1,3,5-triazine-2,4,6(1H,3H,5H)-trione, compound with 1,3,5-triazine-2,4,6-triamine (1:1)

Genetic toxicity: in vivo

Administrative data

Endpoint:

in vivo mammalian somatic cell study: cytogenicity / bone marrow chromosome aberration

Remarks:

Type of genotoxicity: chromosome aberration

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Similar to OECD testing guideline with fewer reporting details

Data source

Reference

Reference Type:

publication

Title:

Absence of mutagenic activity for monosodium cyanurate

Author:

Hammond, B. G. Barbee, S. J. Wheeler, A. G. Cascieri, T.

Year:

1985

Bibliographic source:

Fundam. Appl. Toxicol. 5: 655-664 (1985)

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 475 (Mammalian Bone Marrow Chromosome Aberration Test)

Deviations:

yes

Remarks:

limited reporting details; only 50 metaphases scored per animals (but two concentrations above limit concentrations tested), no historical control data given

GLP compliance:

not specified

Type of assay:

micronucleus assay

Test material

Test material information

Constituent 1

Reference substance name:

sodium;1,3-diaza-5-azanidacyclohexane-2,4,6-trione

Cas Number:

2624-17-1

IUPAC Name:

sodium;1,3-diaza-5-azanidacyclohexane-2,4,6-trione

Details on test material:

- name in publication: monosodium cyanurate
- supplier: Monsanto company
- composition: 77% cyanurate, 13% sodium and 10% water
- solubility in water: 0.7% w/v

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Simonsen Laboratories, Gilroy, California (USA)

- Weight at study initiation: 160 - 210 g
- Assigned to test groups randomly: yes
- Fasting period before study: 24h
- Housing: no data
- Diet (e.g. ad libitum): no data
- Water (e.g. ad libitum): no data
- Acclimation period: no data


ENVIRONMENTAL CONDITIONS
no data


IN-LIFE DATES: no data

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

The test item was given as a suspension in 4% Carboxymethylcellulose in water.

Details on exposure:

not reported

Duration of treatment / exposure:

once

Frequency of treatment:

single

Post exposure period:

sacrife 24h and 48h after treatment

Doses / concentrations

Remarks:

Doses / Concentrations:
1250, 2500 and 5000 mg/kg bw
Basis:
actual ingested

No. of animals per sex per dose:

5

Control animals:

yes, concurrent vehicle

Positive control(s):

Triethylenemelamine (ip, 0.275 mg/kg bw)

Examinations

Tissues and cell types examined:

femoral bone marrow cells

Details of tissue and slide preparation:

Animals were administered 4 mg/ kg eolchicine 2 hr before sacrifice 24 and 48 hr after dosing.

Bone marrow eelis were collected by needle aspiration of both femurs into Hank's balanced salt solution. The cells were processed to break up fibrin, incubated in 0.075 M KCI at 37°C for 20 minutes and then treated with Carnoy's fixative (3 parts absolute methanol: 1 part g1acial acetic acid).
Slides were stained with Giemsa.

50 metaphases were scored for each animal for chromosome aberrations.
1000 cells were scored for each animal for mitotic index

Evaluation criteria:

Statistical difference with p< 0.05%

Statistics:

Student's t-test (for transformed data)

Results and discussion

Test results

Sex:

male

Genotoxicity:

negative

Toxicity:

no effects

Vehicle controls validity:

valid

Negative controls validity:

not examined

Positive controls validity:

valid

Additional information on results:

The polyploidy index was not increased.

Any other information on results incl. tables

24h post dosing

Mean aberrations per cell were 0.08 ± 0.02 for vehicle control, 0.08 ± 0.02 for 1250 mg/kg bw, 0.07 ± 0.02 for 2500 mg/kg bw, 0.05 ± 0.02 for 5000 mg/kg bw and 0.89 ± 0.12 for the positive control

48h post dosing

Mean aberrations per cell were 0.07 ± 0.02 for vehicle control, 0.11 ± 0.02 for 1250 mg/kg bw, 0.12 ± 0.03 for 2500 mg/kg bw, 0.09 ± 0.02 for 5000 mg/kg bw and 2.34 ± 0.7 for the positive control

Values are reported for % abnormal cells, mean gaps per cell, % abnormal cells with chromosome deletions, chromosome exchanges, chromatide deletions, chromatide exchanges, aneuploidy, polyploidy and severe damage

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information): negative