Registration Dossier

Administrative data

Description of key information

Skin irritation. Key study:  Test method OECD 404. GLP study. The test item was not irritating to the skin under test conditions.
Eye irritation. Key study: Test method EU method B.5. GLP study. The test item was not irritating to the eye under test conditions.

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: Test method according to OECD 404. GLP study.
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Qualifier:
according to
Guideline:
EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Type of coverage:
semiocclusive
Preparation of test site:
clipped
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied: 0.5 mL.
Duration of treatment / exposure:
4 hours.
Observation period:
11 days because the reactions resolved in all animals within this period.
Number of animals:
3.
Details on study design:
SCORING SYSTEM: Local dermal irritation was assessed using the prescribed numerical system:
Erythema and Eschar formation
No erythema: 0
Very slight erythema (barely perceptible): 1
Well defined erythema: 2
Moderate to severe erythema: 3
Severe erythema (beef redness) to slight eschar formation (injuries in depth) preventing grading of erythema: 4

Oedema formation
No oedema: 0
Very slight oedema (barely perceptible): 2
Moderate oedema (raised approximately 1 mm): 3
Severe oedema (raised more than 1 mm and extending beyond area of exposure: 4
Irritation parameter:
erythema score
Basis:
animal #1
Remarks:
(mean score 1)
Time point:
other: 24, 48 and 72 h.
Score:
2
Irritation parameter:
erythema score
Basis:
animal #2
Remarks:
(mean score 2)
Time point:
other: 24, 48 and 72 h.
Score:
1.66
Irritation parameter:
erythema score
Basis:
animal #3
Remarks:
(mean score 3)
Time point:
other: 24, 48 and 72 h.
Score:
0.33
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 24, 48 and 72 h.
Score:
1.33
Max. score:
2
Reversibility:
fully reversible within: 11 days
Irritation parameter:
edema score
Basis:
animal #1
Remarks:
(mean score 1)
Time point:
other: 24, 48 and 72 h.
Score:
1.33
Irritation parameter:
edema score
Basis:
animal #2
Remarks:
(mean score 2)
Time point:
other: 24, 48 and 72 h.
Score:
0.66
Irritation parameter:
edema score
Basis:
animal #3
Remarks:
(mean score 3)
Time point:
other: 24, 48 and 72 h.
Score:
0
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 24, 48 and 72 h.
Score:
0.663
Max. score:
2
Reversibility:
fully reversible within: 7 days
Irritant / corrosive response data:
Very slight to well-defined redness with or without very slight to slight swelling was seen in all three animals. This was accompanied by dryness and sloughing of the skin.
Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The substance was determined to be not an irritant to the skin.
Executive summary:

A study was performed to assess the skin irritation potential of OS 2200 to the rabbit in accordance with OECD Guideline 404 (GLP study). Three rabbits received a single four hour, semi-occlusive, dermal administration of approximately 0.5 mL of the test substance as supplied and were observed for eleven days (fully reversible). Very slight to well-defined redness with or without very slight to slight swelling was seen in all three animals. This was accompanied by dryness and sloughing of the skin. These reactions resolved in all animals within 11 days of the exposure. The observed mean scores (24 -72h) for each animal were 2, 1.66 and 0.33 for erythema and 1.33, 0.66 and 0 for oedema. The test item was determined to be not irritating to the skin according to CLP Regulation.

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:
9 May to 18 May, 1995
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Test method according to EU method B.5. GLP study.
Qualifier:
according to
Guideline:
EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)
Version / remarks:
Eye irritation
Deviations:
no
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Froxfield (U.K.) Ltd., Petersfield, Hampshire, England.
- Age at study initiation: 12 to 14 weeks.
- Weight at study initiation: 2.8 to 3.2kg.
- Housing: individually housed in plastic cages with perforated floors.
- Diet (e.g. ad libitum): Ad libitum. Standard laboratory diet SDS Stanrab (P) rabbit diet.
- Water (e.g. ad libitum): Ad libitum.
- Acclimation period: All rabbits were acclimatised to the experimental environment.

ENVIRONMENTAL CONDITIONS
- Temperature : 19ºC.
- Humidity : 30-70%.
- Air changes (per hr): 19 per hour.
- Photoperiod (hrs dark / hrs light): 12hours dark/12 hours artificial light.
Vehicle:
unchanged (no vehicle)
Controls:
yes, concurrent no treatment
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1mL/eye/rabbit.
Duration of treatment / exposure:
The eyelids were gently held together for one second before releasing.
Observation period (in vivo):
7 days
Number of animals or in vitro replicates:
3
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing: After instillation, the eyelids were gently held together for one second before releasing

SCORING SYSTEM:
Ocular irritation was assessed using the prescribed numerical system:
Cornea
Opacity: degree of density (area most dense taken for reading)
No ulceration or opacity 0
Scattered or diffuse areas of opacity (other than slight dulling of normal lustre), details of iris clearly visible 1
Easily discernible translucent areas, details of iris slightly obscured 2
Nacreous areas, no details of iris visible, size of pupil barely discernible 3
Opaque cornea. iris not discernible through the opacity 4
Iris
Normal 0
Markedly deepened rugae, congestion, swelling, moderate circumcorneal hyperaemia or injection, any of these or combination of any thereof, iris still reacting to light (sluggish reaction is positive) 1
No reaction to light, haemorrhage, gross destruction (any or all of these) 2

Conjunctivae
Redness (refers to the most severe reading of palpebral and bulbar conjunctivae, as compared to the control eye)
Blood vessels normal 0
Some blood vessels definitely hyperaemic (injected) 1
Diffuse, crimson colour, individual vessels not easily discernible 2
Diffuse beefy red 3
Chemosis (lids and/or nictating membranes)
No swelling 0
Any swelling above normal (includes nictating membranes) 1
Obvious swelling with partial eversion of lids 2
Swelling with lids about half-closed 3
Swelling with lids more than half-closed 4

TOOL USED TO ASSESS SCORE: Hand-slit lamp.
Irritation parameter:
cornea opacity score
Basis:
animal #1
Time point:
other: 24-72h
Score:
0.7
Max. score:
1
Reversibility:
fully reversible within: 3 days
Irritation parameter:
iris score
Basis:
animal #1
Time point:
other: 24-72h
Score:
0
Max. score:
0
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
animal #1
Time point:
other: 24-72h
Score:
0.7
Max. score:
1
Reversibility:
fully reversible within: 3 days
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
other: 24-72h
Score:
0.3
Max. score:
1
Reversibility:
fully reversible within: 2 days
Irritation parameter:
cornea opacity score
Basis:
animal #2
Time point:
other: 24-72h
Score:
0.7
Max. score:
1
Reversibility:
fully reversible within: 3 days
Irritation parameter:
iris score
Basis:
animal #2
Time point:
other: 24-72h
Score:
0
Max. score:
0
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
animal #2
Time point:
other: 24-72h
Score:
0.7
Max. score:
1
Reversibility:
fully reversible within: 3 days
Irritation parameter:
chemosis score
Basis:
animal #2
Time point:
other: 24-72h
Score:
0.7
Max. score:
1
Reversibility:
fully reversible within: 3 days
Irritation parameter:
cornea opacity score
Basis:
animal #3
Time point:
other: 24-72h
Score:
1
Max. score:
1
Reversibility:
fully reversible within: 7 days
Irritation parameter:
iris score
Basis:
animal #3
Time point:
other: 24-72h
Score:
0
Max. score:
0
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
animal #3
Time point:
other: 24-72h
Score:
1.3
Max. score:
2
Reversibility:
fully reversible within: 4 days
Irritation parameter:
chemosis score
Basis:
animal #3
Time point:
other: 24-72h
Score:
1
Max. score:
2
Reversibility:
fully reversible within: 3 days
Irritant / corrosive response data:
Corneal opacification was seen in all three animals. Stripping of the epithelial cells from the corneal surface was seen in one animal one hour after, dosing only. No iridial inflammation was observed. A diffuse crimson colouration of the conjunctiva was seen in all three animals and was accompanied in one animal by obvious swelling with partial eversion of the eyelids. The eyes were normal 3 or 7 days after instillation.
Other effects:
There were no signs of toxicity or ill health in any rabbit during the observation period.

Table 1. Ocular reactions observed after instillation of OS-2200

Time after instillation

Day after instillation

Rabbit

Region of eye

1 hour

1

2

3

4

7

816*

Cornea

D

1

1

0

0

0

Iris

0

0

0

0

0

0

Conjunctiva

Redness

2

1

1

0

0

0

Chemosis

1

1

0

0

0

0

817

Cornea

aD

1

1

0

0

0

Iris

0

0

0

0

0

0

Conjunctiva

Redness

2

1

1

0

0

0

Chemosis

1

1

1

0

0

0

800

Cornea

D

1

1

1

1

0

Iris

0

0

0

0

0

0

Conjunctiva

Redness

2

2

1

1

0

0

Chemosis

1

2

1

0

0

0

*: Pilot animal

a Stripping of epithelial cells from the corneal surface

D Dulling

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The substance was determined to be not an irritant to the eye.
Executive summary:

An ocular irritation study was performed according to EU method B.5 (GLP study). Eye irritation was assessed by instilling 0.1mL of OS-2200 into one eye of three rabbits. The contralateral eye served as control. The eyes were observed for signs of irritation for 7 days after exposure. Corneal opacity was observed in all three animals. No irritation of the iris occurred. A diffuse crimson discoloration of the tissue surrounding the eye and lining the eyelids (conjunctiva) was noted in all three rabbits. This was accompanied by swelling and partial eversion of the eyelids in one animal. These effects lasted from 3 to 7 days. The test item was determined to be not irritating to eyes according to CLP Regulation.

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

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Skin irritation. Key study: A study was performed to assess the skin irritation potential of OS 2200 to the rabbit in accordance with OECD Guideline 404 (GLP study). Very slight to well-defined redness with or without very slight to slight swelling was seen in all three animals. This was accompanied by dryness and sloughing of the skin. These reactions resolved in all animals within 11 days of the exposure. The observed mean scores (24 -72h) for each animal were 2, 1.66 and 0.33 for erythema and 1.33, 0.66 and 0 for oedema. The test item was determined to be not irritating to the skin.

Eye irritation. Key study: An ocular irritation study was performed according to EU method B.5 (GLP study). Corneal opacity was observed in all three animals. No irritation of the iris occurred. A diffuse crimson discoloration of the tissue surrounding the eye and lining the eyelids (conjunctiva) was noted in all three rabbits. This was accompanied by swelling and partial eversion of the eyelids in one animal. These effects lasted from 3 to 7 days. The test item was determined to be not irritating to the eye.


Justification for selection of skin irritation / corrosion endpoint:
Only one study available.

Justification for selection of eye irritation endpoint:
Only one study available.

Effects on eye irritation: slightly irritating

Justification for classification or non-classification

Skin irritation: Despite the occurrence of the skin effects, their severity and persistence are not sufficient to classify the substance as irritant to the skin in accordance with CLP Regulation (EC). No. 1272/2008 (mean values of < 2.3 for erythema and oedema, fully reversible by day 11). Moreover an acute dermal toxicity study was performed according to EU method B.3 under GLP conditions and its results did not indicate skin irritation up to 2000 mg/kg in rat.

Eye irritation: Despite the occurrence of the eye effects, their severity and persistence are not sufficient to classify the substance for eye irritation or corrosion in accordance with CLP Regulation (EC) No. 1272/2008 (mean values of <1 for opacity and iritis, mean values of <2 for redness and chemosis, fully reversible by day 7).