Aluminium sulphate

Genetic toxicity: in vivo

Administrative data

Endpoint:

in vivo mammalian somatic cell study: cytogenicity / erythrocyte micronucleus

Remarks:

Type of genotoxicity: chromosome aberration

Type of information:

migrated information: read-across based on grouping of substances (category approach)

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Reliable without restrictions. Well-presented study, with relevant measurement of chemical concentrations

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2002

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test)

Principles of method if other than guideline:

- Calcium sulfate, dihydrate was dissolved in 1 % CMC (Sodium carboxymethyl Cellulose) and supersonic wave was used to prepare the
highest dose concentration.
- To observe the cell multiplication of bone mallow, a specimen was fixed with methanol. And 4 % Giemsa solution was used for dyeing to
observe the ratio of polychromatic erythrocytes. To observe the micronucleus in the polychromatic erythrocytes, 40 μg/ml acridine was
dropped for dyeing.

GLP compliance:

yes

Remarks:

Tested by KOSHA, Korea.,(No. ICRC/2002/006)

Type of assay:

other: Mammalian erythrocyte micronucleus test

Test material

Test material information

Constituent 1

Reference substance name:

Calcium sulfate, dihydrate

IUPAC Name:

Calcium sulfate, dihydrate

Constituent 2

Reference substance name:

10101-41-4

EC Number:

600-148-1

Cas Number:

10101-41-4

IUPAC Name:

10101-41-4

Test material form:

solid: compact

Details on test material:

- Name of test material: Calcium sulfate, dihydrate
- Molecular formula (if other than submission substance): CaSO4•2H2O
- Molecular weight (if other than submission substance): 172.171
- Smiles notation (if other than submission substance): O.O.[O-]S(=O)(=O)[O-].[Ca+2]
- Structural formula attached as image file (if other than submission substance): see Fig.1
- Substance type:inorganic
- Physical state:solid
- Density -2.32 g/cm3)
- Solubility in water - 2.05 g/L at 20 °C
- Synonyms: Alabaster
Annaline
C.I. Pigment white 25
Gypsum
Gypsum stone
Land and plaster
Light spar
Magnesia white
Mineral white
Native calcium sulfate
Precipitated calcium sulfate
Sainite
Satin spar
Sulfuric acid, calcium(2+) salt, dihydrate
Terra alba
- Calcium sulfate, dihydrate consists of colorless, monoclinic and hygroscopic crystals

Test animals

Species:

mouse

Strain:

ICR

Sex:

male

Details on test animals or test system and environmental conditions:

Test condition :
- Age at study initiation: 8 weeks
- No. of animals per dose: 6
- Vehicle: 1 % CMC (Sodium Carboxymethyl Cellulose)
- Duration of test: 1 day
- Frequency of treatment: single treatment
- Sampling times and number of samples: 24 hours after administration
- Control groups and treatment: Negative control (1 % CMC (Sodium Carboxymethyl Cellulose)), Positive control (0.5 and 1.0 mg/kg of
Mitomycin C)
- Clinical observations performed: None
- Organs examined at necropsy: not examined
- Criteria for evaluating results: at least 2,000 polychromatic erythrocytes per animals were scored for the incidence of micronuclei.
- Criteria for selection of maximum tolerated dose (M.T.D): preliminary test had conducted with with 1,250, 2,500 and 5,000 mg/kg b.w. to
determine appropriate starting dose level.

Administration / exposure

Route of administration:

oral: feed

Vehicle:

- -Vehicle: 1 % CMC (Sodium Carboxymethyl Cellulose)
-Calcium sulfate, dihydrate was dissolved in 1 % CMC (Sodium carboxymethyl Cellulose) and supersonic wave was used to prepare the
highest dose concentration.
- To observe the cell multiplication of bone mallow, a specimen was fixed with methanol. And 4 % Giemsa solution was used for dyeing to
observe the ratio of polychromatic erythrocytes. To observe the micronucleus in the polychromatic erythrocytes, 40 μg/ml acridine was
dropped for dyeing.

Details on exposure:

Route of administration :
Test substance: oral feed
Positive control: i.p
Dose : 1,250, 2,500 and 5,000 mg/kg b.w
Exposure period : 24 hours
Statistical methods : ANOVA (Using Sigmastat 2.0 statistic programme)
Exposure period : 24 hours

Duration of treatment / exposure:

24 hours

Frequency of treatment:

- Frequency of treatment: single treatment

Doses / concentrations

Remarks:

Doses / Concentrations:
1,250, 2,500 and 5,000 mg/kg b.w
Basis:
nominal in diet

No. of animals per sex per dose:

No. of animals per dose: 6/male

Control animals:

yes

Positive control(s):

GLP : Yes
Route of administration : Test substance: oral feed
Positive control: i.p
Dose : 1,250, 2,500 and 5,000 mg/kg b.w

Examinations

Tissues and cell types examined:

- Clinical observations performed: None
- Organs examined at necropsy: not examined
- Criteria for evaluating results: at least 2,000 polychromatic erythrocytes per animals were scored for the incidence of micronuclei.
- Criteria for selection of maximum tolerated dose (M.T.D): preliminary test had conducted with with 1,250, 2,500 and 5,000 mg/kg b.w. to
determine appropriate starting dose level.

Details of tissue and slide preparation:

- Calcium sulfate, dihydrate was dissolved in 1 % CMC (Sodium carboxymethyl Cellulose) and supersonic wave was used to prepare the
highest dose concentration.
- To observe the cell multiplication of bone mallow, a specimen was fixed with methanol. And 4 % Giemsa solution was used for dyeing to
observe the ratio of polychromatic erythrocytes. To observe the micronucleus in the polychromatic erythrocytes, 40 μg/ml acridine was
dropped for dyeing.

Evaluation criteria:

- Criteria for evaluating results: at least 2,000 polychromatic erythrocytes per animals were scored for the incidence of micronuclei.
- Criteria for selection of maximum tolerated dose (M.T.D): preliminary test had conducted with with 1,250, 2,500 and 5,000 mg/kg b.w. to
determine appropriate starting dose level.

Statistics:

Statistical methods : ANOVA (Using Sigmastat 2.0 statistic programme)
- Statistical results: only positive control group showed statistically increased frequency of micronucleated cells.

Results and discussion

Test results

Sex:

male

Genotoxicity:

negative

Remarks:

- Statistical results: only positive control group showed statistically increased frequency of micronucleated cells.

Toxicity:

no effects

Vehicle controls validity:

valid

Negative controls validity:

valid

Positive controls validity:

valid

Additional information on results:

Results : All things being considered, calcium sulfate, dihydrate showed negative result in micronucleus test in vivo up
to the test concentration of 5,000 mg/kg b.w.
Genotoxic effects : Negative
- Statistical results: only positive control group showed statistically increased frequency of micronucleated cells.
Conclusion : Calcium sulfate, dihydrate showed negative result in the micronucleus test in vivo up to the test concentration of 5,000 mg/kg.

Any other information on results incl. tables

Results : All things being considered, calcium sulfate, dihydrate showed negative

result in micronucleus test in vivo up to the test concentration of 5,000 mg/kg b.w.

 

Effect on mitotic index or PCE/NCE ratio by dose level

 

Dose (mg/kg)	Group mean (PCE/(PCE+NCE)) (%)	Group mean frequency of MNPCE (per 1,000)
Vehicle 1,250 2,500 5,000 Positive control (0.5 mg/kg) Positive control (1.0 mg/kg)	60.49 ± 7.77 56.58 ± 9.07 54.61 ± 6.13 54.48 ± 9.02 46.58 ± 10.76             46.96 ± 7.08	6.5 7.0 7.7 8.0 19.2 44.8

 

Genotoxic effects : Negative

- Statistical results: only positive control group showed statistically increased frequency of micronucleated cells.

Conclusion : Calcium sulfate, dihydrate showed negative result in the micronucleus testin vivoup to the test concentration of 5,000 mg/kg.

 

                     
             
            
             

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information): negative
Calcium sulfate, dihydrate showed negative result in the micronucleus test in vivo up to the test concentration of 5,000 mg/kg.