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Toxicological information

Genetic toxicity: in vivo

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Administrative data

Endpoint:
in vivo mammalian somatic cell study: cytogenicity / erythrocyte micronucleus
Remarks:
Type of genotoxicity: DNA damage and/or repair
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: Study performed to GLP and guideline The rationale to use data from individual constituents and components of the complex is explained in chapter 1 of the CSR and in the adjacent "read-across document".

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2002

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test)
GLP compliance:
yes
Type of assay:
micronucleus assay

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
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 LOT no. - 109H0166

Test animals

Species:
mouse
Strain:
ICR
Sex:
male
Details on test animals and environmental conditions:
TEST ANIMALS
- Age at study initiation: 8 weeks

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
- Vehicle(s)/solvent(s) used: CMC (carboxymethyl cellulose)
Details on exposure:
PREPARATION OF DOSING SOLUTIONS: Calcium sulfate, dihydrate was dissolved in 1 % CMC (Sodium carboxymethyl Cellulose) and supersonic wave was used to prepare the highest dose concentration.



Duration of treatment / exposure:
1 day
Frequency of treatment:
Single treatment
Doses / concentrations
Remarks:
Doses / Concentrations:
1250, 2500 and 5000 mg/kg bw
Basis:

No. of animals per sex per dose:
6
Positive control(s):
- mitomycin C
- Doses / concentrations: 0.5 mg/kg and 1.0 mg/kg

Examinations

Details of tissue and slide preparation:
To observe the cell multiplication of bone marrow, 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 microg/ml acridine was dropped for dyeing



Evaluation criteria:
At least 2000 polychromatic erythrocytes per animal were scored for the incidence of micronuclei
Statistics:
ANOVA (using Sigmastat 2.0 statistic programme)

Results and discussion

Test results
Sex:
male
Genotoxicity:
negative
Toxicity:
not specified
Vehicle controls validity:
valid
Negative controls validity:
not examined
Positive controls validity:
valid

Any other information on results incl. tables

Table 1: 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 (0.5mg/kg)

Positive control (1.0mg/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

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information): negative
Calcium sulfate dihydrate showed negative results in the micronucleus test in vivo up to the test concentration of 5000 mg/kg bw.
Executive summary:

Calcium sulfate dihydrate was tested for induction of micronuclei in an in vivo study according to OECD 474 in mice. Male mice received the test substance in doses up to 5000 mg/kg bw in carboxymethyl cellulose in single applications. At least 2000 polychromatic erythrocytes per animal were scored for the incidence of micronuclei. No significant induction of micronuclei was observed in any of the dose groups.