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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
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: The study was conducted at a GLP facility and according to OECD guidelines.
Qualifier:
according to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Qualifier:
according to guideline
Guideline:
EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
GLP compliance:
yes (incl. QA statement)
Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
Two 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 2.36 or 2.53 kg and were twelve to twenty weeks old. After an acclimatisation 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 Certified 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.Two 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 2.36 or 2.53 kg and were twelve to twenty weeks old. After an acclimatisation 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 Certified 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.
Type of coverage:
semiocclusive
Preparation of test site:
clipped
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
0.5 ml
Duration of treatment / exposure:
4 hours
Observation period:
72 hours
Number of animals:
2
Details on study design:
On the day before the test each of a group of two 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 Spirits.
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:

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


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

Any other skin reactions and clinical signs of toxicity, if present, were also recorded. Individual bodyweights were recorded on Day 0 (the day of dosing) and at the end of the observation period.
Irritation parameter:
primary dermal irritation index (PDII)
Basis:
mean
Time point:
other: 1 hour
Score:
0.8
Max. score:
3
Reversibility:
fully reversible
Irritation parameter:
erythema score
Basis:
mean
Time point:
24/48/72 h
Score:
2
Reversibility:
not specified
Irritation parameter:
edema score
Basis:
mean
Time point:
24/48/72 h
Score:
2
Reversibility:
not specified

Individual Skin Reactions        
Skin Reaction Observation Time (following patch removal) Individual Scores- Rabbit Number and Sex Total
72236 Male 72237 Male
Erythema/Eschar
Formation
Immediately
1 Hour
24 Hours
48 Hours
72 Hours
2
1
1
1
0
2
2
1
1
0
( 2 )
( 3 )
2
( 2 )
0
Oedema
Formation
Immediately
1 Hour
24 Hours
48 Hours
72 Hours
1
1
0
0
0
2
1
1
0
0
( 3 )
 ( 2 )
1
( 0 )
0
Sum of 24 and 72-Hour Readings (S)                   3
Primary Irritation Index (S/4)                                  3/4=0.8
Classification                                                       MILD IRRITANT
Interpretation of results:
slightly irritating
Remarks:
Migrated information Criteria used for interpretation of results: OECD GHS
Conclusions:
The test item produced a primary irritation index of 0.8 and was classified as a mild 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 to the skin of the New Zealand White rabbit. A single 4-Hour, semi-occluded application of the test item to the intact skin of two rabbits produced well-defined erythema and very slight to slight oedema. Both treated skin sites appeared normal at the 72-Hour observation. The test item produced a primary irritation index of 0.8 and was classified as a mild irritant to rabbit skin according to the Draize classification scheme. No corrosive effects were noted.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (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:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: The study was conducted in a GLP facility using OECD guidelines
Qualifier:
according to guideline
Guideline:
EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)
Qualifier:
according to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
GLP compliance:
yes (incl. QA statement)
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
Two 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 2.37 or 2.62 kg and were twelve to twenty weeks old. After an acclimatisation 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 Certified 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°C 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.
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
0.1 ml
Duration of treatment / exposure:
72 hours
Observation period (in vivo):
72 hours
Number of animals or in vitro replicates:
2
Details on study design:
Immediately before the start of the test, both eyes of the provisionally selected test rabbits were examined for evidence of ocular irritation or defect with the aid of a light source from a standard ophthalmoscope. Only animals free of ocular damage were used. Initially, a single rabbit was treated. A volume of 0.1 ml of the test item was placed into the conjunctival sac of the right eye, formed by gently pulling the lower lid away from the
eyeball. The upper and lower eyelids were held together for about one second immediately after treatment, to prevent loss of the test item, and then released. The left eye remained untreated and was used for control purposes. Immediately after administration of the test item, an assessment of the initial pain reaction was made according to the six point scale shown in Appendix 1. After consideration of the ocular responses produced in the first treated animal, a second animal was treated.Any clinical signs of toxicity, if present, were also recorded. Individual bodyweights were recorded on Day 0 (the day of dosing) and at the end of the observation period.
Irritation parameter:
overall irritation score
Basis:
animal #1
Time point:
other: 72 hours
Score:
0
Max. score:
8
Reversibility:
fully reversible
Irritation parameter:
overall irritation score
Basis:
animal #2
Time point:
other: 72 hours
Score:
0
Max. score:
10
Reversibility:
fully reversible
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Reversibility:
not specified
Irritation parameter:
iris score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Reversibility:
not specified
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
24 h
Score:
6
Reversibility:
not specified
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
48 h
Score:
4
Reversibility:
not specified
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
72 h
Score:
0
Reversibility:
not specified
Irritation parameter:
chemosis score
Basis:
mean
Time point:
24/48/72 h
Reversibility:
not specified
Remarks on result:
not measured/tested
Irritant / corrosive response data:
Residual test item was noted around both treated eyes during the study.
- No corneal or iridial effects were noted during the study.
- Moderate conjunctival irritation was noted in both treated eyes one hour after treatment.
- Moderate conjunctival irritation was noted in one treated eye with minimal conjunctival
- irritation noted in the other treated eye at the 24-Hour observation. Minimal conjunctival
- irritation was noted in both treated eyes at the 48-Hour observation.
- Alopecia around the treated eye was noted in one animal at the 24, 48 and 72-Hour observations.
- Both treated eyes appeared normal at the 72-Hour observation.
Interpretation of results:
slightly irritating
Remarks:
Migrated information Criteria used for interpretation of results: OECD GHS
Conclusions:
The test item produced a maximum group mean score of 9.0 and was classified as a mild irritant (Class 4 on a 1 to 8 scale) to the rabbit eye according to a modified Kay and Calandra classification system
Executive summary:

The study was performed to assess the irritancy potential of the test item to the eye of the New Zealand White rabbit. A single application of the test item to the non-irrigated eye of two rabbits produced moderate conjunctival irritation. Alopecia around the treated eye was also noted in one animal. Both treated eyes appeared normal at the 72-Hour observation. The test item produced a maximum group mean score of 9.0 and was classified as a mild irritant (Class 4 on a 1 to 8 scale) to the rabbit eye according to a modified Kay and Calandra classification system.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Additional information

Skin Irritation:

The study was performed to assess the irritancy potential of the test item to the skin of the New Zealand White rabbit. A single 4-Hour, semi-occluded application of the test item to the intact skin of two rabbits produced well-defined erythema and very slight to slight oedema. Both treated skin sites appeared normal at the 72-Hour observation. The test item produced a primary irritation index of 0.8 and was classified as a mild irritant to rabbit skin according to the Draize classification scheme. No corrosive effects were noted.

Eye Irritation:

The study was performed to assess the irritancy potential of the test item to the eye of the New Zealand White rabbit. A single application of the test item to the non-irrigated eye of two rabbits produced moderate conjunctival irritation. Alopecia around the treated eye was also noted in one animal. Both treated eyes appeared normal at the 72-Hour observation. The test item produced a maximum group mean score of 9.0 and was classified as a mild irritant (Class 4 on a 1 to 8 scale) to the rabbit eye according to a modified Kay and Calandra classification system.


Effects on skin irritation/corrosion: slightly irritating

Effects on eye irritation: slightly irritating

Justification for classification or non-classification

The irritation scores in the eye and skin irritation studies do not meet the criteria for classification according to EU CLP.