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Toxicological information

Repeated dose toxicity: oral

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Administrative data

Endpoint:
short-term 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:
Title:
Unnamed
Year:
1993
Report date:
1993

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
other: OECD 407 (1995)
GLP compliance:
yes
Limit test:
yes

Test material

Constituent 1
Reference substance name:
Dastib 845
IUPAC Name:
Dastib 845

Test animals

Species:
other: rat, Han:WIST

Administration / exposure

Route of administration:
oral: unspecified
Vehicle:
other: Maisol
Details on oral exposure:
Method of administration:
Magensonde
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: 5 animals at 40 mg/kg bw/day
Male: 5 animals at 200 mg/kg bw/day
Male: 10 animals at 1000 mg/kg bw/day
Female: 10 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: 10 animals at 1000 mg/kg bw/day

Results and discussion

Results of examinations

Details on results:
Clinical observations:
For key to symbols, see end of the table.


Dose main groups recovery
groups

(mg/kg 0 40 200 1000 0 1000

bw/d) m f m f m f m f m f m f

1) Clinical examinations

Salivation I I I I

Light- p p p p

colored

feces

2ndwk to

1st wk

posttreatm

ent

Spont. D D

activity,

cutaneous

turgor,

righting

reflex

body D*

weight

gain

Food D* D*

consump-

tion

FOB and motor activity: not tested


urinalysis: no treatment-related effects

Laboratory findings:
For key to symbols, see end of the table.


Dose main groups recovery
groups

(mg/kg 0 40 200 1000 0 1000

bw/d) m f m f m f m f m f m f

2) Clinical laboratory investigations

THRO I* I*

Prothromb I* I* I* I* I*

blood chemistry:

ALAT (GPT) I*

GLUC I*

PROT D* D*

TRIGL I*

Effects in organs:
For key to symbols, see end of the table.


Dose main groups recovery
groups

(mg/kg 0 40 200 1000 0 1000

bw/d) m f m f m f m f m f m f

3) Effect on the organs / Pathology

organ weight: no treatment-related effects

macroscopic findings:

Coating & 5 5

Reddening

of

stomach,

swollen 1 5 5

duodenum

histopathology:

Cardiomyop 2

athy

Duodenum: 3 1 5 3

mucosal

hyperplasi

a


Key: p findings/changes present

i increase compared with controls, no

statistically significant but possibly of

toxicological relevance

i* statistically significant increase compared

with controls (p < 0.05)

d decrease compared with controls, no

statistically significant but possibly of

toxicological relevance

d* statistically significant decrease compared

with controls (p < 0.05)

Effect levels

open allclose all
Dose descriptor:
NOAEL
Effect level:
40 mg/kg bw/day (nominal)
Basis for effect level:
other: original NCD unit is mg/kg/day.
Dose descriptor:
NOEL
Effect level:
40 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