2-methylhydroquinone

Genetic toxicity: in vivo

Administrative data

Endpoint:

in vivo mammalian cell study: DNA damage and/or repair

Remarks:

Type of genotoxicity: other: replicative DNA synthesis (RDS)

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: In vivo experimental study, published in peer reviewed literature, minor restrictions in design and/or reporting but otherwise adequate for assessment.

Data source

Reference

Reference 1

Reference Type:

publication

Title:

Possible Tumor-initiating and –promoting Activity of p-Methylcatechol and Methylhydroquinone in the Pyloric Mucosa of Rat Stomach

Author:

Furihata, C et al.

Year:

1993

Bibliographic source:

Japanese journal of cancer research 84: 223-229, 1993

Reference 2

Reference Type:

publication

Title:

In vivo short-term assays for tumor initiation and promotion in the glandular stomach of Fischer rat s

Author:

Furihata, C et al.

Year:

1995

Bibliographic source:

Mutation Research 339 (1995) 15-35

Materials and methods

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

The possible tumor-promoting and tumor-initiating activities of methylhydroquinone in the pyloric mucosa of male F344 rats were studied. Replicative DNA synthesis (RDS) was used as marker of tumor promotion. The compounds were administered by gastric intubation. RDS was determined in small pieces of pyloric mucosa of the stomach in in vitro organ cultures, with and without 10 mM hydoxyurea, an inhibitor of RDS.

GLP compliance:

not specified

Type of assay:

inhibition of DNA-Synthesis

Test material

Test material information

Constituent 1

Reference substance name:

2-methylhydroquinone

EC Number:

202-443-7

EC Name:

2-methylhydroquinone

Cas Number:

95-71-6

Molecular formula:

C7H8O2

IUPAC Name:

2-methylbenzene-1,4-diol

Details on test material:

- Name of test material (as cited in study report): Methylhydroquinone

Test animals

Species:

rat

Strain:

Fischer 344

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Japan, Kanagawa
- Weight at study initiation: 150-200 g
- Age at study initiation: 7 weeks old
- Housing: Individual cages
- Diet/fasting: For 16-h treatment, rats were starved from the morning, given a chemical in the evening, fed a limited amount of diet overnight (commercial pellet diet, Nihon Clea, Tokyo), and examined the next morning.

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

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

Details on exposure:

PREPARATION OF DOSING SOLUTIONS:
- test chemical in 1 mL distilled water

Frequency of treatment:

Single treatment

Post exposure period:

Up to 49 hours

Doses / concentrations

Remarks:

Doses / Concentrations:
90, 200 and 300 mg/kg bw
Basis:
actual ingested

No. of animals per sex per dose:

5

Control animals:

yes, concurrent no treatment

Examinations

Tissues and cell types examined:

Pieces of pyloric mucosa of the stomach in in vitro organ culture.

Details of tissue and slide preparation:

CRITERIA FOR DOSE SELECTION: 300 mg/kg body weight of the test substance was the highest tolerated dose.

METHOD OF ANALYSIS:
- RDS was determined in small pieces of pyloric mucosa of the stomach in an vitro organ culture in the presence of tritiated thymidine without and with 10 mM hydroxyurea, an inhibitor of RDS.
- The DNA fraction was extracted from the tissue, an aliquot was dissolved in ACS II and the incorporation of [3H]dThd into DNA was determined in a Packard Tricarb 1500 liquid scintillation counter.
- The DNA content of the DNA fraction was determined with 3,5-diaminobenzoic acid with calf thymus as a standard.

Statistics:

Data were first converted to logarithmic values, and then homogeneity of variance was tested with Bartlett's test (p<0.05). When the results indicated heterogeneity, data were compared by means of the non-parametric Dunnett test. The results of dose-response tests were analyzed by linearization of dose-response curves. Statistical significance was judged at levels of 1 and 5%.

Results and discussion

Test results

Sex:

male

Genotoxicity:

ambiguous

Additional information on results:

- A time-depended increase in RDS in the pyloric mucosa of rat stomach after administration of the test substance was observed at a dose of 200 mg/kg bw. RDS was stimulated 5-fold (P<0.02) 16 hour after administration and then decreased gradually.
- A slight, but not significant, increase of RDS was observed at a dose of 300 mg/kg body weight (at 17 hour after treatment).

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information): ambiguous