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EC number: 231-203-4 | CAS number: 7446-26-6
- 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
Repeated dose toxicity: oral
Administrative data
- Endpoint:
- sub-chronic toxicity: oral
- Type of information:
- experimental study
- Adequacy of study:
- key study
- 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:
- Subacute Toxicity Studies with Zinc Sulfate in Mice and Rats
- Author:
- Maita et al.,
- Year:
- 1 981
- Bibliographic source:
- J. Pesticide Sci. 6:327 - 336
Materials and methods
Test guideline
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 408 (Repeated Dose 90-Day Oral Toxicity Study in Rodents)
- Deviations:
- yes
- Remarks:
- 10 fold intervals were used between the test concentrations instead of 2 - to 4 fold intervals, the applied statistic is not appropriate to analyse dose-response relationships
- GLP compliance:
- no
- Limit test:
- no
Test material
- Reference substance name:
- 7446-20-0
- EC Number:
- 616-097-3
- Cas Number:
- 7446-20-0
- IUPAC Name:
- 7446-20-0
- Test material form:
- solid: crystalline
- Details on test material:
- - Name of test material (as cited in study report): zinc sulfate heptahydrate
- Physical state: odorless crystal
- Analytical purity: 99.9%
Constituent 1
Test animals
- Species:
- rat
- Strain:
- Wistar
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Shizuoka Agriculture Cooperative Association for Laboratory Animals, Hamamatsu, Japan
- Age at study initiation: 4 weeks
- Housing: 4 animals of the same sex per cage in stainless cages with a wire-meshed bottom
- Diet: pulverized chow, M, Oriental Yeast Co., ad libitum
- Water: ad libitum
- Acclimation period: 1 week
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 24 ± 1
- Humidity (%): 55 ± 5
- Photoperiod (hrs dark / hrs light): 10/14
Administration / exposure
- Route of administration:
- oral: feed
- Vehicle:
- unchanged (no vehicle)
- Details on oral exposure:
- DIET PREPARATION
- Mixing appropriate amounts with standard diet - Analytical verification of doses or concentrations:
- no
- Duration of treatment / exposure:
- 13 weeks
- Frequency of treatment:
- continuous
Doses / concentrationsopen allclose all
- Dose / conc.:
- 23.2 mg/kg bw/day (actual dose received)
- Remarks:
- males, calculated from the food intake average (corresponds to 300 ppm)
- Dose / conc.:
- 234 mg/kg bw/day (actual dose received)
- Remarks:
- males, calculated from the food intake average (corresponds to 3000 ppm)
- Dose / conc.:
- 2 514 mg/kg bw/day (actual dose received)
- Remarks:
- males, calculated from the food intake average (corresponds to 30000 ppm)
- Dose / conc.:
- 24.5 mg/kg bw/day (actual dose received)
- Remarks:
- females, calculated from the food intake average (corresponds to 300 ppm)
- Dose / conc.:
- 243 mg/kg bw/day (actual dose received)
- Remarks:
- females, calculated from the food intake average (corresponds to 3000 ppm)
- Dose / conc.:
- 2 486 mg/kg bw/day (actual dose received)
- Remarks:
- females, calculated from the food intake average (corresponds to 3000 ppm)
- No. of animals per sex per dose:
- 12
- Control animals:
- yes, plain diet
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:
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/day/animal: Yes
- Time schedule for examinations: twice a week
WATER CONSUMPTION AND COMPOUND INTAKE : Yes
- Time schedule for examinations: twice a week
HAEMATOLOGY: Yes
- Anaesthetic used for blood collection: Yes (ether anaestesia)
- Parameters checked: Blood was taken from the posterior vena cava by a heparinized syringe to analyse erythrocyte count, haemoglobin, leukocyte count and haematocrit.
CLINICAL CHEMISTRY: Yes
- Parameters checked: Blood was taken from the posterior vena cava by a heparinized syringe to analyse total plasma protein, alkaline phosphatase (AIP), glucose, urea nitrogen (UN), GOT, GPT, cholesterol and calcium. - Sacrifice and pathology:
- GROSS PATHOLOGY: Yes
- The following organs were weighed: brain, pituitary, thyroid, heart, thymus, liver, kidney, spleen, adrenals, testes, ovaries and muscels (triceps surae)
HISTOPATHOLOGY: Yes
- The following additional organs were examined: submaxillary glands, lungs, mesentery lymph nodes, pancreas, stomach, small and large intestine, accessory genital organs, bone and bone marrow (sternum, femur). Paraffin sections (3 - 4 µm) were stained with haematoxylin-eosin, periodic Schiff´s reaction and azan for microscopic observations. - Statistics:
- Student´s t-test was performed to estimate the statistical differences between control and treated groups.
Results and discussion
Results of examinations
- Clinical signs:
- effects observed, treatment-related
- Description (incidence and severity):
- A female in the control and high dose group (one animal each per test group) showed suppurative pyelitis. One week after commencement of the experiment, high-dose test animals from both sexes discarded the diet from the food jar by picking it out with their fore-limbs. Since the actual food intake of these animals was not decreased enough to indicate anorexia, the symptom might have been induced by the unpalatability of the diet with its high concentration of ZnSO4 rather than by the specific toxicological effect of the chemical.
- Mortality:
- mortality observed, treatment-related
- Description (incidence):
- A female in the control and high dose group (one animal each per test group) were killed in extremis due to suppurative pyelitis. No further moribund animals of either sex were found.
- Body weight and weight changes:
- effects observed, treatment-related
- Description (incidence and severity):
- In the high-dose group, a depressed body weight was observed in males (453 g, 463 g, 430 g and 371 g*** for controls, low-, mid- and high-dose animals, respectively) which correlated to retarded growth resulting in smaller body sizes. In contrast, for females, the decrease in body weight reached significant differences compared to control animals only from the 1st up to the 5th week of the study. At the end of the study, no significant effect on body weight was noted (253 g, 257 g, 255 g and 231 g for control, low-, mid- and high-dose animals) (*p < 0.05, **p < 0.01, ****p < 0.001). Thus, a treatment-related effect was only noted for males which is considered as adverse.
- Food consumption and compound intake (if feeding study):
- effects observed, treatment-related
- Description (incidence and severity):
- 30000 ppm: decreased food intake (non significant)
High-dose animals of both sexes showed a slight, non-significant decrease in food intake. In detail, the average food intake of controls were determined as 24.6 and 15.7 g/rat/day for males and females, respectively, which was reduced to 24.9/16.1 g/rat/day, 23.6/15.6 g/rat/day and 21.3/14.9 g/rat/day in males/females of the low, mid and high-dose group, respectively. For females, the reduced food intake was only recorded from week 1 to 6. - Food efficiency:
- effects observed, treatment-related
- Description (incidence and severity):
- 30000 ppm: decreased food efficiency average in males (non significant)
In contrast to females where no difference in the food efficiency average was determined between control and test animals, a slight, non-significant dose-dependent decrease in food efficiency average was determined in males of the high-dose group (control: 2.2, low-dose group: 2.2, mid-dose group: 2.0, high-dose group: 1.8). - Water consumption and compound intake (if drinking water study):
- effects observed, treatment-related
- Description (incidence and severity):
- 30000 ppm: a slight reduction in water intake was determined for males (non significant)
Males of the high-dose group revealed a slight but non-significant reduction in the water intake average compared to control animals. Specifically, the following values were determined for control, low-, mid- and high-dose groups: 45.5, 43.9, 44.0 and 37.8 mL/day/rat. In contrast, no treatment-related alterations were determined in females ( 36.5, 34.9, 36.2 and 34.2 mL/day/rat for control, low-, mid- and high-dose group animals). - Ophthalmological findings:
- not examined
- Haematological findings:
- effects observed, treatment-related
- Description (incidence and severity):
- 3000 ppm: females showed a slight increment of haemoglobin; 30000 ppm: moderate reduction in leukocyte count in both sexes, decreases in haematocrit and heamoglobin concentrations in males
In detail:
A moderate, statistical significant reduction in leukocyte count was shown in both sexes in the high-dose group. The total amount of leukocytes was determined of 7.3, 8.7, 6.2 and 4.7*** E03/mm³ in males and 4.5, 4.6, 4.0 and 3.3*** E03/mm³ for females of control, low-, mid- and high-dose group animals, respectively. However, no change in the differential distribution of leukocytes have been evaluated. Further, males of the high-dose group disclosed a slight but significant decrease in haematocrit (41.8, 41.5, 41.1 and 40.0**% for control, low-, mid- and high-dose animals, respectively) and haemoglobin concentration (14.9, 14.8, 14.6 and 13.9* g/dL for control, low-, mid- and high-dose animals, respectively). In contrast, no significant effects in females have been determined on the haematocrit value. A slight increase in the haemoglobin value was observed for females of the mid-dose group (13.5, 13.6, 14** and 13.2 g/dL for control, low-, mid- and high-dose animals. No changes have been reported for the amount of red blood cells in both genders (*p < 0.05, **p < 0.01, ***p < 0.001). The reduced haemoglobin level in males might be due to depressed iron content in the blood and tissues. However, as this effect was only observed in males and not in females, such a general mechanism of toxicity might rather be questionable. - Clinical biochemistry findings:
- effects observed, treatment-related
- Description (incidence and severity):
- significant decreased levels in TP, GOT, GPT, Cholesterol and Calcium in males of different dose groups and Ca in females of the mid- and high-dose group (non adverse)
In detail:
Significant reductive tendencies were seen in male rats in the levels of GOT (87, 77*, 76 and 76 for control, low-, mid- and high-dose groups, respectively), GPT (45, 35*, 34*, 34* for control, low-, mid- and high-dose groups, respectively), total protein (6.8, 6.7, 6.6 and 6.3 g/dL*** for control, low-, mid- and high-dose groups, resepectively), cholesterol (60, 59, 65 and 49 mg/dL* for control, low-, mid- and high-dose groups, respectively) and calcium (10.4, 10.2, 10.0 and 10.0 mg/dL* for control, low-, mid- and high-dose groups, respectively). In females, only calcium levels were altered in the mid- and high-dose group compared to the controls (10.1, 10.1, 9.9* and 9.7 mg/dL *** for control, low-, mid- and high-dose groups, respectively) (*p < 0.05, **p < 0.01, ***p < 0.001). As no correlation was observed between the clinical chemistry and histopathology, the observed effects are not interpreted as adverse. - Urinalysis findings:
- not examined
- Behaviour (functional findings):
- not examined
- Organ weight findings including organ / body weight ratios:
- effects observed, non-treatment-related
- Description (incidence and severity):
- 30000 ppm: slight or moderate decreases in relative organ weights of the brain, liver and spleen in males; thyroid in females (non adverse)
In detail:
Statistically significant decreased organ weights were determined in males of the high-dose group for the brain (relative organ weight), the pituitary (absolute organ weight), thymus (absolute organ weight), liver (absolute and relative organ weight), the kidney (absolute organ weight), the spleen (absolute and relative organ weight), the gonads (absolute organ weight) and the muscles (absolute organ weight). In high-dose females, significant reduced organ weights were noted for the liver (absolute organ weight) and the spleen (absolute organ weight). Mid-dose females revealed an increase in absolute thyroid weight. As the effects on relative organ weights were concomitantly without histological findings, the observed effects might rather be fortiutous than treatment-related and is not interpreted as adverse. - Gross pathological findings:
- no effects observed
- Description (incidence and severity):
- No treatment-related remarkable lesions were reported for all dose-groups.
- Neuropathological findings:
- not examined
- Histopathological findings: non-neoplastic:
- effects observed, treatment-related
- Description (incidence and severity):
- Pancreatic lesions, degeneration and necrosis of acinar cells, clarification of centroacinar cells and interstitial fibrosis have been reported for the high-dose group (sex not further specified). No other treatment-related lesions were reported.
- Histopathological findings: neoplastic:
- no effects observed
- Other effects:
- not examined
- Details on results:
- BODY WEIGHT AND WEIGHT GAIN
In the high-dose group, a depressed body weight was observed in males which correlated to retarded growth resulting in smaller body sizes. The food consumption of these animals decreased non-significantly around 24% at most compared to controls. As historical data indicate that a 30% reduced food intake does not cause a reduction in weight gain, this effect is considered as treatment-related. In contrast, for females, the decrease in body weight reached significant differences to control animals only from the 1st up to the 5th week of the study. At the end of the study, no significant effect on body weight was noted. Thus, a treatment-related effect was only noted for males which is considered as adverse.
Effect levels
open allclose all
- Key result
- Dose descriptor:
- NOAEL
- Effect level:
- 234 mg/kg bw/day (actual dose received)
- Based on:
- test mat.
- Sex:
- male
- Basis for effect level:
- other: no adverse effects observed in the examined parameters
- Dose descriptor:
- LOAEL
- Effect level:
- 2 514 mg/kg bw/day (actual dose received)
- Based on:
- test mat.
- Sex:
- male
- Basis for effect level:
- other: body weight; haematology; histopathology; corresponds to 30000 ppm
- Key result
- Dose descriptor:
- NOAEL
- Effect level:
- 243 mg/kg bw/day (actual dose received)
- Based on:
- test mat.
- Sex:
- female
- Basis for effect level:
- other: no adverse effects observed in the examined parameters; corresponds to 3000 ppm
- Dose descriptor:
- LOAEL
- Effect level:
- 2 486 mg/kg bw/day (actual dose received)
- Based on:
- test mat.
- Sex:
- female
- Basis for effect level:
- other: body weight; haematology; histopathology; corresponds to 30000 ppm
Target system / organ toxicity
- Key result
- Critical effects observed:
- no
Any other information on results incl. tables
Table 1: Effects induced by zinc sulfate heptahydrate in rats
Endpoint |
Effect |
Dose group (ppm) |
Gender |
|
Male |
Female |
|||
Body weight (g) |
Control |
453 |
253 |
|
300 |
463 |
257 |
||
3000 |
430 |
255 |
||
30000 |
371*** |
231 |
||
Haematology |
Haematocrit (%) |
Control |
41.8 |
39.4 |
300 |
41.5 |
38.9 |
||
3000 |
41.1 |
40.2 |
||
30000 |
40.0** |
38.7 |
||
Haemoglobin (g/dL) |
Control |
14.9 |
13.5 |
|
300 |
14.8 |
13.6 |
||
3000 |
14.6 |
14.0** |
||
30000 |
13.9* |
13.2 |
||
Red Blood Cell Count (x10E6/mm³) |
Control |
6.9 |
6.4 |
|
300 |
7.0 |
6.5 |
||
3000 |
6.8 |
6.6 |
||
30000 |
6.9 |
6.6 |
||
Leukocyte (total (+E03/mm3) |
Control |
7.3 |
4.5 |
|
300 |
8.7 |
4.6 |
||
3000 |
6.2 |
4.0 |
||
30000 |
4.7*** |
3.3*** |
||
Clinical Chemistry |
Total protein (g/dL) |
Control |
6.8 |
6.8 |
300 |
6.7 |
6.8 |
||
3000 |
6.6 |
6.8 |
||
30000 |
6.3*** |
6.6 |
||
GOT (K-unit) |
Control |
87 |
93 |
|
300 |
77* |
86 |
||
3000 |
76 |
98 |
||
30000 |
76 |
87 |
||
GPT (K-unit) |
Control |
45 |
58 |
|
300 |
35* |
42 |
||
3000 |
34* |
57 |
||
30000 |
34* |
41 |
||
Chol (mg/dL) |
Control |
60 |
66 |
|
300 |
59 |
75 |
||
3000 |
65 |
65 |
||
30000 |
49* |
65 |
||
Ca (mg/dL) |
Control |
10.4 |
10.1 |
|
300 |
10.2 |
10.1 |
||
3000 |
10.0 |
9.9* |
||
30000 |
10.0* |
9.7** |
||
Organ Weights (absolute/relative) |
brain (g) |
Control |
1.93/0.43 |
1.78/0.70 |
300 |
2.05/0.44 |
1.82/0.71 |
||
3000 |
1.97/0.46 |
1.79/0.70 |
||
30000 |
1.87/0.5*** |
1.80/0.78 |
||
pituitary (mg) |
Control |
10.5/0.0023 |
11.5/0.0045 |
|
300 |
10.9/0.0024 |
11.6/0.0045 |
||
3000 |
11.0/0.0026 |
11.3/0.0044 |
||
30000 |
8.4***/0.0023 |
10.3/0.0045 |
||
thyroid (mg) |
Control |
24.2/0.0053 |
14.8/0.0058 |
|
300 |
28.5/0.0062 |
17.6/0.0068 |
||
3000 |
24.0/0.0056 |
17.8*/0.0071 |
||
30000 |
23.3/0.0063 |
17.2/0.0074 |
||
heart (g) |
Control |
1.31/0.29 |
0.80/0.32 |
|
300 |
1.35/0.29 |
0.85/0.33 |
||
3000 |
1.23/0.29 |
0.84/0.33 |
||
30000 |
1.07/0.29 |
0.79/0.34 |
||
thymus (g) |
Control |
0.48/0.11 |
0.40/0.16 |
|
300 |
0.48/0.10 |
0.42/0.16 |
||
3000 |
0.47/0.11 |
0.39/0.15 |
||
30000 |
0.39*/0.11 |
0.35/0.15 |
||
liver (g) |
Control |
16.1/3.55 |
8.8/3.48 |
|
300 |
17.5/3.80 |
9.7/3.77 |
||
3000 |
16.0/3.72 |
9.0/3.53 |
||
30000 |
11.9***/3.20*** |
7.5*/3.25 |
||
kidney (g) |
Control |
2.93/0.65 |
1.55/0.61 |
|
300 |
3.16/0.68 |
1.65/0.64 |
||
3000 |
2.96/0.69 |
1.58/0.62 |
||
30000 |
2.29***/0.62 |
1.45/0.63 |
||
spleen (g) |
Control |
0.65/0.14 |
0.44/0.17 |
|
300 |
0.74/0.16 |
0.45/0.18 |
||
3000 |
0.69/0.16 |
0.46/0.18 |
||
30000 |
0.49***/0.13* |
0.39*/0.17 |
||
adrenal (mg) |
Control |
48.8/0.011 |
53.5/0.021 |
|
300 |
46.0/0.010 |
55.0/0.021 |
||
3000 |
47.3/0.011 |
52.4/0.021 |
||
30000 |
42.2/0.011 |
54.7/0.024 |
||
gonads (mg) |
Control |
3000/0.67 |
67.3/0.027 |
|
300 |
3028/0.66 |
69.5/0.027 |
||
3000 |
2890/0.68 |
67.7/0.027 |
||
30000 |
2663*/0.72 |
71.7/0.031 |
||
muscles (g) |
Control |
2.52/0.56 |
1.58/0.62 |
|
300 |
2.70/0.58 |
1.61/0.063 |
||
3000 |
2.43/0.57 |
1.61/0.63 |
||
30000 |
2.16***/0.58 |
1.44/0.62 |
with *p < 0.05, **p < 0.01, ***p < 0.001
Applicant's summary and conclusion
- Conclusions:
- Under the test conditions, NOAEL of the test material in rats was determined to be 3000 ppm (approximately equivalent to 234 mg/kg/day in male rats and 243 mg/kg/day in female rats).
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