Registration Dossier

Administrative data

Description of key information

Divers studies on acute oral toxicity performed either with tin bis(tetrafluoroborate) or with a structural analogue (i.e., tin(II) methanesulfonate, sodium tetrafluoroborate and tin dichloride) are available with LD50 values between 130 mg/kg bw. (Powers & Derelanko, 1985) and > 2000 m g/kg bw. (Chibanguza, 1986 and Anonymous, 1992). In a weight of evidence approach (see discussion below) it is discussed that the substance tin bis(tetrafluoroborate) should be labeled as harmful if swallowed (LD50 between 300 and 2000 mg/kg bw.).
No study on acute inhalation toxicity are available. Since the substance is placed on the market as solution (50%) only and is not stable without the water additive, the vapour pressure of the aqueous solution is negligible and the exposure to aerosols, particles or droplets of an inhalable size is not foreseeable under the intended use, animal testing for this endpoint is not considered to be justified.
A study for acute dermal toxicity performed with a structural analogue tin(II) bis(methanesulfonate) are available, resulting in a LD50 greater than 2000 mg/kg bw.

Key value for chemical safety assessment

Acute toxicity: via oral route

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Quality of whole database:
No specific study was choosen; C&L is only possible using a weight of evidence approach

Acute toxicity: via inhalation route

Link to relevant study records
Reference
Endpoint:
acute toxicity: inhalation
Data waiving:
other justification
Justification for data waiving:
other:
Endpoint conclusion
Endpoint conclusion:
no study available

Acute toxicity: via dermal route

Link to relevant study records
Reference
Endpoint:
acute toxicity: dermal
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Study period:
1986-11-25 to 1986-12-11
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: no GLP compliance, samples not moistened
Reference:
Composition 0
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Version / remarks:
adopted 1981-05-12
Deviations:
no
GLP compliance:
no
Test type:
standard acute method
Limit test:
yes
Test material information:
Composition 1
Species:
rabbit
Strain:
New Zealand White
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Harald Schriever, Kaninchenfarm, D-2740 Bremervörde, Neuendamm 88
- Weight at study initiation: males: 2.1 - 3.2 kg; females: 2.25 - 2.5 kg
- Housing: single caging in battery of cages with paper roll disposal system; size: 40 cm high, 45 cm wide, 50 cm long
- Diet (ad libitum): Ssniff Mü Z^R (Producer: Ssniff Spezialdiäten GmbH, 4770 Soest/Westfalen; Type: pellets, 1.0 - 1.5 cm large, 0.5 cm diameter
- Water (ad libitum): aqua fontana
- Acclimation period: 7 days at least

ENVIRONMENTAL CONDITIONS
- Temperature: 18 ± 2°C
- Relative humidity: 50 - 85%
- Photoperiod (hrs dark / hrs light): 12/12
Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure/Type of wrap: prior to treatment the back of each animal was clipped (12 x 10 cm) with a small animal clipper. The animals' back of one group was abraded with clean clipper blade so as to penetrate the horny layer of the epidermis, but without causing bleeding. The animals back of the second group was left intact. After treatment the backs of all animals were secured with gauze pads, several wrappings of "Elastoplast" and "Stülpa" for 24 hours.

REMOVAL OF TEST SUBSTANCE
- Washing: the substance was removed with wet disposable gauze.
- Time after start of exposure: 24 hours
Duration of exposure:
24 hours
Doses:
2000 mg/kg
No. of animals per sex per dose:
3 males / 3 females (scarified skin)
3 males / 3 females (intact skin)
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: the evaluation of the clinical-toxicological sings (a modified Irving-Screening by Screnning methods in pharmacology, R.A. Turner, 1965) is done individually and depends on the nature of the sings.
Records were made according to the following intervals: 1 h, 2 + 3 h, 6 h, 24/48 h, 3/14 days post administration.
The skin alterations are recorded once daily after termination of the time of exposition for the entire observations period of 14 days. The scoring was done according to the Draize scale.
The body weights are recorded at day 0 (beginning of the experiment) and at day 14 (terminal necropsy) on the survivng animals.
- Necropsy of survivors performed: yes
Immediately after death a complete necropsy is performed on all acute- and late mortalities.
At the end of the 14-day observation period all surviving animals of all groups are sacrificed and gross necropsies are performed.
Statistics:
no data
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: intact skin
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: scarified skin
Mortality:
No mortalities were observed
Clinical signs:
The sample did not induce any clinical-toxicological symptoms
Body weight:
Body weight changes after the observation period showed a normal weight gain
Gross pathology:
Necropsies performed on all animals at termination exhibited no gross pathological findings
Other findings:
No skin alterations were observed.
Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
LD50 (male/female rats)> 2000 mg/kg bw
According to the EC-Commission directive 67/548/EEC and its subsequent amendments, tin(II) methanesulphonate is not classified as acute toxic via the dermal route.
According to the EC-Regulation 1272/2008 and subsequent regulations, tin(II) methanesulphonate is not classified as acute toxic via the dermal route.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating dose
2 000 mg/kg bw

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.

Acute oral toxicity

Tin bis(tetrafluoroborate):

Two acute oral studies were performed with the test item tin bis(tetrafluoroborate); one range-finding study (OECD 401, dose levels: 200 and 2000 mg/kg bw) indicating an LD50 value between 200 and 2000 mg/kg (Snell, 1995), whereas another substance-specific investigation (Powers & Derelanko, 1985) states a determined LD50 of 130 mg/kg which doesnotmatch with the range finding study.

Both results appear implausible based on other available date for the acute oral toxicity data of the two constituents of tin bis(tetrafluoroborate, for the following reasons:

 

Data for tin(II)chloride:

Published values for the oral LD50 of SnCl2 in rats are scarce, but a value of about 1,200 mg Sn/kg bw corresponding to ~2,000 mg SnCl2 /kg bw is frequently cited (Conine et al., 1975)

 

Data for tin(II) bis(methanesulfonate):

Two acute oral studies were performed with tin(II) methanesulfonate; one with reported LD50 of 1621 mg/kg (Haynes, 1988) and another with a determined LD50 in the range of 3000 - 4000 mg/kg (Chibanguza, 1986).

 

Data for sodium tetrafluoroborate:

One GLP-compliant OECD Guideline 401 study with rats (Anonymous, 1992) is available for the structural analogue sodium tetrafluoroborate. A group of 5 male and 5 female rats was administered a single dose of 2000 mg/kg bw in water by gavage. Animals were observed for 14 days and necropsied. There were no deaths or clinical signs of toxicity. All animals gained weight during the study. No pathological findings were revealed at necropsy. Based on the results of the study, the LD50 was above 2000 mg/kg bw.

 

Weight-of-evidence assessment of acute oral toxicity:

The study results above suggest that the individual constituents of the substance (i.e., tin(II) ions and tetrafluoroborate ions) do not pose a concern for acute oral toxicity, since the respective LD50 values are around 2,000 mg/kg bw.

The two substance-specific studies suffer from several shortcomings, i.e. either limitations in study design (range-finder with limited number of animals, doses etc.) or from a lack of test item characterization (purity, composition, etc.), rendering them of limited reliability.

However, considering that the substance-specific acute oral LD50 in a range-finder was determined to be between 200-2,000 mg/kg bw, but the corresponding LD50 values characteristic of the two ionic components were determined around 2,000 mg/kg bw, it is considered to be adequately conservative (in lack of reliable substance-specific data) to assign a classification as “harmful if swallowed, category 4” (LD50 between 2000 and 300 mg/kg bw) to the substance tin bis(tetrafluoroborate) according to regulation (EC) 1272/2008, and “harmful if swallowed, Xn; R22” according to Directive67/548/EEC.

Acute inhalation toxicity

According to regulation (EC) 1907/2006 Annex VIII column 2 point 8.5.2 acute inhalation toxicity testing is considered not to be required, since the substance tin bis(tetrafluoroborate) is produced, marketed and used exclusively as an aqueous solution and additionally is not stable without the water additive. The vapour pressure of the aqueous solution is negligible and the exposure to aerosols, particles or droplets of an inhalable size is not foreseeable under the intended uses, and therefore not relevant. Therefore, for lack of any inhalation exposure potential, animal testing for this endpoint is not considered to be justified.

Acute dermal toxicity

Tin(II) methanesulfonate: Tin(II) methanesulfonate is non-toxic if applied to the skin as the LD50 is greater than 2000 mg/kg bw (Chibanguza, 1987). The study is used as key information (RL: 2), since no relialbe studies are available conducted with tin bis(tetrafluoroborate).

Tin bis(tetrafluoroborate):

One substance specific study report for tin bis(tetrafluoroborate) is available with significant methodological deficiencies (Gad, 1984, RL3, only two dose levels were tested and exposure period was only 1 hour). The determined LD 50 value is ca. 3000 mg/kg bw.


Justification for selection of acute toxicity – oral endpoint
Divers studies on acute oral toxicity performed either with tin bis(tetrafluoroborate) or with a structural analogue (i.e., tin(II) methanesulfonate, sodium tetrafluoroborate and tin dichloride) are available. LD50 for tin bis(tetrafluoroborate) is between 300 and 2000 mg/kg bw.

Justification for selection of acute toxicity – inhalation endpoint
Tin bis(tetrafluoroborate) is produced, marketed and used exclusively as an aqueous solution and additionally is not stable without the water additive. The vapour pressure of the aqueous solution is negligible and the exposure to aerosols, particles or droplets of an inhalable size is not foreseeable under the intended uses, and therefore not relevant. Therefore, for lack of any inhalation exposure potential, animal testing for this endpoint is not considered to be justified.

Justification for selection of acute toxicity – dermal endpoint
GLP guideline study conducted with a structural analogue (i.e., tin (II) methanesulfonate).

Justification for classification or non-classification

Acute oral toxicity

Considering that the substance-specific acute oral LD50 in a range-finder was determined to be between 200-2,000 mg/kg bw, but the corresponding LD50 values characteristic of the two ionic components were determined above 2,000 mg/kg bw, it is considered to be adequately conservative (in lack of reliable substance-specific data) to assign a classification as “harmful if swallowed, category 4” (LD50 between 2000 and 300 mg/kg bw) to the substance tin bis(tetrafluoroborate) according to regulation (EC) 1272/2008, and “harmful if swallowed, Xn; R22” according to Directive67/548/EEC.

Acute inhalation toxicity

Acute inhalation toxicity data are not available, since the substance tin bis(tetrafluoroborate) is produced, marketed and used exclusively as an aqueous solution and additionally is not stable without the water additive. Thus, inhalation of the substance is not expected and no classification s needed for tin bis(tetrafluoroborate) for the acute inhalation route in accordance to Regulation (EC) 1272/2008 and Directive 67/548/EEC.

Acute dermal toxicity

Tin(II) methanesulfonate has a LD50 greater than 2000 mg/kg bw. Thus, according to Regulation (EC) 1272/2008 and Directive 67/548/EEC

the substance is not classified. Based on the read-across concept, tin bis(tetrafluoroborate) is also not considered to be classified as acute toxic via the dermal route.