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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
Study period:
1993
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Published study wjhich contains sufficient scientific information to be able to judge it as reliable for hazard assessment purposes.

Data source

Reference
Reference Type:
publication
Title:
Toxicology of diethylene glycol monobutyl ether 3. Genotoxicity evaluation in an in vitro gene mutation assay and an in vivo cytogenic test
Author:
Gollapudi, B.B., et al. (1993).
Year:
1993
Bibliographic source:
J. Am. Coll. Toxicol. 12(2), 155-59

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 475 (Mammalian Bone Marrow Chromosome Aberration Test)
Deviations:
no
Remarks:
significant deviations noted.
GLP compliance:
not specified
Remarks:
reported as a GLP compliant study
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): diethylene glycol monobutyl ether (DGBE)
- Analytical purity: 99.51%
- Impurities (identity and concentrations): peroxides 43ppm
- Lot/batch No.: QP-870323-35-S1 ex Dow Chemicals, Midland, MI

Test animals

Species:
mouse
Strain:
CD-1
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Age at study initiation: 8 weeks

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
- water
Details on exposure:
- gavage dose 10ml/kg of substance in vehicle.
Duration of treatment / exposure:
single dose
Frequency of treatment:
not applicable
Post exposure period:
Animals sacrificed at 24, 48 and 72 hours after treatment. Positive control group only for 24hr sacrifice.
Doses / concentrations
Remarks:
Doses / Concentrations:
0, 330, 1100 or 3300 mg/kg bw
Basis:
actual ingested
No. of animals per sex per dose:
5
Control animals:
yes, concurrent vehicle
Positive control(s):
- cyclophosphamide;
- Route of administration: gavage
- Doses / concentrations: 120mg/kg/bw

Examinations

Tissues and cell types examined:
Polychromatic erythrocytes for micronucleation
Details of tissue and slide preparation:
CRITERIA FOR DOSE SELECTION: Top dose was set at 80% of LD50 (4230mg/kg)

TREATMENT AND SAMPLING TIMES ( in addition to information in specific fields): See post exposure period field. Sampling times sufficient to allow for absorption and/or metabolism delays.

DETAILS OF SLIDE PREPARATION: Bone marrow smears allowed to air dry, fixed in methanol and stained with 5% giemsa

METHOD OF ANALYSIS: 1000 polychromatic erythrocytes (PCE) were examined per animal to determine incidence of micronucleated PCE and expressed as ration to normochromatic erythrocytes.
Evaluation criteria:
no further data
Statistics:
Three way ANOVA (sex, time, dose) on log transformed data. Pairwise comparisons of dose groups versus negative control done if required by t-test using Bonferroni correction for multiple comparisons. Significance set at p<0.01.

Results and discussion

Test results
Sex:
male/female
Genotoxicity:
negative
Toxicity:
not examined
Vehicle controls validity:
valid
Negative controls validity:
not specified
Positive controls validity:
valid
Additional information on results:
RESULTS OF DEFINITIVE STUDY
- Induction of micronuclei (for Micronucleus assay): No
- Ratio of PCE/NCE (for Micronucleus assay): 24hrs males: 69-76 (54 in positive control) but not significantly different. females 82-85 (71 in positive control) but not significantly different. 48hrs both sexes: 83-92.
- Appropriateness of dose levels and route:
- Statistical evaluation: No significant increase in the incidence of MN-PCE at any dose level tested and at any time point. Positive control induced significant increase as expected.

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information): negative
The substance does not induce cytogenicity manifest as micronuclei in the bone marrow of mice when evaluated up to the maximum tolerated dose.
Executive summary:

In an in vivo mouse micronucleus test that used 3 post treatment sampling times, 2 -(2 -butoxyethoxy)ethanol did not increase the incidence of micronucleated polychromatic erythrocytes in either sex when tested up to a single maximum tolerated dose of 3300mg/kg/bw.