Amines, N-C10-16-alkyltrimethylenedi-, reaction products with chloroacetic acid

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study with acceptable restrictions

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1988

Report date:

1988

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Version / remarks:

1981

Deviations:

yes

Remarks:

duration of observation was not extended in order to sufficiently evaluate fully the reversibility

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)

Version / remarks:

1984

Deviations:

no

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Amines, N-C10–C16-alkyltrimethylenedi-, reaction products with chloroacetic acid

Cas Number:

139734-65-9

Molecular formula:

Not applicable (UVCB substance)

IUPAC Name:

Amines, N-C10–C16-alkyltrimethylenedi-, reaction products with chloroacetic acid

Test material form:

other: 20% of the pure active substance in water

Details on test material:

- Name of test material: DOPA-Glycinate

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Harald Schriever, Rabbit farm, Bremervörde, Germany
- Weight at study initiation: 2.4–2.6 kg
- Housing: individually
- Diet: pelleted rabbit diet, ad libitum
- Water: drinking water, ad libitum
- Acclimation period: at least 7 d

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18±2
- Humidity (%): 50-85
- Photoperiod (hrs dark / hrs light): 12/12

Test system

Vehicle:

unchanged (no vehicle)

Controls:

other: The untreated right eyes served as controls.

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 mL

Duration of treatment / exposure:

Group 1: Animal 1–3; no removal of test substance
Group2: Animal 4–6 exposure for 4 sec.

Observation period (in vivo):

72 h

Number of animals or in vitro replicates:

6

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Washed out with 10 mL lukewarm water (animal 4–6).
- Time after start of exposure: 4 sec

SCORING SYSTEM: Draize scale

TOOL USED TO ASSESS SCORE: fluorescein

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

cornea opacity score

Basis:

mean

Remarks:

animals 1-3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Results 2

Irritation parameter:

iris score

Basis:

mean

Remarks:

animals 1-3

Time point:

24/48/72 h

Score:

2

Max. score:

2

Reversibility:

not fully reversible within: 72 h

Remarks on result:

other: reversibility cannot be judged as the observation was not continued after the 72 h time point

Results 3

Irritation parameter:

conjunctivae score

Basis:

mean

Remarks:

animals 1-3

Time point:

24/48/72 h

Score:

3

Max. score:

3

Reversibility:

not fully reversible within: 72 h

Remarks on result:

other: reversibility cannot be judged as the observation was not continued after the 72 h time point

Results 4

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

24/48/72 h

Score:

3

Max. score:

4

Reversibility:

not fully reversible within: 72 h

Remarks on result:

other: reversibility cannot be judged as the observation was not continued after the 72 h time point

Results 5

Irritation parameter:

chemosis score

Basis:

mean

Remarks:

animals 2, 3

Time point:

24/48/72 h

Score:

4

Max. score:

4

Reversibility:

not fully reversible within: 72 h

Remarks on result:

other: reversibility cannot be judged as the observation was not continued after the 72 h time point

Irritant / corrosive response data:

Reversibility of the eye reactions could not be observed within the 72 hour-study period. All animals showed absence of the light reflex (iridial response grade 2) which persisted for 72 hours. According to the guidelines, this lesion is generally not reversible.
According to most recent guideline the test substance should not be washed out. Thus, only results from animals 1 to 3 were evaluated where the test substance was not washed out.

Any other information on results incl. tables

Table A6.1.4 -4:Acute eye irritation in rabbits of group 1 (no removal of test substance).

	Cornea	Iris	Conjunctiva
Score (animal #1, #2, #3)	Opacity		Redness	Chemosis
1 h	0/0/0	2/2/2	3/3/3	3/4/4
24 h	0/0/0	2/2/2	3/3/3	3/4/4
48 h	0/0/0	2/2/2	3/3/3	3/4/4
72 h	0/0/0	2/2/2	3/3/3	3/4/4
Average 24, 48, 72 h	0/0/0	2/2/2	3/3/3	3/4/4

 

Table A6.1.4 -5:Acute eye irritation in rabbits of group 2 (removal of test substance).

	Cornea	Iris	Conjunctiva
Score (animal #4/#5/#6)	Opacity		Redness	Chemosis
1 h	0/0/0	2/2/2	2/3/3	3/4/4
24 h	0/0/0	2/2/2	3/3/3	4/4/4
48 h	0/0/0	2/2/2	3/3/3	4/4/4
72 h	0/0/0	2/2/2	3/3/3	4/4/4
Average 24, 48, 72 h	0/0/0	2/2/2	3/3/3	4/4/4

 

Applicant's summary and conclusion

Interpretation of results:

Category 1 (irreversible effects on the eye) based on GHS criteria

Conclusions:

In this eye irritation test in rabbit, the registration substance (20% a.i.) caused diffuse beefy redness and swelling with lids about half closed or more than half closed (grade 3) as well as lesions of the iris grade 2. Thus, Amines, N-C10-16-alkyltrimethylenedi-, reaction products with chloroacetic acid is classified according to the criteria laid down in Regulation (EC) No 1272/2008 as well as the Globally Harmonized System of Classification and Labelling of Chemicals (GHS) of the United Nations as Category 1 (irreversible effects on the eye).

Executive summary:

The acute eye irritation of the registration substance (20% aqueous solution) was tested in New Zealand White rabbits, according to EC method B.5 (1984) and OECD guideline 405 (1981). Six rabbits were administered a dose of 0.1 mL test substance into the left eye. In one group consisting of three animals the eyes were not washed, while in the other group the test substance was removed after 4 seconds. According to the most recent OECD guideline 405 test substance should not be washed out after treatment. Thus, only animals where the test substance was not washed out were considered for classification and labelling.

However, the results with and without removal of the test substance were consistent. No corneal opacity was observed during the study. Diffuse beefy redness and swelling with lids about half closed or more than half closed as well as lesions of the iris grade 2 (no reaction to light, haemorrhage and/or gross destruction) were observed throughout the study period. Reversibility was not observed within the observation period of 72 hours. According to the guidelines, absence of the light reflex (iridial response grade 2) which persists for 72 hours is generally not reversible.

Thus, according to the requirements specified Regulation (EC) 1272/2008 as well as Labelling of Chemicals (GHS) of the United Nations, Amines, N-C10-16-alkyltrimethylenedi-, reaction products with chloroacetic acid requires classification as Category 1 (irreversible effects on the eye).