Methyl 2,5-dihydroxybenzoate

Genetic toxicity: in vitro

Administrative data

Endpoint:

in vitro gene mutation study in mammalian cells

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Data source

Reference

Reference Type:

publication

Title:

Inhibitors of Mammalian Melanocyte Tyrosinase: In Vitro Comparisons of Alkyl Esters of Gentisic Acid with Other Putative Inhibitors

Author:

Curto, Ernest V; Kwong,Cecil; Hermersdörfer, Heino; Glatt,Hansruedi; Santis, Chie; Virador, Victoria; Hearing Jr; Vincent J; and Thomas P. Dooley

Year:

1999

Bibliographic source:

Biochemical Pharmacology, Vol. 57, pp. 663–672, 1999

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 476 (In Vitro Mammalian Cell Gene Mutation Test)

Deviations:

yes

Remarks:

performed without metabolic activation, results availabe as graph only

GLP compliance:

no

Type of assay:

other: mammalian cell gene mutation assay

Test material

Test material information

Constituent 1

Reference substance name:

Methyl 2,5-dihydroxybenzoate

EC Number:

218-427-8

EC Name:

Methyl 2,5-dihydroxybenzoate

Cas Number:

2150-46-1

Molecular formula:

C8H8O4

IUPAC Name:

methyl 2,5-dihydroxybenzoate

Test material form:

solid

Details on test material:

The test substance was synthesized in the laboratory of the authors. Purification steps were performed until the starting material gentisic acid was no longer detectable by thin layer chromatography. Identity was confirmed. A specific value for the purity was not given.

Method

Target gene:

HPRT

Species / strain

Species / strain / cell type:

Chinese hamster lung fibroblasts (V79)

Metabolic activation:

without

Test concentrations with justification for top dose:

0.01 - ca 0.14 mg/L, cytotoxicity

Vehicle / solvent:

DMSO

Controls

Untreated negative controls:

no

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

other: anti-chrysene- 1,2-dihydrodiol-3,4-oxide

Rationale for test conditions:

The cytotoxic LC50 values of methylgentisate in V79 cells was approximately 0.134 mg/mL (or 0.8 mM). Concentrations that produced <5% cell viability were not included in the analysis.

Evaluation criteria:

A compound was considered to be negative in the test if the mutant frequencies of all treatment groups were less than the mean value of the solvent control cultures plus 10 3 1026. It was considered positive if the mutant frequency was at least three times above the value of the solvent control cultures and at least 20 x 10exp-6.

Results and discussion

Test results

Species / strain:

Chinese hamster lung fibroblasts (V79)

Metabolic activation:

not specified

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Vehicle controls validity:

valid

Untreated negative controls validity:

not examined

Positive controls validity:

valid

Additional information on results:

The positive control substance produced a mutant frequency of 825 x 10exp-6 at a concentration of 3.6 micromolar.

Any other information on results incl. tables

The mutant frequencies in the methylgentisate-treated cultures (2–13 x 10exp-6) remained within the range observed in the control cultures (2–15 x 10exp-6).

Hydroquinone was tested in parallel and found to increase the mutant frequencey at lower concentrations.