Pyruvaldehyde

Genetic toxicity: in vivo

Administrative data

Endpoint:

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

Remarks:

Type of genotoxicity: DNA damage and/or repair

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: No guideline study with acceptable restrictions.

Data source

Reference

Reference 1

Reference Type:

publication

Title:

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

Author:

Furihata C. and T. Matsushima

Year:

1995

Bibliographic source:

Mutat. Res. 339, 15-35

Reference 2

Reference Type:

publication

Title:

Induction of ornithine decarboxylase and DNA synthesis in rat stomach mucosa by methylglyoxal

Author:

Furihata, C. et al.

Year:

1985

Bibliographic source:

Carcinogenesis 6 (1), 91-94

Reference 3

Reference Type:

publication

Title:

Mutagens and Carcinogens in Foods

Author:

Furihata, C. and Matsushima, T.

Year:

1986

Bibliographic source:

Ann. Rev. Nutr. 6, 67-94

Reference 4

Reference Type:

publication

Title:

Use of In Vivo / In Vitro Unscheduled DNA Synthesis for Identification of Organ Specific Carcinogens

Author:

Furihata, C. and Matsushima, T.

Year:

1987

Bibliographic source:

CRC Crit. Rev. Toxicol. 17 (3), 245-277

Reference 5

Reference Type:

publication

Title:

Prediction of Possible Carcinogens, Tumor-Promoters and Anti-Tumor Promoters in the Glandular Stomach

Author:

Furihata, C. and Matsushima, T.

Year:

1989

Bibliographic source:

Environ. Mol. Mut. 14, Suppl. 15, 63, Abstract Nr. 178

Reference 6

Reference Type:

publication

Title:

Prediction of Environmental Stomach Carcinogens and Promoters by In Vivo Short-Term Assay

Author:

Furihata, C. and Matsushima, T.

Year:

1987

Bibliographic source:

Environ. Mol. Mut. 9, Suppl. 8, 37, Abstract Nr. 92

Materials and methods

Principles of method if other than guideline:

Method: Determination of unscheduled DNA-synthesis (similar to OECD Guideline 486), ornithindecarboxylase activity, DNA-synthesis, DNA strand breaks and the number of S-phase cells in glandular stomach mucosa cells (Furihata, C. et al.: J. Natl. Cancer Inst. 72, 1327-1334 (1984))

GLP compliance:

not specified

Type of assay:

unscheduled DNA synthesis

Test material

Test material information

Constituent 1

Reference substance name:

Pyruvaldehyde

EC Number:

201-164-8

EC Name:

Pyruvaldehyde

Cas Number:

78-98-8

Molecular formula:

C3H4O2

IUPAC Name:

2-oxopropanal

Details on test material:

Source: Nakarai Chemicals Ltd ., Kyoto, Japan)

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, Inc., Kanagawa, Japan
- Age at study initiation: 8 weeks

Administration / exposure

Route of administration:

other: stomach tube, oral gavage

Vehicle:

- Vehicle(s)/solvent(s) used: water for Methylglyoxal, DMSO for pos. control
- Amount of vehicle: 0.5 mL

Details on exposure:

Animals were not fasted, but given a limited amount of diet (4 g of commercial pellet diet per rat of 200 g body weight) overnight to reduce their stomach contents. The following day they were treated either with 0.5 mL of test item in water or positive control item in DMSO.

Duration of treatment / exposure:

ODC activity (time dep.; 500 mg / kg bw): evaluated 4, 8, 16, 24, 48 and 72h post administration
ODC activity (dose dep.; 16h post admin.): evaluated at 0, 50, 200, 400 and 600 mg / kg bw
DNA synthesis (time dep.; 300 mg / kg bw): evaluated 4, 7, 16, 24, 48 and 72h post administration
DNA synthesis (dose dep.; 16h post admin.): evaluated at 0, 100, 200 and 300 mg / kg bw
DNA synthesis (dose dep.; 4h post admin.): evaluated at 0, 100, 300 and 500 mg / kg bw
S-Phase cells quantification (16h post admin. of 300 mg / kg bw)

Frequency of treatment:

single dose

Doses / concentrations

Remarks:

Doses / Concentrations:
50, 100, 200, 300, 400, 600 mg/kg bw
Basis:
nominal conc.

No. of animals per sex per dose:

five rats per sex per dose / time point (pooled)

Control animals:

yes, concurrent vehicle

Positive control(s):

- N-methyl-N'-nitro-N- nitrosoguanidine (MNNG, Aldrich Chemical Co., Milwaukee, WI, USA)
- Justification for choice of positive control: known glandular stomach carcinogen
- Route of administration: orally (gastric tube)
- Vehicle: DMSO

Examinations

Tissues and cell types examined:

Glandular stomach mucosa

Results and discussion

Test results

Sex:

male

Genotoxicity:

positive

Toxicity:

not specified

Vehicle controls validity:

valid

Negative controls validity:

not applicable

Positive controls validity:

valid

Any other information on results incl. tables

Ornithindecarboxylase activity, DNA-synthesis, unscheduled DNA-synthesis, DNA strand breaks and the number of S-phase cells were determined in the glandular stomach mucosa. All parameters were markedly raised between 300 to 600 mg / kg. Pyruvaldehyde led to a dose-dependent rise of UDS within 16 h and induced ornithine decarboxylase (OCD) activity by 100-fold within 7 h in the glandular stomach mucosa. DNA synthesis returned to the original rate within 24 h post-treatment. The authors discuss Methylglyoxal as a possible tumour promotor and would not exclude a tumour initiating action in the glandular stomach. comparison to the control.