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Toxicological information

Genetic toxicity: in vivo

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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

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