Trilithium orthophosphate

Endpoint summary

Additional information

SHORT-TERM TOXICITY TO FISH:

A short-term toxicity study on fish with lithium phosphate is not available. Consequently, read-across was applied using characteristically similar compounds: lithium carbonate and chloride as well as tricalcium phosphate and calcium hydrogen phosphate.

Read-across with lithium carbonate (Toxikon 1996)
A static freshwater toxicity test was conducted to determine the acute toxicity of lithium carbonate to rainbow trout, Oncorhynchus mykiss according to OECD Guideline 203. Mean measured concentration of lithium carbonate ranged from 4.99 to 77.7 mg/L and from 96 to 100 % of nominal. All test solutions appeared clear and colourless and concentrations remained stable throughout the test. The pH of the test solutions was affected by the presence of lithium carbonate (i.e. the pH increased as the test substance concentrations increased). The pH values of all test solutions ranged from 8.7 to 10.4 at test initiation and from 6.7 to 9.8 for the remainder of the test. Mortality of the rainbow trout exposed for 96 hours to lithium carbonate ranged from 0 % at test concentrations ≤19.1 mg/L to 100 % at 77.7 mg/L. No mortality occurred in the dilution water control. The 96-hour LC50 was 30.3 mg Li2CO3/L with 95 % confidence limits of 19.1 and 38.9 mg/L. The NOEC of 19.1 mg Li2CO3/L was based on a lack of significant mortality and the absence of sublethal effects at this and all lower test concentrations. Based on these data, the calculated LC50 for lithium phosphate is 31.65 mg/L.

Read-across with lithium chloride (Toxicon 1997) 
A static freshwater toxicity test was conducted to determine the acute toxicity of lithium chloride to rainbow trout, Oncorhynchus mykiss according to OECD Guideline No. 203. Mean measured concentration of lithium chloride ranged from 59.4 to 1021 mg/L and from 94 to 103 % of nominal concentrations. All test solutions appeared clear and colourless and concentrations remained stable throughout the test. The pH of the test solutions was affected by the presence of lithium chloride (i.e., the pH increased as the test substance concentrations increased). The pH values of all test solutions ranged from 7.5 to 8.7 at test initiation and from 7.0 to 7.5 for the remainder of the test. Mortality of the rainbow trout exposed for 96 hours to lithium chloride ranged from 0 % at 59.4 mg/L to 100 % at test concentrations smaller or equal to 249 mg/L. No mortality occurred in the dilution water control. The 96-hour LC50 was 158 mg/L with 95 % confidence limits of 118 and 249 mg/L. The slope of the concentration response curve could not be calculated using the binomial method. The NOEC was 59.4 mg/L based on a lack of mortality at the lowest test concentration. Based on these data, the calculated LC50 for lithium phosphate is 143.86 mg/L. 

Read-across with tricalcium phosphate (Kim et al. 2013) 
A static freshwater toxicity test was conducted to determine the acute toxicity of tricalcium phosphate to Japanese rice fish, Oryzias latipes according to OECD Guideline 203. The concentrations of the test substance were calculated to be 0.53 -2.14 mg/L based on measured calcium concentrations. Therefore, the test substance is poorly water soluble. The results of the fish acute toxicity test showed that no mortality or adverse effects were observed at control or 100 mg/L (nominal). The 96 hours LC50 and no observed effect concentration (NOEC) in O. latipes were >100 mg/L (measured concentration: >2.14 mg/L). Based on these data, the calculated LC50 for lithium phosphate is >74.66 mg/L.

Read-across with calcium hydrogen phosphate (Kim et al. 2013) 
A static freshwater toxicity test was conducted to determine the acute toxicity of calcium hydrogen phosphate to Japanese rice fish, Oryzias latipes according to OECD Guideline 203. The concentrations of the test substance were calculated to be 13.0 - 14.2 mg/L based on measured calcium concentrations. Therefore, the test substance is poorly water soluble. The results of the fish acute toxicity test showed that no mortality or adverse effects were observed at control or 100 mg/L (nominal). The 96 hours LC50 and no observed effect concentration (NOEC) in O. latipes were >100 mg/L (measured concentration: >13.5 mg/L). Based on the read-across approach, the calculated LC50 for lithium phosphate is >85.10 mg/L. 

Conclusion:

In this weight of evidence approach the effect concentrations of lithium and phosphate compounds were evaluated in different fish tests. When comparing the results of read-across from lithium carbonate and lithium chloride with tricalcium phosphate and calcium hydrogen phosphate, the magnitude of the calculated LC50 values show that lithium is the relevant toxicological moiety of lithium phosphate with respect to acute toxicity in fish. The result of the acute fish test with lithium carbonate with the guideline compliant species O. mykiss is considered as valid and the LC50 of 31.65 mg Li3PO4/L is chosen as key value for chemical safety assessment.

LONG-TERM TOXICITY TO FISH:

According to Annex VIII, a long-term toxicity on fish with lithium phosphate is not necessary, but a read-across study with the characteristically similar compound, lithium hydroxide monohydrate is available. Since results of long-term tests are preferred to those of short-term tests, because such results give a more realistic picture of effects on the organisms during their entire life cycle, the chronic read-across data was considered for the ecotoxicological risk assessment (Guidance on information requirements and chemical safety assessment R.10, 2008).

Read-across with lithium hydroxide monohydrate (Toxi-Coop 2012):
The purpose of the performed study was to evaluate the chronic toxicity of the test item, lithium hydroxide monohydrate, to early life stages (embryo, larvae and juveniles) of fish (Danio rerio) according to the OECD Guideline 210. Around 40 eggs per treatment / concentration level (2 replicates per treatment) 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 effect 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 the conditions of this test, 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 a read-across approach, the calculated LOEC and NOEC values for lithium phosphate are 22.40 mg/L and 15.96 mg/L, respectively.

Short-term toxicity to aquatic invertebrates:

A short-term toxicity study on aquatic invertebrates with lithium phosphate is not available. Consequently, read-across was applied using characteristically similar compounds: lithium carbonate and chloride as well as tricalcium phosphate and calcium hydrogen phosphate.

Read-across with lithium carbonate (Toxicon 1997)
A static freshwater toxicity test was conducted to determine the acute toxicity of lithium carbonate to the water flea, Daphnia magna according to OECD Guideline 202. Mean measured concentrations of lithium carbonate ranged from 4.76 to 82.8 mg/L and from 95 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 carbonate ranged from 0 % at test concentrations lower than 20.0 mg/L to 100 % at 82.8 mg/L. Control mortality was 0 %. The 48-hour EC50 was 33.2 mg Li2CO3/L with 95 % confidence limits of 20.0 and 43.7 mg/L. The NOEC was 20.0 mg Li2CO3/L, based on a lack of significant mortality and sublethal effects observed at this and all lower test concentrations. Based on these data, the calculated EC50 for lithium phosphate is 34.68 mg/L.

Read-across with lithium chloride (Toxicon 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, his death was not chemically related. Control mortality was 0%. The 48-hour EC50 was 249 mg LiCl/L with 95 % confidence limits of 197 and 315 mg/L. The NOEC was 63.4 mg/L. Based on these data, the calculated EC50 for lithium phosphate is 226.72 mg/L.

Read-across with tricalcium phosphate (Kim et al. 2013) 
A static freshwater toxicity test was conducted to determine the acute toxicity of tricalcium phosphate to the water flea, Daphnia magna according to OECD Guideline 202. Adverse effects and immobility were examined daily. The criterion of immobilization was an inability to swim for approximately 15 seconds after gentle stir. No mortality or adverse effects were observed at control or 100 mg/L (nominal). The 48 hours EC50 of tricalcium phosphate was >100 mg/L (measured concentration: >5.35 mg/L) in Daphnia magna. The concentration of the test substance was calculated using the concentration of calcium expecting the mean calcium concentration at control. The results suggest that the concentration of the test substance was significantly lower than nominal, and the test substance was insoluble in water. Therefore, the test results were expressed as nominal concentration. Based on these data, the calculated LC50 for lithium phosphate is 74.66 mg/L.

Read-across with calcium hydrogen phosphate (Kim et al. 2013)
A static freshwater toxicity test was conducted to determine the acute toxicity of calcium hydrogen phosphate to the water flea, Daphnia magna according to OECD Guideline 202. Adverse effects and immobility were examined daily. The criterion of immobilization was an inability to swim for approximately 15 seconds after gentle stir. No mortality or adverse effects were observed at control or 100 mg/L (nominal). The 48 hours EC50 of calcium hydrogen phosphate was >100 mg/L (measured concentration: >2.9 mg/L) in Daphnia magna. Based on these data, the calculated LC50 for lithium phosphate is 85.10 mg/L. 

Conclusion:

In this weight of evidence approach the effect concentrations of lithium and phosphate compounds were evaluated in different acute tests with Daphnia magna.When comparing the results of read-across from lithium carbonate and lithium chloride with tricalcium phosphate and calcium hydrogen phosphate, the magnitude of the calculated EC50 values show that lithium is the relevant toxicological moiety of lithium phosphate with respect to acute toxicity in daphnia. The lowest determined EC50 value of 34.68 mg Li3PO4/L is considered as key value for chemical safety assessment.

LONG-TERM TOXICITY TO AQUATIC INVERTEBRATES:

According to Annex VIII, a long-term toxicity on aquatic invertebrates with lithium phosphate is not necessary, but a read-across study with lithium is available. Since results of long-term tests are preferred to those of short-term tests, because such results give a more realistic picture of effects on the organisms during their entire life cycle, the chronic read-across data was considered for the ecotoxicological risk assessment (Guidance on information requirements and chemical safety assessment R.10, 2008).

Read-across with lithium (Toxi-Coop 2012)
The purpose of the study was to evaluate the influence of the test item lithium on the reproductive output of Daphnia magna in a semi-static test system according to OECD Guideline 211. Young female Daphnia (the parent animals) aged less than 24 hours at the start of the test were exposed to aqueous test media containing the test item for 21 days at a range of concentrations. The nominal test item concentrations were 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. In the control group two parent animals (20 %) died during the test which was within the acceptable validity criteria. In the concentration range of 0.50 – 1.70 mg/L mortality of parent animals was not observed during the experiment. 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 a read-across approach, the calculated NOEC and LOEC values for lithium phosphate are 9.45 mg/L and 14.07 mg/L.

TOXICITY TO AQUATIC ALGAE AND CYANOBACTERIA

A short-term toxicity study on aquatic invertebrates with lithium phosphate is not available. Consequently, read-across was applied using characteristically similar compounds: lithium carbonate and lithium chloride as well as tricalcium phosphate and calcium hydrogen phosphate. The lithium compounds were considered as key studies, because phosphate shows at low concentrations a growth-promoting effect on algae.

Key studies:

Read-across with lithium chloride (Steinbeis-Transferzentrum 2010)
The effect of lithium chloride on the growth of the algae species Desmodesmus subspicatus over a 72 hour static exposure period was assessed according to OECD guideline 201. The algal were exposed to a control (culture medium) and the test item at concentrations of 25, 50, 100, 200 and 400 mg/L. In this 72-h algal growth inhibition test with D. subspicatus the 72-h EC50 based on growth rate was determined as greater than 400 mg/L. The 72-h EC50 on yield was 112 mg/L. The overall NOEC was determined to be 25 mg/L. The results are based on the nominal concentrations. Based on the results of the read-across from lithium chloride, the calculated EC50 and NOEC values for lithium phosphate are >364.21 mg/L and 22.76 mg/L, respectively.

Read-across with lithium carbonate (Steinbeis-Transferzentrum 2010)
The effect of lithium carbonate on the growth of the algal species Desmodesmus subspicatus over a 72-hour static exposure period was assessed according to OECD Guideline 201. The algae were exposed to a control (culture medium) and the test item at concentrations of 25, 50, 100, 200 and 400 mg/L. Concentration analysis was performed at 0 h and 72 h and demonstrated that the lithium concentrations were stable throughout the exposure period. In this 72-h algal growth inhibition test with D. subspicatus the 72-h EC50 based on growth rate was determined as greater than 400 mg/L for lithium carbonate. The overall NOEC was determined to be 50 mg/L for lithium carbonate. Based on these data, the calculated EC50 and NOEC values for lithium phosphate are >417.88 mg/L and 52.24 mg/L, respectively.

Supporting studies:
Read-across with tricalcium phosphate (Kim et al. 2013)

The effect of tricalcium phosphate on the growth of an algal species Pseudokirchnerella subcapitata over a 72-hour static exposure period was assessed according to OECD Guideline 201.The test was conducted using the nominal concentrations of 4, 9, 21, 45 and 100 mg/L. The mean concentrations of the test substance were 0.08 - 0.88 and 0.61 - 1.56 mg/L at 0 and 72 hours, respectively, ranging between 0.8 and 15.3% of the nominal concentrations. Therefore, all the test results were expressed as nominal concentration because the test substance was insoluble in water. Algal cells were observed after 72 hours of exposure, and the results showed that there were no morphological changes at control, maintaining a semicircular shape. In all the test concentrations, the growth rates of algal cells were higher than those of the control. The algal growth inhibition test, the 72 hours EC50 was calculated to be >100 mg/L (measured concentration: >1.56 mg/L) using the average specific growth rate and the area under the growth curve method. Based on these data, the calculated LC50 for lithium phosphate is >74.66 mg/L.

Read-across with calcium hydrogen phosphate (Kim et al. 2013)
The effect of calcium hydrogen phosphate on the growth of the algal species Pseudokirchneriella subcapitata over a 72-hour static exposure period was assessed according to OECD Guideline 201. The algae were exposed to the nominal concentrations of 0.3, 1, 3.1, 9.8, 31.3 and 100 mg Ca3HPO4/L. The test substance was detected to be significantly lower during the test. The measured concentrations of the test substance were 0.3, 0.4, 0.3, 0.8, 1.7 and 4.4 mg/L at the beginning of the test (0 hours). At 72 hours, the test substance in the test solution was not detected at 0.3, 1.0 and 3.1 mg/L (nominal), but its concentration at 9.8, 31.3 and 100 mg/L (nominal) were estimated to be 0.3, 1.6 and 4.7 mg/L. Algal cells were observed to maintain a similar shape to the control in all test solutions, and microorganisms other than algae were not observed. The 72 hours EC50 was estimated to be >100 mg/L (measured concentration: >4.4 mg/L) using the average specific growth rate and yield. Based on these data, the calculated LC50 for lithium phosphate is >85.95 mg/L.

Conclusion:

The effect concentrations of lithium and phosphate compounds were evaluated in different algae tests. The results for the phosphate compounds showed, that phosphate has the potential to cause increased algal growth at low concentrations. Therefore, lithium was considered as the relevant toxicological moiety of lithium phosphate. The lowest observed EC50 of >364.21 mg Li3PO4/L was chosen as key value for chemical safety assessment.

TOXICITY TO MICROORGANISMS:

Activated sludge respiration inhibition testing with lithium phosphate is not available. Consequently, read-across was applied using a characteristically similar compound, lithium hydroxide.

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. The respiration rate (oxygen consumption) of an aerobic activated sludge fed with a standard amount of synthetic sewage was measured in the presence of various concentrations of the test item after an incubation period of 3 hours. The inhibitory effect of the test item at the particular concentrations was expressed as percentage of the mean respiration rate of two controls. Following test concentrations were used: 10, 32, 100, 320 and 1000 mg lithium hydroxide/L; 3.2, 10 and 32 mg 3,5-Dichlorophenol/L as a positive control and two inoculum controls. 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. Concentrations exceeding 1000 mg/L nominal were not tested. The 3-hour EC50 for the positive control 3,5-Dichlorophenol, which was tested in the same way as the test item, was found to be 7.5 mg/L and is within the range of 5 – 30 mg/L recommended by the test guidelines; thus, confirming suitability of the activated sludge.
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. Based on read-across approach, the calculated EC50 and EC10 for lithium phosphate is 291.37 mg/L and 127.63 mg/L, respectively.