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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:
other information
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
other: Insufficient for assessment (only one dose group, only 3 animals (surviving rabbits of an acute toxicity test), only few evaluated parameters)

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1964
Report date:
1964

Materials and methods

Principles of method if other than guideline:
3 surviving rabbits (of the low dose group of an acute toxicity test) were treated orally with the test substance after a period of 12 - 13 day without treatment up to 21 applications (5 times/week). The animals were observed for clinical signs of toxicity during the study and were necropsied 3 days after the last application.
GLP compliance:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
Suberonitrile
EC Number:
211-089-2
EC Name:
Suberonitrile
Cas Number:
629-40-3
Molecular formula:
C8H12N2
IUPAC Name:
octanedinitrile
Details on test material:
- Name of test substance (as cited in study report): Korksaeuredinitril
- Analytical purity: no data
- Substance No.: XIII/213
- Sample No.: C 520/326
- Physical state: liquid
- Density: 0.942 g/mL

Test animals

Species:
rabbit
Strain:
not specified
Sex:
male
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: "Russian"
- Weight at study initiation: 2.30 - 2.34 kg

No additional information reported.

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
water
Duration of treatment / exposure:
21 applications
Frequency of treatment:
up to 5 times per week
Doses / concentrations
Remarks:
Doses / Concentrations:
23.5 mg/kg/d (calcutlated assuming test substance density = 0.942 g/mL; 25 µL/kg/d)
Basis:
actual ingested
No. of animals per sex per dose:
3 animals (only one dose group)
Control animals:
no
Details on study design:
Post-exposure period: 3 days

Examinations

Observations and examinations performed and frequency:
CAGE SIDE OBSERVATIONS: Yes
- Time schedule: daily (except weekends)

DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: daily (except weekends)

BODY WEIGHT: Yes
- Time schedule for examinations: daily (except weekends)

FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study): No
- Observation, if food intake was normal.

WATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study): No

OPHTHALMOSCOPIC EXAMINATION: No

HAEMATOLOGY: Yes
- Time schedule for collection of blood: day -3 (before application), day 11 and day 24
- Anaesthetic used for blood collection: No data
- Animals fasted: No data
- How many animals: 3
- Parameters checked: haemoglobine, erythrocytes, reticulocytes, leucocytes, eosinophiles, basophiles, lymphocytes and segmented neutrophiles

CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood: day -3 (before application), day 11 and day 24
- Animals fasted: No data
- How many animals: 3
- Parameters checked: blood urea, bromsulphthalein retention, serum-glutamat-pyruvat-transaminase

URINALYSIS: Yes
- Time schedule for collection of urine: day -3, day 1, day 2, day 10 and day 24
- Metabolism cages used for collection of urine: No
- Animals fasted: No data
- Parameters checked: volume, specific weight, pH, protein content, glucose, urobilinogen

NEUROBEHAVIOURAL EXAMINATION: No
Sacrifice and pathology:
GROSS PATHOLOGY: Yes
HISTOPATHOLOGY: Yes (liver, heart, lungs, kidneys, spleen and pancreas)

Results and discussion

Results of examinations

Details on results:
CLINICAL SIGNS AND MORTALITY
- transient increased respiration rate

BODY WEIGHT AND WEIGHT GAIN
- body weight was constant in all animals

FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study)
- food intake was normal in all animals

HAEMATOLOGY
- no abnormalities (see table 1)

CLINICAL CHEMISTRY
- no abnormalities (see table 1)

URINALYSIS
- no abnormalites, except transient increaesed urobilinogen (see table 1)

ORGAN WEIGHTS
- animal#1: liver: 52 g; spleen: 0.5 g; kidneys: 6 g; animal#2: liver: 52 g; spleen: 0.70 g; kidneys: 5 g; animal#3: liver: 49 g; spleen: 0.8 g; kidneys: 5 g

GROSS PATHOLOGY
- no abnormalities detected

HISTOPATHOLOGY:
- liver: slight adiposis (3/3) and hypoxydotic vacuoles (2/3), that was not considered substance related; no further abnormalities detected

Effect levels

Dose descriptor:
NOAEL
Effect level:
23.5 mg/kg bw/day (actual dose received)
Based on:
test mat.
Sex:
male
Basis for effect level:
other: 23.5 mg/kg bw was the only dose tested.

Target system / organ toxicity

Critical effects observed:
not specified

Any other information on results incl. tables

Table 1: Repeated dose toxicity (rabbits): 21 exposures

Dosis

(mg/kg bw)

Sex

Blood

Max. value

Urine

Hb (g%)

Ery /mL

Leuco-cytes (1000)

Diff

BST (%Ret)

SGPT

Blood urea (mg%)

Start

Start

Mid

Mid

End

End

0.025

m

14.1

6.92

6.6 – 7.7

Transient increase granulocytes 22-49%

2.4

17

24

--, urobilinogen: +

13.2

6.19

14.0

6.36

 

polychromatism and anisocytosis

m

14.5

6.72

3.9 – 8.1

Increase granulocytes 21-45%

5.3

31

27

--, urobilinogen: +

11.9

5.47

12.5

5.47

 

Slight polychromatism

m

13.1

6.32

5.9 – 7.8

--

3.4

28

45

--, urobilinogen: +

12.8

5.72

12.8

5.72

 

polychromatism

Hb = haemoglobin

Ery = erythrocytes

Diff = differential haemogram

-- = no abnormalities detected

BST = bromsulphthalein retention (liver function)

SGPT = serum glutamate pyruvate transaminase

Applicant's summary and conclusion