4-morpholinecarbaldehyde

Endpoint summary

Description of key information

When tested for skin and eye irritation in the rabbit the test item induced very slight reactions which were fully reversible within the observation period.

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:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Meets generally accepted scientific standards, acceptable for assessment

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

yes

Remarks:

(longer exposure duration, occlusive conditions, no 72 h reading)

Principles of method if other than guideline:

The test substance was applied to the rabbit skin 1, 5 and 15 minutes and for 20 hours using occlusive conditions.
In addition, skin tissue from the ear was tested by wrapping the ear.

GLP compliance:

not specified

Species:

rabbit

Strain:

Vienna White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Weight at study initiation: mean ca. 2.95 kg



ENVIRONMENTAL CONDITIONS
- no data

Type of coverage:

occlusive

Preparation of test site:

shaved

Vehicle:

unchanged (no vehicle)

Controls:

other: untreated skin

Amount / concentration applied:

TEST MATERIAL
- the test item was applied undiluted

Duration of treatment / exposure:

20 hours (reading at 1, 5 and 15 minutes and after 20 h)

Observation period:

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

Number of animals:

2 rabbits

Details on study design:

Test site
- Area of exposure: 2.5 x 2.5 cm2
- Dressing: occlusive dressing
- Washing: after the application time, the skin was washed with water and Lutrol

Scoring System
- BASF grading for redness and edema

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 5 days

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0.5

Max. score:

4

Reversibility:

fully reversible within: 5 days

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

At 24 h after patch removal, grade 1 erythema was observed in both animals. At 48 h, grade 1 erythema was observed in the first animals but no erythema in the second animal.

No edema was observed in both animals at any time. All findings were fully reversible within 5 days.

Interpretation of results:

not irritating

Remarks:

Migrated information

Executive summary:

Based on the results observed it was concluded that N-formylmorpholine shows no irritating or corrosive potential and should not be classified as skin irritating or corrosive according to Regulation 1272/2008/EC. (BASF, 1967)

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:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Meets generally accepted scientific standards, acceptable for assessment

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

yes

Remarks:

(only 0.05 mL applied, no 72 h reading)

Principles of method if other than guideline:

The test substance was applied undiluted to rabbit eyes and the eyes observed for 8 days.
The eyes were not washed out after 24 hours.

GLP compliance:

no

Species:

rabbit

Strain:

Vienna White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Weight at study initiation: 2.82 and 3.02 kg
- no further data


ENVIRONMENTAL CONDITIONS
- no data

Vehicle:

unchanged (no vehicle)

Controls:

other: untreated eye of the same animals

Amount / concentration applied:

TEST MATERIAL
- Amount applied : 0.05 mL

Duration of treatment / exposure:

- single application (eyes were not washed out after 24 hours)

Observation period (in vivo):

The animals were observed several times on the treatment day and up to 7 or 8 days afterwards, and findings were recorded on working days. Findings were recorded at 10 min, 1, 3, 24 and 48 h and at the end of the observation period.

Number of animals or in vitro replicates:

2 rabbits

Details on study design:

50 µL of the test substance were applied to the conjunctival sac of one eye of 2 animals.
The non- or saline-treated adjacent eye served as a control.

The animals were observed several times on the treatment day and up to 7 or 8 days afterwards,
and findings were recorded on working days.

Removal of the test substance.
The eyes were not washed out after 24 hours as specified in OECD Guideline 405.

Scoring system:
Draize scores

Tool used to assess score:
Fluorescein

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

24/48/72 h

Score:

1

Max. score:

3

Reversibility:

fully reversible within: 24 h

Irritation parameter:

conjunctivae score

Basis:

animal #2

Time point:

24/48/72 h

Score:

1

Max. score:

3

Reversibility:

fully reversible within: 24 h

Irritation parameter:

cornea opacity score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

other: reading after fluorescein application

Irritation parameter:

cornea opacity score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

other: reading after fluorescein application

Irritation parameter:

iris score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

2

Irritation parameter:

iris score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

2

Irritation parameter:

chemosis score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

At the 24 h reading, one animal had a conjunctivae score grade 1, the other animal was without findings. At the 48 h reading, both animals were without findings. No chemosis or injury to cornea and iris was observed at any time.

Interpretation of results:

not irritating

Remarks:

Migrated information Although only 0.05 mL test substance was applied instead of the 0.1 mL recommened (OECD 405 guideline) the test item can be classified as not irritating to the eye according to EU- and GHS criteria due to the very mild reversible eye reactions noted.

Executive summary:

Although only 0.05 mL of the test substance was applied instead of the 0.1 mL recommened in todays OECD 405 guideline, the test substance can be considered as not irritating to the eye due to the very mild reversible eye reactions noted under the conditions of this study according to Regulation 1272/2008/EC. (BASF, 1967)

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Skin:

In the key dermal irritation study (BASF, 1967; XVII 83) two Vienna White rabbits were dermally exposed to the undiluted test substance. The test site (intact dorsal skin) was covered with an occlusive dressing for 20 h with readings at 1, 5, 15 minutes and 20 hours. Rabbits were observed for 8 days and skin changes were recorded on working days. Irritations regarding erythema, edema and necrosis were scored according to a BASF grading system and converted into the numerical grading system according to OECD test guideline 404.

At 24 h after patch removal, grade 1 erythema was observed in both animals. At 48 h, grade 1 erythema was observed in the first animal but no erythema in the second animal. No edema was observed in both animals at any time. The mean value of the scores for either erythema or edema formation at the 24 and 48 h reading calculated over the two animals tested was 0.75 and 0.0, respectively. All findings were fully reversible within 5 days.

Under the conditions of this study, the test item was no irritant to rabbit skin.

Eye:

In the key primary eye irritation study (BASF, 1967; XVII 83), 50 µL of the undiluted test item was instilled into the conjunctival sac of one eye of two White Vienna rabbits. The eyes were not washed out after 24 hours. Animals were observed for 7-8 days and findings were recorded at 10 min, 1, 3, 24 and 48 h and at the end of the observation period. At the 24 h reading, one animal had a conjunctivae score grade 1, the other animal was without findings. At the 48 h reading, both animals were without findings. No injury to cornea was observed at any time. The mean value of the scores at the 24- and 48-hour reading for erythema was 0.5 and 0.0, respectively. The observed changes were fully reversible in both animals within 48 h.

Although only 0.05 mL of the test substance was applied instead of the 0.1 mL recommened in todays OECD 405 guideline, the test substance can be considered as not irritating to the eye due to the very mild reversible eye reactions noted under the conditions of this study.

Justification for selection of skin irritation / corrosion endpoint:
The key study was selected.

Justification for selection of eye irritation endpoint:
The key study was selected.

Justification for classification or non-classification

Based on the results of the skin and eye irritation key toxicity studies, the test item is not subjected to classification according to Regulation 1272/2008/EC.