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Key value for chemical safety assessment

Effects on fertility

Effect on fertility: via oral route
Endpoint conclusion:
adverse effect observed
Dose descriptor:
NOAEL
116.5 mg/kg bw/day
Study duration:
subacute
Species:
rat
Quality of whole database:
GLP complaint OECD guideline study, klimisch 1
Effect on fertility: via inhalation route
Endpoint conclusion:
no study available
Effect on fertility: via dermal route
Endpoint conclusion:
no study available
Additional information

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

Justification for selection of Effect on fertility via oral route:
Only study available.

Effects on developmental toxicity

Description of key information

Under these experimental conditions and results of the developmental toxicity rat study (OECD 414), the NOAEL for maternal parameters was considered to be 250 mg/kg/day. The NOAEL for the embryo-fetal development was considered to be 750 mg/kg/ day.

Therefore, the substance is considered not to be teratogenic in the rat under these exprimental conditions.

Effect on developmental toxicity: via oral route
Endpoint conclusion:
adverse effect observed
Dose descriptor:
NOAEL
40 mg/kg bw/day
Study duration:
subacute
Species:
rat
Quality of whole database:
GLP complaint OECD guideline study, klimisch 1
Effect on developmental toxicity: via inhalation route
Endpoint conclusion:
no study available
Effect on developmental toxicity: via dermal route
Endpoint conclusion:
no study available
Additional information

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 behavior 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.

In a GLP compliant developmental toxicity test, performed according to OECD Guideline 414,time-mated female Sprague-Dawley rats

were orally exposed to potassium tetrafluoroborate. 1% carboxymethylcellulose solution in water (CMC) was used as vehicle.

The test item, Potassium Tetrafluoroborate (batch No. BWF4103) was administered by oral gavage daily from Day 6 to Day 20p.c. inclusive at doses of 85, 250 or 750 mg/kg/day.

The toxicologically significant test item treatment effects were the following:

At 750 mg/kg/day

- one premature sacrifice for bad health condition,

- isolated clinical signs (emaciated appearance and piloerection),

-minimal mean body weight loss in the first 3 days of treatment, followed by a tendency towards  low mean body weight gains until Day 15p.c.

- low mean body weight from Day 9p.c

-low mean food consumption throughout the entire treatment period,

-low mean carcass weight and mean net body weight change,

- low mean fetal body weight and mean fetal body weight/placental weight ratio, together with ossification delay

- increased incidences of fetal skeletal variations (ribs, head and metatarsals).

 

At 250 mg/kg/day:

      - tendency towards low mean body weight gain up to Day 15p.c.,

      - slightly low mean food consumption in the first 3 days of treatment,

      - low mean net body weight change from Day 6p.c.,

      - increased incidences of fetal skeletal variations(ribs).

 

At 85 mg/kg/day:

      - increased incidences of fetal skeletal variations(ribs). 

Under the experimental conditions and results of this study, the NOAEL for maternal parameters was considered to be 250 mg/kg/day. The NOAEL for the embryo-fetal development was considered to be 750 mg/kg/ day.

Therefore, the substance is considered not to be teratogenic in this species under these exprimental conditions.


Justification for selection of Effect on developmental toxicity: via oral route:
Based on studies available.

Justification for classification or non-classification

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, Labeling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008.