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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
Study period:
data not available
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: 2c Comparable to guideline study with acceptable restrictions

Data source

Reference
Reference Type:
publication
Title:
Evaluation of a three-exposure mouse bone marrow micronucleus protocol: results with 49 chemicals.
Author:
Shelby MD, Erexson GL, Hook GJ and Tice RR
Year:
1993
Bibliographic source:
Environ Mol Mutagen, 21, 160-179.

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test)
GLP compliance:
not specified
Type of assay:
micronucleus assay

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): 11-aminoundecanoic acid
no other data

Test animals

Species:
mouse
Strain:
B6C3F1
Sex:
male
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: National toxicology program production facility at taconic farms
- Age at study initiation: 9-14 weeks
- Weight at study initiation: 25-33 g
- Assigned to test groups randomly: data not available
- Fasting period before study: data not available
- Housing: data not available
- Diet (e.g. ad libitum): data not available
- Water (e.g. ad libitum): data not available
- Acclimation period: data not available


ENVIRONMENTAL CONDITIONS
data not available


IN-LIFE DATES: data not available

Administration / exposure

Route of administration:
intraperitoneal
Vehicle:
- Vehicle(s)/solvent(s) used: corn oil
-no other data
Details on exposure:
Groups of 4-6 mice were injected IP on three consecutive days with either the test chemical (at 1x, 1/2X, and 1/4x, where x is the maximum dose determined in the dose determination experiments), a weakly active dose of the positive control chemical (DMBA in corn oil or MMC in PBS), or the appropriate solvent. Mice were euthanized with CO2 24 hr after the third treatment.
Duration of treatment / exposure:
3 days
Frequency of treatment:
daily
Post exposure period:
24 hr
Doses / concentrations
Remarks:
Doses / Concentrations:
0, 62.5, 125, 250 and 500 mg/kg
Basis:
other: actuel injected
No. of animals per sex per dose:
4-6 males
Control animals:
yes, concurrent vehicle
Positive control(s):
7,12-dimethylbenzanthracene or mitomycin C;
no other data

Examinations

Tissues and cell types examined:
Bone marrow cells
Details of tissue and slide preparation:
DETAILS OF SLIDE PREPARATION: Bone marrow smears (two slides mouse) were prepared, fixed inabsolute methanol, and stained with acridine orange.


METHOD OF ANALYSIS: For each animal, slides were evaluated at 1,000x magnification for the number of MN-PCE among 2,000 PCE and for the percentage of PCE among 200 erythrocytes.


Evaluation criteria:
MN-PCE/2000 PCE and % of PCE among 200 erythrocytes
Statistics:
The data were analyzed using the Micronucleus Assay Data Management and Statistical software package (version 1.4), which was designed specifically for in vivo micronucleus data [ILS, 1990]. The %PCE data were analyzed by an analysis of variance (ANOVA) test based on pooled data.
Pairwise comparisons between each group and the concurrent solvent control group was by an unadjusted one-tailed Pearson chisquared test which incorporated the calculated variance inflation factor for the study.

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:
See in field "Remarks on results including tables and figures.

Any other information on results incl. tables

· Effect on PCE/NCE ratio by dose level :
Dose (mg/kg) % PCE
0 53.0
62.5 53.2
125 39.1
250 42.1
500 42.3
· Genotoxic effects : negative
· NOEL : > 500 mg/kg
· Remarks field for Results :
- Mortality at each dose level :
Dose (mg/kg) Mortality
0 0/5
62.5 0/5
125 1/6
250 0/5
500 0/4
- MN-PCE frequency :
Dose (mg/kg) MN-PCE/1000 PCE
0 2.30 ± 0.37
62.5 2.00 ± 0.35
125 1.90 ± 0.62
250 2.30 ± 0.37
500 2.38 ± 0.24
- clinical signs : not reported
- Body weight changes : not reported
- Food/water consumption changes : not reported

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information): negative
Under the conditions of this test, 11-aminoundecanoic acid did not induce a genotoxic effect.
Executive summary:

In a mouse bone marrow micronucleus test (Shelby et al., 1993), male B6C3F1 mice were treated with 11-aminoundecanoic acid, mixed in corn oil, in an i.p. administration at the dose levels of 62.5, 125, 250 and 500 mg/kg (0.4 ml per mouse). The protocol involved three daily treatments and a single sample time 24 hr following the final treatment was performed. Four to six mice were used for each dose level along with a negative control. Mice were injected with 7,12-dimethylbenzanthracene or mitomycin C and served as positive control. The positive controls induced the appropriate response. Results with the test substance did not induced cytogenetic damage to the bone marrow cells in mice. This study is classified as acceptable and satisfies the requirement for Test Guideline OECD 474.