Registration Dossier

Administrative data

Description of key information

Skin irritation
The key study on skin irritation assessed the irritancy potential of the test material to the skin of the New Zealand White rabbit. The method used followed the recommendations of EU Method B.4 and OECD Guideline 404 (Acute Dermal Irritation / Corrosion). A single 4-hour, semi-occluded application of the test material to the intact skin of three rabbits produced no evidence of skin irritation. The test material 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.
Similar results were obtained in supporting studies.
Respiratory irritation
No indication of respiratory irritation from handling and use.
Eye irritation
The key study assessed the irritancy potential of the test material to the eye of the New Zealand White rabbit. The study followed EU Method B.5 and OECD Guideline 405 (Acute Eye Irritation / Corrosion). A single application of the test material to the non-irrigated eye of three rabbits produced a dulling of the normal lustre of the corneal surface, diffuse corneal opacity, iridial inflammation and moderate to severe conjunctival irritation. The test material produced a maximum group mean score of 34.3 and was classified as a moderate irritant (Class 5 on a 1 to 8 scale) to the rabbit eye according to a modified Kay and Calandra classification system.
Similar results were obtained in supporting studies.

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)
Qualifier:
according to
Guideline:
EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
Deviations:
no
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Remarks:
Safepharm Laboratories Ltd.
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Age at study initiation: Twelve to sixteen weeks
- Weight at study initiation: 2.61 to 2.96 kg
- Housing: The animals were individually housed in suspended metal cages
- Diet: Ad libitum
- Water: Ad libitum
- Acclimation period: Minimum acclimatisation period of five days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17 to 23
- Humidity (%): 30 -70 (any occasional deviations from these targets were considered not to have affected the purpose or integrity of the study)
- Air changes (per hr): Fifteen changes per hour
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES:
- From: 05 April 2000
- To: 13 April 2000
Type of coverage:
semiocclusive
Preparation of test site:
clipped
Vehicle:
water
Controls:
no
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 g

VEHICLE
- Amount applied: 0.5 ml
Duration of treatment / exposure:
4 hour exposure
Observation period:
Approximately one hour following the removal of the patches, and 24, 48 and 72 hours later
Number of animals:
1 Male, 2 Females
Details on study design:
TEST SITE
- Area of exposure: 2.5 cm x 2.5 cm
- Type of wrap if used: Cotton gauze patch secured in position with a strip of surgical adhesive tape (BLENDERM: approximate size 2.5 cm x 4.0 cm). To prevent the animals interfering with the patches, the trunk of each rabbit was wrapped in an elasticated corset (TUBIGRIP).

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Residual test material was removed by gentle swabbing with cotton wool soaked in distilled water.
- Time after start of exposure: 4 hours

SCORING SYSTEM:
- Draize J H, (1977) "Dermal and Eye Toxicity Tests" In: Principles and Procedures for Evaluating the Toxicity of Household Substances, National Academy of Sciences, Washington DC p.31.
Irritation parameter:
primary dermal irritation index (PDII)
Basis:
mean
Time point:
other: 24 and 72 hours
Score:
0
Max. score:
0
Reversibility:
other: Not applicable
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 24, 48 and 72 hours
Score:
0
Max. score:
0
Reversibility:
other: Not applicable
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 24, 48 and 72 hours
Score:
0
Max. score:
0
Reversibility:
other: Not applicable
Irritant / corrosive response data:
See table 1 below.

Table 1: Individual irritation scores

Individual scores - rabbit number and sex (body weight kg)
Skin reaction Observation time (hours) 133 Male (2.96) 174 Female (2.62) 63 Female (2.61) Total
Erythema/eschar formation 1 0 0 0 0
24 0 0 0 0
72 0 0 0 0
48 0 0 0 0
Oedema formation 1 0 0 0 0
24 0 0 0 0
48 0 0 0 0
72 0 0 0 0
Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The test material 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:

A study was performed to assess the irritancy potential of the test material to the skin of the New Zealand White rabbit. The method used followed the recommendations of EU Method B.4 and OECD Guideline 404 (Acute Dermal Irritation / Corrosion). A single 4-hour, semi-occluded application of the test material to the intact skin of three rabbits produced no evidence of skin irritation. The test material produced a primary irritation index of 0.0 and was classified as nonirritant 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
Reliability:
1 (reliable without restriction)
Qualifier:
according to
Guideline:
EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)
Deviations:
no
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Remarks:
Safepharm Laboratories Ltd.
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Age at study initiation: 12 to 16 weeks
- Weight at study initiation: 2.54 - 2.97 kg
- Housing: The animals were individually housed in suspended metal cages.
- Diet: Ad libitum
- Water: Ad libitum
- Acclimation period: Minimum acclimatisation period of five days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 16 - 20
- Humidity (%): 43 - 48
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: Fro
- From: 25 April 1990
- To: 3 May 1990
Vehicle:
unchanged (no vehicle)
Controls:
yes, concurrent no treatment
Amount / concentration applied:
TEST MATERIAL
- Amount applied: 0.1 g
Duration of treatment / exposure:
The right eye of each animal was treated. The left eye remained untreated and was used for control purposes.
Observation period (in vivo):
1, 24, 48 and 72-hour and 7 days after exposure
Number of animals or in vitro replicates:
3 female animals. Immediately before the start of the test, both eyes of the three provisionally selected test rabbits were examined for evidence of ocular irritation or defect with the aid of a light source from a standard ophthalmoscope. Animals showing evidence of ocular lesions were rejected and replaced.
Details on study design:
SCORING SYSTEM:
- Draize J.H. 1959, Association of Food and Drug Officials of the United States, Austin, Texas, "The Appraisal of the Safety of Chemicals in Foods, Drugs and Cosmetics"
- Kay J.H. and Calandra J.C., J. Soc. Cosmet. Chern., 1962 13 281-289

TOOL USED TO ASSESS SCORE:
- Standard ophthalmoscope.
Irritation parameter:
maximum mean total score (MMTS)
Basis:
mean
Time point:
other: 1 hour
Score:
19.7
Max. score:
21
Irritation parameter:
maximum mean total score (MMTS)
Basis:
mean
Time point:
other: 24 hours
Score:
34.3
Max. score:
41
Irritation parameter:
maximum mean total score (MMTS)
Basis:
mean
Time point:
other: 48 hours
Score:
27.7
Max. score:
39
Irritation parameter:
maximum mean total score (MMTS)
Basis:
mean
Time point:
other: 72 hours
Score:
17.7
Max. score:
39
Irritation parameter:
maximum mean total score (MMTS)
Basis:
mean
Time point:
other: 7 days
Score:
0
Max. score:
0
Irritation parameter:
cornea opacity score
Basis:
animal #1
Time point:
other: 24, 48 and 72 hours
Score:
1
Max. score:
1
Reversibility:
fully reversible within: 7 days
Irritation parameter:
cornea opacity score
Basis:
animal #2
Time point:
other: 24, 48 and 72 hours
Score:
1
Max. score:
1
Reversibility:
fully reversible within: 7 days
Irritation parameter:
cornea opacity score
Basis:
animal #3
Time point:
other: 24, 48 and 72 hours
Score:
1
Max. score:
1
Reversibility:
not specified
Irritation parameter:
iris score
Basis:
animal #1
Time point:
other: 24, 48 and 72 hours
Score:
0.7
Max. score:
1
Reversibility:
fully reversible within: 7 days
Irritation parameter:
iris score
Basis:
animal #2
Time point:
other: 24, 48 and 72 hours
Score:
0.7
Max. score:
1
Reversibility:
fully reversible within: 7 days
Irritation parameter:
iris score
Basis:
animal #3
Time point:
other: 24, 48 and 72 hours
Score:
1
Max. score:
1
Reversibility:
not specified
Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
other: 24, 48 and 72 hours
Score:
1
Max. score:
2
Reversibility:
fully reversible within: 7 days
Irritation parameter:
conjunctivae score
Basis:
animal #2
Time point:
other: 24, 48 and 72 hours
Score:
1.7
Max. score:
2
Reversibility:
fully reversible within: 7 days
Irritation parameter:
conjunctivae score
Basis:
animal #3
Time point:
other: 24, 48 and 72 hours
Score:
2.7
Max. score:
3
Reversibility:
not specified
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
other: 24, 48 and 72 hours
Score:
0.3
Max. score:
1
Reversibility:
fully reversible within: 7 days
Irritation parameter:
chemosis score
Basis:
animal #2
Time point:
other: 24, 48 and 72 hours
Score:
1.7
Max. score:
2
Reversibility:
fully reversible within: 7 days
Irritation parameter:
chemosis score
Basis:
animal #3
Time point:
other: 24, 48 and 72 hours
Score:
2.3
Max. score:
3
Reversibility:
not specified
Irritant / corrosive response data:
The individual scores are presented. A dulling of the normal lustre of the corneal surface was noted in two treated eyes one hour after treatment. Diffuse corneal opacity was noted in all treated eyes at subsequent 24, 48 and 72-hour observations. Iridial inflammation was noted in all treated eyes one hour after treatment and at the 24 and 48-hour observations and in one treated eye at the 72-hour observation.
Moderate to severe conjunctival irritation was noted in all treated eyes one hour after treatment and at the 24-hour observation. Moderate conjunctival irritation continued to be noted in two treated eyes at the 48-hour observation and in one treated eye at the 72-hour observation.
Minimal conjunctival irritation was noted in one treated eye at the 48- hour observation and in another treated eye at the 72-hour observation.
Two treated eyes appeared normal seven days after treatment. The remaining animal was sacrificed for humane reasons following the 72-hour observation.
The test material produced a maximum group mean score of 34.3 and was classified as a moderate irritant (class 5 on a 1 to 8 scale) to the rabbit eye according to a modified Kay and Calandra classification system.
Interpretation of results:
irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Based on the results obtained in this study, group mean scores calculated (maximum group mean score of 34.3) and scoring according Kay and Calandra (1962) the test item was considered moderately irritant.
Executive summary:

A study was performed to assess the irritancy potential of the test material to the eye of the New Zealand White rabbit. The study followed EU Method B.5 and OECD Guideline 405 (Acute Eye Irritation / Corrosion).

A single application of the test material to the non-irrigated eye of three rabbits produced a dulling of the normal lustre of the corneal surface, diffuse corneal opacity, iridial inflammation and moderate to severe conjunctival irritation. The test material produced a maximum group mean score of 34.3 and was classified as a moderate irritant (Class 5 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)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Effects on eye irritation: highly irritating

Justification for classification or non-classification

Based on the data available the substance is classified and labeled as Eye irritation category 2, H319 Causes serious eye irritation according to Regulation 1272/2008/EEC (CLP) and Irritating Xi, R36 Irritating to eyes according to Directive 67/548/EEC (DSD).