Registration Dossier

Administrative data

Endpoint:
short-term repeated dose toxicity: oral
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:
according to
Guideline:
other: Annex V
Deviations:
not specified
GLP compliance:
yes
Limit test:
no

Test material

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

Test animals

Species:
rat
Strain:
not specified
Sex:
male/female

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
other: 0.5% Carboxymethyl cellulose with 0.1% Tween 80 (test material in suspension)
Analytical verification of doses or concentrations:
not specified
Duration of treatment / exposure:
28 days
Frequency of treatment:
Dosing regime: 7 days/week
Doses / concentrations
Remarks:
Doses / Concentrations:
Male& Female: 0, 50, 200 and 1000 mg/kg bw/day
Basis:
no data
No. of animals per sex per dose:
Male: 5 animals at 0 mg/kg bw/day
Male: 5 animals at 50 mg/kg bw/day
Male: 5 animals at 200 mg/kg bw/day
Male: 5 animals at 1000 mg/kg bw/day
Female: 5 animals at 0 mg/kg bw/day
Female: 5 animals at 50 mg/kg bw/day
Female: 5 animals at 200 mg/kg bw/day
Female: 5 animals at 1000 mg/kg bw/day
Control animals:
not specified

Results and discussion

Results of examinations

Details on results:
Clinical observations:
No deaths. Marked reduction in body weight gain of males at 1000 mg/kg.

Laboratory findings:
Increased activity of plasma ALT and AST at 1000 mg/kg (both sexes) and AST at 200 mg/kg (females). Plasma levels of urea and bilirubin were increased, and total globulins decreased, in males at 1000 mg/kg.
Effects in organs:
Increased relative liver weight, recent hepatic necrosis (extensive with haemorrhages in one high dose male, focal in one male at 200 mg/kg and two males at 50 mg/kg) and hepatocyte hypertrophy (most rats) were noted at 50 mg/kg and above; one male at 50 mg/kg had a liver nodule. Relative kidney weight was clearly increased at 1000 mg/kg and an apparent dose related trend was evident but no treatmentrelated lesions were seen.
Although lesions were seen at 50 mg/kg, no clear dose response was noted and, therefore, the substance should not be classified on the basis of this test.

Effect levels

open allclose all
Dose descriptor:
NOAEL
Effect level:
< 50 mg/kg bw/day (nominal)
Based on:
not specified
Sex:
male/female
Basis for effect level:
other: effects in organs (liver)
Dose descriptor:
NOEL
Effect level:
< 50 mg/kg bw/day (nominal)
Based on:
not specified
Sex:
not specified
Basis for effect level:
other: effects in organs (liver)

Target system / organ toxicity

Critical effects observed:
not specified

Applicant's summary and conclusion

Conclusions:
Although lesions were seen at 50 mg/kg, no clear dose response was noted and, therefore, the substance should not be classified on the basis of this test.