Mycophenolic acid

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:

June 22, 1984 to June 24, 1984

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: This study has been performed according to GLP principles.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1984

Report date:

1984

Materials and methods

Principles of method if other than guideline:

The Ames test was performed according to Ames, B.N. J. and Yamasaki, E.: Methods for detecting carcinogens and mutagens with the Salmonella/mammalian-microsome mutagenicity test. Mutation Res., 31:347-364, 1975.

GLP compliance:

yes

Type of assay:

bacterial reverse mutation assay

Test material

Test material information

Constituent 1

Reference substance name:

Mycophenolic acid

EC Number:

246-119-3

EC Name:

Mycophenolic acid

Cas Number:

24280-93-1

Molecular formula:

C17H20O6

IUPAC Name:

6-(4-hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydro-2-benzofuran-5-yl)-4-methylhex-4-enoic acid

Test material form:

solid: crystalline

Details on test material:

White crystalline powder

Method

Target gene:

-S. typhimurium: Histidine gene

Species / strain

Species / strain 1

Species / strain / cell type:

S. typhimurium TA 1535, TA 1537, TA 98 and TA 100

Species / strain 2

Species / strain / cell type:

S. typhimurium TA 1538

Metabolic activation:

with and without

Metabolic activation system:

A 9,000 x g supernatant prepared from Sprague-Dawley adult male rat liver induced by Aroclor 1254 (described by Ames et. al., 1975) was purchased commercially and used in this assay.

Test concentrations with justification for top dose:

1.22 microg/plate
2.44
4.88
9.77
19.53
39.06
78.13
156.25
312.50
625.00
1250.00
2500.00
5000.00
10,000.00

Controls

Untreated negative controls:

yes

Negative solvent / vehicle controls:

yes

Remarks:

DMSÒ

True negative controls:

yes

Positive controls:

yes

Positive control substance:

9-aminoacridine

2-nitrofluorene

sodium azide

Results and discussion

Test results

Key result

Species / strain:

S. typhimurium, other: S. typhimurium TA 1535, TA 1537, TA 98 and TA 100 and S. typhimurium TA 1538

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

not specified

Any other information on results incl. tables

The results of the tests conducted on the test material in the absence of a metabolic activation system were negative.

The results of the tests conducted on the test material in the presence of a rat liver activation system were negative.

Applicant's summary and conclusion

Conclusions:

The test material, mycophenolic acid, did not exhibit genetic activity in any of the assays conducted in this evaluation and was not mutagenic under these test conditions according to our evaluation criteria.

Executive summary:

INTERPRETATION OF RESULTS:

The test material was examined for the mutagenic activity in a series of in vitro microbial assays employing Salmonella indicator organisms. The test material was examined directly and in the presence of liver microsomal enzyme preparations from Aroclor-induced rats. A negative control consisting of the solvent used for preparing the stock solution and subsequent dilutions of the test material and specific positive compounds were assayed concurrently with the test material. The concurrent negative control data were used as the basis for evaluating the results obtained with the test material.

TEST MATERIAL PREPARATION:

Dimethylsulfoxide (DMSO) was used as a solvent for preparing the stock solution and subsequent dilutions of the test material. The test material was soluble in the dolvent and formed a clear colorless solution.

DOSE RANGE:

Doses for the mutagenesis assays were selected from a preliminary study conducted on the test material at 14 doses of 1.22 microg to 10,000.0 microg per plate using the strain TA-100. In this preliminary study, the test material was toxic to the indicator strain at 10,000.0 microg per plate as evidenced by the reduced number of revertants on the media plates. The mutagenicity assays were conducted at 8 doses of 1.0 microg to 10,000.0 microg per plate using one plate per dose level.

RESULTS:

The results of the tests conducted on the test material in the absence of a metabolic activation system were negative. The results of the tests conducted on the test material in the presence of a rat liver activation system were negative.

CONCLUSIONS:

The test material, mycophenolic acid, did not exhibit genetic activity in any of the assays conducted in this evaluation and was not mutagenic under these test conditions according to our evaluation criteria.