Registration Dossier

Administrative data

Endpoint:
repeated dose toxicity: oral
Adequacy of study:
other information

Data source

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

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
other: OECD 407
GLP compliance:
yes
Limit test:
no

Test animals

Species:
other: rat, Wistar Hsd Cpb:WU (SPF)

Administration / exposure

Route of administration:
oral: unspecified
Vehicle:
other: demineralisiertes Wasser mit Cremophor EL 2 % (v/v)
Details on oral exposure:
Method of administration:
Schlundsonde
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 100 mg/kg bw/day
Male: 5 animals at 300 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 100 mg/kg bw/day
Female: 5 animals at 300 mg/kg bw/day
Female: 5 animals at 1000 mg/kg bw/day

Results and discussion

Results of examinations

Details on results:
Clinical observations:
Die Männchen der hohen Dosierung nahmen im Vergleich zur
Kontrolle vermehrt Wasser auf.

"ENGLISH"

The intake of water of the males of the high dose group was
increased compared to the control group.

Laboratory findings:
Die klinisch-chemischen Untersuchungen ergaben erhöhte
Aktivität von ALAT bei den Männchen und (nicht signifikant)
bei den Weibchen der hohen Dosierung. Die Männchen der hohen
Dosierung wiesen einen verminderten pH-Wert des Urins sowie
geringgradig erhöhte Urinvolumen auf.

"ENGLISH"

The clicnical-chemical tests were indicating an increased
activity of ALAT at the males and ( not significant) at the
females in the high dose group. The males of the high dose
group showed decreased pH-value of the urine and a low
increase of the urine volume.

Effects in organs:
Bei beiden Geschlechtern der hohen Dosierung wurden erhöhte
absolute und relative Lebergewichte ermittelt. Ebenso waren
bei den Weibchen der hohen Dosierung die absoluten
Nierengewichte erhöht.

Die histopathologischen Untersuchungen ergaben keine
behandlungsbedingten Effekte an den Organen.


In einer zusätzlichen Untersuchung wurde die Aktivität von
mikrosomaler N-Demethylase und der Gehalt an Cytochrom P450
in den Leberzellen bestimmt. Die Bestimmungen ergaben
verminderte Werte für beide Parameter, diese Reduktionen
wurden als toxikologisch nicht relevant bewertet.

"ENGLISH"

In both sexes of the high dose group there were determined
increased absolute and relative lever weights. Moreover the
kidney weights of the females in the high dose group were
increased.

The histopathological investigation did not indicate
treatment-related effects at the organs.


In an additional investigation the activity of microsomal
N-Demethylase and the content of Cytochrom P450 in the liver
cells were determined. The finding was a decrease for

both parameters, but these reductions were assessed as not
being toxicological relevant.

Effect levels

open allclose all
Dose descriptor:
NOAEL
Effect level:
300 mg/kg bw/day (nominal)
Basis for effect level:
other: original NCD unit is mg/kg/day.
Dose descriptor:
NOEL
Effect level:
300 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