Silicon boride oxide

Skin sensitisation

Administrative data

Endpoint:

skin sensitisation: in vivo (LLNA)

Type of information:

experimental study

Adequacy of study:

key study

Study period:

February 2012

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP and guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2012

Report date:

2012

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 429 (Skin Sensitisation: Local Lymph Node Assay)

GLP compliance:

yes (incl. QA statement)

Type of study:

mouse local lymph node assay (LLNA)

Test material

Test material information

Constituent 1

Reference substance name:

Boron silicate

EC Number:

603-157-9

Cas Number:

12676-29-8

Molecular formula:

H7 B7 Si57 O128

IUPAC Name:

Boron silicate

Details on test material:

Name of the test substance used in the study report: Silicone boride oxide
Physical State: White solid
Homogeneity: The test substance appeared to be homogeneous.
Storage: At room temperature
Expiration Date: January 01, 2036

In vivo test system

Test animals

Species:

mouse

Strain:

CBA

Sex:

female

Details on test animals and environmental conditions:

TEST ANIMALS
- Source: Harlan Laboratories B.V.
- Age at study initiation: 9-10 weeks
- Weight at study initiation: 20.8 +/- 1.1
- Housing: Group
- Diet (e.g. ad libitum): Pelleted standard diet, ad libitum
- Water (e.g. ad libitum): Tap water, ad libitum
- Acclimation period: At least 5 days prior to the start of dosing

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 + 2°C
- Humidity (%): 30 – 65% (acclimation period)
45 – 65% (pre-test and main study)
- Air changes (per hr): About 10 / hour
- Photoperiod (hrs dark / hrs light): 12/12

DEVIATIONS:
During the acclimation period for animals used for this study the relative humidity in the animal room ranged between 30 – 65 % instead of 45 – 65% for a few hours. This deviation to the study plan, however, did not affect the validity of the study.

Study design: in vivo (LLNA)

Vehicle:

propylene glycol

Concentration:

5, 10, and 25%

No. of animals per dose:

Number of animals for the pre-test: 2 females
Number of animals for the main study: 20 females
Number of animals per group: 5 females (nulliparous and non-pregnant)

Details on study design:

A solubility experiment was performed according to the recommendations given by OECD 429. The highest test item concentration, which could be technically used was a 25% (w/w) suspension in propylene glycol. Vortexing and sonicating and, if required, warming to 37°C, were used to formulate the test item. At higher concentrations, an applicable formulation of the test item was not achieved, neither by the use of other vehicles nor by using additional methods to formulate the test item.
To determine the highest non-irritant test concentration that does not induce signs of systemic toxicity at the same time, a pre-test was performed in two animals. Two mice were treated by topical application to the dorsal surface of each ear with test item concentrations of 10% and 25% (w/w) once daily each on three consecutive days.

Positive control substance(s):

other: alpha-hexyl cinnamaldehyde dissolved in acetone:olive oil (4:1 v/v)

Statistics:

A statistical analysis was conducted on the DPM values, the ear weights, the lymph node weights and the lymph node cell count to assess whether the difference was statistically significant between test item groups and negative control group. For all statistical calculations SigmaStat for Windows (Version 2.0) was used. A One-Way-Analysis-of-Variance was used as statistical method. In case of significant results of the One-Way-ANOVA, multiple comparisons were performed with the Dunnett test. Statistical significance was set at the five per cent level (p < 0.05). The Dean-Dixon-Test was used for identification of possible outliers (performed with Microsoft Excel 2003). Outliers were not identified.

Results and discussion

In vivo (LLNA)

Results

Results 1

Parameter:

SI

Remarks on result:

other: see Remark

Remarks:

In this study Stimulation Indices (S.I.) of 1.45, 1.53, and 2.58 were determined with the test item at concentrations of 5, 10, and 25% (w/w) in propylene glycol, respectively. A statistically significant increase in DPM value was obtained in the high dose group in comparison to the vehicle control group (p<0.05) and a dose response was observed. However, none of the obtained S.I.s exceeded the threshold value of 3 for a positive response.

Results 2

Parameter:

other: disintegrations per minute (DPM)

Remarks on result:

other: A statistically significant increase in DPM value was obtained in the high dose group in comparison to the vehicle control group (p<0.05) and a dose response was observed.

Any other information on results incl. tables

Test item concentration	Group calculation
	Mean DPM per animal	SD	S.I.
Vehicle (propylene glycol)	453.9	228.7	1.00
5% Silicone boride oxide	657.1	332.7	1.45
10% Silicon boride oxide	692.9	111.2	1.53
25% Silicon boride oxide	1169.3*	292.1	2.58

Applicant's summary and conclusion

Interpretation of results:

not sensitising

Remarks:

Migrated information

Conclusions:

A statistically significant increase in lymph node cell count was observed in the highest dose group in comparison to the vehicle control group. Still, the cutoff-value of 1.55 for a positive response regarding the lymph node cell count index reported for BALB/c mice was not exceeded in any test item treated group. The lymph node weight did not show a statistically significant increase in comparison to the control group.
The test item Silicone boride oxide was not a skin sensitiser under the test conditions of this study.