Registration Dossier

Administrative data

Endpoint:
skin irritation: in vivo
Type of information:
migrated 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: The analogue OS1600 which shares the same functional group with OS3600, also has comparable values for the relevant molecular properties for skin irritation. The study has been conducted according to OECD guidance under GLPs.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2012
Report Date:
2012

Materials and methods

Test guidelineopen allclose all
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)

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): OS1600
- Molecular formula (if other than submission substance): C16H33N3O3Si
- Molecular weight (if other than submission substance): 343.55
- Smiles notation (if other than submission substance): CCCC(\C)=N\O[Si](C)(O\N=C(/C)CCC)O\N=C(\C)CCC
- InChl (if other than submission substance): Mixture of all possible stereoisomers.
- Structural formula attached as image file (if other than submission substance): see Fig.

Test animals

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.

Test system

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.

Results and discussion

In vivo

Resultsopen allclose all
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.

Any other information on results incl. tables

The data matrix is included in the reporting format attached.

Applicant's summary and conclusion

Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Based on the read-across approach from the analogue substance OS1600, OS3600 was determined to be not irritating to the skin.
Executive summary:

The skin irritation test was performed on the analogue substance OS1600 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. 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 read-across approach was applied and the substance OS3600 was determined to be not irritating to the skin.