Registration Dossier

Administrative data

Endpoint:
sub-chronic toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
28 days
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP Compliance

Data source

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

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
other: 84/449/EWG, B.7
GLP compliance:
yes
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent

Test animals

Species:
other: rat, Sprague-Dawley

Administration / exposure

Route of administration:
oral: unspecified
Vehicle:
other: 0.5% aqueous carboxymethylcellulose
Details on oral exposure:
Method of administration: gastric or oesophageal feeding tube ( Schlundsonde)
Duration of treatment / exposure:
Test Duration: 28 days
Frequency of treatment:
Dosing regime : 7 days/week
Doses / concentrations
Remarks:
Doses / Concentrations:
0,10,50,500 mg/kg bw/day
Basis:
other: by schlundsonde in water/0.5% Carboxymethylcellulose
No. of animals per sex per dose:
10 males & 10 females

Results and discussion

Results of examinations

Details on results:
Neither premature mortalities nor clear signs of clinical toxicity occured. Slight alopecia, which was not reversible, was observed in the females from the high-dose group as from the second week of testing.

Effect levels

Dose descriptor:
NOAEL
Effect level:
50 mg/kg bw/day (nominal)
Basis for effect level:
other: original 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
Executive summary:

In the high-dose group there was a slight aneamia 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, perticularly among the males. These findings were also reversible.

Effects on 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.