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
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Guideline study performed to GLP
Qualifier:
according to
Guideline:
other: Annex V
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
Source: David Percival Ltd
Environmental conditions:
Housed individually in suspended solid floor cages.
Temperature: 17-23ºC
humidity: 30-70%
Acclimitisation period: 5 days
Air changes: 15 per hour
Lighting: 12 hours continuous light and twelve hours darkness
Free access to mains drinking water and food
Type of coverage:
semiocclusive
Preparation of test site:
clipped
Vehicle:
other: None
Controls:
not specified
Amount / concentration applied:
0.5 ml under a 2.5 x 2.5 cm cotton gauze.
Duration of treatment / exposure:
4 h
Observation period:
Approximatley one hour following the removal of the patches and 24, 48 and 72 hours later, the test sites were observed for evidence of primary irritation and scored.
Number of animals:
3
Details on 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 material was introduced under a 2.5 x 2.5 cm cotton gauze patch and placed in position on the shorn skin. The patch was secured in position with a strip of surgical adhesive tape. To prevent the animal interferring with the patches, the trunk of each animal was wrapped in an elasticated corset and the animals were returned to their cages.
Four hours after application the corset and patches were removed from each animal and any residual test material removed by gentle swabbing with cotton wool soaked in distilled water.
Irritation parameter:
erythema score
Basis:
animal #1
Remarks:
(mean score 1)
Time point:
other: overall at 24, 48 and 72 h
Score:
1
Irritation parameter:
erythema score
Basis:
animal #2
Remarks:
(mean score 2)
Time point:
other: overall at 24, 48 and 72 h
Score:
1
Irritation parameter:
erythema score
Basis:
animal #3
Remarks:
(mean score 3)
Time point:
other: overall at 24, 48 and 72 h
Score:
1
Irritation parameter:
erythema score
Max. score:
1
Remarks on result:
other: Max. duration: 72 d; Max. value at end of observation period: 0 (related to all animals)
Irritation parameter:
edema score
Basis:
animal #1
Remarks:
(mean score 1)
Time point:
other: overall at 24, 48 and 72 h
Score:
1
Irritation parameter:
edema score
Basis:
animal #2
Remarks:
(mean score 2)
Time point:
other: overall at 24, 48 and 72 h
Score:
1
Irritation parameter:
edema score
Basis:
animal #3
Remarks:
(mean score 3)
Time point:
other: overall at 24, 48 and 72 h
Score:
0.66
Irritation parameter:
edema score
Max. score:
1
Remarks on result:
other: Max. duration: 72 d; Max. value at end of observation period: 0 (related to all animals)
Irritant / corrosive response data:
Reversibility of any observed effect: Changes fully reversible within 7 days
Other effects:
None
Interpretation of results:
other: not classified
Conclusions:
The test material produced a primary irritation index of 1.8 and was classified as a mild irritant to rabbit skin according to the Draize classification scheme. No corrosive effects were noted.
Executive summary:

A GLP study was performed in accordance with OECD 404 in order to assess the irritancy potential of Inhibitor AHM P500 to the skin of the New Zealand White Rabbit. 

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 material was introduced under a 2.5 x 2.5 cm cotton gauze patch and placed in position on shorn skin. The patch was secured in position with a strip of surgical adhesive tape. To prevent the animal interfering with the patches, the trunk of each animal was wrapped in an elasticated corset and the animals returned to their cages.

Four hours after application, the corset and patches were removed from each animal and any residual test material removed by gentle swabbing with cotton wool soaked in distilled water.

The single 4-hour semi-occluded application of the test material to the intact skin of three rabbits produced very slight erythema and very slight oedema. Slight desquamation was also noted. One treated skin site appeared normal at the 7-day observation.

The test material produced a primary irritation index of 1.8 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:
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:
27th October - 7th November 2005
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Guideline study performed to GLP
Qualifier:
according to
Guideline:
other: Annex V
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes
Species:
other: Rabbit (New Zealand White)
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
Source: David Percival Ltd
Environmental conditions:
Housed individually in suspended solid floor cages.
Temperature: 17-23ºC
humidity: 30-70%
Acclimitisation period: 5 days
Air changes: 15 per hour
Lighting: 12 hours continuous light and twelve hours darkness
Free access to mains drinking water and food
Vehicle:
not specified
Controls:
not specified
Amount / concentration applied:
0.1 ML
Observation period (in vivo):
Assessment of occular damage/irritation was made approximatley 1 hour, 24,48 and 72 hours following treatment. Any other occular effects were also noted. Examination of the eye was facilitated by the use of a light source from a standard opthalmoscope.
An additional observation was made in one treated eye on Day 7 to assess the reversibility of the occular effects.
Number of animals or in vitro replicates:
3
Details on study design:
Initially, a single rabbit was treated. A volume of 0.1 ml of the test material 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 immediatley after treatment, to prevent loss of the test material, and then released. The left eye remained untreated and was used for control purposes. Immediatley after administration of the test material, an assessment of the initial pain reaction was made.
After consideration of the ocular responses produced in the first treated animal , two additional animals were treated. In order to minimise pain on application of the test material , one drop of local anaethetic was instilled into both eyes of the final animal 1 to 2 minutes before treatment.
Irritation parameter:
conjunctivae score
Remarks:
(redness)
Time point:
other: 72 hrs
Score:
ca. 0.33
Max. score:
1
Reversibility:
fully reversible within: 7 days
Remarks on result:
other: Max value at 72 hrs in one animal, 'score' calculated as average across 3 animals at the time point specified.
Irritation parameter:
chemosis score
Time point:
other: 72 hrs
Score:
ca. 0.33
Max. score:
1
Reversibility:
fully reversible within: 72 hours
Remarks on result:
other: Max. duration: 48 h; Max. value at end of observation period: 0 (related to all animals). 'score' calculated as average across 3 animals at the time point specified.
Irritation parameter:
cornea opacity score
Time point:
other: 72 hrs
Score:
ca. 0.33
Max. score:
1
Reversibility:
fully reversible within: 7 days
Remarks on result:
other: 'score' calculated as average across 3 animals at the time point specified.
Irritation parameter:
iris score
Time point:
other: 72 hrs
Score:
ca. 0.33
Max. score:
1
Reversibility:
fully reversible within: 7 days
Remarks on result:
other: Max. duration: 72 h; Max. value at end of observation period: 0 (related to all animals), 'score' calculated as average across 3 animals at the time point specified.
Irritant / corrosive response data:
Reversibility of any observed effect: Changes fully reversible within 7 days
Other effects:
Brown coloured staining of the fur was noted around the treated eyes during the study.
Interpretation of results:
not classified
Remarks:
Migrated information
Conclusions:
The test material produced a maximum group mean score of 9.0 and was classified as a mild irritant (Class 4 on a 1-8 scale) to the rabbit eye according to a modified Kay and Calandra classification system.
Executive summary:

A GLP study in accordance with OECD guideline 405 was performed in order to assess the irritancy potential of Inhibitor AHM P500 to the eye of the New Zealand White Rabbit.

A single application of the test material to the non-irrigated eye of three rabbits produced scattered or diffuse corneal capacity, iridial inflammation and minimal conjunctival irritation. One treated eye appeared normal at the 48 hour observation, one treated eye appeared normal at the 72 hour observation and the remaining treated eye appeared normal at the 7 day observation.

The test material produced a maximum group mean score of 9.0 and was classified as a mild irritant (Class 4 on a 1-8 scale) to the rabbit eye according to a modified Kay and Calandra classification system.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Additional information

Justification for selection of skin irritation / corrosion endpoint:
Single guideline GLP study available.

Justification for selection of eye irritation endpoint:
Single guideline GLP study available.

Effects on eye irritation: slightly irritating

Justification for classification or non-classification

Based upon the above information the substance does not meet the criteria for classification as set out by both 67/548/EEC and EC Regulation 1272/2008. No classification with respect to skin irritation or eye irritation is required.