Registration Dossier

Toxicological information

Specific investigations: other studies

Currently viewing:

Administrative data

Endpoint:
specific investigations: other studies
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Guideline study obtained through inquiry process; SNIF file obtained from ECHA.

Data source

Reference
Reference Type:
other: SNIF
Title:
Unnamed
Year:
1986

Materials and methods

Test guideline
Qualifier:
no guideline available
Deviations:
not applicable
Principles of method if other than guideline:
According to in-house protocol using recognised biochemical and morphological techniques to investigate the effects of the test substance and its metabolite on selected biochemical and morphological parameters of the male rat liver.
GLP compliance:
not specified
Type of method:
in vivo

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
not specified

Test animals

Species:
rat
Strain:
not specified
Sex:
male

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
other: 0.5% carboxymethylcellulose
Analytical verification of doses or concentrations:
not specified
Duration of treatment / exposure:
14 days
Frequency of treatment:
Daily for 14 days
Doses / concentrations
Remarks:
Doses / Concentrations:
10, 50 and 200 mg/kg
Basis:
no data
No. of animals per sex per dose:
5
Control animals:
other: 10 animals per dose level

Results and discussion

Details on results:
Signs of toxicity:
No deaths and no signs of toxicity. Reduced body weight gain was noted in animals treated with 50 or 200 mg/kg metabolite.
Effects on liver:
Dose-related increase in absolute liver weight at 10 mg/kg and above for both substances (80-90% above controls at highets dose).
Ultrastructural examination of animals treated with 200 mg/kg revealed a striking proliferation of peroxisomes, particularly with metabolite. A marginal proliferation of smooth endoplasmic reticulum was noted with metabolite.
There was a dose-dependent and statistically high significant increase in peroxisomal beta-oxidation at 10 mg/kg and above for both substances. Increased cytochrome P-452 and decreased activity of UDP-glucuronosyltransferase and glutathione S-transferase were also noted with both substances.

Applicant's summary and conclusion

Conclusions:
The liver effects seen with both substances were very similar to those found after repeated administration of known peroxisome proliferators to rats. Both substances can be classified as potent peroxisome proliferators in the rat.