Registration Dossier

Administrative data

Description of key information

In 2 valid skin irritation studies, ditolylether was found as slight/moderately irritating (Maertins, Suberg) to the skin, whereas a study with a semiocclusive application of the test substance over 24 hours at the inside of a rabbit ear found the test item highly irritating to the skin.
2 valid eye irritation studies stated ditolylether as not irritating to the eye (Maertins, Thyssen).

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:
other: guideline study according OECD 404
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Principles of method if other than guideline:
3 white New-Zealand rabbits were treated with 0.5 ml of undiluted test substance. The test item remained under semiocclusion on the skin for 4 hours. Treated animals were inspected for skin effects (erythema, oedema) after removal of patches and after 1, 2, 3 and 7 days. Total observation time was 7 days.
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
White New Zealand rabbits, weight 2.9 to 3.3 kg; husbandry: standardized conventional conditions in individual stainless steel cages.
Type of coverage:
semiocclusive
Preparation of test site:
other: clipped
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
Amount: 500 µl
Duration of treatment / exposure:
4 hours
Observation period:
7 days
Number of animals:
3
Details on study design:
TEST SITE
- Area of exposure: 6 cm²

REMOVAL OF TEST SUBSTANCE
- Washing (if done): with water
- Time after start of exposure: 4 hours

SCORING SYSTEM: according Draize
Irritation parameter:
erythema score
Basis:
mean
Time point:
24/48/72 h
Score:
1.33
Max. score:
4
Reversibility:
fully reversible within: 7 days
Irritation parameter:
edema score
Basis:
mean
Time point:
24/48/72 h
Score:
0.66
Max. score:
4
Reversibility:
fully reversible within: 7 days
Other effects:
no data

No data

Interpretation of results:
GHS criteria not met
Executive summary:

Method: 3 white New-Zealand rabbits were treated with 0.5 ml of undiluted test substance. The test item remained under semiocclusion on the skin for 4 hours. Treated animals were inspected for skin effects (erythma, oedema) after removal of patches and after 1, 2, 3 and 7 days. Total observation time was 7 days

Result: slightly irritating to the skin, but not sufficient for classification

Reference: Maertins (Bayer AG), 1989

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:
other: guideline study according OECD 405
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Principles of method if other than guideline:
100 µl test compound was instilled into the conjunctival sac of one eye of each of 3 rabbits. The lids were then gently held together for about one second. The other eye remained untreated and served as control. The treated eye was washed out with physiological NaCl solution 24 hours after instillation of the test compound.
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
White New Zealand rabbits, weight 3.1 to 3.2 kg; husbandry: standardized conventionel conditionsin individual stainless steel cages.
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
100 µl/undiluted
Duration of treatment / exposure:
4 hours
Observation period (in vivo):
7 days
Number of animals or in vitro replicates:
3
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): yes
- Time after start of exposure: 24 hours


SCORING SYSTEM: as described by Draize


TOOL USED TO ASSESS SCORE: hand-slit lamp / fluorescein
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: score = 0 at any time point
Irritation parameter:
iris score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
2
Reversibility:
other: score = 0 at any time point
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
3
Reversibility:
other: score = 0 at any time point
Irritation parameter:
chemosis score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: score = 0 at any time point
Other effects:
no data

This study reveals that the test substance does not have a significant irritant potential on the eye.

Interpretation of results:
GHS criteria not met
Executive summary:

Method: 100 µl test compound was instilled into the conjunctival sac of one eye of each of 3 rabbits. the lids were then gently held together for about one second. the other eye remained untreated and served as control. the treated eye was washed out with physiological NaCl solution 24 hours after instillation of the test compound

Result: not irritating to the eye

Reference: Maertins (Bayer AG), 1989

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

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Two valid studies conducted according to OECD TG 404 found ditolyl ether to be not irritating according to GHS criterias. A study following no guideline (24 h application, inside rabbit ear) reported irritating observations of ditolylther but this method is known to overestimate potential skin irritating effects.

In 2 valid studies ditolylether was not irritating to the eye.

Justification for classification or non-classification

The findings for skin irritation did not meet the criteria for classification. Also for eye irritation a classification is not required.