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Administrative data

Description of key information

Skin irritation: BASF AG (1997) determined in a K1 study the skin irritation potential of the substance in New Zealand White rabbits according to OECD Guideline 404 and EU Method B.4. The substance was observed not to be irritating to the skin. This study was selected as key study.
Eye irritation: BASF AG (1997) determined in a K1 study the eye irritation potential of the substance in White Vienna rabbits according to OECD Guideline 405 and EU Method B.5. The substance was observed to be irritating to the eyes. This study was selected as key study.

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
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes
Specific details on test material used for the study:
SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: H 50541 H x B (Substance number: 95/452)
- Analytical purity: 98.4%

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: room temperature, exclusion of oxygen (under nitrogen)

OTHER SPECIFICS:
- Name of test substance (as cited in study report): 2,2'-Dimorpholinodiethylether
- Physical state: liquid
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Dr. Thomae GmbH, Biberach
- Age at study initiation: young adult animals
- Weight at study initiation: 2.2 kg and 2.51 kg (males); 2.53 (female)
- Housing: single housing in stainless steel wire mesh cages with grating, floor area: 3000 cm²
- Diet: Kliba-Labordiaet 341, Klingenthalmuehle AG, Kaiseraugust, Switzerland (about 130 g/animal/day)
- Water: about 250 mL per animal per day
- Acclimation period: at least 1 week

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 - 24
- Humidity (%): 30 - 70
- Photoperiod (hrs dark / hrs light): 12/12
Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Controls:
other: untreated skin sites of the same animal
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied: 0.5 mL of the unchanged test substance
Duration of treatment / exposure:
4 h
Observation period:
8 days (reading was performed 1 h, 24 h, 48 h, 72 h and 8 d after application)
Number of animals:
3
Details on study design:
TEST SITE
- Area of exposure: 2.5 cm x 2.5 cm

REMOVAL OF TEST SUBSTANCE
- Washing (if done): with Lutrol conc. and Lutrol/water (1:1)
- Time after start of exposure: 4 h

SCORING SYSTEM: evaluation according to the Draize Scoring System
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
other: 24 h, 48 h and 72 h
Score:
1.7
Max. score:
4
Reversibility:
fully reversible within: 8 days
Remarks on result:
other: scaling at 72 h
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
other: 24 h, 48 h and 72 h
Score:
2
Max. score:
4
Reversibility:
fully reversible within: 8 days
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
other: 24 h, 48 h and 72 h
Score:
2
Max. score:
4
Reversibility:
fully reversible within: 8 days
Irritation parameter:
edema score
Basis:
mean
Remarks:
(3 animals)
Time point:
other: 24 h, 48 h and 72 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable

Irritant response data:

Reading

Animal

Erythema

Edema

Symptoms

1 h

1

2

0

E

2

2

0

E

3

2

0

E

24 h

1

2

0

E

2

2

0

E

3

2

0

E

48 h

1

2

0

E

2

2

0

E

3

2

0

 

72 h

1

1

0

S

2

2

0

E

3

2

0

 

8 d

1

0

0

 

2

0

0

 

3

0

0

 

Mean

(24 h, 48 h, 72 h)

1

1.7

0.0

 

2

2.0

0.0

 

3

2.0

0.0

 

Mean

(1, 2 and 3)

1.9

0.0

 

E: Erythema extending beyond the area of exposure

S: Scaling

Interpretation of results:
GHS criteria not met
Conclusions:
The skin irritation potential of the substance in New Zealand White rabbits was investigated according to OECD Guideline 404 and EU Method B.4. Based on the test results and according to the criteria of the DSD and CLP Regulation, the substance should not be classified as irritating to the skin.
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
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes
Specific details on test material used for the study:
SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: H 50541 H x B (Substance number: 95/452)
- Analytical Purity: 98.4%

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: room temperature, exclusion of oxygen (under nitrogen)

OTHER SPECIFICS:
- Name of test substance (as cited in study report): 2,2'-Dimorpholinodiethylether
- Physical state: liquid
Species:
rabbit
Strain:
Vienna White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Dr. Thomae GmbH, Biberach
- Age at study initiation: yound adult animals
- Weight at study initiation: 3.28 kg and 3.08 kg (males); 3.33 kg (female)
- Housing: single housing in stainless steel mesh cages with grating, floor area: 3000 cm²
- Diet: Kliba-Labordiaet 341, Klingenthalmuehle AG, Kaiseraugust, Switzerland (about 130 g per animal per day)
- Water: about 250 mL tap water per animal per day
- Acclimation period: at least 1 week

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 - 24
- Humidity (%): 30 - 70
- Photoperiod (hrs dark / hrs light): 12/12

Vehicle:
unchanged (no vehicle)
Controls:
other: untreated eye
Amount / concentration applied:
TEST MATERIAL
- Amount applied: 0.1 mL

Duration of treatment / exposure:
24 h
Observation period (in vivo):
8 days (reading was performed at 1 h, 24 h, 48 h, 72 h and 8 days after application)
Number of animals or in vitro replicates:
3
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing: yes (water)
- Time after start of exposure: 24 h

SCORING SYSTEM: evaluation according to the OECD Guideline Scoring System
Irritation parameter:
cornea opacity score
Basis:
animal #1
Time point:
other: 24 h, 48 h and 72 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Irritation parameter:
cornea opacity score
Basis:
animal #2
Time point:
other: 24 h, 48 h and 72 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 8 days
Irritation parameter:
cornea opacity score
Basis:
animal #3
Time point:
other: 24 h, 48 h and 72 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 8 days
Irritation parameter:
iris score
Basis:
animal #1
Time point:
other: 24 h, 48 h and 72 h
Score:
0
Max. score:
2
Reversibility:
other: not applicable
Irritation parameter:
iris score
Basis:
animal #2
Time point:
other: 24 h, 48 h and 72 h
Score:
0.7
Max. score:
2
Reversibility:
fully reversible within: 72 h
Irritation parameter:
iris score
Basis:
animal #3
Time point:
other: 24 h, 48 h and 72 h
Score:
1.3
Max. score:
2
Reversibility:
fully reversible within: 8 days
Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
other: 24 h, 48 h and 72 h
Score:
2
Max. score:
3
Reversibility:
fully reversible within: 8 days
Irritation parameter:
conjunctivae score
Basis:
animal #2
Time point:
other: 24 h, 48 h and 72 h
Score:
2.7
Max. score:
3
Reversibility:
fully reversible within: 8 days
Irritation parameter:
conjunctivae score
Basis:
animal #3
Time point:
other: 24 h, 48 h and 72 h
Score:
3
Max. score:
3
Reversibility:
fully reversible within: 8 days
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
other: 24 h, 48 h and 72 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 8 days
Irritation parameter:
chemosis score
Basis:
animal #2
Time point:
other: 24 h, 48 h and 72 h
Score:
1.7
Max. score:
4
Reversibility:
fully reversible within: 8 days
Irritation parameter:
chemosis score
Basis:
animal #3
Time point:
other: 24 h, 48 h and 72 h
Score:
2
Max. score:
4
Reversibility:
fully reversible within: 8 days
Other effects:
Suppuration (48 h) and loss of corneal tissue (48 h and 72 h) were observed in animal#2.
Small retractions in the eyelids (24 h, 48 h and 72 h), pupil contraction (24 h, 48 h and 72 h) and loss of corneal tissue (48 h and 72 h) were observed in animal#3.

Irritant response

Reading

Animal

Cornea

Iris

Conjunctiva

Symptoms

OP

AR

RED

SW

DI

1 h

1

0

 

0

2

2

2

 

2

0

0

0

2

2

2

 

3

0

0

0

2

2

2

 

24 h

1

0

0

0

2

1

1

 

2

1

2

1

3

2

2

 

3

1

4

1

3

2

2

SR, PC

48 h

1

0

0

0

2

1

1

 

2

1

2

1

3

2

1

S, LC

3

1

3

1

3

2

2

SR, PC, LC

72 h

1

0

0

0

2

1

0

 

2

1

1

0

2

1

0

LC

3

1

3

2

3

2

1

SR, PC, LC

8 d

1

0

0

0

0

0

0

 

2

0

0

0

0

0

0

 

3

0

0

0

0

0

0

 

Mean

1

0.0

 

0.0

2.0

1.0

 

 

2

1.0

 

0.7

2.7

1.7

 

 

3

1.0

 

1.3

3.0

2.0

 

 

Mean

1, 2, 3

0.7

 

0.7

2.6

1.6

 

 

OP: opacity; AR: area of cornea involved (1: > 0; 2: >1/4; 3: >1/2; 4: >3/4); RED: redness; SW: swelling; DI: discharge

SR: small retractions in the eyelids; S: suppuration, PC: pupil contracted, LC: loss of corneal tissue

Interpretation of results:
Category 2B (mildly irritating to eyes) based on GHS criteria
Conclusions:
The eye irritation potential of the test substance was investigated in White Vienna rabbits according to OECD Guideline 405 and EU Method B.5. The test substance was observed to be irritating to the eyes (category 2B).
Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Skin irritation / corrosion:

BASF AG (1997) studied skin irritation/corrosion by applying the test substance to an exposure area of 2.5 cm x 2.5 cm of 3 New Zealand White rabbits (semi-occlusive conditions). The test site was shaved. Four hours after start of exposure, the test sites were washed with Lutrol conc. and Lutrol/water (1:1). Each test site was examined and scored separately for erythema and edema on a graded scale of 0 to 4. The observation period lasted 8 days (reading at 1h, 24h, 48h, 72h and 8 days after application). The erythema score was 0 -2 of 4. The results were fully reversible within 8 days.

The substance should not be classified as irritating to the skin. This study is selected as key study. In addition, Huntsman (1978) made the same conclusions in 6 New Zealand White rabbits.

Huntsman (1978) studied skin irritation/corrosion by applying the test substance to two test sites located lateral to the midline of the back approximately 10 centimeters apart in 6 New Zealand White rabbits (occlusive conditions). One of the test sites was abraded (with a slightly bent tip of a hypodermic needle) by making 4 epidermal abrasions, 2 perpendicular to the other 2, while the other test site remained intact. At the end of the 24 hours, the plastic wrappings and patches were removed. In addition, all residual test material was removed by rinsing the test sites with lukewarm tap water (or a suitable solvent) and gentle rubb. One hour after removal of the test material, each abraded and intact test site was examined and scored separately for erythema and edema on a graded scale of 0 to 4. After 72 hours, the sites were again examined and scored. The erythema score was 0 -2 of 4. Erythema and edema were not fully reversible within 72 hours (based on the group means). The substance should not be classified as irritating to the skin.

Eye irritation:

BASF AG (1997) studied eye irritation by applying 0.1 mL the test substance to the eye of 3 Vienna White rabbits. The other untreated eye served as control. 24 hours after start of exposure the eyes were washed with water. Eye irritation (cornea score, iris score, conjunctivae score and chemosis score) was scored according to OECD Guideline Scoring System. The observation period lasted 8 days (reading was performed at 1h, 24h, 48h, 72h and 8 days after application).

Suppuration (48h) and loss of corneal tissue (48h and 72h) were observed in animal #2. Small retractions in the eyelids (24h, 48h and 72h), pupil contraction (24h, 48h and 72h) and loss of corneal tissue (48h and 72h) were observed in animal #3.

The substance should be classified as category 2 eye irritant. In addition, IBT (1978) made the same conclusions in 6 New Zealand White rabbits.

IBT (1978) studied eye irritation by applying 0.1 mL test substance to the eye of 6 New Zealand White rabbits. The other untreated eye served as control. The eyes were not washed after exposure. Eye irritation (cornea score, iris score, conjunctivae score and chemosis score) was scored according to the Draize scoring system. Scoring intervals were: 1, 24, 48 and 72 hours and 7 and 14 days.

The overall irritation score was 22.1: moderately irritating. The Draize mean scores were (24-48-72h; 6 rabbits): cornea: 0.61; iris: 0.56; conjunctiva redness: 2.1; conjunctiva swelling: 1.6

According to the CLP criteria, the substance should be classified as an eye irritant (category 2).


Effects on eye irritation: irritating

Justification for classification or non-classification

According to the criteria of the CLP Regulation, the test substance should not be classified as irritating to the skin. However, the test substance should be classified as category 2 eye irritant H319 according to the CLP criteria, respectively.