Registration Dossier

Administrative data

Endpoint:
repeated dose toxicity: oral
Remarks:
other: Repeated dose toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)

Data source

Reference
Reference Type:
other: Body responsible for the test
Title:
Unnamed
Year:
1994

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
other: 92/69/EEC
GLP compliance:
yes
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid: particulate/powder
Remarks:
migrated information: powder

Test animals

Species:
other: Rat (Sprague-Dawley)

Administration / exposure

Route of administration:
oral: unspecified
Vehicle:
other: Distilled water
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: 5 animals at 0 mg/kg bw/day
Male: 5 animals at 15 mg/kg bw/day
Male: 5 animals at 150 mg/kg bw/day
Male: 5 animals at 300 mg/kg bw/day
Female: 5 animals at 0 mg/kg bw/day
Female: 5 animals at 15 mg/kg bw/day
Female: 5 animals at 150 mg/kg bw/day
Female: 5 animals at 300 mg/kg bw/day

Results and discussion

Results of examinations

Details on results:
Clinical observations:
There were no mortalities and no treatment related signs
observed during the study.
Laboratory findings:
Water consumption was higher than control for male and
female rats receiving 300 mg/kg/day (+49% and +27%
respectively).
The lymphocyte count and hence the total white blood cell
count, was higher than control for female rats treated at
300 mg/kg/day.
The alkaline phosphatase levels for female rats receiving
150 or 300 mg/kg/day were statistically significantly higher
than control. Urea nitrogen levels were also higher than
control for females treated at 300 mg/kg/day. Lower total
protein levels in the blood were recorded for male and
female rats treated at 300 and for females at 150 mg/kg/day.
Effects in organs:
Higher than control kidney weights (bodyweight adjusted)
were rcorded for male and female rats treated at 300
mg/kg/day.
Thickening and pallor of the stomach corpus mucosa was noted
for the majority of rats at 300 mg/kg and also for some at
150 mg/kg. An increased incidence of pale incisors was
recorded for rats of the intermediate and high dosage group.
Hyperplasia of mucosa neck cells with prominent apoptosis in
the glandular epithelium and associated diffuse submucosal
inflammation in the glandular region was seen in the stomach
of rats receiving 150 and 300 mg/kg/day.

Effect levels

open allclose all
Dose descriptor:
NOAEL
Effect level:
15 mg/kg bw/day (nominal)
Basis for effect level:
other: original NCD unit is mg/kg/day.
Dose descriptor:
NOEL
Effect level:
15 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

Any other information on results incl. tables

Comments:

The findings in the stomach at high and intermediate dosages of 300 or 150 mg/kg/day were considered to be an adaptive, hyperplastic response to an irritant. Other effects seen at 150 mg/kg were not considered serious. Classification and labelling with R48 is therefore not considered appropriate.

Applicant's summary and conclusion

Conclusions:
Classified as: Not classified