N-FAS

Repeated dose toxicity: oral

Administrative data

Endpoint:

repeated dose toxicity: oral

Type of information:

experimental study

Adequacy of study:

other information

Reliability:

1 (reliable without restriction)

Data source

Reference

Reference Type:

other: Body responsible for the test

Title:

Unnamed

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

other: OECD 407 (1995) Siehe Bemerkungen.

GLP compliance:

yes

Limit test:

no

Test animals

Species:

other: rat, Wistar Hsd Cpb:WU

Administration / exposure

Route of administration:

oral: unspecified

Vehicle:

other: Wasser

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 40 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 40 mg/kg bw/day
Female: 5 animals at 200 mg/kg bw/day
Female: 5 animals at 1000 mg/kg bw/day

Results and discussion

Results of examinations

Details on results:

Clinical observations:
During the study no animal died unscheduled.

The body weight gain and food intake were not affected up to
1000 mg/kg. No clinical findings were observed at cage side
detailed weekly clinical observations up to 1000 mg/kg.

Laboratory findings:
Hematology revealed no signs indicating hematoxicity up to
1000 mg/kg.

Up to 1000 mg/kg none of the plasma enzymes, substrates or
electrolytes was affected.

Effects in organs:
Treated females exhibited a pale discoloration of the liver
more frequently than at 0 mg/kg. Furthermore, in the kidneys
a pale discoloration was observed in males and females of
all dose groups. The incidences were in males 0-1-2-4 and in
females 0-3-4-4. No other macroscopical lesions with a
dose-dependent distribution were seen.

A minimal to slight hepatocellular cytoplasmic charge (1-4-
4-4) occurred in treated females with a higher frequency
than at 0 mg/kg. This change consisted of a denser cytoplasm
and could be correlated to a lower glycogen content. Often,
a correlation between this finding and gross discoloration
was present. There was no evidence of any toxic effect on
the liver. In particular, no degenerative liver change could
be found up to and including 1000 mg/kg. The investigation
of Oil-Red O (ORO) stained cryocuts of the liver gave an
increased incidence of minimal lipid in mid dose males.
Since this finding was unrelated to dosing with the test
compound, it is regarded as a random event.

There was no evidence of any substance-induced finding in
the kidneys up to 1000 mg/kg, which could be seen as a
correlate to the pale discolored kidneys ovserved at
necropsy.

Effect levels

1

Dose descriptor:

NOAEL

Effect level:

1 000 mg/kg bw/day (nominal)

Basis for effect level:

other: original NCD unit is mg/kg/day.

2

Dose descriptor:

NOEL

Effect level:

1 000 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