Ibuprofen

Genetic toxicity: in vitro

Administrative data

Endpoint:

in vitro gene mutation study in bacteria

Type of information:

experimental study

Adequacy of study:

key 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:

Comparative mutagenic and genotoxic effects of three propionic acid derivatives ibuprofen, ketoprofen and naproxen

Author:

Philipose, B; Sing, R; Khan, KA; Giri, AK;

Year:

1997

Bibliographic source:

Mutation Research 393 (1997) 123-131

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

Deviations:

yes

Remarks:

see "Principles of method other than guideline"

Principles of method if other than guideline:

Salmonella strains TA 97a, TA 100, TA 102 have been used; the (additional recommended) Salmonella strains TA 1535 and TA98 were absent. Additionally, two experiments were performed with 2 replications for each concentration in stead of 1 experiment with triplicate plating.

GLP compliance:

no

Type of assay:

bacterial reverse mutation assay

Test material

Test material information

Constituent 1

Reference substance name:

Ibuprofen

EC Number:

239-784-6

EC Name:

Ibuprofen

Cas Number:

15687-27-1

Molecular formula:

C13H18O2

IUPAC Name:

2-(4-isobutylphenyl)propanoic acid

Test material form:

solid

Specific details on test material used for the study:

Purchased from Sigma Chemical Company (St. Louis, MO).

Method

Target gene:

Histidine

Species / strain

Species / strain / cell type:

S. typhimurium, other: TA97a, TA100, TA102

Additional strain / cell type characteristics:

not applicable

Metabolic activation:

with and without

Metabolic activation system:

Phenobarbital induced S9 rat liver homogenate

Test concentrations with justification for top dose:

- Test concentrations: 1, 10, 100, 1000, 5000 µg/plate

Vehicle / solvent:

- Vehicle(s)/solvent(s) used: DMSO

Controls

Untreated negative controls:

no

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

sodium azide

methylmethanesulfonate

other: 4-nitro-o-phenylenediamine; 2-aminofluorene

Details on test system and experimental conditions:

METHOD OF APPLICATION: in agar (plate incorporation)

DURATION
- Exposure duration: 48 hours

NUMBER OF REPLICATIONS: 2 experiments performed, 2 replications per experiment (4 total)

Evaluation criteria:

The revertant colonies on all the plates were counted. Statistical calculations were carried out with the mean revertant colonies of each concentration of the each independent treatment group with respective controls

Statistics:

Dunnett’s multiple comparison

Results and discussion

Test results

Key result

Species / strain:

S. typhimurium, other: TA 97a, TA 100, TA 102

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Vehicle controls validity:

valid

Untreated negative controls validity:

not applicable

Positive controls validity:

valid

Additional information on results:

- TA 97a and TA100 without metabolic activation: mean number of revertant colonies per plate were significantly higher at concentrations of 1 and 10 µg/plate in the first experiment, but not in the second experiment. Also, no dose-response was observed.
- TA97a with metabolic activation: mean number of revertant colonies per plate were significantly higher at concentrations of 1, 10, and 100 µg/plate in the second experiment, but not in the first experiment. Also, no dose-response was observed.

Any other information on results incl. tables

The registrant of the test substance noted that the observed increase was relatively small and only statistics were used to determined whether a positive response was observed. Current procedure is that a test substance is considered to be positive in a bacterial gene mutation test if the mean number of revertant colonies on the test plates is increased in a dose-related manner or if a two-fold and/or greater increase was observed compared to the negative control plates. As this is not the case with any of the strains tested, it can be concluded that the test substance is not mutagenic in a bacterial reverse mutation assay.