Nitriles, C12-18

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

22 Jan - 8 Feb 1985

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP and well reported. Some small deviations from guideline study, but study is robust enough for reliable outcome.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1985

Report date:

1985

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

yes

Remarks:

2 M+2F per dose group rather then 5 of same sex.

GLP compliance:

yes

Test type:

standard acute method

Test material

Test material information

Constituent 1

Reference substance name:

C12-18 evennumbered alkyl nitrile

EC Number:

628-856-6

Cas Number:

1218787-29-1

Molecular formula:

No molecular formula

IUPAC Name:

C12-18 evennumbered alkyl nitrile

Details on test material:

Test subsatnce: Nitril KK
Appearance: clear yellow liquid
Subsatnce data sheet included in report:
alkylnitril, technical grade
CAS: 61789-53-5
Specific gravity: 0.82 at 20°C
mp ~0°C
bp ~200-350 °C
flashpoint: > 60 °C

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Strain: HC/CFY (Remote Sprague-Dawley)
- Source: Hacking and Churchill Limited, Huntingdon, Cambridgeshire, England.
- Age at study initiation: 4-6 weeks
- Weight at study initiation: 100-137 g
- Fasting period before study: night before
- Housing: in groups by sex in metal cages with wire mesh floors.
- Diet: ad libitum, standard laboratory rodent diet (Scientific Feeds LAD 1 obtained from Special Diet Services Ltd., Witham, Essex, England)
- Water: ad libitum
Analyse cerificate for doet and water are included in report.
- Acclimation period: minimum 5 days.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21-23
- Humidity (%): mean daily level: 45%
- Air changes (per hr): 15/hr
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: To: 22 Jan - 8 Feb 1985
Dates of dosing: 22.1.1985 (25 mg/kg), 23.1.1985 (200 mg/kg), 24.1.1985 (2000 mg/kg), 25.1.1985 (5000 mg/kg)

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Remarks:

except lowest dose: 25% in water

Details on oral exposure:

Substance was administered as supplied at a volume not exceeding 6.1ml/kg ((= 5 g/kg; S.G. 0.82) or was prepared as a 25% w/v solution in distilled water and administered at a volume of 0.1 ml/kg.
Administration by syringe and plastic catheter or a glass microlitre syringe and metal cannula.
Dosing started with the lowest dose and when no deaths occurred at this level within 24 hours, the next dose was given to another group of two male and two female rats and so on.

Doses:

25, 200, 2000 and 5000 mg/kg

No. of animals per sex per dose:

2 male and 2 female per dose.

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations: frequent after dosing, subsequent days at least twice per day. Recorded were nature, severity, approximate time of onset and duration of each toxic sign.
- Body weight weer recorded on days 1, 4, 8 and 15.
- Necropsy of survivors performed: yes. Consisted of opening the abdominal and thoracic cavities. Macroscopic appearance of abnormal organs when present was recorded.
- Other examinations performed: no

Statistics:

Not needed.

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LD0

Effect level:

> 5 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: No mortality at highest dose.

Mortality:

No

Clinical signs:

other: Yes. Complete recovery by day 4 and 5 (5000 mg/kg group). Signs observed shortly after dosing in all rats: pilo-erection and hunched posture. Additional observations incldued: - Abnormal gait (waddlig): 25 and 2000 mg/kg - Pallor extremities ans salivatio

Gross pathology:

Terminal autopsy findings were normal.

Any other information on results incl. tables

Average body weight (two animals per sex per dose)

Day	Dose levels in mg/kg
	25	200	2000	5000
Males
1	109	113	120	130
4	153	154	165	176
8	198	201	211	222
15	270	277	276	288
Females
1	106	107	112	123
4	137	138	152	153
8	170	166	180	183
15	205	201	208	211

 No. of rats in group of 2 showing signs

Signs	Dose (mg/kg)
	25		200		2000		5000
	M	F	M	F	M	F	M	F
Pilo-erection	2	2	2	2	2	2	2	2
Abnormal body carriage (hunched posture)	2	2	2	2	2	2	2	2
Abnormal gait (waddling)	2	2	0	0	2	2	0	0
Pallor of extremities	0	0	0	0	2	2	0	0
Diarrhoea	0	0	0	0	0	0	2	2
Increased salivation	0	0	0	0	2	2	0	0

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The acute lethal oral dose to rats was found to be > 5000 mg/kg.

Executive summary:

Coco nitrile of technical pure quality was tested for acute oral toxicity in dose levels upto 5000 mg/kg to groups of two female and two male rats. The animals were observed up to14 days after dosing for mortality, clinical signs, body weight and post mortem examination. Dose levels applied were 25, 200, 2000 and 5000 mg/kgbw.

There were no mortalities observed. Body weight gain was normal during the 14 -day observation period for all groups.

Clinical signs observed in all animals were pilo-erection and hunched posture, and abnormal gait (waddling) at 25 and 2000 mg./kg, pallor of the extremities and increased salivation at 2000 mg/kg, and diarrhoea at 5000 mg/kg. All signs weer completely cleared by day 4 (25, 200 and 2000 mg/kg) or day 5 (5000 mg/kg).

Terminal autopsy findings were normal.

Conclusion: The acute lethal oral dose to rats was found to be > 5000 mg/kg.