Suberonitrile

Acute Toxicity: oral

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 guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

no

Test guideline 2

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

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): 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 levels

Effect levels 1

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 300 - < 1 000 mg/kg bw

Based on:

test mat.

Effect levels 2

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:

other: - 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-ab

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