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Description of key information

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records
Reference
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
Study period:
1986-11-12 to 1986-12-17
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
Guideline study with acceptable restrictions The following deviations from the guideline occurred: - the animals were only observed 24 hours after challenge. The 48 hour observation was not conducted during the study. - the Magnusson and Kligman scale was slightly modified. The scale included a 0.5 value (slightly patchy erythema), which is normally not included in the scale. This was the only value recorded during the observation period. - study design did not included a positive control
Reference:
Composition 0
Qualifier:
according to
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Deviations:
yes
GLP compliance:
no
Type of study:
guinea pig maximisation test
Test material information:
Composition 1
Species:
guinea pig
Strain:
other: Pirbright
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS - Hoe:DHPK (SPF - LAC.)/Boe.
- Source: Lippische Versuchstierzucht, Hagemann GmbH & Co. KG, Hamelner Straße 3, 4923 Extertal 1
- Weight at study initiation: 300 - 382 g
- Housing: max. 5 animals in one cage; Macrolon plastic cages IV, 20 cm high, 33 cm width, 55 cm length; bedding material: H-3/4 (producer: Hahn & Co., Bredenbeck); Production: from pure soft wood, dried, dust free and sterilized
- Diet (ad libitum): Ssniff-G (Alleindiät für Meerschweinchen) (producer: Ssniff Spezialdiäten GmbH); pellets, 1.0 cm large, 0.5 cm diameter
- Water (ad libitum): aqua fontana as for human consumption
- Acclimation period: 7 days at least

ENVIRONMENTAL CONDITIONS
- Temperature: 18 °C ± 2°C
- Photoperiod (hrs dark / hrs light): 12/12
Route:
intradermal and epicutaneous
Vehicle:
water
Concentration / amount:
Intradermal: 0.25% of the test substance
Topical induction: 1% of the test substance
Challenge: 1% of the test compound
Route:
epicutaneous, occlusive
Vehicle:
water
Concentration / amount:
Intradermal: 0.25% of the test substance
Topical induction: 1% of the test substance
Challenge: 1% of the test compound
No. of animals per dose:
10 males / 10 females
Details on study design:
Prior to treatment the shoulder of each animal was clipped with a small animal clipper (about 8 x 5 cm).

RANGE FINDING TESTS:
To exclude primary skin irritations two animals/group were treated dermally in a preliminary study under occlusiv conditions with the following concentrations of the sample: 100% (undiluted), 75%, 25%, 5%, 2.5%, 1% and 0.5% in aqua dest..
Results:
100% (undiluted): 24 hours and partly 48 hours slight erythema
75% in aqua dest.: 24 hours and partly 48 hours erythema (24 hours necrosis 1 animal)
25% and 5% in aqua desti.: 24 hours and 48 hours slight erythema
2.5% in aqua dest.: 24 hours partly slight erythema
1% and 0.5% in aqua dest.: no primary skin irritation

MAIN STUDY
A. INDUCTION EXPOSURE
1) Intradermal treatment
On the day of the experiment all animals of both groups were treated intradermally into two skin areas situated bilateral to the spine. The first injection sites were located at the craniodorsal area and the following onces were performed underneath.

Test group:
Injection 1: 0.25% of test compound in aqua dest.(2 injections)
Injection 2: 0.25% of test compound in FCA (2 injections)
Injection 3: 1:1 FCA diluted in aqua dest. (2 injections)
Control group:
Injection 1: undiluted FCA (2 injections)
Injection 2: 0.25% auqa dest. in FCA (2 injections)
Injection 3: undiluted aqua dest. (2 injections)

2) Topical treatment
7 days later the same sites were treated topically with 0.5 mL of the test sample (test group) and the vehicle (control group), in the maximal concentration which is proved to cause no primary irritation (Range finding). After the application the treated areas were covered with a gauze pad and fixed to the animals trunk with "Elstoplast" (Closed Patch Test). 48 hours post administration the bandage was removed.

B. CHALLENGE EXPOSURE
3 weeks after the first dermal treatment a second dermal treatment was carried out on both test- and control group. The test and control group recieved the test substance on the left clipped flank and the vehicle on the right clipped flank.
The animals were treated again analogously to the 1st dermal treatment for 24 hours.
24 hour post administration the bandages were removed and the first evaluation was conducted.
48 hours post administration the second evaluation was done according to slightly modified Magnusson and Kligman grading scale (please refer table 1 in the "Any other information on materials and methods incl. tables" below)
Challenge controls:
Vehicle control group 10 male/10 female
Challenge dose: 1% of the test compound
Positive control substance(s):
no
Positive control results:
no data
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
1% of the test substance in aqua dest.
No. with + reactions:
10
Total no. in group:
20
Clinical observations:
(±) Slight patchy erythema (grade 0.5) was observed in 10/20 guinea pigs.
Remarks on result:
other: see Remark
Remarks:
Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 1% of the test substance in aqua dest.. No with. + reactions: 10.0. Total no. in groups: 20.0. Clinical observations: (±) Slight patchy erythema (grade 0.5) was observed in 10/20 guinea pigs..
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
Aqua dest.
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: Aqua dest.. No with. + reactions: 0.0. Total no. in groups: 20.0.
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
1% of the test substance in aqua dest.
No. with + reactions:
0
Total no. in group:
20
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. Dose level: 1% of the test substance in aqua dest.. No with. + reactions: 0.0. Total no. in groups: 20.0.
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
Aqua dest.
No. with + reactions:
0
Total no. in group:
20
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. Dose level: Aqua dest.. No with. + reactions: 0.0. Total no. in groups: 20.0.

Main study:

24 hours and 48 hours after challenge slight erythema were observed at the side treated with the compound in the test group. The control side of the test and control group (right flank) was without any findings.

In the control group partly slight primary skin reaction were observed 24 hours post administration at the test substance side. After 48 hours post adminsitration the concerning animals of this group were again without any findings.

Interpretation of results:
sensitising
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The test substance is considered to be a skin sensitizer. 10/20 (50%) animals showed a positive response.
According to the EC-Commission directive 67/548/EEC and its subsequent amendments, the test substance is a skin sensitizer.
According to the EC-Regulation 1272/2008 and subsequent regulations, the test item is classified in Category 1.
Endpoint conclusion
Endpoint conclusion:
adverse effect observed (sensitising)
Additional information:

Read-across concept (human health) for tin bis(tetrafluoroborate):

Substance-specific toxicity data for the substance tin bis(tetrafluoroborate) (water solubility >50 % w/w) are not available.However, since upon dissolution in water, full dissociation of the highly water-soluble tin bis(tetrafluoroborate) to (i) Sn2+cations and (ii) tetrafluoroborate anions occurs, read-across to (i) inorganic tin(II) substances and (ii) inorganic salts of tetrafluoroboric acid is made, respectively.

This read-across is considered fully justified in view of the comparable water solubilities of the similarly soluble read-across substances, such as (i) tin(II)chloride, water solubility 178 g/L at 20°C, and (ii) potassium tetrafluoroborate, water solubility 5.4 g/L at 22°C.

Whereas it is noted that upon dilution of aqueous solutions, “clouding” and precipitation of basic tin salts occurs , which can be described by the following equation:

SnX2+ H2O <--> "SnXOH"(s) + HX

this Sn2+-specific behaviour is not considered to restrict the read-cross since oral bioavailability of inorganic tin(II) substances is generally very low.

Potassium tetrafluoroborate is currently not classified according to the criteria specified by Directive 67/548/EEC and subsequent regulations, and is correspondingly considered not to require classification according to the criteria set forth by EC Regulation No. 1272/2008 and subsequent regulations, neither for HH or ENV hazards.

Any toxicological or ecotoxicological hazards (if any) are therefore assumed to be related to Sn2+only.

Skin sensitisation:

One reliable test report according to OECD Guideline 406 (Skin Sensitisation) with the read-across substance tin(II) bis(methanesulfonate) is available. The test substance is considered to be a skin sensitizer. 10/20 (50%) animals showed a positive response.

Potassium tetrafluoroborate:

Skin sensitisation properties of KBF4 were studied in a GLP-compliant OECD Guideline 429 study with mice (TNO Triskelion BV, 2012). Three test groups of 4 female mice each were treated with 10, 25 and 50% KBF4 by means of open application of 25 μL to the dorsum of each ear for three consecutive days. Three days after the last treatment, all animals received an intravenous injection of 3H-thymidine. Five hours later, the 3H-thymidine incorporation in the draining auricular lymph nodes was determined. The results were compared with those of a negative control group which was treated with the vehicle (acetone/olive oil, 4:1 v/v). Group mean 3H-thymidine incorporations of 1356, 1346 and 1235 DPM were found in the auricular lymph nodes of animals treated with respectively 10%, 25% and 50% KBF4 formulations. The group mean value in the vehicle control animals was 919 DPM. The calculated stimulation indices (SI), representative of the change in 3H-thymidine incorporation in KBF4 treated animals compared to controls, were 1.47, 1.46 and 1.34 for the tested doses of 10%, 25% and 50% KBF4, respectively. Since the SI was < 3, the limiting value required for classification as a skin sensitiser, in response to all concentrations of KBF4 tested and no dose response relationship was apparent it was concluded that KBF4 did not have a skin sensitising potential when applied up to concentrations of 50%.


Migrated from Short description of key information:
One reliable study with the read-across substance tin(II) bis(methanesulfonate) and one supporting study for the substance potassium tetrafluoroborate is available. The test substance tin(II) bis(methanesulfonate) is considered to be a skin sensitizer.
Under the experimental conditions of this study, no evidence was obtained that KBF4 has a skin sensitising potential when applied up to concentrations of 50%.

Justification for selection of skin sensitisation endpoint:
Read-across information

Justification for classification or non-classification

Skin sensitisation:

The read-across test substance tin(II) bis(methanesulfonate) is considered to be a skin sensitizer. 10/20 (50%) animals showed a positive response. According to the EC-Commission directive 67/548/EEC and its subsequent amendments, the test substance is a skin sensitizer. According to the EC-Regulation 1272/2008 and subsequent regulations, the test item is classified in Category 1.

Tin bis(tetrafluoroborate):

Based on the assumption that the sensitisation effect originates from Sn2 + and taking into account the proposed read-across approach, the test item tin bis(tetrafluoroborate) has to be classified as a skin sensitiser.

According to the EC-Commission directive 67/548/EEC and its subsequent amendments, the test substance is a skin sensitizer. According to the EC-Regulation 1272/2008 and subsequent regulations, the test item is classified in Category 1.

Potassium tetrafluoroborate:

Based on the findings in the skin sensitisation study, the substance does not need to be classified according to Directive 67/548/EEC and according to the EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008.