3,6,9,12-tetraoxahexadecan-1-ol

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2003

Report date:

2003

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

Test guideline 3

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.2400 (Acute Eye Irritation)

Deviations:

no

Test guideline 4

Qualifier:

according to guideline

Guideline:

other: Japan MAFF Testing Guideline of 12 Nousan No. 8147, November 24, 2003

Deviations:

no

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

3,6,9,12-tetraoxahexadecan-1-ol

EC Number:

216-322-1

EC Name:

3,6,9,12-tetraoxahexadecan-1-ol

Cas Number:

1559-34-8

Molecular formula:

C12H26O5

IUPAC Name:

3,6,9,12-tetraoxahexadecan-1-ol

Details on test material:

- Name of test material (as cited in study report): Tetraethylenglykolmonobutylether
- Physical state: liquid/yellow-clear
- Analytical purity: 84.44 %
- Lot/batch No.: Lab.J.Nr. 03050 Charge 1
- Stability under test conditions: stable under storage conditions and over the exposure period
- Storage condition of test material: room temperature

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Centre Lago S.A., 01540 Vonnas, France
- Age at study initiation: 5-6 month
- Weight at study initiation: 3.57-4.16 kg
- Housing: single housing, stainless steel wire mesh cages, floor area 3000 cm²
- Diet (e.g. ad libitum): Kliba-Labordiät, Provimi Kliba, SA, Kaiseraugust, Swiss about 130g/animal/day
- Water (e.g. ad libitum): Tap water ad libitum
- Acclimation period: at least 5 days before beginning of the experiment


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-24°C
- Humidity (%): 30-70%
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12h/12h

Test system

Vehicle:

unchanged (no vehicle)

Controls:

not specified

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 ml
- Concentration (if solution): undiluted

Duration of treatment / exposure:

24 hours

Observation period (in vivo):

14 days

Number of animals or in vitro replicates:

3

Details on study design:

Comment: rinsed after 24 hours

REMOVAL OF TEST SUBSTANCE
- Washing (if done): rinsing with 3-6 ml of hand warm tap water for 1 to 2 min using a syringe with a blunt probe
- Time after start of exposure: 24 hours


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

Area of cornea involved (ar): (The assessment of these ocular reactions is performed independent of the quoted guidelines)
1 = 0 < =1/4
2 = >1/4<1/2
3 = 2<3/
4 = >3/4

Iris:
0 = Normal
1 = Markedly deepened rugae, congestion, swelling, moderate circumcorneal hyperaemia or injection, any of these observations 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 (red):
(Refers to palpebral and bulbar conjunctivae, not to cornea and iris)
o = Blood vessels normal
1 = Some blood vessels definitely hyperaemic (injected)
2 = Diffuse, crimson colour, individual vessels not easily discernible
3 = Diffuse beefy red


Chemosis (sw):
Lids and/or nictitating membrane
0 = No swelling
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

Discharge (di): (The assessment of these ocular reactions is performed independent of the quoted guidelines)
0 = No discharge
1 = Any amount different from normal (does not include small amounts observed in inner canthus of normal animals)
2 = Discharge with moistening of the lids and hairs just adjacent to Iids
3 = Discharge with moistening of the lids and hairs, and considerable area around the eye
Description of any ocular findings not covered by this scale were recorded.

Key:
h = hour
d = day

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

other: 24, 48, 72 hour average

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 14 days

Results 2

Irritation parameter:

iris score

Basis:

mean

Time point:

other: 24, 48, 72 hour average

Score:

0.11

Max. score:

2

Reversibility:

fully reversible within: 7 days

Results 3

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

other: 24, 48, 72 hour average

Score:

2.22

Max. score:

3

Reversibility:

fully reversible within: 14 days

Results 4

Irritation parameter:

chemosis score

Basis:

mean

Time point:

other: 24, 48, 72 hour average

Score:

1.55

Max. score:

4

Any other information on results incl. tables

Clinical examinations and assessment of ocular findings

Slight corneal opacity (grade 1) was observed in all animals 24 hours after application and persisted in one animal up to 72 hours and in two animals up to day 7. Moderate iritis was seen in one animal 72 hours after application only. Slight to moderate conjunctival redness (grade 1 - 2), moderate to marked conjunctival chemosis (grade 2 - 3) and moderate discharge (grade 2) were observed in all animals 1 hour after application. Moderate or severe conjunctival redness (grade 2 or 3) was observed in all animals after 24 hours up to 72 hours and decreased to slight (grade 1) after 7 days. Moderate conjunctival chemosis (grade 2), noted in all animals 24 hours after application, persisted in one animal up to 72 hours and decreased to slight after 7 days, whereas in the other two animals chemosis decreased to slight after 48 up to 72 hours after application. Slight or moderate discharge (grade 1 or 2) was seen in all animals 24 hours after application. Slight discharge was noted in two animals from 48 hours up to 72 hours. In addition small retraction in the eyelid, suppuration, contracted pupil, discharge of blood, injected scleral vessels, circular or in a circumscribed area and marginal vascularization of the cornea in a circumscribed area were observed over the study period. The ocular reactions were reversible in all animals within 14 days after application. Mean scores calculated for each animal over 24, 48 and 72 hours were 1.0 for corneal opacity, 0.0, 0.3 and 0.0 for iris lesions, 2.0, 2.7 and 2.0 for redness of the conjunctiva and 1.3, 1.3 and 2.0 for chemosis.

Readings	Animal	Cornea		Iris	Conjunctiva			Additional findings
		Opacity	Area of cornea involved		Redness	Chemosis	Discharge
1h	1	0	0	0	2	3	2	PC
	2	0	0	0	2	2	2	49
	3	0	0	0	1	3	2
24h	1	1	2	0	2	2	1	DB, 48
	2	1	4	0	2	2	2	49
	3	1	4	0	2	2	1	49
48h	1	1	1	0	2	1	0	48
	2	1	4	0	3	1	1	S, 49
	3	1	4	0	2	2	1	49
72h	1	1	1	0	2	1	0	48
	2	1	4	1	3	1	1	49
	3	1	4	0	2	2	1	49
7d	1	0	0	0	1	0	0	44
	2	1	1	0	1	0	0	48
	3	1	2	0	1	1	0	SR,PC,44,48
14d	1	0	0	0	0	0	0
	2	0	0	0	0	0	0
	3	0	0	0	0	0	0
Mean	1	1		0	1.3	1.3
	2	1		0.3	1.3	1.3
	3	1		0	2	2.0
Mean		1		0.1	1.6	1.6

Explanation of findings:

SR = Small retraction in the eyelid

S = Suppuration

PC = Pupil contracted

DB = Discharge of blood

44 = Vascularization of the cornea, circumscribed area, marginal

48 = Scleral vessels injected, circumscribed area

49 = Scleral vessels injected, circular

Applicant's summary and conclusion

Interpretation of results:

Category 2 (irritating to eyes) based on GHS criteria

Remarks:

Migrated information

Conclusions:

GHS Classification: Causes severe eye irritation (Cat 2A)

Executive summary:

In a guideline GLP eye irritation study, the substance 3,6,9,12-tetraoxahexadecan-1-ol was tested in rabbit eyes to assess the level of eye irritancy produced. The eyes were washed after 24 hours as permitted under the guideline. This can be considered more representative of the hazard in man as humans have a lachrymatory response to irritants (a response lacking in rabbits.) Under the conditions of the test, moderate eye irritation was observed, the most acute response being moderate to severe conjunctival erythema. All symptoms disappeared within 14 days. However, the corneal response and the amount of redness produced over the first threee days does meet the criteria for classification under the GHS as a severe eye irritant (Cat 2A).