Registration Dossier

Administrative data

Description of key information

No studies on primary irritation are available. The assessment of skin and eye irritation has been based on read-across to closely structure-related substances, such as methylnaphthalene and diisopropylnaphthalene (DIPN). There were no but slight initial effects on rabbit´s skin and eyes in three valid studies each.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records
Reference
Endpoint:
skin irritation: in vivo
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
supporting study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP-guideline study
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: H. Fortkamp, Lengerich, Germany
- Age at study initiation: 11 - 17 weeks
- Weight at study initiation: 2.50 - 2.90 kg
- Housing: singly in steel cages with perforated plate floors above litter-filled dung troughs
- Diet: Ssniff K complete rabbit diet (Ssniff Versuchstier-Diäten GmbH, Soest, Germany), ad libitum
- Water: drinking water, ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 - 23
- Humidity (%): 40 - 70
- Air changes (per hr): 10
- Photoperiod (hrs dark / hrs light): 12 / 12
Type of coverage:
occlusive
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 mL
Duration of treatment / exposure:
4 hour(s)
Observation period:
14 d
Number of animals:
3
Details on study design:
TEST SITE
- Area of exposure: dorsal area of the trunk, size ca. 2.5 x 2.5 cm
- % coverage: no data
- Type of wrap if used: impermeable adhesive dressing

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Remaining test substance was removed by wiping with single-use paper towels.
- Time after start of exposure: 4 h

SCORING SYSTEM: according to Draize (similar to table "Grading of Skin Reactions" of OECD TG 404)
Irritation parameter:
primary dermal irritation index (PDII)
Basis:
mean
Time point:
other: 24, 48, and 72 h
Score:
1
Max. score:
8
Reversibility:
fully reversible
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 24 h
Score:
0.33
Max. score:
4
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 48 h
Score:
0.33
Max. score:
4
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 72 h
Score:
0.33
Max. score:
4
Reversibility:
fully reversible within: 7 d
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 24 h
Score:
1
Max. score:
4
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 48 h
Score:
1
Max. score:
4
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 72 h
Score:
0.33
Max. score:
4
Reversibility:
fully reversible within: 7d
Irritant / corrosive response data:
In 2/3 animals, slight erythemas and edemas (score) were noted 1 h post-applicationion, which was still from 24 through 72 h in one animal. Scab formation was observed at the treatment site of all animals after 7 d.
Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
In a primary skin irritation test, 1-methylnaphthalene, a structure-analogous substance, was found to be slightly irritating according to the scoring system of Draize. According to EU regulations, no classification as to skin irritation is required.
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:
migrated information: read-across based on grouping of substances (category approach)
Adequacy of study:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Comparable to guideline study, basic data given (deviations: first observation 24 h after application, differing scoring system, observation period reduced, limited reporting)
Qualifier:
according to
Guideline:
other: Consumer Product Safety Commission, USA; Code of Federal Regulations, Title 16, Section 1500.42
Principles of method if other than guideline:
The method used is similar to the OECD test guideline 405 (Acute Eye Irritation/Corrosion) with some deviations (first observation 24 h after application, differing scoring system, observation period reduced, limited reporting)
GLP compliance:
no
Remarks:
pre-GLP study
Species:
rabbit
Strain:
other: albino rabbits
Details on test animals or tissues and environmental conditions:
no data
Vehicle:
unchanged (no vehicle)
Controls:
other: the second eye of the animal served as control
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 mL
Duration of treatment / exposure:
single exposure
Observation period (in vivo):
7 d
Number of animals or in vitro replicates:
6
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): no

SCORING SYSTEM: according to Draize (max. score 110) (ETAD recommendation)
Irritation parameter:
cornea opacity score
Basis:
mean
Remarks:
(6 animals)
Time point:
other: 24, 48, and 72 h (1, 2, and 3 days)
Score:
0
Max. score:
4
Remarks on result:
other: no effects were observed in any of the test animals
Irritation parameter:
iris score
Basis:
mean
Remarks:
(6 animals)
Time point:
other: 24, 48, and 72 h (1, 2, and 3 days)
Score:
0
Max. score:
2
Remarks on result:
other: no effects were observed in any of the test animals
Irritation parameter:
conjunctivae score
Basis:
mean
Remarks:
(6 animals)
Time point:
other: 24, 48, and 72 h (1, 2, and 3 days)
Score:
1.22
Max. score:
3
Reversibility:
not fully reversible within: 7 days (5 animals)
Remarks on result:
other: observation period only 7 days
Irritation parameter:
chemosis score
Basis:
mean
Remarks:
(6 animals)
Time point:
other: 24, 48, and 72 h (1, 2, and 3 days)
Score:
1.22
Max. score:
4
Reversibility:
not fully reversible within: 7 days (2 animals)
Remarks on result:
other: observation period only 7 days
Irritation parameter:
maximum mean total score (MMTS)
Basis:
mean
Remarks:
(6 animals)
Time point:
other: 24 h
Score:
6.67
Max. score:
110
Irritation parameter:
maximum mean total score (MMTS)
Basis:
mean
Remarks:
(6 animals)
Time point:
other: 48 h
Score:
6
Max. score:
110
Irritation parameter:
maximum mean total score (MMTS)
Basis:
mean
Remarks:
(6 animals)
Time point:
other: 72 h
Score:
8.33
Max. score:
110
Irritation parameter:
maximum mean total score (MMTS)
Basis:
mean
Time point:
other: day 7
Score:
3
Max. score:
110
Reversibility:
not fully reversible within: 7 days
Remarks on result:
other: observation period only 7 days
Irritant / corrosive response data:
For cornea and iris, no effects were observed. Conjunctivae and chemosis scores were moderate to low. In individual animals, the maximum mean (24 to 72 h) values were 1.67 (one value) or lower. At day 7, four animals still showed effects (conjunctivae 3 animal, grad 1 or 2; chemosis 2 animals, grade 1).
Other effects:
In two animals continuing eye secretion was observed up to day 7.

Eye irritation scores of individual rabbits (grading according to OECD TG 405; original scores are presented in the attached table under Attached background material)

 

 

Cornea

Iris

Conjunctivae

Chemosis

Day after TS installation

1

2

3

mean
(1-3)

7

1

2

3

mean
(1-3)

7

1

2

3

mean
(1-3)

7

1

2

3

mean
(1-3)

7

Rabbit 1

0

0

0

0

0

0

0

0

0

0

0

1

1

0.67

0

0

1

1

0.67

0

Rabbit 2

0

0

0

0

0

0

0

0

0

0

1

1

2

1.33

0

2

2

1

1.67

1

Rabbit 3

0

0

0

0

0

0

0

0

0

0

1

1

2

1.33

2

1

1

2

1.33

1

Rabbit 4

0

0

0

0

0

0

0

0

0

0

1

1

2

1.33

0

1

1

2

1.33

0

Rabbit 5

0

0

0

0

0

0

0

0

0

0

3

1

0

1.33

1

2

1

1

1.33

0

Rabbit 6

0

0

0

0

0

0

0

0

0

0

2

1

1

1.33

1

1

1

1

1.00

0

mean

0

0

0

0

0

0

0

0

0

0

1.33

1.00

1.33

1.22

0.67

1.17

1.17

1.33

1.22

0.33

 

Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The study was not conducted following current test procedures. But readings were taken at the appropriate time points and scoring was performed according to Draize. Thus cornea, iris, conjunctivae and chemosis scores according to OECD TG 405 can be extracted from the reported values. Observation period was only 7 days. But the scores observed were moderate and had in general declined until day 7. Hence, it is estimated that the effects observed will be fully reversible within 21 days.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Justification for selection of skin irritation / corrosion endpoint:
acceptable for assessment, SAR (read-across) to a chemical structure closely related to that of the target substance.

Justification for selection of eye irritation endpoint:
acceptable for assessment, SAR (read-across) to a chemical structure closely related to that of the target substance.

Justification for classification or non-classification

The assessment of skin irritation has been based on read-across to closely structure-related substances, such as methylnaphthalene and diisopropylnaphthalene (DIPN). It is assumed that MIPN isomer mixture (MIPN) shows a similar irritation profile. Hence, no classification is required for the target compound.