Registration Dossier

Administrative data

Description of key information

Skin irritation:

Key study: A study was performed to assess the skin irritation potential of OS 1600 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 seven or nine days. The means of scores for these reactions at approximately 24, 48 and 72 hours after the end of administration were Erythema score 1 (fully reversible) and Oedema score 0 in all three animals. Based on these results, the test substance was determined to be not irritating to the skin.

Eye irritation:

Key study: Read-across approach from experimental data on the analogue substance MPKO: An acute eye irritation/corrosion study was performed in rabbit according to OECD Guideline 405 (GLP study). Based on the read-across approach from the experimental data on the analogue substance MPKO, the hydrolysis product of OS1600 (irritating to the eye based on the following mean 24 -72 h scores for each animal: Corneal opacity: 0, 1.0, 1.0; Iris: 0, 0.7, 0.7; Redness: 0,7, 2.3, 2.0; Chemosis: 0.3, 1.3, 1.3, with all the effects reversible by day 14), the substance OS1600 was determined also to be irritating to the eyes.

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:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
no
Qualifier:
according to
Guideline:
EPA OPPTS 870.2500 (Acute Dermal Irritation)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
Animals for this study were selected from a stock supply of healthy adult rabbits of the New Zealand White strain. They were in the weight range of 2.69 to 3.62 kg and 30 or 35 weeks of age, prior to treatment (Day 1). All rabbits were acclimatised to the experimental environment for a period of at least 12 or 13 weeks prior to the start of the study.
The rabbits were housed individually in plastic cages with perforated floors. Each rabbit was offered 125 g of a standard laboratory rabbit diet per day; drinking water was provided ad libitum. The batch of diet used for the study was analysed for nutrients, possible contaminants and micro-organisms likely to be present in the diet and which, if in excess of specified amounts, might have an undesirable effect on the test system. The animals were given a dietary supplement of hay.
During the acclimatisation and study period the animals were given small soft white untreated wood blocks for environmental enrichment.
Results of routine physical and chemical examination of drinking water, as conducted by the supplier are made available to Huntingdon Life Sciences Limited.
Animal room environmental controls were set to maintain temperature within the range 16 to 20°C, and relative humidity within 40 to 70%. These environmental parameters were recorded and the permanent record archived with other departmental raw data. Lighting was controlled by means of a time switch to give 12 hours of artificial light (06:00 to 18:00 GMT) in each 24 hour period.
Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Controls:
yes, concurrent no treatment
Amount / concentration applied:
0.5 mL as supplied
Duration of treatment / exposure:
4 hours
Observation period:
7 or 9 days
Number of animals:
3 rabbits
Details on study design:
On the day before application of the test substance, hair was removed with clippers from the dorso-lumbar region of each rabbit exposing an appropriate sized area of skin.

Approximately 0.5 mL of the test substance was applied under a 2-ply 25 mm x 25 mm porous gauze pad secured with ‘blenderm’ surgical tape to intact skin sites on three animals. An additional site was similarly treated with the exception of test substance and acted as a control.

A single animal (number 4) received three exposures of three minutes, one or four hour’s duration in a step-wise manner and acted as a preliminary screen. In the absence of a severe effect on removal of the dressings the next exposure was initiated.

For exposures of one hour or more each treatment site was covered with cotton wool and "Tubigrip" elasticated bandage dressing for the duration of the exposure period. The animals were returned to their cages immediately after treatment. At the end of the exposure period the semi-occlusive dressing and gauze pad were removed and the treatment site was washed with lukewarm water (30-40°C) to remove any residual test substance. The treated area was blotted dry with absorbent paper.
Irritation parameter:
erythema score
Basis:
animal #4
Time point:
other: 24, 48, 72 hrs
Score:
1
Max. score:
1
Reversibility:
fully reversible
Irritation parameter:
erythema score
Basis:
animal #5
Time point:
other: 24, 48, 72 hrs
Score:
1
Max. score:
1
Reversibility:
fully reversible
Irritation parameter:
erythema score
Basis:
animal #6
Time point:
other: 24, 48, 72 hrs
Score:
1
Max. score:
1
Reversibility:
fully reversible
Irritation parameter:
edema score
Basis:
animal #1
Time point:
other: 24, 48, 72 h
Score:
0
Max. score:
0
Irritation parameter:
edema score
Basis:
animal #2
Time point:
other: 24, 48, 72 h
Score:
0
Max. score:
0
Irritation parameter:
edema score
Basis:
animal #3
Time point:
other: 24, 48, 72 h
Score:
0
Max. score:
0
Irritant / corrosive response data:
Very slight erythema was evident at the test site of each animal throughout the first five days after bandage removal persisting in two animals on Day 7 and in one on Day 8. The test site of two animals was sticky to touch during the initial period after bandage removal. The test site of each animal was overtly normal nine days after bandage removal.
Interpretation of results:
GHS criteria not met
Conclusions:
The substance was determined to be not irritating to the skin.
Executive summary:

A study was performed to assess the skin irritation potential of OS 1600 to the rabbit in accordance with OECD Guideline 404. 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 seven or nine days. Very slight erythema was evident at the test site of each animal throughout the first five days after bandage removal persisting in two animals on Day 7 and in one on Day 8. The test site of two animals was sticky to touch during the initial period after bandage removal. The test site of each animal was overtly normal nine days after bandage removal. The means of scores for these reactions at approximately 24, 48 and 72 hours after the end of administration were Erythema score 1 and Oedema score 0 in all three animals. Based on these results, the test substance was determined to be not irritating to the skin.

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:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Read-across from an analogue substance for which a guideline study (Klimish =1) is available.
Justification for type of information:
REPORTING FORMAT FOR THE ANALOGUE APPROACH
See attached reporting format.
Reason / purpose:
read-across source
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
24/48/72 h
Score:
0.67
Max. score:
1
Reversibility:
fully reversible within: 7 days
Remarks on result:
other: Results with the analogue substance, read-across is applied.
Irritation parameter:
iris score
Basis:
mean
Time point:
24/48/72 h
Score:
0.5
Max. score:
0.7
Reversibility:
fully reversible within: 72 hours.
Remarks on result:
other: Results with the analogue substance, read-across is applied.
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
mean
Time point:
24/48/72 h
Score:
1.67
Max. score:
2.3
Reversibility:
fully reversible within: 14 days
Remarks on result:
other: Results with the analogue substance, read-across is applied.
Irritation parameter:
conjunctivae score
Remarks:
chemosis
Basis:
mean
Time point:
24/48/72 h
Score:
ca. 1
Max. score:
1.3
Reversibility:
fully reversible within: 7 days.
Remarks on result:
other: Results with the analogue substance, read-across is applied.

The data matrix is included in the reporting format attached.

Interpretation of results:
Category 2 (irritating to eyes) based on GHS criteria
Remarks:
Based on CLP criteria.
Conclusions:
Based on the read-across approach from the analogue substance MPKO, OS1600 was determined to be irritating to the eyes.
Executive summary:

An acute eye irritation/corrosion study was performed with the analogue substance MPKO in rabbit according to OECD Guideline 405. Single samples of 0.1 mL of test item were instilled into one eye of each of three rabbits. Observations were made 1, 24, 48 and 72 hours and 7 and 14 days after instillation. Instillation of the test substance resulted in effects on the cornea, iris and conjuctivae. The corneal injury consisted of opacity (maximum grade 1) and epithelial damage (maximum 50% of the corneal area) in two (of the three) animals. The corneal injury had resolved within 7 days. Iridial irritation grade 1 was observed and had resolved within 24 hours in one animal and within 72 hours in the remaining animals. The irritation of the conjunctivae consisted of redness, chemosis and discharge and had completely resolved within 72 hours in one animal and within 14 days in the other two animals. The mean 24 -72 h scores for each animal were determined to be as follows: Corneal opacity: 0, 1.0, 1.0; Iris: 0, 0.7, 0.7; Redness: 0,7, 2.3, 2.0; Chemosis: 0.3, 1.3, 1.3. Based on these results, the read-across approach was applied and the substance OS1600 was determined to be irritating to the eyes.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Data waiving: In vitro/ ex vivo studies for both skin and eye irritation were considered scientifically unnecessary since there is adequate data from in vivo studies.

Skin irritation: The test substance was determined to be not irritating to the skin.

Eye irritation: Based on the read-across approach from the analogue substance MPKO, OS1600 was determined to be irritating to the eyes.

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: irritating

Justification for classification or non-classification

Skin irritation: Based on the results, the test item is considered to be not irritating to the skin in accordance with CLP Regulation EU No. 1272/2008, since no mean value ≥ 2,3 - ≤ 4,0 for erythema/eschar or for oedema was observed in at least 2 of 3 tested animals from gradings at 24, 48 and 72 hours after patch removal.

Eye irritation: Based on the results, the test item is classified as Eye damage Category 2, H319in accordance with CLP Regulation EU No. 1272/2008, since a positive response of conjunctival redness ≥ 2 (fully reversible) was observed in 2 of 3 tested animals as the mean scores following grading at 24, 48 and 72 hours after installation.