Registration Dossier

Administrative data

Endpoint:
sub-chronic toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Test was conducted according to Directive 84/449/EEC, B.7 and compliant with GLP.

Data source

Reference
Reference Type:
other: Body responsible for the test
Title:
Unnamed
Year:
1991

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
other: Direcitve 84/449/EEC, B.7
Deviations:
not specified
GLP compliance:
yes
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female

Administration / exposure

Route of administration:
oral: unspecified
Vehicle:
other: 0.5% aqueous carboxymethylcellulose
Details on oral exposure:
Method of administration: gavage
Duration of treatment / exposure:
Test duration: 28 days
Frequency of treatment:
Dosing regime: 7 days/week
No. of animals per sex per dose:
Male: 10 animals at 0 mg/kg bw/day
Male: 10 animals at 10 mg/kg bw/day
Male: 10 animals at 50 mg/kg bw/day
Male: 10 animals at 500 mg/kg bw/day
Female: 10 animals at 0 mg/kg bw/day
Female: 10 animals at 10 mg/kg bw/day
Female: 10 animals at 50 mg/kg bw/day
Female: 10 animals at 500 mg/kg bw/day

Results and discussion

Results of examinations

Details on results:
Clinical observations: Neither premature mortalities nor clear signs of clinical toxicity occurred. Slight alopecia, which was not reversible, was observable in the females from the high-dose group as from the second week of testing.
Laboratory findings: in the high-dose group there was a slight anaemia which proved to be completely reversible within the follow-on observation period. In the same dose group some clinico-chemical parameters differed from the control values (reduced potassium values, females; increased total proteins, cholesterol and gamma-GT values, females; increased albumin and creatinine values, males) and an increase in the triglycerides among the females could be observed. Although these changes were not statistically significant, they were assessed as being substance-related. After the end of the follow-on observation period these differences could no longer be measured. Urine analysis revealed an increased number of epithelia in the sediment as well as a slightly increased incidence of reducing substances in the urine in the high-dose group, particularly among the males.
These findings were also reversible.
Effects in organs: Morphologically, an absolute and relative increase in the weight of the liver was observed among the animals from the high-dose group as was an increase in the relative kidney weights among the females from the medium-dose group. In addition, the kidneys of the males from the high-dose group exhibited a surface with greenish patches. In the same dose group, the absolute and relative adrenal weights were elevated. This was also the case among the females from the medium-dose group. After the recovery period, it was no longer possible to observe any of the changes.
Histologically, there were no substance-related changes.

Effect levels

Dose descriptor:
NOAEL
Effect level:
50 mg/kg bw/day (nominal)
Based on:
test mat.
Basis for effect level:
other: orginal NCD unit is mg/kg/day

Target system / organ toxicity

Critical effects observed:
not specified

Applicant's summary and conclusion

Conclusions:
Classified as: Not classified