Lithium bromide

Endpoint summary

Additional information

Short-term toxicity to fish

Key study

Lithium bromide was assessed in a short-term toxicity study for fish according to OECD guideline 203. Young Rainbow Trouts were exposed to the test item in a static test for 96h at measured concentrations of 62.1, 128, 256, 511, and 1011 mg LiBr/L. Mortality of the rainbow trout was 0 % at concentration of 256 mg/L, 70 % at 511 mg/L and 100 % at 1011 mg/L. No mortality occurred in the dilution water control. A 96-hour LC50 of 438 mg/L has been derived. The no-observed-effect-concentration (NOEC) was 128 mg/L based on the lack of mortality and sublethal effects at this concentration and lower. (Toxikon, 1997)

Supporting study

Lithium bromide has been assessed in a short-term acute toxicity study with fish according to OTS guideline 797.1400. Young Inland Silversides were exposed to the test item in a static test for 96 h at the following measured concentrations: 61.5, 123, 245, 495 and 976 mg LiBr/L. Mortality of the Inland Silversides ranged from 5 % at concentration 495 mg LiBr/L to 20 % at test concentrations of 61.5 and 245 mg LiBr/L. Mortality in the dilution water control was 5 %. The 96-hour LC50 was >976 mg LiBr/L. The no-observed-effect-concentration (NOEC) was 976 mg/L based on a lack of statistically significant mortality at this test concentration and lower. (Toxikon, 1998)

Long-term toxicity to fish

Long-term toxicity test in fish with lithium bromide is not available. Consequently, read-across was applied using study results obtained from lithium hydroxide monohydrate.

The purpose of this study was to evaluate the chronic toxicity of the test item lithium hydroxide monohydrate to early life stages (embryo, larvae and juveniles) of fish.

For this purpose, eggs were exposed in a semi-static test to aqueous test media containing the test item for 34 days at a range of concentrations under defined conditions. Lethal and sub-lethal effects were assessed and compared with control values to determine the lowest observed effect concentration (LOEC) and hence the no observed effect concentration (NOEC) for each response assessed.

The test was considered to be valid as assay acceptance criteria were fulfilled.

Based on the preliminary chronic fish toxicity test result the following nominal test concentrations were selected for the early life stage toxicity test: 1.8 mg/L, 3.0 mg/L, 7.2 mg/L, 15.0 mg/L and 21.1 mg/L.

Test item concentrations were analyzed in the test solutions by flame photometry. Lithium hydroxide monohydrate concentration in the test solutions was determined at 5 renewal periods by flame photometry. The measured concentrations of the lithium hydroxide monohydrate varied between 102 % and 151 % of the nominal concentration during the test. Mean measured concentrations were calculated for each parallel test chambers and for each treatment concentrations. The measured concentrations of each parallel treatment were within the range of ± 20 % of the mean measured values meeting the validity criteria. Since concentrations of the test substance were satisfactorily maintained within ± 20 % of the mean measured values during the test in all treatment groups, all biological results are reported on the basis of the mean measured concentrations: 2.43 mg/L, 3.82 mg/L, 8.60 mg/L, 17.35 mg/L and 24.35 mg/L.

79 to 82 eggs were tested per test concentrations and the control in two parallels in the test groups and in the control group (approximately 40-40 eggs per each parallel treatment). Based on microscopic observation embryos were at approximately 64 to 128 cell stages at start of treatment.

Environmental parameters (water temperature, pH, LDo) were monitored during the test. There were no deviations from the defined ranges. Animals were fed from elimination of the yolk sac (free-feeding stage) to the end of the test with appropriate type and amount of food ad libitum, and thus starvation did not have any effect on the results obtained.

Cumulative mortality (observed from Day 0 to the end of the test on Day 34), mortality observed at embryonic/eleutheroembryonic (i.e. early larval) stage (from Day 0 to the end of hatching on Day 5) and mortality observed at larval/juvenile stage (from Day 6 - free feeding stage - to the end of the test on Day 34) were statistically evaluated. Statistically significant (p < 0.01) cumulative mortality compared to the control was observed at a treatment concentration of 24.35 mg/L (21.1 mg/L nominal). No significant lethal effect was observed until embryonic/eleutheroembryonic stage. Since mortality observed from Day 6 to Day 34 was statistically significant (p < 0.01) it is considered that the test item influenced the survival of the test organism at larval/juvenile stage rather than at embryonic stage. No statistically significant lethal effect was observed in other test concentrations (neither during embryonic nor larval/juvenile stage).

No significant effect on hatching of the larvae was observed at any concentrations tested. No significant differences were observed either in starting or duration of hatching. Numbers of larvae hatched daily were statistically evaluated on Day 4 and Day 5 and no significant differences were observed.

At the end of the test, group body weights were measured. No significant differences were observed.

Body length was measured for each animal individually and the data were statistically evaluated. A statistically significant (p < 0.05), but biologically not relevant difference was observed at a test concentration of 8.61 mg/L (7.2 mg/L nominal).

Other sub-lethal effects were monitored with limited extent: numbers of embryos/larvae/juveniles with deformities or abnormal behavior were recorded. No obvious test item related changes in the behavior of fish could be observed.

Under the conditions of this early life stage toxicity study, the test item lithium hydroxide monohydrate had a significant lethal effect on early life stages of Zebrafish (Danio rerio). The observed effect was associated with larval/juvenile stages, but no significant effect was observed during the embryonic stage.

The following endpoints (34 days LOEC and NOEC) were calculated in the study:

The 34 d LOEC 24.35 mg test item/L

The 34 d NOEC 17.35 mg test item/L (Toxicoop, 2012)

Based on read-across approach, the calculated LOEC and NOEC values for lithium bromide were 50.40 and 35.91 mg/L, respectively.

Short-term toxicity to aquatic invertebrates

Key study

Lithium bromide was assessed in a short-term toxicity study for invertebrates according to OECD guideline 202. Daphnia magna neonates were exposed to the test item in a static test for 48h at mean measured concentrations of 64.3, 129, 258, 513, and 1033 mg LiBr/L. Mortality of the water flea ranged from 0 percent at concentration ≤ 258 mg/L to 100 percent at concentration ≥ 513 mg/L. Control mortality was zero percent. A 48-hour LC50 of 364 mg/L has been derived. The no-observed-effect-concentration (NOEC) was 129 mg/L. (Toxikon, 1998)

Supporting study

Lithium bromide was assessed in a short-term toxicity study for invertebrates according to EPA OTS guideline 797.1930. Juvenile Mysid shrimps were exposed to the test item in a static test for 96h at mean measured concentrations of 62.1, 126, 251, 501, and 995 mg LiBr/L. Mortality of the Mysids ranged from 0 percent at concentrations < 501 mg/L to 5 percent at test concentration of 995 mg/L. No mortality occurred in the dilution water control. The 96-hour LC50 was >995 mg/L. The no-observed-effect-concentration (NOEC) was 501 mg/L based on a lack of mortality at this test concentration and lower. (Toxikon, 1998)

Long-term toxicity to aquatic invertebrates

Long-term toxicity test in daphnia with lithium bromide is not available. Consequently, read-across was applied using study results obtained from a supporting substance, lithium.

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 performed 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 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, a statistically significant difference was not observed in the remaining 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. (Toxicoop, 2012)

Based on a read-across approach, the calculated NOEC and LOEC values for lithium bromide were 21.3 and 31.7 mg/L, respectively.

Toxicity to aquatic algae and cyanobacteria

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 test solutions were prepared in a dilution series from a stock solution of 100 mg/L of the test item in culture medium for the range-finding test and from a stock solution of 400 mg/L of the test item in culture medium for the definitive test, respectively. The controls were kept in culture medium. Vessels including culture medium (controls) and test solutions were kept under the same conditions as the test vessels for concentration analysis. 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/L. The overall NOEC was determined to be 25 mg/L. The results are based on the nominal concentrations. (Steinbeis, 2010)

Based on read-across approach, the calculated 72-h EC10 is 164 mg/L, the 72-h EC50 is greater than 820 mg/L and the overall NOEC is 51 mg/L for lithium bromide.

Toxicity to microorganisms

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. the 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 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 EC 50 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 and 22.95 mg/L for lithium ion. (LAB, 2004)

The 3 hours EC10, EC20, EC50, and EC80 values for lithium bromide based on read-across approach are 287, 415, 656 and 1039 mg/L, respectively.

Supporting data regarding sodium bromide studies and publications

The supporting data provided in this section refers to read-across with sodium bromide. In order to support the approach of regarding the lithium ion as ecotoxicological relevant moiety and not bromide, several literature citations from sodium bromide were assessed. The table below summarises the NOEC/EC10 values for lithium bromide (calculated) obtained from these publications.

Aquatic Assay	NOEC/EC10	Species
Long-term toxicity fish	271.8 mg/L (NOEC)	Oryzias latipes
Long-term toxicity invertebrates	77 mg/L (NOEC)	Daphnia magna
Toxicity to algae	2870 mg/L (EC10)	Desmodesmus subspicatus
Toxicity to microorganisms	2720 mg/L (NOEC)	Pseudomonas fluorescens

Compared to the data of the studies conducted with lithium bromide the NOEC and EC10 values determined with sodium bromide (values based on bromide concentration) are much higher (at least by a factor of 2). This indicates a higher ecotoxicological activity of lithium in contrast to bromide.

As the key studies lead to lower NOECs, lithium is used for risk assessment rather than bromide as lithium leads to a more conservative risk characterisation and assessment.