Registration Dossier

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:
2 (reliable with restrictions)
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:
2011
Report Date:
2011

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, May 2008)
GLP compliance:
no
Remarks:
Not relevant for assessment

Test material

Reference
Name:
Unnamed
Type:
Constituent
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

Absorption:

Results of the acute oral study and 28-Day repeated dose study in rats showed evidence to support the gastric absorption of the test item. This is supported by the lipophilic nature of the substance (log10Powof >6).This would suggest that the gastro-intestinal tract provides a route of absorption, following oral administration, before entering the circulatory system via the blood.

 

Absorption may also take place via the skin, the lipophilicity of the test item may allow limited penetration of the dermal membrane. Although the substance is not corrosive 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 (7.0 x 10-3Pa at 20ºC) shows that the substance is not available as a vapour therefore inhalation is not a significant route of exposure.

 

Distribution:

Systemic distribution is evident from the oral acute and sub-acute studies 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 (log10Powof >6).

 

Metabolism:

The results of the 28-Day oral repeated dose study showed the evidence of an adaptive response in the livers in rats which is normally associated with enhanced metabolism. The results of the genotoxicity assays have shown that genotoxicity is neither enhanced nor 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. As there is evidence of hepatic metabolism this does not, however, rule out urinary 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 will be excreted in the faeces.

 

Conclusion:

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 would result in accumulation in the adipose tissues. Bilary excretion may well be a significant route for the susbtance.

 

 

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information): other: See summary in conclusions section
The available information suggests the substance is readily available via the oral route; however absorption via the skin is also possible. This is supported by the physico-chemical properties of the substance. Once absorbed, the substance would result in accumulation in the adipose tissues. Bilary excretion may well be a significant route for the susbtance.