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EC number: 209-042-6 | CAS number: 553-54-8
- 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
Toxicity to reproduction
Administrative data
- Endpoint:
- one-generation reproductive toxicity
- Type of information:
- experimental study
- Adequacy of study:
- weight of evidence
- Study period:
- Dosing up to 4 weeks prior to mating and after mating
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- data from handbook or collection of data
- Justification for type of information:
- Since lithium benzoate will dissociate in biological systems, it is considered valid to assess separately lithium and benzoate.
Data source
Reference
- Reference Type:
- publication
- Title:
- Unnamed
- Year:
- 2 003
Materials and methods
Test guideline
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 415 [One-Generation Reproduction Toxicity Study (before 9 October 2017)]
- Principles of method if other than guideline:
- Female Rats were treated with lithium chloride in food at 280 mg lithium per kg food (ca 7 mg/Li day, or ca 28 mg/kg/day Li, based on typical diet and animal weight). The dose was increased by 50% after mating. There were initially 6 females/group. Females were allowed to give birth. Both groups were split so that half received control diet and half received lithium in food at 280 mg Li/kg during lactation. Pups were assessed at 8-10 weeks postnatal.
- GLP compliance:
- no
- Limit test:
- yes
Test material
- Reference substance name:
- Lithium chloride
- EC Number:
- 231-212-3
- EC Name:
- Lithium chloride
- Cas Number:
- 7447-41-8
- Molecular formula:
- ClLi
- IUPAC Name:
- lithium chloride
Constituent 1
Test animals
- Species:
- rat
- Strain:
- Wistar
- Sex:
- male
Administration / exposure
- Route of administration:
- oral: feed
- Details on exposure:
- Males exposed for 90 days prior to mating
- Details on mating procedure:
- Untreated females
Doses / concentrationsopen allclose all
- Dose / conc.:
- 0 mg/kg diet
- Dose / conc.:
- 500 mg/kg diet
- Remarks:
- As lithium carbonate = 5 mg/kg diet Li
At 125 g/day/kg bw per rat = 0.625 mg/kg Li
- Dose / conc.:
- 800 mg/kg diet
- Remarks:
- As lithium carbonate = 8 mg/kg diet Li
At 125 g/day/kg bw per rat = 1 mg/kg/day Li
- Dose / conc.:
- 1 100 mg/kg diet
- Remarks:
- As lithium carbonate = 11 mg/kg diet Li
At 125 g/day/kg bw per rat = 1.4 mg/kg/day Li
- No. of animals per sex per dose:
- 20 males per group for effects on reproductive organs
Study was repeated at same dose levels with further 20 rats per dose to confirm reproductive indices. Mating took place from 90 days exposure.
A further set of animals were given a treatment free period of 45 days after 90 days treatment before mating and reproductive incides checked - Control animals:
- yes, concurrent no treatment
- Details on study design:
- Rats received a diet containing 0, 500, 800, or 1100 mg lithium carbonate/kg diet for 90 days.
Examinations
- Parental animals: Observations and examinations:
- Body weight, daily intake of food and water were determined
- Sperm parameters (parental animals):
- intact spermatids were counted in a hemocytometer
Two hundred sperm from at least five different areas on the slide were studied microscopically and sperm with abnormal heads and/or abnormal tails were scored - Litter observations:
- Number and viability of foeti were recorded 21 days post mating
- Postmortem examinations (parental animals):
- After 90 days of treatment, the testes, epididymis, prostate glands and seminal vesicles were removed and their wet weight was
determined.
The organ weight/body weight ratio was calculated and histological studies on testis, epididymis, vasdeferens,
seminal vesicle and prostate were carried out - Reproductive indices:
- The females were killed on 21 days post-conception, and fertility index was analysed
Results and discussion
Results: P0 (first parental generation)
General toxicity (P0)
- Clinical signs:
- no effects observed
- Mortality:
- no mortality observed
- Body weight and weight changes:
- no effects observed
- Food consumption and compound intake (if feeding study):
- no effects observed
- Haematological findings:
- effects observed, treatment-related
- Description (incidence and severity):
- The higher doses of lithium significantly reduced serum testosterone level in treated animals as compared to control
group - Organ weight findings including organ / body weight ratios:
- effects observed, treatment-related
Reproductive function / performance (P0)
- Reproductive function: sperm measures:
- effects observed, treatment-related
- Description (incidence and severity):
- The alterations observed consisted mainly of abnormal tail with or without abnormal head at the higher treatment levels
- Reproductive performance:
- effects observed, treatment-related
- Description (incidence and severity):
- No effects at 500 mg/kg diet (0.625 mg/kg Li)
At higher treatment levels, there was a dose response in fertility measured by viable implants
Mating indices were not affects
Effect levels (P0)
open allclose all
- Key result
- Dose descriptor:
- NOEL
- Effect level:
- ca. 0.625 mg/kg bw/day (actual dose received)
- Based on:
- element
- Remarks:
- Lithium
- Sex:
- male
- Basis for effect level:
- haematology
- organ weights and organ / body weight ratios
- gross pathology
- reproductive function (sperm measures)
- reproductive performance
- Dose descriptor:
- LOAEL
- Effect level:
- ca. 1 mg/kg bw/day (actual dose received)
- Based on:
- element
- Remarks:
- Lithium
- Sex:
- male
- Basis for effect level:
- haematology
- organ weights and organ / body weight ratios
- gross pathology
- reproductive function (sperm measures)
- reproductive performance
Target system / organ toxicity (P0)
- Critical effects observed:
- yes
- Lowest effective dose / conc.:
- 1 mg/kg bw/day (actual dose received)
- System:
- male reproductive system
- Organ:
- testes
- Treatment related:
- yes
- Dose response relationship:
- yes
Results: F1 generation
General toxicity (F1)
- Clinical signs:
- not examined
- Description (incidence and severity):
- Study for fertility was terminated prior to birth
- Mortality / viability:
- no mortality observed
- Description (incidence and severity):
- Based on health foeti
Effect levels (F1)
- Key result
- Dose descriptor:
- NOAEL
- Generation:
- F1
- Effect level:
- > 1.4 mg/kg bw/day (actual dose received)
- Based on:
- element
- Remarks:
- Lithium
- Sex:
- male/female
- Remarks on result:
- not determinable due to absence of adverse toxic effects
Target system / organ toxicity (F1)
- Key result
- Critical effects observed:
- no
Overall reproductive toxicity
- Key result
- Reproductive effects observed:
- yes
- Lowest effective dose / conc.:
- 1 mg/kg bw/day (nominal)
- Treatment related:
- yes
- Relation to other toxic effects:
- not specified
- Dose response relationship:
- yes
- Relevant for humans:
- not specified
Applicant's summary and conclusion
- Conclusions:
- Under the conditions of this study, treatment of 1 mg/kg/day and higher led to a reduction in fertily through lower sperm viability and possible damage to testis. At 0.625 mg/kg/day, there were no adverse effects.
It should be noted that company data used by registrants of other litium salts cite regulatory studies showing that a higher dose, up to parental toxicity levels, does not impact on fertility. Access to these company studies is being sought, but it is concluded by other registrants of Li salts that lithium does not affect fertily at concentrations up to parental toxic limits.
As a result, based on conclusions drawn by those with access to study reports for other lithium salts, it is not proposed to classified as toxic to reproduction on the basis of this publication.
However, other published reports (with less detail on methods and results) do suggest damage to male and demal reproductive organs at dose levels higher than the theraputic dose levels used for medicinal purposes.
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.
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