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Administrative data

Description of key information

The test item produced a primary irritation index of 0.0 and was classified as non-irritant to rabbit skin according to the Draize classification scheme.  No corrosive effects were noted

The test item produced a maximum group mean score of 8.0 and was classified as a minimal irritant (Class 3 on a 1 to 8 scale) to the rabbit eye according to a modified Kay and Calandra classification system.

The test item produced a limited amount of irritation observed 1 hour after exposure, the mean irrititaion scores for conjuctival redness and chemosis were below the threshold for classification when considered as the mean value for measurements taken at 24,48 and 72 hours therfore the substance does not meet the criteria for Eye irritation according to Regulation (EC) No.1272/2008, relating to the Classification, Labelling and Packaging of Substances and Mixtures.

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:
This study was conducted between 09 July 2013 and 26 July 2013
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:
24 April 2002
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
Version / remarks:
EC No. 440/2008
Deviations:
no
GLP compliance:
yes (incl. certificate)
Specific details on test material used for the study:

Batch: 20130510
Purity: 99.81%
Expiry date: 10 May 2018
Storage Conditions: room temperature in the dark
Species:
rabbit
Strain:
New Zealand White
Remarks:
Hsdlf:NZW
Details on test animals and environmental conditions:
Three New Zealand White (Hsdlf:NZW) strain rabbits were supplied by Harlan Laboratories UK Ltd., Leicestershire, UK. At the start of the study the animals weighed 2.24 to 3.04 kg and were twelve to twenty weeks old. After an acclimatization period of at least five days each animal was given a number unique within the study which was written with a black indelible marker-pen on the inner surface of the ear and on the cage label.
The animals were individually housed in suspended cages. Free access to mains drinking water and food (2930C Teklad Global Rabbit diet supplied by Harlan Laboratories UK Ltd., Oxon, UK) was allowed throughout the study. The diet and drinking water were considered not to contain any contaminant of a level that might have affected the purpose or integrity of the study.
The temperature and relative humidity were set to achieve limits of 17 to 23 oc and 30 to 70% respectively. Any occasional deviations from these targets were considered not to have affected the purpose or integrity of the study. The rate of air exchange was at least fifteen changes per hour and the lighting was controlled by a time switch to give twelve hours continuous light (06:00 to 18:00) and twelve hours darkness.
The animals were provided with environmental enrichment items which were considered not to contain any contaminant of a level that might have affected the purpose or integrity of the study.
Type of coverage:
occlusive
Preparation of test site:
clipped
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
Test material:
Used as supplied
- Applied volume: 0.5 mL
- Concentration (if solution): undiluted

Duration of treatment / exposure:
3 minutes, 1 hour and 4 Hours
Observation period:
1, 24, 48 and 72 hours
Number of animals:
3
Details on study design:
Study Design
On the day before the test each of a group of three rabbits was clipped free of fur from the dorsal/flank area using veterinary clippers. Only animals with a healthy intact epidermis by gross observation were selected for the study.
On the day of the test a suitable test site was selected on the back of each rabbit. A quantity of 0.5 mL of the test item was applied directly to the skin under a 2.5 cm x 2.5 cm cotton gauze patch. The patch was secured in position with a strip of surgical adhesive tape. To prevent the animals interfering with the patches, the trunk of each rabbit was wrapped in an elasticated corset and the animals were returned to their cages for the duration of the exposure period.
Four hours after application the corset and patches were removed from each animal and any residual test item removed by gentle swabbing with cotton wool soaked in 74% industrial methylated spirit.
Immediately following removal of the patches and approximately 1, 24, 48 and 72 hours later, the test sites were examined for evidence of primary irritation and scored according to the following scale:

EVALUATION OF SKIN REACTIONS
Erythema and Eschar Formation Value
No erythema 0
Very slight erythema (barely perceptible) 1
Well-defined erythema 2
Moderate to severe erythema 3
Severe erythema (beef redness) to eschar formation
preventing grading of erythema 4

Edema Formation
No edema 0
Very slight edema (barely perceptible) 1
Slight edema (edges of area well-defined by definite raising) 2
Moderate edema (raised approximately 1 millimeter) 3
Severe edema (raised more than 1 millimeter and
extending beyond the area of exposure) 4

Any other skin reactions and clinical signs of toxicity, if present, were also recorded.
Additional observations were made on Days 7 and 14 to assess the reversibility of skin reactions.
Individual body weights were recorded on Day 0 (the day of dosing) and at the end of the observation period.
Irritation parameter:
erythema score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
0
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
0
Remarks on result:
no indication of irritation
Irritant / corrosive response data:
The test item produced a primary irritation index of 0.0 and was classified as non- irritant to rabbit skin according to the Draize classification scheme.
Other effects:
Skin Reactions
3-Minute Exposure Period
No evidence of skin irritation was noted during the study (Table 1).

I-Hour Exposure Period
No evidence of skin irritation was noted during the study.

4-Hour Exposure Period
No evidence of skin irritation was noted during the study.

Body Weight
All animals showed expected gain in body weight during the study

Skin Reactions

3-Minute Exposure Period

No evidence of skin irritation was noted during the study (Table 1).

I-Hour Exposure Period

No evidence of skin irritation was noted during the study (Table 1).

4-Hour Exposure Period

No evidence of skin irritation was noted during the study (Table 2).

Body Weight

All animals showed expected gain in body weight during the study

Table 1: Individual Skin Reactions Following 3-Minute and 1-Hour Exposure

 Skin Reaction

 Observation Time (following patch removal)

 Individual Score Rabbit 73321 Male

 

 

 3 -Minute exposure

 1 -Hour exposure

 Erythema/Eschar Formation

 Immediately

 0

 0

 

 1 Hour

 0

0

 

 24 Hours

 0

 0

 

 48 Hours

 0

 0

 

 72 Hours

 0

 0

 Edema Formation

 Immediately

 0

0

 

 1 Hour

 0

 

 24 Hours

 

 48 Hours

 0

0

 

 72 Hours

0

Table 2     Individual Skin Reactions Following 4-Hour Exposure

Skin Reaction

Observation Time
(following patch removal)

Individual Scores

Total

Rabbit Number and Sex

73321Male

73376Male

73375Male

Erythema/Eschar Formation

Immediately

0

0

0

(0 )

1 Hour

0

0

0

( 0 )

24 Hours

0

0

0

0

48 Hours

0

0

0

( 0 )

72 Hours

0

0

0

0

Edema Formation

Immediately

0

0

0

( 0 )

1 Hour

0

0

0

( 0 )

24 Hours

0

0

0

0

48 Hours

0

0

0

( 0 )

72 Hours

0

0

0

0

Sum of 24 and 72‑Hour Readings (S):          0

Primary Irritation Index (S/6)            :          0/6 = 0.0

Classification                                     :          NON‑IRRITANT


(   ) =   Total values not used for calculation of primary irritation index

Interpretation of results:
GHS criteria not met
Conclusions:
The test item produced a primary irritation index of 0.0 and was classified as non-irritant to rabbit skin according to the Draize classification scheme. No corrosive effects were noted
Executive summary:


The study was performed to assess the irritancy potential of the test item following single, 3-Minute, 1 and 4-Hour, semi-occluded applications to the intact rabbit skin.

Results

3-Minute and 1-Hour semi-occluded applications of the test item to the intact skin of one rabbit produced no evidence of skin irritation.

Conclusion

The test item produced a primary irritation index of 0.0 and was classified as non-irritant to rabbit skin according to the Draize classification scheme.  No corrosive effects were noted

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:
06 August 2013 - 15 August 2013
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Harlan Laboratories UK Ltd., Leicestershire, UK.
- Age at study initiation: Twelve to twenty weeks old.
- Weight at study initiation: 2.48 to 3.37 kg
- Housing: The animals were individually housed in suspended cages.
- Diet (e.g. ad libitum):Free access to mains drinking water and food (2930C Teklad Global Rabbit diet supplied by Harlan Laboratories UK Ltd., Oxon, UK) was allowed throughout the study. The diet and drinking water were considered not to contain any contaminant of a level that might have affected the purpose or integrity of the study.
- Acclimation period: Five days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17 to 23 °C
- Humidity (%): 30 to 70%
- Air changes (per hr): The rate of air exchange was at least fifteen changes per hour .
- Photoperiod (hrs dark / hrs light):The lighting was controlled by a time switch to give twelve hours continuous light (06:00 to 18:00) and twelve hours darkness.
Vehicle:
unchanged (no vehicle)
Controls:
yes, concurrent no treatment
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1mL

Duration of treatment / exposure:
8 hours
Observation period (in vivo):
Assessment of ocular damage/irritation was made approximately 1 hour and 24, 48 and 72 hours following treatment, according to the numerical evaluation (Draize, J.H, 1977)
Number of animals or in vitro replicates:
3
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): Not specified
- Time after start of exposure: 8 hours

SCORING SYSTEM: Kay and Calandra system

TOOL USED TO ASSESS SCORE: hand-slit lamp
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
other: 1h
Score:
2
Reversibility:
fully reversible within: 48h
Remarks on result:
positive indication of irritation
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
24 h
Score:
1
Reversibility:
fully reversible within: 48 Hours
Remarks on result:
positive indication of irritation
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
other: 48/72h
Score:
0
Reversibility:
fully reversible
Remarks on result:
no indication of irritation
Irritation parameter:
chemosis score
Basis:
mean
Time point:
24 h
Score:
1
Reversibility:
fully reversible within: 48 hours
Remarks on result:
positive indication of irritation
Irritation parameter:
chemosis score
Basis:
mean
Time point:
other: 48/72h
Score:
0
Reversibility:
fully reversible
Remarks on result:
no indication of irritation
Irritation parameter:
iris score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Reversibility:
fully reversible
Remarks on result:
no indication of irritation
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Reversibility:
fully reversible
Remarks on result:
no indication of irritation
Irritant / corrosive response data:
No corneal or iridial effects were noted during the study.
Moderate conjunctival irritation was noted in all treated eyes one hour after treatment with minimal conjunctival irritation noted at the 24-Hour observation.
All treated eyes appeared normal at the 48-Hour observation.
Interpretation of results:
GHS criteria not met
Conclusions:
The test item produced a maximum group mean score of 8.0 and was classified as a minimal irritant (Class 3 on a 1 to 8 scale) to the rabbit eye according to a modified Kay and Calandra classification system.
The test item produced a limited amount of irritation observed 1 hour after exposure, the mean irrititaion scores for conjuctival redness and chemosis were below the threshold for classification when considered as the mean value for measurements taken at 24,48 and 72 hours therfore the substance does not meet the criteria for Eye irritation according to Regulation (EC) No.1272/2008, relating to the Classification, Labelling and Packaging of Substances and Mixtures.
Executive summary:

Introduction

The study was performed to assess the irritancy potential of the test item to the eye of the New Zealand White rabbit


Results

A single application of the test item to the non-irrigated eye of three rabbits produced moderate conjunctival irritation. All treated eyes appeared normal at the 48-Hour observation.

Conclusion

The test item produced a maximum group mean score of 8.0 and was classified as a minimal irritant (Class 3 on a 1 to 8 scale) to the rabbit eye according to a modified Kay and Calandra classification system.

he test item produced a limited amount of irritation observed 1 hour after exposure, the mean irrititaion scores for conjuctival redness and chemosis were below the threshold for classification when considered as the mean value for measurements taken at 24,48 and 72 hours therfore the substance does not meet the criteria for Eye irritation according to Regulation (EC) No.1272/2008, relating to the Classification, Labelling and Packaging of Substances and Mixtures.

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

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Justification for classification or non-classification

Eye irritation: The test item produced a limited amount of irritation observed 1 hour after exposure, the mean irrititaion scores for conjuctival redness and chemosis were below the threshold for classification when considered as the mean value for measurements taken at 24,48 and 72 hours therfore the substance does not meet the criteria for Eye irritation according to Regulation (EC) No.1272/2008, relating to the Classification, Labelling and Packaging of Substances and Mixtures.

Skin irritation: The test item produced a primary irritation index of 0.0 and was classified as non-irritant to rabbit skin according to the Draize classification scheme.  No corrosive effects were noted. According to the CLP criteria the substance is not classified for skin irritation as no adverse effects were observed.