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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:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1991
Report Date:
1991

Materials and methods

Test guideline
Qualifier:
according 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:
other: red powder
Details on test material:
Content:
The batch was analysed prior to the study initiation. A stability test in the vehicle did not detect a relevant change in the percentage active ingredient.

Test animals

Species:
mouse
Strain:
NMRI
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Age at study initiation: 8 - 12 weeks
- Weight at study initiation: 29 - 43 g
- Housing: females in groups of 3; males singly
- Diet ad libitum
- Water ad libitum
- Acclimation period: at least one week

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22
- Humidity (%): 43-50
- Air changes (per hr): 10
- Photoperiod (hrs dark / hrs light): 12 / 12

Administration / exposure

Route of administration:
intraperitoneal
Vehicle:
Aequeous cremophor emulsion
Details on exposure:
Each group comprised tne mice , 5 males and 5 females. each respective substance was administered once. Animals were sacrificed 16, 24, and 48 hours after the administration and the femoral marrow was prepared for evaluation.
Duration of treatment / exposure:
Once
Frequency of treatment:
Once
Post exposure period:
Up to 48 hours
Doses / concentrations
Remarks:
Doses / Concentrations:
10000 mg/kg bw
Basis:

No. of animals per sex per dose:
10 (5 males and 5 females)
Control animals:
yes, concurrent vehicle
Positive control(s):
cyclophosphamide

Examinations

Tissues and cell types examined:
bone marrow from femur (erythroblasts)
Details of tissue and slide preparation:
bone marrow from femur (erythroblasts)
Evaluation criteria:
Coded slides were evaluated using a light microscope at a magnification about 1000. Micronucei appear as stainde chromatinparticles in the anucleated erythrocytes: 1000 polychromatic erythrocytes were counted per animal
A test is considered positive if, at any of the intervals, there was a relevant and significant increase in the number of polychromatic erythrocytes showing micronuclei in comparison to the negative control.
Statistics:
Wilcoxon's non-parametric rank sum test, one-sided chi-square test

Results and discussion

Test results
Key result
Sex:
male/female
Genotoxicity:
negative
Toxicity:
yes
Vehicle controls validity:
valid
Negative controls validity:
valid
Positive controls validity:
valid
Additional information on results:
After single intraperitoneal administration of 10000 mg/kg bw Macrolex Red E2G treated animals showed the following compound-related symptoms until sacrifice: apathy, rough fur, staggering gait, spasm, eyelids stuck together. Their feeding behaviour was normal. One of the Macrolex Red E2G treated animal died during the test period. All intestinal organs of this animal were covered red and sticked together. The stomach was filled with a light-red liquid.
The ratio of polychromatic to normochromatic erythrocytes was altered by the treatment with Macrolex Red E2G in the 24 hours and in the 48 hours group.
There was no biologically important or statistically significant variations between the negative control and the groups treated intraperitoneally with 10000 mg/kg bw Macrolex E2G with respect to the incidence of micronucleated polychromatic erythrocytes.

Applicant's summary and conclusion

Conclusions:
Interpretation of results: negative
There was no indication of a clastogenic effect of an intraperitoneal dose of 10000 mg/kg bw Macrolex Red E2G in the micronucleus test on the mouse.
Executive summary:

NMRI mice were used to examine the in vivo clastogenic activity of Macrolex Red E2G in a MNT according to OECD TG 474 and GLP. Based on a pilot study a dose of 10000 mg/kg bw dissolved in aequeous cremophor emulsion was chosen for intraperitoneal injection. Animals were sacrificed 16, 24, and 48 hours after the administration and the femoral marrow was prepared for evaluation.

The treated animals showed symptoms of toxicity including apathy, rough fur, staggering gait, spasm, eyelids stuck together and one animal died before the end of the test.

There was an altered ratio between polychromatic and normochromatic erythrocytes. No indications of a clastogenic effect of Macrolex Red E2G were found after a single intraperitoneal treatment with 10000 mg/kg bw Macrolex Red E2G.