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Administrative data

Key value for chemical safety assessment

Effects on fertility

Effect on fertility: via oral route
Endpoint conclusion:
no adverse effect observed
Effect on fertility: via inhalation route
Endpoint conclusion:
no adverse effect observed
Effect on fertility: via dermal route
Endpoint conclusion:
no adverse effect observed
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.

Tin(II) bis(methanesulfonate):

The effects of tin(II)methane-sulfonate on fertility, reproduction and pre-and postnatal development were investigated in Wistar rats in a one generation reproduction toxicity study (OECD Guideline 415). Four groups of 24 male and female rats received the test item in the diet at concentrations of 0, 1200, 3500 and 7000 mg/kg food (target dose levels of 0, 100, 300 and 600 mg/kg bw/d). The animals were treated for 10 weeks before mating and during the mating period. After successful mating (day of finding sperm in vaginal smears = day 0 post conceptionem), treatment of the females was continued until weaning of the offspring and subsequent sacrifice. Exposure of all males and females continued until their sacrifice after determination of sexual maturation in offspring. Animals selected for the investigation of sexual maturation were exposed from weaning to sacrifice. The following results were obtained: All animals of the medium and high dose group showed yellow-brown discoloured faces throughout the study, obviously as a consequence of substance excretion via faeces. These were not considered adverse effects. Other clinical signs occasionally observed in single animals from all groups including the control group were considered incidental. There was a significant decrease in both body weight and body weight gain at the start of treatment in medium and high dose males as well as in high dose females. No effects were observed on gestation body weight, gestation body weight gain and maternal postpartum body weights. However, postpartum weight gain was statistically significantly increased in the high dose group from day 14 p.p. onwards as well as for the total period, as well as in the medium dose group on day 21. These effects are not considered adverse, but led to a catch-up of body weights in females towards the end of the lactation period. There was a significant decrease in food consumption at the start of treatment in medium and high dose males as well as in high dose females. These effects are in good concord with the influences observed on body weight gain and can be interpreted as a repellent effect of the food containing higher doses of the test item. All values returned to normal afterwards, and no effects on food consumption were observed on food consumption during gestation or lactation. For the four groups, mating yielded 24, 22, 23, and 22 sperm positive females, respectively. This resulted in 23, 19, 22, and 21 pregnancies and 23, 19, 22, and 21 females with liveborn offspring, respectively. Based on these results, no effect of test item treatment on mating and pregnancy rates as well as on precoital time could be observed in this study. No effect was observed on the number of implantation sites, pup birth weight, number of live pups or pup loss during lactation, duration of gestation and sex ratio of pups. The only observed effect on pup weight was decrease in the second half of lactation, which reached statistical significance in the high dose group on day 21 (day of weaning). This effect occurred only when pups began to eat food in addition to maternal lactation and, therefore, can be interpreted as a repellent effect of the food containing higher doses of the test item, which was also observed in the beginning of treatment in F0 animals. Clinical findings in pups consisted mainly of poor condition observed in all dose groups. The only remarkable finding was unilateral anophthalmia in one single high dose pup. There was a trend towards a decreased pup postweaning body weight in all test item treated groups, which reached statistical significance in males of the high dose group, and in females of the medium and high dose group. In males, body weight gain remained decreased during the whole post-weaning observation period, while in females the only statistically significant decrease was observed between day 28 and 35 in the medium dose group. No effect was observed on the time of showing preputial separation or vaginal opening in any of the test item treated groups. There was, however, a trend towards a decrease in body weight on the day of completion of sexual maturity, which reached statistical significance in males of the high dose group. This can be interpreted as a consequence of the reduced body weight observed in pups of this dose group at weaning as well as later on. All these effects, again, can be interpreted as a repellent effect of the food containing higher doses of the test item, which was also observed in the beginning of treatment in F0 animals. None of the sporadically occurring necropsy observations was considered test item induced. Consequently, no effect was observed on necropsy observations in F0 or F1 animals. The only statistically significant differences on organ weights were observed in the high dose group for absolute weights of testes, epididymides and ovaries. However, no differences were observed for any relative organ weights in any of the test item exposed groups. It cannot be excluded that the statistically significantly slightly increased incidence of exfoliated germ cells in the lumina of the efferent ducts of the epididymis in the high dose group is due to degenerative lesions in the testes induced by the test item. The findings in the epididymis correspond with very slight, slight and in one male of the high dose group even with moderate testicular changes. Even if the observed degenerative lesions in the testes are not statistically significant compared to the control, they show a tendency to occur more frequent and in a slightly higher severity in the high dose group. The background level of sloughed cells in the epididymis is very low in adult control rats but might be increased in young peripubertal rats so it might reflect age rather than toxicity. As the age range over which rats mature extends from 8-10 weeks so it can happen "by chance" that a higher incidence of rats with incomplete spermatogenesis, increased germ cell degeneration and sloughed germ cells in the epididymidal lumen will be present in the high dose group and the more normal mature testes will be in the control group. In this situation it is difficult to distinguish whether the increased germ cell degeneration, the presence of sloughed germ cells in the epididymal lumen and the reduced epididymal sperm in the high dose group is due to a degenerative lesion induced by the test compound or a reflection of relative immaturity. All these gonadal effects could also be explained by the fact that body weight in the high dose animals was decreased compared to the control group, thus reflecting developmental retardation.

Based on these results, the no observed adverse effect level of Tin(II)methane-sulfonate in this One-generation reproduction toxicity study in Wistar rats was determined at a concentration of 3500 mg/kg food (target dose of 300 mg/kg body weight/day) for developmental endpoints, and 1200 mg/kg food (target dose of 100 mg/kg body weight/day) for adult endpoints. However no effects on fertility and reproductive parameters of parental animals, and no specific effect of pre-and postnatal development of offspring were observed.

Potassium tetrafluoroborate:

In a GLP compliant reproduction/developmental toxicity screening test, performed according to OECD Guideline 421, Wistar rats of both sexes were orally exposed to potassium tetrafluoroborate (TNO Quality of Life, 2007). 1% carboxymethylcellulose solution in water (CMC) was used as vehicle. Groups of 12 rats per sex were dosed daily with 0, 40, 116.5 and 350 mg KBF4/kg body weight for up to approx. 35 days (males) or during 4 weeks premating, mating, gestation and up to day 4 of lactation (females). Initially a group of male rats was dosed with 1000 mg KBF4/kg body weight. These animals showed a weight loss of approx. 10% after 3 daily dosages. For that reason this group was replaced by the 40 mg KBF4/kg body weight. Two female animals of the 350 mg KBF4/kg body weight died during the lactation period. Daily clinical observations during the study did not reveal any remarkable findings in animals' appearance, general condition or behaviour among the dosing and control groups. Effects on water consumption were observed (not exactly measured) in the male and female animals of the 350 mg KBF4/kg body weight group from week 3 onwards. Mean body weight and or body weight change of the male and female animals of the 350 mg KBF4/kg body weight were statistically significantly decreased during several periods of the study. Mean bodyweight or bodyweight change of the 116.5 mg KBF4/kg body weight group was only statistically significantly decreased in the male animals from day 21 onwards. Food consumption of the 350 mg KBF4/kg body weight group was statistically significantly decreased in male and female animals during several periods of the study. Food consumption of the male animals of the 116.5 mg KBF4/kg body weight group was statistically significantly decreased from day 7 to 14. In each group 12 females were placed with males. All females of the KBF4-treated groups and 11 females of the control group were mated within 4 days. The number of pregnant females, the number of females with live born pups and the number of males that became sires amounted to 8, 9, 9 and 5 for the control, 40, 116.5 and 350 mg KBF4/kg body weight groups, respectively. The mating index was 100% in all KBF4-treated groups and 92% in the control group. The female fecundity index, female fertility index and male fertility index were comparable between the control, 40 and 116.5 mg KBF4/kg body weight groups and ranged from 67-75%. In the 350 mg KBF4/kg body weight group fecundity index, female fertility index and male fertility index was 42%.The gestation index was 100% in all groups. The duration of gestation was comparable between the groups. The number of corpora lutea and implantation sites was statistically significantly decreased in the 350 mg KBF4/kg body weight group; no effect was observed in the other KBF4 -treated groups when compared to the control group. Pre- and post-implantation loss was comparable in all groups. The number of litters with live born pups was 8, 9, 9 and 5 for the control, 40, 116.5 and 350 mg KBF4/kg body weight groups, respectively. The number of live pups per litter on post natal day (PN) 1 in the control, 40, 116.5 and 350 mg KBF4/kg body weight groups was 11.9, 12.1, 11.8 and 9.4, respectively. Pup mortality on PN 4 was comparable in all groups except for the mid-dose group and amounted to 3, 13, 3, 29 (incidences 3.2, 12, 2.8 and 62%) in the control, 40, 116.5 and 350 mg KBF4/kg body weight groups, respectively; in the 350 mg KBF4/kg body weight group the mortality was statistically significantly increased. The death of the pups of dam C63 (10 pups and C67 (11 pups) may be secondary to the death of the dams on PN 2 and 3, respectively. In the control, 40, 116,5 and 350 mg KBF4/kg body weight groups 0(8), 1(8), 0(9) and 3(2) litters, respectively were lost entirely between PN 1-4 (between brackets the number of litters with live pups on PN 4). The number of live pups per litter on PN 1 was 11.9, 12.1, 11.8 and 9.4 in the control, 40, 116.5 and 350 mg KBF4/kg body weight groups, respectively and on PN 4 the number of pups was 11.5, 12.0, 11.4 and 9.0 in the control, 40, 116.5 and 350 mg KBF4/kg body weight groups, respectively. The number of live pups per litter of the 350 mg KBF4/kg body weight group was statistically significantly decreased on PN 1. On PN 4 only pups of 2 litters of the mid-dose group were alive. No difference was observed in the sex ratio between the groups. No differences were observed on pup weight and pup weight changes on PN 1 and 4. On PN 1 the number of runts (pup weight less than mean pup weight of the control group minus 2 standard deviations) was statistically significantly increased in the 116.5 and 350 mg KBF4/kg body weight groups. In addition, the number of runts was statistically significantly increased in the 116.5 KBF4/kg body weight group on PN 4. Macroscopic observations in stillborn pups and pups that died between PN 1 -4 are did not reveal any treatment related abnormalities. No differences were observed in the motility, count and morphology of the epididymal sperm at scheduled necropsy. Absolute and relative testes and epididymides weights were comparable in all groups. Terminal body weight of the male animals of the 40 and 16,5 mg KBF4/kg body weight groups was statistically significantly decreased. At scheduled necropsy no treatment related gross changes were observed. Microscopic examination did not reveal treatment related histopathological changes in any of the sampled organs and tissues (epididymides, testes, uterus and ovaria).

Based on the effects on mortality in the 350 mg KBF4 group/ kg body weight group, (terminal) body weight and food consumption in the 116.5 and 350 mg KBF4/kg body weight groups, the NOAEL for parental toxicity is 40 mg KBF4/kg body weight/day. The NOAEL for fertility in the parental animals is 116.5 mg KBF4/kg body weight, based on the decreased number of pregnant females, corpora lutea and implantation sites in the 350 mg KBF4/kg body weight group.


Short description of key information:
Tin(II) bis(methanesulfonate):
No effects on fertility and reproductive parameters of parental animals were observed in the one generation reproduction toxicity study. The only findings were reduced body weights attributed to the palatability of the food in the mid and high dose groups.

Potassium tetrafluoroborate:
The NOAEL in rats is 116.5 and 40 mg/kg bw for fertility and parental toxicity, respectively.

Effects on developmental toxicity

Description of key information
Tin(II) bis(methanesulfonate): 
Developmental study waived as no developmental effects were observed in a one generation reproductive toxicity study except effects related to body weight reductions due to palatability issues.
Effect on developmental toxicity: via oral route
Endpoint conclusion:
no adverse effect observed
Effect on developmental toxicity: via inhalation route
Endpoint conclusion:
no adverse effect observed
Effect on developmental toxicity: via dermal route
Endpoint conclusion:
no adverse effect observed
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.

Tin(II) bis(methanesulfonate):

A developmental toxicity was not conducted. No developmental effects were observed in the one generation reproductive toxicity study with the exception of reduced body weight seen once the pups started eating food. Slight testicular changes were observed in the high dose group but were not statistically significant and could be related to the reduced growth attributed to the palatability of the food.

Potassium tetrafluoroborate:

In a GLP compliant reproduction/developmental toxicity screening test, performed according to OECD Guideline 421, Wistar rats were orally exposed to potassium tetrafluoroborate (TNO Quality of Life, 2007). 1% carboxymethylcellulose solution in water (CMC) was used as vehicle. Groups of 12 rats were dosed daily with 0, 40, 116.5 and 350 mg KBF4/kg body weight during 4 weeks premating, mating, gestation and up to day 4 of lactation (females). Two female animals of the 350 mg KBF4/kg body weight died during the lactation period. Daily clinical observations during the study did not reveal any remarkable findings in animals' appearance, general condition or behaviour among the dosing and control groups. Effects on water consumption were observed (not exactly measured) in the 350 mg KBF4/kg body weight group from week 3 onwards. Mean body weight and or body weight change of the animals of the 350 mg KBF4/kg body weight were statistically significantly decreased during several periods of the study. Food consumption of the 350 mg KBF4/kg body weight group was statistically significantly decreased during several periods of the study. In each group 12 females were placed with males. All females of the KBF4-treated groups and 11 females of the control group were mated within 4 days. The number of pregnant females, the number of females with live born pups and the number of males that became sires amounted to 8, 9, 9 and 5 for the control, 40, 116.5 and 350 mg KBF4/kg body weight groups, respectively. The mating index was 100% in all KBF4-treated groups and 92% in the control group. The female fecundity index and female fertility index were comparable between the control, 40 and 116.5 mg KBF4/kg body weight groups and ranged from 67-75%. In the 350 mg KBF4/kg body weight group fecundity index and female fertility index was 42%.The gestation index was 100% in all groups. The duration of gestation was comparable between the groups. The number of corpora lutea and implantation sites was statistically significantly decreased in the 350 mg KBF4/kg body weight group; no effect was observed in the other KBF4-treated groups when compared to the control group. Pre- and post-implantation loss was comparable in all groups. The number of litters with live born pups was 8, 9, 9 and 5 for the control, 40, 116.5 and 350 mg KBF4/kg body weight groups, respectively. The number of live pups per litter on post natal day (PN) 1 in the control, 40, 116.5 and 350 mg KBF4/kg body weight groups was 11.9, 12.1, 11.8 and 9.4, respectively. Pup mortality on PN 4 was comparable in all groups except for the mid-dose group and amounted to 3, 13, 3, 29 (incidences 3.2, 12, 2.8 and 62%) in the control, 40, 116.5 and 350 mg KBF4/kg body weight groups, respectively; in the 350 mg KBF4/kg body weight group the mortality was statistically significantly increased. The death of the pups of dam C63 (10 pups and C67 (11 pups) may be secondary to the death of the dams on PN 2 and 3, respectively. In the control, 40, 116.5 and 350 mg KBF4/kg body weight groups 0(8), 1(8), 0(9) and 3(2) litters, respectively were lost entirely between PN 1-4 (between brackets the number of litters with live pups on PN 4). The number of live pups per litter on PN 1 was 11.9, 12.1, 11.8 and 9.4 in the control, 40, 116.5 and 350 mg KBF4/kg body weight groups, respectively and on PN 4 the number of pups was 11.5, 12.0, 11.4 and 9.0 in the control, 40, 116.5 and 350 mg KBF4/kg body weight groups, respectively. The number of live pups per litter of the 350 mg KBF4/kg body weight group was statistically significantly decreased on PN 1. On PN 4 only pups of 2 litters of the mid-dose group were alive. No difference was observed in the sex ratio between the groups. No differences were observed on pup weight and pup weight changes on PN 1 and 4. On PN 1 the number of runts (pup weight less than mean pup weight of the control group minus 2 standard deviations) was statistically significantly increased in the 116.5 and 350 mg KBF4/kg body weight groups. In addition, the number of runts was statistically significantly increased in the 116.5 KBF4/kg body weight group on PN 4. Macroscopic observations in stillborn pups and pups that died between PN 1 -4 are did not reveal any treatment related abnormalities. At scheduled necropsy no treatment related gross changes were observed. Microscopic examination did not reveal treatment related histopathological changes in any of the sampled organs and tissues. Based on the effects on mortality, body weight and food consumption in the 350 mg KBF4 group/ kg body weight group, the NOAEL for maternal toxicity is 116.5 mg KBF4/kg body weight/day. The NOAEL for developmental toxicity is 40 mg KBF4/kg body weight based on the increased pup mortality (PN 1-4) in the 350 mg KBF4/kg body weight group and the increased number of runts in the 116.5 and 350 mg KBF4/kg body weight groups.

Justification for classification or non-classification

Tin(II) bis(methanesulfonate):

No reproductive or developmental effects were observed. Slight testicular effects were observed in pups but this was not statistically significant and was attributed to reduced growth noted caused by palatability of the food once the pups starting eating food. Classification of the test material for effects on fertility or developmental toxicity is not warranted in accordance with EU Directive 67/548/EEC and EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008.

Potassium tetrafluoroborate:

Based on the absence of adverse effects on fertility and of developmental toxicity in the absence of parental toxicity, classification of the test material for effects on fertility or developmental toxicity is not warranted in accordance with EU Directive 67/548/EEC and EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008.

Based on the read-across approach, the test item tin bis(tetrafluoroborate) does not require classification for effects on fertility or developmental toxicity

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