Pregna-1,4-diene-3,20-dione, 11,21-bis(acetyloxy)-16,17-dihydroxy-, (11β, 16α)-

Genetic toxicity: in vitro

Administrative data

Endpoint:

in vitro gene mutation study in bacteria

Remarks:

Type of genotoxicity: gene mutation

Type of information:

experimental study

Adequacy of study:

key study

Study period:

20 March 2013 to 3 April 2013

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2013

Report date:

2013

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

GLP compliance:

yes (incl. QA statement)

Type of assay:

bacterial reverse mutation assay

Test material

Test material information

Constituent 1

Reference substance name:

11β,16α,17,21-tetrahydroxypregna-1,4-diene-3,20-dione

EC Number:

237-731-1

EC Name:

11β,16α,17,21-tetrahydroxypregna-1,4-diene-3,20-dione

Cas Number:

13951-70-7

Molecular formula:

C21H28O6

IUPAC Name:

11,16,17,21-tetrahydroxypregna-1,4-diene-3,20-dione

Test material form:

solid: particulate/powder

Method

Target gene:

his

Species / strain

Species / strain / cell type:

S. typhimurium TA 1535, TA 1537, TA 98, TA 100 and E. coli WP2

Metabolic activation:

with and without

Metabolic activation system:

S9 mix

Test concentrations with justification for top dose:

5, 15, 50, 150, 500, 1500 and 5000 µg/plate of hydroxyprednisolone he tests on S. typhimurium TA 1535, TA 1537, TA 98, TA 100 and E. coli WP2

Vehicle / solvent:

- Vehicle(s)/solvent(s) used: DMSO
- Justification for choice of solvent/vehicle: hydroxyprednisolone was insoluble in water but soluble in DMSO

Controls

Negative solvent / vehicle controls:

yes

Positive controls:

yes

Positive control substance:

4-nitroquinoline-N-oxide

9-aminoacridine

2-nitrofluorene

sodium azide

benzo(a)pyrene

other: 2-Aminoanthracene

Details on test system and experimental conditions:

Two independent mutation tests were performed in the presence and absence of liver preparations (S9 mix) from rats treated with phenobarbital and 5,6-benzoflavone. The first test was a standard plate incorporation assay; the second included a pre-incubation stage.

Results and discussion

Test results

Key result

Species / strain:

S. typhimurium TA 1535, TA 1537, TA 98, TA 100 and E. coli WP2

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

no cytotoxicity nor precipitates, but tested up to recommended limit concentrations

Vehicle controls validity:

valid

Untreated negative controls validity:

not specified

Positive controls validity:

valid

Applicant's summary and conclusion

Conclusions:

It was concluded that 16alpha-hydroxyprednisolone showed no evidence of mutagenic activity in this bacterial system at doses up to 5000 micrograms/plate under the test conditions employed.