2-cyano-N-methylacetamide

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1981-06-09

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Guideline study conducted without GLP compliance

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1981

Report date:

1981

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

other: Fed.Reg.38, No.187, Para.1500.42, S.27019 (1973-09-27)

Test guideline 2

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

GLP compliance:

not specified

Test material

Test material information

Constituent 1

Reference substance name:

2-cyano-N-methylacetamide

EC Number:

228-705-0

EC Name:

2-cyano-N-methylacetamide

Cas Number:

6330-25-2

Molecular formula:

C4H6N2O

IUPAC Name:

2-cyano-N-methylacetamide

Details on test material:

- Name of test material: N-Methylcyanacetamid
- Physical state: powder

Test animals / tissue source

Species:

rabbit

Strain:

Vienna White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Firma Gaukler, Offenbach / Main
- Weight at study initiation: male: 2.99 kg / female: 2.43 kg
- Housing: Stainless steel cage with wire shelves, ground area: 40 x 51 cm
- Diet (ca. 130 g/animal): Ovator Solikanin 4mm, Muskator-Werke Düsseldorf
- Water (ca. 250 mL/animal): VE-water on week days, tapwater on holidays
- Acclimation period: about 8 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 - 26
- Humidity (%): ca. 30 - 70
- Photoperiod (hrs dark / hrs light): 12 / 12

Test system

Vehicle:

unchanged (no vehicle)

Remarks:

ca. 50 mg of crushed substance

Controls:

not required

Amount / concentration applied:

TEST MATERIAL
- Amount applied: 0.1 mL bulk volume

Duration of treatment / exposure:

single application

Observation period (in vivo):

10 d

Number of animals or in vitro replicates:

6 (2 male, 4 female)

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing: not performed

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

other: Primary Irritation Index

Basis:

other: Sum of all single stimulus values

Time point:

other: 24, 48, 72 h

Score:

16

Reversibility:

not fully reversible within: 10 days

Remarks on result:

other: two of six animals still showed grade 1 redness of conjunctivae at the last observation day (day 10).

Results 2

Irritation parameter:

iris score

Basis:

mean

Time point:

other: 24, 48, 72h

Score:

0.3

Max. score:

1

Reversibility:

fully reversible within: 72h

Results 3

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

other: 24, 48, 72h

Score:

0.6

Max. score:

1

Reversibility:

fully reversible within: 10 days

Results 4

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

other: 24, 48, 72h

Score:

1.6

Max. score:

2

Reversibility:

not fully reversible within: 10 days

Remarks on result:

other: expected to be reversible within 14 days

Results 5

Irritation parameter:

chemosis score

Basis:

mean

Time point:

other: 24, 48, 72h

Score:

0.5

Max. score:

1

Reversibility:

fully reversible within: 72h

Irritant / corrosive response data:

Ciliary injection as well as a slight opacity of the cornea (three quarters of the area) and significant redness, slight swelling and secretion of the conjunctiva was recorded 24 h after test substance application. In one animal contraction of the pupils was observed after 24 h and 48 h. At day 10 no symptons were recorded.

Other effects:

No other effects are reported.

Any other information on results incl. tables

Table 1: Results of the eye irritation test

(FED. REG. 38, NO. 187, PARA. 1500.42, S. 27019 - 1973 -09 -273)
Animal		1		2		3		4	5	6
Animal number		0383		0371		0361		0337	0365	0292
Animal weight (kg)		2.37		2.50		2.40		3.05	2.45	2. 92
Sex		female		female		female		male	female	male
Time	Animal	Cornea		Iris	Conjunctiva			Symptoms		Single stimulus value
		TR	FL		RO	SW	SE
24 h	1	1	4	1	2	1	1	Contraction of the pupils			33
	2	0	0	0	2	1	1				8
	3	1	4	1	2	1	2				35
	4	0	0	0	1	0	1				4
	5	1	4	0	2	1	1				28
	6	1	4	1	2	1	1				33
48 h										Mean Value	24
	1	1	2	1	2	1	1	Contraction of the pupils			23
	2	0	0	0	0	0	0				0
	3	1	3	1	2	1	1				28
	4	0	0	0	1	0	0				2
	5	1	2	0	2	1	1				18
	6	1	4	1	2	1	1				33
72 h										Mean Value	17
	1	1	2	0	1	0	0				12
	2	0	0	0	1	0	0				2
	3	1	2	0	1	0	0				12
	4	0	0	0	1	0	0				2
	5	0	0	0	0	0	0				0
	6	1	2	0	1	0	0				12
10 d										Mean Value	7
	1	0	0	0	1	0	0				2
	2	0	0	0	0	0	0				0
	3	0	0	0	0	0	0				0
	4	0	0	0	1	0	0				2
	5	0	0	0	0	0	0				0
	6	0	0	0	0	0	0				0
										Mean Value	1
285 / 18 = 16 (rounded)
Primary Irritation Index: 16

Explanation of the rating scale:

a) Conjunctiva - Swelling and Cornea - Opacity:

0 - non-existent / 1 - slight / 2 - significant / 3 - severe / 4 - strong

b) Conjunctiva - Redness:

0 - ordinary / 1 - slightly increased / 2 - significant / 3 - severe

c) Iris:

1 - Ciliary injection / 2 - Iritis

d) Cornea - affected area

1 - >= 0, < 1/4

2 - >= 1/4, < 1/2

3 - > = 1/2, < 3/4

4 - >= 3/4

e) Secretion:

0 - ordinary / 1 - slightly increased / 2 - significantly increased / 3 - proliferated

Calculation of the Primary Irritation Index:

A = 5 x Opacity x Area

B = 5 x Iris

C = 2 x (Redness + Swelling + Secretion)

Single Stimulus Value = A + B + C (1 animal per time)

The Primary Irritation Index is the sum of all single stimulus values of all animals and time points (24, 48 and 72 h) divided by 3 x the number of animals.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Executive summary:

The test substance 2 -cyano-N-methylacetamide was investigated for its potential to cause irritation in a rabbit eye according to Fed.Reg.38, No.187, Para.1500.42, S.27019 (1973) with one single application. About 50 mg of crushed substance (bulk volume of 0.1 mL) was applied into the conjunctival sac and not washed out afterwards. The untreated eye served as negative control. 6 animals (2 males and 4 females) were observed for 10 days after this procedure. Ciliary injection as well as a slight opacity of the cornea (three quarters of the area) and significant redness, slight swelling and secretion of the conjunctiva was recorded 24 h after test substance application. In one animal contraction of the pupils was observed after 24 h and 48 h. At day 10 no symptons were recorded. The Primary Irritation Index was calculated according to the scheme of Draize (1965), resulting in a value of 16, which corresponds to a slightly irritating test substance for the rabbit eye mucosa.