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Ecotoxicological information

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Description of key information

Additional information

Acute toxicity to fish

HF

In the aquatic environment, HF will principally be present in the form of fluoride ion. For this reason, test data obtained using soluble inorganic fluorides can be used to evaluate HF toxicity and LC50 values expressed in terms of mg F-/l are appropriate for assessment of HF toxicity to aquatic organisms (HF: EU Risk Assessment Report, 2001).

 

Fluoride

In freshwater, the presence of calcium carbonate in hard water reduces F- availability and hence toxicity through precipitation of calcium fluoride (HF: EU Risk Assessment Report, 2001; WHO EHC 227, 2002). Tests performed in soft water of hardness ≤25 mg CaCO3/l reported 96h LC50 values ranging from 51-165 mg F-/l (3 studies cited, two using Oncorhynchus mykiss, one Salmo trutta: HF: EU Risk Assessment Report, 2001). Acute fish toxicity tests using waters of different hardness reviewed in EHC 227 showed a clear relationship between 96h LC50 and water hardness. At 17, 49, 182 and 385 mg CaCO3/l, reported rainbow trout LC50 values were 51, 128, 140 and 193 mg F-/l respectively; in other cited studies using the stickleback, reported LC50 values in tests using water with 78, 146 and 300 mg CaCO3/l were 340, 380 and 460 mg F-/l respectively. Toxicity tests with four different marine fish species gave 96h LC50 values in the range >100 to >225 mg F-/l (WHO EHC 227, 2002).

 

Lithium

A 96h LC50 value of 369 mg/l for lithium bromide (corresponding to 29.5 mg Li+/l) has been reported for medaka (Oryzias latipes) by the Japanese Environment Ministry (Japan NITE, 2001). In the fathead minnow, the 96h LC50 and NOEC for lithium have been reported as 42 mg/l and 13 mg/l respectively (study cited by Long, Brown and Woodburn, 1998). However Kzos, Beauchamp and Stewart (2003) measured growth inhibition of fathead minnow larvae exposed to lithium for 7 days in low sodium (ca. 2.8 mg/l) water or natural stream water (ca. 17 mg Na/l) and found lithium toxicity to be inversely related to sodium level: the larvae tolerated lithium concentrations up to 4 mg/l in the presence of sufficient dissolved sodium, while in the low sodium water an IC50 value of 0.57 mg/l was reported. These workers concluded that in natural waters the presence of sodium is sufficient to prevent lithium toxicity, noting that high lithium tolerance limits for three species of river fish were reported by workers who used reconstituted river water (49 mg Na/l) in their tests.

 

Phosphate

Phosphate is widely present in the environment and is naturally present (and necessary) in living organisms. Control of phosphate contamination of surface waters through phosphate discharge or run-off following its use in agriculture or in detergents has been imposed to limit problems of eutrophication, with consequent increase of algal growth, rather than direct toxicity to aquatic organisms. A study of phosphorus supplementation in rainbow trout over 53 days found no evidence that addition of Na2HPO4 into low-phosphorus basal diet at levels giving up to 10.96 g P/kg dry weight (equivalent to 33.6 g PO4/kg or 50.2 g Na2HPO4/kg) adversely affected growth or survival; indeed, weight gain was increased with phosphate supplementation up to a level of approximately 5 g P/kg in diet (equivalent to 8g PO4/kg) (Rodehutscord, 1996). 

 

Key value for assessment

Given the relative quantities of F-, Li+ and PO4- entering solution after contact of LiPF6 with water (LiPF6 + 4H2O → 5HF + LiF + H3PO4 within seconds, followed by slower dissolution then dissociation of the LiF) and the low toxicity of phosphate to fish, it is appropriate to consider the lowest acute fish toxicity 96h LC50 value for fluoride (51 mg F-/l) as the key value for assessment. Conversion of this to an LiPF6 LC50 value could be based on the rapid hydrolysis equation above (i.e. 1 mole LiPF6 releases 5 moles HF which dissociate to 5 F- ions) or, as a worst-case, could also take account of the slower dissolution and ionisation of the LiF hydrolysis product (i.e. 1 mole LiPF6 releases 6 F- ions): for the purposes of assessment the latter is used, giving an LiPF6 96h LC50 value of 68 mg/l.

 

Acute toxicity to invertebrates

In a OECD/EC GLP-compliant study conducted on LiPF6, moderate to low toxicity was observed: 96h EC50 >100 mg/l, NOEC 22 mg/l.

 This result is fully compatible with the reported low acute toxicity of fluoride and lithium to freshwater invertebrates (five different Daphnia 48h EC50 values from 98 to 304 mg F-/l cited in WHO EHC 227, 2002. Lithium bromide Daphnia 48h EC50 110 mg/l, Japan MoE 2001).

 

3. Algal growth inhibition

In a OECD/EC GLP-compliant study conducted on LiPF6, moderate to low toxicity was observed: 96h EC50 >100 mg/l, NOEC 22 mg/l. This result is fully compatible with the reported low/moderate toxicity of fluoride and lithium to freshwater algae (two different algal 96h biomass EC50 values, 43 and 122 mg F-/l cited in HF: EU Risk Assessment Report, 2001. Lithium bromide algal growth rate 72h EC50 290 mg/l, NOEC 10 mg/l: Japan MoE 2001).

 

Long-term toxicity to fish

HF

In the aquatic environment, HF will principally be present in the form of fluoride ion. For this reason, test data obtained using soluble inorganic fluorides can be used to evaluate HF toxicity and LC50 or NOEC values expressed in terms of mg F-/l are appropriate for assessment of HF toxicity to aquatic organisms (HF: EU Risk Assessment Report, 2001).

 

Fluoride

A number of long-term toxicity tests with freshwater fish have been reviewed (WHO EHC 227, 2002): in a 20-day semistatic test using soft water (CaCO3 <3 mg/l), LC50 values of 2.7 – 4.7 mg/l were recorded, but other workers calculated that 5.1 and 7.5 mg F-/l represent safe concentrations for rainbow and brown trout respectively. A long-term NOEC for rainbow trout (21-day semistatic test LC5 value) of 4 mg F-/l in very soft water (CaCO3 12 mg/l) is cited in the HF: EU Risk Assessment Report (2001), and a test of mullet (marine fish) exposed to fluoride at 5.9 or 5.5 mg/l for 68 or 113 days had no effect on survival, although growth of smaller fish was reduced (WHO EHC 227, 2002). In a detailed study of public domain information of fluoride toxicity to various fish species, Fleiss (2011) showed that among LC50 values from studies longer than 4 days, rainbow trout gave both the lowest and highest values: the lowest LC50 value of 2.3 mg/l came from a test conducted in water of zero hardness; the lower 95thpercentile value calculated from all longer term LC50s considered was 2.62 mgF-/l.

 

Lithium

After three separate experiments on rainbow trout, looking at egg integrity, fertilisation, embryogenesis, hatching and then sac-fry and juvenile survival, Emery, Klopfer and Skalski (1981) reported “lowest rejected concentration tested” (LOEC) values of 3.3 mg Li+/l following LiF exposure and 0.6 mg Li+/l after Li2CO3 exposure. 

 

Kzos, Beauchamp and Stewart (2003) measured growth inhibition of fathead minnow larvae exposed to lithium for 7 days in low sodium (ca. 2.8 mg/l) water or natural stream water (ca. 17 mg Na/l) and found lithium toxicity to be inversely related to sodium level: the larvae tolerated lithium concentrations up to 6 mg/l in the presence of sufficient dissolved sodium, while in the low sodium water an IC50 value of 0.57 mg/l was reported.

 

A fish early life stage study using the fathead minnow (conducted according to US EPA and ASTM guidelines and under GLP) and lithium chloride is available (Long, Brown and Woodburn, 1998). Effects on embryos and larvae were assessed over a 26-day period (including 22-23 days post hatching) in treated river water (hardness 56-70 mg/l as CaCO3). EC50 and NOEC values calculated in terms of Li+ ion concentration were 1.0 and 0.2 mg/l respectively.

 

Phosphate

A study of phosphorus supplementation in rainbow trout over 53 days found no evidence that addition of Na2HPO4 into low-phosphorus basal diet at levels giving up to 10.96 g P/kg dry weight (equivalent to 33.6 g PO4/kg or 50.2 g Na2HPO4/kg) adversely affected growth or survival; indeed, weight gain was increased with phosphate supplementation up to a level of approximately 5 g P/kg in diet (equivalent to 8g PO4/kg) (Rodehutscord, 1996). 

 

Key value for assessment

The NOEC value reported for lithium in a fish early life stage test (0.2 mg/l) corresponds to an LiPF6 concentration of 4.4 mg/l. Given the range of long-term fish NOEC and LC50 values reported for fluoride (variable mainly due to variations in water hardness), it is reasonable to consider the lowest LC50 value of 2.3 mg F-/l (well below the long-term fish NOEC cited in the HF: EU Risk Assessment Report, 2001) as an indicative value for fluoride toxicity: this corresponds to an LiPF6 concentration of 3.1 mg/l. Due to its low toxicity, the contribution of phosphate to LiPF6 toxicity is considered insignificant. It is therefore concluded that the fluoride released from LiPF6 in water is the “toxic marker” for long-term toxicity to fish and a long-term NOEC value of 3.1 mg/l for LiPF6 is taken for use in assessment.

 

Long-term toxicity to invertebrates

HF

In the aquatic environment, HF will principally be present in the form of fluoride ion. For this reason, test data obtained using soluble inorganic fluorides can be used to evaluate HF toxicity and EC50 or NOEC values expressed in terms of mg F-/l are appropriate for assessment of HF toxicity to aquatic organisms (HF: EU Risk Assessment Report, 2001).

 

Fluoride

Two different NOEC values in Daphnia 21-day reproduction studies are reported in the HF: EU Risk Assessment Report (2001): 3.7 mg F-/l and 14.1 mg F-/l. In another authoritative review of fluoride toxicity (WHO EHC 227, 2002), two further Daphnia reproduction studies are described: one reported effects on reproduction at concentrations above 26 mg F-/l, but the other presented more detailed findings. NOEC values for Daphnia growth and reproduction from the latter study were calculated to be in the range 3.7 – 7.4 mg F-/l, leading to calculation of 4.4 mg F-/l as a “safe concentration”.

 

Lithium

A series of experiments have been performed investigating the effects of lithium exposure in waters of varying sodium levels on survival and reproduction of Ceriodaphnia dubia (Kzos, Beauchamp and Stewart, 2003). In water with low sodium content (1.7 mg/l), exposure to 1 mg Li+/l proved lethal within 6 days, but with 40 mg Na/l 100% survival was seen at 4 mg Li+/l. Exposure to lithium at concentrations up to 2.55 mg Li+/l had no significant effect on reproduction (except when sodium content was increased to 700 mg/l). In a 21-day Daphnia magna reproduction study with lithium bromide, EC50 and NOEC values of 29 and 10 mg/l were determined (Japan MoE, 2001).

 

Phosphate

Phosphate is widely present in the environment and is naturally present (and necessary) in living organisms. Control of phosphate contamination of surface waters through phosphate discharge or run-off following its use in agriculture or in detergents has been imposed to limit problems of eutrophication, with consequent increase of algal growth, rather than direct toxicity to aquatic organisms. Long-term measurement of daphnid populations in a major European freshwater lake (Lake Constance) showed a marked increase in population (total biomass) associated with increased phosphorus concentrations (input of phosphate): Straile and Geller, 1998. These authors noted compatibility of their findings (increased daphnid biomass with eutrophication) with those reported for several other lakes by other researchers. Later reduction of Lake Constance phosphorus levels did not clearly affect daphnid population size. Overall, only indications of a beneficial effect of phosphate input on daphnid population were reported: no evidence of adverse effects of phosphate input were seen. There is no reason to suppose that phosphate released from LiPF6 could adversely affect aquatic invertebrates.

 

Key value for assessment

The lowest long-term NOEC value reported for fluoride is 3.7 mg F-/l and the lowest NOEC for lithium is 2.55 mg/l; these values correspond to LiPF6 concentrations of 4.9 and 55.8 respectively.  Due to its low toxicity, the contribution of phosphate to LiPF6 toxicity is considered insignificant. It is therefore concluded that the fluoride released from LiPF6 in water is the “toxic marker” for long-term toxicity to invertebrates and a long-term NOEC value of 4.9 mg/l for LiPF6 is taken for use in assessment.

Toxicity to microorganisms

In a respiration inhibition test using activated sewage sludge micro-organisms, LiPF6 gave a 3-Hour EC50 value of greater than 1000 mg/l. The No Observed Effect Concentration (NOEC) after 3 hours exposure was 480 mg/l. Based on these results, it is concluded that LiPF6 is of low toxicity to microorganisms.