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

Skin irritation / corrosion

Administrative data

Endpoint:

skin 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 skin 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:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Basic data given: comparable to guidelines/standards. Rationale for using a read across substance is included in summary record for this end point.

Qualifier:

no guideline followed

Principles of method if other than guideline:

Before OECD Guideline 404 was established in 1982, skin irritation was tested using an internal method (BASF test).

GLP compliance:

no

Species:

rabbit

Strain:

Vienna White

Type of coverage:

occlusive

Preparation of test site:

shaved

Vehicle:

unchanged (no vehicle)

Controls:

not specified

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 1 ml

Duration of treatment / exposure:

20 hours

Observation period:

8 days

Number of animals:

2

Details on study design:

TEST SITE
- An application site of 2.5x2.5 cm was covered with the liquid test substance

REMOVAL OF TEST SUBSTANCE
- Washing (if done): lutriol 50%
- Time after start of exposure: 1; 5; 15 min; 20 h

OTHER
- White Vienna rabbits were used. 2 animals were treated for 1, 5 and 15 minutes and 2 other animals for 20 hours using occlusive conditions. . In addition, skin tissue from the ear was tested by wrapping the ear. These results from the ear, however, would not be taken into account for evaluation as they do not represent testing of the dorsal / lateral flank of the back.

After the application time, the skin was washed with water which sometimes contained a mild detergent.

The animals were observed 7 to 8 days and skin changes were recorded on working days.

The report usually describes findings after 24 hours and at the end of the observation period. Thus, for final evaluation, the findings after 48 and 72 hours from the raw data have to be taken into account.


SCORING SYSTEM:
1 reddening hardly visible
2 slight reddening
3 moderate to strong reddening
4 severe reddening

1 edema hardly visible
2 slight edema
3 moderate edema, about 1 mm raised
4 strong edema, more than 1 mm raised

Irritation parameter:

erythema score

Basis:

mean

Time point:

other: 24-72 h

Score:

0.17

Max. score:

4

Reversibility:

fully reversible within: 48 h

Remarks on result:

other: 15 min application

Irritation parameter:

edema score

Basis:

mean

Time point:

other: 24-72 h

Score:

0

Max. score:

4

Reversibility:

other: no effects

Remarks on result:

other: 15 min application

Irritation parameter:

erythema score

Basis:

mean

Time point:

other: 24-72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 7 d

Remarks on result:

other: 20 h application

Irritation parameter:

edema score

Basis:

mean

Time point:

other: 24-72 h

Score:

0

Max. score:

4

Reversibility:

other: no effects

Remarks on result:

other: 20 h application

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

Readings	Animal	Exposure period
		1 min		5 min		15 min		20 hours
		Eryth.	Ed.	Eryth.	Ed.	Eryth.	Ed.	Erythema	Edema
24 h	1	0	0	0	0	0	0	1	0
	2	0	0	0	0	1 p	0	1 p	0
48 h	1	0	0	0	0	0	0	1	0
	2	0	0	0	0	0	0	2 (brown)	0
72 h	1	0	0	0	0	0	0	0 s	0
	2	0	0	0	0	0	0	1 p (brown)	0
7 d	1	0	0	0	0	0	0	0	0
	2	0	0	0	0	0	0	0	0
14 d	1	-	-	-	-	-	-	-	-
	2	-	-	-	-	-	-	-	-
Mean 24 -72 h	1	0	0	0	0	0	0	0.66	0
	2	0	0	0	0	0.3	0	1.33	0
Mean		0	0	0	0	0.15	0	1.0	0

p = patchy

s = slight desquamation

Interpretation of results:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Executive summary:

In a well reported irritation study in White Vienna rabbits, 2 -(2'-ethoxyethoxy)ethanol was applied to pairs of animals under occlusion. Exposure time was for 1, 5, 15mins and 20 hours. For the longest exposure, there was no sign of odema and mild erythema which disappeared in one animal by 72 hours and by 7 days in the second animal. On these results, the substance would not be classified as a skin irritant.

Cross-reference 2

Reason / purpose for cross-reference:

read-across source

Reference

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

1944

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

Published study which contains sufficient detail, including in results, to judge it reliable for hazard assessment purposes. Limited experimental detail provided. Rationale for using a read across substance is included in summary record for this end point.

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

yes

Remarks:

Exposure period 24hrs; No observations made at 48hrs

GLP compliance:

no

Species:

rabbit

Strain:

other: albino

Details on test animals or test system and environmental conditions:

Weight at study initiation: 2500-3500g

Type of coverage:

occlusive

Preparation of test site:

other: clipped plus abraded and unabraded skin

Vehicle:

unchanged (no vehicle)

Controls:

no

Amount / concentration applied:

0.5ml
3 applications to abraded skin and 3 applications to unabraded skin

Duration of treatment / exposure:

24 hrs

Observation period:

at 24 and 72hrs

Number of animals:

6

Details on study design:

Animals were clipped free of hair at the trunk. Four areas of the back (placed approximately 10 cm apart) were designated for exposure. Two of the areas were abraded by making four epidermal incisions. Patches consisted of 2 layers of light gauze squares (2.5 cm per side). Test material was introduced under each patch and the entire trunk was wrapped in rubberized cloth.
The animals were immobilized in a special holder during the 24 hour exposure. The patches were then removed and the reactions were scored for erythema and eschar (on a scale of 1-4) and edema (on a scale of 1-4) immediately and 72 hours afterward.

Irritation parameter:

primary dermal irritation index (PDII)

Basis:

mean

Time point:

other: 24 and 72 hrs

Score:

ca. 0.5

Max. score:

8

Reversibility:

fully reversible within: 72 hours

Irritant / corrosive response data:

see in remarks

Other effects:

no data

Individual scores:

	Intact		Abraded
	24hrs	72hrs	24hrs	72hrs
	0	0	0	0
	2	0	0	0
	0	0	4	0
Average	0.3		0.7

Interpretation of results:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Test substance has mild skin irritation potential

Executive summary:

In this irritation study in albino rabbits 2 -(2'-ethoxyethoxy)ethanol was applied to 6 animals on to abraded and intact skin under occlusion. The animals were restrained during a 24hr exposure at the end of which the patches were removed and the reactions scored for erythema and edema immediatly and 72 hours afterward. The average irritation score was 0.5 and the substance would be classified as mild irritant according to the GHS classification system.

Cross-reference 3

Reason / purpose for cross-reference:

read-across source

Reference

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

29 Jan 1974 - 06 Feb 1974

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Acceptable study report which meets basic scientific principles. Rationale for using a read across substance is included in summary record for this end point.

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

yes

Remarks:

, only two rabbits used. 20 hours exposure.

Principles of method if other than guideline:

Method: BASF-Test: Two animals were treated for 1, 5, 15 minutes and for 20 hours using occlusive conditions. An application site was covered with the liquid test substance. The animals were observed 8 days and skin changes were recorded daily. The report describes findings after 24 hours and at the end of the observation period (8 days). For a 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 test system and environmental conditions:

TEST ANIMALS
- Source: Gaukler
- Weight at study initiation: 2.63 kg (mean)

Type of coverage:

occlusive

Preparation of test site:

not specified

Vehicle:

unchanged (no vehicle)

Controls:

no

Amount / concentration applied:

no data

Duration of treatment / exposure:

1 min, 5 min, 15 min, 20 h

Observation period:

8 days

Number of animals:

2

Details on study design:

TEST SITE
- Area of exposure: 2.5 x 2.5 cm
- Type of wrap if used: no data

REMOVAL OF TEST SUBSTANCE
- Washing (if done including time after start of exposure: After the application times (1, 5 and 15 min) the skin was washed with Lutrol (100%) and Lutrol solution (50%).

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

Irritation parameter:

erythema score

Basis:

mean

Time point:

other: 24, 48, 72 hours

Score:

0.17

Max. score:

4

Reversibility:

fully reversible within: 48 hours

Remarks on result:

other: 20 hours exposure time

Irritation parameter:

edema score

Basis:

mean

Time point:

other: 24, 48, 72 hours

Score:

0

Max. score:

4

Remarks on result:

other: 20 hours exposure time

Mean erythema score after 24, 48 and 72 h (animal1/animal2)

Exposure time	24h	48h	72h	mean
1min	0/0	0/0	0/0	0/0
5min	0/0	0/0	0/0	0/0
15min	0/0	0/0	0/0	0/0
20h	1/1	0/0	0/0	0.3/0.3

At the end of the observation period after 8 days no erythema were found.

Mean edema score after 24, 48 and 72 h (animal1/animal2)

Exposure time	24h	48h	72h	mean
1min	0/0	0/0	0/0	0/0
5min	0/0	0/0	0/0	0/0
15min	0/0	0/0	0/0	0/0
20h	0/0	0/0	0/0	0/0

At the end of the observation period after 8 days no edema were found. The test subsstance was not irritating.

Interpretation of results:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Executive summary:

In a well reported skin irritancy study, the test substance 2-(2-(2-methoxyethoxy)ethoxy)ethanol was applied under occluded conditions to rabbit skin for exposure periods of up to 20 hours. The test substance was then washed before observing the animals for a period of up to 8 days. Mild erythema was seen in one of the two test animals but odema was not reported. Effects disappeared within 48 hours. On the basis of these results the substance is not regarded as a skin irritant.

Materials and methods

Test material

Test material information

Constituent 1

Reference substance name:

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

EC Number:

203-978-9

EC Name:

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

Cas Number:

112-50-5

Molecular formula:

C8H18O4

IUPAC Name:

2-[2-(2-ethoxyethoxy)ethoxy]ethan-1-ol

Test material form:

liquid

Results and discussion

In vivo

Results

Remarks on result:

no indication of irritation

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met