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Toxicological information

Genetic toxicity: in vivo

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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

Referenceopen allclose all

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 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

Constituent 1
Chemical structure
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