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Description of key information

A NOAEL of 40 mg/kg bw/day was established in a reproduction/developmental toxicity screening test and a NOAEL of 226 mg/m3 was established in a 90-day inhalation study in rats for systemic effects. No local effect were observed at concentrations up to 226 mg/m3 in the 90-day inhalation study.

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
NOAEL
40 mg/kg bw/day
Study duration:
subacute
Species:
rat
Quality of whole database:
GLP-compliant guideline study, klimisch 1

Repeated dose toxicity: inhalation - systemic effects

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEC
226 mg/m³
Study duration:
subchronic
Species:
rat
Quality of whole database:
GLP-compliant guideline study, klimisch 1

Repeated dose toxicity: inhalation - local effects

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEC
226 mg/m³
Study duration:
subchronic
Species:
rat
Quality of whole database:
GLP-compliant guideline study, klimisch 1

Repeated dose toxicity: dermal - systemic effects

Endpoint conclusion
Endpoint conclusion:
no study available

Repeated dose toxicity: dermal - local effects

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Oral studies:

In a GLP-compliant OECD Guideline 407 study, groups of 10 male and 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. Animals were observed for clinical signs, body weight, food and water consumption. Hematological and clinical chemistry examinations were performed at the termination of the study and after the recovery period on all animals. Urinalysis was performed on all animals a few days before termination of the study. After 8 days, at the termination fo the study and after the recovery period, biochemical examination was performed on all animals, including examination of total thyroxine, triiodothyronine and thyroid-stimulation hormone levels. All animals were subjected to necropsy, including macroscopic examination of the skin, orifices, eyes, teeth, oral mucosa and internal organs. Animals of the control and high dose groups were subjected to histopathological examinations. 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. Hematological examinations revealed slight but statistically significant decreases in erythrocytes counts and hematocrit value in female animals of the intermediate and high dose group. Females of the high dose group also showed slightly decreased hemoglobin values. The MCV values were not affected. All findings on hematological 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 hematocrit and hemoglobin 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.

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. Terminal body weight of the male animals of the 40 and 116.5 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.

Inhalation studies:

In a GLP compliant inhalation toxicity study performed according to OECD Guideline 412, potassium tetrafluoroborate was administered to Wistar rats (TNO Triskelion BV, 2012). Four groups of 5 male and 5 female rats were exposed nose-only to target concentrations of 0 (control), 25, 75 or 225 mg/m3 potassium tetrafluoroborate for 6 hours/day, 5 days/week over a 28 -day period, with a total of 20 exposure days. The concentration levels were chosen based on the results of a 7 -day range finding study in which no exposure related changes were found up to a concentration of 104.4 mg/m3, the highest concentration tested. The mean actual concentrations (± standard deviation) of potassium tetrafluoroborate in the various test atmospheres – based on gravimetric analysis – were 20.5 (± 1.8), 74.0 (± 5.1) and 224.2 (± 10.1) mg/m3 for the low, mid and high concentration levels, respectively. The average particle size (Mass Median Aerodynamic Diameter; MMAD) was 1.68μm (with a geometric standard derviation (gsd) of 2.31), 2.57μm (gsd of 2.57) and 2.52μm (gsd of 2.54) for the low, mid and high concentration test atmospheres, respectively. No treatment-related clinical abnormalities or mortality were observed in response to the exposure to potassium tetrafluoroborate. Decreased body weight gain was observed in males of the high concentration group. A concomitant reduction in food consumption was observed in males of this group. No other changes in body weight or food consumption were observed during the study. Hematology, conducted in all rats at necropsy, did not reveal any treatment-related abnormalities. Clinical chemistry, conducted in plasma obtained from all rats at necropsy, did not show any treatment-related changes. An elevated – although within the historical control range – alkaline phosphatase (ALP) activity in males of the mid and high concentration group was not corroborated by changes in other parameters and was therefore considered to be of no toxicological relevance. There were no treatment-related changes in absolute organ weights or in organ to body weight ratios. The slightly decreased absolute weights of almost all organs in males of the high concentration group – of which brain and liver weight reached statistical significance – were considered secondary to the growth impairment, as relative organ weight remained unaffected. Macroscopic examination at necropsy and histopathological examination of organs and tissues – including the complete respiratory tract – did not reveal any treatment-related changes. No visible residues of test material were detected in the airways during histopathological examination. No indications of impaired thyroid function – as judged by possible organ weight or microscopic changes – were observed. In conclusion, exposure to potassium tetrafluoroborate resulted in impaired growth and reduced food intake in male animals of the high concentration group. Therefore, the NOAEL in rats was placed at the mid concentration level of 74.0 mg/m3 potassium tetrafluoroborate.

In a GLP compliant inhalation toxicity study performed according to OECD Guideline 413, potassium tetrafluoroborate was administered to Wistar rats (TNO Triskelion BV, 2015). Four groups of 10 male and 10 female rats were exposed nose-only to target concentrations of 0 (control), 25, 75 or 225 mg/m3 potassium tetrafluoroborate for 6 hours/day, 5 days/week over a 90 -day period, with a total of 65 exposure days. The concentration levels were chosen based on the results of the 28 -day study in which some exposure related changes were found up to a concentration of 225 mg/m3, the highest concentration tested.

The target concentrations were accurately achieved as demonstrated by the results of gravimetric analysis of the test atmospheres. The overall mean actual concentrations (± standard deviation) during exposure were 25.8 (± 1.9), 76.3 (± 2.5) and 225.9 (± 9.7) mg/m3 for the low-, mid- and high concentration groups, respectively. The average (± standard deviation) aerosol particle size was 1.65 (± 0.10), 2.45 (± 0.33) and 2.48 (± 0.22) μm MMAD (mass median aerodynamic diameter) for the low-, mid- and high concentration test atmospheres, with corresponding average geometric standard deviations of 2.39 (± 0.16), 2.19 (± 0.15) and 2.25 (± 0.15), respectively, i.e. well within the recommended range of 1 - 3 μm MMAD with a gsd in the range of 1.5 - 3.0.

All animals survived until scheduled sacrifice. Clinical and ophthalmoscopic observations revealed no exposure-related abnormalities. Growth and food consumption were not adversely affected by the exposure and were comparable across the groups. Analysis of haematology and clinical chemistry parameters did not reveal any adverse exposure-related changes. In the absence of any corroborative changes, a slight - but statistically significant - decrease in MCH (mean corpuscular haemoglobin concentration) and plasma gamma glutamyl transferase (GGT) activity in females of the high concentration group were considered to be of no toxicological relevance. No treatment-related changes in absolute or relative (to body weight) organ weights were observed in response to the exposure to the test material. Macroscopic examination at scheduled termination revealed no treatment-related gross pathological changes. In addition, microscopic examination did not reveal any histopathological changes which were attributable to the exposure to the test material. Under the conditions of the current study, inhalation exposure up to a concentration of 225.9 mg/m3 was tolerated well by the animals and did not result in any adverse exposure-related changes. Therefore, the No-Observed-Adverse-Effect-Concentration (NOAEC) for subchronic inhalation exposure of rats to Potassium tetrafluoroborate was placed at 225.9 mg/m3, the highest concentration tested.

Justification for classification or non-classification

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