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Description of key information

Skin irritation/corrosion (OECD 404): not irritating

Eye irritation (OECD 405): not irritating

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:
11 Oct - 02 Nov 2011
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Version / remarks:
adopted Jul 2015
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
Version / remarks:
May 2008
Deviations:
not specified
Qualifier:
according to guideline
Guideline:
EPA OPPTS 870.2500 (Acute Dermal Irritation)
Version / remarks:
Aug 1998
Deviations:
not specified
Qualifier:
according to guideline
Guideline:
other: Japanese Ministry of Agriculture, Forestry and Fisheries (JMAFF), 12 Nousan, Notification No 8147
Version / remarks:
Nov 2000
Deviations:
not specified
GLP compliance:
yes (incl. QA statement)
Remarks:
Food and Consumer Product Safety Authority (VWA), Utrecht, The Netherlands
Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River Deutschland, Kisslegg, Germany
- Age at study initiation: 25 - 29 weeks
- Weight at study initiation: 3.72 - 3.88 kg
- Housing: Animals were individually housed in labeled cages with perforated floors (67 x 62 x 55 cm) and shelters (40 x 32 x 23 cm).
- Diet: Global Diet 2030, pelleted, 100 grams per day; hay and wooden sticks
- Water: Tap water, ad libitum
- Acclimation period: At least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18.8 – 21.2
- Humidity (%): 43 - 77
- Air changes (per hr): approximately 15
- Photoperiod (hrs dark / hrs light): 12/12
Type of coverage:
semiocclusive
Preparation of test site:
clipped
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 h
Observation period:
7 days
Reading time points: 1, 24, 48, 72 hours and 7 days
Number of animals:
3
Details on study design:
TEST SITE
- Area of exposure: 6 cm² on the dorsal area of the trunk
- Type of wrap if used: The test substance was applied to the skin of one flank using a metalline patch of 2x3 cm. The patch was mounted on Micropore tape, which was wrapped around the abdomen and secured with Coban elastic bandage.

REMOVAL OF TEST SUBSTANCE
- Washing: Residual test substance was removed using tap water and watery ethanol (50% v/v)
- Time after start of exposure: 4 h

OBSERVATION TIME POINTS
The skin irritation effects (erythema, oedema, scales, dryness) were assessed 1, 24, 48, 72 h and 7 days after removoal of the dressings and test substance.

SCORING SYSTEM:
Draize scoring system
Irritation parameter:
erythema score
Basis:
other: Animal #1, #2
Time point:
24/48/72 h
Score:
1.3
Max. score:
4
Reversibility:
fully reversible within: 7 days
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0.7
Max. score:
4
Reversibility:
fully reversible within: 7 days
Irritation parameter:
edema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 72 h
Irritation parameter:
edema score
Basis:
other: Animal #2, #3
Time point:
24/48/72 h
Score:
0.7
Max. score:
4
Reversibility:
fully reversible within: 72 h
Irritant / corrosive response data:
Very slight erythema (grade 1) at the 1-, 48- and 72-h reading time point and well-defined erythema (grade 2) at the 24-h reading time point were observed in Animal #1 and #2. In Animal #3 very slight erythema (grade 1) were noted at the 1-, 24- and 48-h reading time point. Very slight edema (grade 1) at the 1- and 48-h reading time point and well-defined edema (grade 2) at the 24-h reading time point occured in Animal #1, whereas only very slight edema (grade 1) were noted in Animal #2 and #3 at the 1-, 24- and 48-h reading time point. The skin irritation had resolved within 72 h after exposure in Animal #3 and within 7 Days after exposure in Animal #1 and #2, respectively.

Table 1: Individual skin irritation scores

Observation time Rabbit no.
1 2 3
Erythema (0-4) Edema (0-4) comments Erythema (0-4) Edema (0-4) comments Erythema (0-4) Edema (0-4) comments
1 h 1 1 - 1 1 b 1 1 b
24 h 2 2 b 2 1 b 1 1 b
48 h 1 1 b 1 1 b 1 0 b
72 h 1 0 - 1 0 - 0 0 -
7 days 0 0 - 0 0 - 0 0 -

b: Dry remnants of the test substance present

Interpretation of results:
other: CLP/EU GHS criteria not met, no classification required according to Regulation(EC) No. 1272/2008
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:
17 - 27 Oct 2011
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Version / remarks:
adopted Oct 2012
Deviations:
no
Qualifier:
according to guideline
Guideline:
EPA OPPTS 870.2400 (Acute Eye Irritation)
Version / remarks:
Aug 1998
Deviations:
not specified
Qualifier:
according to guideline
Guideline:
EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)
Version / remarks:
May 2008
Deviations:
not specified
Qualifier:
according to guideline
Guideline:
other: Japanese Ministry of Agriculture, Forestry and Fisheries (JMAFF), 12 Nousan, Notification No 8147
Version / remarks:
Nov 2000
Deviations:
not specified
GLP compliance:
yes (incl. QA statement)
Remarks:
Food and Consumer Product Safety Authority (VWA), Utrecht, The Netherlands
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Charles River Deutschland, Kisslegg, Germany
- Age at study initiation: 26 - 29 weeks
- Weight at study initiation: 3.52 - 3.61 kg
- Housing: Individually housed in labeled cages with perforated floors and shelters
- Diet: Global Diet 2030, pelleted diet for rabbity [Harlan Teklad, Milan, Italy], approximately 100 g per days; hay and wooden sticks
- Water: Tap water, ad libitum
- Acclimation period: At least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18.0 - 21.2
- Humidity (%): 43.0 - 77.0
- Air changes (per hr): Approximately 15
- Photoperiod (hrs dark / hrs light): 12/12
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied: 0.1 mL
Duration of treatment / exposure:
24 h
Observation period (in vivo):
Reading time points: 1, 24, 48 and 72 h
Number of animals or in vitro replicates:
3 males
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): the treated eye remained unwashed following the instillation

SCORING SYSTEM: Draize scoring system

TOOL USED TO ASSESS SCORE: 24 h after instillation of the test substance, a 2% fluorescein solution was instilled into both eyes of each animal to quantatively determine the corneal epithelial damage
Irritation parameter:
cornea opacity score
Basis:
mean
Remarks:
of 3 animals
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Irritation parameter:
iris score
Basis:
mean
Remarks:
of 3 animals
Time point:
24/48/72 h
Score:
0
Max. score:
2
Reversibility:
other: not applicable
Irritation parameter:
conjunctivae score
Basis:
mean
Remarks:
of 3 animals
Time point:
24/48/72 h
Score:
0.3
Max. score:
3
Reversibility:
other: not applicable
Irritation parameter:
chemosis score
Basis:
mean
Remarks:
of 3 animals
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Irritant / corrosive response data:
Slight conjunctivae (score 1) was observed in 3/3 animals at the 1-h reading time point; persisting until the 24-h reading time point. The conjunctivae had cleared in all animals within 48 h. The scores for chemosis were 0 at all the reading time points in all animals. No effects on the iris and cornea were noted in any rabbit at any time point.
Other effects:
No symptoms of systemic toxicity were observed in the animals during the test period and no mortality occured.

Table 1: Individual eye irritation scores

Rabbit # Time [h] Conjunctivae Iris (0-2) Corneal opacity (0-4)
Redness (0-3) Chemosis (0-4)
1 1 1 0 0 0
24 1 0 0 0
48 0 0 0 0
72 0 0 0 0
2 1 1 0 0 0
24 1 0 0 0
48 0 0 0 0
72 0 0 0 0
3 1 1 0 0 0
24 1 0 0 0
48 0 0 0 0
72 0 0 0 0
Interpretation of results:
other: CLP/EU GHS criteria not met, no classification required according to Regulation(EC) No. 1272/2008
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Skin

The skin irritation potential of the test substance was determined by an in vivo skin irritation test performed in rabbits according to OECD guideline 404 and in compliance with GLP (Key, 2012). A dose of 0.5 mL of the undiluted test substance was applied to the shaved skin of 3 male rabbits for 4 hours using a semiocclusive dressing. Skin reactions were assessed 1, 24, 48 and 72 hours and 7 days after exposure. Exposure to the test substance resulted in

very slight erythema (grade 1) at the 1-, 48- and 72-h reading time point and well-defined erythema (grade 2) at the 24-h reading time point observed in Animal #1 and #2. In Animal #3 very slight erythema (grade 1) were noted at the 1-, 24- and 48-h reading time point. Very slight edema (grade 1) at the 1- and 48-h reading time point and well-defined edema (grade 2) at the 24-h reading time point occured in Animal #1, whereas only very slight edema (grade 1) were noted in Animal #2 and #3 at the 1-, 24- and 48-h reading time point. The skin irritation had resolved within 72 h after exposure in Animal #3 and within 7 Days after exposure in Animal #1 and #2, respectively.

Under the experimental conditions the mean erythema (over 24/48/72 hours) for 3 animals was 1.3, 1.3, and 0.67, respectively. The mean oedema score (over 24/48/72 hours) for 3 animals was 1.0, 0.67, and 0.33 respectively which results in mean erythema and oedema scores (over 24/48/72) for all animals of 1.1 and 0.67, respectively. The skin irritation had resolved within 72 hours after exposure in one animal and within 7 Days after exposure in the other two animals. Based on these results the test substance is considered to be non-irritating to skin.

Eye

The eye irritation potential of the test substance was determined by an in vivo eye irritation test in rabbits according to OECD guideline 405 and in compliance with GLP (Key, 2012). A dose of 0.1 mL of the undiluted test subtance was instilled into one eye of each of three male rabbits. Observations were made 1, 24, 48 and 72 hours after instillation. Slight conjunctivae (score 1) was observed in 3/3 animals at the 1-h reading time point; persisting until the 24-h reading time point. The conjunctivae had cleared in all animals within 48 h. The scores for chemosis were 0 at all the reading time points in all animals. No effects on the iris and cornea were noted in any rabbit at any time point.

Under the experimental conditions the mean scores for corneal opacity, iris, conjuntivae redness and chemosis (24/48/72 hours) for all animals were 0.0, 0.0, 0.3 and 0.0, respectively. The irritation had completely resolved within 48 hours in all animals. Based on these results the test substance is considered to be non-irritating to the eyes.

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) No 1272/2008, and are therefore conclusive but not sufficient for classification.