Registration Dossier

Administrative data

Description of key information

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records
Reference
Endpoint:
skin irritation: in vitro / ex vivo
Type of information:
migrated information: read-across based on grouping of substances (category approach)
Adequacy of study:
weight of evidence
Study period:
13 to 15 January 2010
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
Study undertaken at GLP accredited laboratory to internationally accepted guidelines but performed with DEGDME a substance used for read across. DEGDME is like DEGDEE part of the diethylene glycol monoalkyl and dialkyl ethers category. These substances have been demonstrated to be very similar in structure, physical/chemical properties and toxicological profile (see Category Approach-Read across Diethylene Glycol Diethyl Ether, 2013). Therefore, a read-across from DEGDEE to data obtained with DEGDME is scientifically justified.
Qualifier:
according to
Guideline:
EU Method B.46 (In Vitro Skin Irritation: Reconstructed Human Epidermis Model Test)
Deviations:
no
Qualifier:
according to
Guideline:
other: OECD Guideline for the Testing of Chemicals, Draft Proposal for a New Guideline In Vitro Skin Irritation: Human Reconstructed Epidermis (RhE) Test Method, Version 4, 11 December 2009
Deviations:
no
GLP compliance:
yes (incl. certificate)
Species:
human
Details on test animals and environmental conditions:
Human Epidermis
- Source: SkinEthic, 45 rue Saint Philippe-Le Palmeira, 06000 Nizza, France
- Age at study initiation: Foreskin Age 4 years

Type of coverage:
open
Amount / concentration applied:
TEST MATERIAL
- Amount applied (volume): 20 µl

Duration of treatment / exposure:
Quality control; 4h (±15min)
Positive control; 42 min (± 1 min)
Negative control; 42 min (± 1 min)
Test substance; 42 min (± 1 min)
Details on study design:
Supplier: SkinEthic, 45 rue Saint Philippe-Le Palmeira, 06000 Nizza, France
Lot No.: 09 022A 1211
Origin: Foreskin Age 4 years
Expiration date: 2010-01·18: day 24 of airlifted culture
Supplier's quality controls: Cell viability at day 17 (MTT test, n=2):
Specification: OD > 0.7 Result: OD = 1.287 ± 0.164
Validity references: Statement on the scientific validity of in-vitro tests for skin irritation testing. Endorsement from the Commission members of the ECVAM Scientific Advisory Committee (ESAC). 29th meeting; 4-5th November, 2008 at the European Commission in Brussels
Irritation / corrosion parameter:
other:
Value:
1.966
Remarks on result:
other:
Remarks:
Basis: mean (Negative control). Time point: 42h. Remarks: Viability (mean) 100%. (migrated information)
Irritation / corrosion parameter:
other:
Value:
0.029
Remarks on result:
other:
Remarks:
Basis: mean (postive control). Time point: 42h. Remarks: Viability (mean) 1.5%. (migrated information)
Irritation / corrosion parameter:
other:
Value:
0.373
Remarks on result:
other:
Remarks:
Basis: mean (Diethyleneglycol EM). Time point: 42h. Remarks: Viability (mean) 19.0%. (migrated information)

After topical application of the test substance Diethylenglycol EM had an unpredictable macroscopic interactions of the test substance diethylenglycol ethyl methyl ether with the inner surface of the cell culture insert. To our present knowledge it remains unclear, if the observed interactions may also have affected the test performance and the corresponding test result.

Interpretation of results:
Category 2 (irritant)
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Based on the results of this in vitro skin irritation study, Diethylenglycol methyl ethyl ether is predicted as a category 2 skin irritant.
Executive summary:

DEGDEE and DEGMEE, which is in the above study tested for its skin irritation, are both part of the diethylene glycol monoalkyl and dialkyl ethers category described and evaluated in the document titled "Category Approach-Read across Bis(2 -ethoxyethyl)ether" (2013).

These substances have been demonstrated to be very similar in structure, physical/chemical properties and toxicological profile . Therefore, a read-across from DEGDEE to data obtained with DEGMEE is scientifically justified.
Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Eye irritation

Link to relevant study records
Reference
Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: respected breeders
- Age at study initiation:36 or 39 weeks
- Weight at study initiation:3.80 to 4.38 kg
- Housing: housed individually in a plastic cage with perforated floors
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period:21 or 22 weeks

ENVIRONMENTAL CONDITIONS
- Temperature (°C):16 to 20°C
- Humidity (%):40 to 70%.
- Air changes (per hr):
- Photoperiod (hrs dark / hrs light): 12hrs/12hrs

IN-LIFE DATES: From: 26 October 2012 To: 15 November 2012
Vehicle:
unchanged (no vehicle)
Controls:
other: The left eye of each animal remained untreated
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 ml


Duration of treatment / exposure:
The eyelids were then gently held together for one second before releasing. The substance was not removed and the eyes were not washed.
Observation period (in vivo):
Ocular reactions to treatment were assessed 1, 24, 48 and 72 hours and eight days after treatment
Number of animals or in vitro replicates:
Three rabbits
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done):
- Time after start of exposure:

SCORING SYSTEM: according to the system of Kay and Calandra (1962)

TOOL USED TO ASSESS SCORE: An ophthalmoscope or pencil beam torch was available for use to facilitate inspection of the eyes.
Irritation parameter:
cornea opacity score
Basis:
animal #1
Time point:
other: 1, 24, 48, 72 h
Score:
0
Max. score:
0
Irritation parameter:
cornea opacity score
Basis:
animal #2
Time point:
other: 1, 24, 48, 72h
Score:
0
Max. score:
0
Irritation parameter:
cornea opacity score
Basis:
animal #3
Time point:
other: 1, 24, 48, 72h
Score:
0
Max. score:
0
Irritation parameter:
iris score
Basis:
animal #1
Time point:
other: 1, 24, 48, 72h
Score:
0
Max. score:
0
Irritation parameter:
iris score
Basis:
animal #2
Time point:
other: 1, 24, 48, 72h
Score:
0
Max. score:
0
Irritation parameter:
iris score
Basis:
animal #3
Time point:
other: 1, 24, 48, 72h
Score:
0
Max. score:
0
Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
other: 1, 24, 48, 72h
Score:
0.3
Max. score:
1
Reversibility:
fully reversible within: 48h
Remarks on result:
other: Redness of conjunctiva - Mean score following grading at 24, 48 and 72 hours after instillation of the test material
Irritation parameter:
conjunctivae score
Basis:
animal #2
Time point:
other: 1, 24, 48, 72h
Score:
1
Max. score:
1
Reversibility:
fully reversible within: 8 days
Remarks on result:
other: Redness of conjunctiva - mean scores following grading at 24, 48 and 72 hours after instillation of the test material
Irritation parameter:
conjunctivae score
Basis:
animal #3
Time point:
other: 1, 24, 48, 72h
Score:
1
Max. score:
1
Reversibility:
fully reversible within: 8 days
Remarks on result:
other: Redness of conjunctiva - mean scores following grading at 24, 48 and 72 hours after instillation of the test material
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
other: 1, 24h
Score:
0.3
Max. score:
1
Reversibility:
fully reversible within: 48h
Remarks on result:
other: mean scores following grading at 24, 48 and 72 hours after instillation of the test material
Irritation parameter:
chemosis score
Basis:
animal #2
Time point:
other: 1, 24h
Score:
0.3
Max. score:
1
Reversibility:
fully reversible within: 48h
Remarks on result:
other: mean scores following grading at 24, 48 and 72 hours after instillation of the test material
Irritation parameter:
chemosis score
Basis:
animal #3
Time point:
other: 1, 24, 48, 72h
Score:
1
Max. score:
2
Reversibility:
fully reversible within: 8 days
Remarks on result:
other: mean scores following grading at 24, 48 and 72 hours after instillation of the test material
Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Executive summary:

Injection of the conjunctival blood vessels and very slight or slight chemosis was evident in all animals during the first 24 hours following instillation; in two cases the conjunctival injection persisted throughout the first 72 hours after instillation. Slight or moderate discharge was apparent in all animals one hour after instillation. The treated eye of one animal was overtly normal by 48 hours after instillation and in the remaining two animals on Day 8. However, DEDG did not require labelling in accordance with European Commission regulation 1272/2008.

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

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Justification for selection of skin irritation / corrosion endpoint:
Although an in vitro study, it was undertaken to GLP. Good reliable study (Klimish 2) performed with DEGMEE

Justification for selection of eye irritation endpoint:
Good reliable study (Klimish 1) undertaken to GLP and recognised international guideline and performed with the test substance.

Effects on skin irritation/corrosion: irritating

Justification for classification or non-classification

The substance, DEGMEE, was found not to be corrosive but was found to be an irritant according to the RHE in vitro study and moderately irritating according to the rabbit in vivo report. This substance is used as read across for the classification of skin irritation of DEGDEE (see read across justification document). Therefore, taking the worst case scenario, DEGDEE is classified as an irritant. Under the DSD the classification will be Xi, R38 and under GHS/CLP, Skin irrit. 2, H315.

Instillation of DEGDEE into the eyes of three rabbits gave rise to some redness of the conjunctiva and chemosis. The highest total mean score was 8.0 occurring at the 1 hour observation; accordingly under the criteria Kay and Calandra (1962) DEGDEE was classified as “minimally irritating” to the eye. DEGDEE did not require labelling in accordance with European Commission regulation 1272/2008.