pentasodium 3,7,11-tris(carboxylatomethyl)-15-(C12-18)-alkyl-3,7,11,15-tetraazaheptadecane-1,17-dioate

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

20 September 1993 - 4 October 1993.

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Only available as final draft report.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1993

Report date:

1993

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

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

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Amines, N-C8-22-alkylpolytrimethylenepoly-, carboxymethyl derivs., sodium salts

EC Number:

307-458-3

EC Name:

Amines, N-C8-22-alkylpolytrimethylenepoly-, carboxymethyl derivs., sodium salts

Cas Number:

97659-53-5

Details on test material:

Identity: Ampholak 7CX
Chemical name: Cocoamphopolycarboxyglycinate
Ref No.: 19882,1458
Batch number: FP 91327
Expiry: 18 August 1995
Purity: 27% in water
Appearance: Clear amber liquid
Storage conditions: Room temperature
Date received: 18 August 1993

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Froxfield Rabbits
- Age at study initiation: 10-14 weeks
- Weight at study initiation: 2.3-3.2 kg
- Housing: individually in metal cages with perforated floors
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: yes, time not reported

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19
- Humidity (%): 30-70
- Air changes (per hr): 19
- Photoperiod (hrs dark / hrs light): 12/12


IN-LIFE DATES: 20 September 1993 - 4 October 1993.

Test system

Vehicle:

unchanged (no vehicle)

Controls:

other: untreated eye of the animal

Amount / concentration applied:

0.1 ml

Duration of treatment / exposure:

One single instillation was performed and the animals were obsreved for 7 days after instillation.

Observation period (in vivo):

7 days

Number of animals or in vitro replicates:

3

Details on study design:

The test substance was not removed from the eye.

SCORING SYSTEM:
Scoring system eye irritation

Cornea: degree of density (area most dense taken for reading)
0 No ulceration or opacity
1 Scattered or diffuse areas of opacity (other than slight dulling of normal lustre), details of iris clearly visible
2 Easily discernible translucent areas, details of iris slightly obscured
3 Nacrous areas, no details of iris visible, size of pupil barely discernible
4 Opaque cornea, iris not discernible through the opacity

Area of Cornea Involved
1 One quarter (or less) but not zero
2 Greater than one quarter but less than half
3 Greater than half but less than three quarters
4 Greater than three quarters, up to whole area

Iris
0 Normal
1 Markedly deepened rugae, congestion, swelling, moderate circumcorneal hyperaemia or injection, any of these or combination of any thereof, iris still reacting to light (sluggish reaction is positive)
2 No reaction to light, haemorrhage, gross destruction (any or all of these)

Conjunctivae
Redness (refers to palpebral and bulbar conjunctivae cornea and iris)

0 Blood vessels normal
1 Some blood vessels definitely hyperaemic
(injected)
2 Diffuse, crimson colour, individual vessels not easily discernible
3 Diffuse, beefy red

Chemosis (lids and/or nictitating membranes)
0 No swelling 0
1 Any swelling above normal (includes nictitating membranes)
2 Obvious swelling with partial eversion of lids
3 Swelling with lids about half-closed
4 Swelling with lids more than half-closed

TOOL USED TO ASSESS SCORE: handheld light

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

other: 24-48-72 hours

Score:

1.1

Max. score:

4

Reversibility:

fully reversible within: 5 days

Results 2

Irritation parameter:

iris score

Basis:

mean

Time point:

other: 24-48-72 hours

Score:

0

Max. score:

2

Results 3

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

other: 24-48-72 hours

Score:

1.3

Max. score:

3

Reversibility:

fully reversible within: 5 days

Results 4

Irritation parameter:

chemosis score

Basis:

mean

Time point:

other: 24-48-72 hours

Score:

0.9

Max. score:

4

Reversibility:

fully reversible within: 5 days

Irritant / corrosive response data:

Corneal opacites developed in two animals. Iridial inflammation was seen in one animal one hour after instillation only. A diffise crimson colouration of the conjunctivae was seen in two animals. Considerable swelling of the conjunctivae with partial eversion of the eyelids was seen in all three animals. The eyes were normal 3 or 7 days after instillation.

Other effects:

There were no signs of toxicity or ill health in any rabbit during the observation period.

Any other information on results incl. tables

Rabbit No and sex	Region of the eye		Hours after instillation						Average 24-48-72 hours
			1	24	48	72	96	5-7(days)
2450-m*	Cornea		0	0	0	0	0	0	0
	Iris		0	0	0	0	0	0	0
	Conjunctivae	Redness	1	1	1	0	0	0	0.6
		Chemosis	2	1	1	0	0	0	0.6
2463-m	Cornea		1	1	1	0	0	0	0.6
	Iris		0	0	0	0	0	0	0
	Conjunctivae	Redness	2	2	1	1	1	0	1.3
		Chemosis	2	1	1	1	1	0	1
2464-m	Cornea		0	2	2	1	1	0	1.6
	Iris		1	0	0	0	0	0	0
	Conjunctivae	Redness	2	2	2	2	2	0	2
		Chemosis	2	1	1	1	1	0	1

* Pilot animal

Applicant's summary and conclusion

Conclusions:

A single instillation of the test material into the eye of the rabbit elicited corneal opacificaton, iridial inflammation and well-defined conjunctival irritation. All reactions had resolved 3 or 7 days after instillation. The composition of the test material is estimated to be 40% active ingredient (incl NaCl) and 60 % water. The active ingredient Amines, N-(3-aminopropyl)-N’-C12-18-alkyltrimethylenedi-, N-(carboxymethyl)derivs., sodium salts (CAS no 2060541-51-5) is therefre not classified as irritating to eyes.

Executive summary:

A study was performed to assess the eye irritation potential of the test material to the rabbit. The method followed was that described in EEC Methods for the determination of toxicity, Amex to Directive 92/69/EEC (OJ No. L383A, 29.12.92), Part 3, Method B.5. Acute toxicity (eye irritation). The composition of the test material is estimated to be 40% active ingredient (incl NaCl) and 60 % water. Three rabbits were each administered a single ocular dose of 0.1 ml of the test material and observed for seven days after instillation. The active ingredient is Amines, N-(3-aminopropyl)-N’-C12-18-alkyltrimethylenedi-, N-(carboxymethyl)derivs., sodium salts (CAS no 2060541-51-5). A single instillation of the test material into the eye of the rabbit elicited corneal opacificaton, iridial inflammation and well-defined conjunctival irritation. All reactions had resolved 3 or 7 days after instillation. The active ingredient Amines, N-(3-aminopropyl)-N’-C12-18-alkyltrimethylenedi-, N-(carboxymethyl)derivs., sodium salts (CAS no 2060541-51-5) is therefre not classified as irritating to eyes.