2-methylglutaronitrile

Acute Toxicity: inhalation

Administrative data

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Study period:

no data

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Study is comparable to OECD 403. Old study, few data but sufficient to conclude that the test substance is toxic by inhalation route.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1974

Report date:

1974

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Deviations:

yes

Remarks:

: The study was only performed on one sex (male). The hisopathological examination of tissues was not performed.

GLP compliance:

no

Remarks:

Study performed before GLP statement

Test type:

standard acute method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

2-methylglutaronitrile

EC Number:

224-923-5

EC Name:

2-methylglutaronitrile

Cas Number:

4553-62-2

Molecular formula:

C6H8N2

IUPAC Name:

2-methylpentanedinitrile

Details on test material:

- Name of test material (as cited in study report): 2-Methylglutaronitrile/ethyl succinonitrile
- Molecular formula (if other than submission substance): no data
- Molecular weight (if other than submission substance): no data
- Smiles notation (if other than submission substance): no data
- InChl (if other than submission substance): no data
- Substance type: no data
- Physical state: no data
- Expiration date of the lot/batch: no data
- Stability under test conditions: no data
- Storage condition of test material: no data
- Purity test date: no data

Test animals

Species:

rat

Strain:

other: ChR-CD

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: no data
- Age at study initiation: young adult
- Weight at study initiation: 250-296 g
- Fasting period before study: not required
- Housing:no data
- Diet (e.g. ad libitum): no data
- Water (e.g. ad libitum): no data
- Acclimation period: no data


ENVIRONMENTAL CONDITIONS
- Temperature (°C): no data
- Humidity (%): no data
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): no data


IN-LIFE DATES: no data

Administration / exposure

Route of administration:

inhalation

Type of inhalation exposure:

whole body

Vehicle:

other: unchanged (no vehicle)

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus:no data
- Exposure chamber volume: 20 L
- Method of holding animals in test chamber: no data
- Source and rate of air: no data
- Method of conditioning air: no data
- System of generating particulates/aerosols: no data
- Method of particle size determination: not relevant
- Treatment of exhaust air: no data
- Temperature, humidity, pressure in air chamber: no data

TEST ATMOSPHERE
- Brief description of analytical method used: gas chromatography
- Samples taken from breathing zone: no data

VEHICLE: not relevant

TEST ATMOSPHERE (if not tabulated)
- Particle size distribution: no data
- MMAD (Mass median aerodynamic diameter) / GSD (Geometric st. dev.): no data

CLASS METHOD (if applicable)
- Rationale for the selection of the starting concentration: no data

Analytical verification of test atmosphere concentrations:

not specified

Duration of exposure:

4 h

Concentrations:

0.33, 0.34, 0.49, 1.11 mg/L

No. of animals per sex per dose:

6 males/dose

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: daily
- Necropsy of survivors performed: no
- Other examinations performed: clinical signs, body weight.

Statistics:

The LC50 was determined according to the statistical method of Finner, DJ (Probit Analysis (1964)).

Results and discussion

Preliminary study:

Not applicable

Effect levels

Key result

Sex:

male

Dose descriptor:

LC50

Effect level:

0.66 mg/L air

95% CL:

0.39 - 1.34

Exp. duration:

4 h

Mortality:

See Table 7.2.2-1

Clinical signs:

other: - At non-lethal levels: Salivation, lacrimation, hyperemia, labored respiration, mild convulsions. - At lethal levels: Severe convulsions, exophthalmos and cyanosis were followed by death immediately to one day post-exposure. This material caused severe c

Other findings:

No data

Any other information on results incl. tables

Table 7.2.2 -1: Concentration of MGN (mg/l)/Mortality

Analytical concentration of 2-methylglutaronitrile (mg/L)					Mortality
0,33					2/6
0,34					0/6
0,49					3/6
1,11					5/6

Applicant's summary and conclusion

Interpretation of results:

Category 2 based on GHS criteria

Conclusions:

Under the test conditions, the LC50/male rats/4 hours for 2-methylglutaronitrile (purity: 85%) was 0.66 mg/L. This material caused severe convulsions prior to death. Therefore, based on this central nervous system effect and LC50 value, 2-methylglutaronitrile/ethylsuccinonitrile (85/14) should be considered in category II (H330: Fatal if inhaled ) according to the CLP regulation 1272/2008 and as toxic by inhalation according to the Directive 67/548/EEC (T, R23).

Executive summary:

In an acute inhalation toxicity study performed similarly to the OECD test guideline No. 403, six male Albino rats were exposed to 2 -methylglutaronitrile/ehtylsuccinonitrile (85%/14%) heated to 200°C for 4 hours at concentrations of 0.33, 0.34, 0.49 and 1.11 mg/L.  Animals were then observed for 14 days. At non-lethal levels, salivation, lacrimation, hyperemia, labored respiration, mild convulsions were observed. At lethal levels, severe convulsions, exophthalmos and cyanosis were followed by death immediately to one day post-exposure.

Inhalation (rat/4h) LC₅₀= 0.66 mg/L (95% confidence limits of 0.39 and 1.34 mg/L).

Under the test conditions, 2 -methylglutaronitrile is considered in Category II (H330: Fatal if inhaled) according to the CLP regulation 1272/2008/EC and as toxic by inhalation according to the directive 67/548/EEC (T, R23).