Registration Dossier

Administrative data

Description of key information

DMEE is considered to be corrosive to skin based on skin irritation studies conducted in rabbits that reported severe irritation (erythema) and corrosion following a 4-hour exposure to DMEE.

DMEE is also considered to be corrosive to the eyes based on an eye irritation study conducted in rabbits indicating that DMEE is extremely irritating and the effects were not reversible within 15 days.

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:
supporting study
Study period:
1983-06-22 to 1983-08-15
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Study did not include the initial test, but was similar to the confirmatory test in OECD 404; the study report lacks full animal information and method details. No GLP certificate or indication of compliance with GLP provided.
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
yes
Remarks:
No initial test; confirmatory test ran with 6 animals instead of up to 3.
Qualifier:
according to
Guideline:
other: U.S. Department of Transportation Skin Irritancy Test
Deviations:
not specified
Principles of method if other than guideline:
N/A
GLP compliance:
not specified
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS

IN-LIFE DATES: From: 1983-06-22 (date of exposure) To: Not specified
Type of coverage:
occlusive
Preparation of test site:
other: clipped
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
0.5 mL
Duration of treatment / exposure:
4 hrs
Observation period:
Skin reaction was scored at one hour, and 1, 2, 3, and 7 days after dosing.
Number of animals:
3/sex
Details on study design:
TEST SITE
- Area of exposure: Trunk
- Type of wrap if used: Gauze patch and impervious sheeting

REMOVAL OF TEST SUBSTANCE
- Washing (if done): No, although the excess was wiped away to avoid ingestion.
- Time after start of exposure: 4 hours

SCORING SYSTEM: Draize
Irritation parameter:
erythema score
Remarks:
and Eschar formation
Basis:
mean
Time point:
other: 5 hrs
Score:
2.3
Max. score:
4
Reversibility:
not fully reversible within: 7 days
Remarks on result:
other: Mean score of 6 animals (3/sex). irritation persisted through 7 days.
Irritation parameter:
erythema score
Remarks:
and Eschar formation
Basis:
mean
Time point:
other: 1 day
Score:
2.8
Max. score:
4
Reversibility:
not fully reversible within: 7 days
Remarks on result:
other: Mean score of 6 animals (3/sex). Irritation persisted through 7 days.
Irritation parameter:
erythema score
Remarks:
and Eschar formation
Basis:
mean
Time point:
other: 2 days
Score:
3.2
Max. score:
4
Reversibility:
not fully reversible within: 7 days
Remarks on result:
other: Mean score of 6 animals (3/sex). Irritation persisted through 7 days.
Irritation parameter:
erythema score
Remarks:
and Eschar formation
Basis:
mean
Time point:
other: 3 days
Score:
3.3
Max. score:
4
Reversibility:
not fully reversible within: 7 days
Remarks on result:
other: Mean score of 6 animals (3/sex). Irritation persisted through 7 days.
Irritation parameter:
erythema score
Remarks:
and Eschar formation
Basis:
mean
Time point:
other: 7 days
Score:
2.8
Max. score:
4
Reversibility:
not fully reversible within: 7 days
Remarks on result:
other: Mean score of 6 animals (3/sex). Irritation persisted through 7 days.
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 5 hrs
Score:
1.3
Max. score:
4
Reversibility:
not fully reversible within: 7 days
Remarks on result:
other: Mean score of 6 animals (3/sex). Irritation persisted through 7 days.
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 1 day
Score:
1.7
Max. score:
4
Reversibility:
not fully reversible within: 7 days
Remarks on result:
other: Mean score of 6 animals (3/sex). Irritation persisted through 7 days.
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 2 days
Score:
2
Max. score:
4
Reversibility:
not fully reversible within: 7 days
Remarks on result:
other: Mean score of 6 animals (3/sex). Irritation persisted through 7 days.
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 3 days
Score:
2.2
Max. score:
4
Reversibility:
not fully reversible within: 7 days
Remarks on result:
other: Mean score of 6 animals (3/sex). Irritation persisted through 7 days.
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 7 days
Score:
2.2
Max. score:
4
Reversibility:
not fully reversible within: 7 days
Remarks on result:
other: Mean score of 6 animals (3/sex). Irritation persisted through 7 days.
Irritant / corrosive response data:
Application of the test substance to covered rabbit skin resulted in moderate to severe erythema and moderate edema in all 6 rabbits. Ecchymosis and necrosis were also evident on each rabbit. Irritation (including erythema, edema, desquamation, necrosis, and scab formation) persisted through 7 days.
Other effects:
Ecchymosis: 6/6 at 5 hrs, 6/6 at 1 day, 5/6 at 2 days, 4/6 at 3 days, 0/6 at 7 days.
Necrosis: 4/6 at 5 hrs, 5/6 at 1 day, 6/6 at 2 days, 6/6 at 3 days, 6/6 at 7 days.
Desquamation: 0/6 at 5 hrs, 0/6 at 1 day, 0/6 at 2 days, 0/6 at 3 days, 6/6 at 7 days.
Scab formation: 0/6 at 5 hrs, 0/6 at 1 day, 0/6 at 2 days, 0/6 at 3 days, 6/6 at 7 days.
One animal was dead at 7 days; observations made immediately after death are included under the 7-day observation period above.

The author stated that the material classifed as "corrosive" by D.O.T. definition.

Interpretation of results:
corrosive
Conclusions:
The test substance was classified as corrosive by the author according to D.O.T. standards. The results also meet the requirements for classification as corrosive to the skin according to OECD 404.
Endpoint conclusion
Endpoint conclusion:
adverse effect observed (corrosive)

Eye irritation

Link to relevant study records
Reference
Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: OECD guideline study with acceptable restrictions (no test substance purity given). Acceptable, well documented report which meets basic scientific principles.
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Version / remarks:
(adopted 1981)
Deviations:
no
Remarks:
(no deviations compared to QECD TG 405 , 1981 & 2002, except testing protocol was according to guideline version from 1981)
GLP compliance:
no
Species:
rabbit
Strain:
Vienna White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Gaukler, Offenbach, Germany
- Weight at study initiation: 3.03, 2.54 kg (males); 2.26 kg (female)
- Housing: 1 animal per cage
- Diet: KLIBA 341, 4 mm; Klingentalmuehle AG, CH, ad libitum
- Water: tap water ad libitum
- Acclimation period: at least 1 week


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 - 24 °C
- Humidity (%): 30 - 70 %
- Photoperiod (hrs dark / hrs light): 12/12
Vehicle:
unchanged (no vehicle)
Controls:
other: untreated eye of the same animal
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 mL
Duration of treatment / exposure:
once, eyes were not washed after application
Observation period (in vivo):
15 days
The study was discontinued after 15 days due to severe eye irritation.
Number of animals or in vitro replicates:
3 (2 males, 1 female)
Details on study design:
APPLICATION
Single application to the conjunctival sac of the right eyelid

REMOVAL OF TEST SUBSTANCE
- Washing (if done): the substance was not washed out

READINGS
1 h, 24 h, 48 h, 72 h, 15 d after application

SCORING SYSTEM: Draize Scoring System

Irritation parameter:
cornea opacity score
Basis:
animal #1
Time point:
other: mean over 24, 48 and 72 h
Score:
1.7
Max. score:
4
Reversibility:
not reversible
Remarks on result:
other: Cornea score increased until study termination (3 out of 4).
Irritation parameter:
cornea opacity score
Basis:
mean
Remarks:
of animal 2 and 3
Time point:
other: mean over 24, 48 and 72 h
Score:
2
Max. score:
4
Reversibility:
not reversible
Remarks on result:
other: Identical scores in both animals. Cornea score increased until study termination (4 out of 4); staphyloma observed in one animal.
Irritation parameter:
iris score
Basis:
mean
Remarks:
of all 3 animals
Time point:
other: mean over 24, 48 and 72 h
Score:
1
Max. score:
2
Reversibility:
not reversible
Remarks on result:
other: Identical scores in all animals. At study termination: iris score: 1
Irritation parameter:
conjunctivae score
Basis:
mean
Remarks:
of all 3 animals
Time point:
other: mean over 24, 48 and 72 h
Score:
2
Max. score:
3
Reversibility:
not reversible
Remarks on result:
other: Identical scores in all animals. At study termination: conjunctivae score: 2
Irritation parameter:
chemosis score
Basis:
mean
Remarks:
of animal 1 and 2
Time point:
other: mean over 24, 48 and 72 h
Score:
2
Max. score:
4
Reversibility:
not reversible
Remarks on result:
other: Identical scores in both animals. At study termination: chemosis score: 2
Irritation parameter:
chemosis score
Basis:
animal #3
Time point:
other: mean over 24, 48 and 72 h
Score:
1
Max. score:
4
Reversibility:
not reversible
Remarks on result:
other: At study termination: chemosis score: 1
Other effects:
Additional findings observed at study termination (after 15 days):
- animal 1: loss of corneal tissue, small retractions in the eyelids, marginal vascularization of the cornea, pannus, suppuration, loss of hair at margins of eyelids
- animal 2: loss of corneal tissue, small retractions in the eyelids, marginal vascularization of the cornea, pannus, suppuration, staphyloma
- animal 3: loss of corneal tissue, small retractions in the eyelids, pupil contracted, marginal vascularization of the cornea
Interpretation of results:
Category 1 (irreversible effects on the eye) based on GHS criteria
Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

In a semiocclusive skin irritation study in rabbits exposed to DMEE for 3 minutes or 1 hour, no corrosive effects were observed.


Justification for selection of skin irritation / corrosion endpoint:
The key skin irritation study had a reliability score of 2 and was conducted according to OECD 404. Three New Zealand White rabbits (2 males, 1 female) were dosed with 0.5 mL of DMEE for 4 hours under semi-occlusive dressings. The animals were observed for 72 hours post-exposure. After the 4 hour exposure, hemorrhages were seen and after 24 hours necrosis occurred in all three animals. At the end of the observation period at 72 hours, full thickness necrosis was observed in all three animals. This finding was confirmed by gross-pathological examination. The substances was reported to be corrosive (Category 1C) to the skin of rabbits.

Justification for selection of eye irritation endpoint:
The key eye irritation study had a reliability score of 2 and was performed in Vienna White rabbits according to the OECD 405 guideline. Following exposure to 0.1 mL of DMEE (unwashed), ocular responses were assessed using the Draize scoring system. Loss of corneal tissue, small retractions in the eyelids and marginal vascularization of the cornea were reported in all three animals. Pannus and suppuration were reported in two of the animals and loss of hair at the margins of the eyelids and staphyloma were reported in one animal each. Eye effects were not reversible in the 15 day observation period. DMEE was reported to be a Category 1 (irreversible effects on the eye) eye irritant.

Effects on skin irritation/corrosion: corrosive

Effects on eye irritation: corrosive

Justification for classification or non-classification

Based on the available results, the suggested classification for DMEE according to EU Regulation 1272/2008 is skin corrosion category 1C and eye damage category 1.