Prasterone

Genetic toxicity: in vivo

Administrative data

Endpoint:

in vivo mammalian somatic cell study: cytogenicity / erythrocyte micronucleus

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

other information

Study period:

Jan to Mar 2005

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Justification for type of information:

Prasterone enantate (Androst-5-en-17-one, 3-hydroxy-, (3.beta.)) is the precursor and structural analogue of Prasterone (CAS 53-43-0). In vivo, it is releasing Prasterone into the body.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2005

Report date:

2005

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:

3 ß-Heptanoyloxy-5-androsten-17-one

IUPAC Name:

3 ß-Heptanoyloxy-5-androsten-17-one

Constituent 2

Reference substance name:

Prasterone enantate

IUPAC Name:

Prasterone enantate

Test animals

Species:

mouse

Strain:

NMRI

Sex:

male/female

Administration / exposure

Route of administration:

intraperitoneal

Vehicle:

Sesame oil

Duration of treatment / exposure:

Animals were treated once.

Frequency of treatment:

Single intraperitoneal administration of the test substance or the positive or negative control substance.

Post exposure period:

The animals were sacrificed for bone marrow preparation 24 hours after test substance administration. Additional groups of animals of negative control and high dose group (2000 mg/kg) were sacrificed 48 hours after test substance administration.

Doses / concentrations

Remarks:

Doses / Concentrations:
0, 500, 1000 and 2000 mg/kg bw
Basis:
actual ingested

No. of animals per sex per dose:

5 for sacrifice time 24 hours, additionally 5 for sacrifice time 48 hours for control and high dose group.

Control animals:

yes, concurrent vehicle

Positive control(s):

cyclophosphamide (administration by gavage)

Examinations

Tissues and cell types examined:

Bone marrow preparations were examined for the incidence of micronucleated cells per 2000 polychromatic (PCE) and 1000 normochromatic (NCE) erythrocytes per animal.

Results and discussion

Test results

Sex:

male/female

Genotoxicity:

negative

Toxicity:

yes

Vehicle controls validity:

valid

Negative controls validity:

not applicable

Positive controls validity:

valid

Any other information on results incl. tables

At the 24 hours time point male and female mice in the high dose group showed a statistically significant (p < 0.05) decrease in the ratio of PCE/NCE, whereas the decrease was more pronounced in the female animals. This decrease in the ratio of PCE/NCE can be taken as indication of bone marrow depression demonstrating that the test compound has reached the target cells.

Applicant's summary and conclusion

Conclusions:

No mutagenic activity of the test item in the described test system.

Executive summary:

A mouse bone marrow micronucleus test (according to OECD 474) was conducted on 5 animals/sex and dose group receiving each a single i.p. injection of the formulated analogue/precursor of Androst-5-en-17-one, 3-hydroxy-, (3.beta.)-, at dosages of 0 (vehicle control), 500, 1000 and 2000 mg/kg bw. Animals were sacrificed 24 hours after test substance administration and bone marrow smears were prepared. Additionally 5 animals were used for vehicle control and high dose (2000 mg/kg bw) group with a sacrifice and sampling time of 48 h after test substance administration.

At the 24 hours time point male and female mice in the high dose group showed a statistically significant (p < 0.05) decrease in the ratio of PCE/NCE, whereas the decrease was more pronounced in the female animals. This decrease in the ratio of PCE/NCE can be taken as indication of bone marrow depression demonstrating that the test compound has reached the target cells. The male and female mice treated with the substance showed at all 3 dose levels ( 0.5, 1.0 and 2.0 g/kg body weight) neither a biologically relevant nor statistically significant increase (p < 0.05) in micronucleated PCE and NCE as compared to the vehicle control at either of the two sampling times, i.e. 24 or 48 hours after a single treatment.

The micronucleus frequencies determined in the vehicle and positive control were within the expected historical range.

From the results obtained, it is concluded that the test substance has no mutagenic activity in the in vivo MNT.