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Administrative data

Description of key information

Skin irritation: not irritating
Eye irritation: irritating

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records
Reference
Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
08 May - 18 May 1990
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions
Qualifier:
according to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Version / remarks:
adopted in 1981
Deviations:
no
GLP compliance:
not specified
Species:
rabbit
Strain:
other: Small White Russian (Chbb-SPF)
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Dr. Karl Thomae GmbH, Biberach, Germany
- Weight at study initiation: 2.3 - 2.7 kg
- Housing: individually in stainless steel cages
- Diet: K4 Alleindiät für Kaninchen, Ssniff Spezialfutter GmbH, Soest, Germany; ad libitum
- Water: tap water; ad libitum
- Acclimation period: 14 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 ± 1
- Humidity (%): 60 ± 5
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12
Type of coverage:
semiocclusive
Preparation of test site:
clipped
Vehicle:
unchanged (no vehicle)
Controls:
other: the untreated sites served as control
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 mL on an approx. 6 cm² area of the skin
Duration of treatment / exposure:
4 hours
Observation period:
10 days
Reading time points: 1, 24, 48, and 72 h and 6, 8, and 10 days after application
Number of animals:
3 males
Details on study design:
TEST SITE
- Test site preparation: Approx. 24 h before application, the dorsal and lateral parts of the trunk were clipped (10 x 10 cm).
- Area of exposure: approx. 6 cm² (2.5 x 2.5 cm)
- Type of wrap if used: gauze patch fixed with an elastic bandage

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Yes, substance residues were washed off softly with warm water.
- Time after start of exposure: 4 hours

SCORING SYSTEM: Draize Scoring System
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 8 days
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0.67
Max. score:
4
Reversibility:
fully reversible within: 72 h
Irritation parameter:
edema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
edema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
edema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritant / corrosive response data:
Only very slight effects (max. score = 1) were observed throughout the study. No edema were seen with the exception of animal #1 at the 1-hour reading. Slight erythema were seen in two animals 1 hour after application which were fully reversible within 72 h and 8 days, respectively.
Interpretation of results:
GHS criteria not met
Conclusions:
CLP: not classified
DSD: not classified
Executive summary:

Acute dermal irritation has been investigated in the rabbit. Minor irritation was observed which was not of sufficient severity to require classification.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records
Reference
Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
08 May - 11 Sep 1990
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions
Qualifier:
according to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Version / remarks:
adopted in 1987
Deviations:
yes
Remarks:
(simultaneous testing of 6 animals, no data on intactness of the eyes before application)
GLP compliance:
not specified
Species:
rabbit
Strain:
other: Small White Russian (Chbb-SPF)
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Dr. Karl Thomae GmbH, Biberach, Germany
- Weight at study initiation: 2.4 - 2.6 kg
- Housing: individually in stainless steel cages
- Diet: K4 Alleindiät für Kaninchen, Ssniff Spezialfutter GmbH, Soest, Germany; ad libitum
- Water: tap water; ad libitum
- Acclimation period: 14 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 ± 1
- Humidity (%): 60 ± 5
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12
Vehicle:
unchanged (no vehicle)
Controls:
other: the other eye of each animal served as control
Amount / concentration applied:
0.1 mL
Duration of treatment / exposure:
one single application
Observation period (in vivo):
21 days
Reading time points: 1, 24, 48, and 72 h and 6, 8, 10, 13, 17, and 21 days after application
Number of animals or in vitro replicates:
6 males
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): Yes, the treated eyes were instilled with Na-fluorescein solution to assess corneal damage followed by washing with water.
- Time after start of exposure: 72 hours

SCORING SYSTEM: Draize Scoring System

TOOL USED TO ASSESS SCORE: fluorescein
Irritation parameter:
cornea opacity score
Basis:
animal #1
Time point:
24/48/72 h
Score:
1.33
Max. score:
4
Reversibility:
fully reversible within: 6 days
Irritation parameter:
cornea opacity score
Basis:
animal #2
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
not fully reversible within: 21 days
Irritation parameter:
cornea opacity score
Basis:
animal #3
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
fully reversible within: 8 days
Irritation parameter:
cornea opacity score
Basis:
animal #4
Time point:
24/48/72 h
Score:
1.67
Max. score:
4
Reversibility:
fully reversible within: 6 days
Irritation parameter:
cornea opacity score
Basis:
animal #5
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 8 days
Irritation parameter:
cornea opacity score
Basis:
animal #6
Time point:
24/48/72 h
Score:
1.33
Max. score:
4
Reversibility:
fully reversible within: 8 days
Irritation parameter:
iris score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
2
Reversibility:
other: reversibility: not applicable
Remarks on result:
other: no effects at any reading time point
Irritation parameter:
iris score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0.67
Max. score:
2
Reversibility:
not fully reversible within: 21 days
Remarks on result:
other: still circumcorneal injections after 21 days
Irritation parameter:
iris score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0.33
Max. score:
2
Reversibility:
fully reversible within: 72 h
Irritation parameter:
iris score
Basis:
animal #4
Time point:
24/48/72 h
Score:
0.33
Max. score:
2
Reversibility:
fully reversible within: 48 h
Irritation parameter:
iris score
Basis:
animal #5
Time point:
24/48/72 h
Score:
0
Max. score:
2
Reversibility:
fully reversible within: 10 days
Remarks on result:
other: circumcorneal injections at day 6-8
Irritation parameter:
iris score
Basis:
animal #6
Time point:
24/48/72 h
Score:
0
Max. score:
2
Reversibility:
fully reversible within: 8 days
Remarks on result:
other: circumcorneal injections at day 6
Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
other: mean over 24, 48, and 72 h
Score:
3
Max. score:
3
Reversibility:
fully reversible within: 21 days
Remarks on result:
other: The scores were decreasing during the study and lasted until day 10
Irritation parameter:
conjunctivae score
Basis:
animal #2
Time point:
24/48/72 h
Score:
3
Max. score:
3
Reversibility:
not fully reversible within: 21 days
Irritation parameter:
conjunctivae score
Basis:
animal #3
Time point:
24/48/72 h
Score:
3
Max. score:
3
Reversibility:
fully reversible within: 21 days
Remarks on result:
other: The scores were decreasing during the study and lasted until day 17
Irritation parameter:
conjunctivae score
Basis:
animal #4
Time point:
24/48/72 h
Score:
3
Max. score:
3
Reversibility:
fully reversible within: 21 days
Remarks on result:
other: The scores were decreasing during the study and lasted until day 17
Irritation parameter:
conjunctivae score
Basis:
animal #5
Time point:
24/48/72 h
Score:
3
Max. score:
3
Reversibility:
fully reversible within: 21 days
Remarks on result:
other: The scores were decreasing during the study and lasted until day 10
Irritation parameter:
conjunctivae score
Basis:
animal #6
Time point:
24/48/72 h
Score:
3
Max. score:
3
Reversibility:
fully reversible within: 21 days
Remarks on result:
other: The scores were decreasing during the study and lasted until day 17
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 6 days
Irritation parameter:
chemosis score
Basis:
animal #2
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
not fully reversible within: 21 days
Irritation parameter:
chemosis score
Basis:
animal #3
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
fully reversible within: 8 days
Irritation parameter:
chemosis score
Basis:
animal #4
Time point:
24/48/72 h
Score:
1.33
Max. score:
4
Reversibility:
fully reversible within: 17 days
Irritation parameter:
chemosis score
Basis:
animal #5
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 10 days
Irritation parameter:
chemosis score
Basis:
animal #6
Time point:
24/48/72 h
Score:
1.67
Max. score:
4
Reversibility:
fully reversible within: 17 days
Irritant / corrosive response data:
All effects decribed below were already present at the 1-h scoring. Slight corneal opacity (score 1 - 2) was present in all animals which was reversible within 8 days in 5/6 animals. Slight effects on iris (score = 0 - 1) were observed in 5/6 animals, that were fully reversible within 2-10 days in 4 animals. Conjunctival redness (scores = 3) and swelling (scores = 1 - 2) was seen in all animals and lasted until day 17 and day 10 in 3/6 animals, respectively. Exudate formation at 24 - 72 h after application was observed in 2/6 animals. Thus, at day 21 effects were still seen in only 1/6 animal.

Table 1 . Results of study.

Rabbit #

Time [h]

conjunctivae

 

iris

cornea

redness

swelling

1

1

3

2

0

1

24

3

1

0

2

48

3

1

0

1

72

3

1

0

1

average

3.0

1.0

0.0

1.3

2

1

3

2

0

1

24

3

2

1

2

48

3

2

1

2

72

3

2

0

2

average

3

2

0.7

2

3

1

3

2

0

1

24

3

2

0

2

48

3

2

1

2

72

3

2

0

2

average

3

2

0.3

2

4

1

3

2

0

1

24

3

2

1

1

48

3

1

0

1

72

3

1

0

2

average

3

1.3

0.3

1.3

5

1

3

1

0

1

24

3

1

0

1

48

3

1

0

1

72

3

1

0

1

average

3

1

0

1

6

1

3

2

0

1

24

3

2

0

1

48

3

1

0

1

72

3

2

0

1

average

3

1.7

0

1

 

 

Time [h]

conjunctivae

 

iris

cornea

 

redness

swelling

 

 

average
score

1

3.00

1.83

0.00

1.00

24

3.00

1.67

0.33

1.50

48

3.00

1.33

0.33

1.33

72

3.00

1.50

0.00

1.50

24+48+72

3.00

1.50

0.22

1.44
Interpretation of results:
irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
CLP: Eye irrit 2, H319
DSD: Xi, R36
Executive summary:

Acute eye irritation has been investigated in the rabbit. Irritation was observed of sufficient severity and duration to require classification.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Skin Irritation/corrosion

The skin irritation properties of 2-(2-ethoxyethoxy)ethyl acetate were tested in a study according to OECD guideline 404 (Mürmann, 1990). In the study, 3 male Small White Russian rabbits were exposed to 0.5 mL of the unchanged test substance, applied to the shaved skin for 4 h using a semiocclusive dressing. The treated skin was observed and evaluated at 1, 24, 48 and 72 h post-application.

Very slight erythema was observed in 2/3 animal being reversible within 6 days h (mean erythema score out of all 3 animals over 24, 48 and 72 h: 0.6). Very slight edema was observed in one animal after 1 h, only.

Thus, no skin irritating properties of 2-(2-ethoxyethoxy)ethyl acetate were apparent.

Eye Irritation/corrosion

The eye irritation properties of 2-(2-ethoxyethoxy)ethyl acetate were tested in a study according to OECD guideline 405 (Mürmann, 1990). In a group of 6 rabbits Small White Russian rabbits, 0.1 mL of the test substance was applied into the eye. Observation of the eyes was performed 24, 48 and 72 h and 6, 8, 10, 13, 17 and 21 days after application.

Slight to moderate corneal opacity was observed in 6/6 animals with a mean cornea score of 1.44 over 24, 48 and 72 h out of all animals. Corneal opacity was fully reversible in 5/6 animals within 8 and 10 days. One animal showed opalescent areas after 21 days. Iritis was observed after 24 and 48 h in 2/6 animals and in 3/6 and 2/6 animals after 6 and 8 days, respectively. The resulting mean score over 24, 48 and 72 h. Iritis was fully reversible 5/6 animals within 10 and 13 days. One animal showed circumconreal injections after 21 days. After 1, 24, 48 and 72 h conjunctival redness was observed in 6/6 animals resulting in a mean score of 3 over 24, 48 and 72 h out of all 6 animals. Redness was fully reversible in 5/6 animals within 21 days. In one animal, moderate redness was still persistent after 21 days. Chemosis was observed in 6/6 animals after 24, 4 and 72 h being fully reversible within 72 h in 5/6 animals. Chemosis was still observed in 1 animal, being still apparent after 21 days.

Thus, the results show that only one single animal did not recover. In all other animals effects were fully reversible. The study report did not include a description of a pre-test to exclude potential pre-existing damage to the cornea of the animal. Therefore, the effects seen in this animal were regarded as an outliner. In addition, mean scores out of the remaining five animals as well as out of all six animals did not meet the criteria for classification as corrosive. Thus, under the experimental conditions described, it was concluded, that evidence of eye irritation was seen after treatment with 2-(2-ethoxyethoxy)ethyl acetate (CAS 112-15-2). Thus, the substance does meet the criteria for classification according to Regulation (EC) 1272/2008 and Directive 67/548/EEC, to have the potential to induce reversible eye irritation and is classified in Category 2.

In addition, the eye irritation properties of 2-(2-ethoxyethoxy)ethyl acetate were tested in an in-vivo study applying differing volumes of the undiluted test substance to rabbit eye (Carpenter, 1946). In groups of 5 albino rabbits (no further information given), 0.5 mL of the undiluted test substance were applied in a single application without washing. The eyes were observed and reactions were evaluated 18-24 h after application. The individual numerical scores of each eye treated with a given volume or concentration of a chemical are added together and then divided by the number of eyes to obtain the score of the injury caused by the treatment. The Grade of 5 was selected as representative of severe injury. This figure corresponded to necrosis, visible after staining and covering about 3/4 of the surface of the cornea; or a more severe necrosis covering a smaller area. The injury grade, after application of 0.5 mL of the undiluted test substance resulted in a calculated score of >1 - ≤ 5 out of five eyes after 18-24 h. This corresponds to a Grade 2 out of 10 injury grade levels. Thus, under the experimental conditions described, the authors concluded, that there was no evidence of irreversible effects on the eye after treatment with 2-(2-ethoxyethoxy)ethyl acetate (CAS 112-15-2).

Conclusion for skin and eye irritation

In conclusion, no evidence of skin irritation properties were seen after treatment with 2-(2-ethoxyethoxy)ethyl acetate (CAS 112-15-2).

Under the experimental conditions described, it was concluded, that evidence of reversible eye irritation was seen after treatment with 2-(2-ethoxyethoxy)ethyl acetate (CAS 112-15-2).

Justification for classification or non-classification

The available data on skin irritation properties of 2-(2-ethoxyethoxy)ethyl acetate (CAS 112-15-2) do not meet the criteria for classification according to Regulation (EC) 1272/2008 or Directive 67/548/EEC, and the data are therefore conclusive but not sufficient for classification.

The available data on eye irritation properties of 2-(2-ethoxyethoxy)ethyl acetate (CAS 112-15-2) do meet the classification criteria for Eye irritation Category 2 (H319) according to Regulation (EC) 1272/2008 and for R36 (Irritating to eyes) according to Directive 67/548/EEC.