Registration Dossier

Administrative data

Description of key information

The test item is neither irritating to the skin nor to the eye. Respiratory irritation is not expected.

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:
1967-03-22 to 1967-04-14
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Study predating guidelines and GLP, but scientifically fully acceptable.
Qualifier:
no guideline followed
Deviations:
not applicable
Principles of method if other than guideline:
other: BASF test (close to Draize test), occlusive, 3 rabbits, intact skin, 20 h exposure (among others)
GLP compliance:
no
Species:
rabbit
Strain:
Vienna White
Details on test animals and environmental conditions:
TEST ANIMALS
- Weight at study initiation: 2.83 kg (male); 3.10 kg (female); 2.72 kg (male)

ENVIRONMENTAL CONDITIONS
- no data

IN-LIFE DATES: From: 1967-03-29 To: 1967-04-14
Type of coverage:
occlusive
Preparation of test site:
not specified
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
undiluted (2 mL / animal (corresponds to 2.23 g)
Duration of treatment / exposure:
1, 5 or 20 minutes
20 hours (data selected as worst case for 4 h test)
Observation period:
Animal 1 (male, 7.6.645): 8 days, (day 3 and 4 lacking)
Animal 2 (female, 6.6.571): 5 days, (day 3 and 4 lacking)
Animal 3 (male, 5.6.427): 3 days
Number of animals:
3 rabbits
Details on study design:
TEST SITE
- Area of exposure: at six sites per rabbit along the dorsum (plus left ear, not considered)
- % coverage: approximately 6 cm2 each


REMOVAL OF TEST SUBSTANCE
- Washing: yes, mild detergent (50% Lutrol)


SCORING SYSTEM: Draize score (converted from recorded grading with detailed instructions provided by data owner)
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
other: 24 h, 48 h, and 5, 6, 7, 8 days (mean)
Score:
0
Max. score:
4
Remarks on result:
other: Exposure duration 20 h (instead of 4 h, OECD 404)
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
other: 24 h, 48 h and 5 days (mean)
Score:
0
Max. score:
4
Remarks on result:
other: Exposure duration 20 h (instead of 4 h, OECD 404)
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
other: 24 h, 48 h, 72 h (mean)
Score:
0.66
Max. score:
4
Reversibility:
fully reversible within: 72 h
Remarks on result:
other: Exposure duration 20 h (instead of 4 h, OECD 404)
Irritation parameter:
edema score
Basis:
animal #1
Time point:
other: 24 h, 48 h, and 5, 6, 7, 8 days (mean)
Score:
0
Max. score:
4
Remarks on result:
other: Exposure duration 20 h (instead of 4 h, OECD 404)
Irritation parameter:
edema score
Basis:
animal #2
Time point:
other: 24 h, 48 h, and 5, 6, 7, 8 days (mean)
Score:
0
Max. score:
4
Remarks on result:
other: Exposure duration 20 h (instead of 4 h, OECD 404)
Irritation parameter:
edema score
Basis:
animal #3
Time point:
other: 24 h, 48, 72 h (mean)
Score:
0
Max. score:
4
Remarks on result:
other: Exposure duration 20 h (instead of 4 h, OECD 404)
Irritant / corrosive response data:
not irritating (minimal signs of skin irritation (erythema grade 1) were noted after the 20 h exposure period in one animal at the 24h and 48h reading).
Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
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:
1967-03-22 to 1967-04-06
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Study predating guidelines and GLP, but obtained by standardised procedures comparable to those presently in use and thus valid for characterising the toxicity of the substance tested.
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
not applicable
Principles of method if other than guideline:
other: BASF test, comparable to OECD 405, but eyes were not washed out after 24 h, standard readouts on workdays, and fluorescin was applied
GLP compliance:
no
Species:
rabbit
Strain:
Vienna White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Weight at study initiation: 3 kg (male); 3.05 kg (female)

ENVIRONMENTAL CONDITIONS
- no data

IN-LIFE DATES: From: 1967-03-29 To: 1967-04-06
Vehicle:
unchanged (no vehicle)
Controls:
other: control eye: left eye of same animal
Amount / concentration applied:
TEST MATERIAL
- Amount applied: 0.05 mL of undiluted test item (corresponds to about 56 mg test item)

CONTROL MATERIAL
- Amount applied: 0.05 mL of "NaCl" (probably physiol. saline solution)
Duration of treatment / exposure:
not applicable - eye not rinsed after 24 hours
Observation period (in vivo):
8 days (readings at 1h, 24h, 48h and 8d after application)
Number of animals or in vitro replicates:
one male, one female
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing: no

SCORING SYSTEM: Draize score (converted from recorded grading with detailed instructions provided by data owner)

TOOL USED TO ASSESS SCORE: fluorescein
Irritation parameter:
overall irritation score
Basis:
animal #1
Time point:
other: 1 h, 24 h, 48 h and 8d (mean)
Score:
0
Max. score:
3
Remarks on result:
other: No 72 h readout in raw data, but as no irritation occurred, data point not necessary for evaluation
Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

In a primary dermal irritation study (BASF 1967), Vienna White rabbits (two males and one female) were dermally exposed to 2 mL of undiluted test item for either 1, 5 or 15 minutes or 20 hours to six sites on the dorsum each (occlusive treatment, approximately 6 cm2 of body surface area each). Animals then were observed for 3 to 8 days. Irritation was scored at first by a grading system of the data owner, converted later into the scoring of Draize. Minimal signs of skin irritation (erythema grade 1) were noted after the 20 h exposure period in one animal at the 24h and 48h reading. In this study, the test item is not a dermal irritant. No labelling is required.

In a primary eye irritation study (BASF 1967), 0.05 mL (56 mg) of 4-acetylmorpholine was instilled into the conjunctival sac of the right eye of Vienna White rabbits (one male / one female). Eyes were not washed. Animals were then observed for 8 days. A 72 h readout could not be identified from the raw data, but as no irritation occurred throughout the entire observation period, the 72 h data point was not necessary for an evaluation. Irritation was scored at first by a grading system of the data owner, converted later into the scoring of Draize. 4-acetylmorpholine did not induce eye irritating effects at any of the time points examinated.

Respiratory irritation is not expected since the substance is not irritating to skin and eye and did not cause any clinical signs in the acute inhalation toxicity study when rats were exposed to a vapor saturated atmosphere (BASF, 1967).



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 available data, the test item is not subject to C&L according to Directive 67/548/EEC or Regulation 1272/2008/EC.