Registration Dossier

Administrative data

Description of key information

The substance was tested for its irritating potential to the skin and eye via a GLP compliant OECD 404 and a study similar/equivalent to OECD 405, respectively.

It can be concluded that the test substance is not irritating after skin or eye contact under the test conditions chosen.

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:
Dec 2019 - Feb 2019
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Version / remarks:
July 28, 2015
Deviations:
no
GLP compliance:
yes (incl. certificate)
Remarks:
Landesanstalt für Umwelt Baden-Württemberg
Specific details on test material used for the study:
SOURCE OF TEST MATERIAL
-Test item No.: 12/0227-2
- Batch No.of test material: 0016046440
- Expiration date of the lot/batch: January 07, 2020
- Purity: 100 g / 100 g (UVCB substance)

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: Room temperature; avoid temperature < 10°C
- The stability of the test item under storage conditions over the test period was guaranteed by the sponsor
- Solubility and stability of the test substance in the solvent/vehicle: The test item was homogeneous by visual inspection

TREATMENT OF TEST MATERIAL PRIOR TO TESTING
- Treatment of test material prior to testing: Undiluted applicaton

OTHER SPECIFICS:
- Density [g/mL]: 0.960 (dertermined by testing facility)
- Physical state/ color: Liquid, viscous / yellowish to pink, clear
- pH-value: Approx. 5.5 (undiluted test item, determined by testing facility)
Species:
rabbit
Strain:
New Zealand White
Remarks:
Crl:KBL(NZW) – (SPF)
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Wiga GmbH, Germany
- Age at study initiation: Approx. 6 months
- Weight at study initiation: 4.03 kg – 4.44 kg
- Sex: Males
- Housing: Single housing in stainless steel wire mesh cages with grating with shallow cage body; floor area: 4225 cm². The animals were housed in fully air-conditioned rooms
- Diet (e.g. ad libitum): STANRAB (P) SQC; SDS Special Diets Services, 67122 Altrip, Germany, ad libitum
- Water (e.g. ad libitum): tap water ad libitum
- Acclimation period: At least 5 days before application

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20°C ± 3°C
- Humidity (%): 30 – 70%
- Photoperiod (hrs dark / hrs light): 12 h / 12 h (6.00 a.m. – 6.00 p.m. / 6.00 p.m. – 6.00 a.m.)
Type of coverage:
semiocclusive
Preparation of test site:
clipped
Vehicle:
unchanged (no vehicle)
Controls:
other: untreated skin sites of the same animal
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 mL
- Concentration (if solution): Undiluted test substance
Duration of treatment / exposure:
Exposure for 4 hours
Observation period:
up to day 21
Number of animals:
3 animals
Details on study design:
TEST SITE
- Area of exposure: 2.5 cm x 2.5 cm
- Type of wrap if used: The test substance was covered with a test patch (Idealbinde, Pfälzische Verbandstoff-Fabrik, Kaiserslautern) and Fixomull® stretch (adhesive fleece), Beiersdorf AG

REMOVAL OF TEST SUBSTANCE
- Washing (if done): The test substance was removed at the end of the exposure period with Lutrol® and Lutrol®/water (1 : 1).
- Time after start of exposure: 4h

OBSERVATION TIME POINTS
- Readings at 24, 48 and 72 h

SCORING SYSTEM:
According to OECD guideline 404
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 24-72 h
Score:
1.1
Max. score:
4
Reversibility:
not fully reversible within: 21 days
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 24-72 h
Score:
0
Max. score:
4
Irritant / corrosive response data:
Mean scores over 24, 48 and 72 hours for each animal were 0.0, 2.0 and 1.3 for erythema and 0.0, 0.0 and 0.0 for edema, respectively.
The cutaneous reactions were reversible in one animal within 24 hours, in a second animal within 14 days after removal of the patch.
In one animal, the cutaneous reactions were not reversible within 21 days. In this animal, very slight erythema (grade 1) and yellowish discoloration were seen on study day 21.

Other effects:
yellowish discoloration of the application area in some animals

Tab.1: Tabulation of irritant response, data for each individual animal at each observation time as well as calculation of the means

Readings

Animal No.

Erythema

Edema

Additional Findings

0h

1

1

0

 

2

1

0

 

3

1

0

 

1h

1

1

0

 

2

2

0

 

3

2

0

 

24h

1

0

0

 

2

2

0

 

3

2

0

 

48h

1

0

0

yellowish discoloration of the application area

2

2

0

-

3

1

0

-

72h

1

0

0

yellowish discoloration of the application area; SD

2

2

0

yellowish discoloration of the application area

3

1

0

yellowish discoloration of the application area

7d

1

-

-

 

2

2

0

yellowish discoloration of the application area

3

1

0

yellowish discoloration of the application area

14d

1

-

-

-

2

0

0

yellowish discoloration of the application area; SD

3

1

0

yellowish discoloration of the application area

21d

1

-

-

-

2

-

-

-

3

1

0

yellowish discoloration of the application area

Mean

24h – 72h

1

0.0

0.0

 

2

2.0

0.0

 

3

1.3

0.0

 

Mean

-

1.1

0.0

 

Interpretation of results:
GHS criteria not met
Conclusions:
Considering the described cutaneous reactions as well as the average score for irritation, the test substance does not show a skin irritating potential under the test conditions chosen.
Executive summary:

The potential of the test substance to cause acute dermal irritation or corrosivity was assessed by a single topical application of an amount of 0.5 mL of the test item for 4 hours to the intact skin of three New Zealand White rabbits (stepwise procedure starting with one animal, supplementing two additional animals), using a patch of 2.5 cm x 2.5 cm, covered with semi-occlusive dressing. After removal of the patch the application area was washed off. The cutaneous reactions were assessed immediately after removal of the patch, approximately 1, 24, 48 and 72 hours after removal of the patch and at weekly intervals until day 21 at the latest.

The following test item-related clinical observations were recorded during the course of the study:

- Very slight to well-defined erythema (grade 1 to 2)

- Yellowish discoloration of the applications area

The cutaneous reactions were reversible in one animal within 24 hours and in a second animal within 14 days after removal of the patch. In one animal, cutaneous reactions were not reversible within 21 days. In this animal, very slight erythema (grade 1) and yellowish discoloration were seen on study day 21.

Mean scores over 24, 48 and 72 hours for each animal were 0.0, 2.0 and 1.3 for erythema and 0.0, 0.0 and 0.0 for edema, respectively.

Considering the described cutaneous reactions as well as the average score for irritation of the test item, it does not show a skin irritating potential under the test conditions chosen.

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:
comparable to guideline study with acceptable restrictions
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
yes
Remarks:
Body weights not reported
GLP compliance:
yes
Specific details on test material used for the study:
Test material name: Naugalube 438L CN 5294300
Supplier: Uniroyal Inc.
Description: Brown viscous liquid
storage at ambient temperature and humidity
Species:
rabbit
Strain:
other: Albino, not further specified
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Nicholas Helf
- Age at study initiation: no data
- Weight at study initiation: no data
- Housing: 2 per cage
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): controlled
- Humidity (%): controlled
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): no data

IN-LIFE DATES: From: 1 August 1983 To: 4 August 1983
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
0.1 ml
Duration of treatment / exposure:
single treatment
Observation period (in vivo):
3 ays
Number of animals or in vitro replicates:
6
Details on study design:
The test article was placed by syringe or syringe-type applicator into the conjunctival sac which was formed by gently pulling the lower eye1 i d away frorn the
eye. After instilllation, the lids were held together briefly to insure adequate distribution of the test article, One eye of each rabbit was dosed. The contralateral
eye served as a control. No washing step was included.
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Remarks on result:
no indication of irritation
Irritation parameter:
iris score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
2
Reversibility:
other: not applicable
Remarks on result:
no indication of irritation
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
3
Reversibility:
other: not applicable
Remarks on result:
no indication of irritation
Irritation parameter:
chemosis score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Remarks on result:
no indication of irritation
Irritant / corrosive response data:
None of the six treated animals showed any sign of ocular irritation.
Interpretation of results:
GHS criteria not met
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Skin irritation/corrosion

The potential of the test substance to cause acute dermal irritation or corrosivity was assessed by a single topical application of an amount of 0.5 mL of the test item for 4 hours to the intact skin of three New Zealand White rabbits (stepwise procedure starting with one animal, supplementing two additional animals), using a patch of 2.5 cm x 2.5 cm, covered with semi-occlusive dressing. After removal of the patch the application area was washed off. The cutaneous reactions were assessed immediately after removal of the patch, approximately 1, 24, 48 and 72 hours after removal of the patch and at weekly intervals until day 21 at the latest.

The following test item-related clinical observations were recorded during the course of the study:

- Very slight to well-defined erythema (grade 1 to 2)

- Yellowish discoloration of the applications area

The cutaneous reactions were reversible in one animal within 24 hours and in a second animal within 14 days after removal of the patch. In one animal, cutaneous reactions were not reversible within 21 days. In this animal, very slight erythema (grade 1) and yellowish discoloration were seen on study day 21.

Mean scores over 24, 48 and 72 hours for each animal were 0.0, 2.0 and 1.3 for erythema and 0.0, 0.0 and 0.0 for edema, respectively.

Considering the described cutaneous reactions as well as the average score for irritation of the test item, it does not show a skin irritating potential under the test conditions chosen.

Eye irritation

The potential of the test substance to cause acute eye irritation was assessed in an in vivo eye irritation study (similar/equivalent to OECD 405) in rabbits. The test substance (0.1 mL) was placed by syringe or syringe-type applicator into the conjunctival sac and effects were observed for an obervation period of 3 days. None of the six treated animals showed any sign of ocular irritation.Thus, the test substance does not show an eye irritating potential under the test conditions chosen.

Justification for classification or non-classification

The available experimental test data are reliable and suitable for classification purposes under Regulation 1272/2008. A GLP-compliant OECD 404 study is available for skin irritation. A GLP-compliant eye irritation study equivalent or similar to the OECD 405 guideline is available for eye irritation. In both studies, the scores for the test item treated tissues were below the thresholds for classification as an irritant. As a result, the substance is not considered to be classified for skin or eye irritation under Regulation (EC) No. 1272/2008, as amended for the thirteenth time in Regulation (EC) No 2018/1480.