Registration Dossier

Administrative data

Description of key information

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:
27-10-2014 - 03-11-2015
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Study according to the guideline under GLP, this was conducted as part of testing plan to meet the China Level III testing requirements
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Qualifier:
according to
Guideline:
EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
Qualifier:
according to
Guideline:
EPA OPPTS 870.2500 (Acute Dermal Irritation)
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: WIL Research stock colony
- Age at study initiation: 10-11 months
- Weight at study initiation: 3491.7 -3767.1 g
- Housing: individually in suspended wire-mesh cages
- Diet: 150 g PMI Nutrition International, LLC, Certified HF Rabbit LabDiet® 5325 per day
- Water: municipal water ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18.6°C to 18.7°C
- Humidity (%): 32.5% to 45.7%
- Air changes (per hr): 10
- Photoperiod (hrs dark / hrs light): 12/12
Type of coverage:
semiocclusive
Preparation of test site:
shaved
Controls:
not required
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 mL

VEHICLE: NA
Duration of treatment / exposure:
4 hours
Observation period:
up to 7 days (scoring at 30-60 minutes , 24, 48 and 72 hours after treatmeneversible earlier)t and on day 4 and 7 (if not reversable earlier))
Number of animals:
3
Details on study design:
TEST SITE
- Area of exposure: 2.5 X 2.5 cm
- Type of wrap if used: 2-ply gauze patch secured in place with Micropore™ tape, overwrapped with a gauze binder and secured with Dermiform
tape.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): wiped with disposable paper towels moistened with deionizedwater
- Time after start of exposure: after the 4 h exposure period

SCORING SYSTEM: Draize
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 24-72 h
Score:
0.9
Max. score:
1
Reversibility:
fully reversible within: 4 days (2 males), 7 days (1 female)
Remarks on result:
other: brown discoloration at all scoring times
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 24-72 h
Score:
0
Max. score:
0
Other effects:
brown discoloration of the applicatoion site at all observations
Interpretation of results:
GHS criteria not met
Conclusions:
The substance is not irritating to the skin
Executive summary:

Rabbits (n=3) were treated with 0.5 mL test substance under semi-occlusion for 4 hours. Very slight erythema, which was fully reversible within 4 to 7 days was observed. The substance is considered to be not irritating to the skin.

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:
03-11-2014 - 13-11-2014
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Remarks:
performed to meet the requirements of the Chinese legislation
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Qualifier:
according to
Guideline:
EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)
Qualifier:
according to
Guideline:
EPA OPPTS 870.2400 (Acute Eye Irritation)
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Covance Research Products, Inc., Greenfield, IN or Denver, PA
- Age at study initiation: 12 to 17 months
- Weight at study initiation: 4109.7 to 4337.8 g
- Housing: individually in stainless steel cages elevated aboveground corncob bedding
- Diet: 150 g PMI Nutrition International, LLC, Certified Rabbit HF LabDiet® 5325 + one kale leaf 3 times weakly
- Water: municipal water ad libitum
- Acclimation period: 0 - 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18.4°C to 18.9°C
- Humidity (%): 32.5% to 39.6%
- Air changes (per hr): 10
- Photoperiod (hrs dark / hrs light): 12/12

Vehicle:
unchanged (no vehicle)
Controls:
other: untreated eye used as control
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 mL

VEHICLE : NA
Duration of treatment / exposure:
NA ( no eye wash performed)
Observation period (in vivo):
3 to 7 days
Number of animals or in vitro replicates:
3
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): none

SCORING SYSTEM: Draize

TOOL USED TO ASSESS SCORE: macropscopic examination and fluorescein for all cornea observations

TOPICAL ANESTHETICS AND SYSTEMIC ANALGESICS: according to the guideline
60 min before application: buneprophine (0.01 mg/ kg bw s.c.)
5 min before application: 0.5% proparacaine hydrochloride in each eye
8 hours after application: buneprophine (0.01 mg/ kg bw s.c.) and meloxicam (0.5 mg/kg s.c.)
thereafter: buneprophine (0.01 mg/ kg bw s.c.) every 12 hours, combined with meloxicam (0.5 mg/kg s.c.) every 24 hours
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
other: 24-72 h
Score:
0
Max. score:
0
Irritation parameter:
iris score
Basis:
mean
Time point:
other: 24-72 h
Score:
0
Max. score:
0
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
mean
Time point:
other: 24-72 h
Score:
ca. 0.8
Max. score:
2
Reversibility:
fully reversible within: 72 h (2 animals), 7 days (1 animal)
Irritation parameter:
conjunctivae score
Remarks:
discharge
Basis:
mean
Time point:
other: 24-72 h
Score:
0
Max. score:
2
Irritation parameter:
chemosis score
Basis:
mean
Time point:
other: 24-72 h
Score:
0
Max. score:
0

Animal no

1

2

3

1

24

48

72

1

24

48

72

1

24

48

72

4

7

cornea

0

0

0

0

0

0

0

0

0

0

0

0

0

0

iris

0

0

0

0

0

0

0

0

0

0

0

0

0

0

conjunctivae

 

 

 

 

 

 

 

 

 

 

 

 

 

 

redness

1

1

1

0

2

2

0

0

0

1

1

1

1

0

chemosis

0

0

0

0

0

0

0

0

0

0

0

0

0

0

discharge

2

0

0

0

2

0

0

0

2

0

0

0

0

0

Interpretation of results:
GHS criteria not met
Conclusions:
The substance is not irritating to the eye
Executive summary:

Three rabbits received 0.1 mL test substance in their eye after receiving topical anesthetics and systemic analgesics. No signs of irritation were observed during the 3 to 7 days test period. Slight redness was fully reversed at the end of the observation period. Therefore it is concluded that the substance is not irritating to the eye.

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

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

In an in vitro test for skin irritation, the relative mean viability of the test item treated tissues was 20.3% after a 15 minute exposure period (Harlan 2013). This would lead to the conclusion that the substance is a skin irritant. In an in vivo study, however, no irritant effects were observed after 4 hour exposure to the rabbit skin (Wil 2015). An in vitro assay for corrosivity showed that the substance is not corrosive (Harlan 2013).

The test item was found to be not irritating in a SkinEthic Reconstructed Human Corneal Epithelial Model study after 10 minutes of exposure.

In a BCOP assay with bovine corneas exposed to the substance opacity and permeability were similar to the negative controls (Harlan 2014).

In an in in vivo test in rabbits was negative (Wil 2015).


Justification for classification or non-classification

The available data on skin and eye irritation of the test substance do not meet the criteria for classification according to Regulation (EC) 1272/2008 and are therefore conclusive but not sufficient for classification.