Reaction products of sulphuric acid, rock phosphate and humic acids, potassium salts

Genetic toxicity: in vivo

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

Guideline:

OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test)

GLP compliance:

yes

Type of assay:

micronucleus assay

Test material

Test material information

Constituent 1

Reference substance name:

10101-41-4

Cas Number:

10101-41-4

IUPAC Name:

10101-41-4

Constituent 2

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 LOT no. - 109H0166

Test animals

Species:

mouse

Strain:

ICR

Sex:

male

Details on test animals or test system 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.