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EC number: 224-736-9 | CAS number: 4468-02-4
- 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
Repeated dose toxicity: other routes
Administrative data
- Endpoint:
- short-term repeated dose toxicity: other route
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 2008
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- study well documented, meets generally accepted scientific principles, acceptable for assessment
Data source
Reference
- Reference Type:
- publication
- Title:
- Unnamed
- Year:
- 2 008
- Report date:
- 2008
Materials and methods
Test guideline
- Qualifier:
- no guideline followed
- Principles of method if other than guideline:
- - Principle of test:
The aim of the study was to determine the maximal iterative dose of zinc that can be administrated in rats without any adverse effect.
- Short description of test conditions: Saline (control group) or zinc gluconate at 1, 2 or 4 mg/kg were intraperitoneally injected in animals daily during 7 days.
- Parameters analysed / observed: The tolerance of zinc treatments was evaluated by the observation of clinical symptoms, haematological parameters and biochemistry, in relation to the zinc and copper levels in blood, liver, pancreas and faeces. - GLP compliance:
- not specified
- Limit test:
- no
Test material
- Reference substance name:
- Bis(D-gluconato-O1,O2)zinc
- EC Number:
- 224-736-9
- EC Name:
- Bis(D-gluconato-O1,O2)zinc
- Cas Number:
- 4468-02-4
- Molecular formula:
- C12H22O14Zn
- IUPAC Name:
- bis(D-gluconato-O1,O2)zinc
- Test material form:
- solid: particulate/powder
- Details on test material:
- - Appearance : White cristalline powder:
- Batch number: 1700001575
- Manufacturing date: 10.08.2017
- Expiry date: 09.08.2020
Constituent 1
Test animals
- Species:
- rat
- Strain:
- Wistar
- Sex:
- male
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: purchased from Charles River Laboratories (Les Oncins, France)
- Weight at study initiation: weighing about 250 g
- Housing: Rats were housed according to the Agriculture and Environment Ministry standards
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: 1 week before the initiation of the treatment
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21±1°C
- Humidity (%): relative humidity of 55%
- Photoperiod (hrs dark / hrs light): 12-hr dark:light cycle
Administration / exposure
- Route of administration:
- intraperitoneal
- Vehicle:
- other: saline intraperitoneal composition.
- Duration of treatment / exposure:
- Saline or zinc gluconate were administered intraperitoneally during 7 days.
- Frequency of treatment:
- Saline or zinc gluconate were administered intraperitoneally every 24 hr.
Doses / concentrationsopen allclose all
- Dose / conc.:
- 1 mg/kg bw/day (nominal)
- Remarks:
- intraperitoneally
- Dose / conc.:
- 2 mg/kg bw/day (nominal)
- Remarks:
- intraperitoneally
- Dose / conc.:
- 4 mg/kg bw/day (nominal)
- Remarks:
- intraperitoneally
- No. of animals per sex per dose:
- 20 animals divided into four groups of rats: one normal control group (saline received) and three zinc groups treated by 1, 2 and 4 mg/kg per day of zinc gluconate.
- Control animals:
- yes, concurrent no treatment
- Details on study design:
- - Dose selection rationale: based on existing litterature (presented in the publication)
- Rationale for animal assignment: 20 animals were randomly divided into four groups of rats
Examinations
- Observations and examinations performed and frequency:
- BODY WEIGHT: Yes
- Time schedule for examinations: every days
HAEMATOLOGY: Yes
- Time schedule for collection of blood: At the end of the study, on day 7, blood was collected
- How many animals: all animals (20) - Sacrifice and pathology:
- At the end of the study, on day 7 (immediately after blood collection), the animals were killed by section of major chest vessels before tissue sampling. The liver and the pancreas were removed, weighed, immediately frozen in liquid nitrogen and stored at −80°C until analysis.
- Other examinations:
- Biochemical assays:
The levels of following parameteres were determined: plasma aspartate aminotransferase (AST), alanine aminotransferase (ALT), cholesterol, creatine kinase (CK), creatinine, glycaemia, lactate dehydrogenase (LDH), alkaline phosphatase (ALP) and urea.
Zinc and copper analysis:
Zinc and copper concentrations in erythrocyte, plasma, liver, pancreas and faeces were determined.
Blood elements:
White blood cells, red blood cells, blood platelets, haematocrit and haemoglobin were determined.
All these parameters were determined at the end of study (on day 7). - Statistics:
- Results are expressed as means for five animals per group ± S.E.M. The global course of each parameter was evaluated by an anova on ranks (Kruskall–Wallis test), and then the comparison between the four groups were performed with nonparametric rank sum tests (Mann–Whitney tests) using Statistica software (StatSoft Inc., Tulsa, OK, USA). Significance was considered at the level of P < 0.05.
Results and discussion
Results of examinations
- Clinical signs:
- not specified
- Mortality:
- no mortality observed
- Body weight and weight changes:
- effects observed, non-treatment-related
- Description (incidence and severity):
- From the second day, we observed a significant weight gain for the rats of control and 1 mg/kg zinc groups, whereas no weight gain was observed in the two other groups during the whole study.
- Food consumption and compound intake (if feeding study):
- not specified
- Food efficiency:
- not specified
- Water consumption and compound intake (if drinking water study):
- not specified
- Ophthalmological findings:
- not specified
- Haematological findings:
- not specified
- Clinical biochemistry findings:
- not specified
- Urinalysis findings:
- not specified
- Behaviour (functional findings):
- not specified
- Immunological findings:
- not specified
- Organ weight findings including organ / body weight ratios:
- effects observed, treatment-related
- Description (incidence and severity):
- Only for the highest zinc dose (4 mg/kg), the autopsy of the rats showed abnormal, abdominal organs on day 7 of the study, with the outcome of a congestive peritonitis and the thickening of the hepatic lobe borders.
- Gross pathological findings:
- not specified
- Neuropathological findings:
- not specified
- Histopathological findings: non-neoplastic:
- no effects observed
- Histopathological findings: neoplastic:
- no effects observed
- Other effects:
- no effects observed
- Details on results:
- Copper levels of zinc in faeces:
A dose-dependent excretion of zinc was observed on and after the fourth day of zinc supplementation. Concerning copper levels in faeces, no significant differences were observed between the control and the zinc-treated groups for the whole study.
Blood constituents:
For doses under 4 mg/kg, no significant effects of zinc on white and red blood cells as well as haematocrit and haemoglobin were observed between the control and the zinc groups. Significantly higher platelet levels were observed after injections with 2 mg/kg of zinc.
Biochemical parameters:
There were very few significant differences between the zinc groups and the normal control group. Only a significant hypoglycaemia (11% decrease) was observed after injection of 4 mg/kg of zinc compared to the
control group (P < 0.05).
Effect levels
- Dose descriptor:
- NOAEL
- Effect level:
- 2 mg/kg bw/day (nominal)
- Based on:
- test mat.
- Sex:
- male
Target system / organ toxicity
- Critical effects observed:
- no
Applicant's summary and conclusion
- Conclusions:
- No serious adverse effect was found within 1 week in rats injected intraperitoneally with 2 mg/kg/day of zinc gluconate. Results at 4 mg/kg/day of zinc gluconate should be used with a cautious manner.
- Executive summary:
Although zinc is an essential trace element involved in many physiological functions, toxicological data concerning acute exposure are scarce. The aim of our study was to determine the maximal iterative dose of zinc that can be administrated in rats without any adverse effect. Saline (control group) or zinc gluconate at 1, 2 or 4 mg/kg were intraperitoneally injected in animals daily during 7 days. The tolerance of zinc treatments was evaluated by the observation of clinical symptoms, haematological parameters and biochemistry, in relation to the zinc and copper levels in blood, liver, pancreas and faeces. We found no serious adverse effect within 1 week in rats injected intraperitoneally with 1 or 2 mg/kg/day of zinc gluconate, which tends to indicate that those doses could be useful in future therapeutic research. During the treatment of adult rats with repeated intraperitoneal injections of a 4 mg/kg/day zinc dose it was observed the occurrence of clinical adverse effects within a few days, as intraperitoneal local intolerance and effect on the body weight of rats. They are considered as minor effects and are used in a cautious manner.
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