1,3,5-tris(oxiranylmethyl)-1,3,5-triazine-2,4,6(1H,3H,5H)-trione

Genetic toxicity: in vivo

Administrative data

Endpoint:

in vivo mammalian germ cell study: cytogenicity / chromosome aberration

Remarks:

Type of genotoxicity: chromosome aberration

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1991

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: all criteria are fulfilled for a high quality study

Cross-reference

Cross-reference 1

Reason / purpose for cross-reference:

reference to same study

Cross-reference 2

Reason / purpose for cross-reference:

reference to other study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1991

Report date:

1991

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 483 (Mammalian Spermatogonial Chromosome Aberration Test)

Deviations:

no

GLP compliance:

yes

Type of assay:

mammalian germ cell cytogenetic assay

Test material

Test material information

Constituent 1

Reference substance name:

1,3,5-tris(oxiranylmethyl)-1,3,5-triazine-2,4,6(1H,3H,5H)-trione

EC Number:

219-514-3

EC Name:

1,3,5-tris(oxiranylmethyl)-1,3,5-triazine-2,4,6(1H,3H,5H)-trione

Cas Number:

2451-62-9

Molecular formula:

C12H15N3O6

IUPAC Name:

tris[(oxiran-2-yl)methyl]-1,3,5-triazinane-2,4,6-trione

Details on test material:

TK 10622 (Araldite PT 810, TGIC, 97%)
Purity: 97%, TGIC (technical grade, batch-no. 144727)

Test animals

Species:

mouse

Strain:

other: strain B6D2F1

Sex:

male

Details on test animals or test system and environmental conditions:

Young adult male B6D2F1 mice were housed in groups of 3 in polypropylene cages with solid floors with saft wood beddings; water and food was available ad libitum, they were kept at a 12-hour dark/light cycle with 20 air changes/hour in the animal rooms at a temperature of 18-24 °C, and a relative humidity of 46-66 %. Acclimatization was 18 days, and the age was 82 days at treatment start (weight 27-31 gm).

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

0.5% carbocymethylcellulose in water

Details on exposure:

Male mice were exposed orally (gavage) to TGIC (technical grade, 97%, batch-no. 144727) in 0.5% CMC (aqueous solution) on 5 consecutive days

Duration of treatment / exposure:

immediate (seconds) for gavaging

Frequency of treatment:

once on 5 consecutive days

Post exposure period:

24 h

Doses / concentrations

Remarks:

Doses / Concentrations:
0, 28.75, 57.5, and 115 mg/kg
Basis:
analytical conc.

No. of animals per sex per dose:

5 males

Control animals:

yes, concurrent vehicle

Positive control(s):

yes, group 0.3 mg/kg mitomycin C (single dose, intra-peritoneally

Examinations

Tissues and cell types examined:

testes were dissected and seminiferous tubules were excised and spermatogonial cells prepared for slides.

Details of tissue and slide preparation:

Standard procedure with Giemsa staining

Evaluation criteria:

as outlined in the guideline

Statistics:

none

Results and discussion

Test results

Sex:

male

Genotoxicity:

positive

Remarks:

increase in major chromosomal aberrations

Toxicity:

yes

Remarks:

change of cytotoxic ratio

Vehicle controls validity:

valid

Negative controls validity:

not applicable

Positive controls validity:

valid

Additional information on results:

The cytotoxic ratio changed from 2.95 (control) to 0.48 (high dose group).
No significant differences in body weight were observed during the 5-day treatment period.
A significant increase in major chromosomal aberrations (without gaps) occurred in high dose and low dose group, as well as in the mitomycin C group (positive control).
The number of gaps was also increased in the same dose groups. Although, the intermediate dose group showed fewer major aberrations, but several chromatid exchanges which were not found in the negative control group

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information): positive
It is concluded that TGIC caused a mutagenic effect in mouse spermatogonial cells upon oral exposure.

Executive summary:

1)     The cytotoxic ratio changed from 2.95 (control) to 0.48 (high dose group).

2)     No significant differences in body weight were observed during the 5-day treatment period.

3)     A significant increase in major chromosomal aberrations (without gaps) occurred in high dose and low dose group, as well as in the mitomycin C group (positive control).

4)     The number of gaps was also increased in the same dose groups. Although, the intermediate dose group showed fewer major aberrations, but several chromatid exchanges which were not found in the negative control group

It is concluded that TGIC caused a mutagenic effect in mouse spermatogonial cells upon oral exposure