Suberonitrile

Repeated dose toxicity: oral

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

Test material information

Constituent 1

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