2-methylglutaronitrile

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

Not stated

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Comparable to guidelile study with acceptable restrictions. The purity is not indicated.

Cross-reference

Reason / purpose for cross-reference:

reference to same study

Reference

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

Not stated

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Comparable to guideline study with acceptable restrictions. The purity is not indicated.

Reason / purpose for cross-reference:

reference to same study

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

yes

Remarks:

4 animals, occlusive dressing, exposure period of 24 hrs, observation time point at 1hr and 48 hrs after dressing removal (24hrs and 72 hrs time point are missing)

Principles of method if other than guideline:

Experimental protocol of DRAIZE or " patch-test technique"
Draize (J.H.) in "Appraisal of the safety of chemicals in foods, drugs and cosmetics", association of Food and Drug Officials of the United States
published by the Editorial Committes, Baltimore (1959), p'46.

GLP compliance:

no

Remarks:

Study performed before GLP statement

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: no data
- Age at study initiation: no data
- Weight at study initiation: 2.5 to 3.5 kg
- Housing: no data
- Diet (e.g. ad libitum): no data
- Water (e.g. ad libitum): no data
- Acclimation period: no data


ENVIRONMENTAL CONDITIONS: No data

Type of coverage:

occlusive

Preparation of test site:

shaved

Vehicle:

unchanged (no vehicle)

Controls:

no

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 mL
- Concentration (if solution): no data


VEHICLE: none

Duration of treatment / exposure:

Duration of the exposure treatment: 24h

Observation period:

Animals are observed 1 and 48 hour after patch removal.

Number of animals:

4

Details on study design:

TEST SITE
- Area of exposure: disk of 3 cm of diameter
- % coverage: no data
- Type of wrap if used: adhesive tape and a bandage enveloping all the trunk of the animal


REMOVAL OF TEST SUBSTANCE
- Washing (if done): No washing
- Time after start of exposure: 1 and 48h


SCORING SYSTEM: Draize scale

After clipping the skin, 0.5 ml of the test substance has been applied to a small disk of 3 cm of diameter which is directly applied to the skin.
Contact with the skin is held with adhesive tape and a bandage around the trunk of the animal.
Before exposure the skin of animals is either left intact or scarified.

Irritation parameter:

erythema score

Basis:

mean

Remarks:

intact skin

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Remarks on result:

other: Overall 25 and 72 hours

Irritation parameter:

edema score

Basis:

mean

Remarks:

intact skin

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Remarks on result:

other: Overall 25 and 72 hours

Irritation parameter:

primary dermal irritation index (PDII)

Basis:

mean

Remarks:

intact and abraded skin

Time point:

other: Overall 25 and 72 hours

Score:

0.25

Max. score:

12

Reversibility:

fully reversible within: 72 hrs

Remarks on result:

other: this index is equal to the sum of the scores for erythema and edema at 25 and 72 hrs after the application for the both intact and abraded skin, divided by 16 (number of treated rabbits multiplied by 4).

Irritant / corrosive response data:

Refering to the table 7.3.1; The Primary Dermal Irritation Index is 0.25. One time point of observation, 24h, is missing.

Other effects:

No other effects reported.

Table 7.3.1/1:Mean irritant/corrosive response data for each animal with intact skin at each observation time up to removal of animals from the test

 

Score at time point / Reversibility	Erythema Max. score 4	Edema Max. score 4
25 h after the start of test item application	0/0/0/0	0/0/0/0
72 h after the start of test item application	0/0/0/0	0/0/0/0
Average 25h, 72h (mean of all animals)	0.0	0.0
Reversibility*)	c/c/c/c	c/c/c/c
Average time (hrs) for reversion	-	-

 

 

Table 7.3.1/2: Mean irritant/corrosive response data for animals with abraded skin at each observation time up to removal of animals from the test

 

Score at time point / Reversibility	Erythema Max. score 4	Edema Max. score 4
25 h after the start of test item application	1/1/1/0	0/1/0/0
72 h after the start of test item application	0/0/0/0	0/0/0/0
Average 25h, 72h	0.375	0.125
Reversibility*)	c/c/c/-	-/c/-/-
Average time (hrs) for reversion	72/72/72/-	-/72/-/-

*) Reversibility: c. = completely reversible

Interpretation of results:

GHS criteria not met

Conclusions:

Under the test conditions, 2-methylglutaronitrile is considered as not irritating to the skin according to the criteria of CLP Regulation (EC) N° (1272-2008) and to the Annex VI to the Directive 67/548/EEC.

Executive summary:

In a skin irritation study, performed according to the Draize experiment protocol, 4 albinos rabbits (New Zealand) were exposed, for 24 hours to 2-methylglutaronitrile. The observation timepoint were 1h and 48h after patch removal. Timepoint 24h and 72 hours after removal of the patch were not been evaluated.

The mean scores (25 and 72 hours after the strat of test item application) were 0.00 for erythema and oedema (intact skin).

The mean scores (25 and 72 hours after the start of test item application) were 0.4 for erythema and 0.1 for oedema (abraded skin). These effects were reversible after 72 hours of exposure.

Under the test conditions, based on the mean scores for erythema end oedema = 0.00 (intact skin), 2 -methylglutaronitrile is considered as not irritating to the skin according to the criteria of CLP Regulation (EC) N° (1272-2008) and to the Annex VI to the Directive 67/548/EEC.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1981

Report date:

1981

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

yes

Remarks:

: 4 animals, eye irritation graded according to the Draize scale.

Principles of method if other than guideline:

This test has been performed according to the experimental protocol similar to the Draize test.
Draize (J.H.), in "Appraisal of the safety of chemicals in foods, drugs and cosmetics", Assocaition of Food and Drug Officials of the United States
published by the Editorial Committe, Baltimore (1959)

GLP compliance:

no

Remarks:

Study performed before GLP statement

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): methylglutaronitrile

- Physical state: colorless liquid

No other data available

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: No data
- Age at study initiation: No data
- Weight at study initiation: 2,0 to 3.0 kg
- 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

Test system

Vehicle:

unchanged (no vehicle)

Controls:

not specified

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 mL
- Concentration (if solution): no data

Duration of treatment / exposure:

Eyes were not rinsed

Observation period (in vivo):

Eyes are observed 1, 24, 48, 72, 96 h and 7 days after application

Number of animals or in vitro replicates:

4

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing (if done): No washing


SCORING SYSTEM: according to Draize scale.


TOOL USED TO ASSESS SCORE: hand-slit lamp / biomicroscope / fluorescein: No data

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

cornea opacity score

Basis:

mean

Remarks:

of all animals (n=4)

Time point:

24/48/72 h

Score:

0.25

Max. score:

4

Reversibility:

fully reversible within: 2 days

Results 2

Irritation parameter:

iris score

Basis:

mean

Remarks:

of all animals (n=4)

Time point:

24/48/72 h

Score:

0.25

Max. score:

2

Reversibility:

fully reversible within: 2 days

Results 3

Irritation parameter:

conjunctivae score

Basis:

mean

Remarks:

of all animals (n=4)

Time point:

24/48/72 h

Score:

0.25

Max. score:

3

Reversibility:

fully reversible within: 2 days

Results 4

Irritation parameter:

chemosis score

Basis:

mean

Remarks:

of all animals (n=4)

Time point:

24/48/72 h

Score:

0.42

Max. score:

4

Reversibility:

fully reversible within: 3 days

Irritant / corrosive response data:

The acute Ocular Irritation Index is 19.75 and after 4 days about 0.00. See details in Table 7.3.2/1

Any other information on results incl. tables

Table 7.3.2/1: Irritant/corrosive response data for each animal at each observation time up to removal of each animal from the test

Score at time point / Reversibility	Cornea	Iris	Conjunctivae	Chemosis
	Max. score: 4	Max. score: 2	Max. score: 3	Max. score: 4
60 min	1/1/1/2	1/1/1/1	2/2/1/2	2/1/1/2
24 h	1/1/0/1	1/1/0/1	1/1/0/1	1/1/1/1
48 h	0/0/0/0	0/0/0/0	0/0/0/0	0/0/0/1
72 h	0/0/0/0	0/0/0/0	0/0/0/0	0/0/0/0
Average 24h, 48h, 72h	0.25	0.25	0.25	0.42
Reversibility*)	c/c/c/c	c/c/c/c	c/c/c/c	c/c/c/c
Average time (day) for reversion	2/2/1/2	2/2/1/2	2/2/1/2	2/2/2/3

 *) Reversibility: c. = completely reversible

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

Under the test conditions, 2-methylglutaronitrile is slighlty irritating to the eyes but is not classified according to the criteria of CLP regulation (EC) N°(1272-2008) and to the Annex VI of the Directive 67/548/EEC.

Executive summary:

In an eye irritation study performed similarly to the OECD guideline No. 405 with some acceptable deviations (Draize experimental protocol), 0.1 mL of undiluted 2-Methylglutaronitrile was instilled into the conjunctival sac of left eye of 4 New Zealand White rabbits. The eyes of the animals were not rinsed after instillation and were examined and the changes graded according to the Draize scale at 1, 24, 48, 72, 96 hrs and 7 days after application.

The mean values for the 4 animals and for the timepoints 24, 48 and 72 hrs were respectively for cornea, iris, conjunctivae and chemosis of 0.25, 0.25, 0.25 and 0.42. All of these effects were totally reversed after 3 days.

Under these test conditions, 2-methylglutaronitrile is considered as slightly irritating to eyes but no classification is required according to the criteria of the CLP regulation (EC) N°(1271 -2008) and to the Annex VI to the Directive 67/548/EEC.