Poly(oxy-1,2-ethanediyl), α-(carboxymethyl)-ω-hydroxy-, C16-18 (even numbered) and C18-unsatd. alkyl ethers

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1994-12-29 to 1995-01-30

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1995

Report date:

1995

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Version / remarks:

adopted February 24th, 1987

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

1992

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test material

Test material information

Constituent 1

Reference substance name:

Reference substance 004

Cas Number:

288259-40-5

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:

liquid

Specific details on test material used for the study:

SOURCE OF TEST MATERIAL
- Purity: 90 % a.i.

Test animals / tissue source

Species:

rabbit

Strain:

Himalayan

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: CHR. FRED LEUSCHNER & CO. D-24601 Löhndorf/Post Wanken dorf
- Age at study initiation: approx. 5 - 7 months
- Weight at study initiation: 1.9 - 2.2 kg
- Housing: individually in suspended wire bottom stainless steel cages
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: at least 20 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20°C ± 3°C
- Humidity (%): 50% ± 20%
- Air changes (per hr):
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 29.12.1994 To: 19.01.199

Test system

Vehicle:

unchanged (no vehicle)

Controls:

yes, concurrent no treatment

Amount / concentration applied:

0.1 mL

Duration of treatment / exposure:

single application, no washing after application of testsubstance

Observation period (in vivo):

20 days

Number of animals or in vitro replicates:

3 females

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing (if done): no


SCORING SYSTEM:
Draize scale (OECD guideline 405)

TOOL USED TO ASSESS SCORE: fluorescein

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

cornea opacity score

Basis:

animal: #1, #2, #3

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

not reversible

Remarks on result:

probability of severe irritation

Results 2

Irritation parameter:

iris score

Basis:

animal: #1, #2, #3

Time point:

24/48/72 h

Score:

2

Max. score:

2

Reversibility:

not reversible

Remarks on result:

probability of severe irritation

Results 3

Irritation parameter:

conjunctivae score

Basis:

animal: #1, #2, #3

Time point:

24/48/72 h

Score:

2

Max. score:

3

Reversibility:

not fully reversible within: 20 d

Remarks on result:

positive indication of irritation

Results 4

Irritation parameter:

chemosis score

Basis:

animal: #1

Time point:

24/48/72 h

Score:

2

Max. score:

4

Reversibility:

fully reversible within: 13 d

Remarks on result:

positive indication of irritation

Results 5

Irritation parameter:

chemosis score

Basis:

animal: #2, #3

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 11 d

Remarks on result:

positive indication of irritation

Irritant / corrosive response data:

Corneal opacity (grade 1 and 2) which was observed in all three rabbits between 24 hours and 20 days after instillation (last examination time-point). From the 12th day after instillation a pericorneal vascular injection was observed for two rabbits, in one of them a commencing detachment of the cornea occurred from the next day onwards. Corneal changes
were confirmed by three fluorescein tests (24 hours, 7 and 14 days after dosing). Opacity covered up to the whole area. Corneal opacity did not subside until the 20th day after instillation (last examination).

At the examinations 24 hours to 20 days after instillation, the iris of all animals was affected with markedly deepened rugae, congestion, swelling, moderate circumcorneal hyperaemia or injection (any of these or combination of any thereof), the iris was still reacting
to light (grade 1) or showed no reaction to light, had haemorrhages and/or gross destruction (any or all of these, grade 2).

Conjunctival redness (grade 1 and 2) was seen during the examinations 1 hour to 16 days after instillation in all rabbits, in two animals the redness was observed until the 20th day after instillation. Conjunctival chemosis (grade 1 and predominantly grade 2) was evident in all rabbits between 24 hours and 10 days after instillation, in one rabbit until the 12th day after instillation.

Conjunctival hypersecretion (grade 1 to 3) was observed in all three rabbits during the examinations 1 hour to 6 days instillation. Conjunctival chemosis had disappeared 13 days after instillation, conjunctival redness had not disappeared until 20 days after instillation (last examination).

Other effects:

- Other observations:
The rabbits behaved normally, their external appearance was inconspicuous. Food consumption and body weight gain did not show any impairment.

Any other information on results incl. tables

Table #: 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	0*/0*/0*	0/0/0	2/2/2	0#/1#/1#
24 h	1/1/1	1/1/1	2/2/2	2#/1#/1#
48 h	1/1/1	1/1/1	2/2/2	2#/1#/1#
72 h	1/1/1	1/1/1	2/2/2	2#/1#/1#
Average 24h, 48h, 72h	1.0/1.0/1.0	1.0/1.0/1.0	2.0/2.0/2.0	2.0/1.0/1.0
4 d	1/1/1	2/1/2	2/2/2	2#/2#/1#
5d	2/1/1	2/1/1	2/2/2	2#/2#/1#
6d	2/1/1	2/1/1	2/2/2	2#/2#/1#
7d (LH)	2/1/2	2/1/1	2/2/2	2/2/1
8d (LH)	1/1/2	2/1/1	1/2/1	2/2/1
9d (LH)	1/1/2	2/1/1	1/2/1	2/1/1
10d (LH)	1/1/2	2/1/1	1/1/1	2/1/1
11d (LH)	1/1/2	2/1/1	1/1/1	1/0/0
12d (LH)	1/1##/2##	2/1/1	1/1/1	1/0/0
13d	1/1/2###	1/1/1	1/1/1	0/0/0
14d	1/1/2###	1/1/2	1/1/1	0/0/0
15d	1/1/2###	1/1/2	1/1/1	0/0/0
16d	1/1/2###	1/1/2	1/1/1	0/0/0
17d	1/1/2###	1/1/2	1/0/1	0/0/0
18d	1/1/2###	1/1/2	1/0/1	0/0/0
19d	1/1/2###	1/1/2	1/0/1	0/0/0
20d	1**/1/2	1/1/2	1/0/1	0/0/0
Reversibility*)	n	n	n	c
Average time (unit) for reversion				14 d

24 hrs, 7 d and 14 d fluorescein tests: confirmed the corneal changes

* transparent substance deposits on the cornea ** detachment of the cornea

# whitish conjunctivalhypersecretion (grades 1 - 3) (LH) loss of hair around the eyelids

## pericorneal vascular injection ### pericorneal vascular injection, commencing detachment of the cornea

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

Applicant's summary and conclusion

Interpretation of results:

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

Conclusions:

In this study, Polyoxyethylene(4.5) lauryl miristyl ether carboxylic acid has irreversible effects on the eyes (Category 1) based on the effects being not reversible at the end of the observation period of 20 d.

Executive summary:

In a primary eye irritation study according to OECD guideline 405 (February 24, 1987) 0.1 mL of Polyoxyethylene(4.5) lauryl miristyl ether carboxylic acid (90% a.i.) was instilled into the conjunctival sac of one eye of 3 young adult Himalayan rabbits not followed by washing. The untreated eyes served as controls. Animals were then observed for 20 days. Irritation was scored by the method of Draize.

Corneal opacity (grade 1 and 2) which was observed in all three rabbits between 24 hours and 20 days after instillation (last examination time-point). From the 12th day after instillation a pericorneal vascular injection was observed for two rabbits, in one of them a commencing detachment of the cornea occurred from the next day onwards. Corneal changes were confirmed by three fluorescein tests (24 hours, 7 and 14 days after dosing). Opacity covered up to the whole area. Corneal opacity did not subside until the 20th day after instillation (last examination).

At the examinations 24 hours to 20 days after instillation, the iris of all animals was affected with markedly deepened rugae, congestion, swelling, moderate circumcorneal hyperaemia or injection (any of these or combination of any thereof), the iris was still reacting to light (grade 1) or showed no reaction to light, had haemorrhages and/or gross destruction (any or all of these, grade 2).

Conjunctival redness (grade 1 and 2) was seen during the examinations 1 hour to 16 days after instillation in all rabbits, in two animals the redness was observed until the 20th day after instillation. Conjunctival chemosis (grade 1 and predominantly grade 2) was evident in all rabbits between 24 hours and 10 days after instillation, in one rabbit until the 12th day after instillation.

Conjunctival hypersecretion (grade 1 to 3) was observed in all three rabbits during the examinations 1 hour to 6 days instillation. Conjunctival chemosis had disappeared 13 days after instillation, conjunctival redness had not disappeared until 20 days after instillation (last examination).

Thus, Polyoxyethylene(4.5) lauryl miristyl ether carboxylic acid (90% a.i.), produced irreversible effects to the eye in this study and thus has to be classified as Category 1 (irreversible effects on the eye) according to the criteria of CLP, EU GHS (Regulation (EC) No 1272/2008).