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Toxicological information

Repeated dose toxicity: oral

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Administrative data

Endpoint:
short-term repeated dose toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: no macroscopic and microscopic examination was performed

Data source

Referenceopen allclose all

Reference Type:
other: SNIF data provided by ECHA
Title:
Unnamed
Report Date:
1990
Reference Type:
secondary source
Title:
Unnamed
Year:
1990

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 407 (Repeated Dose 28-Day Oral Toxicity in Rodents)
Deviations:
not specified
GLP compliance:
yes
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent

Test animals

Species:
rat
Strain:
other: SD
Sex:
male/female

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
not specified
Analytical verification of doses or concentrations:
not specified
Duration of treatment / exposure:
28 d
Frequency of treatment:
no data
Doses / concentrations
Remarks:
Doses / Concentrations:
0, 3, 30 or 300 mg/kg bw/d
Basis:
actual ingested
No. of animals per sex per dose:
5
Control animals:
yes
Details on study design:
- Dose selection rationale: Dose levels were selected on the basis of a 5 day dose range finding study in which increased liver weights occurred in males at 1000 mg/kg/d and in females from 100 mg/kg/d.

Examinations

Observations and examinations performed and frequency:
CAGE SIDE OBSERVATIONS: Yes



BODY WEIGHT: Yes

FOOD CONSUMPTION: Yes

WATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study): Yes

OPHTHALMOSCOPIC EXAMINATION: No data

HAEMATOLOGY: Yes

CLINICAL CHEMISTRY: Yes

URINALYSIS: Yes

NEUROBEHAVIOURAL EXAMINATION: No data
Sacrifice and pathology:
GROSS PATHOLOGY: No data
HISTOPATHOLOGY: No data

Results and discussion

Effect levels

open allclose all
Dose descriptor:
NOAEL
Effect level:
30 mg/kg bw/day (actual dose received)
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: effects suggestive of hepatotoxicity at the next higher dose (300 mg/kg bw/d): clinical chemistry (increased bilirubin in males and females; in males decreased cholesterol); organ weights (increased liver weights in females)
Dose descriptor:
NOEL
Effect level:
3 mg/kg bw/day (actual dose received)
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: Effects observed at the next higher dose (discolouration of the urine in both sexes; in males increased gamma glutamyl transferase) were considered as not adverse

Target system / organ toxicity

Critical effects observed:
not specified

Any other information on results incl. tables

In the 28-day study, there were no deaths or treatment-related clinical signs reported. Body weight gain and food and water consumption were not affected by treatment. An increase in prothrombin time was noted in animals given 3 and 300 mg/kg bw but without dose-effect relationship.

Changes in clinical chemistry parameters included 100% increased levels of bilirubin in males and females given 300 mg/kg/d, and in males 20% decreased levels cholesterol at 300 mg/kg/d and 3 times higher gamma glutamyl transferase activity from 30 mg/kg/d.

Liver weights in females were increased slightly but significantly at 300 mg/kg/d, and at 30 and 300 mg/kg/d discolouration of the urine occurred in both sexes.

There were no other effects attributed to treatment. The results of this study indicate that while the test item produces effects suggestive of hepatotoxicity, it is not classed as harmful or toxic.

Applicant's summary and conclusion