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Administrative data

Description of key information

Tin(II) bis(methanesulfonate):
Oral NOEL 50 mg/kg/day over 90 days.
Potassium tetrafluoroborate:
A NOAEL of 40 mg/kg bw/day was established in a reproduction/developmental toxicity screening test and a NOAEL of 74 mg/m3 was established in a 28-day inhalation study in rats for systemic effects. No local effects were observed at concentrations up to 225 mg/m3 in the 28-day inhalation study.

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion
Dose descriptor:
NOAEL
142 mg/kg bw/day
Study duration:
subchronic
Species:
rat

Repeated dose toxicity: inhalation - systemic effects

Link to relevant study records
Reference
Endpoint:
repeated dose toxicity: inhalation
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
other:
Critical effects observed:
not specified
Endpoint conclusion
Endpoint conclusion:
no study available

Repeated dose toxicity: inhalation - local effects

Link to relevant study records
Reference
Endpoint:
repeated dose toxicity: inhalation
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
other:
Critical effects observed:
not specified
Endpoint conclusion
Endpoint conclusion:
no study available

Repeated dose toxicity: dermal - systemic effects

Link to relevant study records
Reference
Endpoint:
repeated dose toxicity: dermal
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
other:
Critical effects observed:
not specified
Endpoint conclusion
Endpoint conclusion:
no study available

Repeated dose toxicity: dermal - local effects

Link to relevant study records
Reference
Endpoint:
repeated dose toxicity: dermal
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
other:
Critical effects observed:
not specified
Endpoint conclusion
Endpoint conclusion:
no study available

Mode of Action Analysis / Human Relevance Framework

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.

Therefore, the 90 -day GLP repeated dose toxicity study (OECD guideline 408) with Tin(II)methansulfonate conducted in 2007 (LPT) was regarded as the most appropriate study for selection of the starting point for the risk assessment. In this study, groups of 10 male and 10 female CD rats were treated orally by gavage with 50, 150, 450 (450/300) mg/kg bw d test substance. The dose level was reduced from day 20 onwards (450 to 300 mg/kg bw/d) for high dose group males because of severe toxicity. A vehicle (hydroxypropylmethylcellulose) control group was treated concurrently. Severe signs of toxicity were observed in the high dose group animals (450/300 mg/kg bw/d) including mortality and clinical signs of toxicity (ataxia, soft faeces and/or pale or pale-reddish faeces, piloerection, laboured breathing, reduced motility, rough fur, inflated abdomen, pale skin or body parts or salivation) and effects on functional observations (reduced fore-and hindlimb grip strength). Body weight and food consumption was reduced and macroscopic lesions were observed in several organs (reduced spleen size, reduced prostate and seminal vesicle size, dilated stomach with red discoloured mucosa, black discoloured liver with several pale spots, emphysematous lungs with multiple black foci, enlarged adrenals, reduced thymus size, severely enlarged caecum, pale pancreas, reduced kidney size and dilated intestinal tract) of animals that died prematurely. Histopathology revealed a moderate to marked reduction of lymphocytes in spleen, thymus and lymph nodes, and haematological parameters of the white blood cell system (statistically significant increase in WBC, neutrophiles, large unstained cells, lymphocytes and monocytes) were affected mainly in females, but organ weights were not treatment-related affected. In addition, ALAT and ASAT were statistically significantly increased in males and females. No effect on mortality clinical signs body weight, food consumption, haematology, clinical chemistry, urinalysis, ophthalmological examinations, organ weights, macroscopic and histopathology were observed in low and mid dose animals (50 and 150 mg/kg bw/d), with the exception of some minor effects on haematological and clinical chemistry parameters of mid dose female animals only, which reached statistical significance only for one parameter (large unstained cells). However, the NOEL was established at the low dose level of 50 mg/kg bw/d, but because there were no effects on organ weight and no pathological/histopathological correlate to the findings in mid dose female animals, the findings observed were regarded as incidental and not adverse, and thus a NOAEL can be established at the mid dose level of 150 mg/kg bw/d.

A GLP-compliant (OECD Guideline 407) 28 -day rat toxicity study with potassium tetrafluoroborate was considered in addition. Groups of 10 male and 10 female Wistar rats were administered the test substance in aqueous solution by gavage at dose levels of 0, 20, 80 or 320 mg/kg bw/day for 28 days, 7 days per week (Hoechst AG, 1997). In addition 5 male and 5 female animals from the control and high dose group were placed in the recovery groups for a recovery period of 14 days. In addition to standard parameters, all animals were examined for total thyroxine, triiodothyronine and thyroid-stimulation hormone levels. No mortalities or clinical signs were observed in the study. There were no effects on food and water consumption, body weight and body weight gain. No macroscopically visible changes were seen, which were considered to be compound-related. Organ weights were unaffected by treatment. Histopathological examination did not reveal any compound-related effect. Haematological examinations revealed slight but statistically significant decreases in erythrocytes counts and haematocrit value in female animals of the intermediate and high dose group. Females of the high dose group also showed slightly decreased haemoglobin values. The MCV values were not affected. All findings on haematological parameters were completely reversible after a 14 -day recovery period. No treatment-related changes were detected by examination of the thyroid hormone levels in all dose groups. Clinical chemistry examinations revealed no compound-related changes in any dose group. No treatment-related changes were detected by urinalysis. Based on the slight decrease in erythrocytes counts and haematocrit and haemoglobin values in intermediate and high-dose females, which were fully reversible after 14 days recovery period, the lowest dose level of 20 mg/kg bw/day is considered to be a NOEL for females. Based on the lack of adverse changes the highest dose level of 320 mg/kg bw/day is considered to be a NOAEL for males and females.


Justification for selection of repeated dose toxicity via oral route - systemic effects endpoint:
The 90-day toxicity study with Tin(II)methansulfonate in rats was selected, because it is the most appropriate and complete toxicity study with a treatment duration of 90 days.

Justification for classification or non-classification

Tin(II) bis(methanesulfonate):

NOAEL of 150 mg/kg/day for 90 days does not lead to classification as STOT.

According to GHS classification, CLP Reg. No 1272/2008 of 16 Dec 2008, Annex VI, Table 3.1, List of harmonized classification and labelling of hazardous substances, as amended by Reg. No 790/2009, 10 Aug 2009, tin methansulfonate is not classified for STOT- Single or Repeated exposure.

Potassium tetrafluoroborate:

Based on the findings of the repeated dose toxicity studies, the test substance does not meet the criteria of the Directive 67/548/EEC and the EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008 and therefore no classification is needed.

Tin bis(tetrafluoroborate):

Correction of the NOAEL derived for tin bis(methanesulfonate) by molecular weight corresponds to a NOAEL of 142 mg/kg/day

Based on the read-across approach, the test item tin bis(tetrafluoroborate) does not require classification for STOT- Single or Repeated exposure

according to Directive 67/548/EEC and subsequent regulations and according to EC Regulation No. 1272/2008 and subsequent regulations.