Lithium fluoride

Endpoint summary

Additional information

SHORT-TERM TOXICITY TO FISH

A short-term toxicity study on fish with lithium fluoride is not available. Consequently, read-across was applied using characteristically similar compounds, lithium chloride and sodium fluoride.

 

Read-across with lithium chloride (Toxikon 1997): A short-term toxicity study with Oncorhynchus mykiss exposed to lithium chloride was performed according to OECD guideline 203. Rainbow trout were exposed for 96 hours to the following nominal concentrations: 62.5, 125, 250, 500 and 1000 mg LiCl/L and a control group. Mean measured concentrations of lithium chloride ranged from 59.4 to 1021 mg/L and from 94 to 103 % of nominal concentrations. Based on the measured concentrations a 96 -hour LC50 of 158 mg LiCl/L and a NOEC of 59.4 mg LiCl/L was determined. Based on the molecular weight, a recalculation for lithium fluoride was made and revealed an LC50 and NOEC of 96.69 and 36.35 mg LiF/L, respectively.

Read-across with sodium fluoride (Camargo & Tarazona 1991, Camargo 1991, EU RAR 2002): Effect concentrations of several short-term toxicity studies performed with sodium fluoride are available in the literature. Camargo (1991) and Camargo & Tarazona (1991) conducted a static freshwater test with Salmo trutta and Oncorhynchus mykiss exposed to sodium fluoride. LC₅₀ values for salmo trutta were significantly (p < 0.05) higher than those for Oncorhynchus mykiss to sodium fluoride for 96, 120, 144 and 192 hours. This indicates that Oncorhynchus mykiss is the more sensitive species to F- ions than Salmo trutta. After an exposure duration of 96 hours, LC₅₀ values for Salmo trutta and Oncorhynchus mykiss of 129.88 mg F/L (164.5 ppm) and 84.88 mg F/L (107.5 ppm) were determined. Based on the molecular weight, a recalculation for lithium fluoride was performed and revealed LC₅₀ values (96h) for Salmo trutta and Oncorhynchus mykiss of 177.35 LiF/L and 115.9 mg LiF/L, respectively.

The EU RAR (2002) reviews and summarizes the available effect concentrations of fluoride to various fish species. All reported tests were performed with NaF and the test results were corrected for fluoride ion (F-). Reported LC₅₀ values for various fish species ranged from 51 to 340 mg F/L. The lowest LC₅₀ value of 51 mg/L is based on a toxicity study with Oncorhynchus mykiss after an exposure duration of 96 hours. The recalculated 96 -hour LC₅₀ for lithium fluoride for Oncorhynchus mykiss is 69.64 mg LiF/L.

In this weight of evidence approach the effect concentrations of lithium and fluoride compounds were evaluated in different fish species. The results of the studies with the OECD guideline 203 compliant species Oncorhynchus mykiss after an exposure time of 96 hours were considered as the most reliable endpoint. The fish species showed LC₅₀ values in the same range for lithium and fluoride, however, fish seemed to be more sensitive to fluoride compounds. Fluoride was considered as the more toxicological relevant moiety with respect to short-term toxicity to fish and the lowest 96 -hour LC50 for Oncorhynchus mykiss of 69.64 mg LiF/L was considered as key value for chemical risk assessment.

 

LONG-TERM TOXICITY TO FISH

A long-term toxicity study on fish with lithium fluoride is not available. Consequently, read-across was applied using characteristically similar compounds, lithium hydroxide monohydrate and sodium fluoride.

 

Read -across with lithium hydroxide monohydrate (Toxi-Coop, 2012): In a chronic toxicity study early life stages (embryo, larvae and juveniles) of fish (Danio rerio) were exposed to lithium hydroxide monohydrate according to the OECD guideline 210. Around 40 eggs per concentration level were exposed in a semi static test to aqueous test media containing the test item for 34 days at a range of concentrations (based on a preliminary study) under defined conditions. Results showed that lithium hydroxide monohydrate had significant lethal effects on early life stages of Zebrafish (Danio rerio) at a concentration level of 24.35 mg/L (measured concentration). The observed effect was associated with larval/juvenile stages, but no significant effect was observed during the embryonic stage. No significant sub lethal effects (hatching of the larvae, body weight, body length, deformities and abnormal behaviour) were observed in any concentration tested. Under conditions of the study, a LOEC value of 24.35 mg test item/L and a NOEC value of 17.35 mg test item/L were determined. Based on the molecular weight the recalculated NOEC and LOEC values for lithium fluoride are 10.73 mg/L and 15.05 mg/L, respectively.

Read-across with sodium fluoride (RAR 2002, Slooff et al. 1988): In a 21-days test with Oncorhynchus mykiss a LC₅ value of 4 mg F/L was reported (actual concentration). This value is considered to be equivalent to the NOEC for mortality. The test was conducted in very soft (12 mg CaCO₃/L) natural water with daily renewal of the test water. Based on the molecular weight the recalculated NOEC for lithium fluoride is 5.46 mg/L.

The results of the long-term toxicity tests fit well with the results of the short-term toxicity studies. Oncorhynchus mykiss is the most sensitive species in both chronic and acute tests. Further, the results of the long-term toxicity studies available indicates that fish are more sensitive to fluoride compounds. The lowest NOEC value of 5.46 mg LiF/L for Oncorhynchus mykiss is considered as key value for chemical safety assessment.

 

SHORT-TERM TOXICITY TO AQUATIC INVERTEBRATES

A short-term toxicity study on aquatic invertebrates with lithium fluoride is not available. Consequently, read-across was applied using characteristically similar compounds, lithium chloride and sodium fluoride.

Read-across with sodium fluoride (EU-RAR 2001): The EU-RAR reviews and summarizes the available data on short-term toxicity to marine and freshwater invertebrates. Reported EC₅₀ values for Daphnia spp. ranged from 97 - 352 mg/L (based on nominal concentrations). The recalculated EC₅₀ values for lithium fluoride are between 132.44 - 480.62 mg/L for Daphnia spp. For benthic trichoptera larvae EC50 values ranged between 26 – 48 mg F/L after 96 hours of exposure, corresponding to 35.5 – 65.54 mg LiF/L.

Reported EC₅₀ values for the marine species Mysidopsis bahia and Perna perna ranged from 10.5 - 39 mg F/L (based on nominal concentrations). Based on these data, the calculated EC₅₀ values for lithium fluoride are between 14.34 - 53.25 mg/L for the tested marine species.

 

Read-across with lithium chloride (Toxikon 1997): A static freshwater toxicity test was conducted to determine the acute toxicity of lithium chloride to the water flea, Daphnia magna, according to OECD Guideline 202. Mean measured concentrations of lithium chloride ranged from 63.4 to 978 mg/L and from 99 to 109 % of nominal. All test solutions appeared clear and colourless and concentrations remained stable throughout the test. Mortality of the water flea exposed for 48 hours to lithium chloride ranged from 5 % at test concentrations smaller or equal to 123 mg/L and 100 % at a concentration greater than or equal to 501 mg/L. One water flea treated with 63.4 mg/L died as a result of becoming physically stuck to the wall of the test chamber, this death was not chemically related. Control mortality was 0 %.The 48-hour EC₅₀ was 249 mg Lithium chloride/L with 95 % confidence limits of 197 and 315 mg/L. The NOEC was 63.4 mg/L. Based on the molecular weight the recalculated EC₅₀ and NOEC values for lithium fluoride are 152.37 mg/L and 38.8 mg/L, respectively.

Based on the available data, the lowest observed EC₅₀ values were 35.5 - 65 .54 mg LiF/L (based on EC₅₀ of 26 - 48 mg F/L) for benthic trichoptera larvae. These values were not used for the risk assessment, because further information about the study design is not given in the review article. In addition, the use of trichoptera is not recommended in the guideline. The results of the GLP study (Toxikon 1997, J9705004a) and EU RAR (2002) with the guideline compliant species Daphnia magna showed a good agreement with EC₅₀ values of 152.37 mg LiF/L and 132.44 mg LiF/L. Since aquatic invertebrates seemed to be more sensitive to fluoride compounds and for worst-case consideration the lowest observed EC₅₀ value (132.44 mg LiF/L) with the guideline species Daphnia magna was considered as key value. For marine species, the lowest observed EC₅₀ value was 14.34 mg LiF/L for Mysidopsis bahia after 96 hours of exposure and was therefore chosen as key value.

 

LONG-TERM TOXICITY TO AQUATIC INVERTEBRATES

A long-term toxicity study on aquatic invertebrates with lithium fluoride is not available. Consequently, read-across was applied using characteristically similar compounds, lithium and sodium fluoride.

 

Read-across with sodium fluoride (EU-RAR 2001): The EU-RAR reviews and summarises the available data on long-term toxicity to aquatic invertebrates. All reported tests were performed with NaF and the test results were corrected for fluoride ion. Reported NOEC values for long-term toxicity to Daphnia magna were 3.7 and 14.1 mg F-/L after 21 d of exposure, based on effects on reproduction. Based on the molecular weight, the recalculated NOEC values for lithium fluoride are 5.05 and 19.25 mg/L.

 

Read-across with lithium (Toxi-Coop 2012): The influence of lithium on the reproductive output of Daphnia magna was estimated in a semi-static test according to OECD guideline 211. Young female daphnids were exposed to nominal concentrations of the test item of 0.50, 0.75, 1.13, 1.70, 2.53, 3.80 and 5.70 mg lithium/L. The parallel running analytical determinations confirmed that the test item concentrations examined (lowest and highest test concentrations) remained within the range of ± 20 % of the nominal and of the initial concentrations (varied between 98 and 117 per cent of the nominal concentration); thus, all results were based on the nominal test item concentrations. In the three highest tested concentrations (2.53, 3.80 and 5.70 mg/L) all parent animals died by the 13th day of the test without producing any offspring. Therefore the results of these concentrations were excluded from the data analysis related to the reproductive output. The reproduction was not reduced statistically significantly in the concentration range of 0.50 – 1.70 mg/L compared to the untreated control group. During the evaluation of the body length of parent animals at the end of the test, statistically significant difference was not observed in the remained living parent daphnids (in the concentration range of 0.50 – 1.70 mg/L) compared to the control group. Aborted broods, presence of male neonates or ephippia were not noticed during the test. Accordingly, the 21-day NOEC value related to reproduction was determined to be 1.70 mg/L and the LOEC value as 2.53 mg/L. The obtained results were not sufficient for an exact EC₅₀ value estimation. The 21-day EC₅₀ was determined to be higher than 1.70 mg/L.

Based on the molecular weight, the recalculated NOEC and LOEC values for lithium fluoride are 6.35 mg/L and 9.46 mg/L, respectively.

The results of the long-term toxicity tests with Daphnia magna showed NOEC values in the same range. The results indicate that the test species is more sensitive to fluoride compounds. The lowest NOEC value observed was 5.05 mg LiF/L and is therefore considered as key value.

 

TOXICITY TO AQUATIC ALGAE AND CYANOBACTERIA

A toxicity study for aquatic algae and cyanobacteria with lithium fluoride is not available. Consequently, read across was applied using study results obtained from lithium chloride and sodium fluoride.

 

Read-across with lithium chloride (Steinbeis-Transferzentrum 2012): The effect of lithium chloride on the growth of an algal species Desmodesmus subspicatus over a 72 hour static exposure period was assessed according to OECD guideline 201. The algae species were exposed to 0, 25.0 mg/L, 50.0 mg/L, 100 mg/L, 200 mg/L, 400 mg/L of the test item. AES-analysis confirmed that the test solutions were correctly dosed, i.e., the recoveries were within 91.9 to 98.2 % of the nominal concentrations at study start. At the end of the exposure, i.e., after 72 hours, the recoveries ranged from 92.4 to 97.8 % of the nominal concentrations demonstrating that the lithium concentrations were stable throughout the exposure period. Consequently, the results of the definitive test were based on nominal concentrations. In this 72-h algal growth inhibition test with Desmodesmus subspicatus - the 72-h EC₅₀ based on growth rate was determined as greater than 400 mg LiCl/L, - the overall NOEC was determined to be 25 mg LiCl/L. Based on these data, the recalculated LC₅₀ for lithium fluoride is greater than 244.77 mg/L and the NOEC value is 15.3 mg LiF/L.

Read across with sodium fluoride (EU-RAR 2001, Camargo 2003): The EU-RAR (2001) reviews and summarizes the available data on the toxicity of sodium fluoride to freshwater and marine algae species. Expressed in terms of fluoride ion (F-), the EC₅₀ values for freshwater algae are reported to range from 43 to 122 mg F-/L. Recalculations of these data for lithium fluoride, based on the molecular weight, resulted in a corresponding EC₅₀ range of 58.71 to 166.58 mg LiF/L.

The EC₅₀ value for the marine algae Skeletonema costatum was 81 mg F-/L after an exposure duration of 96 hours and corresponds to a value of 110.6 mg LiF/L. NOEC values for other marine species were reported to be in the range between 50 - 200 mg F-/L (68.27 to 273.08 mg LiF/L), however the EU-RAR states that these values should be used with caution due to the relatively long exposure time of 14 - 21 days.

The review paper Camargo (2003) also summarizes the toxic effects of sodium fluoride to algae species. The results are expressed in the terms of fluoride ion (F-). In this paper EC₅₀ values of 123 mg F-/L and 82 mg F-/L after 96 hours of exposure were reported for the freshwater species Selenastrum capricornutum and the marine species Skeletonema costatum, respectively. Based on the molecular weight, the recalculated EC₅₀ values for lithium fluoride are 167.95 mg/L for Selenastrum capricornutum and 111.96 mg/L for Skeletonema costatum.

Results of the aquatic algae toxicity tests in marine and freshwater are available for different species. Based on a worst case approach the EC₅₀ of 58.71 mg/L will be used for fresh water species and an EC₅₀ of 110.6 mg/L for marine water species.

 

TOXICITY TO MICROORANISMS

A microorganism toxicity test with lithium fluoride is not available. Consequently, read-across was applied using study results obtained from lithium hydroxide and sodium fluoride.

 

Read-across with lithium hydroxide (LAB 2004): The influence of the test item lithium hydroxide on the activity of activated sludge by measuring the respiration rate was evaluated according to OECD guideline 209 and EU method C.11. Aerobic activated sludge fed with a standard amount of synthetic sewage was exposed to 0, 10, 32, 100, 320 and 1000 mg lithium hydroxide/L. In comparison to the inoculum controls the respiration rate of the activated sludge was inhibited between –1.8 % and 98.2 % up to the highest nominal test concentration of 1000 mg/L. The 3 hours EC₂₀, EC₅₀, and EC₈₀ values for the test substance, lithium hydroxide, in the Activated Sludge Respiration Inhibition Test were 114.3, 180.8, and 286.1 mg/L (based on measured inhibition rates), respectively. The EC₁₀ value was calculated by linear regression to be 79.2 mg/L for lithium hydroxide anhydrous.

After recalculation of the 3 hours EC₁₀, EC₂₀, EC₅₀ and EC₈₀ values for lithium fluoride the following values were determined: 85.78, 156.07, 195.82 and 390.64 mg LiF/L, respectively.

 

Read-across with sodium fluoride (EU-RAR 2001):

The EU-RAR summarizes and reviews the available data on the toxicity of fluoride to aquatic microorganisms. Expressed in terms of fluoride ion (F-), NOEC values between 7.1 and 231 mg F/L were reported. Based on these data, the recalculated NOEC values for lithium fluoride were between 9.69 and 315.41 mg/L, respectively. The tests were performed with various species and exposed for various periods of time. Therefore, the results of the EU-RAR review were not chosen as key value for chemical safety assessment.

 

The results of the Activated Sludge Respiration Inhibition Test (LAB 2004), performed according to OECD 209, seems to be the most reliable data source. Therefore, the EC₁₀ value of 85.78 mg LiF/L is chosen as key value for chemical safety assessment.