Registration Dossier

Diss Factsheets

Administrative data

Description of key information

The skin sensitisation potential of fluorphlogopite, a substance closely structurally-related to magnesium potassium fluoride silicate (Mg2.7K0.7Si4O10F2), was assessed by the LLNA method according to OECD Test Guideline 429 and to GLP at concentrations of 5, 10 and 25% (in acetone/olive oil, 4:1). There was no evidence of a sensitising effect in any treated group, based on SI values of 1.12, 0.91 and 1.03 at the three respective test concentrations. Fluorphlogopite, and consequently the target substance of this dossier magnesium potassium fluoride silicate (Mg2.7K0.7Si4O10F2), are concluded to be non-sensitising.

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records
Reference
Endpoint:
skin sensitisation: in vivo (LLNA)
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Study period:
07 October 2011 - 26 October 2011
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study
Remarks:
Guideline, GLP study conducted on read-across source substance.
Justification for type of information:
A full justification for the use of data on fluorphlogopite as read-across for this substance, magnesium potassium fluoride silicate (Mg2.7K0.7Si4O10F2), is attached to Section 13 of this dossier.
Reason / purpose for cross-reference:
read-across source
Qualifier:
according to guideline
Guideline:
OECD Guideline 429 (Skin Sensitisation: Local Lymph Node Assay)
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Type of study:
mouse local lymph node assay (LLNA)
Specific details on test material used for the study:
Batch No.: K7211200M
Expiration date: 30 September 2015
Species:
mouse
Strain:
CBA
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Harlan Laboratories B.V., Postbus 6174, 5960 AD Horst, Netherlands
- Females nulliparous and non-pregnant: Yes
- Age at study initiation: 9- 10 weeks
- Weight at study initiation: 20 g
- Housing: Animals were housed 5/cage, with all animals of a treatment group housed together.
- Diet: Pelleted standard diet, available ad libitum
- Water: Tap water, available ad libitum
- Acclimation period: at least 5 days prior start of dosing

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 2°C
- Humidity (%): 31-65%
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 6 am - 6 pm

IN-LIFE DATES: From: day 1 To: day 6
Vehicle:
acetone/olive oil (4:1 v/v)
Concentration:
5%, 10%, 25%
No. of animals per dose:
5
Details on study design:
PRE-SCREEN TESTS:
- Compound solubility: The highest test item concentration which can be technically used was 25% (w/v) in the study vehicle.
- Irritation and systemic toxicity: At the tested concentrations the animals did not show any signs of local skin irritation or systemic toxicity.
- Ear thickness measurements: Ear thickness measurements were made prior to the first application of the test item (day 1), on day 3 and before sacrifice (day 6).

MAIN STUDY

ANIMAL ASSIGNMENT AND TREATMENT

- Name of test method: LLNA

- Criteria used to consider a positive response: A test item is regarded as a sensitiser in the LLNA if the following criteria are fulfilled: First, that exposure to at least one concentration of the test item resulted in an incorporation of 3HTdR at least 3-fold or greater than that recorded in control mice, as indicated by the Stimulation Index.

Second, that the data are compatible with a conventional dose response, although allowance must be made (especially at high topical concentrations) for either local toxicity or immunological suppression.

OBSERVATIONS

Mortality / Viability: At least once daily from experimental start to necropsy.

Body weights: In the pre-test: prior to the first application and prior to sacrifice. In the main experiment: prior to the first application and prior to treatment with 3HTdR.

Ear weights: In the pre-test after sacrifice; biopsy punches were taken from each ear.

Clinical signs (local / systemic): Clinical signs (systemic toxicity or local skin irritation) were recorded at least once daily. Especially the treatment sites were observed carefully.

TEST ITEM PREPARATION AND ADMINISTRATION:
The test item was placed into a volumetric flask on a tared balance and acetone:olive oil (4:1 (v/v)) was quantitatively added. The different test item concentrations were prepared individually. Homogeneity of the test item in vehicle was maintained during treatment using a magnetic stirrer. The preparations were made freshly before each dosing occasion. Concentrations were in terms of material as supplied.

TOPICAL APPLICATION
Each test group of mice was treated by topical (epidermal) application to the dorsal surface of each ear with different test item concentrations of 5, 10, and 25% (w/v) in acetone:olive oil (4:1 (v/v)). The application volume, 25 µL/ear/day, was spread over the entire dorsal surface (8 mm) of each ear once daily for three consecutive days. A further group of mice was treated with an equivalent volume of the relevant vehicle alone (control animals).
Positive control substance(s):
hexyl cinnamic aldehyde (CAS No 101-86-0)
Key result
Parameter:
SI
Value:
1.12
Test group / Remarks:
5%
Key result
Parameter:
SI
Value:
0.91
Test group / Remarks:
10%
Key result
Parameter:
SI
Value:
1.03
Test group / Remarks:
25%

The EC3 value could not be calculated, since all SIs are below the threshold value of 3.

Interpretation of results:
GHS criteria not met
Conclusions:
Fluorphlogopite, a substance closely structurally-related to magnesium potassium fluoride silicate (Mg2.7K0.7Si4O10F2), was found to be non-sensitizing in a guideline LLNA.
Executive summary:

The skin sensitisation potential of fluorphlogopite, a substance closely structurally-related to magnesium potassium fluoride silicate (Mg2.7K0.7Si4O10F2), was assessed by the LLNA method according to OECD Test Guideline 429 and to GLP at concentrations of 5, 10 and 25% (in acetone/olive oil, 4:1). There was no evidence of a sensitising effect in any treated group, based on SI values of 1.12, 0.91 and 1.03 at the three respective test concentrations. Fluorphlogopite, and consequently the target substance of this dossier magnesium potassium fluoride silicate (Mg2.7K0.7Si4O10F2), are concluded to be non-sensitising.

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

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available

Justification for classification or non-classification

In an LLNA study fluorphlogopite, a substance closely structurally-related to magnesium potassium fluoride silicate (Mg2.7K0.7Si4O10F2), was found to be non-sensitizing.

Categories Display