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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.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: 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: oral
Administrative data
- Endpoint:
- sub-chronic toxicity: oral
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 1981
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- comparable to guideline study with acceptable restrictions
Data source
Reference
- Reference Type:
- publication
- Title:
- Unnamed
- Year:
- 1 981
- Report date:
- 1981
Materials and methods
Test guideline
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 408 (Repeated Dose 90-Day Oral Toxicity Study in Rodents)
- GLP compliance:
- not specified
- Limit test:
- no
Test material
- Reference substance name:
- Zinc sulphate
- EC Number:
- 231-793-3
- EC Name:
- Zinc sulphate
- Cas Number:
- 7733-02-0
- Molecular formula:
- H2O4S.Zn
- IUPAC Name:
- Zinc sulphate
- Test material form:
- solid: particulate/powder
1
- Specific details on test material used for the study:
- - Name of test material: Zinc sulphate heptahydrate
- Substance type: Pure active substance
- Physical state: Crystal
- Analytical purity: 99.9 %
Test animals
- Species:
- mouse
- Strain:
- ICR
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Shizuoka Agriculture Cooperative Association for Laboratory Animals
- Age at study initiation: Four weeks
- Weight at study initiation: 25-30 g (male); 20-25 g (female)
- Fasting period before study: No data
- Housing: Four animals housed in each stainless cage with a wire-meshed bottom
- Diet: Pulverized chows F (Oriental Yeast Co.), ad libitum, mixed with test material
- Water: Ad libitum
- Acclimation period: One wk
ENVIRONMENTAL CONDITIONS
- Temperature: 24±1 °C
- Humidity: 55±5 %
- Air changes (per hr): No data
- Photoperiod: 10 h dark/14 h light cycle
Administration / exposure
- Route of administration:
- oral: feed
- Vehicle:
- other: Mixed with basic feed
- Details on oral exposure:
- DIET PREPARATION:
- Mixing appropriate amounts with (Type of food): Pulverized chows M (produced by Oriental Yeast Co. - Analytical verification of doses or concentrations:
- no
- Duration of treatment / exposure:
- 13 weeks
- Frequency of treatment:
- daily
Doses / concentrationsopen allclose all
- Dose / conc.:
- 300 ppm
- Dose / conc.:
- 3 000 ppm
- Dose / conc.:
- 30 000 ppm
- No. of animals per sex per dose:
- 12
- Control animals:
- yes, plain diet
- Details on study design:
- - Dose selection rationale: not specified
- Rationale for animal assignment: random
The animals were divided into four groups, each of which included 12 animals of each sex and fed on diets containing Zinc sulphate at four different concentration levels 0, 300, 3,000 and 30,000 ppm, for 13 weeks. - Positive control:
- No
Examinations
- Observations and examinations performed and frequency:
- DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: Daily
BODY WEIGHT: Yes
- Time schedule for examinations: Weekly
FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study):
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: Yes
- Compound intake calculated as time-weighted averages from the consumption and body weight gain data: Yes
FOOD EFFICIENCY:
- Body weight gain in kg/food consumption in kg per unit time X 100 calculated as time-weighted averages from the consumption and body weight gain data: Yes
WATER CONSUMPTION: Yes
- Time schedule for examinations: Twice a week
HAEMATOLOGY: Yes
- Time schedule for collection of blood: Not specified
- Anaesthetic used for blood collection: Yes (under light ether anaesthesia)
- How many animals: 96
- Parameters checked: Erythrocyte count, hemoglobin, leukocyte count, differential count of leukocyte
CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood: Not specified
- How many animals: 96
- Parameters checked: Total plasma protein, alkaline phosphatase, glucose, urea nitrogen, SGOT, SGPT, cholesterol and calcium. - Sacrifice and pathology:
- GROSS PATHOLOGY: Yes
After necropsy at the termination of the study the following organs were weighed: Brain, pituitary, thyroid, heart, thymus, liver, kidney, spleen, adrenals, gonads (testes or ovaries), and muscles (triceps surae).
HISTOPATHOLOGY: Yes (see table)
- For histopathology following organs and tissues were collected: Brain, pituitary, thyroid, heart, thymus, liver, kidney, spleen, adrenals, gonads (testes or ovaries), and muscles (triceps surae), submaxillary glands, lungs, mesenteric lymph nodes, pancreas, stomach, small and large intestine, accessory genital organs, bone and bone marrow (sternum and femur), and lesions of gross abnormalities
- 3 or 4 µm paraffin sections from the specimens were stained with hematoxylineosin, periodic acid Schiff's reaction and azan for microscopic observations. - Other examinations:
- None
- Statistics:
- Student's t-test was used to estimate the statistical differences between controls and treated groups.
Results and discussion
Results of examinations
- Clinical signs:
- effects observed, treatment-related
- Description (incidence and severity):
- - At 30,000 ppm: Depressed spontaneous motility before death or sacrifice.
- At ≤ 3,000 ppm: No treatment related toxic signs - Mortality:
- mortality observed, non-treatment-related
- Description (incidence):
- - At 30,000 ppm: Four males and one female in this group were found dead or killed in extremis during the study. Histological findings of these animals revealed impairment of the urinary tract and regressive changes in the exocrine gland of the pancreas. Mortality was 33.3% in males and 8.3% in females.
- Body weight and weight changes:
- effects observed, treatment-related
- Description (incidence and severity):
- - At 30,000 ppm: A more prominently retarded growth resulting in smaller body size than those of other groups.
- At 300 ppm: A significant but very slight depression of weight gain was seen in females for a week after commencement, followed by a rapid recovery to the control level. - Food consumption and compound intake (if feeding study):
- effects observed, treatment-related
- Description (incidence and severity):
- - At 30,000 ppm: The food intake of male and female mice was depressed during the first week of the study in comparison to that of the controls but showed a tendency to recover afterwards. Average food intake of these animals then remained at only a slightly lower level than that of the control group.
- Food efficiency:
- effects observed, treatment-related
- Description (incidence and severity):
- Markedly lower than those of the control group during the first week of the study, corresponding to the decrease in food intake.
-At 30,000 ppm: The overall average food efficiency was much lower than the control group.
- At 3,000 ppm: No data - Water consumption and compound intake (if drinking water study):
- effects observed, treatment-related
- Description (incidence and severity):
- -At 30,000 ppm: Decreased in both sexes during the first week. Though males soon recovered, females showed persistent lower intake during the study.
- Ophthalmological findings:
- not examined
- Haematological findings:
- effects observed, treatment-related
- Description (incidence and severity):
- Male and female mice in the 30,000 ppm group showed moderately lower values in hematocrit and hemoglobin concentration than those of the control group; the leukocyte count in males also decreased moderately. Morphological changes of erythrocyte anisocytosis, polychromatophilia and poikilocytosis, were seen in six males and four females which were reported by necropsy or microscopic observation to have fore-stomach ulcers. Though some significant fluctuations were seen in hematocrit, no dose dependent abnormalities were found in hemoglobin concentration and erythrocyte count in males or females at less than 3,000 ppm group.
- Clinical biochemistry findings:
- effects observed, treatment-related
- Description (incidence and severity):
- -At 30,000 ppm: A slight to moderate decrease in total protein, glucose and cholesterol and a moderate to marked increase in alkaline phosphatase and urea nitrogen. Additional significant changes occurring in these animals were depression of SGPT level and increase in calcium level in females, and an increase of SGOT level in males
- At 3,000 ppm: Some fluctuations with significant differences from controls were seen in several parameters but these were all within the acceptable historical limits of mice of this strain and age. - Urinalysis findings:
- not examined
- Behaviour (functional findings):
- not examined
- Immunological findings:
- not examined
- Organ weight findings including organ / body weight ratios:
- effects observed, treatment-related
- Description (incidence and severity):
- -At 30,000 ppm: Coincidental increase in absolute and relative weight was found in the thyroids of males and the kidneys of females.
- At ≤ 3,000 ppm: Statistically not significant values when compared to control. - Gross pathological findings:
- effects observed, treatment-related
- Description (incidence and severity):
- -At 30,000 ppm: Marked emaciation, ischemic discoloration of the kidney and thyroid, atrophy of the pancreas, edematous thickening of the upper small intestine and slight splenomegaly were recorded in addition to several cases of fore stomach ulcer.
- Neuropathological findings:
- not examined
- Histopathological findings: non-neoplastic:
- effects observed, treatment-related
- Description (incidence and severity):
- -At 30,000 ppm: There were lesions attributable to the treatment in the pancreas, upper intestine, stomach, spleen and kidney. The pancreatic acinar cells had swollen nuclei with an increased number of clarified nucleoli and whirl-like profiles in their cytoplasm which were more basophilically stained than the controls. Single cell necrosis of the acinar cells was also a common feature in these animals. Moreover, a decrease in the number of acinus and ductule like metaplasia of acinar cells was demonstrated. There was mucosal catarrh in the upper intestine with proliferation of epithelial cells and edema at lamina propria, slight to moderate ulcerative lesions in the boundary of the fore-stomach and proliferation of erythropoietic immature cells in the splenic red pulp of these animals. Regressive changes of the renal cortex were observed in the females.
- At ≤ 3,000 ppm: Statistically not significant values when compared to control - Histopathological findings: neoplastic:
- no effects observed
Effect levels
open allclose all
- Dose descriptor:
- NOEL
- Effect level:
- 3 000 ppm
- Based on:
- test mat. (total fraction)
- Sex:
- male/female
- Remarks on result:
- other: approximately equivalent to 458 mg/kg/day on male, 479 mg/kg/day on female.
- Dose descriptor:
- LOEL
- Effect level:
- 30 000 ppm
- Based on:
- test mat. (total fraction)
- Sex:
- male/female
- Basis for effect level:
- body weight and weight gain
- clinical biochemistry
- clinical signs
- food consumption and compound intake
- food efficiency
- gross pathology
- haematology
- histopathology: non-neoplastic
- organ weights and organ / body weight ratios
- water consumption and compound intake
Target system / organ toxicity
open allclose all
- Critical effects observed:
- yes
- Lowest effective dose / conc.:
- 30 000 ppm
- System:
- immune system
- Organ:
- leucocyte development
- Treatment related:
- yes
- Critical effects observed:
- yes
- Lowest effective dose / conc.:
- 30 000 ppm
- System:
- gastrointestinal tract
- Organ:
- intestine
- kidney
- pancreas
- spleen
- stomach
- Treatment related:
- yes
- Critical effects observed:
- yes
- Lowest effective dose / conc.:
- 30 000 ppm
- System:
- haematopoietic
- Organ:
- erythrocyte development
- Treatment related:
- yes
Applicant's summary and conclusion
- Conclusions:
- Under the test conditions, the NOEL of the test material in mice was determined to be 3,000 ppm (approximately equivalent to 458 mg/kg/day in male mice or 479 mg/kg/day in female mice).
- Executive summary:
A study was conducted to evaluate the sub chronic (13 wk) toxicity of the test material in ICR mice. The study followed was equivalent or similar to OECD Guideline 408 (Repeated Dose 90-Day Oral Toxicity in Rodents).
Mice of both sexes were fed a diet containing test substance at 0, 300, 3000 and 30000 ppm for 13 wk. The clinical signs of the animals, body weight, food, chemical and water intake, food efficiency, hematological, biochemical examination, necropsy and organ weight and histopathological examination were performed.
Animals in the 30,000 ppm group showed retarded growth along with low food intake, abnormal values in a few hematological parameters, decreased water intake and significant deviations in biochemical parameters. Histopathological lesions included catarrh at the upper intestine, ulcers at the boundary of fore- and glandular stomach, proliferation of erythropoietic immature cells in the splenic red pulp as well as pancreatic lesions.
Under the test conditions, NOEL of the test material in mice was determined to be 3,000 ppm (approximately equivalent to 458 mg/kg/day in male mice or 479 mg/kg/day in female mice.
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.