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Toxicological information

Acute Toxicity: oral

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Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1986
Report date:
1986

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.1 (Acute Toxicity (Oral))
Deviations:
no
GLP compliance:
no
Test type:
standard acute method
Limit test:
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:
suberonitrile
Details on test material:
- Name of test substance (as cited in study report): Korksaeure Dinitril Roh Ber. 100%
- Analytical purity: > 90%
- Substance No.: 86/199
- Physical state: liquid
- Stability: stable

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Additional information on strain: KFM-Han. Wistar (outbred, SPF-Quality)
- Source: Kleintierfarm Madoerin AG, Fuellingsdorf; Switzerland
- Age at study initiation: 9 - 11 weeks
- Weight at study initiation: 185 - 231 g (males); 175 - 210 g (females)
- Fasting period before study: 12 - 18 h
- Housing: 5/cage; Makrolon type-3 cages with standard softwool bedding
- Diet: Pelleted standard Kliba 343; Batch 50/86 rat maintenance diet (Klingentalmuehle AG, Kaiseraugust, Switzerland); ad libitum
- Water: tap water; ad libitum
- Acclimation period: at least one week

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3
- Humidity (%): 40 - 70
- Air changes (per hr): 10 - 15
- Photoperiod (hrs dark / hrs light): 12 / 12

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
CMC (carboxymethyl cellulose)
Remarks:
4%
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 20% or 100%

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg bw
Doses:
100, 300, 1000 and 5000 mg/kg bw
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations: four times during day 1 (day of treatment) and daily during days 2 - 15
- Frequency of weighing: day 1 (before administration), 8 and 15
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, macroscopic findings
Statistics:
The Logit-Model was applied to estimate the toxicity value. Additionally, the 90, 95 and 99% confidence intervals for the toxicity for each sex and the slope of the dose response line were estimated.

Results and discussion

Effect levelsopen allclose all
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 300 - < 1 000 mg/kg bw
Based on:
test mat.
Sex:
male/female
Dose descriptor:
LD50
Effect level:
396 mg/kg bw
Based on:
test mat.
95% CL:
>= 269 - <= 686
Remarks on result:
other: original value from study report
Mortality:
- 100 mg/kg bw: 0/10
- 300 mg/kg bw: 2/10
- 1000 mg/kg bw: 10/10
- 5000 mg/kg bw: 10/10
Clinical signs:
- 100 mg/kg bw: sedation, curved body position, ruffled fur
- 300 mg/kg bw: sedation, dyspnoea, ataxia, curved body postion, latero-abdominal position (females), ruffled fur
- 1000 mg/kg bw: sedation, somnolence, rales, dyspnoea (males), ataxia, latero-abdominal position, curved body position, spasms, tremor, ruffled fur
- 5000 mg/kg bw: sedation, somnolence, dyspnoea (females), ataxia, latero-abdominal position, ruffled fur
The surviving animals recovered within 3 to 5 observation days.
Body weight:
- 100 mg/kg bw: (males) day 1: 200 g, day 8: 247 g, day 15: 272 g; (females) day 1: 191 g, day 8: 208 g, day 15: 214 g
- 300 mg/kg bw: (males) day 1: 204 g, day 8: 247 g, day 15: 275 g; (females) day 1: 183 g, day 8: 202 g, day 15: 213 g
- 1000 mg/kg bw: (males) day 1: 220 g; (females) day 1: 181 g
- 5000 mg/kg bw: (males) day 1: 222 g; (females) day 1: 185 g
Gross pathology:
The following macroscopic organ changes were observed:
- 100 mg/kg bw: (sacrificed) lung: red foci, diameter 1mm (2/10); reddish discoloured (1/10)
- 300 mg/kg bw: (dead) cannibalism: abdominal region (2/10); (sacrificed) lung: apical lobe, black discoloured (3/10)
- 1000 mg/kg bw: (dead) lung: left lobe red foci, induration (2/10); intestines: yellowish, hard contents (1/10); red to brown contents (3/10)
- 5000 mg/kg bw: (dead) lung: dark-red (5/10); red foci (1/10); left lobe dark-red (1/10); jejenum: yellowish contents (1/10)

Any other information on results incl. tables

Table 1. Table for acute oral toxicity (mortality)

Dose
[mg/kg bw]

Toxicological results*

Time of death

Mortality (%)

Males

100

0/5

---

0

300

1/5

24H

20

1000

5/5

3H – 5H

100

5000

5/5

1H – 2H

100

LD50 (males) = 392 mg/kg bw

Females

100

0/5

--

0

300

1/5

24H

20

1000

5/5

5H and 3D

100

5000

5/5

1H and 3H

100

LD50 (females) =  392 mg/kg bw

LD50 =  396 mg/kg bw

* first number = number of dead animals                                          

 second number = number of animals used

Table 2: Acute oral toxicity: Clinical signs

Dose (mg/kg bw)

100

300

1000

5000

M

F

M

F

M

F

M

F

Sedation

2H – 4D

2H – 4D

1H – 2D

1H – 2D

1H – 3H

n.d.

n.d.

n.d.

Curved body position

2H – 4D

2H – 4D

1H – 5H

1H – 5H

1H – 3H

n.d.

n.d.

n.d.

Ruffled fur

2H – 4D

2H – 4D

1H – 2D

1H – 2D

1H – 3H

n.d.

n.d.

n.d.

Dyspnoea

 

 

2H – 5H

1H – 5H

2H – 3H

n.d.

n.d.

n.d.

Ataxia

 

 

2H – 5H

1H – 5H

1H – 3H

n.d.

n.d.

n.d.

Latero-abdom. position

 

 

 

2H

1H – 3H

n.d.

n.d.

n.d.

Rales

 

 

 

 

3H

n.d.

n.d.

n.d.

Spasms

 

 

 

 

3H

n.d.

n.d.

n.d.

Tremor

 

 

 

 

2H – 3H

n.d.

n.d.

n.d.

Somnolence

 

 

 

 

1H – 3H

n.d.

n.d.

n.d.

H = hour; D = hour

n.d. = no data (missing pages in study report)

Applicant's summary and conclusion

Interpretation of results:
harmful
Remarks:
Migrated information