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EC number: 231-104-6 | CAS number: 7439-95-4
- 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
Toxicity to reproduction
Administrative data
- Endpoint:
- one-generation reproductive toxicity
- Remarks:
- based on test type (migrated information)
- Type of information:
- migrated information: read-across from supporting substance (structural analogue or surrogate)
- Adequacy of study:
- key study
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- other: GLP guideline study
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 009
- Report date:
- 2009
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)
- Deviations:
- yes
- Remarks:
- please see 'overall remark' below
- GLP compliance:
- yes
- Remarks:
- Testing laboratory:Biotoxtech Co., Ltd.,Report № B09179
- Limit test:
- no
Test material
- Reference substance name:
- magnesium sulphate
- IUPAC Name:
- magnesium sulphate
- Reference substance name:
- Magnesium sulphate
- EC Number:
- 231-298-2
- EC Name:
- Magnesium sulphate
- Cas Number:
- 7487-88-9
- IUPAC Name:
- 7487-88-9
- Test material form:
- solid: compact
- Details on test material:
- - Name of test material (as cited in study report): Magnesium sulfate
- Molecular formula (if other than submission substance): MgSO4
- Molecular weight (if other than submission substance): 120.37
- Physical state: White powder
- Analytical purity: 100.2 %
- Lot/batch No.: 039K0150
- Storage condition of test material: Room temperature (16.0–27.1 degree C)
- Other: Hydrophilic
- Supplier: ALDRICH
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]
- Source: ORIENTBIO INC., Korea
- Age at study initiation: Male, 9 weeks old, 311.6–344.1 g ; Female, 8 weeks old, 190.6–232.3 g
- Weight at study initiation: Male, 311.6–344.1 g ; Female, 190.6–232.3 g
- Housing: Stainless wire mesh cages, 260W×350D×210H (mm), Polycarbonate cage 260W×420L×180H (mm)
- Number of animals per cage: One animal (during pre- and post mating periods), One male and one female (during mating period), One female and pups (during lactation period)
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: approximately 7 days
[ENVIRONMENTAL CONDITIONS]
- Temperature (°C): 20.8–23.1 °C
- Humidity (%): 38.4–77.8 %
- Air changes (per hr): 10–15 clean, fresh, filtered air changes per hr
- Photoperiod (hrs dark / hrs light): 12 hour light/dark cycle
Administration / exposure
- Route of administration:
- oral: gavage
- Vehicle:
- other: water for injection
- Details on exposure:
- Amount of vehicle : 5 mL/kg
- Details on mating procedure:
- - M/F ratio per cage: 1 to 1
- Length of cohabitation: 14 days
- Proof of pregnancy: a vaginal plug twice a day, AM and PM.
- the mating indices : 100 %
- the mating periods : 2.2 - 2.7 days - Analytical verification of doses or concentrations:
- not specified
- Duration of treatment / exposure:
- Male in main group and both sexes in recovery group : a total of six weeks (two weeks each prior to, during and post mating).Female in main group : two weeks prior to mating, throughout gestation and five days (six days in twelve females) after delivery
- Frequency of treatment:
- Once a day
Doses / concentrations
- Remarks:
- Doses / Concentrations:
0, 50, 150, and 450 mg/kg bw
Basis:
actual ingested
- No. of animals per sex per dose:
- Control : Male-13 rats(main group)+6 rats(recovery group, not mating), Female-13 rats(main group)+6 rats(recovery group, not mating)
Low dose : Male-13 rats, Female-13 rats
Mid dose : Male-13 rats, Female-13 rats
High dose : Male-13 mice(main group)+6 mice(recovery group), Female-13 mice(main group)+6 mice(recovery group) - Control animals:
- yes, concurrent vehicle
- Details on study design:
- - Dose selection rationale: In the preliminary study (Biotoxtech Study No. : B09179P), acute diarrhea was observed in animals dosed with 1000 mg/kg, and soft stool and diarrhea were observed in animals dosed with 500 mg/kg. Based on the results, 450 mg/kg was selected as the high dose level for this study and sequentially divided by a geometric ratio of 3 to produce two additional lower doses of 150 and 50 mg/kg as mid- and low dose levels. The control group received vehicle only (water for injection) at the same dose volume as the dosed groups.
Examinations
- Parental animals: Observations and examinations:
- CLINICAL OBSERVATIONS:
- All animals were observed once a day throughout the study on mortality, general condition and gross evidence of clinical signs and symptoms
Detailed physical examinations :
- All animals were once in pretest period, once a week throughout the dosing and recovery periods on central and autonomic nervous system effects, motor activity, and behaviour.
BODY WEIGHT: Body weight were measured just prior to dosing, once a week throughout the dosing period, and the day prior to necropsy - Litter observations:
- The following parameters were examined in F1 offspring:
- Number and sex of pups
- Number of corpora lutea and uterine implants
- Mean litter size
- Live births
- Postnatal mortality
- Body weights of pups on postnatal days 0 and 4.
- External examination : All pups on delivery day and on postnatal day 4 - Postmortem examinations (parental animals):
- Necropsy : Yes (see table [No. 15-1 and 15-2] and appendix [No. 15-1 and 15-2]) Urinalysis : Yes (see table [No. 10-1 and 10-2] and appendix [No. 10-1 and 10-2] )
Blood biochemistry : Yes (see table [No. 11-1 and 11-2] and appendix [No. 11-1 and 11-2] ) Hematology : Yes (see table [No. 12-1 and 12-2] and appendix [No. 12-1 and 12-2] ) Histopathology : Yes (see table [No. 16-1 and 16-2] and appendix [No. 16-1 and 16-2] ) - Statistics:
- - The SAS program
- Bartlett's test, ANOVA, Dunnett's test, Kruskal-wallis test, Mann-whitney u-test :
the data including body weights, food consumption, mating period, gestation period, pre- and post-implantation loss rate, live birth index, viability index postnatal Day 0 and 4, traction test, rotarod test, spontaneous motor activity test, urine volume, hematology and blood biochemistry parameters and organ weights data.
- Kruskal-wallis test, Mann-whitney u-test : the data of external examinations
- Folded-F test, Aspin-Welch t-test : the data of recovery groups - Reproductive indices:
- - The gestation indices : 100 %
- The pre-implantation loss rates : 10.5 % (control), 6.5 % (50 mg/kg), 7.1 % (150 mg/kg), 4.8 % (450 mg/kg)
- The post-implantation loss rates : 7.9 % (control), 6.9 % (50 mg/kg), 8.4 % (150 mg/kg), 5.5 % (450 mg/kg) - Offspring viability indices:
- - The live birth indices : 92.1 % (control), 93.1 % (50 mg/kg), 91.6 %(150 mg/kg), 94.5 %(450 mg/kg)
- The viability index postnatal day 0 : 97.6 % (control), 95.6 % (50 mg/kg), 100 %(150 mg/kg), 99.0 %(450 mg/kg)
Results and discussion
Results: P0 (first parental generation)
General toxicity (P0)
- Clinical signs:
- effects observed, treatment-related
- Body weight and weight changes:
- no effects observed
- Food consumption and compound intake (if feeding study):
- no effects observed
- Organ weight findings including organ / body weight ratios:
- effects observed, treatment-related
- Histopathological findings: non-neoplastic:
- effects observed, treatment-related
- Other effects:
- no effects observed
Reproductive function / performance (P0)
- Reproductive function: oestrous cycle:
- not examined
- Reproductive function: sperm measures:
- not examined
- Reproductive performance:
- no effects observed
Details on results (P0)
BODY WEIGHT AND WEIGHT GAIN - In parental animals, no statistically significant differences in body weights were noted in all animals in main and recovery groups compared to the control group during the study. In pubs, statistically significant decrease in body weight was noted in male pubs in 450 mg/kg dosed group compared to the control group on postnatal Day 4. No dose-related effects were noted.
FOOD CONSUMPTION (PARENTAL ANIMALS) - Statistically significant decrease in food consumption was noted in males dosed with 150 mg/kg in main group compared to the control group on Day 7 after dosing. Statistically significant increase was noted in males dosed with 450 mg/kg in recovery group compared to the control group on the day prior to dosing (Day 0). No statistically significant differences were evident in the other dosed groups.
REPRODUCTIVE PERFORMANCE (PARENTAL ANIMALS) - In 0, 50, 150, and 450 mg/kg dosed groups, the mating periods were 2.3, 2.2, 2.9 and 2.7 days, the mating indices were 100 %, the gestation periods were 22.1, 21.9, 22.1 and
22.2 days, the fertility indices of both sexes were 92.3, 84.6, 100 and 92.3 %, respectively. There were no statistically significant differences in any dose group.
ORGAN WEIGHTS (PARENTAL ANIMALS) - In the main group, absolute organ weights of kidneys in males dosed with 50 and 150 mg/kg were statistically significantly decreased (p<0.05) compared to the control group. Relative organ weights of testes in males dosed with 150 mg/kg were statistically significantly increased (p<0.05) compared to the control group. No statistically significant differences on absolute and related organ weights were noted in females. In the recovery group, absolute and relative organ weights of males were not statistically significantly different from control, but relative organ weights of ovaries in females dosed with 450 mg/kg were statistically significantly increased (p<0.05) compared to the control group.GROSS PATHOLOGY (PARENTAL ANIMALS) - Results of the gross postmortem examinations performed on all animals in the study did not reveal any evidence of grossly visible morphologic abnormalities in all groups.
HISTOPATHOLOGY (PARENTAL ANIMALS): NON-NEOPLASTIC - The squamous cell hyperplasia of forestomach, edema of submucosa, inflammation of submucosa, focal erosion of mucosa, focal ulcer of mucosa into forestomach and hyperplasia of mucosa into cecum were evident in one female dosed with 450 mg/kg in main group. Stomach and cecum were conducted for histopathology in animals dosed with 50 and 150 mg/kg in main group and in all recovery groups. There were no abnormal findings. In addition, in the control and 450 mg/kg main groups of both sexes, focal basophilic tubules of kidneys, mineralization of corticomedullary junction, mononuclear pyelitis, bilateral lymphocytic, focal lymphocytic cell infiltration of liver, focal mononuclear cell infiltration of liver, interstital lymphocytic cell infiltration of prostate and lymphocytic depletion of cortical into thymus were spontaneously or sporadically observed. In the recovery group of both sexes, no abnormal findings were observed.
Other findings : Normal deliveries were observed in all animals.
Results: F1 generation
General toxicity (F1)
- Clinical signs:
- no effects observed
- Mortality / viability:
- no mortality observed
- Body weight and weight changes:
- no effects observed
- Sexual maturation:
- not examined
- Organ weight findings including organ / body weight ratios:
- not examined
- Gross pathological findings:
- no effects observed
- Histopathological findings:
- not examined
Details on results (F1)
10.5±1.2 g (150 mg/kg) and 9.5±1.6 g (450 mg/kg). The decrease in body weight in male pups treated with 450 mg/kg group was statistically significant (p<0.05), but no dose-related effects were noted. So, we concluded no effect on body weight of offspring. See appendix [No. 3-3].
External findings : Edema of left in hind limb was observed in one pup (0.55%) in 50 mg/kg group on postnatal Day 0, and brachyury was observed in one pup (0.62%) in 150 mg/kg group on Days 0 and 4. No effects were evident in the other dosed groups. Detailed data was suggested below.
Effect levels (F1)
- Dose descriptor:
- NOAEL
- Generation:
- F1
- Effect level:
- >= 450 mg/kg bw/day
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- other: see 'Remark'
Overall reproductive toxicity
- Reproductive effects observed:
- not specified
Any other information on results incl. tables
Group
|
Implantation loss rate (%) |
Live birth index (%)
|
Viability index (%)
|
Sex ratio (male/Female)
|
|||
Pre-
|
Post-
|
PND 0
|
PND 4
|
PND 0
|
PND 4
|
||
Control
|
10.5(+/-) 7.5
|
7.9(+/-)8.1
|
92.1(+/-)8.1
|
97.6(+/-)6.0
|
99.6(+/-)1.5
|
1.0 (85/82)
|
1.0 (85/81)
|
50mg/kg
|
6.5(+/-)6.5
|
6.9(+/-)7.1
|
93.1(+/-)7.1
|
95.6(+/-)7.8
|
97.4(+/-)6.0
|
1.2 (87/75)
|
1.2 (86/72)
|
150mg/kg
|
7.1(+/-)5.1
|
8.4(+/-)11.1
|
91.6(+/-) 11.1
|
100.0(+/-) 0.0
|
99.1(+/-)2.3
|
0.9 87/96)
|
0.9 (86/95)
|
450mg/kg
|
4.8(+/-)4.9
|
5.5(+/-)6.3
|
94.5(+/-)6.3
|
99.0(+/-)2.3
|
96.8(+/-)5.9
|
1.1 (99/89)
|
1.1 (96/86)
|
Applicant's summary and conclusion
- Conclusions:
- No dose-related effects were noted in reproduction function. The NOAEL was considered to be 450 mg/kg bw/day for reproduction toxicity study.
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