a vapour therefore inhalation is not a significant route of exposure.
Details on distribution in tissues:
Systemic distribution is evident from the repeated dose reproductive screening study as a result of the organ changes observed. The positive response in a skin sensitisation study (LLNA) in mouse suggests that the test item may bind to carrier proteins in the circulatory system, thereby facilitating systemic distribution.

Once absorbed, the substance may potentially accumulate in the adipose tissue due to the high log octanol/water partition coefficient value (Log10 Pow 6.2).
Details on excretion:
Poor water-soluble products are not favourable for urinary excretion and therefore biliary excretion may well be a significant route for this material. However as there is evidence of hepatic metabolism which suggests urinary excretion cannot be ruled out. The results of the repeated dose reproductive screening study did show evidence of this as a potential route of excretion. The main reason for xenobiotic metabolism is to render the product more water soluble thereby allowing urinary excretion. Any test item that is not absorbed from the gut will be excreted in the faeces.

Metabolite characterisation studies

Metabolites identified:
no
Details on metabolites:
The results of the repeated dose reproductive screening study showed evidence of an adaptive response in the liver and thyroids in rats; which is normally associated with enhanced metabolism.

Any other information on results incl. tables

The substance is a clear colourless liquid and the molecular weight is 236.35 g/mol. The low vapour pressure value (6.64 x 10-2 Pa at 25°C) and predicted negative explosive and oxidising 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 6.2) and low water solubility 0.179 mg/L. The available acute oral, acute inhalation and skin and eye irritation studies as well as the reproduction/developmental study showed evidence of absorption, metabolism and excretion.

The test item was non-mutagenic in bacteria or in the mouse or non-clastogenic in mammalian cells in vitro in either the absence or presence of an auxiliary metabolising system. The test item is considered to be irritant and a skin sensitizer.

Applicant's summary and conclusion

Conclusions:
The available information suggests that absorption of the test substance from the gastrointestinal tract can 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 can potentially accumulate in the adipose tissues and may bind to circulatory proteins. Biliary excretion may well be significant route for the substance however urinary excretion may also be possible.