1-Propanaminium, 3-amino-N-(carboxymethyl)-N,N-dimethyl-, N-(C8-18(even numbered) and C18 unsaturated acyl) derivs., hydroxides, inner salts

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1986-01-24 to 1986-06-02

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1986

Report date:

1986

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

1984

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Version / remarks:

1981

Deviations:

no

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

1-Propanaminium, 3-amino-N-(carboxymethyl)-N,N-dimethyl-, N-(C8-18(even numbered) and C18 unsaturated acyl) derivs., hydroxides, inner salts

EC Number:

931-333-8

Cas Number:

147170-44-3

Molecular formula:

not applicable

IUPAC Name:

1-Propanaminium, 3-amino-N-(carboxymethyl)-N,N-dimethyl-, N-(C8-18(even numbered) and C18 unsaturated acyl) derivs., hydroxides, inner salts

Constituent 2

Reference substance name:

Water

EC Number:

231-791-2

EC Name:

Water

Cas Number:

7732-18-5

Molecular formula:

H2O

IUPAC Name:

dihydrogen oxide

Test material form:

solid - liquid: aqueous solution

Test animals / tissue source

Species:

rabbit

Strain:

Himalayan

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Strain: Himalayan, termed in study report as Kleinrusse Chbb: HM
- Age at study initiation: no data
- Weight at study initiation: 2028 to 2092 g
- 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

Test system

Vehicle:

water

Controls:

other: untreated eye served as control

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 ml
- Concentration (if solution): 5 % active substance

VEHICLE
- water

Duration of treatment / exposure:

eyes were not rinsed after treatment

Observation period (in vivo):

10 days
scorings at 1, 6, 24, 48, 72, 96 and 168 hour(s) and 10 days after test substance instillation

Number of animals or in vitro replicates:

4

Details on study design:

APPLICATION OF TEST SUBSTANCE
- 100 mg test substance was instilled into the conjunctival sac of the left eye. The untreated right eye served as control.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): the treated eyes were not rinsed after treatment

SCORING SYSTEM: as stipulated in Foods, Drugs and Cosmetics. Ass. of Food and Drug Officials of the U.S., pp. 49 - 52 (1959) (Draize scheme)

TOOL USED TO ASSESS SCORE: no tools mentioned

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

cornea opacity score

Basis:

animal: #1, #3

Time point:

24/48/72 h

Score:

0.67

Max. score:

4

Reversibility:

fully reversible within: 72 h

Remarks on result:

other: at 24 h whole cornea affected

Results 2

Irritation parameter:

cornea opacity score

Basis:

animal: #2

Time point:

24/48/72 h

Score:

0.33

Max. score:

4

Reversibility:

fully reversible within: 48 h

Remarks on result:

other: at 24 h whole cornea affected

Results 3

Irritation parameter:

cornea opacity score

Basis:

animal: #4

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 72 h

Remarks on result:

other: at 24 h whole cornea affected

Results 4

Irritation parameter:

iris score

Basis:

animal: #1, #2

Time point:

24/48/72 h

Score:

0.33

Max. score:

2

Reversibility:

fully reversible within: 48 h

Results 5

Irritation parameter:

conjunctivae score

Basis:

animal: #1

Time point:

24/48/72 h

Score:

2.33

Max. score:

3

Reversibility:

fully reversible within: 96 h

Results 6

Irritation parameter:

conjunctivae score

Basis:

animal: #2

Time point:

24/48/72 h

Score:

2

Max. score:

3

Reversibility:

fully reversible within: 72 h

Results 7

Irritation parameter:

conjunctivae score

Basis:

animal: #3

Time point:

24/48/72 h

Score:

2.67

Max. score:

3

Reversibility:

fully reversible within: 168 h

Results 8

Irritation parameter:

conjunctivae score

Basis:

animal: #4

Time point:

24/48/72 h

Score:

3

Max. score:

3

Reversibility:

fully reversible within: 168 h

Results 9

Irritation parameter:

chemosis score

Basis:

animal: #1

Time point:

24/48/72 h

Score:

0.33

Max. score:

4

Reversibility:

fully reversible within: 48 h

Results 10

Irritation parameter:

chemosis score

Basis:

animal: #2, #3

Time point:

24/48/72 h

Score:

0.67

Max. score:

4

Reversibility:

fully reversible within: 72 h

Results 11

Irritation parameter:

chemosis score

Basis:

animal: #4

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 96 h

Results 12

Irritation parameter:

iris score

Basis:

animal: #3, #4

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritant / corrosive response data:

All animals showed 1 hour after treatment, cornea opacity score 1 which affected one quarter of the cornea (area score 1). Until the 24 h scoring cornea opacity worsened in one animal to score 2 and trespassed in all four animals to the whole cornea (area score 4). Cornea effects were fully reversible in one animals by the 48 h scoring and in the other three animals by the 72 h scoring. Iritis was singly seen in two of the four animals at the 24 h scoring. Conjunctival redness worsened in all animals from initial scores 1 or 2 to score 3 at the 24 and 48 h scorings and was fully reversible in one animal each by the 72 or 96 h scoring and in two animals by the 168 h scoring. Maximal chemosis was seen at the 6 h scoring with score 1 in one and score two in the other three animals and was fully reversible in one animal each by the 48 or 96 h scoring and in two animals by the 72 h scoring. All animals showed discharge formation, which had its maximum at the 6 h scoring and was fully reversible in the individually animals 72 to 168 h after treatment.

Any other information on results incl. tables

Table 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 opacity	Cornea area affected	Iris	Conjunctivae	Chemosis	Discharge
	Max. score: 4	Max. score: 4	Max. score: 2	Max. score: 3	Max. score: 4	Max. score: 3
1h	1/1/1/1	1/1/1/1	0/0/0/0	2/1/1/1	1/1/1/2	2/3/3/3
6 h	1/1/1/1	1/4/1/4	0/0/0/0	2/2/2/2	1/2/2/2	3/3/3/3
24 h	1/1/1/2	4/4/4/4	1/1/0/0	3/3/3/3	1/1/1/1	2/1/2/3
48 h	1/0/1/1	2/0/1/2	0/0/0/0	3/3/3/3	0/1/1/1	1/1/1/2
72 h	0/0/0/0	0/0/0/0	0/0/0/0	1/0/2/3	0/0/0/1	1/0/1/1
96 h	0/0/0/0	0/0/0/0	0/0/0/0	0/0/1/2	0/0/0/0	0/0/0/1
168 h	No data	No data	No data	0/0/0/0	0/0/0/0	0/0/0/0
10 d	No data	No data	No data	0/0/0/0	0/0/0/0	0/0/0/0
Average 24h, 48h, 72h	0.67/0.33/0.67/1	2/1.33/1.67/2	0.33/0.33/0/0	2.33/2/2.67/3	0.33/0.67/0.67/1	1.33/0.67/1.33/2
Reversibility*)	c.	c.	c.	c.	c.	c.
Time for reversion (h)	72/48/72/72	72/48/72/72	48/48/-/-	96/72/168/168	48/72/72/96	96/72/96/168

*) Reversibility: c. = completely reversible; n.c. = not completely reversible; n. = not reversible

Applicant's summary and conclusion

Interpretation of results:

Category 2 (irritating to eyes) based on GHS criteria

Conclusions:

Classification is based on effects on the cornea, iris and conjunctiva calculated as mean scores following grading at 24, 48 and 72 hours after instillation of the test material, in consideration of reversibility.
The test substance is considered to be irritating according to CLP, EU GHS (Regulation (EC) No 1272/2008).

Executive summary:

In a primary eye irritation study according to EU Method B.5 (1984) and OECD Guideline 405 (1981), 0.1 ml of Coco AAPB (5 % a.i. in water) was instilled into the conjunctival sac of four Himalayan rabbits. The treated eyes were not rinsed after test substance instillation. Animals were then observed for 10 days. Irritation was scored according to Draize.

All animals showed 1 hour after treatment, cornea opacity score 1 which affected one quarter of the cornea (area score 1). Until the 24 h scoring cornea opacity worsened in one animal to score 2 and trespassed in all four animals to the whole cornea (area score 4). Cornea effects were fully reversible in one animal by the 48 h scoring and in the other three animals by the 72 h scoring. Iritis was solely seen in two of the four animals at the 24 h scoring. Conjunctival redness worsened in all animals from initial scores 1 or 2 to score 3 at the 24 and 48 h scorings and was fully reversible in one animal each by the 72 or 96 h scoring and in two animals by the 168 h scoring. Maximal chemosis was seen at the 6 h scoring with score 1 in one and score two in the other three animals and was fully reversible in one animal each by the 48 or 96 h scoring and in two animals by the 72 h scoring. All animals showed discharge formation, which had its maximum at the 6 h scoring and was fully reversible in the individually animals 72 to 168 h after treatment.

 

In this study, Coco AAPB (5 % a.i. in water) is an eye irritant.