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Toxicological information

Genetic toxicity: in vitro

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Administrative data

Endpoint:
in vitro cytogenicity / chromosome aberration study in mammalian cells
Remarks:
Type of genotoxicity: chromosome aberration
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1994
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
No metabolic activation system used (although the study also tested the key metabolite separately – see separate record .) No information on number of samples (but >1). Contact with test substance longer than normally recommended. Only 100 metaphase cells analysed per dose but no information recorded to suggest that results are unreliable.
Cross-reference
Reason / purpose:
reference to other study

Data source

Reference
Reference Type:
publication
Title:
Cytogenetic effects of 2-methoxyethanol and its metabolite methoxyacetaldehyde, in mammalian cells in vitro
Author:
Chiewchanwit T, Au WW
Year:
1994
Bibliographic source:
Mutation Res, 320 125-132.

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 473 (In Vitro Mammalian Chromosome Aberration Test)
Deviations:
yes
Remarks:
, see comments on reliability above
GLP compliance:
not specified
Type of assay:
in vitro mammalian chromosome aberration test

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Analytical purity: No data on purity.
- supplied by Aldrich Chemical Company

Method

Target gene:
k1-BH4 cells: single copy of hprt gene on X chromosome. AS52 has single copy of gpt gene on an autosome.
Species / strainopen allclose all
Species / strain / cell type:
lymphocytes: (mammalian cell line)
Species / strain / cell type:
Chinese hamster Ovary (CHO)
Details on mammalian cell type (if applicable):
K1-BH4 and AS52 cell lines from Texas University Medical Branch
Metabolic activation:
without
Test concentrations with justification for top dose:
0,1,5,10,50,150,400,600mM.
Controls
Untreated negative controls:
yes
Positive controls:
yes
Positive control substance:
mitomycin C
Statistics:
Raw data was transformed according to the procedure of Whorton (1984, 1985). Transformed data were analysed using MYSTAT for linear regression. Statistical difference between samples and controls were assessed using Dunnett’s test, p<0.05.

Results and discussion

Test results
Species / strain:
lymphocytes: mammalian cell
Metabolic activation:
not specified
Genotoxicity:
positive
Remarks:
at 150mM
Cytotoxicity / choice of top concentrations:
cytotoxicity
Remarks:
at 600mM
Untreated negative controls validity:
valid
Positive controls validity:
valid
Remarks on result:
other: all strains/cell types tested
Remarks:
Migrated from field 'Test system'.

Any other information on results incl. tables

In terms of abberant cells: No effect concentration 50mM. Significant difference from controls (LOEL) at 150mM. Cytotoxic concentration 600mM. In a separate study where contact time was only 1 hour, no effects were seen at the maximum dose tested (125mM.) Proliferation index was only significantly reduced at 300mM. There was no significant change in the mitotic index. The doses tested can be considered very high.

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information):
other: In terms of abberant cells: No effect concentration 50mM. Significant difference from controls (LOEL) at 150mM. Cytotoxic concentration 600mM. In a separate study where contact time was only 1 hour, no effects were seen at the maximum dose tested (125mM

Positive results observed but only at very high test doses. The results can be considered negative at more appropriate test doses.
Executive summary:

In an in vitro cytogenetics assay using lymphocytes, 2-methoxyethanol produced a significant increase in the number of aberrant cells exposed for 24 hours at 150 mM.  These positive responses were only seen at very high doses. No effects were seen at the maximum concentration tested (125mM) after 1 hour exposure. Metabolic activation was not used but metabolites were examined in separate studies