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Toxicological information

Genetic toxicity: in vivo

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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: well performed and documented study, no Guideline mentioned but equivalent to Guideline

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1987

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test)
GLP compliance:
yes
Type of assay:
micronucleus assay

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid: pellets
Details on test material:
- Name of test material (as cited in study report): Preventol CI 7-100

- Physical state: solid
- Analytical purity: 99.3 %
- Composition of test material, percentage of components: 40 % 4-Methylbenzotriazole and 60 % 5-Metyhlbenzotriazole
- Storage condition of test material: at 4 °C

Test animals

Species:
mouse
Strain:
NMRI
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: F. Winkelmann, Borchen, Germany
- Age at study initiation: 8 - 12 weeks
- Weight at study initiation: 31 - 44 g
- Assigned to test groups randomly: [yes, under following basis: company randomising plan]
- Housing: standard Kakrolon cages type I and II
- Diet: Altromin 1324 ad libitum
- Water: ad libitum
- Acclimation period: 1 week

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +- 2°C
- Humidity (%): 50 %
- Air changes (per hr): 10
- Photoperiod (hrs dark / hrs light): 12

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
- Vehicle(s)/solvent(s) used: Polyethylenglycole
- Justification for choice of solvent/vehicle: suitable solvent for Tolyltriazole
- Concentration of test material in vehicle: no data
- Amount of vehicle (if gavage or dermal): no data
Details on exposure:
PREPARATION OF DOSING SOLUTIONS: the test item was solved in polyethylene glycol and
administered by gavage
Duration of treatment / exposure:
not applicable
Frequency of treatment:
once
Post exposure period:
24 / 48 / 72 hours
Doses / concentrations
Remarks:
Doses / Concentrations:
600 mg / kg bw
Basis:
nominal conc.
No. of animals per sex per dose:
5
Control animals:
yes, concurrent vehicle
Positive control(s):
cyclophosphamide
- Justification for choice of positive control(s): common substance, reommended by the OECD Guideline
- Route of administration: gavage
- Doses / concentrations: 20 mg / kg bw

Examinations

Tissues and cell types examined:
bone marrow from the femur
Details of tissue and slide preparation:
CRITERIA FOR DOSE SELECTION: a range finding study indicated the dose

TREATMENT AND SAMPLING TIMES ( in addition to information in specific fields):

DETAILS OF SLIDE PREPARATION:
The bonemarrow is purged with fetal calve serum
Dyeing with an Ames Hema-Tek Slide Stainer

METHOD OF ANALYSIS:
manual counting with a microscope (magnification 1000)
Evaluation criteria:
for the test item the number of polychromatic cells with micro nuclei is compared to the controls
A difference is significant, if the error probability is below 5 %
Statistics:
distrribution free rank sum test according to wilcoxon
Chi2-Test
Mean values and 1s-range

Results and discussion

Test results
Sex:
male/female
Genotoxicity:
negative
Toxicity:
yes
Vehicle controls validity:
valid
Positive controls validity:
valid
Additional information on results:
RESULTS OF RANGE-FINDING STUDY
- Dose range: 500 - 1000 mg/kg bw
- Clinical signs of toxicity in test animals: apathy, horrent fur, narcotic state, prone position, spasm, breathlessness

RESULTS OF DEFINITIVE STUDY
- Induction of micronuclei (for Micronucleus assay): normal
- Ratio of NCE/PCE (for Micronucleus assay): 1000:1715

Any other information on results incl. tables

 Group evaluable polychromatic Erythrocytes   Ratio NCE/PCE  Micronuclei per 1000 NCE Micronuclei per 1000 PCE 
 negative control 10000  1320  0.5  1.2 
 Tolyltriazole, 24 h 10000 1540  0.9  1.7 
 Tolyltriazole, 48 h 10000  1715  0.6  1.4 
 Tolyltriazole, 72 h 10000  994  0.5  1.0 
 positive control 10000  1393  0.8  14.7 

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information): negative
Tolyltriazole does not show genetic toxicity in this study.
Toxic effects were observed in a range finding study at 750 mg /kg bw