2-(2-(2-ethoxyethoxy)ethoxy)ethanol

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Justification for type of information:

1. HYPOTHESIS FOR THE ANALOGUE APPROACH
The source and target substances are either trietheylen glycol alkyl ethers with identical structural groups and differing only in the length of the terminal alkyl chain or are from the same homologous series (ethylene glycol ethyl ethers differing only in the number of EO groups in the molecule and are as close together in th e series as possible - in this case adjacent). All of the groups in the target substances are seen in the source substance. Physicochemical properties are similar and vary in a predictable pattern. Read across is by interpolation using data from source substances adjacent to the target substance in the glycol ethers matrix.

2. SOURCE AND TARGET CHEMICAL(S) (INCLUDING INFORMATION ON PURITY AND IMPURITIES
Target: Tetraethylene glycol ethyl ether (TetraEGME)
Sources: Triethylene glycol methyl ether (TEGME) and Diethylene glycol ethyl ether (DEGEE).

3. ANALOGUE APPROACH JUSTIFICATION
See hypothesis above.

4. DATA MATRIX

Molecular weight: TEGME: 164, TEGEE: 178, DEGEE: 134
Partition coefficient (logkow): TEGME: -1.1, DEGEE: -0.5.
Water solubility: all fully water miscible
In vivo eye irritation results TEGME: not irritating. DEGEE: not irritating. Both show no edema and only faint initial erythema. None of the ethyl or methyl series exhibit skin irritation potential
Dermal LD50, rabbit: TEGME: 7.5, TEGBE: 3.5.
There is sufficient information to conclude that the target substance will not need to be classified for skin irritation

Cross-reference

Cross-reference 1

Reason / purpose for cross-reference:

read-across source

Reference

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

1987

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: A study that has been reported in a number of publications which between them contain sufficient detail to be able to reliably judge the eye irritancy properties of this substance.

Reason / purpose for cross-reference:

reference to same study

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

yes

Remarks:

, observations for only 7 days but not regarded as signficant for this material.

GLP compliance:

not specified

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Proefstations voor veeteelt (Merelbeke, Belgium)
- Weight at study initiation: 2-3.5kg
- Housing: individually in mesh wire bottom cages. 40x46x47.5cm
- Diet (e.g. ad libitum): ad libitum, pelleted Aliment Complet, 'lapins entretien ref 112, animolabo, Brussels.
- Water (e.g. ad libitum): ad libitum Brussels tap water.
- other: sex, male and female, albino

Vehicle:

unchanged (no vehicle)

Controls:

other: experiment was part of a larger study which examined a large number of chemicals for their eye irritancy

Amount / concentration applied:

0.1ml

Duration of treatment / exposure:

Single application

Observation period (in vivo):

7 days

Number of animals or in vitro replicates:

6

Details on study design:

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

SCORING SYSTEM: Draize scoring criteria used for Erythema, chemosis, iritis and corneal opacity

TOOL USED TO ASSESS SCORE: Application of one drop of 2% sodiumfluoroscein before visual scoring of percentage corneal damage. This was also done 72 hrs before testing to check for absence of existing lesions. Reading of ocular lesions was facilitated by use of a handslit lantern.

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

24/48/72 h

Score:

1.37

Max. score:

3

Reversibility:

other: see result details below.

Remarks on result:

other: mean score range for individual rabbits 1.3-1.44

Irritation parameter:

chemosis score

Basis:

mean

Time point:

24/48/72 h

Score:

0.17

Max. score:

4

Reversibility:

other: see result details below.

Remarks on result:

other: mean score range for individual rabbits 0.11-0.22

Irritation parameter:

iris score

Basis:

mean

Time point:

24/48/72 h

Score:

0.17

Max. score:

2

Reversibility:

other: see result details below.

Remarks on result:

other: mean score range for individual rabbits 0-0.33

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

24/48/72 h

Score:

0.22

Max. score:

4

Reversibility:

other: see result details below.

Remarks on result:

other: mean score range for individual rabbits 0-.44

Irritant / corrosive response data:

The mean corneal upper layer damage (loss of epithelium measured by fluorescein retention on the cornea using a hand-slit lamp) was 33% after 4 hrs and an average of 5% over the 72 hour test period. Pain response was measured and described as between "a few blinks only, normal within one or two minutes; animals didn't squeal or rub their eyes" and "rabbit blinks and tries to open eyes but reflex closes it; rabbit rubs its nose". There was no evidence of Pannus. Healing time described as >48 hours. Based on results for other substances this is interpreted as healing (reversibility) within 72 hours. Corneal swelling after 4 hours reported as 21% and average of 24, 48 and 72 hour measurements 20%.

Interpretation of results:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

On the basis of the infomation available, the substance does not meet the criteria for classification as irritant.

Executive summary:

A well reported study assessed the eye irritancy potential of 2 -(2 -ethoxyethoxy)ethanol along with a number of other test substances in rabbits. Even without a washing stage, the substance showed minimal iritis or corneal effects and minimal chemosis. Mild to moderate onjunctival effects were seen but insufficient to warrant classification. All significant effects appeared to reverse within 72 hours. The conclusion from this study is that the substance does not warrant classification as an eye irritant.

Cross-reference 2

Reason / purpose for cross-reference:

read-across source

Reference

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

11 Feb 1974 - 18 Feb 1974

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Acceptable study report which meets basic scientific principles. Some data missing for one animal.

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

yes

Remarks:

, 2 animals only

Principles of method if other than guideline:

Method: BASF-Test. The test substance were applied to the conjunctival sac of one eye in 2 animals. The animals were observed after 10 min, 1 and 3h on the day of treatment and up to 8 days afterwards. Findings were recorded daily. The eyes were not washed out after 24 hour. The report describes findings after 1 and 24 hours and at the end of the observation period. For final evaluation, the findings after 48 and 72 hours from the raw data were taken into account.

GLP compliance:

no

Species:

rabbit

Strain:

Vienna White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Gaukler
- Weight at study initiation: 2.94 kg (mean)

Vehicle:

unchanged (no vehicle)

Controls:

other: The adjacent eye served as saline-control.

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.05 ml

Duration of treatment / exposure:

8 days

Observation period (in vivo):

8 days

Number of animals or in vitro replicates:

2

Details on study design:

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

SCORING SYSTEM: The original BASF grading was converted into the numerical grading according to the OECD Draize system.

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

other: 1h

Score:

1

Max. score:

3

Reversibility:

fully reversible

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

other: 24h

Score:

0

Max. score:

3

Reversibility:

fully reversible

Irritation parameter:

conjunctivae score

Basis:

animal #2

Time point:

other: 1h

Score:

1

Max. score:

3

Reversibility:

fully reversible

Irritation parameter:

conjunctivae score

Basis:

animal #2

Time point:

other: 24h

Score:

1

Max. score:

3

Reversibility:

fully reversible

Irritation parameter:

conjunctivae score

Basis:

animal #2

Time point:

other: 8 days

Score:

0

Max. score:

3

Reversibility:

fully reversible

Irritant / corrosive response data:

No response for any parameter apart from conjunctiva.

Findings animal 1:

Time	erythema	chemosis	opacity	iritis
1h	1	0	0	0
24h	0	0	0	0
48h	0	0	0	0
72h	0	0	0	0
8d	0	0	0	0

Findings animal2

Time	erythema	chemosis	opacity	iritis
1h	1	0	0	0
24h	1	0	0	0
48h	-	-	-	-
72h	-	-	-	-
8d	0	0	0	0

"-" The original readings for animal 2 for timepoints 48h and 72h are missing.

Mean values over 24, 48 and 72 hours:

-------------------------------------

Animal 1: Erythema: 0, Chemosis: 0, Opacity: 0, Iritis: 0

Animal 2: data not available. Information for 24 hrs only: Erythema: 1, Chemosis: 0, Opacity: 0, Iritis: 0

Interpretation of results:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Executive summary:

In an eye irritation study which broadly followed the OECD guideline but for which only comprehensive data was available for a single animals, 2 -(2 -(2 -methoxyethoxy)ethoxy)ethanol was instilled in the eyes of 2 rabbits, which were then observed for up to 8 days. No washout was used. Minimal effects were observed. No chemosis, corneal opacity or iritis was seen and only mild conjunctival odema which had certainly disappeared within 8 days and possibly sooner. On the basis of this information, this substance has a low potential for eye irritancy and does not warrant classification as an eye irritant.

Materials and methods

Test material

Test material information

Constituent 1

Reference substance name:

Reaction mass of 3,6,9,12,15-pentaoxahexadecanol and 3,6,9,12-tetraoxotridecanol

EC Number:

915-389-0

Molecular formula:

C9H20O5 and C11H24O6

IUPAC Name:

Reaction mass of 3,6,9,12,15-pentaoxahexadecanol and 3,6,9,12-tetraoxotridecanol

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

cornea opacity score

Remarks on result:

no indication of irritation

Results 2

Irritation parameter:

iris score

Remarks on result:

no indication of irritation

Results 3

Irritation parameter:

chemosis score

Remarks on result:

no indication of irritation

Results 4

Irritation parameter:

conjunctivae score

Reversibility:

fully reversible within: 48 hours

Remarks on result:

probability of weak irritation

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met