Registration Dossier

Administrative data

Endpoint:
basic toxicokinetics
Type of information:
other:
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Expert statement based on subchronic toxicity data.

Data source

Reference
Reference Type:
other company data
Title:
Unnamed
Year:
2014
Report Date:
2014

Materials and methods

Test material

Reference
Name:
Unnamed
Type:
Constituent

Results and discussion

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information): no bioaccumulation potential based on study results expert statementSpecific information on the metabolism and excretion of the substance is not available. Metabolism of the test material in the liver can be assumed, because the liver and kidney were found to be target organs (relative organ weight change) in the repeat dose toxicity study of a structural analogue as a result of metabolic adaptation (28d: key study). Because of the reversibility of the observed effects, the substance is most likely eliminated from the body. Due to the molecular properties of the test material, excretion via the kidneys is considered to be the main route of elimination.
Executive summary:

Resorption

Because of the molecular structure, low molecular weight (234.42 g/mol) and octanol-water partition coefficient (>5.7), resorption of the test item via the gastrointestinal tract is considered to be likely. After single treatment of rats with the test item at a dose of 2000 mg/kg bw no signs of toxicity were observed (acute oral: key study).

Daily oral treatment with 5, 20 and 100 mg/kg the test material to Wistar (Han) rats was clinically tolerated over 90 days.

At main kill on day 90 histopathology of the main kill animals revealed a multifocal/focal minimal to mild intracytoplasmic vacuolation of hepatocytes due to lipid storage at all dose levels in both sexes. In addition, a slight increase of absolute (females only) and relative liver weights was seen in both sexes at 100 mg/kg/d. These findings are considered to be non-adverse.

At the end of the treatment-free recovery period the treatment-related lesions in the liver showed full reversibility in all dose groups, except for a minor finding in the liver of a single 100 mg/kg/d male. From these effects it can be concluded that the compound is resorbed after oral administration.

Distribution

Due to the low water solubility and the high octanol/water-coefficient, in combination with the low molecular weight, permeation of membranes is assumed to be possible. The toxicological effects found in the repeat dose toxicity study (90d: key study) clearly show that this compound is distributed throughout the body after oral uptake and is thus systemically available.

Metabolism and Excretion

Specific information on the metabolism and excretion of the substance is not available. Metabolism in the liver can be assumed as a tendency towards an increase of absolute and relative liver weights in both sexes at 100 mg/kg/d was found. Because of the reversibility of the observed effects (e.g. on relative organ weight of liver), the substance is most likely eliminated from the body. Due to the molecular properties, excretion via the kidneys is considered to be the main route of elimination.