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EC number: 244-343-6 | CAS number: 21351-39-3
- 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
![](https://chesar.echa.europa.eu/o/diss-blank-theme/images/factsheets/A-REACH/factsheet/print_toxicological-information.png)
Repeated dose toxicity: oral
Administrative data
- Endpoint:
- short-term repeated dose toxicity: oral
- Remarks:
- combined repeated dose and reproduction / developmental screening
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- other: Study conducted to GLP and guideline
Cross-reference
- Reason / purpose for cross-reference:
- reference to same study
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 002
Materials and methods
Test guideline
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 422 (Combined Repeated Dose Toxicity Study with the Reproduction / Developmental Toxicity Screening Test)
- GLP compliance:
- yes
Test material
- Reference substance name:
- 10101-41-4
- EC Number:
- 600-148-1
- Cas Number:
- 10101-41-4
- IUPAC Name:
- 10101-41-4
- Reference substance name:
- calcium sulfate, dihydrate
- IUPAC Name:
- calcium sulfate, dihydrate
- Details on test material:
- - Name of test material (as cited in study report): Calcium sulfate dihydrate
- Analytical purity: 99.9%
- Lot/batch No.: Sigma Aldrich Corporation, Lot No. - 109H0166
Constituent 1
Constituent 2
Test animals
- Species:
- rat
- Strain:
- Sprague-Dawley
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Age at study initiation: 8 weeks
- Weight at study initiation: 254.2 - 297.8 g (males) and 182.7 - 208.2 g (females)
Administration / exposure
- Route of administration:
- oral: gavage
- Duration of treatment / exposure:
- 35 days for male animals and 41-45 days for female animals
- Frequency of treatment:
- Daily
Doses / concentrations
- Remarks:
- Doses / Concentrations:
0, 100, 300 and 1000 mg/kg/day
Basis:
- No. of animals per sex per dose:
- 60
- Control animals:
- yes, concurrent no treatment
Examinations
- Observations and examinations performed and frequency:
- - Clinical observations performed and frequency: Clinical symptoms were observed once a day but were observed once a week in detail; a death rate was observed twice a day; and body weight was observed once a week and just before the necropsy, but in case of pregnant females, it was measured on the day 0, 7, 14, 20 of gestation period, date of delivery, and 4 days after the delivery; consumption rate of fodder was observed once a week except mating period.
Tests for sensory organ and reflex action: 5 animals were randomly selected from each test group. Both preyer reflex test and corneal reflex test were performed before necropsy and during lactation for males and females, respectively.
Behaviour test: 5 animals were randomly selected from each test group to do grip strength test in terms of behaviour test. This test was performed before necropsy and during lactation for males and females, respectively.
- Haematological and biochemical test of blood: randomly selected 5 male and female animals from each test group were fasted a day before necropsy for both tests. Animals were anesthetized using ether and cut the abdomen open to collect blood. In case of the haematological test, blood coagulation preventative chemicals for the test of blood coagulation and the calculation of blood-corpuscles were 3.2 % sodium citrate and EDTA- 2K, respectively. On the other hand, blood coagulation preventative chemical was not used for the biochemical test, but gathered blood was left itself in the room temperature then the sera were separated using a centrifuge. For haematological test, 6 following items were measured; Haematocrit, hemoglobin concentration, erythrocyte count, total and different leucocyte count, platelet count, prothrombin time, and active partial thromboplastin time. For biochemical test of blood, eleven following items were measured; sodium, potassium, glucose, total cholesterol, blood urea nitrogen, creatinine, total protein, albumin, alanine aminotransferase, aspatate aminotransferase, and total bilirubin.
Organs examined at necropsy: Organ weight: testes, epididymider (all males) liver, kidney, adrenals, thymus, spleen, brain and heart (5 male and female animals from each test group).
Fixation: 22 kinds of tissues were fixed to do histopathologic tests such as testes, epididymides, ovaries, accessory sex organs for all animals, brain (including cerebrum, cerebellum and pons), spinal cord, stomach, small and large intestines (including peyer’s patches), liver, kidneys, adrenals, spleen, heart, thymus, thyroid, trachea, lungs, uterus, urinary bladder, lymph nodes (cervical mesenteric), peripheral nerve (sciatic or tibial), and bone marrow. - Statistics:
- Statistical decision tree, but in case of recovery group, either two-side Students t-test or two-side Apsin Welch t-test was used. In case of categorical data, two-sided Fishers exact test was used.
Results and discussion
Results of examinations
- Clinical signs:
- effects observed, treatment-related
- Mortality:
- mortality observed, treatment-related
- Body weight and weight changes:
- effects observed, treatment-related
- Food consumption and compound intake (if feeding study):
- not examined
- Food efficiency:
- not examined
- Water consumption and compound intake (if drinking water study):
- not examined
- Ophthalmological findings:
- not examined
- Haematological findings:
- effects observed, treatment-related
- Clinical biochemistry findings:
- effects observed, treatment-related
- Urinalysis findings:
- not examined
- Behaviour (functional findings):
- no effects observed
- Organ weight findings including organ / body weight ratios:
- effects observed, treatment-related
- Gross pathological findings:
- effects observed, treatment-related
- Histopathological findings: non-neoplastic:
- effects observed, treatment-related
- Histopathological findings: neoplastic:
- no effects observed
- Details on results:
- Mortality: There was one death at day 8 for male, and each death on the day 7 and 14 for female in the treatment group of 300 mg/kg/day. These were occurred during the administration process, so it did not have relationship with test substance.
Body weight: In male groups, temporarily, a case of diminishment in the amount of body weight change was observed at week 2 within the
control group in which some clinical signs were observed such as damage to esophagus. Body weight loss for female animals was observed several times during lactation period in every treatment group including the control group. However, these were occurred temporarily because of the lactation.
- Clinical signs: In male control group, a case of salivation and bloodylike secretion was observed on the day 11 and 12. In the 1,000 mg/kg/day treatment group, a case of depilation, dcab and pus was observed on the left cheek between the day 25 and the closing day. However, the frequency of occurrence was low and no dose-response correlation. Thus these symptoms were not influenced by test substance. In female control group, a case of genitalia bloody-like secretion was observed at day 29. In the 100 mg/kg/day treatment group, each case of hypoactivity and depilation was observed on the day 8 and 9, and between day 44 and the closing day, respectively. However, these symptoms were disappeared in short, thus these did not have relationship with test substance.
Amount of fodder consumption: No crucial difference between the treatment group and the control group was observed for both male and female animals during test period. For recovery group, no significant change was observed within themselves.
Test of reflex action: Five male and female animals were randomly selected from each test group, in which no specific reaction was observed.
Grip strength test: For male animals, 6 animals were left out from the treatment group. For female animals, 5 animals were left out from the control group, and the treatment group. All things being considered, there was no dose-response correlation and was no illness at the related organs such as the cerebellum and muscle.
Organ weight: Both absolute weight of the liver and the left kidney were increased at the recovery group with administration of 1,000 mg/kg/day as compared with that of the control group within the recovery group. There was no histopathological illness at the organs, so increased organ weight did not have relationship with test substance.
Necropsy opinions: For male animals, in the control group within the recovery group, a case of left and right caput epididymis cyst was observed and the 1,000 mg/kg/day recovery group had symptom of right caput epididymis cyst. However, its frequency of occurrence was low and it was even observed at the control group within the recovery group, so it did not have relationship with test substance. For female animals, in the 300 mg/kg/day treatment group, each animal was dead on the day 7 and 14 and; each case of lung dark-red discolouration was observed, but white particle in a lobe of the lung was observed just from one of carcasses. A case of spleen white nodule was observed for an animal in the 300 mg/kg/day treatment group. There was a case of right adrenal gland white spots at the 1,000 mg/kg/day treatment group. In the control group within the recovery group, each case of right adrenal gland hemorrhagia and atrophy and liver adhesion with diaphragm was observed.
Analysis of haematological test of blood: In the 1,000 mg/kg/day male recovery group, segments were increased (p < 0.05) in contrast with that of the control group within the recovery group. Prothrombin time (PT) was decreased in the 1,000 mg/kg/day female recovery group in comparison with that of the control group within the recovery group. However, these symptoms were not observed in the definitive test
groups, so these symptoms were not influenced by test substance. In addition, level of WBC (white blood cell) was increased (p < 0.001) in the 100 mg/kg/day female treatment group in contrast with that of the control group. However, its increased value was in the normal range and no
dose-response correlation, so it did not have relationship with test substance.
- Analysis of biochemical test of blood: In the 100 mg/kg/day treatment group for male animals, BUN (Blood urea nitrogen) was decreased as compared with that of the control group. The male treatment groups with both administration of 300 mg/kg/day and the 1,000 mg/kg/day decreased in TP (Total protein), ALB (Albumin), AST (Aspatate aminotransferase), ALT (Alanine aminotransferase), BUN (Blood urea nitrogen), CREA (Creatinine), Na (Sodium), TCHO (Total cholesterol), and Cl (Chloride) as compared with those of the control group. In case of the 1,000 mg/kg/day male recovery group, the value of AST was decreased significantly in contrast with that of the control group within the recovery group.
No significant difference was found at every test item between female control and treatment group. The female recovery group with administration of 1,000 mg/kg/day decreased in AST in contrast with that of the control group within the recovery group, but TCHO and GLU (Glucose) were increased. In fact, decreased values of AST and ALT could be no toxicological effects. In addition, the changed values of AST, TCHO, and GLU in this
test were in the normal range and no histopathological opinion in terms of related organs, so these changed values were not influenced by test substance. However, decreased values of TP, ALB, BUN, and CREA were possibly influenced by excretion process or metabolism of test substance in relation to the kidney, and these symptoms were possibly recovered in 2 weeks from reversible effects.
- Histopathology: For male animals, in the control group, each case of heart focal inflammatory cell infiltration, submadibular lymph node blood absorption, liver mononuclear cell foci, and adrenal gland cortical vacuolation was observed. In the 300 mg/kg/day treatment group, two cases of pancreas vacuolation, and a case of liver mononuclear cell foci were observed. In the treatment group with administration of 1,000 mg/kg/day, there were three cases of liver mononuclear cell foci; and a case of heart focal inflammatory cell infiltration was found.
For female animals, in the control group, two cases of liver mononuclear cell foci, a case of kidney cortical scaring, and a case of pancreas vacuolation were observed. In the treatment group with administration of 100 mg/kg/day, one case of esophagus submucosal gland proliferation was observed. In the 300mg/kg/day treatment group, a case of trachea submucosal gland proliferation was observed. In the 1,000 mg/kg/day treatment group, each case of pancreas vacuolation and liver mononuclear cell foci was observed. However, these symptoms for both sexes were just subtle level and were occurred spontaneously, so there was no significant difference between the treatment group and the control group.
Effect levels
open allclose all
- Dose descriptor:
- NOAEL
- Effect level:
- 79 mg/kg bw/day (nominal)
- Sex:
- male
- Basis for effect level:
- other: see 'Remark'
- Dose descriptor:
- LOAEL
- Effect level:
- 237 mg/kg bw/day (nominal)
- Sex:
- male
- Basis for effect level:
- other: The LOAEL for calcium sulfate dihydrate was determined to be 300 mg/kg/day for males. The value has been corrected for calcium sulfate anhydrous
Target system / organ toxicity
- Critical effects observed:
- not specified
Applicant's summary and conclusion
- Conclusions:
- The study was performed with calcium sulfate dihydrate and the results calculated for calcium sulfate anhydrous.
The NOAEL for calcium sulfate anhydrous was 79 mg/kg/day for males based on a significant decrease in TP (Total Protein), ALB (Albumin), BUN (Blood Urea Nitrogen), and CREA (Creatinine) at the 300 mg/kg b.w./day and 1,000 mg/kg b.w./day groups. No effects were observed in females. - Executive summary:
In a Combined Repeated Dose and Reproduction/Developmental Toxicity Screening Test in rats [OECD TG 422], calcium sulfate, dihydrate was administered by gavage at the dose levels of 0, 100, 300 and 1,000 mg/kg bw/day for more than 35 days and 41 ~ 45 days for male and female animals, respectively. Calcium sulfate, dihydrate had no critical influence on test items such as mortality, body weights (organ weight), food consumption, necropsy, reflex action, grip strength and behaviour of the animals. However, the values of total protein, albumin, blood urea nitrogen, aspartate minotransferase, alanine aminotransferase and creatinine were decreased at 300 mg/kg bw/day and 1,000 mg/kg bw/day treatment for male animals showing that the test substance might affect the excretion process, distribution or metabolism of test substance in relation to the kidney. Based on these results, the LOAEL and NOAEL were determined to be 300 mg/kg bw/day and 100 mg/kg bw/day for male rats. In case of female rats, no effects were observed at the top dose tested (1,000 mg/kg bw/day).
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