Registration Dossier
Registration Dossier
Data platform availability banner - registered substances factsheets
Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.
The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.
Diss Factsheets
Use of this information is subject to copyright laws and may require the permission of the owner of the information, as described in the ECHA Legal Notice.
EC number: 612-032-8 | CAS number: 6080-58-6
- Life Cycle description
- Uses advised against
- Endpoint summary
- Appearance / physical state / colour
- Melting point / freezing point
- Boiling point
- Density
- Particle size distribution (Granulometry)
- Vapour pressure
- Partition coefficient
- Water solubility
- Solubility in organic solvents / fat solubility
- Surface tension
- Flash point
- Auto flammability
- Flammability
- Explosiveness
- Oxidising properties
- Oxidation reduction potential
- Stability in organic solvents and identity of relevant degradation products
- Storage stability and reactivity towards container material
- Stability: thermal, sunlight, metals
- pH
- Dissociation constant
- Viscosity
- Additional physico-chemical information
- Additional physico-chemical properties of nanomaterials
- Nanomaterial agglomeration / aggregation
- Nanomaterial crystalline phase
- Nanomaterial crystallite and grain size
- Nanomaterial aspect ratio / shape
- Nanomaterial specific surface area
- Nanomaterial Zeta potential
- Nanomaterial surface chemistry
- Nanomaterial dustiness
- Nanomaterial porosity
- Nanomaterial pour density
- Nanomaterial photocatalytic activity
- Nanomaterial radical formation potential
- Nanomaterial catalytic activity
- Endpoint summary
- Stability
- Biodegradation
- Bioaccumulation
- Transport and distribution
- Environmental data
- Additional information on environmental fate and behaviour
- Ecotoxicological Summary
- Aquatic toxicity
- Endpoint summary
- Short-term toxicity to fish
- Long-term toxicity to fish
- Short-term toxicity to aquatic invertebrates
- Long-term toxicity to aquatic invertebrates
- Toxicity to aquatic algae and cyanobacteria
- Toxicity to aquatic plants other than algae
- Toxicity to microorganisms
- Endocrine disrupter testing in aquatic vertebrates – in vivo
- Toxicity to other aquatic organisms
- Sediment toxicity
- Terrestrial toxicity
- Biological effects monitoring
- Biotransformation and kinetics
- Additional ecotoxological information
- Toxicological Summary
- Toxicokinetics, metabolism and distribution
- Acute Toxicity
- Irritation / corrosion
- Sensitisation
- Repeated dose toxicity
- Genetic toxicity
- Carcinogenicity
- Toxicity to reproduction
- Specific investigations
- Exposure related observations in humans
- Toxic effects on livestock and pets
- Additional toxicological data
Endpoint summary
Administrative data
Description of key information
Read-across with lithium carbonate:
LD50 (rat, oral): 525 mg/kg bw,
corresponding to 1336 mg/kg bw for lithium citrate tetrahydrate
Read-across with nitrate:
LD50 (rat, oral): 1317 (male), 1519 (female) and 1426 (combined)
mg/kg bw, corresponding to 1795 mg/kg (male), 2071 mg/kg (female), and
1944 mg/kg (combined) for lithium citrate tetrahydrate.
Read-acorss with citric acid:
LD50 (mice, oral): of 5400 mg/kg, corresponding to 7926 mg/kg bw for
lithium citrate tetrahydrate.
LD50 (rat, oral): Several LD50 values for citric acid in rat are
reported in the OECD SIDS Initial Assessment Report. The LD50 values
ranged from 3000 mg/kg to 12000 mg/kg bw, corresponding to LD50 values
between 4403 and 17613 mg/kg bw for lithium citrate tetrahydrate.
Key value for chemical safety assessment
Acute toxicity: via oral route
Link to relevant study records
- Endpoint:
- acute toxicity: oral
- Type of information:
- read-across from supporting substance (structural analogue or surrogate)
- Adequacy of study:
- weight of evidence
- Justification for type of information:
- HYPOTHESIS FOR THE ANALOGUE APPROACH
Lithium citrate tetrahydrate highly reacts with water and dissociates forming lithium hydroxide and citric acid. Thus, lithium hydroxide and citric acid were found to be suitable candidates for read-across. (Eco)toxicological properties were extrapolated to different endpoints by using the lowest effect concentration.
For further information, please refer to the read-across justification in IUCLID, section 13. - Reason / purpose for cross-reference:
- read-across source
- Reason / purpose for cross-reference:
- read-across source
- Reason / purpose for cross-reference:
- read-across source
- Reason / purpose for cross-reference:
- read-across source
- Reason / purpose for cross-reference:
- read-across source
- Reason / purpose for cross-reference:
- read-across source
- Reason / purpose for cross-reference:
- read-across source
- Reason / purpose for cross-reference:
- read-across source
- Reason / purpose for cross-reference:
- read-across source
- Sex:
- male/female
- Dose descriptor:
- LD50
- Effect level:
- 1 944 mg/kg bw
- Based on:
- other: recalculated for Li citrate tetrahydrate
- Remarks on result:
- other: Based on LiNO3 (I99-2283, 1999); rat
- Sex:
- not specified
- Dose descriptor:
- LD50
- Effect level:
- 1 336 mg/kg bw
- Based on:
- other: recalculated for Li citrate tetrahydrate
- Remarks on result:
- other: Based on Li2CO3 (Kiso to Rinsho); rat
- Sex:
- female
- Dose descriptor:
- LD50
- Effect level:
- 1 839 mg/kg bw
- Based on:
- other: recalculated for Li citrate tetrahydrate
- Remarks on result:
- other: Based on Li2CO3 (Kushneva et al.); rat
- Sex:
- male
- Dose descriptor:
- LD50
- Effect level:
- 1 628 mg/kg bw
- Based on:
- other: recalculated for Li citrate tetrahydrate
- Remarks on result:
- other: Based on Li2CO3 (Kushneva et al.); rat
- Sex:
- not specified
- Dose descriptor:
- LD50
- Effect level:
- 1 916 mg/kg bw
- Based on:
- other: recalculated for Li citrate tetrahydrate
- Remarks on result:
- other: Based on Li2CO3 (Kushneva et al.); mouse
- Sex:
- not specified
- Dose descriptor:
- LD50
- Effect level:
- >= 4 403 - <= 17 613 mg/kg bw
- Based on:
- other: recalculated for Li citrate tetrahydrate
- Remarks on result:
- other: Based on citric acid (OECD SIDS 2001); rat
- Sex:
- not specified
- Dose descriptor:
- LD50
- Effect level:
- 7 926 mg/kg bw
- Based on:
- other: recalculated for Li citrate tetrahydrate
- Remarks on result:
- other: Based on citric acid (OECD SIDS 2001); mouse
- Endpoint:
- acute toxicity: oral
- Type of information:
- experimental study
- Adequacy of study:
- weight of evidence
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: According to OECD SIDS Initial Assessment Report (2001)
- Principles of method if other than guideline:
- method not stated
- GLP compliance:
- no
- Limit test:
- no
- Species:
- mouse
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Specied: mouse, SPF, albino, source on record
- Housing: single sex groups in macrolon cages in a climate-controlled room with environmental parameters defined and on record
- Diet: ad libitum access to NAFAG 850 complete rodent maintenance diet feed
- Water: ad libitum access to water
- Route of administration:
- oral: gavage
- Vehicle:
- water
- Details on oral exposure:
- VEHICLE
- Concentration in vehicle: The test substance was dissolved in food grade tap water at such concentrations that in every group 20 mL/kg, corresponding to approx. 0.4 mL per animal, were given.
- Doses:
- 3000, 4243, 6000, 8485 and 12000 mg/kg
- No. of animals per sex per dose:
- 5 (60 animals in total in main study)
- Control animals:
- yes
- Details on study design:
- - Duration of observation period following administration: 10 days
- Preliminary study:
- Range -finding study: Performed with the following doses: 2,000, 2,828, 4,000, 5,657, 8,000 and 10,000 mg/kg; 100% mortality after 24 h in highest dose group, 50% at 8,000 mg/kg, 20% at 5,657 mg/kg and 0% in all lower dose groups.
- Key result
- Sex:
- male/female
- Dose descriptor:
- LD50
- Effect level:
- 5 400 mg/kg bw
- Based on:
- test mat.
- Remarks:
- citric acid
- 95% CL:
- >= 4 500 - <= 6 400
- Mortality:
- All mortalities occurred in the first 24 h after administration.
- Conclusions:
- An LD50 of 5400 mg/kg in mice is reported in the OECD SIDS Initial Assessment Report for citric acid.
- Endpoint:
- acute toxicity: oral
- Type of information:
- experimental study
- Adequacy of study:
- weight of evidence
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: According to OECD SIDS Initial Assessment Report (2001)
- Principles of method if other than guideline:
- method not stated
- GLP compliance:
- no
- Species:
- rat
- Route of administration:
- oral: unspecified
- Key result
- Sex:
- not specified
- Dose descriptor:
- LD50
- Effect level:
- 3 000 mg/kg bw
- Based on:
- test mat.
- Remarks:
- Citric acid
- Conclusions:
- An LD50 of 3000 mg/kg in rats is reported in the OECD SIDS Initial Assessment Report for citric acid.
- Endpoint:
- acute toxicity: oral
- Type of information:
- experimental study
- Adequacy of study:
- weight of evidence
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: According to OECD SIDS Initial Assessment Report (2001)
- Principles of method if other than guideline:
- method not stated
- GLP compliance:
- no
- Species:
- rat
- Route of administration:
- oral: unspecified
- Key result
- Sex:
- not specified
- Dose descriptor:
- LD50
- Effect level:
- 5 000 mg/kg bw
- Based on:
- test mat.
- Remarks:
- citric acid
- Conclusions:
- An LD50 of 5000 mg/kg in rats is reported in the OECD SIDS Initial Assessment Report for citric acid.
- Endpoint:
- acute toxicity: oral
- Type of information:
- experimental study
- Adequacy of study:
- weight of evidence
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: According to OECD SIDS Initial Assessment Report (2001)
- Principles of method if other than guideline:
- method not stated
- GLP compliance:
- not specified
- Species:
- rat
- Key result
- Sex:
- not specified
- Dose descriptor:
- LD50
- Effect level:
- >= 6 730 mg/kg bw
- Based on:
- test mat.
- Remarks:
- citric acid
- Conclusions:
- An LD50 of >= 6730 mg/kg in rats is reported in the OECD SIDS Initial Assessment Report citric acid.
- Endpoint:
- acute toxicity: oral
- Type of information:
- experimental study
- Adequacy of study:
- weight of evidence
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: According to OECD SIDS Initial Assessment Report (2001)
- Principles of method if other than guideline:
- method not stated
- GLP compliance:
- no
- Species:
- rat
- Key result
- Sex:
- not specified
- Dose descriptor:
- LD50
- Effect level:
- 12 000 mg/kg bw
- Based on:
- test mat.
- Remarks:
- citric acid
- Conclusions:
- An LD50 of 12000 mg/kg in rats is reported in the OECD SIDS Initial Assessment Report for citric acid.
- Endpoint:
- acute toxicity: oral
- Type of information:
- experimental study
- Adequacy of study:
- weight of evidence
- Reliability:
- 4 (not assignable)
- Rationale for reliability incl. deficiencies:
- other: According to OECD SIDS Initial Assessment Report (2001)
- Principles of method if other than guideline:
- method not stated
- GLP compliance:
- no
- Species:
- rat
- Key result
- Sex:
- not specified
- Dose descriptor:
- LDLo
- Effect level:
- 7 000 mg/kg bw
- Based on:
- test mat.
- Remarks:
- Citric acid
- Conclusions:
- A lowest lethal dose of 7000 mg/kg in rats is reported in the OECD SIDS Initial Assessment Report for citric acid.
- Endpoint:
- acute toxicity: oral
- Type of information:
- experimental study
- Adequacy of study:
- weight of evidence
- Study period:
- 1973
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- data from handbook or collection of data
- Principles of method if other than guideline:
- Only data from review article available. No guideline or method indicated.
- GLP compliance:
- not specified
- Species:
- rat
- Strain:
- not specified
- Sex:
- not specified
- Control animals:
- not specified
- Sex:
- not specified
- Dose descriptor:
- LD50
- Effect level:
- 525 mg/kg bw
- Interpretation of results:
- Category 4 based on GHS criteria
- Conclusions:
- According to the review article, the LD50 of lithium carbonate is 525 mg/kg bw after oral administration to rats.
- Executive summary:
According to the review article, the LD50 of lithium carbonate is 525 mg/kg bw after oral administration to rats. Thus, lithium carbonate has to be classified as H302 ('Harmful if swallowed') according to Regulation (EC) 1272/2008 as the LD50 per oral route in rats is in the range of 300 < LD50 <= 2000 mg/kg.
- Endpoint:
- acute toxicity: oral
- Type of information:
- experimental study
- Adequacy of study:
- weight of evidence
- Study period:
- 1999
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- data from handbook or collection of data
- Qualifier:
- no guideline followed
- Principles of method if other than guideline:
- Only handbook data available. No guideline or method indicated.
- GLP compliance:
- not specified
- Species:
- mouse
- Strain:
- not specified
- Sex:
- not specified
- Details on study design:
- Not applicable
- Preliminary study:
- Not applicable
- Sex:
- not specified
- Dose descriptor:
- LD50
- Effect level:
- 753 mg/kg bw
- Interpretation of results:
- Category 4 based on GHS criteria
- Conclusions:
- According to the handbook data, the LD50 of lithium carbonate is 753 +/- 27.5 mg/kg bw after oral administration to mice.
- Executive summary:
According to the handbook data, the LD50 of lithium carbonate is 753 +/- 27.5 mg/kg bw after oral administration to mice.
This result is in line with those obtained in rat and supports the classification of lithium carbonate:
- Category IV (300 < LD50 <= 2000 mg/kg), hazard statement H302 (harmful if swallowed), according to Regulation (EC) No 1272/2008 (CLP).
- Endpoint:
- acute toxicity: oral
- Type of information:
- experimental study
- Adequacy of study:
- weight of evidence
- Study period:
- 1999
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- data from handbook or collection of data
- Qualifier:
- no guideline followed
- Principles of method if other than guideline:
- Only handbook data available. No guideline or method indicated.
- GLP compliance:
- not specified
- Species:
- rat
- Strain:
- not specified
- Sex:
- male/female
- Control animals:
- not specified
- Preliminary study:
- Not applicable
- Sex:
- female
- Dose descriptor:
- LD50
- Effect level:
- 723 mg/kg bw
- Sex:
- male
- Dose descriptor:
- LD50
- Effect level:
- 640 mg/kg bw
- Interpretation of results:
- Category 4 based on GHS criteria
- Conclusions:
- According to the handbook data, the LD50 of lithium carbonate is 723 +/- 38 mg/kg bw after oral administration to female rats and 640 +/- 30 mg/kg bw to male rats.
- Executive summary:
According to the handbook data, the LD50 of lithium carbonate is 723 +/- 38 mg/kg bw after oral administration to female rats and 640 +/- 30 mg/kg bw to male rats. Thus, lithium carbonate has to be classified as H302 ('Harmful if swallowed') according to Regulation (EC) 1272/2008 as the LD50 per oral route in rats is in the range of 300 < LD50 <= 2000 mg/kg.
Additional remark: Since lithium carbonate hydrolyses in aqueous matrices and thereby generates basic solution due to resulting lithium hydroxide and lithium hydrogen carbonate systemic effects will always be accompanied by local effects (tissue damage), causing secondary also systemic toxicity. Consequently, the toxicity noted represents a sum of local and systemic effects.
- Endpoint:
- acute toxicity: oral
- Type of information:
- experimental study
- Adequacy of study:
- weight of evidence
- Study period:
- 1999-03-26 to 1999-05-06
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 401 (Acute Oral Toxicity)
- Version / remarks:
- February 24th 1987
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- EU Method B.1 (Acute Toxicity (Oral))
- Version / remarks:
- January 1993
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- EPA OPPTS 870.1100 (Acute Oral Toxicity)
- Version / remarks:
- August 1998
- Deviations:
- no
- GLP compliance:
- yes
- Test type:
- standard acute method
- Limit test:
- no
- Species:
- rat
- Strain:
- Sprague-Dawley
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Charles River Laboratories
- Age at study initiation: young adults
- Weight at study initiation: 207-275 g
- Fasting period before study: yes
- Housing: individually housed in stainless steel, suspended cages
- Diet: Purina Rodent Chow 5001 (pellets), ad libitum
- Water: Fresh tap water, ad libitum
- Acclimation period: 5 days
ENVIRONMENTAL CONDITIONS
- Temperature (°F): 65-71
- Humidity (%): 50-61
- Photoperiod (hrs dark / hrs light): 12/12 - Route of administration:
- oral: gavage
- Vehicle:
- water
- Details on oral exposure:
- - Amount of vehicle (if gavage):
Dosage group 2000 mg/kg, males: 1.8 - 1.9 mL
Dosage group 2000 mg/kg females: 1.7 - 1.8 mL
Dosage group 1500 mg/kg males: 1.3 - 1.4 mL
Dosage group 1500 mg/kg females: 1.3 mL
Dosage group 1000 mg/kg males: 0.94 - 1.1 mL
Dosage group 1000 mg/kg females: 0.83 - 0.90 mL - Doses:
- 1000, 1500, 2000 mg/kg bw
- No. of animals per sex per dose:
- 5 animals/dose/sex
- Control animals:
- no
- Details on study design:
- - Duration of observation period following administration: 14 days
- Frequency of observations and weighing: 0.5, 1, 2, 3, 4, 6 h following dosing and daily thereafter for 14 days
- Necropsy of survivors performed: yes , any animal not surviving to termination were also necropsied.
- clinical signs: 0.5, 1, 2, 3, 4, 6 h following dosing and daily thereafter for 14 days
- body weight: was recorded on days 0, 7 and 14 - Statistics:
- The oral LD50 value and 95 % confidence limits for separate and combined sexes were calculated using a modified Logit-Linear Regression Program written by Jim Gibbons, Texas Instruments Calculator Products Division.
- Key result
- Sex:
- male
- Dose descriptor:
- LD50
- Effect level:
- 1 317 mg/kg bw
- Based on:
- test mat.
- 95% CL:
- >= 993 - <= 1 640
- Key result
- Sex:
- female
- Dose descriptor:
- LD50
- Effect level:
- 1 519 mg/kg bw
- Based on:
- test mat.
- 95% CL:
- >= 1 179 - <= 1 859
- Key result
- Sex:
- male/female
- Dose descriptor:
- LD50
- Effect level:
- 1 426 mg/kg bw
- Based on:
- test mat.
- 95% CL:
- >= 1 242 - <= 1 609
- Mortality:
- All deaths occurred within 5 days of dosing. Data is summarized below.
- Clinical signs:
- other: All deaths occurred within 5 days after dosing. The most significant clinical signs were twitching, rolling over in cage, recumbency, loss of muscle control, squinting eyes and tremors. All signs subsided by study day 6.
- Gross pathology:
- Red liquid was found in the stomach of one decedent and red liquid was found in the intestines of another decedent. Animals sacrificed at study termination on day 14 were found to be normal at necropsy.
- Interpretation of results:
- Category 4 based on GHS criteria
- Conclusions:
- Based on the results of the acute oral toxicity study of lithium nitrate a LD50 of 1317 (male), 1519 (female) and 1426 (Combined) mg/kg bw was derived.
- Executive summary:
Groups of five male and female Sprague-Dawley rats were orally administered lithium nitrate by a 25 % (w/v) preparation in tap water. Observations for toxicity were conducted 0.5, 1, 2, 3, 4, and 6 hours post-dosing, and daily thereafter for fourteen days. Body weights were recorded weekly and prior to necropsy. Gross necropsies were performed on all animals. All deaths occurred within 5 days of dosing. The most significant clinical signs were twitching, rolling over in cage, recumbency, loss of muscle control, squinting eyes and tremors. All signs subsided by study day 6; surviving rats remained healthy and gained weight until study termination. Red liquid was found in the stomach of one and in the intestine of another decedent. Animals sacrificed at study termination on day 14 were found to be normal at necropsy. The LD50 values determined were 1317 mg/kg in male rats, 1519 mg/kg in female rats, and 1426 mg/kg in combined sexes.
Referenceopen allclose all
Main study: 5 male and 5 female mice in each treatment group were administered 3,000, 4,343, 6,000, 8,485 or 12,000 mg/kg of citric acid by gavage. The test substance was dissolved in food grade tap water at such concentrations that in every group 20 mL/kg, corresponding to approx. 0.4 mL per animal, were given. Controls were administered 0.4 mL tap water by gavage. Clinical symptoms were observed 2 h and 24 h after administration. The survivors were followed-up for 10 days after dosing, mortalities were recorded daily, then survivors were sacrificed.
The summarized mortality data:
Male | Female | Combined | |||
Dosage Level (mg/kg bw) | No. dead / No. dosed | Dosage Level (mg/kg bw) | No. dead / No. dosed | Dosage Level (mg/kg bw) | No. dead / No. dosed |
2000 | 5/5 | 2000 | 5/5 | 2000 | 10/10 |
1500 | 4/5 | 1500 | 2/5 | 1500 | 6/10 |
1000 | 0/5 | 1000 | 0/5 | 1000 | 0/10 |
Endpoint conclusion
- Endpoint conclusion:
- adverse effect observed
- Dose descriptor:
- LD50
- Value:
- 1 336 mg/kg bw
Acute toxicity: via inhalation route
Endpoint conclusion
- Endpoint conclusion:
- no study available
Acute toxicity: via dermal route
Endpoint conclusion
- Endpoint conclusion:
- no study available
Additional information
Acute toxicity via oral route
An acute oral toxicity study with lithium citrate tetrahydrate is not available. Consequently read-across was applied using characteristically similar compounds. A weight of evidence approach was performed with read-across data from lithium nitrate, lithium carbonate and citric acid.
Read-across with lithium nitrate (FMC, Albemarle, I99-2283, 1999)
The acute oral toxicity of lithium nitrate was investigated in a study according to OECD guideline 401. Groups of five male and female Sprague-Dawley rats were orally administered lithium nitrate by a 25 % (w/v) preparation in tap water. Observations for toxicity were conducted 0.5, 1, 2, 3, 4, and 6 hours post-dosing, and daily thereafter for fourteen days. Body weights were recorded weekly and prior to necropsy. Gross necropsies were performed on all animals. The LD50 values in mg/kg bw and the corresponding 95 % confidence limits are as follows: Male: 1317 (993-1640); Female: 1519 (1179-1859); Combined: 1426 (1242-1609). All deaths occurred within 5 days of dosing. The most significant clinical signs were twitching, rolling over in cage, recumbency, loss of muscle control, squinting eyes and tremors. All signs subsided by study day 6; surviving rats remained healthy and gained weight until study termination. Red liquid was found in the stomach of one and in the intestines of another decedent. Animals sacrificed at study termination on day 14 were found to be normal at necropsy. The recalculated LD50 values for lithium citrate tetrahydrate are 1795 mg/kg in male rats, 2071 mg/kg in female rats, and 1944 mg/kg in combined sexes. Based on these results the substance has to be classified as H302 'Harmful if swallowed' according to Regulation (EC) 1272/2008 as the LD50 per oral route in rats is in the range of 300 < LD50 <= 2000 mg/kg.
Read-across with lithium carbonate (Kiso to Rinsho 1973; Kushneva 1999)
According to Kushneva et al. (1999) an LD50 of lithium carbonate of 723 +/- 38 mg/kg bw after oral administration to female rats and LD50 of 640 +/- 30 mg/kg bw to male rats is reported. The recalculated acute oral LD50 values for lithium citrate tetrahydrate are 1839 mg/kg bw in females and 1628 mg/kg bw in males. Kiso to Rinsho (1973) reported an LD50 of lithium carbonate of 525 mg/kg bw after oral administration to rats. This value correspond to an acute oral LD50 of 1336 mg/kg bw for lithium citrate tetrahydrate. Thus, even when considering the lower study result, the substance has to be classified as H302 'Harmful if swallowed' according to Regulation (EC) 1272/2008 as the LD50 per oral route in rats is in the range of 300 < LD50 <= 2000 mg/kg.
Read-across with citric acid (OECD 2001)
Acute oral toxicity data for citric acid are reported in the OECD SIDS Initial Assessment Report for citric acid (2001). In mice an LD50 of 5400 mg/kg is reported for citric acid, which correspond to an LD50 of 7926 mg/kg bw for lithium citrate tetrahydrate. Several LD50 values for citric acid in rat are reported in the OECD SIDS Initial Assessment Report. The LD50 values ranged from 3000 mg/kg to 12000 mg/kg bw. The recalculated acute oral LD50 values for lithium citrate tetrahydrate in rat are between 4403 and 17613 mg/kg bw. Based on these results, a low acute toxicity by oral application in both rat and mouse is expected for lithium citrate tetrahydrate.
Conclusion:
Acute oral toxicity data are available for the read-cross substances lithium nitrate, lithium carbonate and citric acid. Since citric acid is generally recognized as safe (GRAS) direct food additive by the Food and Drug Administration (FDA) a low acute oral toxicity was expected. This assumption is supported by the available data with citric acid and it was confirmed that lithium is the relevant toxicological moiety of lithium citrate tetrahydrate. The available experimental data with the lithium salts were considered valid and the lowest LD50 of 525 mg Li2CO3/kg bw, corresponding to 1336 mg/kg bw for the target substance is chosen as key value.
Justification for classification or non-classification
Classification, Labelling, and Packaging
Regulation (EC) No 1272/2008:
The available experimental test
data with the read-across substances are reliable and suitable for
classification purposes under Regulation (EC) No 1272/2008. Based on
available data on acute toxicity, the test substance is classified as
cat. 4, H302 (Harmful if swallowed) according to Regulation (EC) No
1272/2008 (CLP), as amended for the tenth time in Regulation (EU) No
2017/776.
Information on Registered Substances comes from registration dossiers which have been assigned a registration number. The assignment of a registration number does however not guarantee that the information in the dossier is correct or that the dossier is compliant with Regulation (EC) No 1907/2006 (the REACH Regulation). This information has not been reviewed or verified by the Agency or any other authority. The content is subject to change without prior notice.
Reproduction or further distribution of this information may be subject to copyright protection. Use of the information without obtaining the permission from the owner(s) of the respective information might violate the rights of the owner.