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:
guideline study without detailed documentation

Data source

Materials and methods

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
other: solid

Results and discussion

Applicant's summary and conclusion

Executive summary:

Resorption

Because of the molecular structure, low molecular weight 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).

Data from a subacute study of the test item are available (dosing 100, 300 and 1000 mg/kg/d). 300 and 1000 mg/kg were not tolerated by the male rats and proved to be toxic for the female rats because of premature death especially at 1000 mg/kg, effects on body weight, reduced food consumption, changes in behavioral parameters, influence on a few clinico-chemical parameters and histopathological organ lesions (100 mg/kg are considered to be the NOAEL (no adverse effect level).

From these effects it can be concluded that the test item 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 of the test item (28d: 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. From the subacute study it can be conclududed, that metabolism in the liver can be assumed as a tendency towards an increase of absolute and relative liver weights in both sexes at 100 and 300 mg/kg/d was found. Due to the molecular properties, excretion via the kidneys is considered to be the main route of elimination.