Dihydrogen hexafluorotitanate(2-)

Short-term toxicity to fish

Link to relevant study record(s)

Reference

Reference 1

Endpoint:

short-term toxicity to fish

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Guideline study with acceptable restrictions

Qualifier:

according to guideline

Guideline:

OECD Guideline 203 (Fish, Acute Toxicity Test)

Version / remarks:

adopted 1992-07-17

Deviations:

no

GLP compliance:

no

Analytical monitoring:

yes

Details on sampling:

Samples of all test solutions were taken for chemical analysis. Samples were taken from all respective test solutions at test start (fresh) and after 48 h exposure (aged), and also from the renewed media at 48 h (fresh) and after 96 h exposure (aged). The test solutions were analysed for fluoride and titanium. Samples of fresh and aged test media of all treatments and the control were analysed using an ISE probe for fluoride and ICP-MS for titanium.
Results can be found in the field "Any other information on results incl. tables" below.

Vehicle:

no

Details on test solutions:

PREPARATION AND APPLICATION OF TEST SOLUTION (especially for difficult test substances)
Each test solution was prepared individually by dissolving 0.02, 0.2, 2, 6, and 20 g of the test item in 20 L of copper-reduced dilution water and stirring for 2 h at 300 rpm. The control test media was copper-reduced dilution water only.

Test organisms (species):

Danio rerio (previous name: Brachydanio rerio)

Details on test organisms:

TEST ORGANISM
- Common name: Zebra fish
- Feeding during test: fish were not fed 24h before and during the test.

Test type:

semi-static

Water media type:

freshwater

Limit test:

no

Total exposure duration:

96 h

Remarks on exposure duration:

no

Post exposure observation period:

none

Hardness:

1.1 mmol/L

Test temperature:

22.9 – 23.2°C

pH:

The pH was between 7.9 - 8.6 in the control and in solutions with nominal concentrations of 1.0 and 10 mg/L. In solutions with the nominal concentration of 100 mg/L, a slight pH decrease was observed while the pH decreased to a mean pH of 4.3 and 3.9 in solutions with 300 and 1000 mg/L (nominal), respectively.

Dissolved oxygen:

The oxygen saturation was between 93 – 104% in all solutions.

Salinity:

not applicable

Nominal and measured concentrations:

Test concentrations (nominal loadings): 1.0, 10, 100, 300 and 1000 mg/L

Details on test conditions:

TEST SYSTEM
- Test vessel: the test vessels were 3 L glass beakers. Approximately 3 L of test solution was added to the test vessels followed by the introduction of the fish.
- Renewal rate of test solution: the test solutions were renewed after 48 h.
- Aeration: slightly aeration via glass capillary
- No. of organisms per vessel: 5
- No. of vessels per concentration (replicates): 1
- No. of vessels per control (replicates): 1

OTHER TEST CONDITIONS
- Photoperiod: light/dark cycle of 14/10 hours
- The pH and oxygen saturation of the test solutions were measured in each test vessel before addition of the fish and daily afterwards.

EFFECT PARAMETERS MEASURED (with observation intervals if applicable) :
- Mortality and clinical signs (sub-lethal and abnormal behaviour) of the fish were recorded after 3, 24, 48, 72, and 96 h.

TEST CONCENTRATIONS
- Test concentrations (nominal concentration): 1.0, 10, 100, 300 and 1000 mg/L

Reference substance (positive control):

no

Duration:

96 h

Dose descriptor:

LC50

Effect conc.:

172.4 mg/L

Nominal / measured:

nominal

Conc. based on:

test mat.

Basis for effect:

mortality (fish)

Remarks on result:

other: 95% CL: 98.1- 281.1

Duration:

96 h

Dose descriptor:

NOEC

Effect conc.:

100 mg/L

Nominal / measured:

nominal

Conc. based on:

test mat.

Basis for effect:

mortality (fish)

Duration:

96 h

Dose descriptor:

LOEC

Effect conc.:

300 mg/L

Nominal / measured:

nominal

Conc. based on:

test mat.

Basis for effect:

mortality (fish)

Details on results:

- Turbidity of the test media was observed in solutions with 10 and 100 mg/L and the test item precipitated on the bottom of the beakers containing 300 and 100 mg/L test item (all nominal).
- Mortality of 100% compared to the control was observed at 300 and 1000 mg/L after 24 h. No further mortalities were observed in any of the tested treatments, including the control.
- No signs of disease or stress were observed.
- All surviving specimens gave the impression of healthy condition.

Results with reference substance (positive control):

not examined

Reported statistics and error estimates:

The endpoint of the test was mortality, and the respective LCx, NOEC, and LOEC values were determined. The NOEC and LOEC were determined based on the observation of mortality. Probit analysis was performed to plot dose-response curves and to estimate the LC10 and LC50, assuming log-normal distribution of the values. The computer software ToxRat® Professional was used for statistical evaluations.

Sublethal observations / clinical signs:

TEST CONCENTRATIONS

The chemical analysis of dissolved fluoride in fresh test medium at test start revealed a recovery of 96 - 119% of nominal concentrations. Fluoride concentrations of the aged test medium at test end were 93 - 127% of nominal fluoride concentrations. As there was no difference between the measured and nominal concentrations (i.e. < 20%), the arithmetic mean of measured concentrations was calculated in accordance with the OECD guidance document on aquatic toxicity testing of difficult substances and mixtures (Series on testing and assessment, number 23; 2000))*.

The chemical analysis of dissolved titanium in the fresh test medium at test start revealed a recovery of 15 - 105% of nominal concentrations. Titanium concentrations of the aged test medium at test end were < 1 - 96% of the nominal titanium concentrations. As a decrease in titanium concentrations was observed, the geometric mean of the measured concentrations was calculated in accordance with the OECD guidance document on aquatic toxicity testing of difficult substances and mixtures (Series on testing and assessment, number 23; 2000)*.

Table 2: Measured concentration of titanium and fluoride

K2TiF6concentration [mg/L]	Measured Ti 0h - % nominal	Measured Ti 48 h old - % nominal	Measured Ti 48 h fresh - % nominal	Measured Ti96 h - % nominal	Geomean measured conc. of fresh & aged Ti [% of nominal Ti]	Measured F6 0h - % nominal	Measured F6 48 h old - % nominal	Measured F6 48 h fresh - % nominal	Measured F 96 h - % nominal	Mean measured conc. of fresh & aged F6[% of nominal F6]	Test start pH (0h)	Test end pH (96h)
Control	-	-	-	-	-	-	-	-	-	-	8.33	8.47
1.0	24.6	36.6	0.61	0.61	4.3	117	119	127	119	122.4	8.29	8.48
10.0	23.6	33.1	0.06	0.06	1.3	97.5	97.5	97.5	97.5	97.5	8.04	8.44
100	15.3	38.6	0.01	0.01	0.4	96.6	95.5	98.5	97.4	97.3	6.78	7.45
300	85.1	*	81.6	*	83.3	97.4	*	96.3	*	96.9	4.39	*
1000	105	*	96.3	*	100.7	96	*	95.3	*	95.7	3.94	*

*After 48 h the test media solutions of the test levels 300 and 1000 mg/L were not prepared since all fish had been found dead before.

Validity criteria fulfilled:

not specified

Conclusions:

The estimated LC50 values for the tested substance dipotassium hexafluorotitanate is 172.4 mg K2TiF6/L. The NOEC value for the tested substance is 100 mg/L.

Reference 2

Endpoint:

short-term toxicity to fish

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Justification for type of information:

1. HYPOTHESIS FOR THE ANALOGUE APPROACH
Dihydrogen hexafluorotitanate is an inorganic substance which will rapidly dissociate into fluoride, potassium and titanium ions upon dissolution in the environment or the human body, and so, similar toxicological properties can be assumed. However, titanium ions do not remain in solution, only fluoride ions do. The approach follows scenario 1 of the RAAF (ECHA 2017). For details, see attached Read-Across statement in IUCLID chapter 13.2.

2. SOURCE AND TARGET CHEMICAL(S) (INCLUDING INFORMATION ON PURITY AND IMPURITIES)
Source
Dipotassium hexafluorotitanate (CAS 16919-27-0)
Target
Dihydrogen hexafluorotitanate (CAS 17439-11-1)

3. ANALOGUE APPROACH JUSTIFICATION
Since dihydrogen hexafluorotitanate rapidly dissociates into fluoride, protons and titanium ions upon dissolution in aqueous solutions, such as the environment or human body, and only fluoride but not titanium ions will remain in solution, it can be assumed that toxicity (if any) will be driven by the fluoride anion. The non-common dissociation products, potassium, sodium, or just hydrogen ions, are considered not to influence the (eco)toxicological profile of Ti2-F6 to a significant degree. These ions are present in the environment and in the human body in considerable amounts. Potassium and sodium levels influence multiple physiological processes. The body has mechanisms to protect from the intake of harmful concentrations of those.
This read-across is based on the hypothesis that source and target substances have similar (eco)toxicological properties, because they dissociate to common anion. The target substance dihydrogen hexafluorotitanate and the source substance dipotassium hexafluorotitanate form hexafluorotitanate species in aqueous solution. Hexafluorotitanate is considered to be (eco)toxicologically relevant, whereas potassium ions are essential elements and practically non-toxic.
For additional information, please refer to the attached read-across statement in IUCLID chapter 13.2.

4. DATA MATRIX
Please refer to the attached read-across statement in IUCLID chapter 13.2.

Reason / purpose for cross-reference:

read-across source

Duration:

96 h

Dose descriptor:

LC50

Effect conc.:

192.7 mg/L

Nominal / measured:

nominal

Conc. based on:

test mat.

Basis for effect:

mortality (fish)

Remarks on result:

other: converted to the target substance

Duration:

96 h

Dose descriptor:

NOEC

Effect conc.:

111.8 mg/L

Nominal / measured:

nominal

Conc. based on:

test mat.

Basis for effect:

mortality (fish)

Remarks on result:

other: converted to the target substance

Duration:

96 h

Dose descriptor:

LOEC

Effect conc.:

335.3 mg/L

Nominal / measured:

nominal

Conc. based on:

test mat.

Basis for effect:

mortality (fish)

Remarks on result:

other: converted to the target substance

Details on results:

- Turbidity of the test media was observed in solutions with 10 and 100 mg/L and the test item precipitated on the bottom of the beakers containing 300 and 100 mg/L test item (all nominal).
- Mortality of 100% compared to the control was observed at 300 and 1000 mg/L after 24 h. No further mortalities were observed in any of the tested treatments, including the control.
- No signs of disease or stress were observed.
- All surviving specimens gave the impression of healthy condition.

Results with reference substance (positive control):

not examined

Reported statistics and error estimates:

The endpoint of the test was mortality, and the respective LCx, NOEC, and LOEC values were determined. The NOEC and LOEC were determined based on the observation of mortality. Probit analysis was performed to plot dose-response curves and to estimate the LC10 and LC50, assuming log-normal distribution of the values. The computer software ToxRat® Professional was used for statistical evaluations.

Sublethal observations / clinical signs:

TEST CONCENTRATIONS

The chemical analysis of dissolved fluoride in fresh test medium at test start revealed a recovery of 96 - 119% of nominal concentrations. Fluoride concentrations of the aged test medium at test end were 93 - 127% of nominal fluoride concentrations. As there was no difference between the measured and nominal concentrations (i.e. < 20%), the arithmetic mean of measured concentrations was calculated in accordance with the OECD guidance document on aquatic toxicity testing of difficult substances and mixtures (Series on testing and assessment, number 23; 2000))*.

The chemical analysis of dissolved titanium in the fresh test medium at test start revealed a recovery of 15 - 105% of nominal concentrations. Titanium concentrations of the aged test medium at test end were < 1 - 96% of the nominal titanium concentrations. As a decrease in titanium concentrations was observed, the geometric mean of the measured concentrations was calculated in accordance with the OECD guidance document on aquatic toxicity testing of difficult substances and mixtures (Series on testing and assessment, number 23; 2000)*.

Table 2: Measured concentration of titanium and fluoride

K2TiF6concentration [mg/L]	Measured Ti 0h - % nominal	Measured Ti 48 h old - % nominal	Measured Ti 48 h fresh - % nominal	Measured Ti96 h - % nominal	Geomean measured conc. of fresh & aged Ti [% of nominal Ti]	Measured F6 0h - % nominal	Measured F6 48 h old - % nominal	Measured F6 48 h fresh - % nominal	Measured F 96 h - % nominal	Mean measured conc. of fresh & aged F6[% of nominal F6]	Test start pH (0h)	Test end pH (96h)
Control	-	-	-	-	-	-	-	-	-	-	8.33	8.47
1.0	24.6	36.6	0.61	0.61	4.3	117	119	127	119	122.4	8.29	8.48
10.0	23.6	33.1	0.06	0.06	1.3	97.5	97.5	97.5	97.5	97.5	8.04	8.44
100	15.3	38.6	0.01	0.01	0.4	96.6	95.5	98.5	97.4	97.3	6.78	7.45
300	85.1	*	81.6	*	83.3	97.4	*	96.3	*	96.9	4.39	*
1000	105	*	96.3	*	100.7	96	*	95.3	*	95.7	3.94	*

*After 48 h the test media solutions of the test levels 300 and 1000 mg/L were not prepared since all fish had been found dead before.

Validity criteria fulfilled:

not specified

Conclusions:

The estimated LC50 values for the tested substance dipotassium hexafluorotitanate is 172.4 mg K2TiF6/L. The NOEC value for the tested substance is 100 mg/L. Converted to the target substance this corresponds to a LC50 of 192.7 mg H2TiF6/L and a NOEC of 111.8 mg H2TiF6/L.

Description of key information

The acute toxicity of of the structural analogue dipotassium hexafluorotitanate to Danio rerio (zebra fish) was tested according to OECD 203; an LC50 of 192.7 mg/L was recalculated for dihydrogen hexafluorotitanate.

Key value for chemical safety assessment

Fresh water fish

Fresh water fish

Dose descriptor:

LC50

Effect concentration:

192.7 mg/L

Additional information

Dihydrogen / dipotassium hexafluorotitanate

The acute toxicity of the structural analogue dipotassium hexafluorotitanate to Danio rerio (zebra fish) was tested according to OECD 203. An LC50 of 192.7 mg/L was recalculated for dihydrogen hexafluorotitanate (conversion from K2TiF6 value and corrected to max. purity). Information on the read-across approach has been attached in IUCLID section 13.2.