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Toxicological information

Skin sensitisation

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Administrative data

Endpoint:
skin sensitisation: in vivo (non-LLNA)
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: see 'Remark'
Remarks:
OS3600 undergoes rapid hydrolysis in aqueous to MPKO and the corresponding silanol. Silanols undergo continuous condensation reactions to produce higher molecular weight siloxanes which are considered biologically unavailable. Therefore, the observed toxicity is likely due to MPKO and their values are comparable. The study has been conducted according to OECD guidance under GLPs.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2009
Report Date:
2009

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 406 (Skin Sensitisation)
GLP compliance:
yes
Type of study:
Buehler test

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Methyl propyl ketoxime (MPKO)
- Molecular formula (if other than submission substance): C5H11NO
- Molecular weight (if other than submission substance): 101.15
- Smiles notation (if other than submission substance): C\C(CCC)=N\O
- InChl (if other than submission substance): Mixture of all possible stereoisomers
- Structural formula attached as image file (if other than submission substance): see Fig.

In vivo test system

Test animals

Species:
guinea pig
Strain:
Hartley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Elm Hill Breeding Labs, Chelmsford, MA
- Weight at study initiation: 296-350 g males, 292-352 g females
- Housing: Individually in suspended wire cages with paper bedding.
- Diet: ad libitum
- Water: ad libitum
- Acclimation for at least 5 days

ENVIRONMENTAL CONDITIONS
- Photoperiod (hrs dark / hrs light): 12 hrs

IN-LIFE DATES: From: 01/04/2009 To: 08/05/09

Study design: in vivo (non-LLNA)

Inductionopen allclose all
Route:
epicutaneous, occlusive
Vehicle:
corn oil
Concentration / amount:
induction - 100%, challenge 25%
Challengeopen allclose all
Route:
epicutaneous, occlusive
Vehicle:
corn oil
Concentration / amount:
induction - 100%, challenge 25%
No. of animals per dose:
Test groups: 10 M/10 F
Control group: 5 M/5 F
Details on study design:
RANGE FINDING TESTS: non irritating dose = 25%

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 3
- Exposure period: 6 hours
- Test groups: 10 males and 10 females
- Control group: 5 males and 5 females were untreated for the three week induction period and served as the naive control.
- Site: Left shoulder area (site 1)
- Frequency of applications: once a week
- Duration: 3 weeks
- Concentrations: 100% (0.4 ml)

B. CHALLENGE EXPOSURE
- No. of exposures: 1
- Day(s) of challenge: 2 weeks following last induction
- Exposure period: 6 hours
- Test groups: 10 males and 10 females
- Control group: 5 males and 5 females
- Site: Lower left dorsal area (site 3)
- Concentrations: 25%
- Evaluation (hr after challenge): 24 and 48 hours following patch removal.

OTHER: SCREEN (Site 2): Each animal received 4 concentrations of the test article, one/site. Each concentration (10, 25, 50 and 100%) under occlusive conditions. After 6 hours, the dams and test article were removed, the sites cleansed with distilled water and dried with soft towelling. Treated sites were examined and scored 24 and 48 hours following patch removal.

All the reactions were evaluated for Erythema:
Scoring code:
No erythema: 0
Very faint, usually non-confluent: 0.5
Faint, usually confluent: 1
Moderate 2
Strong, with or without edema: 3

All animals were observed once/day for mortality and toxicity.
Body weights were recorded pretest and at termination.
Positive control substance(s):
yes
Remarks:
HCA

Results and discussion

Positive control results:
Testing with 85% hexylcinnamaldehyde are confirmed in the laboratory every 6 months. Data from the study conducted in summer 2009 included with results as expected.

In vivo (non-LLNA)

Resultsopen allclose all
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
Induction 0%, challenge 25%
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. Dose level: Induction 0%, challenge 25%. No with. + reactions: 0.0. Total no. in groups: 10.0.
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
Induction 0%, challenge 25%
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: negative control. Dose level: Induction 0%, challenge 25%. No with. + reactions: 0.0. Total no. in groups: 10.0.
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
Induction 100%, challenge 25%
No. with + reactions:
0
Total no. in group:
20
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: Induction 100%, challenge 25%. No with. + reactions: 0.0. Total no. in groups: 20.0.
Reading:
2nd reading
Hours after challenge:
48
Group:
test group
Dose level:
Induction 100%, challenge 25%
No. with + reactions:
1
Total no. in group:
20
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: Induction 100%, challenge 25%. No with. + reactions: 1.0. Total no. in groups: 20.0.

Any other information on results incl. tables

Dermal observations: Induction: Erythema was absent to faint. Challenge: Erythema was absent to faint in the induced group and absent in the naive control group.

Body weights: Body weight changes were normal.

Systemic observations: In the treated group, one male and one female were observed with soiling of the anogenital area and one male was observed with soiling/wetness of the anogenital area. In the control group one male was observed with soiling of the anogenital area. All others appeared normal.

The data matrix is included in the reporting format attached.

Applicant's summary and conclusion

Interpretation of results:
not sensitising
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Based on the read-across approach from MPKO, OS3600 was determined to be non-sensitizer to the skin under conditions of this study.
Executive summary:

A skin sensitization study was performed with the analogue substance MPKO according to OECD Guideline 406 (GLP study). 15 male and 15 female Guinea pigs were used. In the first group, 10 animals per sex were induced with MPKO at 100% receiving 3 topical induction applications once a week for 3 weeks. Skin reactions were recorded after 24 and 48 patch removal. In the second group, the animals were not induced and served as a naive control. Based on preliminary screening results, 25% was chosen as the highest non-irritating concentration for the challenge and was administered to both groups two weeks after the third induction. The skin reactions were recorded at 24 and 48 hours following patch removal. After the induction, erythema was absent to faint. After the challenge, erythema was absent to faint in the induced group and absent in the naive control group. MPKO was determined to be non-sensitizer to the skin. Based on these results, the read-across approach was applied and OS3600 was also determined to be non-sensitizer to the skin.