Registration Dossier

Administrative data

Endpoint:
in vivo mammalian somatic cell study: cytogenicity / erythrocyte micronucleus
Remarks:
Type of genotoxicity: chromosome aberration
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP-report according to guideline.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1990

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test)
Version / remarks:
; 1983
GLP compliance:
yes
Type of assay:
micronucleus assay

Test material

Reference
Name:
Unnamed
Type:
Constituent

Test animals

Species:
mouse
Strain:
NMRI
Sex:
male/female
Details on test animals and environmental conditions:
Source: Winkelmann, Borchen
Age at study initiation: 6 weeks
Weight at study initiation: males 21-27
females 21-30

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
Peanut oil
Details on exposure:
Three groups of mice, the negative and positiv control groups (18 animals per sex) and the test material group
(21 animals per sex), each received a single administration by oral gavage (diet withdrawal: 16 h before treatment).
Group 1, the negative control, received peanut oil, group 2, the test material group, received 316 mg/kg body weight of the test material.
Group 3, the positive control, received cyclophosphamide (51.1 mg/kg body weight) dissolved in physiological saline solution (0.9 %).
Duration of treatment / exposure:
24, 48 or 72 hours
Frequency of treatment:
Single administration
Post exposure period:
No
Doses / concentrations
Remarks:
Doses / Concentrations:
316 mg/kg
Basis:
nominal conc.
No. of animals per sex per dose:
control groups: 18
test group: 21
Control animals:
yes, concurrent vehicle
Positive control(s):
cyclophosphamide (51.1 mg/kg body weight) dissolved in physiological saline solution (0.9 % (w/w))

Examinations

Tissues and cell types examined:
Bone marrow smears (at least two slides per animal) from the first 5 animals per sex and group were used for evaluation.
One slide per animal was examined. The remaining smears of each sex and group per interval were evaluated if macroscopical examination
of the first smears revealed technical imperfections which precluded aceurate microscopical analysis.
From each animal 1000 polychromatic erythrocytes (PCE) were scored for the incidence of micronuclei.
The ratio of polychromatic to normochromatic erythrocytes (PCE/NCE) was calculated, based on 1000 erythrocytes (PCE + NCE) scored per slide,
as a measure of the toxic efficacy of the test material.

Evaluation criteria:
If a test material produced no statistically significant and reproducible positive response at any one of the test points compared to the negative
control group, it was considered non-mutagenic.
Statistics:
Poisson test

Results and discussion

Test results
Sex:
male/female
Genotoxicity:
negative
Toxicity:
yes
Vehicle controls validity:
valid
Negative controls validity:
not specified
Positive controls validity:
valid
Additional information on results:
Triallylcyanurate (TAC) related toxic symptoms were registered in all test material group animals. The symptoms consisted in coordination
disturbances, clonic convulsions, decrease of muscle tone, loss of righting reflexes, loss of pinna reflex, loss of pain reflex, loss of corneal reflex,
ptosis, tear formation, strenuous respiration, and reduced temperature of the body surface. One female animal of the test material group died.

Reduction in the ratio of polychromatic to normochromatic erythrocytes was present in all dose groups of the test material indicating a toxic effect 
on the bone marrow. No statistically significant test material-related increase in the number of micronucleated polychromatic erythrocytes was 
observed in either male or female animals and also if both sexes were analysed combined at the 48 hr and 72 hr sampling times and in females at the 24 hr sampling time. At the 24 hr sampling time a statistically significant increase in micronuclei was observed only in male animals of the main test. 

This increase could not be verified in the repetition test using two additional dose levels and is therefore considered an incidental finding. 

Applicant's summary and conclusion

Conclusions:
Triallylcyanurate does not cause cytogenic effects in the mouse micronucleus test.